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Summer 2018 Vol. 4. No. 1

2018 National Conference Preview

DEPRESSION New Perspectives for Improving Patient Care Page 20

OPIOIDS How Mental Health Clinicians Can Help Solve the Crisis Page 30

BIPOLAR DISORDER Tips for Treating Older Adults Page 21

psychcongress.com Use code * October 25– 28 PCS100 2018 to save $100 ORLANDO 2018 Psych Congress Highlights

Featured Sessions Enhance your full day of learning with a Psych Congress staple — our featured sessions, a series of noteworthy lectures designed to educate and inspire. Our DAVID 2018 lineup includes presentations by Anna Lembke, MD, Robin Carhart-Harris, GRANIRER PhD, and David Granirer, RPC, MPCC, MSM, and will also feature a debate on the RPC, MPCC, MSM use of to treat bipolar depression with Nassir Ghaemi, MD, MPH, and Joseph Goldberg, MD. Solving Clinical Challenges Series These sessions address complex conundrums that are faced by attendees in managing their patients battling different mental health disorders. Topics to be addressed include: ADHD & Substance Use Disorder, Geriatric Psychiatry, Sleep Disorders, and Women’s Mental Health. New Perspectives in Advanced Psychopharmacology Preconference Understanding the mind-body connection is an essential part of selecting the appropriate treatments for patients with mental health disorders. Join members of the Steering Committee for a full day of clinically relevant information designed to transform your approach to caring for patients who suffer from depression. Preconference attendees will receive two complimentary books, written by the faculty, that can be used as resources. Psych Congress Networking Event at Epcot® Join your colleagues, Psych Congress faculty, and members of the Steering Committee for an evening networking event featuring the IllumiNations: Reflections of Earth fireworks spectacular and a dessert and drinks reception at Walt Disney World’s Epcot® on Thursday, October 25. Limited to only 300 attendees.

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*Discount good on new registrations only. Cannot be combined with other offers.

Program Co-Chairs  Identify the etiology, pathophysiology and Center (ANCC) to provide continuing education continuing education for psychologists. NAC- *Accreditation information pertains only to the reserved. No part of this accredited continuing neural pathways of various psychiatric disorders for the healthcare team. CME maintains responsibility for this program main conference; accreditation information for education activity may be reproduced or trans- Rakesh Jain, MD, MPH Clinical Professor, Department of Psychiatry, and their effects on patients and its content. the preconference program and Psych Con- mitted in any form or by any means, electronic or CME gress On-Demand will be provided separately. mechanical, without first obtaining permission Texas Tech Health Sciences Center School of  Implement evidence-based models on the use NACCME designates this live activity for a Attendees will have the opportunity to earn up from North American Center for Continuing Medicine, Midland, Texas of psychotherapeutic and pharmacotherapeutic maximum of 27.25 AMA PRA Category 1 Cred- Instructional Level: Advanced interventions to develop treatment plans, predict to 6.0 additional credits for participating in a Medical Education. Charles Raison, MD its™. Physicians should claim only the credit treatment response, optimize remission and Requirements for Credit one-day preconference. If you claim credit for Mary Sue and Mike Shannon Chair for Healthy commensurate with the extent of their partic- a live session at Psych Congress, you cannot Grant Support prevent relapse To be eligible for documentation of credit, Minds, Children & Families; Professor, School ipation in the activity. claim credit for the same session via Psych This activity is supported by educational grants participants must attend the educational ac- of Human Ecology, Department of Psychiatry,  Employ strategies to identify and remove Congress On-Demand. Total credit hours are from Neurocrine Biosciences and Teva Phar- CNE tivity and complete the evaluation form. After School of Medicine and Public Health, University barriers to treatment to improve patient out- subject to change. maceuticals. of Wisconsin, Madison, Wisconsin comes in the acute and long-term management This continuing nursing education activity successful completion of the evaluation form awards 27.25 contact hours. online, participants may immediately print their ADA Statement To view faculty bios, call 609.371.1137 of psychiatric disorders; and Provider approved by the California Board of documentation of credit. North American Center for Continuing Medical  Assess psychiatric disorders, as well as patients’ Intended Learners overall health, including comorbidities, with Registered Nursing, Provider #13255, for 27.25 Physician assistants, nurse practitioners and Education complies with the legal requirements This activity is intended for psychiatrists, pri- the goal of improving diagnosis and treatment. contact hours. nurses may participate in this educational activity of the Americans with Disabilities Act and the mary care physicians, psychologists, nurse This continuing nursing educational activity and earn a certificate of completion, as AAPA, rules and regulations thereof. If any participant practitioners, physician assistants, psychiatric Accreditation Information* awards up to 18.75 pharmacology hours. Sessions AANP, and ANCC accept AMA PRA Category 1 in this educational activity is in need of accom- nurses, and other healthcare professionals who In support of improving patient care, that award pharmacology hours will be outlined Credits™ through their reciprocity agreements. modations, please call 609.371.1137. seek to improve the care of patients with mental North American Center for Continu- in the conference syllabus. Other healthcare professionals treating patients Contact Information health disorders. ing Medical Education (NACCME) with mental health disorders should check with is jointly accredited by the Accreditation Council CE INFORMATION: APA their state licensing and certification boards For questions regarding this educational activity, Learning Objectives for Continuing Medical Education (ACCME), the North American Center for Continuing Medical to determine if Psych Congress meets their please call 800.205.8233. After completing this activity, participants Accreditation Council for Pharmacy Education Education, LLC (NACCME) is approved by the continuing education requirements. Copyright © 2018 by North American Center for should be able to: (ACPE), and the American Nurses Credentialing American Psychological Association to sponsor Continuing Medical Education, LLC. All rights LETTERLETTER FROM FROM THE THE CO-CHAIRS COCHAIRS

e hope you all enjoyed your summer. The Psych Congress team is hard at work putting together another clinically focused conference and exhibition, one that is sure to be unforgettable! In this Wedition of the official publication of Psych Congress, learn about several of the dynamic sessions offered at this year’s conference in Orlando, Florida, including a Q&A with Robin Carhart-Harris, PhD, who will present “Psychedelics: A Psychiatric Revolution in Waiting?” Other noteworthy happenings at the nation’s leading conference for advancing psychopharmacology, psychotherapy, and wellness include:

• The New Perspectives in Advanced Psychopharmacology Preconference, where members of the Psych Congress Steering Committee will provide a full day of clinically relevant information designed to transform your approach to caring for patients suffering from depression.

• Four featured sessions led by trailblazers in the field of mental health. We are excited to have Robin Carhart-Harris, PhD; David Granirer, RPC, MPCC, MSM; Nassir Ghaemi, MD, MPH; Joseph F. Goldberg, MD; and Anna Lembke, MD, educate and inspire us in Orlando.

• Our annual networking event, this year being held at Walt Disney World’s Epcot® theme park. Join your colleagues, Psych Congress faculty, and members of the Steering Committee for this evening event on Thursday, October 25. Attendees who add this event will be able to watch the IllumiNations: Reflections of Earth fireworks spectacular from a private viewing area and enjoy a dessert and drinks reception.

With a diverse agenda of more than 50 sessions over four days, Psych Congress enables attendees to gain insights into current and emerging treatment strategies with the very best minds in the field, embrace in- novation, and learn how to implement measurement-based care in everyday clinical practice.

We look forward to seeing you in Orlando this October and hope you enjoy the conference preview!

Rakesh Jain, MD, MPH Charles Raison, MD Psych Congress 2018 Co-Chair Psych Congress 2018 Co-Chair

ADVANCE YOUR PSYCHOPHARMACOLOGY, PSYCHOTHERAPY, & WELLNESS KNOWLEDGE psychcongress.com • Summer 2018 • Psych Congress Network 3 IN THIS ISSUE SUMMER 2018

STAFF EDITORIAL Managing Editor: Terri Airov Graphic Designers: Caitlin Keenan, Alicia Indico

BUSINESS 3 A Letter From the Psych Congress Co-Chairs President: Randy Robbin Associate Vice President, National Accounts – Rakesh Jain, MD, MPH, and Charles Raison, MD Exhibits and Sponsorship Services: Jennifer Griffith Senior Manager, National Accounts – Exhibits and Digital Services: Ken Palmer

5 Bulletin Board HMP Chairman and Chief Executive Officer: Jeff Hennessy Highlights from recent mental health news Senior Vice President of Finance: Greg Salter Executive Vice President of Operations: Anthony Mancini Controller: Meredith Cymbor-Jones NEWS CONNECTION Senior Director, Digital Strategy and Media: Tim Shaw Senior Manager, IT: Ken Roberts

20 Looking at Depression Through an Evolutionary Lens North American Center for Continuing Medical Education, LLC, In a preconference before Psych Congress, Steering Committee members will present a full an HMP Company 104 Windsor Center Drive, Suite 200 | East Windsor, NJ 08520 day of clinically relevant information designed to transform the care of patients with 609.371.1137 www.naccme.com

depression. © Copyright 2018 North American Center for Continuing Medical Education, LLC, an HMP Company

21 Optimizing the Treatment of Bipolar Disorder in Older Adults STEERING COMMITTEE Charles Raison, MD Martha Sajatovic, MD, discusses the growing population of older adults and unique Co-Chair 2018 Psych Congress Professor, School of Human Ecology considerations for treating them for bipolar disorder and other mental health disorders. Professor, Department of Psychiatry School of Medicine and Public Health University of Wisconsin, Madison

22 Clearing Up Confusion About Cannabis Therapeutics Rakesh Jain, MD, MPH Co-Chair 2018 Psych Congress Maria Mangini, PhD, FNP-BC, outlines some concerns that clinicians and patients have about Clinical Professor Department of Psychiatry medical cannabis and shares some tips on it from her decades of clinical experience. Texas Tech Health Sciences Center School of Medicine Midland, Texas 24 Future Opportunities in the Treatment of James Cannon, PhD, MS, PA-C, CAQ-Psy, DFAPA John M. Kane, MD, looks ahead to significant changes that could transform the treatment of Associate Professor, A.T. Still University Mesa, Arizona schizophrenia over the next 10 years. Senior Psychiatric Physician Assistant Community Health Systems Southern Virginia Regional Medical Center 25 A New Generation of Depression Treatment Approaches Emporia, Virginia Julie Carbray, PhD, FPMHNP, PMHCNS Michael Thase, MD, reviews the evolution of depression treatments, the current landscape of Clinical Professor of Psychiatry and Nursing University of Illinois at Chicago available interventions, and emerging pharmacotherapies. Administrative Director, Pediatric Mood Disorder Clinic  Pediatric Brain Research and Intervention Center FEATURE STORIES Department of Psychiatry Jon W. Draud, MD, MS Clinical Professor of Psychiatry 26 Using Comedy to Confront Mental Illness and Its Public Stigma University of Tennessee College of Medicine Memphis, Tennessee David Granirer, RPC, MPCC, MSM, explains how performing stand-up comedy can help Medical Director of Psychiatry Pain Management Group people cope with mental health issues and reduce public stigma about psychiatric disorders. Trust Point Psychiatric Hospital St. Thomas Rutherford Hospital Medical Director and Principal Draud Sudbury Psychiatric Solutions 28 The Growing Role of Neurobiology in Mental Health Care Private Practice, Adult and Adolescent Psychiatry Sheldon H. Preskorn, MD, reflects on changes in psychiatry over his 40-year career and where Nashville, Tennessee he sees the mental health field and treatments headed as the understanding of neurobiology Saundra Jain, MA, PsyD, LPC Adjunct Clinical Affiliate continues to grow. University of Texas at Austin, School of Nursing Austin, Texas

Catherine Judd, MS, PA-C, CAQ-Psy, DFAPA 30 Hidden Forces Behind the US Epidemic Clinical Assistant Professor UT Southwestern Medical Center Anna Lembke, MD, explores the state of the US prescription drug epidemic, factors that may Dallas, Texas Senior, Physician Assistant, Mental Health Services have contributed to it, and her provocatively titled book on the crisis. Parkland Health and Hospital System Dallas, Texas

Vladimir Maletic, MD, MS 32 Uncovering the Therapeutic Potential of Psychedelics Clinical Professor of Psychiatry and Behavioral Science Robin Carhart-Harris, PhD, addresses misconceptions surrounding psychedelics, discusses University of South Carolina School of Medicine Greenville, South Carolina their potential therapeutic utility and possible dangers, and weighs in on the renewed Andrew Penn, RN, MS, NP, APRN-BC scholarly interest in the compounds. Psychiatric Nurse Practitioner Kaiser Permanente Redwood City, California Associate Clinical Professor University of California, San Francisco

4 Psych Congress Network • Summer 2018 • psychcongress.com BULLETIN BOARD

PSYCH CONGRESS REMEMBERS ERIC C. ARAUZ

Keynote Address at Psych Congress PSYCH CONGRESS SNAPSHOT 2018 Remembering Eric C. Arauz, MLER WEDNESDAY, OCTOBER 24 | 4:30 P.M. — 6:00 P.M. Join the Psych Congress family as we pay tribute to steering committee member Eric C. Arauz, MLER, who passed away on March 25, 2018. The session will feature Stephen W. Porges, PhD, who developed the Polyvagal Theory, which Eric spoke about often.

Eric joined the Psych Congress faculty in moderator for our inaugural re:Think initiative, 2014. His contributions to shaping mental launched in February at Elevate by Psych health education are countless. Eric brought Congress. The success of this educational Eric C. Arauz, MLER, will be honored during the Psych Congress 2018 Keynote Address. a unique perspective to the committee as experience—which challenges mental health someone who himself had a mental illness professionals to rethink their approach to and was a champion deeply committed to mental health care—was due largely to Eric’s fighting the stigma of mental illness. He was leadership, enthusiasm, and vision. ric C. Arauz, MLER, was a dear and Eric will be honored during the Keynote a frequent keynote speaker at Psych Congress Above all, Eric’s gift was in using his abun- well-respected colleague, passionate Address kicking off this year’s Psych Congress events across the US. An attendee who once dant empathy and energy to help people feel mental health advocate, Psych Con- conference, featuring Stephen W. Porges, heard him speak said, “Eric is a true gift to hope when they may have felt none. He Egress Steering Committee member and fac- PhD. Dr. Porges developed the Polyvagal humanity.” touched the lives of so many—both within ulty, and above all, friend. Theory, which Eric spoke about often. Most recently, Eric served as a mentor and our community and beyond. ■

PSYCH CONGRESS MOBILE APP The official conference app of Psych Congress offers everything you need to get the most out of your educational experience. Download Now Available Free on iPhone & Android Just download the “HMP Conferences” app and search for “Psych Congress 2018”

Key Features

• View the most up-to-date conference agendas • Access session presentations • Create your personal schedule • Search the exhibitor listings and floor plan • Create a profile and connect with other participants through social sharing • Receive timely notifications and updates on conference functions SPONSORED CONTENT From 3 Weeks to 1 Day: A New Schizophrenia Treatment Initiation By Peter J. Weiden, M.D.

have spent the better part of my career ' research and its long- the suspension. ARISTADA INITIO is formulated helped provide patients with schizophrenia as a clinician and investigator specializing acting technology platform contributed to the into smaller, nanometer-sized particles that have with more treatment options, but it’s critical in the treatment of schizophrenia and development of some of the first LAIs available a relatively faster dissolution rate than the mi- that we don’t stop here. Progress can often feel Ihave focused on gaining an understanding for the treatment of schizophrenia, as well as our crometer-sized particles in ARISTADA. Faster slow, but these consistent, incremental steps of the problem of adherence to antipsychot- own long-acting injectable, ARISTADA, which dissolution of ARISTADA INITIO results in ear- forward are essential to understanding and ic medication.1,2 Over the years, my work on is available in monthly (441 mg, 662 mg or 882 lier appearance of circulating plasma aripipra- better meeting the needs of patients. ■ 11 pharmacologic and psychosocial interven- mg), six-week (882 mg) and two-month (1064 zole. With the addition of a single intramuscu- Peter J. Weiden, M.D., is the Schizophrenia Lead, tions included the topic of long-acting inject- mg) formulations.5,6 The flexible dosing options lar injection of ARISTADA INITIO and 30 mg oral Medical Affairs @Alkermes. This article is promotional able (LAIs), with my first of ARISTADA are informed by years of Alkermes’ at the time of the first ARISTADA content sponsored by Alkermes. publication on LAIs dating back to the 1980s.3 long-acting drug research and development. dose, aripiprazole concentrations reach relevant ALKERMES® is a registered trademark of Alkermes, I joined Alkermes in 2016 not only to con- levels within four days.4 Inc. and ARISTADA® and logo are registered trademarks tinue my work on LAIs, but also to become a Understanding Slow Dissolution Particle size is at the crux of dissolution, where of Alkermes Pharma Ireland Limited and ARISTADA INITIO™ is a trademark of Alkermes Pharma Ireland part of a company known for its innovation in One of the major drivers behind the develop- the rate is a function of surface rate of exposure. Limited, used by Alkermes, Inc., under license. ©2018 drug-delivery technology. I was particularly ment of both ARISTADA and ARISTADA INITIO Similar to how ice cubes melt faster than larger Alkermes, Inc. All rights reserved. drawn to the company’s commitment to patient- is Alkermes’ understanding of dissolution, or ice blocks, the smaller particle size of ARISTADA centered drug development for people living rate of release. Slowing the rate of dissolution INITIO enables faster dissolution, releasing ar- REFERENCES 1. Weiden PJ, Olfson M. Cost of relapse in schizophrenia. with schizophrenia. Since then, I’ve been for- allows for longer dosing intervals and a sustained ipiprazole at a faster rate while achieving blood Schizophr. Bull. 1995;21(3):419-429. tunate to be a part of a broader team of excep- release with an extended pharmacokinetic pro- concentrations comparable to the 21-day initia- 2. Weiden PJ, Rapkin B, Mott T, Zygmunt A, Goldman D, Frances A: Rating of Medication Influences (ROMI) scale in schizophre- 6,7 12 tionally talented individuals who have worked file of ARISTADA. tion regimen. nia. Schizophr. Bull. 1994;20:297–310. to provide more LAI options for the treatment Release of an active medication is based on 3. Weiden PJ, Frances A: Promoting compliance with outpatient of schizophrenia. The notable milestones speak two drug design factors: the and the Difference between ARISTADA and drug treatment. Hosp Community Psychiatry 1987;38: 1158–60. 4. Alkermes, Inc. Prescribing Information: ARISTADA INITIO. 6 for themselves and include the 2015 FDA ap- suspension. ARISTADA is a prodrug of aripip- ARISTADA INITIO Waltham, MA; 2018. proval of ARISTADA® (aripiprazole lauroxil), an razole, meaning when the medication is injected, The primary formulation difference between 5. Alkermes, Inc. Prescribing Information: ARISTADA. Waltham, LAI for the treatment of it is initially in inactive form formulated as ar- ARISTADA and ARISTADA INITIO is the differing MA; 2018. 6. Remenar JF. Making the leap from daily oral dosing to long-act- schizophrenia in adults, the subsequent 2017 ipiprazole lauroxil, which is then converted into particle size, which results in a faster dissolution ing injectables: lessons from the antipsychotics. Mol. Pharm. FDA approval of a two-month option for ARIS- active form of aripiprazole through the body’s rate for ARISTADA INITIO.11 Both contain aripip- 2014;11(6):1739-1749. TADA (1064 mg), and, most recently, the FDA normal metabolic processes.5,8 The prodrug was razole lauroxil, but ARISTADA INITIO and ARIS- 7. Hard M, Mills R, Sadler B, Turncliff R, Citrome L. Aripiprazole Lauroxil Pharmacokinetic Profile of This Long-Acting Injectable approval of ARISTADA INITIO™ (aripiprazole developed using Alkermes’ proprietary platform, TADA are not interchangeable due to differing Antipsychotic in Persons With Schizophrenia. J. Clin. Psycho- lauroxil).4,5 ARISTADA INITIO, in combination LinkeRx®. The suspension is made of aqueous pharmacokinetic profiles. ARISTADA INITIO is pharmacol. June 2017;37(3):289-295. 8. Turncliff R, Hard M, Du Y, Risinger R, Ehrich EW. Relative bio- with oral aripiprazole, is indicated for the ini- liquid and ARISTADA particles, which contributes intended for single administration only and availability and safety of aripiprazole lauroxil, a novel once- tiation of ARISTADA when used for the treatment to the dissolution at which the resulting active should not be substituted for ARISTADA.4 monthly, long-acting injectable atypical antipsychotic, following 4 7 deltoid and gluteal administration in adult subjects with schizo- of schizophrenia in adults. Both ARISTADA aripiprazole is released. The particle size for ARISTADA is comprised of micron-sized par- phrenia. Schizophr. Res. 2014;159(2-3):404-410. INITIO and ARISTADA carry a Boxed Warning ARISTADA was designed for slow release, which ticles, whereas ARISTADA INITIO utilizes Alkermes' 9. Hard M, Mills R, Sadler B, et a. Pharmacokinetic Profile of a for increased mortality in elderly patients with enabled the active medication to maintain con- NanoCrystal® technology to create much smaller- 2-Month Dose Regimen of Aripiprazole Lauroxil: A Phase I Study and a Population Pharmacokinetic Model. CNS drugs. 2017; 9 12 -related psychosis. ARISTADA INITIO centrations for as long as two months. sized particles in the nanometer range. As a result, Jul;31(7):617-624. and ARISTADA are not approved to treat de- physicians can initiate appropriate patients onto 10. Brissos S, Veguilla M, Taylor D, Martinez V. The Role of Long-Act- ing Injectable Antipsychotics in Schizophrenia: a Critical Ap- mentia-related psychosis. any dose of ARISTADA in one day with a single The Challenge of LAI Initiation praisal. Ther Adv Psychopharmacol. 2014;4(5):198-219. Long-acting injectables can face a common oral dose of 30 mg aripiprazole and a single of 11. Hard M, Wehr A, Sadler B, Mills R, Moltke L. Population Pharma- What is ARISTADA INITIO? challenge: there can be a delay between the first injection of ARISTADA INITIO (675 mg).4 cokinetic Analysis and Model-Based Simulations of Aripiprazole for a 1-Day Initiation Regimen for the Long-Acting Antipsychotic ARISTADA INITIO marks the latest milestone injection and the achievement of relevant thera- Aripiprazole Lauroxil. Eur. J. Drug Metab. Pharmacokinet. 2018 by Alkermes regarding available long-acting peutic levels of active ingredient.8 However, there Summary (epub ahead of print). options for people living with schizophrenia. are ways to address this sub-therapeutic period. Schizophrenia can be a disabling disorder, so 12. Hard M, Wehr A, Du Y, Weiden P, Walling D, Moltke L. Pharma- cokinetic Evaluation of a 1-Day Treatment Initiation Option for For patients with established tolerability to oral One way is to provide continued oral antipsychot- it is critical that new treatments address the Starting Long-Acting Aripiprazole Lauroxil for Schizophrenia. J. aripiprazole, one injection of ARISTADA INITIO, ics for a period of time until the LAI “catches up.” needs and symptoms that patients face. I’m proud Clin. Psychopharmacol. 2018 (epub ahead of print). 13. Walling D, Hard M, Wehr A, Du Y, Weiden P, Moltke L. Aripipra- in combination with a single 30 mg dose of oral Another way to bridge this gap is through load- to work at Alkermes and see first-hand the ad- zole Lauroxil NanoCrystal® Dispersion: A Potential 1-day Initia- aripiprazole, offers physicians another way to ing doses, which deliver more of an LAI medica- vances that have taken place in a relatively short tion Regimen for Long-Acting Aripiprazole Lauroxil. Poster pre- sented at: American Psychiatric Association Annual Meeting; begin ARISTADA treatment that, for the first tion upfront and then lower the amount later on time (at least short as drug development timelines May 5-9, 2018; New York City, NY. time, enables the initiation of patients onto any according to the intended long-term regimen.10 go!). Since I have dose of ARISTADA—including the two-month For ARISTADA, until now, the only way to initiate been here, I have option—on day one.4 Previously, the standard had been to prescribe 21 days of concomitant worked on the initiation regimen for ARISTADA included 21 oral aripiprazole in conjunction with the first dose launch of the first- consecutive days of oral aripiprazole starting of ARISTADA.5 Alkermes recognized the need to ever two-month LAI with the first ARISTADA dose, which remains provide another option to start ARISTADA treat- formulation (ARIS- an available option for starting ARISTADA.5 ment and began focusing our efforts on finding TADA 1064 mg), The particle size for ARISTADA was designed for slow release.8 ARISTADA is made into drug parti- an alternative to the 21-day initiation. The result and, now, a way to cles, which are then placed into a suspension and then deposited into the tissue upon injection.5 Alkermes and the New Generation of Atypical is a one-day initiation regimen with one injection initiate patients onto LAIs of ARISTADA INITIO in combination with a single that formulation on By the 1990s, atypical antipsychotics were dose of oral aripiprazole.4 day one. I also now more widely prescribed for schizophrenia than better appreciate the older generation of antipsychotics. How- ARISTADA INITIO and Faster Dissolution that the work the ever, the availability of atypical LAIs lagged ARISTADA is formulated as a suspension with industry is doing to behind, and for about a decade the only LAIs micrometer-sized drug particles, placed into an push forward ad- available were the older, first generation LAIs. aqueous solution. Upon injection, these particles vancements is es- The delay between first available oral atypical dissolve slowly over time. ARISTADA INITIO is sential to improving and first atypical LAI speaks to the daunting the same prodrug of aripiprazole lauroxil. The patient care. technologic challenges inherent in the develop- main difference is the particle size made up of Alkermes’ LAI The nano-sized drug particles of ARISTADA INITIO enable faster release than the micron-sized ment of long-acting formulations. 6 aripiprazole lauroxil molecules that is put into technology has particles of ARISTADA. This illustrates how particle size affects the dissolution.12,13

6 Psych Congress Network • Summer 2018 • psychcongress.com Please see adjacent page for additional Important Safety Information. INDICATION and IMPORTANT SAFETY Metabolic Changes: Atypical antipsychotic drugs Body Temperature Regulation: Disruption of the INFORMATION for ARISTADA INITIO™ have been associated with metabolic changes body’s ability to reduce core body temperature has that include: been attributed to antipsychotic agents. Advise (aripiprazole lauroxil) and ARISTADA® • /Diabetes Mellitus: patients regarding appropriate care in avoiding (aripiprazole lauroxil) extended- Hyperglycemia, in some cases extreme and overheating and dehydration. Appropriate care is release injectable suspension, for associated with ketoacidosis, coma, or death, advised for patients who may exercise strenuously, intramuscular use has been reported in patients treated with may be exposed to extreme heat, receive atypical antipsychotics. There have been concomitant medication with anticholinergic INDICATION reports of hyperglycemia in patients treated activity, or are subject to dehydration. ARISTADA INITIO, in combination with oral with oral aripiprazole. Patients with diabetes Dysphagia: Esophageal dysmotility and aspiration aripiprazole, is indicated for the initiation of should be regularly monitored for worsening have been associated with antipsychotic drug use; ARISTADA when used for the treatment of of glucose control; those with risk factors use caution in patients at risk for aspiration schizophrenia in adults. for diabetes should undergo baseline and pneumonia. periodic fasting blood glucose testing. Any ARISTADA is indicated for the treatment of patient treated with atypical antipsychotics Concomitant Medication: ARISTADA INITIO is schizophrenia. should be monitored for symptoms of only available at a single strength as a single dose hyperglycemia, including polydipsia, polyuria, pre-filled syringe, so dosage adjustments are not IMPORTANT SAFETY INFORMATION polyphagia, and weakness. Patients who possible. Avoid use in patients who are known develop symptoms of hyperglycemia should CYP2D6 poor metabolizers or taking strong also undergo fasting blood glucose testing. CYP3A4 inhibitors, strong CYP2D6 inhibitors, or WARNING: INCREASED MORTALITY strong CYP3A4 inducers, antihypertensive drugs or IN ELDERLY PATIENTS WITH In some cases, hyperglycemia has resolved when the atypical antipsychotic was benzodiazepines. DEMENTIA-RELATED PSYCHOSIS discontinued; however, some patients require Depending on the ARISTADA dose, adjustments Elderly patients with dementia-related continuation of antidiabetic treatment may be recommended if patients are 1) known as psychosis treated with antipsychotic drugs despite discontinuation of the suspect drug. CYP2D6 poor metabolizers and/or 2) taking CYP3A4 inhibitors, CYP2D6 inhibitors, or CYP3A4 are at an increased risk of death. ARISTADA • Dyslipidemia: Undesirable alterations in lipids INITIO and ARISTADA are not approved for have been observed in patients treated with inducers for greater than 2 weeks. Avoid use of the treatment of patients with dementia- atypical antipsychotics. ARISTADA 662 mg, 882 mg, or 1064 mg for related psychosis. patients taking both strong CYP3A4 inhibitors and • Weight Gain: Weight gain has been observed strong CYP2D6 inhibitors. (See Table 4 in the with atypical antipsychotic use. Clinical ARISTADA full Prescribing Information.) Contraindication: Known hypersensitivity reaction monitoring of weight is recommended. to aripiprazole. Reactions have ranged from Commonly Observed Adverse Reactions: In Pathological Gambling and Other Compulsive pruritus/urticaria to anaphylaxis. pharmacokinetic studies the safety profile of Behaviors: Compulsive or uncontrollable urges to ARISTADA INITIO was generally consistent with Cerebrovascular Adverse Reactions, Including gamble have been reported with use of aripiprazole. that observed for ARISTADA. The most common Increased incidence of cerebrovascular Stroke: Other compulsive urges less frequently reported adverse reaction (≥5% incidence and at least adverse reactions (e.g., stroke, transient ischemic include sexual urges, shopping, binge eating and twice the rate of placebo reported by patients attack), including fatalities, have been reported other impulsive or compulsive behaviors which may treated with ARISTADA 441 mg and 882 mg in placebo-controlled trials of elderly patients result in harm for the patient and others if not monthly) was . with dementia-related psychosis treated with recognized. Closely monitor patients and consider , aripiprazole, and . dose reduction or stopping aripiprazole if a patient Injection-Site Reactions: In pharmacokinetic studies ARISTADA INITIO and ARISTADA are not develops such urges. evaluating ARISTADA INITIO, the incidences of approved for the treatment of patients with injection-site reactions with ARISTADA INITIO were : Aripiprazole may dementia-related psychosis. similar to the incidence observed with ARISTADA. cause orthostatic hypotension which can be Injection-site reactions were reported by 4%, 5%, Potential for Dosing and Medication Errors: associated with dizziness, lightheadedness, and and 2% of patients treated with 441 mg ARISTADA Medication errors, including substitution and . Monitor heart rate and blood (monthly), 882 mg ARISTADA (monthly), and dispensing errors, between ARISTADA INITIO pressure, and warn patients with known placebo, respectively. Most of these were injection- and ARISTADA could occur. ARISTADA INITIO is cardiovascular or cerebrovascular disease and site pain and associated with the first injection and intended for single administration only. Do not risk of dehydration and syncope. decreased with each subsequent injection. Other substitute ARISTADA INITIO for ARISTADA Falls: Antipsychotics including ARISTADA INITIO injection-site reactions (induration, swelling, and because of differing pharmacokinetic profiles. and ARISTADA may cause , postural redness) occurred at less than 1%. A Neuroleptic Malignant Syndrome (NMS): hypotension or motor and sensory instability which : Symptoms of dystonia, prolonged potentially fatal symptom complex may occur with may lead to falls and subsequent injury. Upon abnormal contractions of muscle groups, may occur administration of antipsychotic drugs, including initiating treatment and recurrently, complete fall in susceptible individuals during the first days of ARISTADA INITIO and ARISTADA. Clinical risk assessments as appropriate. treatment and at low doses. manifestations of NMS include hyperpyrexia, muscle , , and : rigidity, altered mental status, and evidence of Pregnancy/Nursing: May cause extrapyramidal Leukopenia, neutropenia and agranulocytosis autonomic instability (irregular pulse or blood and/or withdrawal symptoms in neonates with have been reported with antipsychotics. Monitor pressure, tachycardia, diaphoresis, and cardiac third trimester exposure. Advise patients to notify complete blood count in patients with pre-existing dysrhythmia). Additional signs may include their healthcare provider of a known or suspected low white blood cell count (WBC)/absolute elevated creatine phosphokinase, myoglobinuria pregnancy. Inform patients that there is a pregnancy neutrophil count or history of drug-induced (rhabdomyolysis), and acute renal failure. The exposure registry that monitors pregnancy leukopenia/neutropenia. Discontinue ARISTADA management of NMS should include: 1) immediate outcomes in women exposed to ARISTADA INITIO INITIO and/or ARISTADA at the first sign of a discontinuation of antipsychotic drugs and and/or ARISTADA during pregnancy. Aripiprazole is clinically significant decline in WBC and in severely other drugs not essential to concurrent therapy; present in human breast milk. The benefits of neutropenic patients. 2) intensive symptomatic treatment and medical breastfeeding should be considered along with the monitoring; and 3) treatment of any concomitant Seizures: Use with caution in patients with a mother’s clinical need for ARISTADA INITIO and/or serious medical problems for which specific history of seizures or with conditions that lower ARISTADA and any potential adverse effects on the treatments are available. the seizure threshold. infant from ARISTADA INITIO and/or ARISTADA or from the underlying maternal condition. Tardive Dyskinesia (TD): The risk of developing TD Potential for Cognitive and Motor Impairment: (a syndrome of abnormal, involuntary movements) ARISTADA INITIO and ARISTADA may impair and the potential for it to become irreversible are judgment, thinking, or motor skills. Patients should Please see Brief Summaries of full believed to increase as the duration of treatment be cautioned about operating hazardous machinery, Prescribing Information, including and the total cumulative dose of antipsychotic including automobiles, until they are certain therapy Boxed Warning, for ARISTADA INITIO increase. The syndrome can develop, although with ARISTADA INITIO and/or ARISTADA do not and ARISTADA on the following pages. much less commonly, after relatively brief treatment affect them adversely. periods at low doses. Prescribing antipsychotics should be consistent with the need to minimize TD. Discontinue ARISTADA if clinically appropriate. TD may remit, partially or completely, if antipsychotic treatment is withdrawn.

ALKERMES® is a registered trademark of Alkermes, Inc. and ARISTADA® and logo are registered trademarks of Alkermes Pharma Ireland Limited and ARISTADA INITIO™ is a trademark of Alkermes Pharma Ireland Limited, used by Alkermes, Inc., under license. ©2018 Alkermes, Inc. All rights reserved. Printed in the U.S.A. ARI-003430-v1 ARISTADA INITIO™ (aripiprazole lauroxil) extended-release injectable suspension, Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic for intramuscular use changes that include hyperglycemia/diabetes mellitus, dyslipidemia, and weight gain. While BRIEF SUMMARY OF PRESCRIBING INFORMATION all drugs in the class have been shown to produce some metabolic changes, each drug has (For complete details, please see full Prescribing Information and Medication Guide.) its own specific risk profile. Hyperglycemia/Diabetes Mellitus: Hyperglycemia, in some cases extreme and WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH associated with ketoacidosis or hyperosmolar coma or death, has been reported in DEMENTIA-RELATED PSYCHOSIS patients treated with atypical antipsychotics. There have been reports of hyperglycemia in • Elderly patients with dementia-related psychosis treated with antipsychotic patients treated with oral aripiprazole. Assessment of the relationship between atypical drugs are at an increased risk of death antipsychotic use and glucose abnormalities is complicated by the possibility of an • ARISTADA INITIO is not approved for the treatment of patients with increased background risk of diabetes mellitus in patients with schizophrenia and the dementia-related psychosis increasing incidence of diabetes mellitus in the general population. Given these confounders, the relationship between atypical antipsychotic use and hyperglycemia- INDICATIONS AND USAGE: ARISTADA INITIO, in combination with oral aripiprazole, is indicated related adverse events is not completely understood. However, epidemiological studies for the initiation of ARISTADA® (aripiprazole lauroxil) when used for the treatment of suggest an increased risk of hyperglycemia-related adverse reactions in patients treated schizophrenia in adults. with the atypical antipsychotics. CONTRAINDICATIONS: ARISTADA INITIO is contraindicated in patients with a known Patients with an established diagnosis of diabetes mellitus who are started on atypical hypersensitivity reaction to aripiprazole. Hypersensitivity reactions have ranged from antipsychotics should be monitored regularly for worsening of glucose control. Patients pruritus/urticaria to anaphylaxis. with risk factors for diabetes mellitus (e.g., obesity, family history of diabetes) who are starting treatment with atypical antipsychotics should undergo fasting blood glucose WARNINGS AND PRECAUTIONS testing at the beginning of treatment and periodically during treatment. Any patient Increased Mortality in Elderly Patients With Dementia-related Psychosis: Elderly patients treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms death. Analyses of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients of hyperglycemia during treatment with atypical antipsychotics should undergo fasting taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between blood glucose testing. In some cases, hyperglycemia has resolved when the atypical 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a was discontinued; however, some patients require continuation of anti- 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared diabetic treatment despite discontinuation of the suspect drug. to a rate of about 2.6% in the placebo group. Dyslipidemia: Undesirable alterations in lipids have been observed in patients treated Although the causes of death were varied, most of the deaths appeared to be either with atypical antipsychotics. cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Weight Gain: Weight gain has been observed with atypical antipsychotic use. Clinical Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with monitoring of weight is recommended. conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as Pathological Gambling and Other Compulsive Behaviors: Post-marketing case reports opposed to some characteristic(s) of the patients is not clear. ARISTADA INITIO is not approved suggest that patients can experience intense urges, particularly for gambling, and the for the treatment of patients with dementia-related psychosis. inability to control these urges while taking aripiprazole. Other compulsive urges, reported less frequently include: sexual urges, shopping, eating or binge eating, and other impulsive Cerebrovascular Adverse Reactions, Including Stroke: In placebo-controlled trials with or compulsive behaviors. Because patients may not recognize these behaviors as risperidone, aripiprazole, and olanzapine in elderly patients with dementia, there was a higher abnormal, it is important for prescribers to ask patients or their caregivers specifically incidence of cerebrovascular adverse reactions (cerebrovascular accidents and transient about the development of new or intense gambling urges, compulsive sexual urges, ischemic attacks) including fatalities compared to placebo-treated patients. ARISTADA INITIO compulsive shopping, binge or compulsive eating, or other urges while being treated with is not approved for the treatment of patients with dementia-related psychosis. aripiprazole. It should be noted that impulse-control symptoms can be associated with the Potential for Dosing and Medication Errors: Medication errors, including substitution and underlying disorder. In some cases, although not all, urges were reported to have stopped dispensing errors, between ARISTADA INITIO and ARISTADA could occur. ARISTADA INITIO is when the dose was reduced or the medication was discontinued. Compulsive behaviors intended for single administration only. Do not substitute ARISTADA INITIO for ARISTADA may result in harm for the patient and others if not recognized. If compulsive urges because of differing pharmacokinetic profiles. develop, consider discontinuing aripiprazole. Neuroleptic Malignant Syndrome: A potentially fatal symptom complex sometimes referred Orthostatic Hypotension: Aripiprazole may cause orthostatic hypotension, perhaps due to as Neuroleptic Malignant Syndrome (NMS) may occur in association with antipsychotic to its a1- antagonism. Associated adverse reactions related to drugs, including ARISTADA INITIO. Clinical manifestations of NMS are hyperpyrexia, muscle orthostatic hypotension can include dizziness, lightheadedness and tachycardia. rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood Generally, these risks are greatest at the beginning of treatment and during dose pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include escalation. Patients at increased risk of these adverse reactions or at increased risk of elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. developing complications from hypotension include those with dehydration, hypovolemia, The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a treatment with antihypertensive medication, history of cardiovascular disease (e.g., heart diagnosis, it is important to identify cases in which the clinical presentation includes both failure, myocardial infarction, ischemia, or conduction abnormalities), history of serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or cerebrovascular disease, as well as patients who are antipsychotic-naïve. In such inadequately treated extrapyramidal signs and symptoms (EPS). Other important patients, monitor orthostatic vital signs. considerations in the differential diagnosis include central anticholinergic toxicity, heat Falls: Antipsychotics including ARISTADA INITIO may cause somnolence, postural stroke, drug fever, and primary central nervous system pathology. hypotension, or motor and sensory instability, which may lead to falls and, consequently, The management of NMS should include: (1) immediate discontinuation of antipsychotic fractures or other injuries. For patients with diseases, conditions, or medications that could drugs and other drugs not essential to concurrent therapy; (2) intensive symptomatic exacerbate these effects, complete fall risk assessments when initiating antipsychotic treatment and medical monitoring; and (3) treatment of any concomitant serious medical treatment and recurrently for those patients on long-term antipsychotic therapy. problems for which specific treatments are available. There is no general agreement about Leukopenia, Neutropenia, and Agranulocytosis: In clinical trials and/or postmarketing specific pharmacological treatment regimens for uncomplicated NMS. experience, events of leukopenia and neutropenia have been reported temporally related to If a patient appears to require antipsychotic drug treatment after recovery from NMS, reintroduction antipsychotic agents. Agranulocytosis has also been reported. of drug therapy should be closely monitored, since recurrences of NMS have been reported. Possible risk factors for leukopenia/neutropenia include pre-existing low white blood cell Tardive Dyskinesia: A syndrome of potentially irreversible, involuntary, dyskinetic count (WBC)/absolute neutrophil count (ANC) and history of drug-induced leukopenia/ movements may develop in patients treated with antipsychotic drugs. Although the neutropenia. In patients with a history of a clinically significant low WBC/ANC or drug-induced prevalence of the syndrome appears to be highest among the elderly, especially elderly leukopenia/neutropenia, perform a complete blood count (CBC) frequently during the first few women, it is impossible to predict which patients will develop the syndrome. Whether months of therapy. In such patients, consider discontinuation of antipsychotics at the first sign antipsychotic drug products differ in their potential to cause tardive dyskinesia is unknown. of a clinical significant decline in WBC in the absence of other causative factors. The risk of developing tardive dyskinesia and the likelihood that it will become irreversible Monitor patients with clinically significant neutropenia for fever or other symptoms or signs appear to increase as the duration of treatment and the total cumulative dose of of infection and treat promptly if such symptoms or signs occur. Discontinue antipsychotics antipsychotic drugs administered to the patient increase, but the syndrome can develop in patients with severe neutropenia (absolute neutrophil count <1000/mm3) and follow after relatively brief treatment periods at low doses, although this is uncommon. their WBC until recovery. Tardive dyskinesia may remit, partially or completely, if antipsychotic treatment is Seizures: As with other antipsychotic drugs, use ARISTADA INITIO cautiously in patients with withdrawn. Antipsychotic treatment itself may suppress (or partially suppress) the signs a history of seizures or with conditions that lower the seizure threshold. Conditions that lower and symptoms of the syndrome and may thus mask the underlying process. The effect of the seizure threshold may be more prevalent in a population of 65 years or older. symptomatic suppression on the long-term course of the syndrome is unknown. Potential for Cognitive and Motor Impairment: ARISTADA INITIO, like other antipsychotics, Given these considerations, antipsychotics should be prescribed in a manner that is most has the potential to impair judgment, thinking or motor skills. Patients should be cautioned likely to minimize the occurrence of tardive dyskinesia. Chronic antipsychotic treatment about operating hazardous machinery, including automobiles, until they are reasonably should generally be reserved for patients who suffer from a chronic illness that is known to certain that therapy with ARISTADA INITIO does not affect them adversely. respond to antipsychotic drugs. In patients who do require chronic treatment, the smallest Body Temperature Regulation: Disruption of the body’s ability to reduce core body dose and the shortest duration of treatment producing a satisfactory clinical response temperature has been attributed to antipsychotic agents. Appropriate care is advised should be sought. The need for continued treatment should be reassessed periodically. when prescribing ARISTADA INITIO for patients who will be experiencing conditions If signs and symptoms of tardive dyskinesia appear in a patient treated with antipsychotics, which may contribute to an elevation in core body temperature, (e.g., exercising consider discontinuation of the antipsychotic drug. However, some patients may require strenuously, exposure to extreme heat, receiving concomitant medication with antipsychotic treatment despite the presence of the syndrome. anticholinergic activity, or being subject to dehydration). Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotic Skin and Subcutaneous Tissue Disorders: rash, hyperhidrosis, pruritus, photosensitivity drug use. ARISTADA INITIO and other antipsychotic drugs should be used cautiously in reaction, alopecia, urticaria patients at risk for aspiration pneumonia. Vascular Disorders: hypotension, ADVERSE REACTIONS Postmarketing Experience: The following adverse reactions have been identified during post-approval use of oral aripiprazole. Because these reactions are reported voluntarily Clinical Studies Experience: Because clinical trials are conducted under widely varying from a population of uncertain size, it is not always possible to reliably estimate their conditions, adverse reaction rates observed in the clinical trials of a drug cannot be frequency or to establish a causal relationship to drug exposure: occurrences of allergic directly compared to rates in the clinical trials of another drug and may not reflect the reaction (anaphylactic reaction, angioedema, laryngospasm, pruritus/urticaria, or rates observed in practice. oropharyngeal spasm), pathological gambling, hiccups, and blood glucose fluctuation. The safety of ARISTADA INITIO, in combination with oral aripiprazole, for the initiation of ARISTADA when used for the treatment of schizophrenia in adults has been established DRUG INTERACTIONS and is based on clinical trials of ARISTADA (aripiprazole lauroxil) including 1019 adult Table 1: Clinically Important Drug Interactions With ARISTADA INITIO patients with schizophrenia. Strong CYP3A4 Inhibitors and CYP2D6 Inhibitors Patient Exposure: ARISTADA INITIO has been evaluated for safety in 170 adult patients in clinical trials in schizophrenia. Clinical Impact Concomitant use of oral aripiprazole with strong CYP3A4 or CYP2D6 In pharmacokinetic studies, the safety profile of ARISTADA INITIO was generally inhibitors increased the exposure of aripiprazole compared to the use consistent with that observed for ARISTADA. of oral aripiprazole alone ARISTADA (Aripiprazole Lauroxil) Trials in Adults with Schizophrenia Intervention Avoid concomitant use of ARISTADA INITIO with strong CYP3A4 or Commonly Observed Adverse Reactions with Aripiprazole Lauroxil: The most common adverse strong CYP2D6 inhibitors because the dosage of ARISTADA INITIO reaction (incidence ≥5% and at least twice the rate of placebo in patients treated with aripiprazole cannot be modified lauroxil) was akathisia. Adverse Reactions Occurring at an Incidence of 2% or More in Aripiprazole Lauroxil-Treated Examples , clarithromycin, , , paroxetine Patients: Adverse reactions associated with the use of aripiprazole lauroxil (incidence of 2% or Strong CYP3A4 Inducers greater, rounded to the nearest percent and aripiprazole lauroxil incidence greater than placebo) that occurred were: injection site pain, increased weight, increased blood creatinine Clinical Impact Concomitant use of oral aripiprazole and carbamazepine decreased the phosphokinase, akathisia, headache, insomnia, and restlessness. exposure of aripiprazole compared to the use of oral aripiprazole alone Injection Site Reactions Intervention Avoid concomitant use of ARISTADA INITIO with strong CYP3A4 ARISTADA INITIO inducers because the dosage of ARISTADA INITIO cannot be modified. In pharmacokinetic studies evaluating ARISTADA INITIO, the incidences of injection site reactions with ARISTADA INITIO were similar to the incidence observed with aripiprazole lauroxil. Examples carbamazepine, rifampin ARISTADA (Aripiprazole Lauroxil) Antihypertensive Drugs Injection site reactions were reported by 4% of patients treated with 441 mg aripiprazole lauroxil and 5% of patients treated with 882 mg aripiprazole lauroxil compared to 2% of patients treated Clinical Impact Due to its alpha adrenergic antagonism, aripiprazole has the potential with placebo. Most of these were injection site pain (3%, 4% and 2% in the 441 mg aripiprazole to enhance the effect of certain antihypertensive agents. lauroxil, 882 mg aripiprazole lauroxil and placebo groups, respectively). Other injection site Intervention Avoid concomitant use of ARISTADA INITIO with antihypertensive reactions (induration, swelling and redness) occurred at less than 1%. drugs because the dosage of ARISTADA INITIO cannot be modified. Extrapyramidal Symptoms: In a schizophrenia efficacy study in aripiprazole lauroxil- treated patients, the incidence of other EPS-related events, excluding akathisia and Examples , lisinopril, restlessness, was 5% and 7% for patients on 441 mg and 882 mg, respectively, versus Benzodiazepines 4% for placebo-treated patients. Dystonia: Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may Clinical Impact The intensity of sedation was greater with the combination of oral occur in susceptible individuals during the first few days of treatment. Dystonic symptoms aripiprazole and lorazepam as compared to that observed with aripiprazole include: spasm of the neck muscles, sometimes progressing to tightness of the throat, alone. The orthostatic hypotension observed was greater with the swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While these combination as compared to that observed with lorazepam alone. symptoms can occur at low doses, they occur more frequently and with greater severity with Intervention Avoid concomitant use of ARISTADA INITIO with benzodiazepines high potency and at higher doses of first generation antipsychotic drugs. An elevated risk of because the dosage of ARISTADA INITIO cannot be modified. acute dystonia is observed in males and younger age groups. Other Adverse Reactions Observed in Clinical Studies with Aripiprazole Lauroxil: The Examples lorazepam following listing does not include reactions: 1) already listed in previous tables or elsewhere in labeling, 2) for which a drug cause was remote, 3) which were so general as to be USE IN SPECIFIC POPULATIONS uninformative, 4) which were not considered to have significant clinical implications, or Pregnancy 5) which occurred at a rate equal to or less than placebo. Pregnancy Exposure Registry: There is a pregnancy exposure registry that monitors Cardiac – angina pectoris, tachycardia, palpitations pregnancy outcomes in women exposed to ARISTADA INITIO during pregnancy. For more Gastrointestinal disorders – constipation, dry mouth information, contact the National Pregnancy Registry for Atypical Antipsychotics at General disorders – asthenia 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/ Musculoskeletal – muscular weakness pregnancyregistry/. Nervous system disorders – dizziness Risk Summary: Neonates exposed to antipsychotic drugs during the third trimester of Psychiatric disorders – anxiety, suicide pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. Adverse Reactions Reported in Clinical Trials with Oral Aripiprazole: The following is a Limited published data on aripiprazole use in pregnant women are not sufficient to inform list of additional adverse reactions that have been reported in clinical trials with oral any drug-associated risks for birth defects or miscarriage. No teratogenicity was observed in aripiprazole and not reported above for ARISTADA INITIO or aripiprazole lauroxil. animal reproductive studies with intramuscular administration of aripiprazole lauroxil to rats Blood and Lymphatic System Disorders: thrombocytopenia and rabbits during organogenesis at doses up to 8 and 23 times, respectively, the maximum Cardiac Disorders: , atrial flutter, cardiorespiratory arrest, atrioventricular block, atrial recommended human dose (MRHD) of 675 mg based on body surface area (mg/m2). fibrillation, myocardial ischemia, myocardial infarction, cardiopulmonary failure However, aripiprazole caused developmental toxicity and possible teratogenic effects in rats Eye Disorders: photophobia, diplopia and rabbits. The background risk of major birth defects and miscarriage for the indicated Gastrointestinal Disorders: gastroesophageal reflux disease population are unknown. In the U.S. general population, the estimated background risk of General Disorders and Administration-Site Conditions: peripheral edema, chest pain, face edema major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and Hepatobiliary Disorders: hepatitis, jaundice 15-20%, respectively. Advise pregnant women of the potential risk to a fetus. Immune System Disorders: hypersensitivity Clinical Considerations: Fetal/Neonatal Adverse Reactions: Extrapyramidal and/or Injury, Poisoning, and Procedural Complications: fall, heat stroke withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, Investigations: weight decreased, hepatic enzyme increased, blood glucose increased, blood respiratory distress and feeding disorder have been reported in neonates who were exposed lactate dehydrogenase increased, gamma glutamyl transferase increased, blood prolactin to antipsychotic drugs during the third trimester of pregnancy. These symptoms have varied increased, blood urea increased, blood creatinine increased, blood bilirubin increased, electrocardiogram QT prolonged, glycosylated hemoglobin increased in severity. Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately. Some neonates recover within hours or days without specific Metabolism and Nutrition Disorders: anorexia, , hyponatremia, hypoglycemia Musculoskeletal and Connective Tissue Disorders: muscle tightness, rhabdomyolysis, treatment; others required prolonged hospitalization. mobility decreased Data: Animal Data for ARISTADA (Aripiprazole Lauroxil): Aripiprazole lauroxil did not cause Nervous System Disorders: memory impairment, cogwheel rigidity, hypokinesia, adverse developmental or maternal effects in rats or rabbits when administered bradykinesia, akinesia, myoclonus, coordination abnormal, speech disorder, choreoathetosis intramuscularly during the period of organogenesis at doses of 18, 49, or 144 mg/animal in Psychiatric Disorders: , loss of libido, delirium, libido increased, anorgasmia, tic, pregnant rats which are approximately 1 to 8 times the MRHD of 675 mg based on mg/m2, homicidal ideation, catatonia, sleep walking and at doses of 241, 723, and 2893 mg/animal in pregnant rabbits which are approximately Renal and Urinary Disorders: urinary retention, nocturia 2 to 23 times the MRHD based on mg/m2. However, aripiprazole caused developmental Reproductive System and Breast Disorders: erectile dysfunction, gynaecomastia, toxicity and possible teratogenic effects in rats and rabbits [see Data below]. menstruation irregular, amenorrhea, breast pain, priapism Animal Data for Aripiprazole: Pregnant rats were treated with oral doses of 3, 10, and Respiratory, Thoracic, and Mediastinal Disorders: nasal congestion, dyspnea 30 mg/kg/day which are approximately 1 to 10 times the oral MRHD of 30 mg/day based on mg/m2 of aripiprazole during the period of organogenesis. Treatment at the highest ARISTADA® (aripiprazole lauroxil) extended-release injectable suspension, Metabolic Changes: Atypical antipsychotic drugs have been associated with dose caused a slight prolongation of gestation and delay in fetal development, as for intramuscular use metabolic changes that include hyperglycemia/diabetes mellitus, dyslipidemia, and evidenced by decreased fetal weight, and undescended testes. Delayed skeletal BRIEF SUMMARY OF PRESCRIBING INFORMATION weight gain. While all drugs in the class have been shown to produce some metabolic 2 ossification was observed at 3 and 10 times the oral MRHD based on mg/m . (For complete details, please see full Prescribing Information and Medication Guide.) changes, each drug has its own specific risk profile. At 3 and 10 times the oral MRHD based on mg/m2, delivered offspring had decreased Hyperglycemia/Diabetes Mellitus: Hyperglycemia, in some cases extreme and body weights. Increased incidences of hepatodiaphragmatic nodules and diaphragmatic WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH associated with ketoacidosis or hyperosmolar coma or death, has been reported in hernia were observed in offspring from the highest dose group (the other dose groups DEMENTIA-RELATED PSYCHOSIS patients treated with atypical antipsychotics. There have been reports of hyperglycemia were not examined for these findings). A low incidence of diaphragmatic hernia was also • Elderly patients with dementia-related psychosis treated with antipsychotic in patients treated with oral aripiprazole. Assessment of the relationship between atypical seen in the fetuses exposed to the highest dose. Postnatally, delayed vaginal opening drugs are at an increased risk of death antipsychotic use and glucose abnormalities is complicated by the possibility of an was seen at 3 and 10 times the oral MRHD based on mg/m2 and impaired reproductive • ARISTADA is not approved for the treatment of patients with increased background risk of diabetes mellitus in patients with schizophrenia and performance (decreased fertility rate, corpora lutea, implants, live fetuses, and increased dementia-related psychosis the increasing incidence of diabetes mellitus in the general population. Given these post-implantation loss, likely mediated through effects on female offspring) along with confounders, the relationship between atypical antipsychotic use and hyperglycemia- some maternal toxicity were seen at the highest dose; however, there was no evidence INDICATIONS AND USAGE: ARISTADA is an atypical antipsychotic indicated for the related adverse events is not completely understood. However, epidemiological studies to suggest that these developmental effects were secondary to maternal toxicity. treatment of schizophrenia. suggest an increased risk of hyperglycemia-related adverse reactions in patients treated with the atypical antipsychotics. In pregnant rabbits treated with oral doses of 10, 30, and 100 mg/kg/day which are 2 to CONTRAINDICATIONS: ARISTADA is contraindicated in patients with a known 11 times human exposure at the oral MRHD based on AUC and 6 to 65 times the oral hypersensitivity reaction to aripiprazole. Hypersensitivity reactions have ranged from Patients with an established diagnosis of diabetes mellitus who are started on atypical MRHD based on mg/m2 of aripiprazole during the period of organogenesis decreased pruritus/urticaria to anaphylaxis. antipsychotics should be monitored regularly for worsening of glucose control. Patients maternal food consumption and increased abortions were seen at the highest dose as WARNINGS AND PRECAUTIONS with risk factors for diabetes mellitus (e.g., obesity, family history of diabetes) who are well as increased fetal mortality. Decreased fetal weight and increased incidence of Increased Mortality in Elderly Patients With Dementia-related Psychosis: Elderly starting treatment with atypical antipsychotics should undergo fasting blood glucose fused sternebrae were observed at 3 and 11 times the oral MRHD based on AUC. patients with dementia-related psychosis treated with antipsychotic drugs are at testing at the beginning of treatment and periodically during treatment. Any patient an increased risk of death. Analyses of 17 placebo-controlled trials (modal duration treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia In rats treated with oral doses of 3, 10, and 30 mg/kg/day which are 1 to 10 times the including polydipsia, polyuria, polyphagia, and weakness. Patients who develop 2 of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk oral MRHD based on mg/m of aripiprazole perinatally and postnatally (from day 17 of symptoms of hyperglycemia during treatment with atypical antipsychotics should gestation through day 21 postpartum), slight maternal toxicity and slightly prolonged of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved gestation were seen at the highest dose. An increase in stillbirths and decreases in pup when the atypical antipsychotic was discontinued; however, some patients require weight (persisting into adulthood) and survival were also seen at this dose. rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. continuation of anti-diabetic treatment despite discontinuation of the suspect drug. Lactation: Risk Summary: Aripiprazole is present in human breast milk; however, there are insufficient data to assess the amount in human milk, the effects on the breastfed Although the causes of death were varied, most of the deaths appeared to be either In the long-term, open-label schizophrenia study with ARISTADA, 14% of patients infant, or the effects on milk production. The development and health benefits of cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in with normal hemoglobin A1c (<5.7%) at baseline developed elevated levels (≥5.7%) breastfeeding should be considered along with the mother’s clinical need for ARISTADA nature. Observational studies suggest that, similar to atypical antipsychotic drugs, post-baseline. INITIO and any potential adverse effects on the breastfed infant from ARISTADA INITIO or treatment with conventional antipsychotic drugs may increase mortality. The extent to Dyslipidemia: Undesirable alterations in lipids have been observed in patients from the underlying maternal condition. which the findings of increased mortality in observational studies may be attributed to treated with atypical antipsychotics. the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. Pediatric Use: Safety and effectiveness of ARISTADA INITIO in pediatric patients have not been ARISTADA is not approved for the treatment of patients with dementia-related psychosis. In the long-term, open-label schizophrenia study with ARISTADA, shifts in baseline established. Cerebrovascular Adverse Reactions, Including Stroke: In placebo-controlled trials fasting total cholesterol from normal (<200 mg/dL) to high (≥240 mg/dL) were Geriatric Use: Safety and effectiveness of ARISTADA INITIO in patients >65 years of age with risperidone, aripiprazole, and olanzapine in elderly patients with dementia, there reported in 1% of patients; shifts in baseline fasting LDL cholesterol from normal have not been evaluated. was a higher incidence of cerebrovascular adverse reactions (cerebrovascular (<100 mg/dL) to high (≥160 mg/dL) were reported in 1% of patients; and shifts in Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an accidents and transient ischemic attacks) including fatalities compared to placebo- baseline fasting triglycerides from normal (<150 mg/dL) to high (≥200 mg/dL) increased risk of death. ARISTADA INITIO is not approved for the treatment of patients with treated patients. ARISTADA is not approved for the treatment of patients with dementia- were reported in 8% of patients. In the same study, shifts in baseline fasting total dementia-related psychosis. related psychosis. cholesterol from borderline (≥200 mg/dL and <240 mg/dL) to high (≥240 mg/dL) were reported in 15% of patients; shifts in baseline fasting LDL cholesterol from CYP2D6 Poor Metabolizers: Approximately 8% of Caucasians and 3-8% of Black/African Neuroleptic Malignant Syndrome: A potentially fatal symptom complex sometimes borderline (≥100 mg/dL and <160 mg/dL) to high (≥160 mg/dL) were reported in Americans cannot metabolize CYP2D6 substrates and are classified as poor metabolizers (PM). referred to as Neuroleptic Malignant Syndrome (NMS) may occur in association with 8% of patients; and shifts in baseline fasting triglycerides from borderline Avoid use of ARISTADA INITIO in these patients because dosage adjustments are not possible antipsychotic drugs, including ARISTADA. Clinical manifestations of NMS are hyperpyrexia, (≥150 mg/dL and <200 mg/dL) to high (≥200 mg/dL) were reported in 35% of (it is only available in one strength in a single-dose pre-filled syringe). muscle rigidity, altered mental status, and evidence of autonomic instability (irregular patients. In addition, the proportion of patients with shifts in fasting HDL cholesterol Hepatic and Renal Impairment: No dosage adjustment for ARISTADA INITIO is required based pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional from normal (≥40 mg/dL) to low (<40 mg/dL) was reported in 15% of patients. on a patient’s hepatic function (mild to severe hepatic impairment, Child-Pugh score between 5 signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and 15), or renal function (mild to severe renal impairment, glomerular filtration rate between and acute renal failure. Weight Gain: Weight gain has been observed with atypical antipsychotic use. Clinical 15 and 90 mL/minute). The diagnostic evaluation of patients with this syndrome is complicated. In arriving at monitoring of weight is recommended. Other Specific Populations: No dosage adjustment for ARISTADA INITIO is required on the a diagnosis, it is important to identify cases in which the clinical presentation includes The proportion of adult patients with weight gain ≥7% of body weight is presented basis of a patient’s sex, race, or smoking status. both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated in Table 1. or inadequately treated extrapyramidal signs and symptoms (EPS). Other important Table 1: Proportion of Adult Patients With Shifts in Weight in the 12-Week, OVERDOSAGE considerations in the differential diagnosis include central anticholinergic toxicity, heat Placebo-Controlled, Fixed-Dose Schizophrenia Trial Human Experience: Common adverse reactions (reported in at least 5% of all overdose stroke, drug fever, and primary central nervous system pathology. cases) reported with oral aripiprazole overdosage (alone or in combination with other The management of NMS should include (1) immediate discontinuation of antipsychotic ARISTADA substances) include , somnolence, and tremor. Other clinically important signs and drugs and other drugs not essential to concurrent therapy; (2) intensive symptomatic symptoms observed in one or more patients with aripiprazole overdoses (alone or with other treatment and medical monitoring; and (3) treatment of any concomitant serious medical Placebo 441 mg 882 mg substances) include acidosis, aggression, aspartate aminotransferase increased, atrial problems for which specific treatments are available. There is no general agreement N = 207 N = 207 N = 208 fibrillation, bradycardia, coma, confusional state, convulsion, blood creatine phosphokinase about specific pharmacological treatment regimens for uncomplicated NMS. (%) (%) (%) increased, depressed level of consciousness, hypertension, hypokalemia, hypotension, lethargy, Weight gain loss of consciousness, QRS complex prolonged, QT prolonged, pneumonia aspiration, If a patient appears to require antipsychotic drug treatment after recovery from NMS, respiratory arrest, , and tachycardia. reintroduction of drug therapy should be closely monitored, since recurrences of NMS have been reported. ≥7% increase from baseline 6 10 9 Management of Overdosage: In case of overdosage, call the Poison control center Tardive Dyskinesia: A syndrome of potentially irreversible, involuntary, dyskinetic immediately at 1-800-222-1222. movements may develop in patients treated with antipsychotic drugs. Although the Pathological Gambling and Other Compulsive Behaviors: Post-marketing case To report SUSPECTED ADVERSE REACTIONS, contact Alkermes, Inc. at prevalence of the syndrome appears to be highest among the elderly, especially elderly reports suggest that patients can experience intense urges, particularly for gambling, 1-866-274-7823 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. women, it is impossible to predict which patients will develop the syndrome. Whether and the inability to control these urges while taking aripiprazole. Other compulsive antipsychotic drug products differ in their potential to cause tardive dyskinesia is unknown. urges, reported less frequently include: sexual urges, shopping, eating or binge PATIENT COUNSELING INFORMATION eating, and other impulsive or compulsive behaviors. Because patients may not Physicians are advised to discuss the FDA-approved patient labeling (Medication Guide) with The risk of developing tardive dyskinesia and the likelihood that it will become irreversible recognize these behaviors as abnormal, it is important for prescribers to ask patients patients for whom they prescribe ARISTADA INITIO. appear to increase as the duration of treatment and the total cumulative dose of or their caregivers specifically about the development of new or intense gambling antipsychotic drugs administered to the patient increase, but the syndrome can develop urges, compulsive sexual urges, compulsive shopping, binge or compulsive eating, or after relatively brief treatment periods at low doses, although this is uncommon. This Brief Summary is based on ARISTADA INITIO Full Prescribing Information Rev June 2018. other urges while being treated with aripiprazole. It should be noted that impulse- Tardive dyskinesia may remit, partially or completely, if antipsychotic treatment is control symptoms can be associated with the underlying disorder. In some cases, Manufactured and marketed by Alkermes, Inc., Waltham, MA 02451-1420. withdrawn. Antipsychotic treatment itself may suppress (or partially suppress) the although not all, urges were reported to have stopped when the dose was reduced or signs and symptoms of the syndrome and may thus mask the underlying process. the medication was discontinued. Compulsive behaviors may result in harm for the ALKERMES® is a registered trademark of Alkermes, Inc. and ARISTADA® and logo are The effect of symptomatic suppression on the long-term course of the syndrome patient and others if not recognized. Consider dose reduction or stopping the is unknown. registered trademarks of Alkermes Pharma Ireland Limited and ARISTADA INITIO™ is a medication if a patient develops such urges. trademark of Alkermes Pharma Ireland Limited, used by Alkermes, Inc. under license. Given these considerations, ARISTADA should be prescribed in a manner that is most Orthostatic Hypotension: Aripiprazole may cause orthostatic hypotension, perhaps likely to minimize the occurrence of tardive dyskinesia. Chronic antipsychotic treatment due to its a1-adrenergic receptor antagonism. Associated adverse reactions related ©2018 Alkermes, Inc. All rights reserved. ARI-003280-v1 should generally be reserved for patients who suffer from a chronic illness that is known to orthostatic hypotension can include dizziness, lightheadedness, and tachycardia. to respond to antipsychotic drugs. In patients who do require chronic treatment, the Generally, these risks are greatest at the beginning of treatment and during dose smallest dose and the shortest duration of treatment producing a satisfactory clinical escalation. Patients at increased risk of these adverse reactions or at increased risk of response should be sought. The need for continued treatment should be reassessed developing complications from hypotension include those with dehydration, hypovolemia, periodically. treatment with antihypertensive medication, history of cardiovascular disease (e.g., If signs and symptoms of tardive dyskinesia appear in a patient treated with ARISTADA, heart failure, myocardial infarction, ischemia, or conduction abnormalities), history of drug discontinuation should be considered. However, some patients may require cerebrovascular disease, as well as patients who are antipsychotic-naïve. In such treatment with ARISTADA despite the presence of the syndrome. patients, consider using a lower starting dose, and monitor orthostatic vital signs. ARISTADA® (aripiprazole lauroxil) extended-release injectable suspension, Metabolic Changes: Atypical antipsychotic drugs have been associated with for intramuscular use metabolic changes that include hyperglycemia/diabetes mellitus, dyslipidemia, and BRIEF SUMMARY OF PRESCRIBING INFORMATION weight gain. While all drugs in the class have been shown to produce some metabolic (For complete details, please see full Prescribing Information and Medication Guide.) changes, each drug has its own specific risk profile. Hyperglycemia/Diabetes Mellitus: Hyperglycemia, in some cases extreme and WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH associated with ketoacidosis or hyperosmolar coma or death, has been reported in DEMENTIA-RELATED PSYCHOSIS patients treated with atypical antipsychotics. There have been reports of hyperglycemia • Elderly patients with dementia-related psychosis treated with antipsychotic in patients treated with oral aripiprazole. Assessment of the relationship between atypical drugs are at an increased risk of death antipsychotic use and glucose abnormalities is complicated by the possibility of an • ARISTADA is not approved for the treatment of patients with increased background risk of diabetes mellitus in patients with schizophrenia and dementia-related psychosis the increasing incidence of diabetes mellitus in the general population. Given these confounders, the relationship between atypical antipsychotic use and hyperglycemia- INDICATIONS AND USAGE: ARISTADA is an atypical antipsychotic indicated for the related adverse events is not completely understood. However, epidemiological studies treatment of schizophrenia. suggest an increased risk of hyperglycemia-related adverse reactions in patients treated CONTRAINDICATIONS: ARISTADA is contraindicated in patients with a known with the atypical antipsychotics. hypersensitivity reaction to aripiprazole. Hypersensitivity reactions have ranged from Patients with an established diagnosis of diabetes mellitus who are started on atypical pruritus/urticaria to anaphylaxis. antipsychotics should be monitored regularly for worsening of glucose control. Patients WARNINGS AND PRECAUTIONS with risk factors for diabetes mellitus (e.g., obesity, family history of diabetes) who are Increased Mortality in Elderly Patients With Dementia-related Psychosis: Elderly starting treatment with atypical antipsychotics should undergo fasting blood glucose patients with dementia-related psychosis treated with antipsychotic drugs are at testing at the beginning of treatment and periodically during treatment. Any patient an increased risk of death. Analyses of 17 placebo-controlled trials (modal duration treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk including polydipsia, polyuria, polyphagia, and weakness. Patients who develop of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in symptoms of hyperglycemia during treatment with atypical antipsychotics should placebo-treated patients. Over the course of a typical 10-week controlled trial, the undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved rate of death in drug-treated patients was about 4.5%, compared to a rate of about when the atypical antipsychotic was discontinued; however, some patients require 2.6% in the placebo group. continuation of anti-diabetic treatment despite discontinuation of the suspect drug. Although the causes of death were varied, most of the deaths appeared to be either In the long-term, open-label schizophrenia study with ARISTADA, 14% of patients cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in with normal hemoglobin A1c (<5.7%) at baseline developed elevated levels (≥5.7%) nature. Observational studies suggest that, similar to atypical antipsychotic drugs, post-baseline. treatment with conventional antipsychotic drugs may increase mortality. The extent to Dyslipidemia: Undesirable alterations in lipids have been observed in patients which the findings of increased mortality in observational studies may be attributed to treated with atypical antipsychotics. the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. ARISTADA is not approved for the treatment of patients with dementia-related psychosis. In the long-term, open-label schizophrenia study with ARISTADA, shifts in baseline Cerebrovascular Adverse Reactions, Including Stroke: In placebo-controlled trials fasting total cholesterol from normal (<200 mg/dL) to high (≥240 mg/dL) were with risperidone, aripiprazole, and olanzapine in elderly patients with dementia, there reported in 1% of patients; shifts in baseline fasting LDL cholesterol from normal was a higher incidence of cerebrovascular adverse reactions (cerebrovascular (<100 mg/dL) to high (≥160 mg/dL) were reported in 1% of patients; and shifts in accidents and transient ischemic attacks) including fatalities compared to placebo- baseline fasting triglycerides from normal (<150 mg/dL) to high (≥200 mg/dL) treated patients. ARISTADA is not approved for the treatment of patients with dementia- were reported in 8% of patients. In the same study, shifts in baseline fasting total related psychosis. cholesterol from borderline (≥200 mg/dL and <240 mg/dL) to high (≥240 mg/dL) were reported in 15% of patients; shifts in baseline fasting LDL cholesterol from Neuroleptic Malignant Syndrome: A potentially fatal symptom complex sometimes borderline (≥100 mg/dL and <160 mg/dL) to high (≥160 mg/dL) were reported in referred to as Neuroleptic Malignant Syndrome (NMS) may occur in association with 8% of patients; and shifts in baseline fasting triglycerides from borderline antipsychotic drugs, including ARISTADA. Clinical manifestations of NMS are hyperpyrexia, (≥150 mg/dL and <200 mg/dL) to high (≥200 mg/dL) were reported in 35% of muscle rigidity, altered mental status, and evidence of autonomic instability (irregular patients. In addition, the proportion of patients with shifts in fasting HDL cholesterol pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional from normal (≥40 mg/dL) to low (<40 mg/dL) was reported in 15% of patients. signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Weight Gain: Weight gain has been observed with atypical antipsychotic use. Clinical The diagnostic evaluation of patients with this syndrome is complicated. In arriving at monitoring of weight is recommended. a diagnosis, it is important to identify cases in which the clinical presentation includes The proportion of adult patients with weight gain ≥7% of body weight is presented both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated in Table 1. or inadequately treated extrapyramidal signs and symptoms (EPS). Other important Table 1: Proportion of Adult Patients With Shifts in Weight in the 12-Week, considerations in the differential diagnosis include central anticholinergic toxicity, heat Placebo-Controlled, Fixed-Dose Schizophrenia Trial stroke, drug fever, and primary central nervous system pathology. The management of NMS should include (1) immediate discontinuation of antipsychotic ARISTADA drugs and other drugs not essential to concurrent therapy; (2) intensive symptomatic treatment and medical monitoring; and (3) treatment of any concomitant serious medical Placebo 441 mg 882 mg problems for which specific treatments are available. There is no general agreement N = 207 N = 207 N = 208 about specific pharmacological treatment regimens for uncomplicated NMS. (%) (%) (%) If a patient appears to require antipsychotic drug treatment after recovery from NMS, Weight gain reintroduction of drug therapy should be closely monitored, since recurrences of NMS have been reported. ≥7% increase from baseline 6 10 9 Tardive Dyskinesia: A syndrome of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs. Although the Pathological Gambling and Other Compulsive Behaviors: Post-marketing case prevalence of the syndrome appears to be highest among the elderly, especially elderly reports suggest that patients can experience intense urges, particularly for gambling, women, it is impossible to predict which patients will develop the syndrome. Whether and the inability to control these urges while taking aripiprazole. Other compulsive antipsychotic drug products differ in their potential to cause tardive dyskinesia is unknown. urges, reported less frequently include: sexual urges, shopping, eating or binge eating, and other impulsive or compulsive behaviors. Because patients may not The risk of developing tardive dyskinesia and the likelihood that it will become irreversible recognize these behaviors as abnormal, it is important for prescribers to ask patients appear to increase as the duration of treatment and the total cumulative dose of or their caregivers specifically about the development of new or intense gambling antipsychotic drugs administered to the patient increase, but the syndrome can develop urges, compulsive sexual urges, compulsive shopping, binge or compulsive eating, or after relatively brief treatment periods at low doses, although this is uncommon. other urges while being treated with aripiprazole. It should be noted that impulse- Tardive dyskinesia may remit, partially or completely, if antipsychotic treatment is control symptoms can be associated with the underlying disorder. In some cases, withdrawn. Antipsychotic treatment itself may suppress (or partially suppress) the although not all, urges were reported to have stopped when the dose was reduced or signs and symptoms of the syndrome and may thus mask the underlying process. the medication was discontinued. Compulsive behaviors may result in harm for the The effect of symptomatic suppression on the long-term course of the syndrome patient and others if not recognized. Consider dose reduction or stopping the is unknown. medication if a patient develops such urges. Given these considerations, ARISTADA should be prescribed in a manner that is most Orthostatic Hypotension: Aripiprazole may cause orthostatic hypotension, perhaps likely to minimize the occurrence of tardive dyskinesia. Chronic antipsychotic treatment due to its a1-adrenergic receptor antagonism. Associated adverse reactions related should generally be reserved for patients who suffer from a chronic illness that is known to orthostatic hypotension can include dizziness, lightheadedness, and tachycardia. to respond to antipsychotic drugs. In patients who do require chronic treatment, the Generally, these risks are greatest at the beginning of treatment and during dose smallest dose and the shortest duration of treatment producing a satisfactory clinical escalation. Patients at increased risk of these adverse reactions or at increased risk of response should be sought. The need for continued treatment should be reassessed developing complications from hypotension include those with dehydration, hypovolemia, periodically. treatment with antihypertensive medication, history of cardiovascular disease (e.g., If signs and symptoms of tardive dyskinesia appear in a patient treated with ARISTADA, heart failure, myocardial infarction, ischemia, or conduction abnormalities), history of drug discontinuation should be considered. However, some patients may require cerebrovascular disease, as well as patients who are antipsychotic-naïve. In such treatment with ARISTADA despite the presence of the syndrome. patients, consider using a lower starting dose, and monitor orthostatic vital signs. Orthostatic hypotension was reported for 1 patient in the ARISTADA 882 mg group In an open-label pharmacokinetic study, the adverse reactions associated with (0.5%) and no patients in the ARISTADA 441 mg and placebo groups in the the use of 441 mg monthly, 882 mg every 6 weeks, and 1064 mg every 2 months 12-week schizophrenia efficacy study. In the long-term open-label schizophrenia were similar across the dose groups. study, orthostatic hypotension was reported for 1 (0.2%) patient treated with Injection-Site Reactions: Injection-site reactions were reported by 4% of patients ARISTADA. Orthostatic hypotension was defined as a decrease in systolic blood treated with 441 mg ARISTADA and 5% of patients treated with 882 mg ARISTADA pressure ≥20 mmHg accompanied by an increase in heart rate ≥25 bpm when compared to 2% of patients treated with placebo. Most of these were injection-site comparing standing to supine values. pain (3%, 4%, and 2% in the 441 mg ARISTADA, 882 mg ARISTADA, and placebo groups, Falls: Antipsychotics including ARISTADA may cause somnolence, postural hypotension, respectively), and most were associated with the first injection and decreased with each or motor and sensory instability, which may lead to falls and, consequently, fractures or subsequent injection to less than or equal to 1% for both doses of ARISTADA and other injuries. For patients with diseases, conditions, or medications that could placebo. Other injection-site reactions (induration, swelling, and redness) occurred exacerbate these effects, complete fall risk assessments when initiating antipsychotic at less than 1%. In an open-label pharmacokinetic study evaluating 441 mg monthly, treatment and recurrently for those patients on long-term antipsychotic therapy. 882 mg every 6 weeks, and 1064 mg every 2 months, injection-site reactions were Leukopenia, Neutropenia, and Agranulocytosis: In clinical trials and/or similar across the dose groups. postmarketing experience, events of leukopenia and neutropenia have been Extrapyramidal Symptoms: In the 12-week schizophrenia efficacy study, for reported temporally related to antipsychotic agents. Agranulocytosis has also ARISTADA-treated patients, the incidence of other EPS-related events, excluding been reported. akathisia and restlessness, was 5% and 7% for patients on 441 mg and 882 mg, Possible risk factors for leukopenia/neutropenia include pre-existing low white respectively, versus 4% for placebo-treated patients (Table 3). blood cell count (WBC)/absolute neutrophil count (ANC) and history of drug-induced Table 3: Incidence of EPS Compared to Placebo leukopenia/neutropenia. In patients with a history of a clinically significant low WBC/ANC or drug-induced leukopenia/neutropenia, perform a complete blood ARISTADA count (CBC) frequently during the first few months of therapy. In such patients, Placebo 441 mg 882 mg consider discontinuation of ARISTADA at the first sign of a clinical significant N = 207 N = 207 N = 208 decline in WBC in the absence of other causative factors. Adverse Reaction Term (%) (%) (%) Monitor patients with clinically significant neutropenia for fever or other symptoms Akathisia 4 11 11 or signs of infection and treat promptly if such symptoms or signs occur. Discontinue ARISTADA in patients with severe neutropenia (absolute neutrophil count Restlessness 1 3 1 3 <1000/mm ) and follow their WBC until recovery. Other EPS 4 5 7 Seizures: As with other antipsychotic drugs, use ARISTADA cautiously in patients with a history of seizures or with conditions that lower the seizure threshold. Conditions that Dystonia 1 2 2 lower the seizure threshold may be more prevalent in a population of 65 years or older. Parkinsonism 3 3 4 Potential for Cognitive and Motor Impairment: ARISTADA, like other antipsychotics, has the potential to impair judgment, thinking, or motor skills. Patients should be Dystonia: Symptoms of dystonia, prolonged abnormal contractions of muscle groups, cautioned about operating hazardous machinery, including automobiles, until they may occur in susceptible individuals during the first few days of treatment. Dystonic are reasonably certain that therapy with ARISTADA does not affect them adversely. symptoms include: spasm of the neck muscles, sometimes progressing to tightness of Body Temperature Regulation: Disruption of the body’s ability to reduce core body the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. temperature has been attributed to antipsychotic agents. Appropriate care is advised While these symptoms can occur at low doses, they occur more frequently and with when prescribing ARISTADA for patients who will be experiencing conditions which greater severity with high potency and at higher doses of first-generation antipsychotic may contribute to an elevation in core body temperature (e.g., exercising strenuously, drugs. An elevated risk of acute dystonia is observed in males and younger age groups. exposure to extreme heat, receiving concomitant medication with anticholinergic Other Adverse Reactions Observed in Clinical Studies: The following listing does activity, or being subject to dehydration). not include reactions: 1) already listed in previous tables or elsewhere in labeling, 2) Dysphagia: Esophageal dysmotility and aspiration have been associated with for which a drug cause was remote, 3) which were so general as to be uninformative, antipsychotic drug use. ARISTADA and other antipsychotic drugs should be used 4) which were not considered to have significant clinical implications, or 5) which cautiously in patients at risk for aspiration pneumonia. occurred at a rate equal to or less than placebo. Cardiac – angina pectoris, tachycardia, palpitations ADVERSE REACTIONS Gastrointestinal disorders – constipation, dry mouth Clinical Studies Experience: Because clinical trials are conducted under widely General disorders – asthenia varying conditions, adverse reaction rates observed in the clinical trials of a drug Musculoskeletal – muscular weakness cannot be directly compared to rates in the clinical trials of another drug and may Nervous system disorders – dizziness not reflect the rates observed in practice. Psychiatric disorders – anxiety, suicide Patient Exposure: ARISTADA has been evaluated for safety in 1019 adult patients in Adverse Reactions Reported in Clinical Trials with Oral Aripiprazole: The clinical trials in schizophrenia. following is a list of additional adverse reactions that have been reported in clinical Commonly Observed Adverse Reactions: The most common adverse reaction (incidence trials with oral aripiprazole and not reported above for ARISTADA. ≥5% and at least twice the rate of placebo in patients treated with ARISTADA) was akathisia. Blood and Lymphatic System Disorders: thrombocytopenia Adverse Reactions Occurring at an Incidence of 2% or More in ARISTADA-Treated Cardiac Disorders: bradycardia, atrial flutter, cardiorespiratory arrest, atrioventricular block, Patients. Adverse reactions associated with the use of ARISTADA (incidence of 2% , myocardial ischemia, myocardial infarction, cardiopulmonary failure or greater, rounded to the nearest percent and ARISTADA incidence greater than Eye Disorders: photophobia, diplopia placebo) that occurred are shown in Table 2. Gastrointestinal Disorders: gastroesophageal reflux disease General Disorders and Administration-Site Conditions: peripheral edema, chest pain, Table 2: Adverse Reaction in 2% or More of ARISTADA-Treated Patients and That face edema Occurred at Greater Incidence Than in the Placebo-Treated Patients in Hepatobiliary Disorders: hepatitis, jaundice the 12-Week, Placebo-Controlled, Fixed-Dose Schizophrenia Trial Immune System Disorders: hypersensitivity Injury, Poisoning, and Procedural Complications: fall, heat stroke Aripiprazole Lauroxil Investigations: weight decreased, hepatic enzyme increased, blood glucose increased, Placebo 441 mg 882 mg blood lactate dehydrogenase increased, gamma glutamyl transferase increased, blood Adverse Reaction System Organ Class N = 207 N = 207 N = 208 prolactin increased, blood urea increased, blood creatinine increased, blood bilirubin increased, electrocardiogram QT prolonged, glycosylated hemoglobin increased Preferred Term (%) (%) (%) Metabolism and Nutrition Disorders: anorexia, hypokalemia, hyponatremia, hypoglycemia General disorders and administration site conditions Musculoskeletal and Connective Tissue Disorders: muscle tightness, rhabdomyolysis, mobility decreased Injection site pain 2 3 4 Nervous System Disorders: memory impairment, cogwheel rigidity, hypokinesia, myoclonus, bradykinesia, akinesia, myoclonus, coordination abnormal, speech disorder, Investigations choreoathetosis Increased weight 1 2 2 Psychiatric Disorders: aggression, loss of libido, delirium, libido increased, anorgasmia, tic, homicidal ideation, catatonia, sleep walking Increased blood creatine Renal and Urinary Disorders: urinary retention, nocturia phosphokinase 0 2 1 Reproductive System and Breast Disorders: erectile dysfunction, gynaecomastia, menstruation irregular, amenorrhea, breast pain, priapism Nervous system disorders Respiratory, Thoracic, and Mediastinal Disorders: nasal congestion, dyspnea Akathisia 4 11 11 Skin and Subcutaneous Tissue Disorders: rash, hyperhidrosis, pruritus, photosensitivity reaction, alopecia, urticaria Headache 3 3 5 Vascular Disorders: hypotension, hypertension Postmarketing Experience: The following adverse reactions have been identified Psychiatric disorders during post-approval use of oral aripiprazole. Because these reactions are reported Insomnia 2 3 4 voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or to establish a causal relationship to drug exposure: Restlessness 1 3 1 occurrences of allergic reaction (anaphylactic reaction, angioedema, laryngospasm, pruritus/urticaria, or oropharyngeal spasm), pathological gambling, hiccups, and blood glucose fluctuation. DRUG INTERACTIONS At 3 and 10 times the oral MRHD on mg/m2 basis, delivered offspring had decreased Drugs Having Clinically Important Interactions With ARISTADA body weights. Increased incidences of hepatodiaphragmatic nodules and diaphragmatic Table 4: Clinically Important Drug Interactions With ARISTADA hernia were observed in offspring from the highest dose group (the other dose groups were not examined for these findings). A low incidence of diaphragmatic hernia was also Concomitant Drug Clinical seen in the fetuses exposed to the highest dose. Postnatally, delayed vaginal opening Name or Drug Class Clinical Rationale Recommendations was seen at 3 and 10 times the oral MRHD on mg/m2 basis and impaired reproductive performance (decreased fertility rate, corpora lutea, implants, live fetuses, and increased Strong CYP3A4 Inhibitors The concomitant use of With concomitant use of post-implantation loss, likely mediated through effects on female offspring) along with (e.g., itraconazole, oral aripiprazole with ARISTADA with a strong some maternal toxicity were seen at the highest dose; however, there was no evidence clarithromycin) or strong strong CYP3A4 or CYP3A4 inhibitor or to suggest that these developmental effects were secondary to maternal toxicity. CYP2D6 inhibitors (e.g., CYP2D6 inhibitors CYP2D6 inhibitor for quinidine, fluoxetine, increased the exposure more than 2 weeks In pregnant rabbits treated with oral doses of 10, 30, and 100 mg/kg/day, which are 2 paroxetine) of aripiprazole compared reduce the ARISTADA to 11 times human exposure at the oral MRHD based on AUC and 6 to 65 times the oral to the use of oral dose. MRHD on mg/m2 basis of aripiprazole during the period of organogenesis, decreased aripiprazole alone. maternal food consumption and increased abortions were seen at the highest dose as well as increased fetal mortality. Decreased fetal weight and increased incidence of Strong CYP3A4 Inducer The concomitant use of With concomitant use of fused sternebrae were observed at 3 and 11 times the oral MRHD based on AUC. (e.g., carbamazepine, oral aripiprazole and ARISTADA with a strong In rats treated with oral doses of 3, 10, and 30 mg/kg/day which are 1 to 10 times the rifampin) carbamazepine CYP3A4 inducer for more oral MRHD on mg/m2 basis of aripiprazole perinatally and postnatally (from day 17 of decreased the exposure than 2 weeks consider gestation through day 21 postpartum), slight maternal toxicity and slightly prolonged of aripiprazole compared increasing the ARISTADA to the use of oral dose. gestation were seen at the highest dose. An increase in stillbirths and decreases in aripiprazole alone. pup weight (persisting into adulthood) and survival were also seen at this dose. Lactation: Risk Summary: Aripiprazole is present in human breast milk; however, Antihypertensive Drugs Due to its alpha Monitor blood pressure there are insufficient data to assess the amount in human milk, the effects on the adrenergic antagonism, and adjust dose breastfed infant, or the effects on milk production. The development and health aripiprazole has the accordingly. benefits of breastfeeding should be considered along with the mother’s clinical need potential to enhance for ARISTADA and any potential adverse effects on the breastfed infant from ARISTADA the effect of certain or from the underlying maternal condition. antihypertensive agents. Pediatric Use: Safety and effectiveness of ARISTADA in patients <18 years of age have Benzodiazepines The intensity of sedation Monitor sedation and not been evaluated. (e.g., lorazepam) was greater with the blood pressure. Adjust Geriatric Use: Safety and effectiveness of ARISTADA in patients >65 years of age have combination of oral dose accordingly. not been evaluated. aripiprazole and Hepatic and Renal Impairment: No dosage adjustment for ARISTADA is required based lorazepam as compared on a patient’s hepatic function (mild to severe hepatic impairment, Child-Pugh score to that observed with aripiprazole alone. The between 5 and 15), or renal function (mild to severe renal impairment, glomerular orthostatic hypotension filtration rate between 15 and 90 mL/minute). observed was greater Other Specific Populations: No dosage adjustment for ARISTADA is required on the with the combination as basis of a patient’s sex, race, or smoking status. compared to that OVERDOSAGE observed with lorazepam Human Experience: The largest known case of acute ingestion with a known outcome alone. involved 1260 mg of oral aripiprazole (42 times the maximum recommended daily dose) in a patient who fully recovered. USE IN SPECIFIC POPULATIONS Common adverse reactions (reported in at least 5% of all overdose cases) reported Pregnancy with oral aripiprazole overdosage (alone or in combination with other substances) Pregnancy Exposure Registry: There is a pregnancy exposure registry that monitors include vomiting, somnolence, and tremor. Other clinically important signs and pregnancy outcomes in women exposed to ARISTADA during pregnancy. For more symptoms observed in one or more patients with aripiprazole overdoses (alone or information, contact the National Pregnancy Registry for Atypical Antipsychotics at with other substances) include acidosis, aggression, aspartate aminotransferase 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research- increased, atrial fibrillation, bradycardia, coma, confusional state, convulsion, programs/pregnancyregistry/. blood creatine phosphokinase increased, depressed level of consciousness, Risk Summary: Neonates exposed to antipsychotic drugs during the third trimester hypertension, hypokalemia, hypotension, lethargy, loss of consciousness, QRS of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following complex prolonged, QT prolonged, pneumonia aspiration, respiratory arrest, delivery. Limited published data on aripiprazole use in pregnant women are not status epilepticus, and tachycardia. sufficient to inform any drug-associated risks for birth defects or miscarriage. Management of Overdosage: In case of overdosage, call the Poison control center No teratogenicity was observed in animal reproductive studies with intramuscular immediately at 1-800-222-1222. administration of aripiprazole lauroxil to rats and rabbits during organogenesis at doses up to 5 and 15 times, respectively, the maximum recommended human dose To report SUSPECTED ADVERSE REACTIONS, contact Alkermes, Inc. at (MRHD) of 1064 mg based on body surface area (mg/m2). However, aripiprazole 1-866-274-7823 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. caused developmental toxicity and possible teratogenic effects in rats and rabbits PATIENT COUNSELING INFORMATION [see Data]. The background risk of major birth defects and miscarriage for the Physicians are advised to discuss the FDA-approved patient labeling (Medication Guide) indicated population are unknown. In the U.S. general population, the estimated with patients for whom they prescribe ARISTADA. background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively. Advise pregnant women of the This Brief Summary is based on ARISTADA Full Prescribing Information potential risk to a fetus. Rev September 2017 Clinical Considerations: Fetal/Neonatal Adverse Reactions: Extrapyramidal and/or Manufactured and marketed by Alkermes, Inc., Waltham, MA 02451-1420 withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder have been reported in neonates who were ALKERMES® is a registered trademark of Alkermes, Inc. and ARISTADA® and logo exposed to antipsychotic drugs during the third trimester of pregnancy. These symptoms are registered trademarks of Alkermes Pharma Ireland Limited, used by Alkermes, have varied in severity. Monitor neonates for extrapyramidal and/or withdrawal Inc. under license. symptoms and manage symptoms appropriately. Some neonates recover within hours or days without specific treatment; others required prolonged hospitalization. ©2017 Alkermes, Inc. All rights reserved. ARI-002805 Data: Animal Data for Aripiprazole Lauroxil: Aripiprazole lauroxil did not cause adverse developmental or maternal effects in rats or rabbits when administered intramuscularly during the period of organogenesis at doses of 18, 49, or 144 mg/animal in pregnant rats which are approximately 0.6 to 5 times the maximum recommended human dose (MRHD) of 1064 mg ARISTADA on mg/m2 basis and at doses of 241, 723, and 2893 mg/animal in pregnant rabbits which are approximately 1 to 15 times the MRHD on mg/m2 basis. However, aripiprazole caused developmental toxicity and possible teratogenic effects in rats and rabbits. Animal Data for Aripiprazole: Pregnant rats were treated with oral doses of 3, 10, and 30 mg/kg/day, which are approximately 1 to 10 times the oral maximum recommended human dose (MRHD) of 30 mg/day on mg/m2 basis of aripiprazole during the period of organogenesis. Treatment at the highest dose caused a slight prolongation of gestation and delay in fetal development, as evidenced by decreased fetal weight, and undescended testes. Delayed skeletal ossification was observed at 3 and 10 times the oral MRHD on mg/m2 basis. BULLETIN BOARD

FDA NOD CLEARS THE WAY FOR EARLIER LAI USE IN SCHIZOPHRENIA By Terri Airov

door with up to two months of coverage with ment and medical affairs at Alkermes. a proven medication in their system.” The new drug, approved for adults only, Previously, Aristada’s standard initiation can be used for initiation onto any dose of regimen included 21 concurrent consecutive Aristada: 441 mg, 662 mg, or 882 mg monthly, days of oral aripiprazole. Aristada Initio 882 mg once every 6 weeks, or 1064 mg once establishes relevant levels of aripiprazole in every 2 months. the body within 4 days of initiation, according Like Aristada, Aristada Initio will carry a to a statement from Alkermes. Boxed Warning stating it is not approved for “The ability to initiate Aristada on day one use in patients with dementia-related psycho- may be particularly useful in the hospital sis, who have an increased risk of death when setting, where more than one-third of patients treated with antipsychotics. ■ initiate onto long-acting therapies,” said Craig Hopkinson, MD, chief medical officer and REFERENCE FDA approves Aristada Initio for the initiation of Aristada senior vice president of medicines develop- for schizophrenia [press release]. Dublin, Ireland: Alker- mes plc; July 2, 2018.

he U.S. Food and Drug Administration drug—more quickly. The first dose of Aris- (FDA) has approved the first drug tada can be given on the same day as Aris- RELATED designed to initiate patients onto a tada Initio or up to 10 days later. Presentation at Psych Congress 2018 by Tlong-acting injectable from the first day of “The approval of Aristada Initio makes PSYCH CONGRESS SNAPSHOT treatment for schizophrenia, Alkermes Aristada the first and only long-acting atypi- Joseph McEvoy, MD announced. cal antipsychotic that can be initiated on day Aristada Initio, which is to be given with one, representing an important addition to Mitigating Stigma in Severe Mental Illness one 30 mg dose of oral aripiprazole, was the treatment paradigm for the complex ill- THURSDAY, OCTOBER 25 2:15 P.M. — 3:30 P.M. expected to be on the market by mid-July. ness of schizophrenia,” said David Walling, | Like the long-acting injectable Aristada, PhD, chief executive officer and principal This session will review strategies clinicians can utilize to mitigate patients’ Aristada Initio contains aripiprazole lauroxil. investigator of the Collaborative Neuroscience internalized stigma related to the presence of severe mental illness (SMI). But the new formulation utilizes Alkermes’ Network, a clinical research organization. Efforts to change stigmatizing societal views of patients with SMI will also proprietary NanoCrystal technology, which “For physicians and caregivers alike, the be reviewed, including evidence for their great expense vs limited uses a smaller particle size designed to dis- Aristada Initio regimen provides a level of efficacy. solve—and provide relevant levels of the confidence that patients can walk out the

FDA REVERSES COURSE ON PROPOSED ADJUNCTIVE DEPRESSION TREATMENT By Terri Airov

he US Food and Drug Administration duced for major depressive disorder in 30 safety, and tolerability in the adjunctive REFERENCE Alkermes announces FDA acceptance for review of New accepted the application for pro- years. treatment of MDD,” the company said in its Drug Application for ALKS 5461 for the adjunctive treat- posed adjunctive depression treat- ALKS 5461 is a novel, once-daily, oral statement. ■ ment of major depressive disorder [press release]. Dublin, Ireland: Alkermes plc; April 16, 2018. Tment ALKS 5461, changing course after investigational treatment intended for pa- refusing to accept it 2 weeks earlier, drug- tients who have had an inadequate response maker Alkermes announced. to standard antidepressants. It combines RELATED The move comes after Alkermes clarified buprenorphine, a partial mu-opioid recep- certain aspects of its New Drug Application tor agonist and kappa-opioid receptor an- Featured Session at Psych Congress submission, according to a press release tagonist, with samidorphan, a mu-opioid PSYCH CONGRESS 2018 by Nassir Ghaemi, MD, MPH, and from the company. It says no additional data receptor antagonist. SNAPSHOT or analyses were submitted. In refusing to accept the application on Joseph F. Goldberg, MD The FDA set Jan. 31, 2019, as its target March 30, the FDA asked Alkermes for more The Great Debate in Contemporary Psychiatry: The Use of date for taking action on the application. well-controlled trials. "We will continue to engage with the FDA But Alkermes says its application is “based Antidepressants in Bipolar Depression throughout the review process, as we work on results from a clinical efficacy and FRIDAY, OCTOBER 26 | 4:15 P.M. — 5:15 P.M. to bring this important medicine to patients," safety package with data from more than said Craig Hopkinson, MD, chief medical 30 clinical trials and more than 1500 patients Drs. Ghaemi and Goldberg—internationally recognized clinicians, officer and senior vice president of medicines with MDD.” researchers, and experts in the field of mood disorders—will debate the development and medical affairs at Alkermes, “Throughout the clinical development issue of using antidepressants in bipolar depression. Attendees will have noting that there have been no new phar- program, ALKS 5461 demonstrated a con- the opportunity to vote on the “winning” argument. macological treatment approaches intro- sistent profile of activity,

14 Psych Congress Network • Summer 2018 • psychcongress.com GAIN INSIGHTS INTO CURRENT AND EMERGING TREATMENT STRATEGIES WITH THE BEST MINDS IN MENTAL HEALTH www.PsychU.org

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POSTPARTUM DEPRESSION DRUG APPLICATION HEADS TO FDA By Terri Airov

age Therapeutics has submitted a New significantly lower depression scores, com- Drug Application to the US Food and pared with placebo, at 60 hours after dosing Drug Administration (FDA) for its pro- in 126 patients with moderate or severe PPD, RELATED Sposed postpartum depression (PPD) treatment, the company reported at the time. Results PSYCH CONGRESS Presentation at Psych Congress 2018 by the biopharmaceutical company announced. were maintained to 30 days. SNAPSHOT The drug is an intravenous formulation of Brexanolone, an allosteric modulator of Marlene Freeman, MD brexanolone, formerly called SAGE-547. It synaptic and extrasynaptic GABAA receptors, received Breakthrough Therapy Designation is the lead product candidate for Sage Ther- Solving Clinical Challenges in Postpartum Depression and from the FDA for PPD in September 2016, and apeutics, based in Cambridge, Massachusetts. Mood Disorders would become the first drug approved spe- The company focuses on developing novel cifically for PPD. medicines for life-altering central nervous FRIDAY, OCTOBER 26 | 9:15 A.M. — 10:30 A.M. The NDA submission—the first for Sage system (CNS) disorders. This session will address complex conundrums faced by Psych Congress Therapeutics—is based on 3 trials analyzing An estimated 11.5% of new mothers in the attendees in managing their female patients with psychiatric disorders, the safety and effectiveness of brexanolone US experience PPD, and suicide is the leading focusing on postpartum depression. Dr. Freeman will discuss and respond in postpartum women aged 18 to 45 years cause of maternal death following childbirth, with moderate or severe PPD. The studies according to a company press release. ■ to real cases and issues from attendees surveyed prior to the conference. were known as the Hummingbird Program. Positive phase 3 results from 2 of those REFERENCE Sage Therapeutics submits new drug application to U.S. studies were announced in November 2017. FDA for intravenous brexanolone in the treatment of post- They showed the drug was associated with partum depression [press release]. Cambridge, MA: Sage Therapeutics; April 23, 2018.

KETAMINE EFFECTIVE AS MAINTENANCE TREATMENT FOR ANXIETY By Jolynn Tumolo

quoted from the study. “Reduced anxiety Of the 20 patients enrolled in the study, meant everyday tasks were less onerous. 18 completed all 3 months of maintenance Most patients reported an increase in their treatment—and all reported improvements ability to concentrate, leading to improve- in social and work functioning, Psychiatric ment in their functionality.” News Alert reported. Two weeks after their The open-label study involved 20 patients last injection, 8 patients experienced with generalized anxiety disorder and/or some return of anxiety and 5 patients expe- social anxiety disorder who responded to rienced full re-emergence. Three months ketamine in a previous ascending-dose study. after maintenance treatment ended, 5 patients Patients in the maintenance treatment study remained well. had 1-2 weekly doses of 1 mg/kg of ketamine Nausea, dizziness, and blurred vision were injected subcutaneously for 3 months. the most common adverse events during the Just 1 hour after injection, ratings on both study. ■ the Fear Questionnaire and the Hamilton Anxiety Rating Scale dropped by 50%, REFERENCE Glue P, Neehoff SM, Medlicott NJ, Gray A, Kibby G, Mc- researchers reported. Over the course of the Naughton N. Safety and efficacy of maintenance ketamine study, mean scores on the Clinician Admin- treatment in patients with treatment-refractory gener- alised anxiety and social anxiety disorders. Journal of Psy- istered Dissociative States Scale decreased, chopharmacology. 2018 March 21;[Epub ahead of print]. dropping from 20 points at week 1 to 8.8 Maintenance ketamine may offer alternative for patients with treatment-refractory anxiety disorders. Psychiatric points at week 14. News Alert. March 29, 2018.

RELATED

PSYCH CONGRESS Presentation at Psych Congress 2018 by SNAPSHOT Sanjay Mathew, MD

n patients with treatment-refractory anx- amine may be a therapeutic alternative for Ketamine in Psychiatric Practice: Taking the Long-Term iety who responded to ketamine, weekly that patient population, researchers con- View maintenance doses over 3 months were cluded. Iwell tolerated and significantly improved “Their experience of ketamine treatment SUNDAY, OCTOBER 28 | 9:00 A.M. — 10:15 A.M. social and work functioning, according to a enabled them to make substantial changes This clinically oriented session will discuss emerging data on ketamine small study published online in the Journal to their lives (for example, employment, therapy across many psychiatric indications and examine the role of of Psychopharmacology. study, making friends, engaging socially, and ketamine in long-term management and relapse prevention. The findings suggest maintenance ket- travelling),” a Psychiatric News Alert article

16 Psych Congress Network • Summer 2018 • psychcongress.com VISIT PSYCHCONGRESS.COM/2018 OR CALL 800-205-8233 TO REGISTER TODAY Sign up for a daily email on the Psych Congress Network is a multiplatform source of most important information featuring clinical news coverage, peer perspective developments and analysis, audio and video resources, and continuing mental in mental health. health education. This is your year-round resource for staying current in the ever-changing field of mental health.

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Download the Psych Congress Network app for FREE today and sign up for push alerts on the latest mental health news. Schedule at a Glance Day 1 Thursday, October 25

7:00 A.M.—8:45 A.M. WELCOME SESSION Psychedelics: A Psychiatric Revolution in Waiting?

8:45 A.M.—9:00 A.M. BREAK 9:00 A.M.—10:15 A.M. Sugar, Food, Binge, and Overeating: The Addressing and Overcoming Burnout in Cannabis Therapeutics: Advising Patients on Severity and Treatment of Depression: A Addiction Connection and Treatment Clinical Practice Safe and Effective Use Review of Two Controversies Implications

10:15 A.M.—10:30 A.M. BREAK 10:30 A.M.—11:45 A.M. Solving Clinical Challenges in Geriatric Understanding and Treating Behavioral Diagnosis and Treatment of Military-Relat- Handling Negative Reviews Online Psychiatry Addictions ed PTSD: Differential Diagnosis, Clinical Tools, and Effective Care

11:45 A.M.—12:00 P.M. BREAK

12:00 P.M.—2:00 P.M. INDUSTRY–SUPPORTED SYMPOSIA LUNCH

2:00 P.M.—2:15 P.M. BREAK 2:15 P.M.—3:30 P.M. Mitigating Stigma in Severe Mental Illness What’s Hot: An Inflammatory Take on the Persistent Symptoms After Concussion: A Update on Borderline Personality Disor- Immune System in Psychiatry Neuropsychiatric Perspective der: What Every Clinician Needs to Know

3:30 P.M.—3:45 P.M. BREAK 3:45 P.M.—5:00 P.M. Why People Die by Suicide Parkinson’s Disease Psychosis: What Mental Health Neurobiologic Insights into Major Depressive Disorder: Professionals Need to Know An Update on Emerging Therapies With Novel Mechanisms of Action

5:00 P.M.—5:15 P.M. BREAK

5:15 P.M.—6:15 P.M. FEATURED SESSION I’M OK BUT YOU NEED PROFESSIONAL HELP: CREATING RECOVERY ONE LAUGH AT A TIME

6:15 P.M.—6:30 P.M. BREAK

6:30 P.M.—8:00 P.M. OPENING NIGHT RECEPTION IN THE EXHIBIT HALL

9:00 P.M.—10:30 P.M. PSYCH CONGRESS NETWORKING EVENT AT EPCOT® Day 2 Friday, October 26 7:00 A.M.—9:00 A.M. INDUSTRY-SUPPORTED SYMPOSIA BREAKFAST

9:00 A.M.—9:15 A.M. BREAK 9:15 A.M.—10:30 A.M. The New Clinical Science of ECT Solving Clinical Challenges in Postpartum Clinical Relevance of the DSM-5 Mixed Tantalizingly Close: An Update on Depression and Mood Disorders Features Specifier: Diagnostic and Thera- Emerging Psychedelic Research and a peutic Implications Report from a Psychedelic Psychothera- pist Trainee

10:30 A.M.—10:45 A.M. BREAK

10:45 A.M.—12:00 P.M. Differential Diagnosis of ADHD and Bipo- Bipolar Disorder in Women: Consider- Leaky Gut, Leaky Brain: The Emerging What’s Preventing Us From Preventing lar Disorder ations Across the Reproductive Lifespan Role of Intestinal Permeability and Mental Alzheimer’s Disease? Health

12:00 P.M.—12:15 P.M. BREAK

12:15 P.M.—1:30 P.M. INNOVATION THEATER LUNCH (NON-ACCREDITED)

12:15 P.M.—2:30 P.M. EXHIBIT HALL AND POSTER PAVILION

12:30 P.M.—1:00 P.M. PRODUCT SHOWCASE IN THE EXHIBIT HALL

1:45 P.M.—2:15 P.M. INNOVATION SHOWCASE (NON-ACCREDITED)

1:30 P.M.—2:30 P.M. POSTER PRESENTATIONS

2:30 P.M.—2:45 P.M. BREAK 2:45 P.M.—4:00 P.M. Rethinking Our Relationship to Sadness: Therapeutic An Individualized Approach to ADHD Management: Doing More by Prescribing Less: Top 10 Drug Interac- Importance of Differentiating Grief From Depression Pediatric, Adolescent, and Adult Patient Considerations tions That Limit Efficacy

4:00 P.M.—4:15 P.M. BREAK 4:15 P.M.—5:15 P.M. FEATURED SESSION THE GREAT DEBATE IN CONTEMPORARY PSYCHIATRY: THE USE OF ANTIDEPRESSANTS IN BIPOLAR DEPRESSION 5:15 P.M.—5:30 P.M. BREAK

5:30 P.M.—7:30 P.M. EXHIBIT HALL RECEPTION AND POSTER GALA

5:45 P.M.—6:45 P.M. INNOVATION SHOWCASE (NON-ACCREDITED)

7:30 P.M.—7:45 P.M. BREAK

7:45 P.M.—9:00 P.M. INNOVATION THEATER DINNER (NON-ACCREDITED) With nearly 55 sessions spread across numerous dynamic tracks, navigating through the full Psych Congress scientific program can be a very daunting task. To ensure you are getting the most out of Psych Congress, plan out your agenda before the meeting. Agenda subject to change. Please visit psychcongress.com/2018 or download the conference mobile app for the latest agenda.

Day 3 Saturday, October 27

7:00 A.M.—9:00 A.M. INDUSTRY-SUPPORTED SYMPOSIA BREAKFAST

9:00 A.M.—9:15 A.M. BREAK

9:15 A.M.—10:30 A.M. Glutamate: An Update for Today’s Solving Clinical Challenges in Sleep Circuitopathies, Genes, Interventions, Diagnosis and Management of Psychiat- Practicing Clinician Disorders and the Treatment of Psychiatric Illnesses ric Sequelae of Catastrophes

10:30 A.M.—10:45 A.M. BREAK

10:45 A.M.—12:00 P.M. TMS: Scientific Underpinnings and Practi- Overcoming Diagnostic and Therapeutic Malpractice and Clinical Pharmacology: Treating Obsessive-Compulsive Disorder cal Applications Challenges in the Individualized Manage- Lessons from Real-Life Cases on How to with Cognitive-Behavioral Therapy ment of Binge Eating Disorder Improve Care and Avoid Problems

12:00 P.M.—12:15 P.M. BREAK

12:15 P.M.—1:30 P.M. INNOVATION THEATER LUNCH (NON-ACCREDITED)

12:15 P.M.—2:30 P.M. EXHIBIT HALL AND POSTER PAVILION

12:30 P.M.—1:00 P.M. PRODUCT SHOWCASE IN THE EXHIBIT HALL

1:45 P.M.—2:15 P.M. INNOVATION SHOWCASE (NON-ACCREDITED)

1:30 P.M.—2:30 P.M. POSTER PRESENTATIONS

2:30 P.M.—2:45 P.M. BREAK

2:45 P.M.—4:00 P.M. Calming the Unquiet Mind: An Integrative Better Together: Mental Wellness as Predicting What the Treatment of Schizo- Ketamine and Other Putative Rapid-Act- Understanding and Treatment of General- an Effective Augmentation Strategy in phrenia Will Look Like in a Decade ing Antidepressant Medications: What ized Anxiety Disorder Psychiatry Have They Taught Us About Neurobiology

4:00 P.M.—4:15 P.M. BREAK

4:15 P.M.—5:30 P.M. Practice Pearls for Managing ADHD in Children and Planet of the Apps: Enabling Technology to Make You a Bipolar Disorder in Later Life Adolescents Better Clinician

5:30 P.M.—5:45 P.M. BREAK

5:45 P.M.—6:45 P.M. FEATURED SESSION DRUG DEALER, MD: HOW DOCTORS WERE DUPED, PATIENTS GOT HOOKED, AND WHY IT’S SO HARD TO STOP

6:45 P.M.—7:00 P.M. BREAK

7:00 P.M.—8:15 P.M. INNOVATION THEATER DINNER (NON-ACCREDITED) Day 4 Sunday, October 28 7:30 A.M.—8:45 A.M. INNOVATION THEATER BREAKFAST (NON-ACCREDITED)

8:45 A.M.—9:00 A.M. BREAK

9:00 A.M.—10:15 A.M. My Personal and Professional Journey Through Autism: Boundary Issues in Clinical Practice Ketamine in Psychiatric Practice: Taking the Long-Term Update on Autism Treatment Through the Lifespan View

10:15 A.M.—10:30 A.M. BREAK

10:30 A.M.—11:45 A.M. The Role of Sleep, Weight, and Cognitive Difficulties in Treatment of MDD Solving Clinical Challenges in ADHD and Substance Use Disorders

11:45 A.M.—12:00 P.M. BREAK

12:00 P.M.—1:15 P.M. INNOVATION THEATER LUNCH (NON-ACCREDITED)

1:15 P.M.—1:30 P.M. BREAK

1:30 P.M.—2:45 P.M. PsychoNeuroImmunology 101: Practical Tips on How Immunology Can Serve Psychiatry in Improving Outcomes

2:45 P.M.—3:00 P.M. BREAK

2:45 P.M.—3:45 P.M. RE:THINK @ PSYCH CONGRESS

3:45 P.M.—4:00 P.M. PSYCH CONGRESS 2018: FINAL THOUGHTS AND PANEL DISCUSSION NEWS CONNECTION

Looking at Depression Through an Evolutionary Lens PRECONFERENCE TO EXPLORE VARIED TREATMENT APPROACHES By Terri Airov

COLUMBUS, OHIO—Psych Congress cochair relationships half of the time. Charles Raison, MD, gave attendees a “10,000- “These are the things that really are depres- foot view” of depression at the Psych Congress sogenic—loss of status, loss of connection Regionals meeting here, and will explore the with somebody that you rely upon for your Upcoming Presentation at PSYCH CONGRESS idea more at the upcoming Psych Congress sense of who you are, being shamed, failing SNAPSHOT Psych Congress 2018 2018 preconference. at what you think you should be doing in life As 1 of 4 speakers who presented “New …and then this feeling that you are trapped in New Perspectives in Advanced Psychopharmacology Perspectives in Advanced Psychopharmacol- your circumstances and you can’t get out of ogy: Improving the Quality of Care for Patients them,” Dr. Raison told attendees. Preconference: Improving the Quality of Care for Patients With Depression,” Dr. Raison offered clinicians “So it’s this combination of losing one’s With Depression a new way of thinking about depression, based health and wellness in the world and then on work which he and other researchers have having losses that make you feel like a failure WEDNESDAY, OCTOBER 24 | 7:00 A.M. — 4:30 P.M. done. as a human being, compared to other human Members of the Psych Congress Steering Committee will present a full “I’m not claiming that this provides a uni- beings.” day of clinically relevant information designed to transform the care of versal understanding of depression or even Why is it that these experiences contribute patients with depression. The sessions will explore mind-body necessarily that it’s right,” Dr. Raison said in to depression? The answer, Dr. Raison said, opening his talk. “But it’s good to think about may be rooted in human evolution. connections, neurobiology, positive psychiatry, and wellness. Attendees things, sometimes raise our head a little bit Humans are naturally driven to survive, will receive 2 complimentary resource books written by the faculty. above the intense struggle we have on a daily reproduce, and leave offspring in order to pass basis in the clinical world and just think about on their genes. Dr. Raison suggested that things their life that are making them depressed. The “One of the core features is transforming a 10,000-foot view.” that indicate to humans that they are failing concept may provide a clue as to why certain people’s consciousness and perceptions in Dr. Raison is the Mary Sue and Mike Shan- at this evolutionary mandate are the things factors contribute to depression, when it may ways to give them the powerful perception non Chair for Healthy Minds, Children & Fam- that make them the most depressed. not be clear on the surface, he said. that they have agency in their lives and are ilies and professor, Human Development and For example, being ostracized from a group The theory has broad implications for men- interconnected in ways they didn’t realize they Family Studies, School of Human Ecology, you were born into 10,000 years ago was an tal health treatment, Dr. Raison argued. were,” he said. and professor, Department of Psychiatry, School almost certain death sentence, he said. Today, Across human evolution, three proximal Dr. Raison will discuss the modality, which of Medicine and Public Health, University of being left out of a group would not have the mechanisms have been reliably associated he calls “ancient practices,” further at the day- Wisconsin-Madison. same practical effect, but can still lead to with overall reproductive success: health, af- long Psych Congress 2018 preconference, Although there is little known about the serious depression. filiation, and agency—the ability to chart your being held Oct. 24 in Orlando, Florida, in genetic causes of depression, Dr. Raison said “The things that make us depressed today own course and influence your life and the advance of the national Psych Congress much has been established about the envi- that seem unrealistic were not unrealistic lives of others. meeting. ronmental causes. The most depressing things 10,000 years ago, 50,000 years ago,” Dr. Rai- While clinicians can work to help patients The concepts play a large part in a book Dr. in the world, he said, are getting sick and son said. “They were true signals that you achieve these 3 mechanisms, a set of tech- Raison coauthored with Psych Congress Steer- experiencing circumstances that induce or were at risk of failing at these twin mandates— niques being brought into mental health treat- ing Committee member Vladimir Maletic, MD, cause the perception of loss, primarily in per- survival and reproduction.” ment can target depression by just giving MS, titled The New Mind-Body Science of sonal relationships. When the cause of a sui- He urged clinicians to remember the theory people the perception that they have these Depression. The book will be given to all cide is known, he noted, it is related to disrupted when talking to patients about the things in mechanisms, Dr. Raison said. attendees of the preconference. Dr. Maletic will also speak at the preconference, present- ing “Do Glia Get the Blues? Neurobiological Basis for Advanced Treatment of Depression.” In addition, Psych Congress cochair Rakesh Jain, MD, MPH, will present “What a Wonder- ful World: Positive Psychiatry and Its Implica- tions for the Advanced Psychopharmacolo- gist,” and Steering Committee member Saun- dra Jain, MA, PsyD, LPC, will present “Walking on Sunshine: Wellness Interventions in Med- ication Partial Responders—A Practical Man- ual-Based Approach.” A book by Drs. Jain, WILD 5 Wellness Ancient Practices for Modern Times: A Prescriptive & Proven 90-Day Mental Wellness Program, will also be given to all preconference attendees. Following their presentations, all 4 speak- ers will take part in an interactive panel dis- cussion on several complex patient cases. ■

REFERENCE “New perspectives in advanced psychopharmacology: im- proving the quality of care for patients with depression.” Pre- sented at the Psych Congress Regionals meeting; Colum- Psych Congress Steering Committee members (L-R) Rakesh Jain, MD, MPH, Saundra Jain, MA, PsyD, LPC, Vladimir Maletic, MD, MS, and Charles Raison, MD, answer bus, OH; June 9, 2018. questions from attendees at the Psych Congress Regionals meeting in Columbus, Ohio.

20 Psych Congress Network • Summer 2018 • psychcongress.com SAVE $100 ON YOUR REGISTRATION FOR THE 31ST ANNUAL PSYCH CONGRESS WITH PROMO CODE PCS100 NEWS CONNECTION

Optimizing the Treatment of Bipolar Disorder in Older Adults DEMOGRAPHIC SHIFTS CREATING LARGER GERIATRIC POPULATION By Terri Airov

concentrating or focusing on things, which Her talk will also cover medication safety In her talk, she will present some data from sometimes leads to a misdiagnosis of demen- and tolerability issues and interactions be- a study that she was involved in, on a self- tia or Alzheimer’s disease, said Dr. Sajatovic, tween psychiatric medications and other management program designed to help a practicing clinician who has performed types of drugs in the OABD population. people with serious mental illness and research and clinical care in the field for Generally, “older people are much more comorbid health conditions manage their more than 20 years. likely to have side effects, and tend to toler- health. BD and other chronic serious mental “That’s another reason why it’s really im- ate the drug less well,” Dr. Sajatovic said. “A illness generally shorten a person’s life span portant for clinicians to at least have some rule of thumb to treat older people is to start by 1 to 2 decades, Dr. Sajatovic said. ■ familiarity with what mood disorders look low and go slow with drugs. I would also like in elderly people,” she added. throw in a third one—­don’t stop too soon.” REFERENCES World Health Organization. Are you ready? What you Taking a thorough clinical history is crit- As is the case with the general population need to know about ageing. World Health Day 2012. ical in distinguishing between bipolar of people with BD, there is little data on non- http://www.who.int/world-health-day/2012/toolkit/back- ground/en/. Accessed July 17, 2018. depression and dementia, she said. She sug- pharmacological interventions that may help gests clinicians ask about patients’ previous OABD. Social support is one element that Young RC, Mulsant B, Sajatovic M, et al. GERI-BD: a ran- domized double-blind controlled trial of lithium and dival- mood-related symptoms, mania, and bouts has been shown to be beneficial, Dr. Sajato- proex in the treatment of mania in older patients with of depression, including postpartum depres- vic said. bipolar disorder. The American Journal of Psychiatry. 2017;174(11):1086-1093. sion. Women with BD are particularly prone Martha Sajatovic, MD to postpartum mood disorders, and there used to be much less appreciation of those conditions, she said. he world’s population of people aged Some people have a misconception about Suggestions for Treatment of Older Adults 60 years and older has doubled since BD—that it burns out or goes away as people With Bipolar Disorder 1980, and, for the first time ever, the age, Dr. Sajatovic said, adding that the data Tnumber of adults aged 65 years and older is do not suggest that is true. expected to exceed the number of children Despite the differences between older and • Prescribe mood stabilizers with evidence of efficacy under 5 by 2020. younger people with BD, the US Food and Considering such demographic trends, Drug Administration (FDA) does not differ- in this population, which include lithium, valproate, Martha Sajatovic, MD, believes mental health entiate between the groups for pharmaco- olanzapine, , , and lamotrigine. clinicians need to be educated about mood logical treatments. disorders in older adults, even if they are not In addition, very few published clinical • Consider lithium at appropriate doses as a first-line specifically practicing geriatric psychiatry. trials have focused on older adults with bi- “It’s my opinion, and I think a number of polar disorder (OABD), Dr. Sajatovic said. She agent. clinicians agree, that as a field we need to knows of only one such randomized, con- • Dosages should be one-half to two-thirds of dosages be more familiar with working with older trolled , and she will discuss it people,” said Dr. Sajatovic, Professor of Psy- in her Psych Congress presentation. That used in younger people with bipolar disorder. chiatry and Neurology and Willard Brown research, funded by the US National Institute Chair in Neurological Outcomes, Case West- of Mental Health, compared lithium with • Be attentive to drug interactions/medical comorbidity. ern Reserve University School of Medicine, divalproex in people aged 60 years and older • Promote self-management/exercise and use of other Cleveland, Ohio. who have type 1 bipolar mania. “People are living longer. Unfortunately, Many clinicians believe lithium should not behavioral modalities. the downside of that is…we have more years be used in older people—a concept which that we’re dealing with different kinds of Dr. Sajatovic hopes to also address in her • Recognize that the illness may change over time. chronic health conditions.” presentation, titled “Bipolar Disorder in Later Dr. Sajatovic will speak at the annual Psych Life.” Congress conference about one such condi- “I think our understanding in recent years tion—bipolar disorder (BD), which often is a bit more nuanced than that,” she said. “I affects older adults and younger adults dif- think we just have to be careful how we use ferently. it, but it can actually be a highly effective Although the research is somewhat lim- medication for older age bipolar disorder.” Dr. Martha Sajatovic’s Upcoming ited, studies have suggested the manic symp- Data has suggested that lithium can pre- PSYCH CONGRESS SNAPSHOT toms of BD are often—but not always— serve or protect cognitive functioning, and Presentation at Psych Congress 2018 attenuated or milder in older adults, compared the US National Institutes of Health is fund- with younger people with BD. Older people ing more research on the topic, Dr. Sajatovic Bipolar Disorder in Later Life may also be more irritable and may experi- noted. SATURDAY, OCTOBER 27 4:15 P.M. — 5:30 P.M. ence physical complications related to BD “I think that’s an area that everybody can | more frequently. Conversely, depressive get behind,” she said. “It potentially has prop- Given demographic trends, older adults with bipolar disorder (OABD) symptoms are generally the same in the two erties that can really help brain health and, are a growing segment of patients with bipolar disorder. This session will groups. again, given the demographic changes that build on a 2016 report on treatment recommendations for this Older people with bipolar depression may we’re seeing globally, I think that’s very ex- population, educate participants about OABD, and review new research. think more slowly and may have difficulty citing.”

ADVANCE YOUR PSYCHOPHARMACOLOGY, PSYCHOTHERAPY, & WELLNESS KNOWLEDGE psychcongress.com • Summer 2018 • Psych Congress Network 21 NEWS CONNECTION

Clearing Up Confusion About Cannabis Therapeutics CLINICIANS REMAIN CONCERNED ABOUT RECOMMENDING USE By Mike Bederka

upcoming Psych Congress. She has 35 years other areas need further investigation, she difficult for her to recommend CBD oil, she of experience in family practice and women’s said. For example, relative to the general said. “Hemp is used for bioremediation—they health, including 24 years with the primary paucity of cannabis research, much is known plant it at Superfund sites, and it’s not a food care practice of Frank Lucido, MD, a pioneer about tetrahydrocannabinol (THC), the can- crop, so they can spray it with anything.” of the medical cannabis movement. Their nabinoid that causes the euphoria felt by Patients also want to discuss vaping, a practice led the way to implementation of cannabis users. Yet, about 8 other major popular and convenient way to reap the ben- California’s Compassionate Use Act of 1996, cannabinoids potentially could be included efits of cannabis. Dr. Mangini, who prefers one of the first medical cannabis laws in the in therapeutics. to recommend tinctures or edibles, remains country. Dr. Mangini also plans to discuss concerns conservative about endorsing the vaporiza- Dr. Mangini estimates the practice has she frequently hears from patients. Senior tion of cannabis concentrates. The impact advised several thousand medical cannabis citizens, in particular, often worry that can- of additives that may be in concentrates or patients over the years. Patients get relief nabis use will become a gateway to drug chemicals that may be added to enhance the with cannabis from a wide variety of prob- addiction, and patients always ask about the flow of the concentrate toward the heat source lems, such as pain, insomnia, migraines, and safety of (CBD) oil extracted from aren’t well-studied and may have unwanted muscle spasms. Calling cannabis a “very safe hemp plants. effects. and effective medicine,” she will share what For the latter, the answer doesn’t come “Even for those who feel knowledgeable she has learned from decades of clinical ex- easily. Minimal control of added ingredients about cannabis, there is still a lot to be Maria Mangini, PhD, FNP-BC perience, starting with a basic review of and questionable growing practices make it learned,” she said. ■ cannabis’ physiologic aspects. The talk will educate prescribers on med- ical cannabis topics such as drug interac- wenty-nine states and Washington, tions, genetic polymorphisms, safety prac- DC currently allow medical cannabis, tices, and the importance of proper dosing, Prescribers don’t want to but concern about the consequences Dr. Mangini said. Tof recommending its use still runs high among She alluded to the high-profile 2014 New suggest or recommend a practitioners. York Times column by Maureen Dowd, who “ “There’s a lot of misapprehension about wrote about how she overdosed on a pot what it involves and what potential risks a candy bar in Colorado. “As my paranoia deep- medicine about which they provider is taking—even in a state where ened, I became convinced that I had died cannabis is allowed as a medicine,” said Maria and no one was telling me,” the Pulitzer Prize have no clinical training. Mangini, PhD, FNP-BC. winner penned at the time. But Dr. Mangini, director of the Family Words like this sent many people into a ” Nurse Practitioner Program at Holy Names panic about the potential harms of cannabis, University, Oakland, California, doesn’t even Dr. Mangini said. “You can easily get into consider this confusion the biggest road- trouble with orally administered cannabis if Dr. Maria Mangini’s Upcoming block to widespread adoption of cannabis you don’t understand how much difference PSYCH CONGRESS therapeutics. there is between inhalation and oral inges- SNAPSHOT Presentation at Psych Congress 2018 “Prescribers don’t want to suggest or rec- tion.” ommend a medicine about which they have Also during Dr. Mangini’s Psych Congress Cannabis Therapeutics: Advising Patients on Safe and no clinical training,” she said. “The research session, she will review terpenes, the group environment has been severely constricted of substances that gives different cannabis Effective Use by prohibition. We’re about 40 years behind cultivars their smell. She gave the example THURDAY, OCTOBER 25 | 9:00 A.M. — 10:15 A.M. where we should be in terms of understand- of linalool, a terpene present in many can- ing the way cannabis can be used as a med- nabis plants as well as lavender, which peo- This session will provide an introduction to the endocannabinoid system icine. Some of that information just isn’t ple have used as a sedative in aromatherapy and the principal phytocannabinoids and terpenes. Dr. Mangini will available yet.” applications for generations. “Cannabis plants share rules of thumb for cannabis dosing and interactions with standard To help clinicians catch up, Dr. Mangini high in linalool might be good to help people pharmaceuticals to help clinicians guide patients in the safe and will present “Cannabis Therapeutics: Advis- sleep or relax,” she said. effective use of cannabis medications. ing Patients on Safe and Effective Use” at the Along with the exact effects of terpenes,

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Future Opportunities in the Treatment of Schizophrenia RESEARCHERS EXPLORING WAYS TO IDENTIFY SYMPTOMS SOONER By Mike Bederka

“How do we use modern technology and of debate as to whether or not we should very widely to treat depression and the tremendous presence of young people stop them after awhile. Do they cause mood disorders, so in effect, we’re see- on social media to help inform this issue?” unwanted changes in brain function in ing more people get these drugs. Peo- asked Dr. Kane, who is also the Senior Vice and of themselves? We still struggle ple need to be reminded of the risk.” President for Behavioral Health Services, with these questions.” • The great deal of imaging-related data Northwell Health, in New Hyde Park, New • The FDA’s recent approvals of 2 drugs that show differences in the brains of York. to combat tardive dyskinesia (TD), a people with schizophrenia, compared Along with this topic, he will explore many syndrome of abnormal, involuntary with healthy controls. In addition, early other areas during his upcoming Psych Con- movements associated with antipsy- study findings suggest some specific gress session, “Predicting What the Treat- chotic drugs. “A lot of clinicians assume changes in magnetic resonance imag- ment of Schizophrenia Will Look Like in a tardive dyskinesia is no longer a major ing (MRI) resting state striatal connec- Decade,” such as the advantages of coordi- concern because the newer antipsy- tivity are associated with antipsychot- nated specialty care. This multimodal team chotic drugs tend to have a lower risk ic drug response. “These are future approach to the management of early-phase of TD,” Dr. Kane said. “At the same time, opportunities of which we need to take schizophrenia includes individual and fam- some of the newer drugs are being used advantage,” Dr. Kane said. ■ ily therapy, cutting-edge medication man- agement, and support to help people return John M. Kane, MD to school and work. The National Institute of Mental Health (NIMH) funded the Recovery After an Initial nticipate some significant changes Schizophrenia Episode–Early Treatment We have people in the treatment of schizophrenia Program (RAISE–ETP) study, which sought over the next 10 years, from a move to determine if coordinated specialty care Atoward coordinated specialty care to harness- would produce better outcomes in people experiencing psychosis ing the power of social media to help iden- with first episode psychosis, compared with “ tify symptoms sooner, said John M. Kane, usual care. It found advantages in outcome MD. measures such as quality of life, symptoms, and all of the sequelae and The median time between the develop- return to work and school, and retention in ment of their first psychotic symptoms to treatment. However, the research found no when people receive treatment is a stagger- benefit in the rate of hospitalization. not getting any treatment. ing 18 months in the United States, according “That’s something we need to address,” to a recent study conducted by Dr. Kane, noted Dr. Kane, a frequent speaker at Psych Professor and Chairman, Department of Psy- Congress who has worked with schizophre- The question is what can chiatry at the Donald and Barbara Zucker nia patients for 35 years. “Adherence plays School of Medicine at Hofstra/Northwell, a big part in that, and it’s hard to get people Glen Oaks, New York. to stay on medication for long periods of you do about that. “This is a huge challenge,” he said. “We time.” have people experiencing psychosis and all To that end, Dr. Kane also will discuss a of the sequelae and not getting any treatment. tool recently approved by the US Food and ” The question is what can you do about that.” Drug Administration (FDA)—a “digital” anti- A number of factors contribute to untreat- psychotic medication that features a novel ed psychosis, Dr. Kane said, including issues way to track adherence. A tiny sensor, such as stigma, confusion on where to seek embedded in the tablet, emits a signal when help, and lack of mental health awareness. it hits the body’s gastric contents. The mes- “They often think this is a reaction to stress sage transmits through bodily tissue to a Dr. John Kane’s Upcoming Presentation and will go away if they get more sleep or sensing patch worn on the torso and it is PSYCH CONGRESS SNAPSHOT exercise,” he added. then transmitted to a mobile device showing at Psych Congress 2018 Fortunately, researchers continue to explore the exact date and time at which the drug new methods of tightening the window of was swallowed. Predicting What the Treatment of Schizophrenia Will Look untreated psychosis, he said. For example, Other topics Dr. Kane plans to cover Like in a Decade social media may help identify people with include: psychiatric symptoms more quickly than • A large ongoing study that explores SATURDAY, OCTOBER 27 | 2:45 P.M. — 4:00 P.M. usual. whether a long-acting injectable formu- Schizophrenia treatment has many gaps and unmet needs, ranging from With people’s consent, investigators have lation could reduce the risk of hospital- reducing the duration of untreated psychosis to fostering adherence and tracked their social media posts and found ization, particularly in young people preventing relapse and hospitalization. Dr. Kane will provide participants their picture and language usage change as with early-phase schizophrenia. “There’s they develop psychosis, he said. In addition, still controversy about the need for and with an overview of recent progress in the treatment of schizophrenia looking at internet search history can reveal impact of long-acting formulations and and an understanding of how current unmet needs could be addressed what individuals might be thinking or expe- the general use of medication for long in the future. riencing. periods of time,” he said. “There’s a lot

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A New Generation of Depression Treatment Approaches EMERGING THERAPIES COULD ADDRESS UNMET NEEDS IN PATIENTS By Terri Airov

ince Michael Thase, MD, became a ketamine. Dr. Thase was skeptical about it intranasally, will likely be approved by the • Sage Therapeutics’ intravenous for- psychiatrist in 1983, the landscape then. But today he is optimistic about what US Food and Drug Administration (FDA) in mulation of brexanolone, formerly of depression treatments and ketamine—and other emerging psychiatric 2019. And he wouldn’t be surprised if, one SAGE-547, which is also under review Sapproaches has changed dramatically. medications with new mechanisms of day, ketamine programs can be found at by the FDA. The neurosteroid was “first The antidepressants and mono- action—may mean for the future of mental most major treatment centers, as electro- thought to be specifically relevant for amine oxidase inhibitors of the early 1980s health treatment. convulsive therapy (ECT) and neuromodu- postpartum depression but may actu- were followed by selective reup- “There’s just more and more evidence lation programs are. ally have antidepressant effects for take inhibitors, serotonin– that although ketamine itself may ulti- “I think having a pharmacologic therapy both men and woman irrespective of reuptake inhibitors, first-generation anti- mately not be the way forward, the way it that could be used ahead of, or instead of, whether pregnancy is involved,” Dr. psychotics, and modern forms of psycho- engages a different receptor system in the ECT, that has a 50/50 chance of treating Thase said. therapy. brain is truly different than the old mono- patients that aren’t responsive to several • Potential oral medications in the same In the early 2000s, a few successful mono- amine reuptake inhibitors,” he said. “So that lines of standard therapy, and having a treat- class as the Sage compound. amine-targeted antidepressants emerged. does create the excitement of a new way ment that you can say ‘go’ or ‘no go,’ is it Aside from pharmacotherapy, Dr. Thase But after that, activity in the field dwindled, forward.” going to work or not work, within a week or is also hopeful about the future potential of said Dr. Thase, Professor of Psychiatry, Perel- Dr. Thase will review data on some of two is a pretty dramatic development,” he neuromodulation, such as transcranial mag- man School of Medicine, University of Penn- those emerging medications, outline the said. netic stimulation (TMS), which he sees as sylvania, and Corporal Michael J. Crescenz pathophysiology of depression, and discuss Approval of , being developed a treatment alternative for people who may Veterans Affairs Medical Center, Philadel- the limitations of available treatments at a by Janssen Pharmaceuticals, Inc., could set discontinue antidepressants because of side phia, Pennsylvania. session at the upcoming Psych Congress in motion the approvals of other drugs with effects. “None of the potentially exciting new- 2018 conference. new approaches to alleviating depression, “I think that we’re only at the beginning generation treatments that were being “There’s clearly not a sense that we’ve won, Dr. Thase said. of this approach and era and I’m eager to researched at that time came to fruition as that we’ve got all that we need,” he said. “One It is conceivable that rapastinel, under know if this deeper TMS delivery actually antidepressants,” he said, noting that many out of 3 people who begin treatment don’t development by Allergan, could come to tangibly improves upon conventional TMS,” large pharmaceutical companies moved achieve, ultimately, the goal of having a full market in 2020 or 2021, he said. Rapastinel he said, referring to a system that reaches away from research and development of and sustained remission, and that’s an unac- is a fast-acting intravenous formulation of deeper into the skull than conventional TMS. antidepressants after major trials failed. “No ceptably high failure rate given all the ways a novel NMDA receptor partial agonist. It is It may be possible to fuse TMS with con- new truly different antidepressants came that depression can complicate or poten- in phase 3 clinical trials for treating both ventional therapies such as cognitive ther- out for over a decade.” tially even ruin your life or lead to suicide.” treatment-resistant depression and acute apy, Dr. Thase said. Simultaneously, about 12 years ago, Dr. Thase believes that esketamine, a ste- suicidal crisis associated with depression, “If TMS does indeed facilitate learning the first reports began to emerge about reoisomer of ketamine which is administered he noted. potential then it’s possible that people who Other drugs in development to watch, Dr. are basically too depressed to make good Thase said, include: use of cognitive therapy may be able to start • ALKS 5461, an investigational com- making better use of it,” he said. pound from Alkermes that is under Dr. Thase noted that treating depression review by the FDA. It combines is not just about biology. Integrating psy- buprenorphine, a partial mu-opioid chopharmacology with focused psycho- receptor agonist and kappa-opioid therapies and other rehabilitation strategies receptor antagonist, with samidorphan, can make a big difference in improving the a mu-opioid receptor antagonist. Dr. lives of patients, he said. Thase said the drug could tap into the “Even if the treatment stabilizes the ill- body’s opiate system to improve mood ness process, they’ve still got to roll their without carrying a risk of abuse or sleeves up and work on mending their lives,” addiction. he said. ■

Dr. Michael Thase’s Upcoming PSYCH CONGRESS SNAPSHOT Presentation at Psych Congress 2018 Neurobiologic Insights Into Major Depressive Disorder: An Update on Emerging Therapies With Novel Mechanisms of Action THURSDAY, OCTOBER 25 | 3:45 P.M. — 5:00 P.M. Dr. Thase will discuss the prevalence and burden of major depressive disorder (MDD) and the limitations of current medications. He will also review the current understanding of the pathophysiology involved in MDD and present data on emerging MDD pharmacotherapies. Michael Thase, MD, gives a presentation at Psych Congress 2017.

VISIT PSYCHCONGRESS.COM/2018 OR CALL 800-205-8233 TO REGISTER TODAY psychcongress.com • Summer 2018 • Psych Congress Network 25 Using Comedy to Confront Mental Illness and Its Public Stigma Stand Up For Mental Health Program Has Helped Hundreds of People

By Terri Airov Using Science and Genetics to Transform Everyday Practice

or David Granirer, comedy is more was in high school and I actually attempted WHY DO YOU THINK PEOPLE than a way to get laughs out of an suicide and ended up in a psychiatric ward Q:DIDN'T RECOGNIZE IT UNTIL audience. for I think about 6-8 weeks. To me it's amaz- YOUR MID 30S? FAs a community college comedy instruc- ing—I obviously had depression. Here I am tor, he noticed how life-changing it could be a teenager. I tried to commit suicide, all that I had lots of casual friends from musi- for someone to take on and conquer the kind of stuff, but no one ever caught it. So I A: cian circles, but I didn't really have a challenge of performing as a stand-up co- wasn't diagnosed until my mid 30s. I went lot of close friends who would've known it. median. So, in 2004, Granirer founded Stand around with untreated, undiagnosed depres- I just think they saw me and thought every- Up For Mental Health and began teaching sion for almost 20 years. And then finally in thing was fine. people with mental health issues how to my mid 30s, I was seeing a psychiatrist for perform stand-up comedy — as a way to help therapy and she kept saying, “David, you're DID YOUR PERSONAL STRUG- build their confidence as well as reduce pub- depressed.” And I thought depression was Q:GLES LEAD YOU TO WORK, lic stigma around mental illness. Granirer, a feeling, so I would say no, “I'm just going OR WANT TO WORK, IN THE MENTAL who has depression himself, has since taught through some family issues. I'm not depressed, HEALTH FIELD? hundreds of people how to tell their stories I'm just sad.” She kept on saying that, so I through comedy. said “OK fine. I'll try to use the medication Yes. So just to backtrack a little bit— Granirer, a certified counselor in Canada, that she wants me to take. Nothing will hap- A: during my time as a guitar player I recently received the Meritorious Service pen. It's just stuff bugging me.” ended up getting tendinitis 4 times. That's Medal from the Governor General of Canada Well, I went on an antidepressant and all kind of an occupational hazard, but I got it for his work. He has also been named one of of a sudden it was like “Oh my God, this is way worse. So, each time I got tendinitis I David Granirer, RPC, MPCC, 150 Difference Makers in Canadian Mental what people feel like when they feel good, was basically isolating myself and sometimes MSM Health, and received a Life Unlimited Award like people actually want to get out of bed, it took a year to get better. And I would just from the Depression and Bipolar Support they actually want to do stuff.” So, to me, it isolate myself. I would watch like 14 hours of Alliance, an Award of Excellence from the was this huge revelation. Obviously I'm not TV a day. I wouldn't see anyone, I wouldn't National Council for Behavioral Health, and saying that medication is alright for everyone, talk to anyone. And the last time it happened a Champion of Mental Health Award, which but it's certainly alright for me.” I did the usual isolating myself but then all recognizes people who have helped advance of sudden I got this thing like “Wow, I need the mental health agenda in Canada. DID YOU FEEL DEPRESSED to do something. If I want to live I need to do On Oct. 25, he will share his story and Q:ALL THROUGHOUT YOUR 20S? something.” So, I ended up volunteering at perspectives with Psych Congress attendees, OR WAS IT ON AND OFF? the Vancouver Crisis Center. And about 5-6 as one of the conference’s Featured Speakers. years later, they hired me as their trainer. I He hopes to bring attendees a mixture of I would say it was on and off. But I was training crisis line volunteers in suicide comedy, education, and inspiration. Here, A: was constantly depressed. I was a prevention and crisis intervention, which I Granirer discusses the path that led him to musician at this point and I loved to play the had done myself as a volunteer. I was there establish Stand Up For Mental Health, how guitar. However, there would be times when for almost 10 years as their trainer. it helps participants, and his goals and plans I just couldn't play. Sometimes it would last for the program. a couple days. Sometimes it was a couple SO THAT WAS THE weeks. And I used to think, “Oh, I'm just not Q:BEGINNING OF YOUR WORK CAN YOU DESCRIBE WHEN feeling any inspiration right now.” But now IN MENTAL HEALTH? Q:AND HOW YOUR STRUGGLE I look back on it and I think those were de- WITH MENTAL HEALTH ISSUES pressive episodes. No wonder I couldn't play. Yes. And then around that time I got BEGAN? So certainly, when I started to feel better I A: my counselor training and became a looked back at the past 20 years and I could counselor. I did some private practice for My struggle with mental health issues see so clearly how depression had such a quite a few years. I never had full caseload. A: began when I was about 16 or 17. I big effect in my life. I always had like a third or a half of a caseload,

26 Psych Congress Network • Summer 2018 • psychcongress.com ADVANCE YOUR PSYCHOPHARMACOLOGY, PSYCHOTHERAPY, & WELLNESS KNOWLEDGE Using Comedy to Confront Mental Illness and Its Public Stigma

which was fine with me because I was doing HAVE YOU SEEN A LOT OF Yes, I think we're making progress in people and encourage them and help them other things. I don't do much counseling Q:THEM GO ON TO DO STAND- A. removing the stigma surrounding to build their strengths, and I think humor anymore at all but I'm still busy with Stand UP COMEDY? mental illness. I think the fact that we're talk- is a strength. Up For Mental Health. I see maybe 2 people ing about it more is a real big step. I still think One of the comics I worked with, she has on a really intermittent basis. No. There’s a couple. But I think that's there's quite a bit of stigma left to cope with. schizophrenia and one of her really difficult A:not why people are taking the program. But it's certainly better than it was 10 years things to do was riding public transit because DID YOU HAVE ANY OTHER A lot of them are taking the program just ago. she'd be on transit and her voices would be Q:MENTAL HEALTH-RELATED because they want to challenge themselves telling her, “Everyone's looking at you. They POSITIONS? and do something different. And they also IS THERE ANYTHING YOU think you're a freak and something's wrong want to be able to see the humor in their lives. Q:CAN POINT TO, SAY, IN THE with you.” Well, after she did Stand Up For I started Stand Up For Mental Health Because let's face it: when you're dealing with LAST 10 YEARS THAT HAS HELPED Mental Health and developed her sense of A: in 2004. a mental health condition there's also not a REMOVE SOME OF THAT STIGMA? humor, she said the next time she got on a lot of humor in that. bus she started joking around with people HOW DID THAT COME Well, I like to think that Stand Up For and it was a great bus ride. So here she was, Q:ABOUT? HOW WOULD YOU SAY CLINI- A: Mental Health has helped. But I also she had a skill that leveled the playing field Q:CIANS CAN USE COMEDY IN think that we're having situations where between her and these so-called scary, nor- For about the past 20 years now, I've THE CARE OF THEIR PATIENTS? IF A more people are out in the public telling mal people. And so, it was through, rather A: been teaching the stand-up comedy CLINICIAN HASN'T BEEN TRAINED BY their stories. And that's what’s powerful for than focusing on what was wrong with her, course at one of the local colleges. It has YOU, BUT THEY WANT TO USE THIS people. What I've understood in terms of it was focusing on what was right with her absolutely nothing to do with mental health. CONCEPT, IS THERE ANYTHING YOU the research is it says that taking out ads on and helping bring it out. But occasionally, I would see people come TV or the internet is not very effective. The And I would say too that one of the things CAN TELL THEM THEY CAN DO IN through the course and they would have this effective thing is when people get to interact I think that makes my program a success is THERAPY? life-changing experience. And I would think, with somebody who has a mental health that people aren't coming because there's “Wow, wouldn't it be great to be able to give Well, first of all, they shouldn't try to condition. And I think that's happening a something wrong with them. They're com- this to people who wanted the life-changing A:be stand-up comics in their work with lot more these days in terms of educating ing because there's something right with experience and who also wanted to do com- clients. But, sometimes they can just ask the people. them and that's a whole different way of edy.” And so, I figured I'd start in mental health question “So, here we are, we've talked about doing things. because I had mental health issues and those x, y, and z, so can you see the humor in that? IS THERE ANYTHING ELSE were essentially my people. Do you see anything funny and if so, what is Q:THAT YOU THINK NEEDS TO DO YOU HAVE ANY NEW To give an example, I remember one woman it?” And so, you're not necessarily writing HAPPEN TO CONTINUE TO LESSEN Q:PROJECTS ON THE who took my community college course and stand-up comedy, but I think sometimes it THE STIGMA? HORIZON? said she had a fear of flying. And the day after helps a little bit to say, “Well, you know what's our showcase she had to get on a plane. And funny is that…” Once again, I think as much engage- In 2005, there was a documentary she said, “My fear was gone. I felt like once I'd The other thing I think clinicians can do is A: ment as possible between people who A: made on Stand Up For Mental Health done stand-up comedy, I could do anything.” ask people, “So, what do you do to get a laugh have the condition and people who don't. and it was really a great documentary, a And that's what made me think, “Wow, this in the course of your life?” Because we ask 45-minute documentary. The director of that would be great to give to other people.” people, “What do you do for stress manage- AS FAR AS YOUR PSYCH CON- documentary has decided that she wants to ment?” and “What do you do for exercise?” Q:GRESS PRESENTATION, IS turn it into a feature-length documentary, HOW DID YOU BECOME THE And I think humor and laughing is on par with THERE A MAIN MESSAGE THAT which is 90 minutes long, and include foot- Q:COMEDY TEACHER AT THE those things in terms of helping to recover. YOU'RE HOPING THE ATTENDEES age from back in 2005, but also follow the COMMUNITY COLLEGE? HAD YOU WILL TAKE AWAY THAT WE HAVEN'T comics and see where they are now. So, I'm DONE COMEDY YOURSELF AS WHAT KIND OF PROGRAM TALKED ABOUT YET? really excited about that documentary and WELL? Q:WILL YOU DO AT PSYCH CON- she's going to be submitting it to all sorts of GRESS? I guess part of the message is that film festivals like Hot Docs [Canadian Inter- Yes. I was doing comedy for about 2 A: folks with a mental health condition national Documentary Festival] and Sundance A: years. It was kind of a fluke. Someone I'm just speaking myself. My presen- have way more resources than we give them [Film Festival]. So hopefully that'll create who was a board member at the crisis center A: tation will be a combination of com- credit for. And I think sometimes it helps more recognition for the program and allow worked at this college and he came to me edy and education and inspiration. the clinicians to be able to spot that in me to help more people. ■ one day and he said, “Listen, we just fired our comedy instructor because he didn't show HAVE YOU EVER HAD ANY- up to class. Are you interested?” And I said, Q:BODY TELL YOU THEY DON'T “Sure,” and that's how it all started. THINK COMEDY HAS A PLACE IN David Granirer’s Upcoming Presentation MENTAL HEALTH, THAT YOU'RE PSYCH CONGRESS WHAT ARE YOUR MAIN GOALS COMBINING SOMETHING TOO FUN SNAPSHOT at Psych Congress 2018 Q:FOR STAND UP FOR MENTAL WITH SOMETHING SERIOUS? AND HEALTH? WHAT WOULD YOU SAY TO SOME- I'm OK But You Need Professional Help: Creating Recovery BODY WHO HAD THAT OPINION? Well, my main goal is to train as many One Laugh at a Time A: folks as I can who want to do stand-up No one's really told me that. I've had THURSDAY, OCTOBER 25 | 5:15 P.M. — 6:15 P.M. comedy in order to build their confidence A: a lot of support from both clinicians and also reduce public stigma around men- and people with mental health conditions. I David Granirer will use comedy, education, and inspiration to present a tal health. think it's an idea whose time has come. And different perspective on mental health in this Featured Session. people understand the value of having humor Attendees will learn about Stand Up For Mental Health, a program DO YOU HAVE AN IDEA OF in their lives. Granirer started that has helped hundreds of people with mental health Q:HOW MANY PEOPLE YOU issues. HAVE TRAINED? DO YOU THINK, AS A SOCIETY, Q:WE ARE MAKING PROGRESS I've run the class in over 50 cities in IN REMOVING THE STIGMA ASSOCI- A: Canada, the US, and Australia. So, I'm ATED WITH MENTAL ILLNESS? Psych Congress is your home for: guessing around 350-400 people. Knowledge. News. Networking.

GAIN INSIGHTS INTO CURRENT AND EMERGING TREATMENT STRATEGIES WITH THE BEST MINDS IN MENTAL HEALTH psychcongress.com • Summer 2018 • Psych Congress Network 27 The Growing Role of Neurobiology in Mental Health Care Using Science and Genetics to Transform Everyday Practice

By Jolynn Tumolo

heldon H. Preskorn, MD, has spent mon patterns in its organization (see Figure cancer chemotherapy, which targets the 4 decades in the mental health field 1). It will focus on addiction as perhaps the mechanisms that make cells cancerous. heavily involved in research. He has best example of a well-established circuit Sreceived continuous grant funding since (actually 3 interrelated circuits underlying YOU’VE RECEIVED the late 1970s, which has enabled him to the development of addiction). It will explain Q: CONTINUOUS GRANT pursue hundreds of investigations that have how genes of interest fit into those circuits FUNDING SINCE 1978—FOR added to the current understanding of psy- and how they, in turn, will become the basis chopharmacology and the neuroscience for developing new treatment interventions. AN ESTIMATED $150 MILLION of psychiatric illnesses. His overarching —TO RESEARCH THE NEURO- goal is to bring science to the practice of YOU’VE BEEN IN PSY- SCIENCE OF PSYCHIATRIC psychiatry. Q:CHIATRY FOR 40 YEARS. ILLNESSES AND PSYCHO- Dr. Preskorn is a professor at the Univer- WHAT ARE SOME OF THE BIG- sity of Kansas School of Medicine, Wichita, PHARMACOLOGY. WHAT IS chief science officer for the medical school’s GEST OVERALL CHANGES YOUR SECRET FOR OBTAIN- clinical trials unit, and a professor at the YOU’VE WITNESSED IN THE ING GRANT FUNDING? Laureate Institute for Brain Research, Tulsa, FIELD? Oklahoma. He recently reflected on changes The secret is hard work. In my expe- he has seen in psychiatry over his career Science has started coming to psy- A: rience, 2 adages have held true. First and where he sees the field and patient A: chiatry. The biggest change has been is Thomas Edison’s ratio of 1% inspiration to treatments headed. the development of rationally designed 99% perspiration for creativity. Second is Sheldon H. Preskorn, MD medications such as selective serotonin that scientific discovery favors the prepared WHAT CAN ATTENDEES reuptake inhibitors (SSRIs) and serotonin- mind. It is important to put yourself in the Q:EXPECT TO LEARN norepinephrine reuptake inhibitors (SNRIs). right place at the right time and to recognize FROM YOUR PSYCH CON- They have moved us from a time of reserv- when that alignment occurs. ing therapy for the GRESS TALK? most severely ill because of concern about WHAT ARE SOME OF The talk will be about our emerging their narrow therapeutic index to now, when Q:THE MAJOR FINDINGS A: understanding of the neurobiology the adverse consequences of illness outweigh YOU’VE DISCOVERED AND of psychiatric illness. It may be an introduc- the risk of SSRI and SNRI antidepressants tion to the topic for some attendees and a from a population perspective. ARE MOST PROUD OF? refresher for others. I have developed the We have also entered an era in which My career so far has covered 40 talk with both groups in mind with the re- genetics has come to psychiatry. While that A: years. In the late 1970s and early alization that it is a huge topic for a 60-min- may be of uncertain value now, that will 1980s, I contributed to the following find- ute lecture. undoubtedly change over the next decade. ings: the relationship between tricyclic I will take a big-picture approach and Next and in the not-too-distant future, we antidepressant plasma concentration and give clinical examples to show its relevance will be designing treatments based on an efficacy and safety; that children and to everyday practice. It will start with an understanding of the neurobiology underly- adolescents can suffer from a major depres- overview of the organization of the brain ing specific psychiatric illnesses. That will sive disorder and can receive safe and ef- based on its evolution and will explain com- be as profound as the development of novel fective treatment through a combination

28 Psych Congress Network • Summer 2018 • psychcongress.com VISIT PSYCHCONGRESS.COM/2018 OR CALL 800-205-8233 TO REGISTER TODAY The Growing Role of Neurobiology in Mental Health Care

Dr. Sheldon Preskorn’s Upcoming PSYCH CONGRESS SNAPSHOT Presentation at Psych Congress 2018 Circuitopathies, Genes, Interventions, and the Treatment of Psychiatric Illnesses SATURDAY, OCTOBER 27 | 9:15 A.M. — 10:30 A.M. As more becomes known about the neurobiology underlying psychiatric illnesses, the understanding of such illnesses and the development of treatments are being revolutionized. Genetic information is being used to individualize treatment in increasingly sophisticated ways. This session will educate clinicians on using this cutting-edge approach to diagnose and treat patients.

By dividing patients with major depression enhance the effectiveness of both approaches, into these 3 groups, we can work to determine much like building a better computer leads how these patients differ in terms of genet- to the development and implementation of ics and epigenetics. Discoveries for that better software. Reference: Preskorn SH, Drevets WC. Neuroscience basis of clinical depres- work can spark a major leap forward in un- sion: implications for future antidepressant drug development. Journal of derstanding the pathophysiology of these Psychiatric Practice. 2009;15(2):125-132. DURING ANOTHER illnesses and, in turn, fuel further develop- Q:PSYCH CONGRESS SES- ment of new treatments, whether they be SION, YOU PLAN TO DISCUSS somatic and/or psychosocial interventions of antidepressants and psychotherapeutic FOR HOW LONG HAVE and whether they are aimed at treating the PHARMACOLOGY AND MAL- interventions; that the locus coeruleus Q:FINDINGS ABOUT THE illness or preventing it. PRACTICE LAWSUITS. WHAT regulates cerebral blood flow and blood- NEUROBIOLOGY BEHIND PSY- WILL YOU ADDRESS? brain permeability, and this regulation can HOW DO GENETICS be modified with psychiatric medications; CHIATRIC ILLNESSES BEEN Q:FACTOR INTO TREAT- Most prescribers do not understand that there is genetically determined vari- IMPACTING TREATMENT? MENT INDIVIDUALIZATION? A: the importance of the package insert ability in the metabolism of psychiatric in a malpractice lawsuit alleging negligence medications; and the rules or rationale for Such findings have been impacting CAN YOU GIVE AN EXAMPLE? in the prescribing of a psychiatric medica- therapeutic drug monitoring to guide dose A: the treatments and outcomes of The most immediate impact of genet- tion. Most practitioners do not realize the adjustment of specific drugs or classes of patients with psychiatric illness for more A: ics for clinicians is the fact that vari- package insert is the last step in the approv- drugs. than 100 years. In the early 1900s, 20% of all ants of genes for CYP enzymes can substan- al of any medication and that it is a joint Over a 25-year period starting in the 1980s, psychiatric admissions were for conditions tially alter the safety-efficacy dose-response statement by the US Food and Drug Admin- I participated in the development of every that no longer exist: neurosyphilis and pel- curves for specific drugs for specific indi- istration (FDA) and the manufacturer of the antidepressant and antipsychotic drug lagra. Much more recently, there has been viduals who carry specific variants of the drug. marketed in the United States. I also worked recognition that some forms of psychosis are normal wild type gene. We also now recognize to educate the field about the importance caused by the development of autoanti- that more important than the genotype is the YOU’VE STATED YOUR of cytochrome P450 (CYP) enzymes and bodies against NMDA receptors. current phenotype (functional status) of the Q:OVERALL GOAL IS TO genetic variability in their activity, and the individual. For example, phenotypic conver- BRING SCIENCE TO THE fact that some psychiatric medications, WHAT ARE SOME CUR- sion to CYP 2D6 poor metabolism status is such as fluoxetine, could cause phenocon- Q:RENT NEUROBIOLOGY- just as important as genotypic CYP 2D6 poor PRACTICE OF PSYCHIATRY. version from extensive to poor metabolism BASED TREATMENTS THAT metabolism status. WHEN IT COMES TO EVI- via specific CYP enzymes (such as CYP EXCITE YOU? DENCE-BASED PRACTICE, 2D6). DO ADVANCES IN THE HOW IS THE FIELD FARING? More recently, I contributed to the find- Currently, outpatient psychiatrists Q:NEUROBIOLOGICAL WHERE WOULD YOU LIKE TO ing that approximately 40% of patients with A: have a sizeable population of patients UNDERSTANDING OF PSYCHI- major depressive disorder are not meaning- with a form of major depression that is either SEE IT GO IN THE FUTURE? fully responsive to biogenic amine (sero- not helped or only marginally helped by ATRIC CONDITIONS LEAN TO- tonin, norepinephrine, and ) biogenic amine antidepressants alone and WARD A MORE PHARMACEU- The field has made tremendous strides antidepressants but that a larger percentage, in combination with other such antidepres- TICAL-BASED TREATMENT A: in the last 40 years. It has gone from perhaps 60%, of these individuals robustly sants and various augmentation strategies. APPROACH AND AWAY FROM an era when it had a theory that could explain respond, and rapidly so, to treatment with Their prognosis will dramatically change all human behavior—psychoanalysis—to the glutaminergic antidepressants. The first with the availability of glutaminergic anti- A PSYCHOTHERAPY humble recognition that no single theory can such drug in this class—esketamine—may depressants like esketamine, which can APPROACH? OR IS THERE A explain all human behavior, that different well be marketed next year. produce a robust response in approximate- PLACE FOR BOTH? treatments work for different patients, and A focus of mine for the last decade or ly 60% of such patients within a few days. that the brain is the organ of the soul. more has been how drug development for We can now type patients into 3 groups: There’s a place for both. It is not an Patients will sometimes tell me “people psychiatric illnesses is poised to move from the 50%-60% who are well treated by bio- A: either/or proposition, but rather a say it is all in my head.” I sometimes respond chance discovery (tricyclic antidepressants) genic amine antidepressants, the 30% whose complementary situation. “those people may well be correct but unwit- and rational refinement of pharmacology major depression is not responsive to those Some worry about reductionist science tingly so because what is in your head is your (SSRIs) to new drugs based on an under- antidepressants but is to glutaminergic leaving out psychotherapy and psychosocial brain, and that is the most complicated standing of the neurobiology underlying antidepressants, or the 20% who are not interventions, but that is not warranted. organ in the body by far and what makes us major psychiatric illnesses. responsive to either. Instead, these scientific advancements will uniquely human. ■

SAVE $100 ON YOUR REGISTRATION FOR THE 31ST ANNUAL PSYCH CONGRESS WITH PROMO CODE PCS100 psychcongress.com • Summer 2018 • Psych Congress Network 29 Hidden Forces Behind the US Prescription Drug Epidemic Examining How Myths, Policies, and Practices Contributed to a Crisis

By Jolynn Tumolo

fter noticing more and more patients 1990s, 4 times as many as are prescribed in I was astounded by how much the in her practice struggling with pre- Europe, and more than 10 times as many as A: pharmaceutical industry has a hand scription drug addiction, psychia- in Japan. Europe and Japan are apt com- in dictating standards of medical care. Their Atrist Anna Lembke, MD, investigated the parisons because they are also rich areas outsized influence on what is hailed as “evi- problem of rampant overprescribing in the with aging populations and comparable needs dence-based medicine” was a huge factor in US medical community and the hidden for analgesia. creating the prescription drug epidemic we forces encouraging it. Her resulting 2016 In other words, although we’ve made prog- face today. For example, The Joint Commis- release, Drug Dealer, MD: How Doctors Were ress, we still have a long way to go. sion, which confers the gold standard ap- Duped, Patients Got Hooked, and Why It’s proval that hospitals need for Medicare re- So Hard to Stop, became an influential best- SINCE THE PUBLICATION OF imbursement, acquired opioid propaganda seller. Health Affairs deemed the work a Q:DRUG DEALER, MD, YOU’VE for free from Purdue Pharma [the maker of “thought-provoking book [that] should be CONSULTED WITH LAWMAKERS Oxycontin] and sold it to hospitals trying to a must-read for medical trainees, providers, AND OTHER OFFICIALS LOOKING meet the new Joint Commission quality mea- and health policy leaders working at the TO STEM THE OPIOID EPIDEMIC IN sure of “pain as the 5th vital sign.” Not only forefront of addressing the prescription drug THE UNITED STATES. WHAT LED did the Joint Commission profit from this epidemic." strategy, but it also perpetuated the myth YOU TO BECOME AN AUTHORITY IN Associate professor of psychiatry and that opioids were being underprescribed. THIS AREA AND THEN TO WRITE behavioral sciences at Stanford University School of Medicine, California, Dr. Lembke THIS INFLUENTIAL EXPOSÉ ON THE THE TITLE OF YOUR BOOK— recently talked with Psych Congress about CAUSES OF OPIOID ADDICTION? Q:DRUG DEALER, MD—IS CER- Anna Lembke, MD the state of the US prescription drug epi- In the late 1990s and early 2000s, I TAINLY ATTENTION-GRABBING. AS demic, our modern-day aversion to pain of A: was seeing more and more patients AN MD YOURSELF, WERE YOU COM- all forms, and how her medical colleagues in my practice struggling with addiction to FORTABLE WITH THE TITLE? DO have reacted to her book’s provocative title. opioids and benzodiazepines prescribed by YOU FIND MEDICAL PROFESSION- their doctors. I myself was also prescribing ALS GENERALLY ACCEPT THEIR IS THERE ANY GOOD NEWS benzodiazepines and stimulants too liber- ROLE IN THE CURRENT OPIOID CRI- WITH THE CURRENT STATE ally without recognizing I was harming my Q: SIS, OR DO THEY TEND TO GET OF THE OPIOID EPIDEMIC, OR IS patients. When I realized there was a problem DEFENSIVE AT THE “DRUG DEALER” THE SITUATION STILL ESPECIALLY and tried to alert my colleagues, I met strong TAG? BLEAK? resistance, even among well-educated, com- passionate, and well-intentioned health care The good news is that opioid prescrib- providers. That made me curious about what The title has been a double-edged A: ing in this country has decreased by I now recognize as the invisible forces inside A: sword. It’s the same title I used for approximately 20% relative to its peak in medicine that can cause even a good doctor early drafts of my manuscript, so I kept it 2012. Efforts to re-educate doctors and imple- to provide bad care. when I submitted my final copy. My editors ment policies to curb overprescribing have liked it because it’s attention-grabbing while had an impact. WHAT SURPRISED YOU IN also capturing the major theme of the book: The bad news is that we are still prescrib- Q:YOUR RESEARCH FOR THE the problem of rampant overprescribing. ing 3 times as many opioids as we did in the BOOK? On the other hand, the title has been

30 Psych Congress Network • Summer 2018 • psychcongress.com ADVANCE YOUR PSYCHOPHARMACOLOGY, PSYCHOTHERAPY, & WELLNESS KNOWLEDGE Hidden Forces Behind the US Prescription Drug Epidemic

off-putting for some readers, especially phy- sicians who believe, mistakenly, that I’m Figure 1. Top 25 Prescribing Fields by Total Medicare Part D Claims for Schedule II Opioids in 2013 blaming doctors. In fact, the whole point of the book is to demonstrate that doctors have been victims as much as patients, caught up in a system in which they have limited control over how they practice medicine and are forced to practice in ways that don’t align with their values. I’ve had physicians tell me they didn’t want to read the book because they were dismayed by the title but, after they read it, realized there is little or no doc- tor-blaming. The subtitle, How Doctors Were Duped, Patients Got Hooked, and Why It’s So Hard to Stop, is in many ways a better descrip- tion of the book than Drug Dealer, MD. But I don’t regret the title. I think it’s the right title for this book at this particular time in his- tory. I’ve gotten pushback from health care providers about my message and hate-mail from doctors and patients alike. But my mes- sage, which was radical at first, is now pret- ty well accepted: opioid overprescribing has Reference: Chen JH, Humphreys K, Shah NH, Lembke A. Distribution of opioids by different types of Medicare prescribers. JAMA been a major cause of the epidemic, caused Internal Medicine. 2016;176(2):259-261. not just by pill-mill doctors but also by a wholesale paradigm shift in how we treat pain (see Figure 1). about their health. Cultural factors also played AMID ALL THE SADNESS AND Don’t be afraid to ask your patients CAN YOU TALK ABOUT HOW a role, having to do with patients’ unrealistic Q:ENORMITY OF THE EPIDEMIC, A: about substance use problems and Q:OUR VIEW OF PAIN HAS expectations about how much pain is too IS THERE A PLACE FOR HOPE? other addictions like gambling, gaming, or CHANGED OVER THE CENTURIES? much pain and what doctors can do to help. sex. If you ask, you will be amazed at how There’s always reason to hope, and eager they are to talk. You will also be The modern medical view of pain WHAT ARE SOME OF THE A: the opioid epidemic is no exception. impressed by how much you are able to help, A: stands in stark contrast to how pain Q:MAJOR BARRIERS TO TURN- The silver lining of the epidemic is that it has just by opening a dialogue. was viewed 150 years ago. Today we believe ING AROUND THE EPIDEMIC? raised national awareness inside and outside For far too long we as a field have ignored pain in all its forms is dangerous and can of medicine about the problem of addiction. the problem of substance use and addiction, leave patients with a psychic scar that sets Barriers include the perverse incen- Local, state, and federal entities are putting preferring to talk about every single child- them up for future pain. As such, it has become A: tives inside of medicine driving over- unprecedented resources toward the problem, hood memory before asking simple questions the role of the medical doctor to eradicate prescribing, and the lack of infrastructure in and people across ethnic and sociopolitical about drug and use. In that regard, all pain at any cost. But doctors used to believe the House of Medicine to target and treat divides are engaging in discussion about the many of us, including myself, have been that pain was salutary, that it expedited heal- addiction. problem. complicit in perpetuating the problem. It’s ing and conferred spiritual benefits. With increased awareness and dialogue, time to shine the spotlight on addiction and I certainly don’t believe in leaving people HOW DO YOU SUGGEST MEN- we are reducing stigma and improving access do our part to help, and that includes all of in pain out of some gratuitous, sadistic Q:TAL HEALTH PROVIDERS to treatment for those who need it. us, not just those working in specialty addic- impulse. But the reality is we’re not much ADDRESS THE ISSUE OF OPIOIDS IN tion treatment. better today at treating chronic pain than we THEIR DAILY PRACTICE? DO YOU HAVE ANY I believe that addiction is and will be the were 50 years ago. And in our efforts to elim- Q:ADDITIONAL ADVICE FOR single most important public health problem inate all pain with opioids, we have done our It’s essential to go beyond the single MENTAL HEALTH PROVIDERS WANT- of the 21st century. Mental health providers patients more harm than good. A:data point of what the patient tells you ING TO TRULY HELP THEIR across the board have an important role to Since we can’t eliminate all pain, we have about how opioids are affecting them. Because PATIENTS? play in helping to find solutions. ■ to teach our patients how to achieve some opioids work on the brain’s reward pathway quality of life, even with pain. We have to in addition to pain receptors, patients are li- think about the long view, not just what will able to overestimate the benefit of the drug help them feel better today. on pain relief and functionality. Therefore, getting other data points becomes crucial. Dr. Anna Lembke’s Upcoming Featured WHEN IT COMES DOWN TO Talk to family members and significant PSYCH CONGRESS SNAPSHOT Q:IT, WHO IS TO BLAME FOR others who have the opportunity to observe Session at Psych Congress 2018 THIS EPIDEMIC? DID BIG PHARMA the patient in their daily lives. Data show fam- JUST WANT TO SELL MORE DRUGS ily members are concerned about opioid mis- Drug Dealer, MD: How Doctors Were Duped, Patients Got AND MAKE MORE MONEY? use and addiction even when the patient isn’t. Hooked, and Why It’s So Hard to Stop Check the prescription drug monitoring da- The whole point of my book is that tabase before initiating any controlled drug SATURDAY, OCTOBER 27 | 5:45 P.M. — 6:45 P.M. A: no single person or institution is to and then every 3 to 6 months after. Patients Perhaps the most frightening aspect of the nation’s prescription drug blame. Opioid manufacturers played an im- can insidiously develop problems over time, portant role, but they were propagating false- even with no history of drug misuse or addic- epidemic is that it’s built on well-meaning doctors treating patients with hoods that turned out to be convenient myths tion. If an opioid misuse problem is detected, real problems. Dr. Lembke will explore the complex relationship for doctors with too many patients, too little don’t fire the patient. Instead, put opioid mis- between doctors and patients, the science of addiction, and the barriers time, and a reimbursement structure that use/use disorder on your problem list, discuss to successfully addressing drug dependence and addiction. favors prescribing pills and performing pro- the problem with the patient, and triage them cedures over talking to and educating patients to the right kind of care.

GAIN INSIGHTS INTO CURRENT AND EMERGING TREATMENT STRATEGIES WITH THE BEST MINDS IN MENTAL HEALTH psychcongress.com • Summer 2018 • Psych Congress Network 31 Uncovering the Therapeutic Potential of Psychedelics Research Resurgence Points to Mental Health Benefits

By Jolynn Tumolo

s a graduate student studying psy- times receive a disproportionate amount of larly dangerous or harmful compounds. choanalysis, Robin Carhart-Harris, press attention. They may, in fact, have beneficial effects if PhD, came across research on the If we look at the scientific data, psychedel- taken in a responsible way. Ause of LSD (lysergic acid diethylamide) in ics are actually treated as aversive by animals, psychotherapy that brought clarification meaning they actively avoid them. A not- WHAT DREW YOU TO THE and direction to his subsequent career. “I too-dissimilar phenomenon is seen in hu- Q:FIELD OF PSYCHEDELIC realized that key principles of psychoanaly- mans, where people often do not wish to DRUG RESEARCH? sis were most likely valid because the phe- repeat a psychedelic experience for quite nomenology of the psychedelic experience some time, if ever, after having had one. I was studying psychoanalysis prior seemed to verify them in quite a compelling Somewhat ironically, psychedelics are show- A:to my PhD and discovered literature way,” he told Psych Congress Network. “In ing promise as treatments for drug and al- on the use of LSD in psychotherapy. This my view, marrying psychoanalysis and psy- cohol addiction—with impressive results. changed everything for me. I realized that key chopharmacology by way of psychedelics Similarly, meta-analyses and population principles of psychoanalysis were most like- promises to yield major advances for psy- studies have not found a relationship between ly valid because the phenomenology of the chiatry and psychology…People have good psychedelic use and negative mental health psychedelic experience seemed to verify them reason to be very excited about this.” outcomes. Rather, a trend in the opposite in quite a compelling way. For example, peo- Carhart-Harris is the head of psychedelic direction was found in at least 1 large popu- ple commonly report a dissolution of their research for the center for neuropsycho- lation study. Those who had a history of use egos under psychedelics. This is an experience pharmacology at Imperial College London of psychedelics had lower levels of psycho- that is typically met with struggle, as the ego in England. Here, he addresses misconcep- logical distress and lower suicidality scores. does not relinquish control easily. However, Robin Carhart-Harris, PhD tions surrounding psychedelics, discusses These findings reflect what we see in the if control is ceded, people appear to experi- their potential therapeutic utility, and name- lab with controlled studies of healthy indi- ence remarkable insight into the depths of drops a prominent US politician who once viduals and patients with psychiatric disor- their psyches under psychedelics. Indeed, noted “LSD can be very, very helpful in our ders such as treatment-resistant depression. psychedelic means “mind-revealing,” and this, society if used properly.” They also mirror what we have seen when in my view, is a valid term. sampling people using psychedelics in a The mind-revealing effects of psychedelics WHAT ARE SOME OF THE naturalistic way, such as web-based ques- can sometimes be unpleasant if people are Q:BIGGEST MISCONCEPTIONS tionnaires with a prospective design. It is faced with dealing with painful psychological YOU ENCOUNTER ABOUT PSYCHE- important to emphasize we have found material they have omitted from conscious DELIC DRUGS? evidence that context is important for de- awareness. But they can also be profoundly termining response. People who have a cathartic and blissful. Discovering this litera- There are several misconceptions, therapeutic intention experience greater ture triggered a sea change in my thinking A: although it does seem the public and improvement in well-being post-use. But we about the mind, but I have also always been mental health professionals are wising up have also seen that people can report ben- as much drawn to biological accounts of the to “the truth” about psychedelics. One spe- efits even if they are not using these com- mind as deep psychological ones. For me, cific misconception I’ve encountered on pounds for a specific psychiatric purpose, neurobiology provides a grounding for psy- several occasions is the idea that psychedel- such as if they report using them for self- chology, particularly if that psychology is ics are particularly dangerous compounds exploration. abstract. In my view, marrying psychoanaly- that can lead to addiction and/or insanity. Granted, anomalous responses and side sis and psychopharmacology by way of psy- The truth is that psychedelics have little-to- effects occur with all drugs. But the point chedelics promises to yield major advances no addiction potential and have only been here is to address your question, and the for psychiatry and psychology in the coming associated with enduring psychotic respons- data say that, contrary to a common mis- years and decades. People have good reason es in very rare, individual cases that some- conception, psychedelics are not particu- to be very excited about this.

32 Psych Congress Network • Summer 2018 • psychcongress.com VISIT PSYCHCONGRESS.COM/2018 OR CALL 800-205-8233 TO REGISTER TODAY Uncovering the Therapeutic Potential of Psychedelics

WHICH MENTAL HEALTH DIS- we have found measures of the complexity and comfortable environment for the experi- would otherwise supply the drug for this Q:ORDERS ARE PSYCHEDELIC or entropy of brain activity provide a remark- ence, and having in place a number of con- research, most notably Sandoz (now Novar- COMPOUNDS OFFERING HOPE ably reliable index of the intensity of the tingency measures if adverse responses are tis), causing them to cease supply, and other FOR? subjective effects of psychedelics. observed. These mainly take the form of bodies important for sanctioning and/or Using functional magnetic resonance im- psychological intervention from experienced funding psychedelic research. Not all main- Psychedelics are showing potential aging (fMRI) to measure brain activity at an staff trained for such situations. stream figures were complicit in this “bail A: for a range of different disorders. Re- even broader temporal scale, we can look at out” however, as exemplified by a fascinating cent news has tended to focus on depression. the properties of large-scale brain networks PSYCHEDELIC COMPOUNDS US Senate committee meeting in 1966 in We published a small-scale study on psilo- and how these change under psychedelics. Q:GENERATED A LOT OF INTER- which Sen. Robert Kennedy commented, cybin (“magic mushrooms”) for treatment- When we do, we see 2 main effects: a decrease EST IN THE MID-1900s BUT THEN FIZ- “Perhaps to some extent we have lost sight resistant depression in 2016, which was fol- in the integrity of these large-scale networks, ZLED OUT UNTIL RECENTLY. WHAT of the fact that LSD can be very, very helpful lowed by 2 larger and more rigorously de- and an increase in the cross-talk between HAPPENED TO DULL THE INITIAL in our society if used properly.” Unfortu- signed US studies showing improvements in them. A valid summary description of the EXCITEMENT, AND WHAT’S FUELING nately for psychedelic science, such rational anxiety and depression scores after psilocy- brain effects of psychedelics, therefore, is voices were drowned out by those of the THE RECENT RENEWED bin therapy for existential distress linked to they broaden the state space in which the ill-informed but nevertheless maddened SCHOLARLY INTEREST? life-threatening illness. This work was pre- mind and brain can wander, and they do this crowd. ceded by other notable studies. However, by breaking down conventional, ordinarily A combination of factors led to the over the last 12 years, papers have been pub- dominant modes of brain functioning. A: downfall of psychedelic research and WHAT DO YOU HOPE PSYCH lished about psychedelics for obsessive com- therapy in the late 1960s. Some have blamed Q:CONGRESS ATTENDEES WILL pulsive disorder, end-of-life anxiety, depres- WHAT ARE THE POTENTIAL excessive proselytising from psychedelic TAKE AWAY FROM YOUR SESSION? sion (including treatment-resistant depres- Q:DANGERS OF PSYCHEDELIC figureheads such as Timothy Leary, once a sion), and tobacco and alcohol addiction. COMPOUNDS, AND HOW DO YOU Harvard professor in psychiatry, who, after I hope attendees will take away some Added to this are papers showing lasting ENSURE PARTICIPANTS IN YOUR “turning on” to the effects of psychedelics, A: new learnings about the short- and improvements in well-being in healthy indi- STUDIES ARE AS SAFE AS POSSIBLE? decided to drop academic pursuits in favor long-term brain and mind effects of psyche- viduals after just 1 or 2 dosing sessions with of dedicating himself to a more political cam- delics and perhaps an increased curiosity a psychedelic, MDMA-assisted psychother- There may be potential dangers not paign in which he energetically and pro- and openness to learn more about their apy for post-traumatic stress disorder, and A: known to us. Although some cultures vocatively promoted indiscriminate use of therapeutic potential. I wouldn’t want or conceptual work positing efficacy for func- have been using psychedelic plants for sev- psychedelics. This, unsurprisingly, created expect people to become overnight converts. tional neurological disorders and eating eral hundred years, scientific research into a political backlash, which, with the help of As Carl Jung said, “Skepticism is the mother disorders. their effects has never really been allowed alarmist media reporting, involved the dis- of all scientific truths.” So I hope people go Despite all this literature, it should be to flourish. What we do know, however, is semination and promotion of misinformation away with a heightened interest in the topic acknowledged that these data derive mostly that psychedelics can potently alter the qual- about the harms of psychedelics. but with no less skepticism than when they from small-scale studies. One interpretation ity of conscious experience, and this can be This backlash had impacts on those who arrived. ■ of the collective excitement they are now frightening for some people. If this occurs generating is that we are witnessing a bias in a stressful environment, or if it happens that can happen in the early phase of research to someone with latent or manifest psycho- in which effect sizes are inflated for a number logical vulnerabilities, then this could, in of reasons. While this may be so, another not theory, trigger a negative psychological re- Despite all this mutually exclusive interpretation is that psy- sponse with potentially lasting negative con- chedelics do indeed have considerable sequences. Relatedly, if a psychedelic is taken therapeutic potential efficacy for a broad in a suboptimal environment without proper “literature, it should be range of different psychiatric disorders supervisory care, individuals may put them- because they have an exceptional ability to selves in dangerous situations and suffer address something common to all of them. physical injury. acknowledged that these One potential complication is so-called CAN YOU GIVE A SIMPLIFIED “hallucinogen persisting perception disorder” Q:OVERVIEW OF WHAT HAP- (HPPD). HPPD refers to cases in which indi- data derive mostly from PENS IN THE BRAIN AFTER A PER- viduals report residual perceptual abnor- SON TAKES A PSYCHEDELIC COM- malities after a psychedelic has been me- POUND? WHAT IS YOUR RESEARCH tabolized from the body. Although this con- small-scale studies. SHOWING? dition appears to be rare and associated with certain psychedelics (LSD) more than others ” A variety of different evidence sup- (), it can be distressing for those A: ports the view that activation of the who suffer from it, and there are no obvious serotonin 2A receptor subtype is key to the effective treatments other than convention- action of psychedelics. If you give a drug that al psychiatric interventions such as psycho- blocks this receptor before you give a psy- therapy and pharmacotherapy (antipsychotic Dr. Robin Carhart-Harris’ Upcoming chedelic, essentially the psychedelic won’t medication). In our recent clinical trial with PSYCH CONGRESS SNAPSHOT work. psilocybin for depression, the main side Featured Session at Psych Congress 2018 Serotonin 2A receptors appear to mediate effects were anxiety on drug-onset, some neural and behavioral plasticity. They are associated nausea (but no vomiting), some Psychedelics: A Psychiatric Revolution in Waiting? heavily expressed on excitatory neurons, expected changes in cognition that can cre- — particularly in the cortex, and activation of ate a temporary sense of confusion, and THURSDAY, OCTOBER 25 | 7:45 A.M. 8:45 A.M. these receptors increases excitability but in headaches the next day or sometimes 2 days Research on psychedelic compounds has gained momentum in recent an irregular way, so that the activity of large after the higher-dose session. No clear cases years, and new trials suggest they may have therapeutic efficacy for populations of neurons is dysregulated under of HPPD have been reported in modern some psychiatric disorders. This session aims to educate attendees on psychedelics. research with psychedelics. the current state of that research. Dr. Carhart-Harris will explain the basic When we use electroencephalogram (EEG) We ensure people are safe in our studies or magnetoencephalography (MEG), we see through careful screening, the provision of pharmacology and mechanism of action of psychedelics both acutely in brain activity become less organized and psychological support before, during, and healthy populations and in therapeutic contexts. more complex under psychedelics. Indeed, after the experience, the provision of a safe

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