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Pindolol of the Activation of Postsynaptic 5-HT1A Receptors
Potentiation by (-)Pindolol of the Activation of Postsynaptic 5-HT1A Receptors Induced by Venlafaxine Jean-Claude Béïque, Ph.D., Pierre Blier, M.D., Ph.D., Claude de Montigny, M.D., Ph.D., and Guy Debonnel, M.D. The increase of extracellular 5-HT in brain terminal regions antagonist WAY 100635 (100 g/kg, i.v.). A short-term produced by the acute administration of 5-HT reuptake treatment with VLX (20 mg/kg/day ϫ 2 days) resulted in a inhibitors (SSRI’s) is hampered by the activation of ca. 90% suppression of the firing activity of 5-HT neurons somatodendritic 5-HT1A autoreceptors in the raphe nuclei. in the dorsal raphe nucleus. This was prevented by the The present in vivo electrophysiological studies were coadministration of (-)pindolol (15 mg/kg/day ϫ 2 days). undertaken, in the rat, to assess the effects of the Taken together, these results indicate that (-)pindolol coadministration of venlafaxine, a dual 5-HT/NE reuptake potentiated the activation of postsynaptic 5-HT1A receptors inhibitor, and (-)pindolol on pre- and postsynaptic 5-HT1A resulting from 5-HT reuptake inhibition probably by receptor function. The acute administration of venlafaxine blocking the somatodendritic 5-HT1A autoreceptor, but not and of the SSRI paroxetine (5 mg/kg, i.v.) induced a its postsynaptic congener. These results support and extend suppression of the firing activity of dorsal hippocampus CA3 previous findings providing a biological substratum for the pyramidal neurons. This effect of venlafaxine was markedly efficacy of pindolol as an accelerating strategy in major potentiated by a pretreatment with (-)pindolol (15 mg/kg, depression. -
ZHONG-THESIS-2016.Pdf
ANTIDEPRESSANTMINING AZ AMAZ DESIGNING A WEBBASED ALGORITHM AND VISUAL LANGUAGE FOR ANTIDEPRESSANT DRUG SELECTION TO EDUCATE PRIMARY CARE PRACTITIONERS By Amy Zhong A thesis submitted to Johns Hopkins University in conformity with the requirements for the degree of Master of Arts Baltimore, Maryland March, 2016 © 2016 Amy Zhong All Rights Reserved ABSTRACT Depression is a common mental disorder that affects approximately 14.8 million American adults each year. In addition to being a debilitating condition, depression often occurs in tandem with other medical conditions such as diabetes, heart disease, and cancer. While psychiatric professionals are essential for the management of mental health, majority of patients seek care from their primary care practitioners. This phenomenon is of great concern because diagnosis of depression within primary care settings has only been accurate 25-50% of the time. The antidepressant drug selection algorithm utilizes a unique formula to integrate patient and family medical histories, patient symptoms, and patient preferences to make optimal treatment selections. The development of a visual language explores the use of graphic elements to improve understanding of major pharmacological mechanisms, knowledge essential to making rational DQWLGHSUHVVDQWGUXJVHOHFWLRQV,QFUHDWLQJWKLVPRELOHZHEEDVHGDSSOLFDWLRQZHKRSHWR¿OOD void in resources available to primary care practitioners, and improve management of mental health within the primary care setting. By Amy Zhong Chairpersons of the Supervisory Committee Adam I. Kaplin, M.D., Ph.D., esis Preceptor Assistant Professor, Departments of Psychiatry and Neurology e Johns Hopkins University School of Medicine Kristen Rahn Hollinger, Ph.D., esis Preceptor Instructor, Departments of Psychiatry and Neurology e Johns Hopkins University School of Medicine Jennifer E. -
Print Your Symptom Diary
MEDICATION GUIDE FETZIMA® (fet-ZEE-muh) (levomilnacipran) extended-release capsules, for oral use What is the most important information I should know about FETZIMA? FETZIMA may cause serious side effects, including: • Increased risk of suicidal thoughts or actions in some children, adolescents, and young adults. FETZIMA and other antidepressant medicines may increase suicidal thoughts or actions in some children and young adults, especially within the first few months of treatment or when the dose is changed. FETZIMA is not for use in children. o Depression or other serious mental illnesses are the most important causes of suicidal thoughts or actions. Some people may have a higher risk of having suicidal thoughts or actions. These include people who have (or have a family history of) depression, bipolar illness (also called manic-depressive illness) or have a history of suicidal thoughts or actions. How can I watch for and try to prevent suicidal thoughts and actions? o Pay close attention to any changes, especially sudden changes in mood, behavior, thoughts, or feelings, or if you develop suicidal thoughts or actions. This is very important when an antidepressant medicine is started or when the dose is changed. o Call your healthcare provider right away to report new or sudden changes in mood, behavior, thoughts, or feelings. o Keep all follow-up visits with your healthcare provider as scheduled. Call your healthcare provider between visits as needed, especially if you have concerns about symptoms. Call your healthcare provider or -
Strategies for Managing Sexual Dysfunction Induced by Antidepressant Medication
King’s Research Portal DOI: 10.1002/14651858.CD003382.pub3 Document Version Publisher's PDF, also known as Version of record Link to publication record in King's Research Portal Citation for published version (APA): Taylor, M. J., Rudkin, L., Bullemor-Day, P., Lubin, J., Chukwujekwu, C., & Hawton, K. (2013). Strategies for managing sexual dysfunction induced by antidepressant medication. Cochrane Database of Systematic Reviews, (5). https://doi.org/10.1002/14651858.CD003382.pub3 Citing this paper Please note that where the full-text provided on King's Research Portal is the Author Accepted Manuscript or Post-Print version this may differ from the final Published version. If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections. General rights Copyright and moral rights for the publications made accessible in the Research Portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognize and abide by the legal requirements associated with these rights. •Users may download and print one copy of any publication from the Research Portal for the purpose of private study or research. •You may not further distribute the material or use it for any profit-making activity or commercial gain •You may freely distribute the URL identifying the publication in the Research Portal Take down policy If you believe that this document breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim. -
Levomilnacipran (Fetzima®) Indication
Levomilnacipran (Fetzima®) Indication: Indicated for the treatment of major depressive disorder (MDD), FDA approved July 2013. Mechanism of action Levomilnacipran, the more active enantiomer of racemic milnacipran, is a selective SNRI with greater potency for inhibition of norepinephrine relative to serotonin reuptake Compared with duloxetine or venlafaxine, levomilnacipran has over 10-fold higher selectivity for norepinephrine relative to serotonin reuptake inhibition The exact mechanism of the antidepressant action of levomilnacipran is unknown Dosage and administration Initial: 20 mg once daily for 2 days and then increased to 40 mg once daily. The dosage can be increased by increments of 40 mg at intervals of two or more days Maintenance: 40-120 mg once daily with or without food. Fetzima should be swallowed whole (capsule should not be opened or crushed) Levomilnacipran and its metabolites are eliminated primarily by renal excretion o Renal impairment Dosing: Clcr 30-59 mL/minute: 80 mg once daily Clcr 15-29 mL/minute: 40 mg once daily End-stage renal disease (ESRD): Not recommended Discontinuing treatment: Gradually taper dose, if intolerable withdrawal symptoms occur, consider resuming the previous dose and/or decrease dose at a more gradual rate How supplied: Capsule ER 24 Hour Fetzima Titration: 20 & 40 mg (28 ea) Fetzima: 20 mg, 40 mg, 80 mg, 120 mg Warnings and Precautions Elevated Blood Pressure and Heart Rate: measure heart rate and blood pressure prior to initiating treatment and periodically throughout treatment Narrow-angle glaucoma: may cause mydriasis. Use caution in patients with controlled narrow- angle glaucoma Urinary hesitancy or retention: advise patient to report symptoms of urinary difficulty Discontinuation Syndrome Seizure disorders: Use caution with a previous seizure disorder (not systematically evaluated) Risk of Serotonin syndrome when taken alone or co-administered with other serotonergic agents (including triptans, tricyclics, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. -
M2021: Pharmacogenetic Testing
Pharmacogenetic Testing Policy Number: AHS – M2021 – Pharmacogenetic Prior Policy Name and Number, as applicable: Testing • M2021 – Cytochrome P450 Initial Presentation Date: 06/16/2021 Revision Date: N/A I. Policy Description Pharmacogenetics is defined as the study of variability in drug response due to heredity (Nebert, 1999). Cytochrome (CYP) P450 enzymes are a class of enzymes essential in the synthesis and breakdown metabolism of various molecules and chemicals. Found primarily in the liver, these enzymes are also essential for the metabolism of many medications. CYP P450 are essential to produce many biochemical building blocks, such as cholesterol, fatty acids, and bile acids. Additional cytochrome P450 are involved in the metabolism of drugs, carcinogens, and internal substances, such as toxins formed within cells. Mutations in CYP P450 genes can result in the inability to properly metabolize medications and other substances, leading to increased levels of toxic substances in the body. Approximately 58 CYP genes are in humans (Bains, 2013; Tantisira & Weiss, 2019). Thiopurine methyltransferase (TPMT) is an enzyme that methylates azathioprine, mercaptopurine and thioguanine into active thioguanine nucleotide metabolites. Azathioprine and mercaptopurine are used for treatment of nonmalignant immunologic disorders; mercaptopurine is used for treatment of lymphoid malignancies; and thioguanine is used for treatment of myeloid leukemias (Relling et al., 2011). Dihydropyrimidine dehydrogenase (DPD), encoded by the gene DPYD, is a rate-limiting enzyme responsible for fluoropyrimidine catabolism. The fluoropyrimidines (5-fluorouracil and capecitabine) are drugs used in the treatment of solid tumors, such as colorectal, breast, and aerodigestive tract tumors (Amstutz et al., 2018). A variety of cell surface proteins, such as antigen-presenting molecules and other proteins, are encoded by the human leukocyte antigen genes (HLAs). -
Flibanserin (Addyi)
STEPS New Drug Reviews Flibanserin (Addyi) for Hypoactive Sexual Desire Disorder in Premenopausal Women HARRY HOLT, MD, and JEFFREY TINGEN, PharmD, MBA, University of Virginia Health System, Charlottesville, Virginia STEPS new drug reviews Flibanserin (Addyi) is labeled for the treatment of acquired, generalized hypoactive sexual cover Safety, Tolerability, desire disorder (HSDD) in premenopausal women. It is a nonhormonal medication that Effectiveness, Price, and 1 Simplicity. Each indepen- affects serotonin receptors to increase libido. dent review is provided by authors who have no financial association with Drug Dosage Dose form Cost* the drug manufacturer. Flibanserin (Addyi) 100 mg per day at bedtime 100-mg tablet $830 This series is coordinated by Allen F. Shaughnessy, *—Estimated retail price of one month’s treatment based on information obtained at http://www.goodrx.com PharmD, MMedEd, (accessed April 1, 2016). Contributing Editor. A collection of STEPS pub- lished in AFP is available at http://www.aafp.org/ SAFETY EFFECTIVENESS afp/steps. The main risks of flibanserin are hypoten- Flibanserin has been evaluated in three ran- sion (2%) and syncope (0.4%), which are domized, double-blind, placebo-controlled more likely to occur in patients who have studies of 2,375 premenopausal women also ingested alcohol. For this reason, women with acquired, generalized HSDD, defined should not drink alcohol when taking fliban- as low sexual desire causing marked dis- serin; about one in six persons taking this tress or interpersonal difficulties.2 Women combination will experience clinically signif- in monogamous, heterosexual relationships icant hypotension and syncope.1 Flibanserin with no known cause of HSDD reported should not be taken by women with hepatic an average increase of 1.6 to 2.5 additional impairment or women who are also taking satisfying sexual events per month with treat- moderate or strong cytochrome P450 3A4 ment, from a baseline of 2.5 to 3.0 per month. -
Levomilnacipran for the Treatment of Major Depressive Disorder
Out of the Pipeline Levomilnacipran for the treatment of major depressive disorder Matthew Macaluso, DO, Hala Kazanchi, MD, and Vikram Malhotra, MD An SNRI with n July 2013, the FDA approved levomil- Table 1 once-daily dosing, nacipran for the treatment of major de- Levomilnacipran: Fast facts levomilnacipran pressive disorder (MDD) in adults.1 It is I Brand name: Fetzima decreased core available in a once-daily, extended-release formulation (Table 1).1 The drug is the fifth Class: Serotonin-norepinephrine reuptake symptoms of inhibitor serotonin-norepinephrine reuptake inhibi- MDD and was well Indication: Treatment of major depressive tor (SNRI) to be sold in the United States disorder in adults tolerated in clinical and the fourth to receive FDA approval for FDA approval date: July 26, 2013 trials treating MDD. Availability date: Fourth quarter of 2013 Levomilnacipran is believed to be the Manufacturer: Forest Pharmaceuticals more active enantiomer of milnacipran, Dosage forms: Extended–release capsules in which has been available in Europe for 20 mg, 40 mg, 80 mg, and 120 mg strengths years and was approved by the FDA in Recommended dosage: 40 mg to 120 mg 2009 for treating fibromyalgia. Efficacy of capsule once daily with or without food levomilnacipran for treating patients with Source: Reference 1 MDD was established in three 8-week ran- domized controlled trials (RCTs).1 cial and occupational functioning in addi- Clinical implications tion to improvement in the core symptoms Levomilnacipran is indicated for treating of depression.5 -
Premium Non-Specialty Quantity Limit List January 2016
Premium Non-Specialty Quantity Limit List January 2016 Therapeutic Category Drug Name Dispensing Limit Anti-infectives Antibiotics DIFICID (fidaxomicin) 200 mg 2 tabs/day & 10 days/30 days SIVEXTRO (tedizolid) Solr 6 vials/30 days SIVEXTRO (tedizolid) Tabs 6 tabs/30 days ZYVOX (linezolid) 28 tabs/30 days ZYVOX (linezolid) Suspension 4 bottles (600 mL)/28 days Antifungals LAMISIL (terbinafine) 250 mg 84 days supply/180 days Antimalarial QUALAQUIN (quinine) QL varies* Antivirals, Herpetic FAMVIR (famciclovir) 125 mg 1 tab/day FAMVIR (famciclovir) 250 mg 2 tabs/day FAMVIR (famciclovir) 500 mg 21 tabs/30 days SITAVIG (acyclovir) 50 mg 2 tabs/30 days VALTREX (valacyclovir) 1000 mg 3 tabs/day VALTREX (valacyclovir) 500 mg 2 tabs/day Antivirals, Influenza RELENZA (zanamivir) QL is 40 inh per 365 days. TAMIFLU (oseltamivir) 30 mg 40 caps per 365 days TAMIFLU (oseltamivir) 45 mg, 75 mg 20 caps per 365 days TAMIFLU (oseltamivir) Suspension 360 mL/365 days Cardiology Anticoagulants ELIQUIS (apixiban) 2 tabs/day ELIQUIS (apixiban) 5 mg 3 tabs/day IPRIVASK (desirudin) 35 days supply/180 days PRADAXA (dabigatran) 2 caps/day SAVAYSA (edoxaban) 1 tab/day XARELTO (rivaroxaban) 10 mg 35 days supply/180 days XARELTO (rivaroxaban) 15 mg 2 tabs/day XARELTO (rivaroxaban) 20 mg 1 tab/day XARELTO (rivaroxaban) Starter Pack 2 starter packs/year Heart Failure CORLANOR (ivabradine) 2 tabs/day Central Nervous System ADHD Agents ADDERALL (amphetamine/dextroamphetamine) 3 tabs/day ADDERALL XR (amphetamine/dextroamphetamine mixed salts) 1 cap/day APTENSIO XR (methylphenidate) -
Pristiq (Desvenlafaxine Succinate) – First-Time Generic
Pristiq® (desvenlafaxine succinate) – First-time generic • On March 1, 2017, Teva launched AB-rated generic versions of Pfizer’s Pristiq (desvenlafaxine succinate) 25 mg, 50 mg, and 100 mg extended-release tablets for the treatment of major depressive disorder. — Teva launched the 25 mg tablet with 180-day exclusivity. — In addition, Alembic/Breckenridge, Mylan, and West-Ward have launched AB-rated generic versions of Pristiq 50 mg and 100 mg extended-release tablets. — Greenstone’s launch plans for authorized generic versions of Pristiq 25 mg, 50 mg, and 100 mg tablets are pending. — Lupin and Sandoz received FDA approval of AB-rated generic versions of Pristiq 50 mg and 100 mg tablets on June 29, 2015. Lupin’s and Sandoz’s launch plans are pending. • Other serotonin-norepinephrine reuptake inhibitors approved for the treatment of major depressive disorder include desvenlafaxine fumarate, duloxetine, Fetzima™ (levomilnacipran), Khedezla™ (desvenlafaxine) , venlafaxine, and venlafaxine extended-release. • Pristiq and the other serotonin-norepinephrine reuptake inhibitors carry a boxed warning for suicidal thoughts and behaviors. • According to IMS Health data, the U.S. sales of Pristiq were approximately $883 million for the 12 months ending on December 31, 2016. optumrx.com OptumRx® specializes in the delivery, clinical management and affordability of prescription medications and consumer health products. We are an Optum® company — a leading provider of integrated health services. Learn more at optum.com. All Optum® trademarks and logos are owned by Optum, Inc. All other brand or product names are trademarks or registered marks of their respective owners. This document contains information that is considered proprietary to OptumRx and should not be reproduced without the express written consent of OptumRx. -
Dosing and Monitoring: Children and Adolescents
Dosing and Monitoring: Children and Adolescents Glenn S. Hirsch, MD Keith S. Ditkowski, MD Child & Adolescent Dosing.indd 1 08-01-2018 14:56:52 Adapted from Child & Adolescent Dosing.indd 76 08-01-2018 14:56:50 DISCLAIMER This pocket reference is provided as a service to medicine by the publisher, Medworks Media Inc. This review does not imply the publisher’s agreement with the views expressed herein. Although every effort has been made to ensure that drug doses and other information are presented accurately in this publication, the ultimate responsibility rests with the prescribing physician. Neither the publisher, nor the authors can be held responsible for errors or for any consequences arising from the use of information contained herein. Readers are strongly urged to consult any relevant primary literature. No claims or endorsements are made for any drug or compound currently under clinical investigation. In an effort to allow for the widest distribution of these guidelines, the authors have modified the originally printed material to more closely conform to the limitations of product labeling. For many of the drugs discussed herein, initiation at lower doses may increase tolerability and efficacy. Copyright ©2018, MedWorks Media Inc., 2205 Rockefeller Lane, Redondo Beach, CA 90278. Printed in the USA. All rights reserved, including the right of reproduction, in whole or in part, in any form. Child & Adolescent Dosing.indd 2 08-01-2018 14:56:52 Dosing and Monitoring: Children and Adolescents Glenn S. Hirsch, MD Keith S. Ditkowski, MD Dr. Hirsch is the deputy director of the New York University Child Study Center, the medical director in the Division of Child and Adolescent Psychiatry, and the assistant professor of psychiatry at the New York University School of Medicine. -
(Flibanserin) (Flibanserin) Tablets
™ MEDICATION GUIDE addyi ADDYI™ (add-ee) (flibanserin) (flibanserin) Tablets Read this Medication Guide before you start taking ADDYI™ and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor. What is the most important information I should know about ADDYI? Your risk of severe low blood pressure and fainting (loss of consciousness) is increased if you take ADDYI and: • drink alcohol. Do not drink alcohol if you take ADDYI. • take certain prescription medicines, over-the-counter medicines, or herbal supplements. Do not take or start taking any prescription medicines, over-the-counter medicines, or herbal supplements while taking ADDYI until you have talked with your doctor. Your doctor will tell you if it is safe to take other medicines or herbal supplements while you are taking ADDYI. • have liver problems. Do not take ADDYI if you have liver problems. If you take ADDYI and you feel lightheaded or dizzy, lie down right away. Get emergency medical help or ask someone to get emergency medical help for you if the symptoms do not go away or if you faint (lose consciousness). If you faint (lose consciousness), tell your doctor as soon as you can. ADDYI is only available through the ADDYI Risk Evaluation and Mitigation Strategy (REMS) Program because of the increased risk of severe low blood pressure and fainting (loss of consciousness) with alcohol use. You can only get ADDYI from pharmacies that are enrolled in the ADDYI REMS Program. For more information about the Program and a list of pharmacies that are enrolled in the ADDYI REMS Program, go to www.AddyiREMS.com or call 1-844-PINK-PILL (1-844- 746-5745).