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Advances in the Treatment of Schizophrenia: Integrating New and Emerging Options Into Therapy to Meet Unmet Needs

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Advances in the Treatment of Schizophrenia: Integrating New and Emerging Options Into Therapy to Meet Unmet Needs Advances in the Treatment of Schizophrenia: Integrating New and Emerging Options into Therapy to Meet Unmet Needs © 2020. All rights reserved. © 2020. All rights reserved. No part of this report may be reproduced or distributed without the expressed written permission of PTCE. No part of this report may be reproduced or distributed without the expressed written permission of PTCE. Faculty Information Lindsey N. Miller, PharmD, BCPP Megan Maroney, PharmD, BCPP Associate Professor Clinical Associate Professor Department of Pharmacy Practice Ernest Mario School of Pharmacy Lipscomb University Rutgers, the State University of College of Pharmacy New Jersey Clinical Psychiatric Pharmacist Clinical Psychiatric Pharmacist Vanderbilt Psychiatric Hospital Monmouth Medical Center Nashville, Tennessee Long Branch, New Jersey This activity is supported by an educational grant from Alkermes. Current Landscape for the Treatment of Schizophrenia Lindsey Miller, PharmD, BCPP © 2020. All rights reserved. No part of this report may be reproduced or distributed without the expressed written permission of PTCE. Educational Objectives At the completion of this activity, participants will be able to: • Explain goals associated with acute phase and maintenance phase schizophrenia treatment and the need for updated treatment guidelines • Illustrate treatment challenges, risk of relapse, and the subsequent impact on patient outcomes • Study new and emerging therapies, and their unique abilities to meet unmet needs • Identify how to safely and effectively incorporate new therapies into patient-specific treatment plans Natural Progression of Schizophrenia Schizophrenia is a chronic thought disorder characterized by disturbances in perceptions, emotional response, and social interactions. Stages of Illness First psychotic episode Worsening Variable degrees of recovery severity of signs and symptoms Prodromal Premorbid Psychotic Chronic/residual phase phase phase Birth 10 20 Years 30 40 50 Adapted from: Tandon R, et al. Schizophr Res. 2009;110(1-3):1-23; Lieberman JA, First MB. N Engl J Med. 2018;379:270-280; National Institute of Mental Health. Accessed April 9, 2020. nimh.nih.gov/health/topics/schizophrenia/index.shtml Schizophrenia Overview The World Health Organization estimates that 20 million people are affected by schizophrenia worldwide The incidence of schizophrenia is approximately 0.6%-1.9% in the United States Worldwide, schizophrenia is among the leading causes of disability • Nearly 5% of people with schizophrenia die by suicide National Institute of Mental Health. Accessed April 9, 2020. nimh.nih.gov/health/statistics/schizophrenia.shtml; World Health Organization. Accessed April 9, 2020. who.int/news-room/fact-sheets/detail/schizophrenia; van Os J, Kapur S. Lancet. 2009;374(9690):635-645; Patel KR, et al. P T. 2014; 39(9):638-645; Global Health Metrics. Lancet. 2017;390(10100):1211-1259; Palmer BA, et al. Arch Gen Psychiatry. 2005;62(3):247-253. DSM-5 Criteria for Schizophrenia • 2 or more symptoms* present for a period of 1 month or more: Disorganized Disorganized Negative Hallucinations Delusions speech behavior symptoms *1 symptom must include hallucinations, delusions, or disorganized speech. • Must cause a significant disturbance in one’s life • Total duration of symptoms lasts at least 6 months • Other disorders (eg, schizoaffective disorder, substance use) should be ruled out Adapted from: American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fifth edition. 2013. Statistics Adherence Approximately 50%-75% of people with schizophrenia are nonadherent to medication treatment. Nearly 75% of patients discontinue medication due to adverse effects. Partial adherence may occur in as high as 70% of patients with schizophrenia. Masand PS, et al. Prim Care Companion J Clin Psychiatry. 2009;11(4):147-154; Brissos S, et al. Ther Adv Psychopharmacol. 2014;4(5):198-219; Emsley R, et al. BMC Psychiatry. 2013;13:50; Lieberman JA, et al. N Engl J Med. 2005;353(12):1209-1223; Rummel-Kluge C, et al. Aust N Z J Psychiatry. 2008;42(5):382-388. Statistics 13%-27% of patients with schizophrenia experience persistent negative General symptoms. Patients with multiple negative symptoms have nearly a 60% higher risk of readmission at 1 year post hospitalization. Due to the impact of negative symptoms in schizophrenia, new treatment therapies are being developed to help target these symptoms. Hovington CL, et al. BMC Psychiatry. 2012;12:224; Patel R, et al. BMJ Open. 2015;5(9):e007619. Current Treatment Treatment Response Relapse Nonadherence HCP Involvement Adverse Effects Treatment Goals Reduce acute Prevent Optimize symptoms relapse functioning Minimize Improve adverse effects quality of life of treatment Keepers GA, et al. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia [draft]. American Psychiatric Association; 2019. Accessed February 14, 2020. psychiatry.org/psychiatrists/practice/clinical-practice-guidelines; Gottdiener WH, Haslam N. J Am Acad Psychoanal Dyn Psychiatry. 2003;31(1):191-208. Treatment Response Relapse Nonadherence HCP Involvement Adverse Effects Treatment Approach • American Psychiatric Association (APA) recommends that patients with schizophrenia have a documented, comprehensive, and person-centered treatment plan that includes evidence-based nonpharmacologic and pharmacologic treatments • Treatment plan should include • Patient involvement • Social support • Engaging family members • Addressing barriers to treatment • Assess risk for harm to self and others • Collaboration with other providers Keepers GA, et al. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia [draft]. American Psychiatric Association; 2019. Accessed February 14, 2020. psychiatry.org/psychiatrists/practice/clinical-practice-guidelines Treatment Response Relapse Nonadherence HCP Involvement Adverse Effects General Pharmacologic Approach to Treatment Second-generation antipsychotic 1 Switch to a second-generation antipsychotic or first-generation antipsychotic 2 Clozapine 3 Combination treatment and adjunctive therapies 4 Keepers GA, et al. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia [draft]. American Psychiatric Association; 2019. Accessed February 14, 2020. psychiatry.org/psychiatrists/practice/clinical-practice-guidelines; Gottdiener WH, Haslam N. J Am Acad Psychoanal Dyn Psychiatry. 2003;31(1):191-208. Treatment Response Relapse Nonadherence HCP Involvement Adverse Effects Medications for the Treatment of Schizophrenia First-generation Antipsychotics Second-generation Antipsychotics Chlorpromazineab Aripiprazolede Olanzapinebde Thioridazine Asenapinefg Paliperidonedi c Loxapine Brexpiprazole Quetiapine i Perphenazine Cariprazine Risperidonede Trifluoperazine Clozapineeh Ziprasidoneb Pimozide Iloperidone Thiothixene Lurasidone Fluphenazinebd abd a intravenous formulation available f sublingual formulation available Haloperidol b intramuscular- immediate release available g transdermal formulation available Keepers GA, et al. The American Psychiatric Association Practice Guideline for c inhalation formulation available h oral solution formulation available the Treatment of Patients With Schizophrenia [draft]. American Psychiatric d intramuscular- long-acting formulation available i extended-release oral formulation available Association; 2019. Accessed February 14, 2020. e oral disintegrating formulation available psychiatry.org/psychiatrists/practice/clinical-practice-guidelines Treatment Response Relapse Nonadherence HCP Involvement Adverse Effects Treatment Selection Considerations Previous Patient Adverse effect Medical response and preference profile conditions tolerability Pharmacokinetic Drug-drug Receptor- Formulations considerations interactions binding profiles Keepers GA, et al. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia [draft]. American Psychiatric Association; 2019. Accessed February 14, 2020. psychiatry.org/psychiatrists/practice/clinical-practice-guidelines; Gottdiener WH, Haslam N. J Am Acad Psychoanal Dyn Psychiatry. 2003;31(1):191-208. Treatment Response Relapse Nonadherence HCP Involvement Adverse Effects Role of Long-acting Injectable (LAI) Antipsychotics What do the guidelines say about LAI antipsychotics? Potential to Should be Should be reduce considered if the considered if the hospitalizations, patient prefers patient has mortality, and this formulation known poor discontinuation adherence due to inefficacy Keepers GA, et al. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia [draft]. American Psychiatric Association; 2019. Accessed February 14, 2020. psychiatry.org/psychiatrists/practice/clinical-practice-guidelines Treatment Response Relapse Nonadherence HCP Involvement Adverse Effects Role of LAI Antipsychotics • Effect on relapse • Meta-analysis included 10 studies with 1700 participants • Reduce relapse: depot injection (21.6%) versus oral (33.3%) (RR, 0.70; number needed to treat [NNT], 10) • Limited data on adherence and rehospitalization rates • Effect on reduced hospitalizations and cost • Purpose: Assess change in hospitalization and cost of care from 6 months pre- to 6 months post-initiation of any depot antipsychotic among patients with schizophrenia Parameter Pre-LAI Post-LAI P-value Psychiatric hospitalization
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