Schizophrenia Update Treatment Options and Side Effects

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Slide 1 : Schizophrenia Update: Treatment Options and Side Effects Jonathan M. Meyer, M.D Assistant Professor Department of Psychiatry University of California San Diego
Slide 2 : Outline Recent Data from the NIMH Sponsored CATIE Schizophrenia Study Medical Issues in Schizophrenia Side Effect Concerns With Antipsychotics What’s New?
Slide 3 : Timeline of Major Antipsychotic Therapies Ziprasidone 1950 1960 1970 1980 1990 2001 2003 2007 ECT, etc. Chlorpromazine Fluphenazine Thioridazine Haloperidol Clozapine Risperidone Olanzapine Quetiapine Aripiprazole Consta Paliperidone Consta = Long-acting injectable risperidone
Slide 4 : The CATIE Schizophrenia Trial
Slide 5 :
Slide 6 : CATIE Study Phase 1: Time to Discontinuation for Any Cause Lieberman JA et al. N Engl J Med. 2005;353:1209-1223. Olanzapine (N=330) Risperidone (N=333) Ziprasidone (N=183) Quetiapine (N=329) Perphenazine (N=257) 0.8 0.9 0.7 0.6 0.4 0.3 0.1 0.5 0.2 0.0 0 3 6 9 12 15 18 1.0 Time to Discontinuation for Any Cause (months) Proportion of Patients Continuing Treatment
Slide 7 : Stroup TS et al. Am J Psychiatry. 2006; 163:611-622. Proportion of Patients Continuing Treatment Time to Phase 2 Discontinuation (months) 1.0 0.8 0.6 0.4 0.2 0 3 6 9 12 15 18 Olanzapine (N=66) Quetiapine (N=63) Risperidone (N=69) Ziprasidone (N=135) CATIE Study Phase 2T: Time to Discontinuation for Any Cause
Slide 8 : Average Monthly Symptom Scores Rosenheck R et al. Cost Effectiveness of Second-Generation Antipsychotics and Perphenazine in a Randomized Trial of Treatment for Chronic Schizophrenia Am J Psychiatry 2006; 163:2080-89
Slide 9 : Medical and Safety Issues During Antipsychotic Treatment
Slide 10 : Recent Multi-State Study Mortality Data: Years of Potential Life Lost Compared with the general population, persons with major mental illness typically lose more than 25 years of normal life span Colton CW, Manderscheid RW. Preventing Chronic Disease. Apr 2006;3:1-14 Miller BJ, et al. Psych Services Oct 2006; 57: 1482-87
Slide 11 : Medical Issues in Schizophrenia and Bipolar Disorder Meyer JM and Nasrallah H eds. Medical Illness and Schizophrenia. APPI 2003 Regenold WT, et al. Increased prevalence of type 2 diabetes mellitus among psychiatric inpatients with bipolar I affective and schizoaffective disorders independent of psychotropic drug use. Journal of Affective Disorders. 2002 Jun;70(1):19-26
Slide 12 : Undertreatment of Common Disorders in the CATIE Schizophrenia Trial at Enrollment Nasrallah HA, Meyer JM et al. Schiz Res 2006.
Slide 13 : Side Effects of Atypical Antipsychotics CLOZ = clozapine; RIS = risperidone; OLZ = olanzapine; QUET = quetiapine; ZIP = ziprasidone; ARIP = aripiprazole; Adapted from: Nasrallah HA, Mulvihill T. Ann Clin Psychiatry. 2001(Dec);13(4):215-227 0 0 ++ +++ + +++ Blood sugar 0 0 ++ +++ + +++ Lipids -/+ -/+ ++ ++++ + ++++ Weight gain 0 0 +++ ++ +/- +++ Sedation 0 +/0 0 0/+ +/++ 0 Tremors, stiffness, endocrine problems 0 0 0 +/++ 0 +++ Dry mouth, constipation 0/+ 0/+ ++ +/0 + +++ Low Blood Pressure INVEGA/ CLOZARIL RISPERDAL ZYPREXA SEROQUEL GEODON ABILIFY
Slide 14 : Past Areas of Concern Current Medical Realities Shift in Risk Perception of Antipsychotics Sedation Weight Gain Insulin Resistance CHD Hyper- lipidemia Weight Gain Diabetes Prolactin Insulin Resistance Sedation Hyperlipidemia Coronary Heart Disease Tardive Dyskinesia TD Prolactin
Slide 15 : ADA/APA Consensus Conference on Antipsychotic Drugs and Obesity and Diabetes Summary + = increase effect; - = no effect; D = discrepant results. *Newer drugs with limited long-term data.
Slide 16 : What We Should Be Doing And - trying to use medications which have fewer metabolic side effects!
Slide 17 : Equipment
Slide 18 : Clinical Issues Lack of access to medical care for patients with severe mental illnesses Switching to more metabolically neutral medications may reverse many problems, but requires careful attention by the psychiatrist and motivation by the client
Slide 19 : Change in Body Weight Following Switch to Aripiprazole-8 Wk Study * † *p<0.001; †p=0.077 LOCF analysis. Casey, et al. Int J Neuropsychopharmacol. 2002;5(suppl 1):S187. n = 169 106 14 Prior antipsychotic
Slide 20 : Estimated Weight Change (lb) After Switch to Ziprasidone† †Repeated measures analysis Improvement Presented at APA 2004, New York, NY
Slide 21 : What’s New?
Slide 22 : Newer Antipsychotics Paliperidone (Invega®) - Risperdal metabolite Very similar side effect profile to Risperdal Very similar effectiveness to Risperdal Bifeprunox - similar in mechanism to Abilify More nausea than Abilify -> Long titration (8 days) - not for acute use Questions about effectiveness - awaiting FDA decision Asenapine - another atypical antipsychotic No major efficacy or safety benefits - awaiting FDA decision Iloperidone - another atypical antipsychotic No major efficacy benefits, QTc concerns - awaiting FDA decision Long-Acting Injectables (Not Yet Approved) Olanzapine Pamoate: 2-4 wks, effective, major safety concerns Paliperidone Palmitate: 4 wks, not yet filed with FDA (?2009)
Slide 23 : On the Horizon Some features of schizophrenia may be due to decreased levels of activity at a certain type of receptor (NMDA glutamate receptors) Glycine can stimulate those receptors and might prove useful as a treatment for schizophrenia Glycine Transport Inhibitors (GlyT1 Blockers) The GlyT1 transporter is localized to important areas of the brain Interesting data in animal models of psychosis induced by PCP
Slide 24 : How A Reuptake Inhibitor Works Glycine Reuptake Pump Postsynaptic Neuron Presynaptic Nerve Ending NMDA Receptors Synaptic vesicles with Glycine Glycine
Slide 25 : Conclusions Except for clozapine, most of the currently available agents, and those on the horizon, are more alike than different in terms of effectiveness Safety and avoidance of metabolic side effects are major reasons to choose certain medications Providers have a duty to monitor weight, blood pressure, blood sugar and cholesterol (lipids) Long-acting injectable medications are useful, will have more options in the next few years Ongoing research may help identify newer classes of medications

 


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