The Optimization of Treatment and Management of Schizophrenia in Europe (OPTiMiSE) Trial: Rationale for Its Methodology and a Review of the Effectiveness of Switching Antipsychotics
Abstract
Background:
Methods:
Results:
Discussion:
Introduction
Review of Prospective Randomized Studies on Switching the Drug in Initial Nonresponders to Antipsychotics
Method
Results
Author, Country | Diagnosis | “Run-in” phase: drugs (dose), duration, blinding, number of participants | Randomized phasea: drug groups (n), duration, blinding | Main resultb |
---|---|---|---|---|
Kinon et al,15 USA | Schizophrenia, schizoaffective, or schizophreniform disorder DSM-III-R | Fluphenazine 20 mg/d, 4 wk, open, n = 156 | Switch to haloperidol 20 mg/d (n = 13), increase fluphenazine dose to 80 mg/d (n = 16) or stay on fluphenazine 20 mg/d (n = 18), 4 wk, db | No significant efficacy difference between groups. Only 9% responded in the randomized phase |
Klimke et al,19 Germany | Acute schizophrenia, ICD-9 | Haloperidol, 15 mg/d, 3 days, open, n = 50 | Switch to perazine 300 mg/d (n = 12) or stay on haloperidol 15 mg/d (n = 13), 3 wk, db | No significant difference between groups |
Shalev et al,20 Israel | Schizophrenia, chronic, or subchronic with acute exacerbation DSM-III | Haloperidol (target dose 20 mg/d, perphenazine (target 32 mg/d), levomepromazine (target 300 mg/d), open, n = 75 | Second phase: Switch to one of the remaining antipsychotics (n = 20), 4 wk, open third phase: Switch to the remaining drug (n = 9), 4 wk, open | No significant difference between groups. Overall improvement rate 95% |
Suzuki et al,21 Japan | Schizophrenia, DSM-IV | Olanzapinec (flexible dose), quetiapine (flexible dose)c, risperidone (flexible dose)c, max. 8 wk, open, n = 78 | Second phase: Switch to one of the remaining antipsychotics (n = 37), max. 8 wk, open. Third phase: Switch to the remaining drug (n = 19), max. 8 wk, open | No significant differences between drugs in the primary outcome. Quetiapine less effective than olanzapine and risperidone in secondary outcomes |
Hatta et al,22 Japan | Schizophrenia, schizophreniform, or schizoaffective disorder, DSM-IV | Risperidone (max. dose 6 mg/d), 2 wk, open, n = 73 | Olanzapine (max. 20 mg/d) or risperidone (max. 6 mg/d), n = 20, 2 wk, sb | No significant difference between switchers and stayers. Early responders improved more than early nonresponders |
Hatta et al,22 Japan | Schizophrenia, schizophreniform, or schizoaffective disorder, DSM-IV | Olanzapine (max. dose 20 mg/d), 2 wk, sb, n = 58 | Risperidone (max. 6 mg/d), olanzapine (max. 20 mg/d) or, n = 20, 2 wk, sb | No significant difference between switchers and stayers. Early responders improved more than early nonresponders |
Hatta et al,23 Japan | Schizophrenia, schizophreniform, or schizoaffective disorder, DSM-IV | Risperidone (starting dose 3 mg/d, n = 74) or olanzapine (starting dose 10 mg/d, n = 86) chosen at the physicians’ discretion, 2 wk, sb | Add the other drug or switch to the respective other drug, same doses, 10 wk, n = 51, sb | No significant difference between combining drugs and switching to the other drug |
McEvoy et al,25 USA | Schizophrenia DSM-IV | Olanzapine (7.5–30 mg/d), perphenazine (8–32 mg/d), quetiapine (200–800 mg/d), risperidone (1.5–6 mg/d), ziprasidone (80–160 mg/d), max. 18 mo, db, n = 1493 | Participants who discontinued phase 1d were randomized to clozapine, olanzapine, quetiapine or risperidone (patients could not receive the same drug as in phase I), n = 99, max. 18 mo, db except clozapine | Time to discontinuation was significantly longer for clozapine than for quetiapine and risperidone, but not longer than for olanzapine |
Stroup et al,26 USA | Schizophrenia DSM-IV | Olanzapine (7.5–30 mg/d), perphenazine (8-32 mg/d), quetiapine (200-800 mg/d), risperidone (1.5-6 mg/d), ziprasidone (80–160 mg/d), max. 18 mo, db, n = 1493 | Participants who discontinued phase Id were randomized to ziprasidone, olanzapine, quetiapine, or risperidone (patients could not receive the same drug as in phase I), n = 444, max. 18 mo, db | Time to discontinuation was significantly longer for olanzapine and risperidone than for quetiapine and ziprasidone |
Kinon et al,30 USA | Schizophrenia, schizophreniform, or schizoaffective disorder, DSM-IV | Risperidone (2–6 mg/d), 2 wk, open, n = 628 | Switch to olanzapine 10–20 mg/d or staying on risperidone, n = 378, 10 wk, db | Switchers to olanzapine had a statistically significantly larger symptom reduction than stayers on risperidone. |
Leucht et al31 ongoing Germany, Romania | Schizophrenia or schizoaffective disorder DSM-IV | Amisulpride (200–800 mg/d) or olanzapine (5–20 mg/d), 2 wk, randomized, db, n = 350 | Switching to the respective other drug or staying on the same drug, same doses, 6 wk, n = not indicated, db | Ongoing study |
OPTiMiSE Trial Design
Study Flow
Participants
Rationale for Study Medication
Phase I.
Phase II.
Phase III.
Choice of Outcomes
Statistical Analysis
Study Progress and Outlook
References
Information & Authors
Information
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History
Authors
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