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Relapse prevention in schizophrenia: a systematic review and meta-analysis of second-generation antipsychotics versus first-generation antipsychotics.

ABSTRACT: Few controlled trials compared second-generation antipsychotics (SGAs) with first-generation antipsychotics (FGAs) regarding relapse prevention in schizophrenia. We conducted a systematic review/meta-analysis of randomized trials, lasting ?6 months comparing SGAs with FGAs in schizophrenia. Primary outcome was study-defined relapse; secondary outcomes included relapse at 3, 6 and 12 months; treatment failure; hospitalization; and dropout owing to any cause, non-adherence and intolerability. Pooled relative risk (RR) (±95% confidence intervals (CIs)) was calculated using random-effects model, with numbers-needed-to-treat (NNT) calculations where appropriate. Across 23 studies (n=4504, mean duration=61.9±22.4 weeks), none of the individual SGAs outperformed FGAs (mainly haloperidol) regarding study-defined relapse, except for isolated, single trial-based superiority, and except for risperidone's superiority at 3 and 6 months when requiring ?3 trials. Grouped together, however, SGAs prevented relapse more than FGAs (29.0 versus 37.5%, RR=0.80, CI: 0.70-0.91, P=0.0007, I(2)=37%; NNT=17, CI: 10-50, P=0.003). SGAs were also superior regarding relapse at 3, 6 and 12 months (P=0.04, P<0.0001, P=0.0001), treatment failure (P=0.003) and hospitalization (P=0.004). SGAs showed trend-level superiority for dropout owing to intolerability (P=0.05). Superiority of SGAs regarding relapse was modest (NNT=17), but confirmed in double-blind trials, first- and multi-episode patients, using preferentially or exclusively raw or estimated relapse rates, and for different haloperidol equivalent comparator doses. There was no significant heterogeneity or publication bias. The relevance of the somewhat greater efficacy of SGAs over FGAs on several key outcomes depends on whether SGAs form a meaningful group and whether mid- or low-potency FGAs differ from haloperidol. Regardless, treatment selection needs to be individualized considering patient- and medication-related factors.

SUBMITTER: Kishimoto T

PROVIDER: S-EPMC3320691 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Relapse prevention in schizophrenia: a systematic review and meta-analysis of second-generation antipsychotics versus first-generation antipsychotics.

Kishimoto T T Agarwal V V Kishi T T Leucht S S Kane J M JM Correll C U CU

Molecular psychiatry 20111129 1

Few controlled trials compared second-generation antipsychotics (SGAs) with first-generation antipsychotics (FGAs) regarding relapse prevention in schizophrenia. We conducted a systematic review/meta-analysis of randomized trials, lasting 6 months comparing SGAs with FGAs in schizophrenia. Primary outcome was study-defined relapse; secondary outcomes included relapse at 3, 6 and 12 months; treatment failure; hospitalization; and dropout owing to any cause, non-adherence and intolerability. Pool ...[more]

PMID: 22124274

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Project description:Because early treatment choice is critical in first-episode schizophrenia-spectrum disorders (FES), this meta-analysis compared efficacy and tolerability of individual second-generation antipsychotics (SGAs) with first-generation antipsychotics (FGAs) in FES. We conducted systematic literature search (until 12 December 2010) and meta-analysis of acute, randomized trials with ?1 FGA vs. SGA comparison; patients in their first episode of psychosis and diagnosed with schizophrenia-spectrum disorders; available data for psychopathology change, treatment response, treatment discontinuation, adverse effects, or cognition. Across 13 trials (n = 2509), olanzapine (seven trials) and amisulpride (one trial) outperformed FGAs (haloperidol: 9/13 trials) in 9/13 and 8/13 efficacy outcomes, respectively, risperidone (eight trials) in 4/13, quetiapine (one trial) in 3/13 and clozapine (two trials) and ziprasidone (one trial) in 1/13, each. Compared to FGAs, extrapyramidal symptom (EPS)-related outcomes were less frequent with olanzapine, risperidone and clozapine, but weight gain was greater with clozapine, olanzapine and risperidone. Pooled SGAs were similar to FGAs regarding total psychopathology change, depression, treatment response and metabolic changes. SGAs significantly outperformed FGAs regarding lower treatment discontinuation, irrespective of cause, negative symptoms, global cognition and less EPS and akathisia, while SGAs increased weight more (p < 0.05-0.01). Results were not affected by FGA dose or publication bias, but industry-sponsored studies favoured SGAs more than federally funded studies. To summarize, in FES, olanzapine, amisulpride and, less so, risperidone and quetiapine showed superior efficacy, greater treatment persistence and less EPS than FGAs. However, weight increase with olanzapine, risperidone and clozapine and metabolic changes with olanzapine were greater. Additional FES studies including broader-based SGAs and FGAs are needed.

Project description:BackgroundObservational studies have reported higher mortality among older adults treated with first-generation antipsychotics (FGAs) versus second-generation antipsychotics (SGAs). A few studies examined risk for medical events, including stroke, ventricular arrhythmia, venous thromboembolism, myocardial infarction, pneumonia, and hip fracture.Objectives1) Review robust epidemiologic evidence comparing mortality and medical event risk between FGAs and SGAs in older adults; 2) Quantify how much these medical events explain the observed mortality difference between FGAs and SGAs.Data sourcesPubmed and Science Citation Index.Study eligibility criteria, participants, and interventionsStudies of antipsychotic users that: 1) evaluated mortality or medical events specified above; 2) restricted to populations with a mean age of 65 years or older 3) compared FGAs to SGAs, or both to a non-user group; (4) employed a "new user" design; (5) adjusted for confounders assessed prior to antipsychotic initiation; (6) and did not require survival after antipsychotic initiation. A separate search was performed for mortality estimates associated with the specified medical events.Study appraisal and synthesis methodsFor each medical event, we used a non-parametric model to estimate lower and upper bounds for the proportion of the mortality difference-comparing FGAs to SGAs-mediated by their difference in risk for the medical event.ResultsWe provide a brief, updated summary of the included studies and the biological plausibility of these mechanisms. Of the 1122 unique citations retrieved, we reviewed 20 observational cohort studies that reported 28 associations. We identified hip fracture, stroke, myocardial infarction, and ventricular arrhythmias as potential intermediaries on the causal pathway from antipsychotic type to death. However, these events did not appear to explain the entire mortality difference.ConclusionsThe current literature suggests that hip fracture, stroke, myocardial infarction, and ventricular arrhythmias partially explain the mortality difference between SGAs and FGAs.

Dataset Information

Relapse prevention in schizophrenia: a systematic review and meta-analysis of second-generation antipsychotics versus first-generation antipsychotics.

Publications

Relapse prevention in schizophrenia: a systematic review and meta-analysis of second-generation antipsychotics versus first-generation antipsychotics.

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