Clozapine and Psychosocial Function in Schizophrenia: A Systematic Review and Meta-Analysis
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BACKGROUND: Clozapine has unique efficacy for symptoms in treatment-resistant schizophrenia; however, symptomatic remission is not necessary nor sufficient for functional improvement. No study has pooled the effect of clozapine on psychosocial function across clinical trials. OBJECTIVE: We conducted a systematic review and meta-analysis to compare the effects of clozapine with other antipsychotics on psychosocial function, and described the predictors of functional outcome. METHODS: We searched MEDLINE/PubMed, PsychINFO, EMBASE, CINAHL, Scopus, Web of Science, Cochrane Central Register of controlled trials and clinical trial registries till April 2018, with no language limits. Eligible studies were randomised controlled trials of clozapine vs. typical or atypical antipsychotics among adults with treatment-resistant schizophrenia. We included studies with flexible or fixed doses of antipsychotics within the therapeutic range to reflect naturalistic care. Effect sizes of studies were pooled using generic inverse variance and random-effects models and presented as standard mean differences. Study quality was assessed in accordance with the Cochrane Collaboration guideline, and subgroup analyses were carried out to identify potential moderators and methodological biases. RESULTS: Nine studies with 1279 participants (69.7% male) were included. Clozapine showed beneficial effects on psychosocial function, but both short-term trials [n = 3; comparing 99 people taking clozapine with 97 controls (standardised mean difference = 0.04; 95% confidence interval - 0.24, 0.32; p = 0.77; I2 = 0%)] and long-term trials [n = 5; comparing 415 people taking clozapine with 427 controls (standardised mean difference = 0.05; 95% confidence interval - 0.16, 0.27; p = 0.64; I2 = 50%)] showed no superiority of clozapine to other antipsychotics in this regard. Only one study explored the predictors of psychosocial function. Baseline severity of illness, illicit drug use, extrapyramidal side effects, sex and cognition explained the variability in functional outcome. A range of scales measured psychosocial function, and the quality of reporting varied across trials. CONCLUSIONS: Clozapine does not appear superior to other antipsychotics for improvement of psychosocial function. Standardisation of psychosocial function measurement is needed to improve the quality of evidence. Further exploration of the predictors of good psychosocial outcomes with clozapine treatment may improve personalisation of care.
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