Any comparison of different outcomes in different diseases can only serve the purpose of a qualitative perspective. The increment of improvement by drug over placebo must be viewed in the context of the disease's seriousness, suffering induced, natural course, duration, outcomes, adverse events and societal values.

IMPORTANCEThere is debate about the effectiveness of psychiatric treatments and whether pharmacotherapy or psychotherapy should be primarily used.OBJECTIVES To perform a systematic overview on the efficacy of pharmacotherapies and psychotherapies for major psychiatric disorders and to compare the quality of pharmacotherapy and psychotherapy trials. EVIDENCE REVIEWWe searched MEDLINE, EMBASE, PsycINFO, and the Cochrane Library (April 2012, with no time or language limit) for systematic reviews on pharmacotherapy or psychotherapy vs placebo, pharmacotherapy vs psychotherapy, and their combination vs either modality alone. Two reviewers independently selected the meta-analyses and extracted efficacy effect sizes. We assessed the quality of the individual trials included in the pharmacotherapy and psychotherapy meta-analyses with the Cochrane risk of bias tool.FINDINGS The search yielded 45 233 results. We included 61 meta-analyses on 21 psychiatric disorders, which contained 852 individual trials and 137 126 participants. The mean effect size of the meta-analyses was medium (mean, 0.50; 95% CI, 0.41-0.59). Effect sizes of psychotherapies vs placebo tended to be higher than those of medication, but direct comparisons, albeit usually based on few trials, did not reveal consistent differences. Individual pharmacotherapy trials were more likely to have large sample sizes, blinding, control groups, and intention-to-treat analyses. In contrast, psychotherapy trials had lower dropout rates and provided follow-up data. In psychotherapy studies, wait-list designs showed larger effects than did comparisons with placebo.CONCLUSIONS AND RELEVANCE Many pharmacotherapies and psychotherapies are effective, but there is a lot of room for improvement. Because of the multiple differences in the methods used in pharmacotherapy and psychotherapy trials, indirect comparisons of their effect sizes compared with placebo or no treatment are problematic. Well-designed direct comparisons, which are scarce, need public funding. Because patients often benefit from both forms of therapy, research should also focus on how both modalities can be best combined to maximize synergy rather than debate the use of one treatment over the other.

In treatment-resistant schizophrenia, clozapine is considered the standard treatment. However, clozapine use has restrictions owing to its many adverse effects. Moreover, an increasing number of randomized clinical trials (RCTs) of other antipsychotics have been published. OBJECTIVE To integrate all the randomized evidence from the available antipsychotics used for treatment-resistant schizophrenia by performing a network meta-analysis. DATA SOURCES MEDLINE, EMBASE, Biosis, PsycINFO, PubMed, Cochrane Central Register of Controlled Trials, World Health Organization International Trial Registry, and clinicaltrials.gov were searched up to June 30, 2014. STUDY SELECTION At least 2 independent reviewers selected published and unpublished single-and double-blind RCTs in treatment-resistant schizophrenia (any study-defined criterion) that compared any antipsychotic (at any dose and in any form of administration) with another antipsychotic or placebo. DATA EXTRACTION AND SYNTHESIS At least 2 independent reviewers extracted all data into standard forms and assessed the quality of all included trials with the Cochrane Collaboration's risk-of-bias tool. Data were pooled using a random-effects model in a Bayesian setting. MAIN OUTCOMES AND MEASURES The primary outcome was efficacy as measured by overall change in symptoms of schizophrenia. Secondary outcomes included change in positive and negative symptoms of schizophrenia, categorical response to treatment, dropouts for any reason and for inefficacy of treatment, and important adverse events. RESULTS Forty blinded RCTs with 5172 unique participants (71.5% men; mean [SD] age, 38.8 [3.7] years) were included in the analysis. Few significant differences were found in all outcomes. In the primary outcome (reported as standardized mean difference; 95% credible interval), olanzapine was more effective than quetiapine (−0.29; −0.56 to −0.02), haloperidol (−0. 29; −0.44 to −0.13), and sertindole (−0.46; −0.80 to −0.06); clozapine was more effective than haloperidol (−0.22; −0.38 to −0.07) and sertindole (−0.40; −0.74 to −0.04); and risperidone was more effective than sertindole (−0.32; −0.63 to −0.01). A pattern of superiority for olanzapine, clozapine, and risperidone was seen in other efficacy outcomes, but results were not consistent and effect sizes were usually small. In addition, relatively few RCTs were available for antipsychotics other than clozapine, haloperidol, olanzapine, and risperidone. The most surprising finding was that clozapine was not significantly better than most other drugs. CONCLUSIONS AND RELEVANCE Insufficient evidence exists on which antipsychotic is more efficacious for patients with treatment-resistant schizophrenia, and blinded RCTs-in contrast to unblinded, randomized effectiveness studies-provide little evidence of the superiority of clozapine compared with other second-generation antipsychotics. Future clozapine studies with high doses and patients with extremely treatment-refractory schizophrenia might be most promising to change the current evid...

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Because of the high number of patients with obsessive-compulsive disorder (OCD) not responding satisfactorily to initial monotherapy with serotonin reuptake inhibitors (SRIs), the evaluation of additional treatment options is highly relevant. To examine efficacy of add-on pharmacotherapy with antipsychotics, a systematic literature search was applied to identify all double-blind, randomized, placebo-controlled trials (DB-PC-RCTs) determining the efficacy of antipsychotic augmentation of SRIs in treatment-resistant OCD. The primary outcome of the pooled meta-analytic data analysis was response to the adjunctive antipsychotic treatment measured by both the rates of participants achieving response [defined as ≥ 35% reduction in Yale-Brown Obsessive-Compulsive Scale (YBOCS)] and mean changes in YBOCS total score. Twelve DB-PC-RCTs investigating quetiapine (N = 5), risperidone (N = 3), olanzapine (N = 2), aripiprazole (N = 1) and haloperidol (N = 1) with a total of 394 subjects were included. Significantly more patients responded to augmentation with antipsychotics than with placebo [relative risk = 2.10, 95% confidence intervals (CI) 1.16-3.80]. Additionally, the mean reduction of the YBOCS total score revealed an efficacy in favour of the antipsychotic medication [standardized mean difference (SMD) = 0.54, 95% CI 0.15-0.93]. Significant efficacy was identifiable only for risperidone, but not for quetiapine and olanzapine. The results regarding aripiprazole and haloperidol were inconsistent. Overall, about one-third of SRI-resistant OCD patients benefited from an augmentation strategy with antipsychotics. Based on the favourable risk:benefit ratio, risperidone can be considered as the agent of first choice and should be preferred to quetiapine and olanzapine. Further trials, mainly with higher antipsychotic doses, are required to optimize pharmacological treatment recommendations for SRI-refractory OCD.