Summary Background The question of which antipsychotic drug should be preferred for the treatment of schizophrenia is controversial, and conventional pairwise meta-analyses cannot provide a hierarchy ...based on the randomised evidence. We aimed to integrate the available evidence to create hierarchies of the comparative efficacy, risk of all-cause discontinuation, and major side-effects of antipsychotic drugs. Methods We did a Bayesian-framework, multiple-treatments meta-analysis (which uses both direct and indirect comparisons) of randomised controlled trials to compare 15 antipsychotic drugs and placebo in the acute treatment of schizophrenia. We searched the Cochrane Schizophrenia Group's specialised register, Medline, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for reports published up to Sept 1, 2012. Search results were supplemented by reports from the US Food and Drug Administration website and by data requested from pharmaceutical companies. Blinded, randomised controlled trials of patients with schizophrenia or related disorders were eligible. We excluded trials done in patients with predominant negative symptoms, concomitant medical illness, or treatment resistance, and those done in stable patients. Data for seven outcomes were independently extracted by two reviewers. The primary outcome was efficacy, as measured by mean overall change in symptoms. We also examined all-cause discontinuation, weight gain, extrapyramidal side-effects, prolactin increase, QTc prolongation, and sedation. Findings We identified 212 suitable trials, with data for 43 049 participants. All drugs were significantly more effective than placebo. The standardised mean differences with 95% credible intervals were: clozapine 0·88, 0·73–1·03; amisulpride 0·66, 0·53–0·78; olanzapine 0·59, 0·53–0·65; risperidone 0·56, 0·50–0·63; paliperidone 0·50, 0·39–0·60; zotepine 0·49, 0·31–0·66; haloperidol 0·45, 0·39–0·51; quetiapine 0·44, 0·35–0·52; aripiprazole 0·43, 0·34–0·52; sertindole 0·39, 0·26–0·52; ziprasidone 0·39, 0·30–0·49; chlorpromazine 0·38, 0·23–0·54; asenapine 0·38, 0·25–0·51; lurasidone 0·33, 0·21–0·45; and iloperidone 0·33, 0·22–0·43. Odds ratios compared with placebo for all-cause discontinuation ranged from 0·43 for the best drug (amisulpride) to 0·80 for the worst drug (haloperidol); for extrapyramidal side-effects 0·30 (clozapine) to 4·76 (haloperidol); and for sedation 1·42 (amisulpride) to 8·82 (clozapine). Standardised mean differences compared with placebo for weight gain varied from −0·09 for the best drug (haloperidol) to −0·74 for the worst drug (olanzapine), for prolactin increase 0·22 (aripiprazole) to −1·30 (paliperidone), and for QTc prolongation 0·10 (lurasidone) to −0·90 (sertindole). Efficacy outcomes did not change substantially after removal of placebo or haloperidol groups, or when dose, percentage of withdrawals, extent of blinding, pharmaceutical industry sponsorship, study duration, chronicity, and year of publication were accounted for in meta-regressions and sensitivity analyses. Interpretation Antipsychotics differed substantially in side-effects, and small but robust differences were seen in efficacy. Our findings challenge the straightforward classification of antipsychotics into first-generation and second-generation groupings. Rather, hierarchies in the different domains should help clinicians to adapt the choice of antipsychotic drug to the needs of individual patients. These findings should be considered by mental health policy makers and in the revision of clinical practice guidelines. Funding None.
Summary Background Conventional meta-analyses have shown inconsistent results for efficacy of pharmacological treatments for acute mania. We did a multiple-treatments meta-analysis, which accounted ...for both direct and indirect comparisons, to assess the effects of all antimanic drugs. Methods We systematically reviewed 68 randomised controlled trials (16 073 participants) from Jan 1, 1980, to Nov 25, 2010, which compared any of the following pharmacological drugs at therapeutic dose range for the treatment of acute mania in adults: aripiprazole, asenapine, carbamazepine, valproate, gabapentin, haloperidol, lamotrigine, lithium, olanzapine, quetiapine, risperidone, topiramate, and ziprasidone. The main outcomes were the mean change on mania rating scales and the number of patients who dropped out of the allocated treatment at 3 weeks. Analysis was done by intention to treat. Findings Haloperidol (standardised mean difference SMD −0·56 95% CI −0·69 to −0·43), risperidone (–0·50 –0·63 to −0·38), olanzapine (–0·43 –0·54 to −0·32, lithium (–0·37 –0·63 to −0·11), quetiapine (–0·37 –0·51 to −0·23), aripiprazole (–0·37 –0·51 to −0·23), carbamazepine (–0·36 –0·60 to −0·11, asenapine (–0·30 –0·53 to −0·07), valproate (–0·20 –0·37 to −0·04), and ziprasidone (–0·20 –0·37 to −0·03) were significantly more effective than placebo, whereas gabapentin, lamotrigine, and topiramate were not. Haloperidol had the highest number of significant differences and was significantly more effective than lithium (SMD −0·19 95% CI −0·36 to −0·01), quetiapine (–0·19 –0·37 to 0·01), aripiprazole (–0·19 –0·36 to −0·02), carbamazepine (–0·20 –0·36 to −0·01), asenapine (–0·26 –0·52 to 0·01), valproate (–0·36 –0·56 to −0·15), ziprasidone −0·36 –0·56 to −0·15), lamotrigine (–0·48 –0·77 to −0·19), topiramate (–0·63 –0·84 to −0·43), and gabapentin (–0·88 −1·40 to −0·36). Risperidone and olanzapine had a very similar profile of comparative efficacy, being more effective than valproate, ziprasidone, lamotrigine, topiramate, and gabapentin. Olanzapine, risperidone, and quetiapine led to significantly fewer discontinuations than did lithium, lamotrigine, placebo, topiramate, and gabapentin. Interpretation Overall, antipsychotic drugs were significantly more effective than mood stabilisers. Risperidone, olanzapine, and haloperidol should be considered as among the best of the available options for the treatment of manic episodes. These results should be considered in the development of clinical practice guidelines. Funding None.
Summary This review links practice, funding, and evidence for interventions for mental health and psychosocial wellbeing in humanitarian settings. We studied practice by reviewing reports of mental ...health and psychosocial support activities (2007–10); funding by analysis of the financial tracking service and the creditor reporting system (2007–09); and interventions by systematic review and meta-analysis. In 160 reports, the five most commonly reported activities were basic counselling for individuals (39%); facilitation of community support of vulnerable individuals (23%); provision of child-friendly spaces (21%); support of community-initiated social support (21%); and basic counselling for groups and families (20%). Most interventions took place and were funded outside national mental health and protection systems. 32 controlled studies of interventions were identified, 13 of which were randomised controlled trials (RCTs) that met the criteria for meta-analysis. Two studies showed promising effects for strengthening community and family supports. Psychosocial wellbeing was not included as an outcome in the meta-analysis, because its definition varied across studies. In adults with symptoms of post-traumatic stress disorder (PTSD), meta-analysis of seven RCTs showed beneficial effects for several interventions (psychotherapy and psychosocial supports) compared with usual care or waiting list (standardised mean difference SMD −0·38, 95% CI −0·55 to −0·20). In children, meta-analysis of four RCTs failed to show an effect for symptoms of PTSD (–0·36, −0·83 to 0·10), but showed a beneficial effect of interventions (group psychotherapy, school-based support, and other psychosocial support) for internalising symptoms (six RCTs; SMD −0·24, −0·40 to −0·09). Overall, research and evidence focuses on interventions that are infrequently implemented, whereas the most commonly used interventions have had little rigorous scrutiny.
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