History of genomics Comparative genomics has a root in the comparison of virus genomes in the early s. The system helps researchers to identify large rearrangements, single base mutations, reversals, tandem repeat expansions and other polymorphisms.
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.
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 suitable trials, with data for 43 participants. All drugs were significantly more effective than placebo. 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.Featured Articles.
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