The review included 41 studies (4,015 participants, range nine to 302). The meta-analysis reportedly included 93 arms: between four and 25 arms for each active intervention and 23 control arms (untreated or placebo). Quality of reporting was rated as moderate (mean score of 5 points out of 13).
Clozapine data were only sufficient for analyses of weight gain and somnolence; other drugs were assessed for all outcomes. Findings reported here showed a significant difference between the intervention group and placebo or no treatment; findings for other comparisons were not significant.
Weight gain was reported by 25 studies (62 arms, 3,401 participants). Aripiprazole, clozapine, olanzapine, quetiapine and risperidone were associated with significant gain. Odds ratios for risk of weight gain ranged from 3.77 (CI 0.37 to 16.27) for ziprasidone to 15.1 (CI 6.56 to 31.1) for olanzapine. Mean weight gain ranged from 0.89 to 3.99kg (30 studies, 66 arms, 3,221 participants) and was highest for olanzapine (mean gain 2.99kg). Ziprasidone was associated with a mean weight loss of -0.1kg, which was not statistically significant.
Metabolic outcomes were reported by 10 studies (27 arms, 1,655 to 1,784 participants). Risperidone and olanzapine significantly increased glucose (mean increases ranged from 2.09 to 3.7mg/dL). Quetiapine and olanzapine significantly increased cholesterol (mean increases ranged from 4.46 to 10.77mg/dL) and triglycerides (mean increases ranged from 19.5 to 20.18mg/dL).
Increases in prolactin were reported by 12 studies (26 arms, 1,180 participants). Risperidone, olanzapine and ziprasidone statistically significantly increased the risk of a meaningful increase in prolactin (odds ratios 15.6 to 38.63). Sedation and somnolence were reported by 29 studies (66 arms, 3,348 participants) and all drugs significantly increased the risk (odds ratios 5.44 to 54.82). Extrapyramidal syndrome (including akathisia) was reported by 28 studies (63 arms, 3,258 participants) and ziprasidone, olanzapine, aripiprazole and risperidone all significantly increased the risk (odds ratios 3.71 to 20.56).
Credible intervals were reported for all analyses. The findings of sensitivity analyses did not differ substantially from those of the main analyses.