Centrally-acting opioid receptor antagonists as a treatment for antipsychotic-induced weight gain: A systematic review and meta-analysis of clinical trial data.

BACKGROUND

Antipsychotic-induced weight gain (AIWG) is a major concern in psychiatry, where there is a mortality gap between those with mental illness, particularly schizophrenia, and the general population. One development proposed is using centrally-acting opioid receptor antagonists (CORAs) such as naltrexone and samidorphan.

OBJECTIVE

The systematic review and meta-analysis evaluated the available human clinical trial data on the effect of CORA on AIWG.

METHODOLOGY: Four online databases (MEDLINE, EMBASE, PsycINFO, and Cochrane) were searched for randomized-controlled trials (RCTs) on the topic. The primary outcome was change in bodyweight. Secondary anthropometric outcomes included percentage bodyweight change, BMI change, and absolute risk of weight gain. Meta-analysis was conducted on primary outcome.

RESULTS

Nine RCT articles (samidorphan = 6, naltrexone = 3) and two extension studies from RCTs (both samidorphan) were identified. Meta-analysis of four RCTs (n = 1416) found olanzapine/samidorphan was associated with less weight gain than olanzapine alone (mean difference in bodyweight change: -1.18 kg; 95% CI: -1.67 to -0.68). Olanzapine/samidorphan was also superior to olanzapine for changes in BMI (-0.65 kg/m2; 95% CI: -1.1 to -0.28), waist circumference (-1.5 cm; 95% CI: -2.67 to -0.32), and risk reduction for gaining 7% body weight (-12.4%; 95% CI: -18.27 to -6.54) or 10% body weight (-10.8%; 95% CI: -16.21 to -5.45). Naltrexone did not separate from placebo for change in weight or BMI.

CONCLUSION

CORA, specifically samidorphan, was effective at reducing weight gain in individuals prescribed olanzapine. The small effect sizes and discrepancy between samidorphan and naltrexone suggest effects may be timing dependent, not a class effect, or dependent on the antipsychotic combination.