Effectiveness of medications used to attenuate antipsychotic-related weight gain
and metabolic abnormalities: a systematic review and meta-analysis.
Author(s): Maayan L, Vakhrusheva J, Correll CU.
Affiliation(s): Child Study Center, New York University School of Medicine, New York, NY, USA.
Publication date & source: 2010, Neuropsychopharmacology. , 35(7):1520-30
Antipsychotic-related weight gain and metabolic effects are a critical outcome
for patients requiring these medications. A literature search using MEDLINE, Web
of Science, PsycNET, and EMBASE for randomized, open and double-blind,
placebo-controlled trials of medications targeting antipsychotic-induced weight
gain was performed. Primary outcome measures were change and endpoint values in
body weight and body mass index (BMI). Secondary outcomes included >or=7% weight
gain, all-cause discontinuation, change in waist circumference, glucose and lipid
metabolism parameters, and psychiatric symptoms. Sensitivity analyses were
conducted to explain heterogeneity of the results. Across 32 studies including
1482 subjects, 15 different medications were tested: amantadine,
dextroamphetamine, d-fenfluramine, famotidine, fluoxetine, fluvoxamine,
metformin, nizatidine, orlistat, phenylpropanolamine, reboxetine, rosiglitazone,
sibutramine, topiramate, and metformin+sibutramine. Compared with placebo,
metformin had the greatest weight loss (N=7, n=334, -2.94 kg (confidence interval
(CI:-4.89,-0.99)), followed by d-fenfluramine (N=1, n=16, -2.60 kg
(CI:-5.14,-0.06)), sibutramine (N=2, n=55, -2.56 kg (CI:-3.91,-1.22)), topiramate
(N=2, n=133, -2.52 kg (CI:-4.87,-0.16)), and reboxetine (N=2, n=79, -1.90 kg
(CI:-3.07,-0.72)). Weight loss remained significant with metformin initiation
after weight gain had occurred, but not when started concomitantly with
antipsychotics. Nausea rates were not higher with any treatment compared with
placebo. In all, 5 of 15 psychopharmacologic interventions aimed at ameliorating
antipsychotic-induced weight gain outperformed placebo. Results were most robust
for metformin, although these were modest and heterogeneous. Only one (negative)
combination treatment study was available and head-to-head studies are absent.
None of the agents were able to entirely reverse weight gain because of
antipsychotics. At present, no treatment has sufficient evidence to recommend
broad clinical usage. Antipsychotics with no or minimal cardiometabolic
liability, as well as interventions that prevent or normalize adverse
antipsychotic cardiometabolic effects are needed.
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