Weight gain and metabolic effects of mood stabilizers and antipsychotics in pediatric bipolar disorder: A systematic review and pooled analysis of short-term trials

Objective: To review weight and metabolic effects of mood-stabilizing treatments in pediatric bipolar disorder. Method: Systematic PubMed/fidedfine search of studies reporting on change in weight and/or glucose/lipid values with mood-stabilizing drugs in at least nine pediatric patients with bipolar disorder. Results: Nineteen studies, including 24 medication trials in 684 patients (mean age, 12.3 +/- 2.9 years) were included. Youngsters received lithium, antiepileptics, or their combinations (n = 459), or second-generation antipsychotics, alone or combined with lithium or divalproex (n = 225), for 4 to 48 (mean, 15.4 +/- 12.7) weeks. Weight increase was significant/clinically relevant in 18 (75.0%) trials. Weight loss was significant with topiramate (2 studies, 38 subjects) and present with aripiprazole (1 study, 14 subjects). In trials lasting <= 12 weeks, weight gain was greater with second-generation antipsychotics plus mood stabilizers (5.5 +/- 1.8 kg) compared to mood-stabilizer monotherapy (1.2 +/- 1.9 kg, p < .05, Cohen's d = 2.33) or mood-stabilizer cotreatment (2.1 +/- 1.3 kg, p < .05, Cohen's d = 2.17), but not compared to antipsychotic monotherapy (3.4 +/- 1.3 kg, p > .05, Cohen's d = 1.34). Nonfasting glucose/lipid changes were nonsignificant in two second-generation antipsychotic trials (n = 61, 8.9%). Conclusions: Data are sparse regarding body composition effects and lacking for fasting metabolic effects of mood stabilizers in pediatric bipolar disorder. Combining antipsychotics with mood stabilizers seems to lead to greater weight gain than treatment with one or two mood stabilizers.