REVIEW OF: Arman S and Haghshenas M, J Res Med Sci 2022;27:23

STUDY TYPE: Randomized double-blind placebo-controlled trial

There is already a small open-label trial that used topiramate added to olanzapine to prevent weight gain in youth with bipolar disorder (BD) (Wozniak J et al, J Child Adolesc Psychopharmacol 2009;19(5):539). But does topiramate also help prevent weight gain with aripiprazole?

In a study from Iran, 40 patients with BD (ages 6–18; mean age 13) were started on aripiprazole 5 mg and were randomly assigned to receive either adjunctive topiramate 12.5 mg or placebo, along with weekly dosage adjustments as needed, with a target dose of 150 mg. The researchers measured weight, height, BMI, waist circumference, abdominal circumference, and blood pressure at one- and three-month follow-up.

At three-month follow-up, patients who received topiramate gained less weight compared to those who received placebo. Patients on topiramate saw their BMIs decrease from 25.41 to 24.09, while those on adjunctive placebo saw their BMIs increase from 23.92 to 24.41. These results translate to approximately eight pounds lost for a 66-inch-tall teen on topiramate vs three pounds gained on placebo. However, there were no clinically significant differences between the groups on other metabolic outcomes at three-month follow-up. Topiramate was also associated with lower Young Mania Rating Scale scores, which was statistically significant but not clinically significant.

The study had limitations, including the lack of an intent-to-treat analysis, small sample size, unblinding due to topiramate side effects, lack of comment on cognitive side effects, the short three-month duration, and the lack of reported confidence intervals.

CARLAT TAKE

Despite the limitations and side effects, these results for BMI are notable. Topiramate may prevent several pounds of weight gain in youths taking atypical antipsychotics for BD, but we suggest you consider metformin first. If you try topiramate, watch for cognitive side effects.