Levetiracetam as an Adjunctive Treatment for Mania: A Double-Blind, Randomized, Placebo-Controlled Trial

Levetiracetam is an anticonvulsant with a low side effect profile and favorable properties for individuals with bipolar I disorder during their manic phase. Despite initial promising results until about 2008, it appears that this track of research has not been followed-up. To counter this, we tested the influence of adjuvant levetiracetam on acute mania, compared to placebo. More specifically, we performed a randomized, double-blind, placebo-controlled clinical trial among inpatients with bipolar disorder I during their acute phase of mania.

A total of 72 inpatients (mean age: 33.98 years; 23.6% females) with diagnosed bipolar disorder I and during their acute manic phase were randomly assigned either to the adjuvant levetiracetam (250 mg to a maximum of 1,500 mg) or to the placebo condition. Standard medication was lithium at therapeutic dosages. At baseline, participants completed a series of self-rating questionnaires covering sociodemographic information and subjective sleep. Subjective sleep was re-assessed 24 days later at the end of the study. Experts rated participants' acute state of mania with the Young Mania Rating Scale at baseline and at day 12 and day 24. Participants' cognitive performance was assessed at baseline and at day 24 at the end of the study.

Over time, mania scores significantly decreased (large effect size), but more so in the levetiracetam condition, compared to the placebo condition (medium effect size). Likewise, over time, subjective sleep improved (large effect size), but more so in the levetiracetam condition, compared to the placebo condition (large effect size). Over time, cognitive performance improved (large effect size), irrespective of the study condition.

Compared to placebo, adjuvant levetiracetam to lithium improved symptoms of mania, as rated by experts, and subjective sleep quality. Adjuvant levetiracetam had no further favorable (or detrimental) impact on cognitive performance.