Abstracts

Rationale: Levetiracetam has been reported to have negative psychotropic effects on various psychological and psychiatric symptoms, including aggression, anxiety, and depression. Despite these reports, high-quality evidence using a wide range of assessment instruments remains limited. This study aimed to systematically review the psychotropic effects of levetiracetam across different psychological and psychiatric domains.


Methods: This meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Inclusion criteria for the systematic review were: (1) randomized, placebo- or comparator-controlled trials (RCTs) involving human subjects; (2) RCTs assessing the quantitative differences in psychotropic effects between levetiracetam and placebo or comparator. Two authors independently searched electronic databases, including PubMed, Web of Science, Cochrane CENTRAL, and ClinicalTrials.gov, from inception until May 28, 2024.


Results: A random-effects model was used to perform a meta-analysis of 30 eligible RCTs, including 2681 participants.

The overall effect size of levetiracetam on global mood outcomes was small and not statistically significant (Hedges' g = 0.095, 95% confidence interval [CI] = -0.235 to 0.425, p = 0.573, I² = 69.3%), indicating that levetiracetam does not significantly impact overall mood compared to comparators.

Levetiracetam appears to potentially worsen anger compared to comparators (Hedges' g = 0.331, 95% CI = 0.127 to 0.535, p = 0.001, I² = 0.0%), which is statistically significant. In contrast, levetiracetam does not show a significant impact on aggression (Hedges’ g = 0.138, 95% CI = 0.562 to 0.838, p = 0.699, I² = 69.1%).

Levetiracetam does not show a significant impact on anxiety (Hedges' g = -0.008, 95% CI = -0.109 to 0.093, p = 0.877, I² = 0.0%) or depression (Hedges' g = 0.153, 95% CI = -0.047 to 0.353, p = 0.133, I² = 72.6%). The effect sizes are small and not statistically significant.

The effect size of levetiracetam on mania is small and not statistically significant (Hedges' g = -0.277, 95% CI = -0.693 to 0.140, p = 0.193, I² = 39.3%).

Levetiracetam showed a significant favorable effect on symptoms of schizophrenia compared to comparator (Hedges' g = -0.981, 95% CI = -1.450 to -0.512, p < 0.001, I² = 0.0%).

In a subgroup analysis by comparator type, levetiracetam showed a significant negative effect on global mood, anger, and depression compared to lamotrigine. Conversely, levetiracetam showed a significant positive effect on global mood compared to carbamazepine, but not on other individual mood measurements.


Conclusions: In summary, levetiracetam does not have a significant overall impact on global mood. However, it may worsen anger and improve schizophrenia symptoms. Subgroup analyses indicate that the effect of levetiracetam on psychological well-being can vary depending on the comparator, with significant differences observed when compared to lamotrigine and carbamazepine.


Funding: Taichung Veterans General Hospital