Investigating the Efficacy of Levetiracetam As an Adjunct to Olanzapine for Acute Manic Episodes of Bipolar Disorder: A Double-Blind Placebo-Controlled Randomized Clinical Trial Publisher Pubmed



H Mirzazadeh HASAN ; M Nourollahi MARYAM ; K Assadian KASRA ; S Bordbar SANAZ ; L Razeghian Jahromi LEILA ; R Moshfeghinia REZA
Source: Journal of Affective Disorders Published:2025

Abstract

Background: Bipolar disorder (BD) involves severe mood swings, particularly manic episodes. While antipsychotics like olanzapine are common treatments, adjunct therapies are necessary to improve effectiveness and reduce side effects. This study investigates the safety and efficacy of levetiracetam, an anticonvulsant, as an adjunct treatment for acute mania in BD patients. Methods: This double-blind, placebo-controlled study involved 65 patients diagnosed with bipolar I disorder (BD-I) who were experiencing acute mania. Participants were randomly assigned to receive either levetiracetam combined with olanzapine (n = 32) or a placebo with olanzapine (n = 33) over a period of 16 weeks. The primary outcomes measured included variations in Young Mania Rating Scale (YMRS) scores, Beck Scale for Suicidal Ideation (BSSI) scores, and the occurrence of adverse events. The data analysis was conducted using SPSS-23. Results: There were no differences in the baseline characteristics between the case and control groups. The levetiracetam group showed a significantly greater reduction in YMRS scores compared to the placebo group, with mean scores of 2.03 (3.38) versus 16.63 (8.95) at week 16 (P < 0.001). Improvements were noted in subcategories such as mood elevation, motor activity, and sleep disturbances (P < 0.001). BSSI scores decreased in both groups (P < 0.001), but there was no significant difference between the groups (P = 0.07). Adverse events were minimal; however, lethargy occurred more frequently in the levetiracetam group (23.3 % compared to 3.3 %, P = 0.05). Conclusions: Levetiracetam combined with olanzapine may benefit BD patients unresponsive to olanzapine alone. Further research is required to evaluate long-term effects and confirm these findings. © 2025 Elsevier B.V., All rights reserved.