Original article Comparative efficacy and safety of oxcarbazepine versus divalproex sodium in the treatment of acute mania: A pilot study Ashish Kumar Kakkar a , H.S. Rehan a , K.E.S. Unni b , Neeraj Kumar Gupta b , Deepti Chopra a, * , Dinesh Kataria b a Department of Pharmacology, Lady Hardinge Medical College and SSK Hospital, Connaught Place, New Delhi 110001, India b Department of Psychiatry and Drug De-addiction Centre, Lady Hardinge Medical College and SSK Hospital, New Delhi 110001, India Received 11 September 2008; received in revised form 12 December 2008; accepted 26 December 2008 Available online 25 March 2009 Abstract Objective. e This study compared the efficacy and safety of oxcarbazepine and divalproex sodium in acute mania patients. Subjects and methods. e In this 12 week, randomized, double-blind pilot study, 60 patients diagnosed with acute mania (DSM-IV) and a baseline Young Mania Rating Scale (YMRS) score of 20 or more received flexibly dosed oxcarbazepine (1000e2400 mg/day) or divalproex (750e2000 mg/day). The mean decrease in the YMRS score from baseline was used as the main outcome measure of response to treatment. A priori protocol-defined threshold scores were 12 for remission and 15 for relapse. Number of patients showing adequate response and the time taken to achieve improvement was compared. Adverse events were systematically recorded throughout the study. Results. e Over 12 weeks, mean improvement in YMRS scores was comparable for both the groups including the mean total scores as well as percentage fall from baseline. There were no significant differences between treatments in the rates of symptomatic mania remission (90% in divalproex and 80% in oxcarbazepine group) and subsequent relapse. Median time taken to symptomatic remission was 56 days in divalproex group while it was 70 days in the oxcarbazepine group ( p ¼ 0.123). A significantly greater number of patients in divalproex group experienced one or more adverse drug events as compared to patients in the oxcarbazepine group (66.7% versus 30%, p < 0.01). Conclusion. e Oxcarbazepine demonstrated comparable efficacy to divalproex sodium in the management of acute mania. Also the overall adverse event profile was found to be superior for oxcarbazepine. Ó 2009 Elsevier Masson SAS. All rights reserved. Keywords: Oxcarbazepine; Divalproex; Acute mania 1. Introduction Bipolar disorder is a severe and disabling psychiatric disorder with worldwide lifetime prevalence estimated between 0.3% and 1.5% [17]. The natural course of bipolar disorder is characterized by acute severe affective episodes followed by high rates of relapse and recurrence [7]. The primary goal of treatment thus is to treat the acute episode as well as to prevent recurrences. The treatment of bipolar disorder remains a challenge for physicians. Although lithium has been the gold standard mood stabilizer for more than 25 years, there has been increasing recognition of lithium’s effi- cacy limitations. It is now understood that more than 50% of patients in most centers do not show adequate, complete or sustained response to lithium even when adjunctive medica- tions are used [13]. Also lithium has the narrowest gap between therapeutic and toxic concentrations of any agent routinely prescribed in psychiatric practice [8]. To improve clinical outcomes for significant number of patients with bipolar disorder, anticonvulsants and atypical antipsychotics are often used as alternatives or augmentation strategies to lithium. Divalproex and carbamazepine have proven efficacy in treating acute mania and remain the principally accepted anticonvulsants for effective antimanic therapy [18]. Approved * Corresponding author. Tel.: þ91 9818710237. E-mail address: drdeeptichopra@yahoo.co.in (D. Chopra). 0924-9338/$ - see front matter Ó 2009 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.eurpsy.2008.12.014 Available online at www.sciencedirect.com European Psychiatry 24 (2009) 178e182