Original Article Topiramate versus Bupropion SR when added to mood stabilizer therapy for the depressive phase of bipolar disorder: a preliminary single-blind study McIntyreRS,ManciniDA,McCannS,SrinivasanJ,SagmanD,Kennedy SH. Topiramate versus Bupropion SR when added to mood stabilizer therapy for the depressive phase of bipolar disorder: a preliminary single- blind study Bipolar Disord 2002: 4: 207–213. Ó Blackwell Munksgaard, 2002 Objective: Antiepileptic drugs (AEDs) are commonly employed in the treatmentofbipolardisorder.Theefficacyandtolerabilityoftopiramate, anovelanticonvulsant,andbupropionSRwhenaddedtomoodstabilizer therapy were compared under single-blind conditions (rater-blinded) in patients meeting DSM-IV criteria for bipolar I/II depression. Methods: A total of 36 out-patients with Hamilton Depression Rating Scale (HDRS-17) scores ‡16 were randomized to receive escalating doses ofeithertopiramate(50–300mg/day)orbupropionSR(100–400mg/day) for8weeks.Datawereanalyzedonanintent-to-treatbasisusingthelast observation carried forward method. Results: The percentage of patients meeting a priori response criteria (‡50% decrease from baseline in mean HDRS-17 total score) was significant for both topiramate (56%) and bupropion SR (59%) [t(17) ¼ 2.542,p ¼ 0.04and t(17) ¼ 2.661,p ¼ 0.03,respectively].Baseline demographic and clinical parameters were comparable between the two treatment groups. The mean doses of study medication were 176 mg/day (SD ¼ 102 mg/day) for the topiramate-treated group and 250 mg/day (SD ¼ 133mg/day)forthebupropionSR-treatedgroup.Asignificantand comparablereductionindepressivesymptomswasobservedfrombaseline toendpointfollowingtopiramateandbupropionSRtreatment,according toa ‡ 50% reduction in the HDRS-17. Total mean HDRS-17 scores significantly decreased from baseline to endpoint in both groups (p ¼ 0.001), however, differences between the topiramate-treated group and the bupropion SR-treated group were not significant [t(36) ¼ 1.754, p ¼ 0.097]. Both topiramate and bupropion SR were generally well tolerated. Thirteen patients discontinued the study: 2 because of lack of efficacy, 1 due to withdrawal of consent and 10 following side-effects (six in the topiramate and four in the bupropion SR-treated group). There were no cases of affective switch in either arm. Weight loss was experiencedbypatientsinbothgroups(meanweightlossatendpointwas 1.2kginbupropionSRand5.8kgintopiramate)[t(17) ¼ 2.325, p ¼ 0.061 and t(17) ¼ 2.481, p ¼ 0.043, respectively]. Conclusions: These preliminary data suggest that adjunctive topiramate may reduce depressive symptom severity in acute bipolar depression. The antidepressant efficacy of this compound requires confirmation via double-blind placebo controlled investigation. Roger S McIntyre a , Deborah A Mancini b , Sonia McCann b , Janaki Srinivasan a , Doron Sagman b and Sidney H Kennedy a a Department of Psychiatry, University of Toronto; Mood and Anxiety Disorders Program, Center for Addiction and Mental Health, Clarke Site, b Mood and Anxiety Program, Center for Addiction and Mental Health, Clarke Site, Toronto, Ontario, Canada Key words: bipolar disorder – bupropion – depression – remission – topiramate Received 27 June 2001, revised and accepted for publication 1 November 2001 Corresponding author: Dr Roger S. McIntyre, Center for Addiction and Mental Health, Clarke Site, 250 College Street, Toronto, Ontario, Canada M5T 1R8. Fax: 416-979-4297; e-mail: roger_mcintyre@camh.net Bipolar Disorders 2002: 4: 207–213 Copyright Ó Blackwell Munksgaard 2002 BIPOLAR DISORDERS ISSN 1398-5647 207