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 Jun;4(3):207-13. doi: 10.1034/j.1399-5618.2002.01189.x.


Objective: Antiepileptic drugs (AEDs) are commonly employed in the treatment of bipolar disorder. The efficacy and tolerability of topiramate, a novel anticonvulsant, and bupropion SR when added to mood stabilizer 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 > or = 16 were randomized to receive escalating doses of either topiramate (50-300 mg/day) or bupropion SR (100-400 mg/day) for 8 weeks. Data were analyzed on an intent-to-treat basis using the last observation carried forward method.

Results: The percentage of patients meeting a priori response criteria (> or = 50% decrease from baseline in mean HDRS-17 total score) was significant for both topiramate (56%) and bupropion SR (59%) [t(17) = 2.542, p = 0.04 and t(17) = 2.661, p = 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 = 102 mg/day) for the topiramate-treated group and 250 mg/day (SD = 133 mg/day) for the bupropion SR-treated group. A significant and comparable reduction in depressive symptoms was observed from baseline to endpoint following topiramate and bupropion SR treatment, according to a > or = 50% reduction in the HDRS-17. Total mean HDRS-17 scores significantly decreased from baseline to endpoint in both groups (p = 0.001), however, differences between the topiramate-treated group and the bupropion SR-treated group were not significant [t(36) = 1.754, p = 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 experienced by patients in both groups (mean weight loss at endpoint was 1.2 kg in bupropion SR and 5.8 kg in topiramate) [t(17) = 2.325, p = 0.061 and t(17) = 2.481, p = 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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Evaluation Study
  • Randomized Controlled Trial

MeSH terms

  • Acute Disease
  • Adult
  • Anticonvulsants / administration & dosage*
  • Anticonvulsants / adverse effects
  • Antimanic Agents / administration & dosage*
  • Antimanic Agents / adverse effects
  • Bipolar Disorder / diagnosis
  • Bipolar Disorder / drug therapy*
  • Bupropion / administration & dosage*
  • Bupropion / adverse effects
  • Depressive Disorder / diagnosis
  • Depressive Disorder / drug therapy*
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Fructose / administration & dosage*
  • Fructose / adverse effects
  • Fructose / analogs & derivatives*
  • Humans
  • Male
  • Middle Aged
  • Psychiatric Status Rating Scales
  • Single-Blind Method
  • Topiramate
  • Treatment Outcome


  • Anticonvulsants
  • Antimanic Agents
  • Bupropion
  • Topiramate
  • Fructose