Double-Blind, Randomized, Placebo-Controlled Trial of Topiramate Plus Cognitive-Behavior Therapy in Binge-Eating Disorder

Background: The authors wanted to assess topiramate’s potential for controlling BED.  Topiramate has been shown to induce weight-loss, as well as having several psychiatric effects.

Objective:  To determine the efficacy and tolerability of adjunctive topiramate compared to placebo in reducing weight and binge eating in patients with binge-eating disorder (BED) who were also receiving cognitive-behavioral therapy (CBT).
 
Methods: This was a multi-center, double blind, randomized, placebo-controlled, parallel-group trial.  Inclusion criteria consisted of a body mass index (BMI) greater than or equal to 30 kg/m2 and met DSM-IV-TR criteria for BED.  Exclusion criteria consisted of:  Prior exposure to or known contraindication for the use of topiramate, exposure to any experimental drug within 1 year prior to enrollment, pregnancy, lactation, or not using a medically accepted form of birth control, clinically significant or unstable psychiatric disorders, clinically significant or unstable medical illnesses, history of nephrolithiasis, previous surgical procedures that cause weight loss, recent smoking cessation or intention to quit, or the concurrent use of antipsychotics, cyproheptidine, antiepileptics, systemic steroids (with the exception of HRT or OC) or other any drugs known to affect mood or weight on a regular basis, within 3 months of study. Seventy-three patients were randomly assigned, 37 to the topiramate group, and 36 to the placebo group.  Doses of topiramate were titrated by 25 mg every two weeks up to 150 mg, and then 25 mg per week until the target dose of 200 mg was reached.  Patients were treated for a duration of 21 weeks. The primary outcome measure was weight change at the end of the 21-week treatment period. Secondary measures include BMI, binge frequencies (main measure being binge-day frequencies), Binge-Eating Scale Scores (BES), depressive symptoms (Beck Depression Inventory scores), and treatment tolerability (reported ADEs and dropouts).  Power was 0.8, and intention-to-treat analysis was used.

Results:  Fifty-six (76.7%) patients completed the trial.  Weight loss for the topiramate group was -6.8 kg, weight loss for placebo group was –0.9. kg (p < 0.001).   BMI for topiramate patients decreased by 2.4% compared to 0.7% for placebo.  The topiramate group’s mean BMI was 35 kg/m2 (SD = 10.5) and the placebo group’s mean BMI was 36.7 kg/m2 (SD = 4.7).  The percent weight loss in the topiramate group was 6.8% (SD = 5.2) while that of the placebo group was 4.1 % (SD = 4.3) p=0.04, A greater percentage of topiramate patients  (33.3 %) attained a weight loss > 10% compared to those that took placebo (11.5 %)  p=0.05.  Binge-eating behavior improved for both groups (p < 0.001).  Random regression analysis found no significant difference for the rate of change of binge days/wk, binge episodes/wk, or BES scores between treatments.  Greater rates of remission of binge eating in the intention-to-treat group were found for patients taking topiramate (83.8%) compared to placebo (61.1 %) p=0.3.  Depressive symptoms were reduced (p=0.001) from baseline in both treatment groups.  Ten patients from the placebo group withdrew and 7 patients from the topiramate group withdrew (p = 0.37).  One patient from the topiramate group dropped out due to adverse events.  The most frequent side effects were paresthesia, taste perversion, dysuria, and leg pain (p<0.05).  Insomnia occurred more often in the placebo group.  The authors concluded that this study revealed the efficacy of adjunctive topiramate in conjunction with CBT for patients with BED, particularly with weight reduction and binge remission.

Strengths:  This study utilizes the gold standard for study designs.  It also used multiple treatment centers, which helps to ensure a better-represented patient population. 

Weaknesses:  The potential conflicts of interest on nearly all the researchers, coupled with funding provided by the drug manufacturer introduce bias into the study.  This may be why standard error was reported in the effect of topiramate on outcome measures table instead of standard deviation. Also, the CBT portion of patient therapy was underplayed, as this often garnered results for a number of outcomes that were statistically very similar to that of combination topiramate-CBT treatment and there was little mention of drug efficacy without CBT. The title refers to BED, but the primary outcome for this study was weight loss and not a change in binge eating episodes.  The stringent criteria, coupled with the knowledge that BED also affects men and does not just affect patients with a BMI of greater than 30 limits the application of these results.  In addition, the researchers were able to pinpoint nearly half of the patients taking active drug, which questions the success of blinding.

Conclusion:  Based on this study alone, it appears that topiramate may be a helpful adjunct to patients with BED in addition to CBT, particularly when used for weight loss rather than decreasing the frequency of binge-eating episodes.  However, further studies with more patients may be required to establish long-term efficacy and other adverse effects.

Claudino AM, de Oliveira IR, Appolinario JC, Cordas TA, Duchesne M, Sichieri R, et al. Double-Blind, Randomized, Placebo-Controlled Trial of Topiramate Plus Cognitive-Behavior Therapy in Binge-Eating Disorder. J Clin Psychiatry. 2007 Sep;68(9):1324-32.

Prepared by:  Jeremy R. Armentrout, Doctor of Pharmacy Candidate, February 2008
Revised:  March 2008