Topiramate for Binge-Eating Disorder
Abstract & commentary
Source: Shapira NA, et al. Treatment of binge-eating disorder with topiramate: A clinical case series. J Clin Psych 2000;61:368-372.
Binge-eating disorder is defined as recurrent episodes of binge eating that are not associated with the regular use of in appropriate compensatory behaviors (e.g., purging, fasting, excessive exercise). It occurs in approximately 30% of obese (body mass index [BMI] > 30 kg/m2) patients seeking treatment in weight-loss programs, 79% of those in Overeaters Anonymous programs, and is common in the general population.1-3
Topiramate (Topimax) is a novel agent approved for epilepsy. Several possible mechanisms of action have been identified: 1) state-dependent blockade of voltage-activated Na+ channels; 2) enhancement of GABA-ergic activity at a nonbenzodiazepine site on GABAA receptors; and 3) antagonism of kainate/c-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) type glutamate receptors. Shapira and associates discuss several lines of evidence that suggested topiramate’s efficacy for binge eating. First, it appeared to suppress appetite and eating in clinical trials for patients with epilepsy. Second, in animal studies, stimulation of the lateral hypothalamus by glutamate agonists (including kainate/ AMPA agonists) causes intense rapid dose-dependent increase in food intake. Third, some patients with bulimia have EEG abnormalities and had reduced binge eating in response to phenytoin.
Thirteen female outpatients with binge-eating disorder were treated with topiramate in an naturalistic, open-label fashion with a dose range of 100 to 1400 mg/d (mean = 492 mg/d), given in a b.i.d. or q.h.s. regimen, after starting with 25 mg/night and increased to 25-50 mg/w. Response and side effect assessment was done at monthly visits from three to 30 months (mean = 18.7). Response was categorized into quartiles labeled as none, mild, moderate, marked, or remission. Patient weight and BMI were recorded at baseline and follow-up visits. Patients ranged from 22 to 54 years of age; all had comorbid mood disorders (9 bipolar, 4 major depression), and took on an average of two other psychotropic medications. Nine patients displayed a moderate or better response to binge eating with the addition of topiramate. Mean weight decreased from 99.3 kg to 87.5 kg and mean BMI decreased from 36.5 to 32.2kg/m2. Overall, though, only seven patients lost more than 5 kg, one lost less than 5 kg, three had no change, and two gained weight. Topiramate was well tolerated, though sedation, cognitive dulling, and gastrointestinal upset were reported; three stopped because of side effects but were restarted with no further problems. No interactions were observed between topiramate and other psychotropic drugs (e.g., valproate, lithium, quetiapine, clozapine, bupropion, fluoxetine, paroxetine, trazodone, venlafaxine, clonazepam, or lorazepam). Limitations included: 1) the naturalistic design, which was nonrandomized, unblinded, and uncontrolled; 2) lack of standardized assessment; 3) the addition of topiramate to other psychotropics rather than monotherapy; 4) comorbid conditions; and 5) presence of other medications known to be associated with hyperphagia and/or weight gain.
COMMENT BY DONALD M. HILTY, MD
The relationship(s) between health, weight, metabolism, endocrine function, eating habits, eating disorders, mood disorders, other medical disorders, and treatments is a complex web to untangle. Eating behavior and weight are modulated many factors. This study lends hope that topiramate and other kainate/AMPA antagonists may be helpful for binge eating in patients with mood disorders. Controlled trials are needed in all of subsets of patients before any conclusions can be drawn. Use of topiramate for binge eating, for bipolar disorder, and for weight reduction as an adjunct to psychotropic medications that case significant weight gain (e.g., lithium) should be considered experimental and this should be conveyed to the patient in the consent process. Finally, topiramate has been reported to lower the level of estrogen in concomitant birth control pills, which is a special consideration in women of child-bearing age.
References
1. de Zwaan M, et al. Binge eating disorder: Clinical features and treatment of a new diagnosis. Harv Rev Psychiatry 1994;1:310-325.
2. Spitzer RL, et al. Binge eating disorder: A multisite field trial of the diagnostic criteria. Int J Eat Disord 1992;11:191-203.
3. Spitzer RL, et al. Binge eating disorder: Its further validation in a multisite study. Int J Eat Disord 1993;13: 137-153.
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