Mood Stabilization and Weight Loss With Topiramate
To the Editor: The anticonvulsants valproate and carbamazepine have gained increasing popularity in the treatment of bipolar disorder and other conditions involving affect or impulse dysregulation. As with lithium, however, a major adverse effect of these drugs is weight gain. While the newer anticonvulsants lamotrigine and gabapentin have generated interest as possible mood stabilizers, their potential for causing weight gain is unclear. In contrast, the novel anticonvulsant topiramate (1) a monosaccharide derivative, has the unique adverse effect of weight loss. To our knowledge, the thymoleptic efficacy of this drug has not been described. We report our initial experience with topiramate in two patients with mood disorders for whom weight gain had been a major problem.
Mr. A was a 37-year-old man with a 10-year history of rapid-cycling bipolar disorder, including two episodes of manic psychosis and at least five episodes of severe melancholia. For 10 months, he had presented with primarily depressive features, including hopelessness and psychomotor slowing, although with continuing grandiosity. His condition was complicated by obesity, with a weight of 245 lb. He was on a maintenance dose of valproate, 2500 mg/day; bupropion, 300 mg/day; and olanzapine, 10 mg/day. A 4-month trial of levothyroxine, 0.1 mg/day, yielded no weight change. Valproate was discontinued, and a dose of topiramate was titrated to 200 mg/day. In the next 3 months, Mr. A lost 25 lb. He initially reported no change in food consumption but subsequently described a greater motivation to exercise. His mood remained stable, with improved depressive symptoms and no emergence of anxiety.
Ms. B was a 33-year-old woman with a long history of recurrent major depression complicated by marked mood lability and impulsivity. She was also obese, with a weight of 226 lb. She was demoralized by failed attempts to lose weight, despite dieting and exercise. Her mood had stabilized after many psychotropic trials on a regimen of valproate, 2000 mg/day, and bupropion, 450 mg/day. She requested appetite suppressants, but a past history of substance abuse contraindicated stimulants. She was given a dose of levothyroxine, 0.1 mg/day, with no effect. One month later, her dose of valproate was discontinued and a dose of topiramate was titrated to 300 mg/day. Within 2 months, she lost 15 lb. However, she became increasingly irritable, depressed, and anxious. Topiramate was discontinued and replaced with a regimen of gabapentin, 1500 mg/day; fluoxetine, 40 mg/day; and clonazepam, 2 mg/day. Her anxiety and irritability were markedly reduced, but she regained 8 lb. within 2 weeks.
In these patients, the substitution of topiramate for valproate resulted in significant weight loss. Mr. A, with bipolar disorder, experienced no loss of thymoleptic efficacy; Ms. B, with unipolar depression and impulsivity, experienced increasing depression and anxiety. Anxiety has been reported as an adverse effect of topiramate (1). Like other thymoleptic anticonvulsants, topiramate has significant effects on γ-aminobytyric acid function (2)), but the mechanism of its effects on weight is unknown. Further study should clarify topiramate’s utility in treating mood disorders.
1. Langtry HD, Gillis JC, Davis R: Topiramate: a review of its pharmacodynamic and pharmacokinetic properties and clinical efficacy in the management of epilepsy. Drugs 1997; 54:752–773Crossref, Medline, Google Scholar
2. Meldrum BS: Update on the mechanism of action of antiepileptic drugs. Epilepsia 1996; 37:S4–S11Google Scholar
