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.