To the Editor: Several antiepileptic agents have been found to be effective in the treatment of mania and the prophylaxis of affective episodes in bipolar disorder (1). Whereas carbamazepine and valproate have been widely used in those patients, several studies support a role for the newer antiepileptic drugs, such as lamotrigine (2) and gabapentin (3).

Topiramate is a chemically novel antiepileptic drug that is available in a number of countries for the treatment of partial seizures. Although the mechanism of action of this substance is not yet fully understood, preclinical evidence suggests that it interferes with sodium conductance, augments the effect of γ-aminobutyric acid, blocks glutamate receptors, and has weak carbonic anhydrase inhibiting properties (4). Topiramate has a favorable pharmacokinetic profile and is generally well tolerated in patients with epilepsy (5). Psychotropic side effects (such as abnormal thinking) can usually be controlled by slow escalation of the dose. Unlike most other psychopharmacological drugs, the substance is associated with substantial weight loss. Here we report the efficacy of topiramate in a patient with acute mania by using an on-off-on study design.

This case report suggests the antimanic properties of topiramate. Whereas this patient’s initial improvement could have been caused by combination therapy and thus cannot unequivocally be attributed to topiramate alone, the interruption of topiramate administration clearly provoked a severe and reversible manic relapse. The reinstitution of topiramate, however, again led to rapid improvement. The drug has been effective in a lower dose than is used for the treatment of epilepsy (target dose=200 to 400 mg/day) and was well tolerated. Valproate and haloperidol plasma levels remained unchanged after the addition of topiramate.

Although preliminary results on the use of topiramate therapy in treating bipolar disorder have been presented (6, 7), further double-blind studies to elucidate the antimanic and mood stabilizing effects of topiramate are warranted.