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Treatment of Acute Mania With Topiramate

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 -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.

Ms. A was a 36-year-old nurse with a 10-year history of bipolar disorder that resulted in at least 15 hospitalizations, predominantly for episodes of psychotic mania. She was admitted to our closed ward for acute mania that was characterized by a euphoric mood, logorrhea, psychomotor agitation, insomnia, and religious delusions. Previous treatment with carbamazepine was stopped because of inefficacy. Ms. A started treatment with a loading dose of valproate, 1800 mg/day, and haloperidol, 6 mg/day. Topiramate was added to this standard regimen in a dose of 25 mg on day 1 and 50 mg on day 2. Ms. A improved rapidly, as shown by a decrease in her Young Mania Rating Scale score from 41 on day 1 to 13 on day 15. Sedation and extrapyramidal dyskinesia were recorded as side effects. On day 15, her topiramate therapy was discontinued, whereas her valproate and haloperidol therapy was continued with an unchanged dose. Ms. A experienced a serious relapse of her manic symptoms that resulted in a Young Mania Rating Scale score of 33 on day 19. Her topiramate therapy was restarted on day 19. Her Young Mania Rating Scale score decreased to 20 on day 23 and 11 on day 30. Her haloperidol treatment was discontinued on day 35 without any further recurrence of her manic or psychotic symptoms. Her plasma levels of valproate were 41.6 mg/liter on day 1, 64.5 mg/liter on day 13, 66.6 mg/liter on day 18, and 60.0 mg/liter on day 25. Her haloperidol plasma levels were reported to be below 2 mg/liter on days 3 and 13.

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.

REFERENCES

1. Joffe R, Calabrese J (eds): Anticonvulsants in Mood Disorders. New York, Marcel Dekker, 1994
2. Calabrese J, Rapport D, Shelten M, Kimmel S: Clinical studies on the use of lamotrigine in bipolar disorder. Neuropsychobiology 1998; 38:185–191[Medline]
3. Erfurth A, Kammerer C, Grunze H, Normann C, Walden J: Efficacy of the new antiepileptic drug gabapentin in the treatment of acute mania. J Psychiatry Res 1998; 32:261–264[Medline]
4. Shank R, Gardocki J, Vaught J, Davis C, Schupsky J, Raffa R, Dogson S, Nortey S, Maryanoff B: Topiramate: preclinical evaluation of a structurally novel anticonvulsant. Epilepsia 1997; 38:450–460
5. Ben-Menachem E, Henriksen O, Mikkelsen M, Schmidt D, Reid S, Reife R, Kramer L, Pledger G, Karim R: Double-blind, placebo-controlled trial of topiramate as add-on therapy in patients with refractory partial seizures. Epilepsia 1996; 37:539–543[Medline]
6. Marcotte D: Use of topiramate, a new anti-epileptic, as a mood stabilizer. J Affect Disord 1998; 50:245–251[Medline]
7. Calabrese JR, Shelton MD III, Keck PE Jr, McElroy SL, Werkner JE: Topiramate in severe treatment-refractory mania, in Abstracts of the 151st Annual Meeting of the American Psychiatric Association. Washington, DC, APA, 1998, pp 121–122

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