LETTERS TO THE EDITORS
Treatment emergent affective switch with topiramate
Indução de mania associada ao tratamento com topiramato
Topiramate is a novel anticonvulsant that has been used for bipolar disorder. However, no clear evidence of efficacy was found in clinical trials. More recently, topiramate has been used for the management of weight gain associated with the use of mood stabilizer and atypical antipsychotics.
There are only two reported cases of treatment emergent affective switch (TEAS) to mania or hypomania associated with the use of topiramate.1-2 These patients were using topiramate for treatment of epilepsy and had no previous diagnosis of bipolar disorder. In this letter we report the emergence of manic symptoms within a period of one month after the introduction of topiramate in the pharmacological treatment of two euthymic patients previously diagnosed with bipolar disorder.
The medical records of all outpatients treated in our Bipolar Disorder Research Program from 1997 to 2004 were retrospectively analyzed. Out of a total of 123 outpatients, 34 received topiramate combined with mood stabilizers and/or atypical antipsychotics. For the diagnosis of topiramate-associated TEAS it was required the fulfillment of DSM-IV criteria for a manic or hypomanic episode and a Young Mania Rating Scale (YMRS) total score equal to or greater than 12.
Four patients (11.7%) presented TEAS but only two (5.8%) during the first month of treatment with topiramate, which represents a more rigorous criterion for TEAS.3
Case 1: A 56-year-old female was in remission for two months, on lithium carbonate 900 mg/day, carbamazepine 600 mg/day and olanzapine 20 mg/day. One week after introducing topiramate for weight loss, the patient presented insomnia, irritability, increased rate of speech and motor agitation, fulfilling criteria for a hypomanic episode. Her YMRS score changed from 1 (before topiramate introduction) to 14 points. Topiramate was discontinued and olanzapine was increased up to 25 mg/day, with remission of the episode after two weeks.
Case 2: A 40-year-old male was in remission for 12 months, on lithium carbonate 2100 mg/day. Topiramate was introduced for treatment of obesity. The patient lost 7 kg in the course of one month of treatment, but presented insomnia, racing thoughts, irritability, aggressiveness, talkativeness and motor excitement, fulfilling criteria for a manic episode. His YMRS score increased from 2 (before topiramate introduction) to 29 points. Topiramate was discontinued, and olanzapine plus clonazepam were introduced. The patient and his family decided to seek treatment in a different service and he was lost to follow-up.
Topiramate has been used mainly as an add-on drug in acute and prophylactic treatment of bipolar disorder, especially for weight loss. To our knowledge this is the first report of bipolar patients taking topiramate who presented TEAS. We detected a 5.8% incidence of TEAS in our sample, using a strict diagnosis criterion. Since topiramate has been widely used for weight loss, we think it is very important to study its safety and tolerability, specially the incidence of TEAS. Data from placebo controlled double-blind topiramate studies should be analyzed. Prospective trials may help to shed light in this issue.
Renata Sayuri Tamada, Jose Antonio de Mello Siqueira Amaral, Cilly Kluger Issler, Beny Lafer
Bipolar Disorder Research Program (PROMAN), Institute of Psychiatry, Universidade de São Paulo Medical School, São Paulo (SP), Brazil
1. Schlatter FJ, Soutullo CA, Cervera-Enguix S. First break of mania associated with topiramate treatment. J Clin Psychopharmacol. 2001;21(4):464-6.
2. Jochum T, Bar KJ, Sauer H. Topiramate induced manic episode. J Neurol Neurosurg Psychiatry. 2002;73(2):208-9.
3. Tamada RS, Issler CK, Amaral JA, Sachs GS, Lafer B. Treatment emergent affective switch: a controlled study. Bipolar Disord. 2004;6(4):333-7.
Conflict of interests: None
Publication in this collection
26 June 2006
Date of issue