Is there any documentation for the use of topiramate as an antidepressive agent?/nThe question rela

Fråga: Is there any documentation for the use of topiramate as an antidepressive agent?

The question relates to a depressed patient who is treated with mianserin and sertraline due to depression. Due to weight gain the treating psychiatrist is considering replacing this medication with topiramate as an antidepressant.

Sammanfattning: In our search we found one randomized controlled trial, studying the effect of topiramate in mild to moderate depression. In this study the primary objective was poorly described and the included patients only suffered from mild depression. A statistically significant, but clinically insignificant decrease in depression score was seen. The use of topiramate as an antidepressant in the treatment of depression has not been demonstrated to be effective or safe.

Svar: Topiramate is a recently developed anticonvulsant drug for which the mechanism of action is not fully understood. In Sweden topiramate is approved for treating epilepsy and as a second line alternative for prophylactic treatment of migraine.

In an extensive search in literature and databases for studies of the antidepressive effect of topiramate, one randomized controlled trial was found (1). Additionally, a retrospective chart review dealing with the same subject was found (2).

In the randomized controlled trial, 64 moderately depressed (assessed by Hamilton depression rating scale) female outpatients were included (1). The women included were selected through telephone interviews after they had responded to advertisement for the study. 32 patients were randomized to placebo and 32 to topiramate monotherapy. The main objective was not clearly defined, but it seems as if the main objective was to study the effect of topiramate as a mood stabilizer with special emphasis on anger symptoms. An intention to treat design was used and there were two dropouts in the topiramate group and three in the placebo group during the 10-week study. A statistically significant decrease in total Hamilton depression rating scale score from 23.1 to 19.2 was seen in the group treated with topiramate, and this change was not seen in the placebo group. However, this should be considered a clinically insignificant change, as the decrease in score was so small. Normally a decrease in total Hamilton depression rating scale score of more than 50-60% is considered a clinically significant change in studies of depression. Additionally the use of Hamilton depression rating scale as a valid rating scale in depression has recently been questioned (3).

In conclusion this study used a small sample size; only studied moderately depressive female outpatients; had a short duration; and were only able to demonstrate a small change in depression rating score, which must be considered clinically insignificant.

From the retrospective chart review no conclusions regarding the efficacy of topiramate in depression can be drawn due to design of the study (2). Nickel C, Lahman C, Tritt K, Muehlbacher M, Kaplan P, Kettler C, et al. Topiramate in treatment of depressive and anger symptoms in female depressive patients: A randomized, double-blind, placebo-controlled study. J Affect Disord 2005;87:243-52. Carpenter LL, Leon Z, Yasmin S, Price LH. Do obese depressed patients respond to topiramate? a retrospective chart review. J Affect Disord 2002;69:251-5. Bagby RM, Ryder AG, Schuller DR, Marshall MB. The Hamilton depression rating scale: Has the gold standard become a lead weight? Am J Psychiatry 2004;161:2163-77.