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Topiramate May Have Role in Treatment-Resistant Obsessive-Compulsive Disorder: Presented at CINP

By Jill Stein

PARIS, FRANCE -- June 23, 2004 -- Results of a small pilot study suggest that adjunctive use of topiramate may benefit patients with obsessive-compulsive disorder (OCD) that is resistant to treatment with a serotonin reuptake inhibitor (SRI).

The new data on topiramate, an anticonvulsant agent that is thought to have glutamatergic properties, were reported here on June 23rd at the XXIV Collegium Internationale Neuro-psychopharmacologicum Congress.

Michael Van Ameringen, MD, Associate Professor, Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Canada, presented results on 16 patients in whom topiramate was gradually added in titrated dose increments to a maximum of 400 mg/day over a period of 14 to 26 weeks.

All patients were enrolled from a university-affiliated outpatient anxiety disorders clinic and were diagnosed with OCD using criteria set out in the Diagnostic and Statistical Manual of Mental Disorders – Revision IV. All had partial or nonresponse to SRI monotherapy or combination therapy.

"Serotonin reuptake inhibitors (SRIs) are considered first-line treatment for OCD, with response rates ranging from 42% to 53%," Dr. Van Ameringen, pointed out. "While most patients achieve some response, many remain symptomatic despite an adequate SRI trial."

Little practical advice is available for clinicians on next-step treatment strategies for patients who have not responded to two or more trials of SRIs, he added.

In the present trial, topiramate was selected for evaluation because of recent imaging data that showed an association between decreased caudate glutamatergic concentrations and a reduction in OCD symptoms as well as topiramate's inhibitory effects on glutamate.

The sample consisted of a consecutive series of treatment-resistant OCD patients. In the trial, subjects were seen approximately every 4 weeks for the first 16 weeks or until they achieved a treatment response.

Patients were permitted to continue taking concurrent benzodiazepines, antipsychotics, sedative hypnotics, or antidepressant medications, provided that they had been on a stable dose of these medications for at least 8 weeks prior to entering the study. They also had to agree not to change the dose of the concurrent medication over the course of the study.

All patients completed at least 14 of 26 weeks of topiramate augmentation treatment.

The rate of nonresponse to treatment was 68.8%. Seven patients had a Clinical Global Impression of Improvement score of 2 (much improved), and four had a score of 1 (very much improved).

The mean dose of topiramate was 253.1 mg/day, and the mean time to response was 9.2 weeks. Clinical Global Impression of Improvement and of Severity scores decreased significantly from baseline to end point, from 6.1 to 4.5 (P <.001).

The findings suggest that topiramate augmentation may be an effective strategy for treatment-resistant OCD, Dr. Van Ameringen said. He also called for a placebo-controlled augmentation trial that would include a larger population of patients who are refractory to SRI treatment.

The study was supported by funding from Janssen-Ortho Inc.


[Presentation title: "Topiramate Augmentation in a Case Series of Treatment Resistant Obsessive Compulsive Disorder." Abstract #P02.242]

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