Levetiracetam as Adjunctive Therapy for Refractory Anxiety Disorders

Gustavo Kinrys, M.D.; John J. Worthington, M.D.; Lisa Wygant, B.A.; Fernanda Nery, B.A.; Hannah Reese, B.A.; and Mark H. Pollack, M.D.

Background: Anxiety disorders are the most prevalent psychiatric disorders as a group, and despite the effectiveness of currently available treatments for anxiety, many patients (40%-65%) remain symptomatic after initial intervention. Thus, there is a significant need for efficacious pharmacologic agents that are safe and well tolerated and lead patients to remission of symptoms. We present a retrospective analysis that assessed the efficacy and tolerability of adjunctive levetiracetam, a novel anticonvulsant agent, in the treatment of refractory anxiety.

Method: Forty patients with DSM-IV anxiety disorders, who were deemed partial responders or nonresponders to anxiolytic therapy, received adjunctive levetiracetam in a naturalistic fashion during the time period from January 2004 through December 2004. We conducted a retrospective chart review. The primary outcome measures were the Clinical Global Impressions-Severity of Illness (CGI-S) scale and the Clinical Global Impressions-Improvement (CGI-I) scale. Mean change from baseline to endpoint was assessed using 2-tailed paired t tests.

Results: Levetiracetam at a mean ± SD dose of 1969 ± 819 mg/day for a mean ± SD time period of 9.3 ± 5.1 weeks was generally well tolerated. Patients were markedly ill with a mean ± SD baseline CGI-S score of 6.2 ± 0.6. Patients improved significantly, with an endpoint CGI-S score of 4.2 ± 1.8 (p < .001) and CGI-I score of 2.6 ± 1.2. Adverse events were generally mild, and only 4 patients discontinued levetiracetam because of side effects.

Conclusion: These preliminary data suggest that levetiracetam may be an effective adjunctive treatment for patients with anxiety disorders who remain symptomatic despite initial anxiolytic therapy.

(J Clin Psychiatry 2007;68:1010-1013)

Received Aug. 17, 2006; accepted Dec. 13, 2006. From the Anxiety Disorders Research Program, Cambridge Health Alliance, Cambridge (Dr. Kinrys and Mss. Wygant and Nery); the Center for Anxiety and Traumatic Stress Disorders, Massachusetts General Hospital, Boston (Drs. Worthington and Pollack and Ms. Reese); and the Department of Psychiatry, Harvard Medical School, Boston (Drs. Kinrys, Worthington, and Pollack and Mss. Wygant and Nery), Mass.

Supported in part by an unrestricted educational grant from UCB Pharma, Smyrna, Ga.

Presented at the XXIVth Collegium Internationale Neuro-Psychopharmacologicum Congress; June 20-24, 2004; Paris, France.

Financial disclosure is listed at the end of the article.

Corresponding author and reprints: Gustavo Kinrys, M.D., Cambridge Health Alliance/Harvard Medical School, Department of Psychiatry, 1493 Cambridge St., Cambridge, MA 02139 (e-mail: gkinrys@challiance.org).