An Open-Label Trial of Risperidone Augmentation for Refractory Anxiety Disorders

Naomi M. Simon, M.D., M.Sc.; Elizabeth A. Hoge, M.D.; Diana Fischmann, B.A.; John J. Worthington III, M.D.; Kelly M. Christian, B.S.; Gustavo Kinrys, M.D.; and Mark H. Pollack, M.D.

Background: There is a paucity of data to support "next-step" treatments for the many patients with anxiety disorders who remain symptomatic after initial pharmacotherapy.

Method: Thirty patients with a primary diagnosis of an anxiety disorder-panic disorder (PD), social anxiety disorder (SAD), or generalized anxiety disorder (GAD)-refractory to initial pharmacotherapy with an adequate (or maximally tolerated) antidepressant and/or benzodiazepine trial of at least 8 weeks' duration prior to study initiation received open-label augmentation with flexibly dosed risperidone for 8 weeks. Participants were diagnosed using the Structured Clinical Interview for DSM-IV.

Results: Risperidone augmentation at a mean ± SD dose of 1.12 ± 0.68 mg/day (range, 0.25-3.00 mg/day) resulted in a significant reduction in anxiety symptoms across disorders as measured by the Clinical Global Impressions-Severity of Illness scale and Hamilton Rating Scale for Anxiety (HAM-A) scores and for each disorder-specific primary outcome measure-the Panic Disorder Severity Scale, the Liebowitz Social Anxiety Scale, and HAM-A-in the intent-to-treat sample. Seventy percent (21/30) of participants completed the 8-week trial, with premature discontinuation due primarily to sedation and weight gain.

Conclusions: Although conclusions are limited by the open-label, relatively brief nature of this trial, our data suggest that augmentation with low-dose risperidone may be a useful option for patients with PD, SAD, or GAD refractory to adequate initial intervention with antidepressants and/or benzodiazepines. Longer-term, controlled safety and efficacy data are needed to understand the place of risperidone augmentation in the algorithm of treatment options for refractory anxiety disorders.

(J Clin Psychiatry 2006;67:381-385)

Received April 27, 2005; accepted July 24, 2005. From the Center for Anxiety and Traumatic Stress Disorders (Drs. Simon, Hoge, Worthington, and Pollack and Mss. Fischmann and Christian), Massachusetts General Hospital; the Department of Psychiatry, Harvard Medical School (Drs. Simon, Hoge, Worthington, Kinrys, and Pollack and Mss. Fischmann and Christian), Boston, Mass.; and the Anxiety Disorders Research Program, Cambridge Health Alliance (Dr. Kinrys), Cambridge, Mass.

Work on this study was supported by an investigator-initiated study grant from Janssen, L.P., Titusville, N.J.

Financial disclosure appears at the end of the article.

Corresponding author and reprints: Naomi M. Simon, M.D., M.Sc., Simches Research Building, 2nd Floor, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114 (e-mail: nsimon@partners.org).