Mirtazapine for Obsessive-Compulsive Disorder: An Open Trial Followed by Double-Blind Discontinuation

Lorrin M. Koran, M.D.; Nona N. Gamel, M.S.W.; Helen W. Choung, M.S.; Emily H. Smith, M.S.W.; and Elias N. Aboujaoude, M.D.

Background: Many patients with obsessive-compulsive disorder (OCD) experience little response to standard treatment with serotonin reuptake inhibitors. Mirtazapine enhances serotonergic function by a mechanism distinct from reuptake inhibition. Because a pilot study suggested effectiveness of mirtazapine in OCD, we conducted a controlled trial.

Method: We recruited 30 subjects, 15 treatment-naive and 15 treatment-experienced, with DSM-IV OCD of > = 1 year's duration and a Yale-Brown Obsessive Compulsive Scale (YBOCS) score of > = 20. In the 12-week, open-label phase, subjects received mirtazapine starting at 30 mg/day and titrated over 2 weeks as tolerated to 60 mg/day. At week 12, responders (YBOCS score decrease > 25%) were randomly assigned, double-blind, to continue mirtazapine or switch to placebo for 8 weeks, including a 1-week, double-blind taper week for placebo subjects.

Results: In the open-label phase, the mean ± SD YBOCS score fell from 28.3 ± 3.7 to 20.3 ± 8.5 (paired samples t = 4.81, p < .0001). Four subjects (13.3%) discontinued for side effects. Sixteen subjects (53.3%) (8 treatment-naive, 8 treatment-experienced) were responders and 15 agreed to randomization. Response was independent of comorbid mood disorders. In the 8-week, double-blind, placebo-controlled discontinuation phase, the mirtazapine group's mean YBOCS score fell a mean ± SD of 2.6 ± 8.7 points while the placebo group's mean score rose a mean ± SD of 9.1 ± 7.5 points (Mann Whitney U = 6.5, p = .005, 1-tailed). All other outcome measures were consistent with mirtazapine's superiority versus placebo.

Conclusion: Mirtazapine may be an effective pharmacotherapy for OCD. If our results are replicated, larger double-blind studies would be indicated.

(J Clin Psychiatry 2005;66:515-520)

Received April 13, 2004; accepted Sept. 7, 2004. From the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif.

Supported by an educational grant from Organon, Inc., which also provided active medication and matched placebo pills.

Dr. Koran has received grant/research support from Forest and Pfizer and serves on the speakers/advisory board of Forest. Dr. Aboujaoude has received honoraria from and is on the speakers/advisory board of Forest.

Sue Thiemann, M.S., aided in the statistical analyses.

Corresponding author and reprints: Lorrin M. Koran, M.D., OCD Clinic, 401 Quarry Rd., Room 2363, Stanford, CA 94305 (e-mail: lkoran@stanford.edu).