Double-Blind Study of Dextroamphetamine Versus Caffeine Augmentation for Treatment-Resistant Obsessive-Compulsive Disorder

Introduction: Two small, double-blind, placebo-controlled, single-dose, crossover studies found dextroamphetamine (d-amphetamine) 30 mg clearly superior to placebo in relieving symptoms of obsessive-compulsive disorder (OCD). We conducted a 5-week, double-blind, caffeine-controlled study to test the hypothesis that d-amphetamine, added after an adequate selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) trial, would be more effective than caffeine in reducing residual OCD symptoms of moderate or greater severity.

Method: Between August 2006 and February 2008, we enrolled adults with DSM-IV OCD and a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of = 20 after = 12 weeks of adequate treatment with an SSRI or SNRI. Subjects were randomly assigned to double-blind d-amphetamine 30 mg/d or caffeine 300 mg/d added to their SSRI/SNRI and other medications. Responders (first week mean Y-BOCS score decrease of = 20%) entered the study’s 4-week double-blind extension phase.

Results: We enrolled 24 subjects, 11 women and 13 men, with a mean (SD) age of 40 (13.2) years and mean baseline Y-BOCS scores of 26.5 (4.1) for the d-amphetamine group (n = 12) and 29.1 (4.0) for the caffeine group (n = 12). At the end of week 1, six of 12 d-amphetamine subjects (50%) and 7 of 12 caffeine subjects (58%) were responders. At week 5, the responders’ mean Y-BOCS score decreases were, for the d-amphetamine group (last observation carried forward), 48% (range, 20%-80%); and, for the caffeine group, 55% (range, 27%-89%). Obsessive-compulsive disorder and depression improvement were independent. The double-blind remained intact. No subject discontinued the study due to side effects.

Conclusions: Larger, double-blind, placebo-controlled trials of both d-amphetamine and caffeine augmentation are needed in OCD subjects inadequately responsive to adequate doses of an SSRI or SNRI.

Trial Registration: clinicaltrials.gov Identifier: NCT00363298

Submitted: August 7, 2008; accepted October 9, 2008.

Online ahead of print: June 30, 2009.

Corresponding author: Lorrin M. Koran, MD, OCD Clinic, Room 2363, 401 Quarry Road, Stanford, CA 94305 (lkoran@stanford.edu).