We're unable to sign you in at this time. Please try again in a few minutes.
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Investigation |

Cognitive-Behavioral Therapy vs Risperidone for Augmenting Serotonin Reuptake Inhibitors in Obsessive-Compulsive Disorder:  A Randomized Clinical Trial

Helen Blair Simpson, MD, PhD1,2; Edna B. Foa, PhD3; Michael R. Liebowitz, MD1; Jonathan D. Huppert, PhD3,4; Shawn Cahill, PhD3,5; Michael J. Maher, PhD2; Carmen P. McLean, PhD3; James Bender Jr, PsyD2; Sue M. Marcus, PhD1,2; Monnica T. Williams, PhD3,6; Jamie Weaver, MPH2; Donna Vermes, PMHNP2; Page E. Van Meter, PhD2; Carolyn I. Rodriguez, MD, PhD1; Mark Powers, PhD3; Anthony Pinto, PhD2; Patricia Imms, RN3; Chang-Gyu Hahn, MD, PhD3; Raphael Campeas, MD2
[+] Author Affiliations
1Department of Psychiatry, Columbia University, New York, New York
2New York State Psychiatric Institute, New York, New York
3Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania
4Department of Psychology, The Hebrew University of Jerusalem, Mount Scopus, Jerusalem
5Department of Psychology, University of Wisconsin–Milwaukee, Milwaukee, Wisconsin
6Department of Psychological and Brain Sciences, University of Louisville, Louisville, Kentucky
JAMA Psychiatry. 2013;70(11):1190-1199. doi:10.1001/jamapsychiatry.2013.1932.
Text Size: A A A
Published online

Importance  Obsessive-compulsive disorder (OCD) is one of the world’s most disabling illnesses according to the World Health Organization. Serotonin reuptake inhibitors (SRIs) are the only medications approved by the Food and Drug Administration to treat OCD, but few patients achieve minimal symptoms from an SRI alone. In such cases, practice guidelines recommend adding antipsychotics or cognitive-behavioral therapy consisting of exposure and ritual prevention (EX/RP).

Objective  To compare the effects of these 2 SRI augmentation strategies vs pill placebo for the first time, to our knowledge, in adults with OCD.

Design, Setting, and Participants  A randomized clinical trial (conducted January 2007-August 2012) at 2 academic outpatient research clinics that specialize in OCD and anxiety disorders. Patients (aged 18-70 years) were eligible if they had OCD of at least moderate severity despite a therapeutic SRI dose for at least 12 weeks prior to entry. Of 163 who were eligible, 100 were randomized (risperidone, n = 40; EX/RP, n = 40; and placebo, n = 20), and 86 completed the trial.

Interventions  While continuing their SRI at the same dose, patients were randomized to the addition of 8 weeks of risperidone (up to 4 mg/d), EX/RP (17 sessions delivered twice weekly), or pill placebo. Independent assessments were conducted every 4 weeks.

Main Outcome and Measure  The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) to measure OCD severity.

Results  Patients randomized to EX/RP had significantly greater reduction in week 8 Y-BOCS scores based on mixed-effects models (vs risperidone: mean [SE], −9.72 [1.38]; P < .001 vs placebo: mean [SE], −10.10 [1.68]; P < .001). Patients receiving risperidone did not significantly differ from those receiving placebo (mean [SE], −0.38 [1.72]; P = .83). More patients receiving EX/RP responded (Y-BOCS score decrease ≥25%: 80% for EX/RP, 23% for risperidone, and 15% for placebo; P < .001). More patients receiving EX/RP achieved minimal symptoms (Y-BOCS score ≤12: 43% for EX/RP, 13% for risperidone, and 5% for placebo; P = .001). Adding EX/RP was also superior to risperidone and placebo in improving insight, functioning, and quality of life.

Conclusions and Relevance  Adding EX/RP to SRIs was superior to both risperidone and pill placebo. Patients with OCD receiving SRIs who continue to have clinically significant symptoms should be offered EX/RP before antipsychotics given its superior efficacy and less negative adverse effect profile.

Trial Registration  clinicaltrials.gov Identifier: NCT00389493.

Figures in this Article

Sign in

Create a free personal account to sign up for alerts, share articles, and more.

Purchase Options

• Buy this article
• Subscribe to the journal


Place holder to copy figure label and caption
Figure 1.
Consolidated Standards of Reporting Trials Diagram

Flow of patients through the study. CBT indicates cognitive-behavioral therapy; EX/RP, cognitive-behavioral therapy consisting of exposure and ritual prevention; OCD, obsessive-compulsive disorder; SRI, serotonin reuptake inhibitor; and Y-BOCS, Yale-Brown Obsessive Compulsive Scale.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
Change in Symptom Severity During Augmentation

Mixed-effects linear regression was used to model change in severity of obsessive-compulsive disorder (OCD) as measured by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) in 100 adults who were receiving a stable dose of a serotonin reuptake inhibitor and who were randomized to the addition of 8 weeks of risperidone (n = 40), exposure and ritual prevention (EX/RP) therapy (n = 40), or pill placebo (n = 20). Patients randomized to EX/RP had significantly greater reduction in Y-BOCS scores at week 8 than those randomized to risperidone or placebo (see text for details). The x-axis is weeks of augmentation. The y-axis is OCD severity as measured by the Y-BOCS. A score of 16 (arrow) or higher is considered clinically meaningful OCD symptoms warranting treatment.

Graphic Jump Location




Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment


Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 11

Sign in

Create a free personal account to sign up for alerts, share articles, and more.

Purchase Options

• Buy this article
• Subscribe to the journal

Related Content

Customize your page view by dragging & repositioning the boxes below.

See Also...
Articles Related By Topic
Related Collections
PubMed Articles

Users' Guides to the Medical Literature
Clinical Resolution

Users' Guides to the Medical Literature
Using the Guide—Part 7