Cognitive-Behavioral Therapy vs Risperidone for Augmenting Serotonin Reuptake Inhibitors in Obsessive-Compulsive Disorder: A Randomized Clinical Trial
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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.
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Evidence indicates that dopamine antagonism can also exacerbate symptoms or fail to produce a clinical benefit in OCD.
“evidence that dopamine antagonism can also exacerbate symptoms or fail to produce a clinical benefit (Denys et al., 2004a; Klanker et al., 2013; Simpson et al., 2013)”
From A framework for understanding the emerging role of corticolimbic-ventral striatal networks in OCD-associated repetitive behaviors (2015) · cites this paper as Simpson et al., 2013
Extinguishing negative conditioned associations via exposure to symptom provoking stimuli has proven efficacious in OCD patients.
“extinguishing negative conditioned associations via exposure to symptom provoking stimuli has proven efficacious in OCD patients (Foa et al., 2005; Franklin and Foa, 2011; Simpson et al., 2013; Lewin et al., 2014; Ludvik et al., 2015)”
From A framework for understanding the emerging role of corticolimbic-ventral striatal networks in OCD-associated repetitive behaviors (2015) · cites this paper as Simpson et al., 2013
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- Authors
- Simpson, H. B., Foa, E. B., Liebowitz, M. R., Huppert, J. D., Cahill, S., Maher, M. J., McLean, C. P., Bender, J., Marcus, S. M., Williams, M. T., Weaver, J., Vermes, D., Van Meter, P. E., Rodriguez, C. I., Powers, M., Pinto, A., Imms, P., Hahn, C.-G., & Campeas, R.
- Affiliations
- New York State Psychiatric Institute (US)
- University of Pennsylvania (US)
- Columbia University (US)
- Hebrew University of Jerusalem (IL)
- University of Wisconsin–Milwaukee (US)
- University of Louisville (US)
- Corresponding author
- Simpson, Helen Blair
- ORCID
- Venue
- JAMA Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2013-11-01
- Volume
- 70
- Issue
- 11
- Pages
- 1190
- ISSN
- 2168-622X (ISSN-L)
- PMC
- PMC3955365
- OpenAlex
- W2167904835
- Cited by
- 248
- References
- 44
- Citations by year
- 2026: 10 · 2025: 16 · 2024: 15 · 2023: 19 · 2022: 19 · 2021: 14 · 2020: 17 · 2019: 21 · 2018: 22 · 2017: 22 · 2016: 26 · 2015: 22 · 2014: 19 · 2013: 5 · 2012: 1
- FWCI
- 26.70
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- JAMA Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (K24MH091555, R10MH045404, R01MH045404, R01MH-45404, K23MH092434, R01MH045436)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Social Sciences › Psychology › Clinical Psychology › Psychoanalysis and Psychopathology Research
- Keywords
- obsessive-compulsive disorder, serotonin reuptake inhibitors, risperidone, cognitive behavioral therapy, exposure and response prevention, augmentation therapy, antipsychotic augmentation, placebo comparison, Yale-Brown Obsessive Compulsive Scale, treatment response, treatment-resistant OCD, relapse prevention
- MeSH terms
- Adolescent, Adult, Aged, Combined Modality Therapy, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Obsessive-Compulsive Disorder, Antipsychotic Agents, Cognitive Behavioral Therapy, Single-Blind Method, Selective Serotonin Reuptake Inhibitors, Risperidone
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