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Moderators and predictors of response to cognitive-behavioral therapy augmentation of pharmacotherapy in obsessive–compulsive disorder

  • M. J. Maher (a1), J. D. Huppert (a2) (a3), H. Chen (a1) (a4), N. Duan (a1) (a4), E. B. Foa (a2), M. R. Liebowitz (a1) (a4) and H. B. Simpson (a1) (a4)...

Cognitive-behavioral therapy (CBT) consisting of exposure and response prevention (EX/RP) is efficacious as a treatment for obsessive–compulsive disorder (OCD). However, about half of patients have a partial or poor response to EX/RP treatment. This study examined potential predictors and moderators of CBT augmentation of pharmacotherapy, to identify variables associated with a poorer response to OCD treatment.


Data were drawn from a large randomized controlled trial that compared the augmenting effects of EX/RP to stress management training (SMT; an active CBT control) among 108 participants receiving a therapeutic dose of a serotonin reuptake inhibitor (SRI). Stepwise regression was used to determine the model specification.


Pretreatment OCD severity and gender were significant moderators of outcome: severity affected SMT (but not EX/RP) outcome; and gender affected EX/RP (but not SMT) outcome. Adjusting for treatment type and pretreatment severity, significant predictors included greater co-morbidity, number of past SRI trials, and lower quality of life (QoL). Significant moderators, including their main-effects, and predictors accounted for 37.2% of the total variance in outcome, comparable to the impact of treatment type alone (R2=30.5%). These findings were replicated in the subgroup analysis of EX/RP alone (R2=55.2%).


This is the first randomized controlled study to examine moderators and predictors of CBT augmentation of SRI pharmacotherapy. Although effect sizes for individual predictors tended to be small, their combined effect was comparable to that of treatment. Thus, future research should examine whether monitoring for a combination of these risk factors and targeting them with multi-modular strategies can improve EX/RP outcome.

Corresponding author
*Address for correspondence: H. B. Simpson, M.D., Ph.D., Associate Professor of Clinical Psychiatry, Columbia University, 1051 Riverside Drive, Unit 69, New York, NY 10032, USA. (Email:
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Abramowitz J, Foa E (2000). Does comorbid major depressive disorder influence outcome of exposure and response prevention for OCD? Behavior Therapy 31, 795800.
Abramowitz JS, Franklin ME, Schwartz SA, Furr JM (2003). Symptom presentation and outcome of cognitive-behavioral therapy for obsessive-compulsive disorder. Journal of Consulting and Clinical Psychology 71, 10491057.
AuBuchon PG, Malatesta VJ (1994). Obsessive compulsive patients with comorbid personality disorder: associated problems and response to a comprehensive behavior therapy. Journal of Clinical Psychiatry 55, 448453.
Baxter LR Jr., Schwartz JM, Bergman KS, Szuba MP, Guze BH, Mazziotta JC, Alazraki A, Selin CE, Ferng HK, Munford P, Phelps ME (1992). Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder. Archives of General Psychiatry 49, 681689.
Black DW, Monahan P, Gable J, Blum N, Clancy G, Baker P (1998). Hoarding and treatment response in 38 nondepressed subjects with obsessive-compulsive disorder. Journal of Clinical Psychiatry 59, 420425.
Blanco C, Olfson M, Stein DJ, Simpson HB, Gameroff MJ, Narrow WH (2006). Treatment of obsessive-compulsive disorder by U.S. psychiatrists. Journal of Clinical Psychiatry 67, 946951.
Buchanan AW, Meng KS, Marks IM (1996). What predicts improvement and compliance during the behavioral treatment of obsessive compulsive disorder? Anxiety 2, 2227.
Burnham KP, Anderson DR (2002). Model Selection and Multimodel Inference: A Practical-Theoretic Approach. Springer-Verlag: New York.
Cottraux J, Note I, Yao SN, Lafont S, Note B, Mollard E, Bouvard M, Sauteraud A, Bourgeois M, Dartigues J-F (2001). A randomized controlled trial of cognitive therapy versus intensive behavior therapy in obsessive compulsive disorder. Psychotherapy and Psychosomatics 70, 288297.
de Haan E, van Oppen P, van Balkom AJ, Spinhoven P, Hoogduin KA, Van Dyck R (1997). Prediction of outcome and early vs. late improvement in OCD patients treated with cognitive behaviour therapy and pharmacotherapy. Acta Psychiatrica Scandinavica 96, 354361.
Denys D, Burger H, van Megen H, de Geus F, Westenberg H (2003). A score for predicting response to pharmacotherapy in obsessive-compulsive disorder. International Clinical Psychopharmacology 18, 315322.
Endicott J, Nee J, Harrison W, Blumenthal R (1993). Quality of Life Enjoyment and Satisfaction Questionnaire: a new measure. Psychopharmacology Bulletin 29, 321326.
First MB, Gibbon M, Spitzer R, Williams J, Benjamin L (1997). Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II). American Psychiatric Press, Inc.: Washington, DC.
First MB, Spitzer RL, Gibbon M, Williams JB (1996). Structured Clinical Interview for DSM-IV Axis I Disorders, Patient Edition (SCID-P), version 2. Biometrics Research Department, New York State Psychiatric Institute: New York, NY.
Foa E, Abramowitz J, Franklin M, Kozak MJ (1999). Feared consequences, fixity of belief, and treatment outcome in patients with obsessive-compulsive disorder. Behavior Therapy 30, 717724.
Foa EB, Grayson JB, Steketee GS, Doppelt HG, Turner RM, Latimer PR (1983 a). Success and failure in the behavioral treatment of obsessive-compulsives. Journal of Consulting and Clinical Psychology 51, 287297.
Foa EB, Liebowitz MR, Kozak MJ, Davies S, Campeas R, Franklin ME, Huppert JD, Kjernisted K, Rowan V, Schmidt AB, Simpson HB, Tu X (2005). Randomized, placebo-controlled trial of exposure and ritual prevention, clomipramine, and their combination in the treatment of obsessive-compulsive disorder. American Journal of Psychiatry 162, 151161.
Foa EB, Steketee G, Grayson JB, Doppelt HG (1983 b). Treatment of obsessive-compulsives: when do we fail? In Failures in Behavior Therapy (ed. Foa E. B. and Emmelkamp P. M. G.), pp. 1034. John Wiley and Sons: New York.
Gershuny BS, Baer L, Jenike MA, Minichiello WE, Wilhelm S (2002). Comorbid posttraumatic stress disorder: impact on treatment outcome for obsessive-compulsive disorder. American Journal of Psychiatry 159, 852854.
Goodman WK, Price LH, Rasmussen SA, Mazure C, Fleischmann RL, Hill CL, Heninger GR, Charney DS (1989). The Yale–Brown Obsessive Compulsive Scale. I. Development, use, and reliability. Archives of General Psychiatry 46, 10061011.
Hamilton M (1959). The assessment of anxiety states by rating. British Journal of Medical Psychology 32, 5055.
Hamilton M (1960). A Rating Scale for Depression. Journal of Neurology, Neurosurgery, and Psychiatry 23, 5662.
Hohagen F, Winkelmann G, Rasche-Raeuchle H, Hand I, Koenig A, Muenchau N, Hiss H, Geiger-Kabisch C, Kaeppler C, Schramm P, Rey E, Aldenhoff J, Berger M (1998). Combination of behaviour therapy with fluvoxamine in comparison with behaviour therapy and placebo: results of a multicentre study. British Journal of Psychiatry 173, 7178.
Hoogduin CA, Duivenvoorden HJ (1988). A decision model in the treatment of obsessive-compulsive neuroses. British Journal of Psychiatry 152, 516521.
Huppert JD, Simpson HB, Nissenson K, Liebowitz M, Foa EB (2009). Quality of life and functional impairment in obsessive-compulsive disorder: a comparison of patients with and without comorbidity, patients in remission, and healthy controls. Depression and Anxiety 26, 3945.
Jacobson D, Wu A, Feinberg J (2003). Health-related quality of life predicts survival, cytomegalovirus disease, and study retention in clinical trial participants with advanced HIV disease. Journal of Clinical Epidemiology 56, 874879.
Keijsers GP, Hoogduin CA, Schaap CP (1994). Predictors of treatment outcome in the behavioural treatment of obsessive-compulsive disorder. British Journal of Psychiatry 165, 781786.
Lelliott PT, Noshirvani HF, Basoglu M, Marks IM, Monteiro WO (1988). Obsessive-compulsive beliefs and treatment outcome. Psychological Medicine 18, 697702.
Little R, Rubin D (2002). Statistical Analysis with Missing Data. Wiley: New York.
Mataix-Cols D, Marks IM, Greist JH, Kobak KA, Baer L (2002). Obsessive-compulsive symptom dimensions as predictors of compliance with and response to behaviour therapy: results from a controlled trial. Psychotherapy and Psychosomatics 71, 255262.
SAS Institute (2007). Statistical Analysis System, Version 9.1. SAS Institute: Cary, NC.
Saxena S, Maidment KM, Vapnik T, Golden G, Rishwain T, Rosen RM, Tarlow G, Bystritsky A (2002). Obsessive-compulsive hoarding: symptom severity and response to multimodal treatment. Journal of Clinical Psychiatry 63, 2127.
Simpson HB, Foa EB, Liebowitz MR, Roth Ledley D, Huppert JD, Cahill SP, Vermes D, Schmidt AB, Hembree EA, Franklin M, Campeas R, Hahn C, Petkova E (2008). A randomized, controlled trial of cognitive-behavioral therapy for augmenting pharmacotherapy in obsessive-compulsive disorder. American Journal of Psychiatry 165, 621630.
Simpson HB, Huppert JD, Petkova E, Foa EB, Liebowitz MR (2006). Response versus remission in obsessive-compulsive disorder. Journal of Clinical Psychiatry 67, 269276.
Steketee G, Chambless DL, Tran GQ (2001). Effects of axis I and II comorbidity on behavior therapy outcome for obsessive-compulsive disorder and agoraphobia. Comprehensive Psychiatry 42, 7686.
Steketee G, Henninger NJ, Pollard C (2000). Predicting treatment outcomes for obsessive-compulsive disorder: effects of comorbidity. In Obsessive-Compulsive Disorder: Contemporary Issues in Treatment (ed. Goodman W. K., Rudorfer M. V. and Maser J. D.), pp. 257274. Lawrence Erlbaum: Mahwah, NJ.
Steketee G, Shapiro LJ (1995). Predicting behavioral treatment outcome for agoraphobia and obsessive compulsive disorder. Clinical Psychology Review 15, 317346.
Stewart SE, Yen C-H, Stack DE, Jenike MA (2006). Outcome predictors for severe obsessive-compulsive patients in intensive residential treatment. Journal of Psychiatric Research 40, 511519.
Storch EA, Merlo LJ, Larson MJ, Geffken GR, Lehmkuhl HD, Jacob ML, Murphy TK, Goodman WK (2008). Impact of comorbidity on cognitive-behavioral therapy response in pediatric obsessive-compulsive disorder. Journal of the American Academy of Child and Adolescent Psychiatry 47, 583592.
Tenneij NH, van Megen HJ, Denys DA, Westenberg HG (2005). Behavior therapy augments response of patients with obsessive-compulsive disorder responding to drug treatment. Journal of Clinical Psychiatry 66, 11691175.
Tolin DF, Maltby N, Diefenbach GJ, Hannan SE, Worhunsky P (2004). Cognitive-behavioral therapy for medication nonresponders with obsessive-compulsive disorder: a wait-list-controlled open trial. Journal of Clinical Psychiatry 65, 922931.
Weissman MM, Bothwell S (1976). Assessment of social adjustment by patient self-report. Archives of General Psychiatry 33, 11111115.
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Psychological Medicine
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