Importance: Serotonin reuptake inhibitors (SRIs) are the only medications approved for obsessive-compulsive disorder (OCD), yet most patients taking SRIs exhibit significant symptoms. Adding exposure/response prevention (EX/RP) therapy improves symptoms, but it is unknown whether patients maintain wellness after discontinuing SRIs. Objective: To assess whether patients with OCD who are taking SRIs and have attained wellness after EX/RP augmentation can discontinue their SRI with noninferior outcomes compared with those who continue their SRI therapy. Design, Setting, and Participants: A 24-week, double-blind, randomized clinical trial was performed from May 3, 2013, to June 25, 2018. The trial took place at US academic medical centers. Participants included 137 adults with a principal diagnosis of OCD (≥1 year) who were taking an SRI (≥12 weeks), had at least moderate symptoms (defined as Yale-Brown Obsessive-Compulsive Scale [Y-BOCS] score ≥18 points), and received as many as 25 sessions of EX/RP therapy. Those who attained wellness (Y-BOCS score ≤14 points; 103 patients [75.2%]) were study eligible. Data were analyzed from June 29, 2019, to October 2, 2021. Intervention: Participants were randomly assigned either to receive taper to placebo (taper group) or to continue their SRI (continuation group) and monitored for 24 weeks. Main Outcome and Measures: The Y-BOCS score (range, 0-40 points) was the primary outcome; the Hamilton Depression Rating Scale (HDRS; range, 0-52 points) and the Quality-of-Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF; range, 0%-100%) scores were secondary outcomes. Outcomes were assessed at 8 time points by independent evaluators who were blinded to randomization. The taper regimen was hypothesized to be noninferior to continuation at 24 weeks using a 1-sided α value of.05. Results: A total of 101 patients (mean [SD] age, 31.0 [11.2] years; 55 women [54.5%]) participated in the trial: 51 patients (50.5%) in the taper group and 50 patients (49.5%) in the continuation group. At 24 weeks, patients in the taper group had noninferior results compared with patients in the continuation group (mean [SD] Y-BOCS score: taper group, 11.47 [6.56] points; continuation group: 11.51 [5.97] points; difference,-0.04 points; 1-sided 95% CI,-∞ to 2.09 points [below the noninferiority margin of 3.0 points]; mean [SD] HDRS score: taper group, 5.69 [3.84] points; continuation group, 4.61 [3.46] points; difference, 1.08 points; 1-sided 95% CI,-∞ to 2.28 points [below the noninferiority margin of 2.5 points]; mean [SD] Q-LES-Q-SF score: taper group, 68.01% [15.28%]; continuation group, 70.01% [15.59%]; difference, 2.00%; 1-sided 95% CI,-∞ to 6.83 [below the noninferiority margin of 7.75]). However, the taper group had higher rates of clinical worsening (23 of 51 [45%] vs 12 of 50 [24%]; P =.04). Conclusions and Relevance: Results of this randomized clinical trial show that patients with OCD who achieve wellness after EX/RP therapy could, on average, discontinue their SRI with noninferior outcomes compared with those who continued their SRI. Those who tapered the SRI had higher clinical worsening rates. Future research should evaluate if SRI half-life alters these rates. Trial Registration: ClinicalTrials.gov Identifier: NCT01686087.
Bibliographical noteFunding Information:
receiving royalties from Bantam and Oxford University Press for book sales, including a manual of cognitive behavioral therapy for obsessive-compulsive disorder; receiving payment for training she conducts on treatment of obsessive-compulsive disorder; and receiving grants from the National Institutes of Health during the conduct of the study. Drs Foa and Simpson reported receiving research support from Biohaven Pharmaceuticals and royalties from Cambridge University Press and UpToDate, Inc, during the conduct of this study. Dr. Puliafico reported receiving royalties from UpToDate, Inc. Dr Rosenfield reported receiving stipends from JAMA Psychiatry and Behavior Research and Therapy for duties related to their editorial boards, receiving fees from Rosenfield Analytics for data analysis and statistical consulting, and receiving grants from the National Institutes of Health, the Department of Defense, and the Cancer Prevention and Research Institute of Texas for research outside the submitted work. No other disclosures were reported.
Funding/Support: This work was supported by grant R01MH045404 (Dr Foa) and grant R01MH045436 (Dr Simpson) from the National Institute of Mental Health.
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- Cognitive Behavioral Therapy/methods
- Combined Modality Therapy
- Implosive Therapy
- Obsessive-Compulsive Disorder/diagnosis
- Serotonin Uptake Inhibitors/therapeutic use
- Treatment Outcome