Early Onset of Response With Selective Serotonin Reuptake Inhibitors in Obsessive-Compulsive Disorder: A Meta-Analysis

Objective: Selective serotonin reuptake inhibitors (SSRIs) are recommended as the first-line pharmacologic treatment for obsessive-compulsive disorder (OCD). SSRI response is thought to be delayed in OCD, even more so than in major depression. We conducted a meta-analysis to examine the trajectory of treatment response to SSRIs and how this trajectory is modulated by dosage.

Data Sources: PubMed and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched on May 22, 2013, for randomized, placebo-controlled SSRI trials in OCD with the search terms “serotonin uptake inhibitors” [MeSH] OR “serotonin uptake inhibitors” [Pharmacologic Action] AND “obsessive-compulsive disorder” [MeSH]. There were no language limitations on the search.

Study Selection: Randomized, placebo-controlled trials that examined the efficacy of SSRIs in the treatment of adults with OCD and utilized the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) as an outcome were selected.

Data Extraction: We extracted weekly symptom data from randomized, placebo-controlled trials of SSRIs for the treatment of adults with OCD in order to characterize the trajectory of pharmacologic response. Our primary outcome was weighted mean difference on the Y-BOCS of SSRI treatment compared to placebo. We used the PROC MIXED procedure in SAS to examine 6 possible models of SSRI response. Interaction terms were utilized to examine the effect of dose, individual agent, and year of publication on SSRI response.

Results: The meta-analysis included 17 trials of SSRIs including 3,276 subjects. A statistically significant benefit of SSRIs compared to placebo was seen within 2 weeks after the start of treatment (weighted mean difference = −0.91 [95% CI, −0.54 to −1.28], P < .001). A logarithmic response curve, indicating decreasing symptom improvement over time, provided the best fit for the trajectory of OCD symptom improvement. A significantly greater response was associated with using higher doses of SSRIs (P < .0001).

Conclusions: These results suggest that the greatest incremental treatment gains in OCD are seen early on in SSRI treatment. This is consistent with a previous meta-analysis examining time course of SSRI action in major depressive disorder and contrasts with the widely held belief that SSRI response in OCD is delayed.