Meta-analysis of the dose-response relationship of SSRI in obsessive-compulsive disorder

Abstract

We sought to determine differences in efficacy and tolerability between different doses of selective serotonin reuptake inhibitors in the treatment of obsessive-compulsive disorder (OCD) using meta-analysis. We identified 9 studies involving 2268 subjects that were randomized, double-blind placebo-controlled clinical trials that compared multiple, fixed-doses of selective serotonin reuptake inhibitors (SSRIs) to each other and to placebo in the treatment of adults with OCD. Change in Y-BOCS score, proportion of treatment responders, and dropouts (all-cause and due to side-effects) were determined for each included study. Weighted mean difference was used to examine mean change in Y-BOCS score. Pooled absolute risk difference was used to examine dichotomous outcomes. Meta-analysis was performed using a fixed effects model in RevMan 4.2.8. We found that compared with either low or medium doses, higher doses of SSRIs were associated with improved treatment efficacy, using either Y-BOCS score or proportion of treatment responders as an outcome. Dose of SSRIs was not associated with the number of all-cause dropouts. Higher doses of SSRIs were associated with significantly higher proportion of dropouts due to side-effects. These results suggests that higher doses of SSRIs are associated with greater efficacy in the treatment of OCD. This SSRI efficacy pattern stands in contrast to other psychiatric disorders like Major Depressive Disorder. This greater treatment efficacy is somewhat counterbalanced by the greater side-effect burden with higher doses of SSRIs. At present, there are insufficient data to generalize these findings to children or adolescents with OCD.

Figure 1. SSRI Dose-Response Relationship

Plots track changes in Y-BOCS ratings (blue) and Absolute Difference in Percentage Treatment Responders (red) of Selective Serotonin-Reuptake Inhibitors (SSRIs) when compared to placebo. *=statistically significantly greater response compared to placebo, #= statistically significantly greater response when compared to low-dose SSRI pharmacotherapy and ^= statistically significantly greater response when compared to medium-dose SSRI pharmacotherapy. Threshold for statistical significance is less than 0.05 and results apply to both measures of response

Figure 2. SSRI Dose-Tolerability Relationship

plots absolute risk of dropout, all-cause (blue) and attributable to side-effects (red) of Selective Serotonin-Reuptake Inhibitor (SSRI) dose categories when compared to placebo. *=statistically significantly greater dropout due to side-effects compared to placebo, #= statistically significantly greater dropout rate due to side-effects when compared to low-dose SSRI pharmacotherapy. Threshold for statistical significance was less than 0.05 and there were no significant findings related to all-cause dropouts.