P.4.d.005 Combining clomipramine and paroxetine for treatment-resistant obsessive compulsive disorder

Abstract

Second-generation antidepressants, such as the selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), are considered first-line treatments for anxiety. Recent studies in major depressive disorder have suggested that antidepressants are more effective for severely depressed patients than for mildly depressed patients [1,2]. As a consequence, guidelines for the treatment of milder depression have changed. Little is known, however, about whether this relationship between baseline severity and antidepressant efficacy also holds for anxiety disorders. Objective: To examine the influence of baseline severity of anxiety on antidepressant efficacy for generalized anxiety disorder (GAD), social anxiety disorder (SAD), obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and panic disorder (PD). Methods: Data from Food and Drug Administration (FDA) reviews of approved second-generation antidepressants was used. All premarketing randomized controlled trials of secondgeneration antidepressants for the short-term treatment of an anxiety disorder were included, with the exception of three trials with incompatible primary outcomes. Baseline symptom scores and change in symptom scores were extracted for placebo and treatment groups in each study. For PD, remission rates were also extracted. Hedges' g was calculated from the change score and its standard deviation for GAD, SAD, OCD, and PTSD. For 10 trials, data on the standard deviation or remission rate was missing; multiple imputation was used to impute these missing data. Mixed-effects meta-regression was used to investigate the effects of treatment group, baseline severity, and their interaction on the standardized change from baseline or the remission rate (for PD only). Results: Fifty-six trials with a total of 14,710 participants were included. Placebo effect sizes ranged from 0.49 for OCD to 1.03 for GAD, while drug effect sizes ranged from 0.83 for OCD to 1.35 for GAD. Increasing baseline severity did not predict greater improvement in drug groups compared to placebo groups. Standardized regression coefficients of the interaction term between baseline severity and treatment group were 0.04 (95% confidence interval −0.13 to 0.20, p = 0.65) for GAD, −0.06 (−0.20 to 0.09, p = 0.43) for SAD, 0.04 (−0.07 to 0.16, p = 0.46) for OCD, 0.16 (−0.22 to 0.53, p = 0.37) for PTSD, and 0.002 (−0.10 to 0.10, p = 0.96) for PD. For OCD, baseline severity did predict improvement in both placebo and drug groups equally (b = 0.11, 95% confidence interval 0.05 to 0.17, p = 0.001). Conclusions: No relationship between baseline severity and the drug-placebo difference was found for anxiety disorders. These results suggest that mildly or moderately anxious patients may experience as much benefit from antidepressants as severely anxious patients. The size of the drug-placebo difference was small to moderate; whether these effects may be considered clinically relevant remains a matter of debate. If considered clinically rel...