A DOUBLE-BLIND COMPARISON OF SERTRALINE AND CLOMIPRAMINE IN OUTPATIENTS WITH OBSESSIVE-COMPULSIVE DISORDER

The aim of this study was to compare the efficacy, safety, and tolerab ility of sertraline and clomipramine in the treatment of obsessive-com pulsive disorder (OCD). Outpatients with DSM-III-R defined OCD for 1 y ear or longer and scores of greater than or equal to 20 on the Yale-Br own Obsessive Compulsive Scale (Y-BOCS), greater than or equal to 7 on the National Institute of Mental Health Global Obsessive-Compulsive S cale (NIMH-OC), greater than or equal to 4 on the Clinical Global Impr ession Severity of Illness Scale (CGI-S) and less than or equal to 17 on the Hamilton Depression Scale (17 item HAMD) were randomized to ser traline (n = 86) or clomipramine (n = 82) once daily for 16 weeks. Ini tial daily doses of sertraline and clomipramine were 50 mg. After a mi nimum of 4 weeks, these doses could be increased by 50 mg increments e very 2 weeks to a maximum of 200 mg daily if the response was thought inadequate. Efficacy was assessed at the end of 1, 2, 4, 6, 8, 12 and 16 weeks of therapy using the Y-BOCS, NIMH-OC, CGI-S, CGI Improvement Scale (CGI-I) and Clinical Anxiety Scale (GAS). One hundred sixty-eigh t patients were randomized and received at least one dose of double-bl ind medication; 86 received sertraline and 82 clomipramine. Mean final daily doses at final visit were clomipramine 90 mg (efficacy evaluabl e patients 101 mg, completers 110 mg), and sertraline 129 mg (efficacy evaluable patients 132 mg, completers 136 mg). Mean baseline Y-BOCS, NIMH-OC and CGI-S totals were 27.7, 10.1 and 5.5, respectively, for se rtraline and 27.4, 9.9 and 5.5, respectively, for clomipramine. Sertra line demonstrated greater efficacy than clomipramine in the intent-to- treat patient group: mean baseline to final visit changes were 50.8% ( Y-BOCS), 41.9% (NIMH-OC) and 37.7% (CGI-S) for sertraline and 42.9% (Y -BOCS), 33.8% (NIMH-OC) and 30.0% (CGI-S) for clomipramine (P < 0.05). The number of patients withdrawing because of adverse events was subs tantially greater for clomipramine (26%) than sertraline (11%) (P < 0. 05). The most frequent adverse events for clomipramine were dry mouth (20%), anxiety (17%), constipation (16%), nausea (15%) and somnolence (11%), and for sertraline, diarrhea (12%) and nausea (12%). In this st udy, sertraline was more effective than clomipramine in the intent-to- treat analysis. The difference in efficacy between the treatments is a lmost wholly accounted for by a greater number of clomipramine withdra wals due to the poor patient acceptance of clomipramine. The superior tolerability of sertraline and the lower rate of premature treatment w ithdrawal relative to clomipramine may offer considerable quality of l ife and compliance benefits in the long-term management of a chronic d isorder such as OCD.