A double-blind comparison of sertraline and clomipramine in outpatients with obsessive-compulsive disorder

Abstract

The aim of this study was to compare the efficacy, safety, and tolerability of sertraline and clomipramine in the treatment of obsessive-compulsive disorder (OCD). Outpatients with DSM-III-R defined OCD for 1 year or longer and scores of >/=20 on the YaleBrown Obsessive Compulsive Scale (Y-BOCS), >/=7 on the National Institute of Mental Health Global Obsessive-Compulsive Scale (NIMH-OC), >/=4 on the Clinical Global Impression Severity of Illness Scale (CGI-S) and </=17 on the Hamilton Depression Scale (17 item HAMD) were randomized to sertraline (n = 86) or clomipramine (n = 82) once daily for 16 weeks. Initial daily doses of sertraline and clomipramine were 50 mg. After a minimum of 4 weeks, these doses could be increased by 50 mg increments every 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 (CAS). One hundred sixty-eight patients were randomized and received at least one dose of double-blind medication; 86 received sertraline and 82 clomipramine. Mean final daily doses at final visit were clomipramine 90 mg (efficacy evaluable 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 sertraline and 27.4, 9.9 and 5.5, respectively, for clomipramine. Sertraline 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 substantially 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 study, sertraline was more effective than clomipramine in the intent-to-treat analysis. The difference in efficacy between the treatments is almost wholly accounted for by a greater number of clomipramine withdrawals due to the poor patient acceptance of clomipramine. The superior tolerability of sertraline and the lower rate of premature treatment withdrawal relative to clomipramine may offer considerable quality of life and compliance benefits in the long-term management of a chronic disorder such as OCD.

World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders – First Revision

“…Clomipramine efficacy could also be demonstrated in DBPC studies in children and adolescents with OCD (DeVeaugh-Geiss et al 1992;Flament et al 1985)(A). The available evidence based on eight head-tohead comparisons suggests that there are no differences in efficacy between clomipramine and SSRIs (Zohar and Kindler 1992), and contradicts other (not head-to-head) studies which propose that clomipramine has greater anti-obsessional efficacy than do the SSRIs (Abramowitz 1997; Bisserbe et al 1997;Greist et al 1995c;Piccinelli et al 1995;Pigott and Seay 1999;Todorov et al 2000). Some direct comparisons suggest that SSRIs are better tolerated than clomipramine while having the same efficacy (Bisserbe et al 1997;Milanfranchi et al 1997;Mundo et al 2000;Zohar and Judge 1996;Zohar 2008).…”

“…The study failed to differentiate between placebo and paroxetine on relapse measures, possibly because the duration of follow-up was too short (Geller et al 2003) (A). Á Sertraline was effective in DBPC (Chouinard et al 1990;Greist et al 1995a;Kronig et al 1999) and clomipramine-controlled (Bisserbe et al 1997) studies. Long-term studies showed efficacy over 1 year in a DBPC study (Greist et al 1995b) and a 1-year open-label extension (Rasmussen et al 1997).…”

Management of Obsessive Compulsive Disorder

“…The studies comparing SSRI and clomipramine have shown that they all demonstrated efficacy [23, 24]. However, clomipramine is also associated with an increased incidence of adverse effects [25, 26, 27, 28, 29]. In a flexible dose trial of paroxetine compared with clomipramine in 406 patients with OCD [26], paroxetine and clomipramine were more effective than placebo.…”

On the Pharmacotherapy of Obsessive—Compulsive Disorder: Is a Consensus Possible?

“…The SSRIs have therefore emerged as the new gold standard in the pharmacotherapy ofOCD, at the expense of clomipramine. Moreover, one recent study even claims that, because of its better side effect profile and consequent greater tolerability, sertraline is more efficacious than clomipramine (8). Unfortunately, trials directly comparing clomipramine and the SSRIs are scarce, and most ofthem are small.…”