Randomized, Placebo-Controlled Trial of Exposure and Ritual Prevention, Clomipramine, and Their Combination in the Treatment of Obsessive-Compulsive Disorder
Foa EB, Liebowitz, MR, Kozak MJ, Davies S, Campeas R, et al. ;
Commented by , 24 Jan 2005
Background
Exposure and Ritual (or Response) Prevention (ERP) is the main technique used in Cognitive-Behavioral Therapy (CBT) to treat Obsessive-Compulsive Disorder (OCD). Clomipramine is a serotonine reuptake inhibitor that has been studied extensively in the treatment of OCD. The efficacy of both ERP and clomipramine for treating OCD have been confirmed in randomized controlled studies.
Aims of the study
To investigate whether the efficacy of a combination of CRP and clomopramine is more efficacious than either treatment alone.
Method
In a twelve week, three-site, randomised controlled study, 122 patients with OCD were assigned to one of 4 treatment groups: ERP alone, clomipramine alone, ERP plus clomipramine, and placebo.
ERP consisted in manual-based treatment procedures (described in detail in the article), provided in 15 daily sessions (5 times a week) - each lasting 2 hours - over a period of three weeks, followed by 8 weekly sessions - each lasting 45 minutes.
Clomipramine was given in a fixed dosage for the first 5 weeks, (starting at 25 mg/day, increasing to 200 mg/day) and increased up to 250 mg/day if tolerated and indicated.
Results
At week 12:
- the scores of patients receiving active treatments were significantly lower than those of patients receiving placebo
- exposure and ritual prevention alone was superior to clomipramine alone
- exposure and ritual prevention plus clomipramine was superior to clomipramine
- no differences were found between exposure and ritual prevention alone and exposure and ritual prevention plus clomipramine
Discussion
Obsessive-Compulsive Disorder (OCD) is a highly prevalent, pervasive, and mostly persistent, chronic disorder. It is associated with significant distress and leads to considerable impairment in professional and daily life functioning.
As shown by the results of this study, both ERP and clomipramine are efficacious treatment for OCD, with the efficacy of ERP possibly superior to that of clomipramine.
ERP is, however, a complex and time-consuming treatment, which needs to be administered by fully trained, experienced CBT psychotherapists. Since there is a shortage of such psychotherapists in almost any part of the world, only a minority of sufferers can profit from this treatment.
As such, there is a need for other types of treatment, including, in particular, pharmacotherapy, either as a stand-alone treatment or to enhance the efficacy of ERP, and/or to shorten the duration of the treatment. Unfortunately, the results of the present study do not confirm that a combination of the two treatments presents any advantage to what can be achieved with ERP alone.
This is a study of outstanding methodological quality. It does, however, have a few important limitations. In particular, it does not provide answers to several important questions concerning the course of a disorder that is known to be persistent and/or chronic. What will happen after 3 months (or after 6 months, after a year, after several years)
- when clomipramine is discontinued, in a stand-alone treatment?
- when ERP is discontinued, in a stand-alone treatment?
- when either ERP or clomipramine, or both, are discontinued, in a combination treatment?
Efficacious pharmacotherapy for OCD currently includes, besides clomipramine, several selective serotonine reuptake inhibitors or SSRIs (citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline). It will be of particular interest to see whether the results obtained with clomipramine in the present study apply to the SSRIs as well.