23. PharmacotherapyPCNA

Pharmacotherapyof Obsessive-compulsive Disorderand Obsessive-CompulsiveSpectrum Disorders

Damiaan Denys, MD, PhD*

Department of Anxiety Disorders, Rudolf Magnus Institute of Neuroscience,Department of Psychiatry, University Medical Center, Utrecht, The Netherlands

In one of the first articles addressing pharmacotherapy for obsessive-compulsive disorder (OCD) published in 1969, intravenous clomipramineunexpectedly proved effective for 11 of 13 patients[1]. The authors offeredthe following hypotheses to explain the improvement:1. OCD symptoms remitted spontaneously2. Clomipramine relieved the depression, and OCD symptoms subse-quently receded3. OCD patients are all hysterics who would respond to any dramaticmethod of treatment4. OCD patients habitually employ magical mental mechanisms and aretherefore more susceptible than most to ‘‘magical’’ treatment methodssuch as intravenous treatment5. Clomipramine induced sleep, which is an anxiety-reducing form of de-conditioning similar to pentothal injections6. OCD symptoms may be symptoms of disturbed brain chemistryIn addition to the open-mindedness of the authors, the surprising contentof these hypotheses illustrates how dramatically the attitude towards OCShas shifted in a few decades, from obsessional neurosis rooted in psycho-analysis to OCD embedded in neurobiology. In 2006, the hypothesis of dis-turbed brain chemistry and potential improvement with drugs in OCDseems self-evident.

* Correspondence. University Medical Center (B.01.206), P.O. Box 85500, GA Utrecht3508, The Netherlands.

E-mail address:

d.a.j.p.denys@umcutrecht.nl0193-953X/06/$ - see front matter

Ó

psych.theclinics.com

Psychiatr Clin N Am 29 (2006) 553–584

During the past 25 years a large number of controlled studies have estab-lished the efficacy of pharmacologic treatment for OCD. Thanks to pharma-cotherapy, as many as 90% of OCD patients eventually have a clinicallymeaningful response. Nonetheless, a recent survey at the author’s institutionrevealed that a large proportion of OCD patients still fail to receive ade-quate pharmacotherapy. On admission, 35% of patients declared thatthey never had received pharmacotherapy, 16% had received inappropriatedrugs, and 50% never had taken the maximal effective dose of serotonin-re-uptake inhibitors (SRIs) during the course of their treatment[2]. Despitecurrent evidence of disturbed brain pathophysiology and apparent efficacyof pharmacotherapy, for some mental health professionals, OCD still carriesan association with obsessional neurosis.This article reviews pharmacologic approaches to the treatment of OCDand obsessive-compulsive spectrum disorders. The first section is devotedto OCD and discusses developments of pharmacotherapy during the past5 years since the publication of the last review of pharmacotherapy inOCD in the

Psychiatric Clinics of North America

. For comprehensive re-views of earlier literature on pharmacotherapy of OCD, the reader shouldsee Fineberg and colleagues[3], Kaplan and colleagues[4], Hollander and colleagues[5], and Jenike and colleagues[6]. The second section reviews pharmacologic treatment studies in obsessive-compulsive spectrum disor-ders such as skin picking, nail biting, compulsive buying disorder, and com-pulsive non-paraphilic sexual disorders.

OCD

Developments in pharmacotherapy of OCD during the past 5 years pri-marily involve (1) the extension of evidence of eﬃcacy of SRIs as treatmentfor drug-naı ¨ve patients, (2) the use of atypical antipsychotics in addition toSRIs for patients who have treatment-refractory OCD, (3) an expansion of studies examining the combination of pharmacotherapy and behavior ther-apy, and (4) studies assessing predictors of response.

Treating drug-naı ¨ ve OCD patientsPlacebo-controlled studies of SRIs

The cornerstone of pharmacotherapy for OCD is inhibition of serotoninreuptake, either with clomipramine or with selective serotonin-reuptake in-hibitors (SSRIs). During the past 25 years, a number of double-blind, ran-domized, placebo-controlled studies in OCD have confirmed the efficacy of clomipramine and the SSRIs: fluvoxamine, paroxetine, sertraline, and fluox-etine. Novel placebo-controlled trials of SSRIs include two paroxetine stud-ies, a large multicenter citalopram study, and a study of controlled-release(CR) formulation of fluvoxamine. The efficacy of drug trials is expressedin absolute changes in scores on the Yale-Brown Obsessive Compulsive

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DENYS

Scale (Y-BOCS). The Y-BOCS is a clinician-rated 10-item scale with a totalrange of 0 to 40 that measures severity of obsessions and compulsions[7,8].In many cases, patients are classiﬁed as responders when their scores on theY-BOCS decrease by 25% to 35%. A recent paper reported that a Y-BOCSreduction of 30% is optimal for predicting improvement on the clinicalglobal impression rating scale (CGI)[9].

Clomipramine

. The efficacy of clomipramine was established in more than10 placebo-controlled trials. In a recent meta-analysis, clomipramine showsa net improvement (difference) compared with placebo of 8.20 points on theY-BOCS[10]. Responder rates to clomipramine vary from 40% to 50% of patients. Although in some cases low doses of clomipramine over a short pe-riod of time may result in significant improvement of symptoms, clomip-ramine treatment should last at least 10 to 12 weeks in a dose of 250 to300 mg/d to demonstrate a full effect. Clomipramine has never been testedin a controlled fixed-dose study to assess optimal doses.

Fluvoxamine

. Fluvoxamine was superior to placebo in four placebo-controlled trials and was equipotent to clomipramine in five comparisontrials[11]. The pooled difference of fluvoxamine compared with placebo inthese trials was 4.8 points on the Y-BOCS[10]. Fluvoxamine has neverbeen examined in a fixed-dose trial but seems to be efficacious at dosagesfrom 150 to 300 mg/d. Recently, Hollander and colleagues[12]assessedthe CR formulation of fluvoxamine in a 12-week placebo-controlled study(Table 1). At end point, the mean Y-BOCS score decreased 8.5 in the fluvox-amine CR treatment group versus 5.6 in the placebo group. Thirty-twopercent of patients treated with fluvoxamine CR were responders, comparedwith 21% given placebo. Of particular interest is the early onset of therapeu-tic effect: fluvoxamine CR was superior to placebo as early as week 2.

Table 1Recent placebo-controlled studies of SRIs for OCDAuthor Drug N Weeks Dose (mg/day) Baseline*End Point*Change* Hollander[12]ﬂuvoxamine CR 127 12 200 26.8 18.3 8.5placebo 126 12 26.4 21.0 5.4Kamijima[17]paroxetine 94 12 40–50 24.3 14.8 8.1placebo 94 12 23.4 18.6 3.5Hollander[18]paroxetine 88 12 20 25.9 22.0 3.9paroxetine 86 12 40 25.4 18.7 6.7paroxetine 85 12 60 25.3 17.5 7.8placebo 89 12 25.6 22.0 3.6Montgomery[19]citalopram 102 12 20 25.1 16.7 8.4citalopram 98 12 40 26.0 17.1 8.9citalopram 100 12 60 25.9 15.5 10.4placebo 101 12 25.4 19.8 5.6* Absolute Y-BOCS scores555

PHARMACOLOGY OF OCD AND OCD SPECTRUM DISORDERS

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