Pharmacotherapy of Obsessive-Compulsive Disorder

Although a wide variety of medications have been utilized in the treatment of Obsessive-compulsive disorder, there is little doubt as to the consistent efficacy of serotonin reuptake inhibitors, of which clomipramine is the most widely researched. Placebo controlled trials have in general attested to its efficacy and comparison to other antidepressants have also demonstrated its superiority in decreasing obsessional symptoms. Average symptom reduction, however, is only moderate.

Although not as extensively researched as clomipramine, other more potent SSPJ appear to be of equal benefit in the treatment of Obsessive-compulsive disorder, and in general have the added benefit of a lower side-effect profile. The efficacy of fluoxetine at three fixed doses (20,40, and 60 mg) was examined in a multicenter trial by Tollefson et al. (1994), who reported symptom reduction of 32.1%, 32.4%, and 35.1%, respectively, as compared with 8.5% for placebo after a 13 week trial. Pigott et al. (1990) in a randomized double-blind crossover design compared clomipramine to fluoxetine and reported similar therapeutic effects. Fluvoxamine has also been shown to be superior to placebo in the treatment of Obsessive-compulsive disorder in a number of double-blind studies and in a multicenter trial.

Fluvoxamine was also compared with desipramine in a study by Goodman et al. (1990) and was found to be superior in reducing the severity of ОС symptoms. A direct comparison of fluvoxamine with clomipramine by Lorin et al. (1996) reported similar levels of symptom reduction in a similar proportion of patients in both groups. Sertraline, another specific serotonin reuptake inhibitor, has also had mixed results initially, with one placebo controlled study finding no effect in a small number of patients. Other studies have attested to the efficacy of sertraline in Obsessive-compulsive disorder.

Chouinard et al. (1990) reported that sertraline resulted in significant decreases in Obsessive-compulsive disorder symptoms on three of the four measures used. Greist et al. (1995) reporting on a large multicenter placebo controlled trial of fixed-dose sertraline (50, 100, 200 mg) found that doses of 50 mg and 200 mg were significantly more effective than placebo in reducing obsessional symptoms. More recently, Kronig et al. (1999) found sertraline at varying doses from 50 to 200 mg per day to be significantly more effective than placebo on all measures used. Paroxetine has also been reported to be more effective than placebo in a multicenter trial but only at doses of 40 mg and 60 mg per day, with 20 mg being no different from placebo. There also is growing evidence concerning the effectiveness of citalopram in the treatment of Obsessive-compulsive disorder. Mundo et al. (1997) reported equal effectiveness of fluvoxamine, paroxetine and citalopram in a single-blind comparative trial of 30 patients with Obsessive-compulsive disorder.

The issue of treatment-refractory Obsessive-compulsive disorder patients has been addressed by a number of authors, and several pharmacological agents (e.g., lithium, buspirone, haloperidol, olanzapine) have been suggested as possible augmenting strategies. Few controlled trials of such substances have been reported. However, in a recent placebo controlled trial, McDougle et al. (2000) found augmentation of selective serotonin re-uptake inhibitors with risperidone to be of assistance in patients who did not respond to specific serotonin reuptake inhibitor monotherapy. The issue of how to define a treatment-refractory patient was addressed by Rasmussen and Eisen (1997), who suggested that the emerging consensus is “someone who has failed both adequate trials of an specific serotonin reuptake inhibitor and exposure with response prevention” (ibid., p. 11), rather than monotherapy with either exposure or selective serotonin re-uptake inhibitors.

Perhaps the major difficulty with the use of selective serotonin re-uptake inhibitors in the treatment of Obsessive-compulsive disorder is the high relapse rate with medication discontinuation. For example, Pato et al. (1988) reported that 89% of patients treated with clomipramine over a 5- to 27-month period experienced substantial recurrence of ОС symptoms. Significant worsening of depression was reported in 11 of the 18 subjects. Estimates of relapse following discontinuation of medication range from 65% to 90%. Such findings have resulted in some authors suggesting that the addition of behavior therapy to medication may prevent relapse and assist patients to discontinue medication.

No study has as yet specifically addressed the issue of medication discontinuation following behavior therapy, though a number of studies have compared the effects of combining selective serotonin re-uptake inhibitors and behavior therapy with either monotherapy. A number of studies have suggested that combining selective serotonin re-uptake inhibitors with behavior therapy may be useful for depressed Obsessive-compulsive disorder sufferers in the short term, with behavior therapy an effective and sufficient treatment for nondepressed Obsessive-compulsive disorder sufferers, while others have found no difference in outcome when comparing combined specific serotonin reuptake inhibitor and behavior therapy to behavior therapy alone.

Kobak et al. (1998) conducted a meta-analytic study that examined the efficacy of selective serotonin re-uptake inhibitors and behavior therapy. From the medications that included clomipramine, fluoxetine, flu-voxamine and paroxetine, for clomipramine the effect size at 1.02 was largest; however, the difference as a whole was not statistically different from the other selective serotonin re-uptake inhibitors. Although the effect size for exposure and response prevention was not significantly different from clomipramine, it was significantly larger than the effect size for the selective serotonin re-uptake inhibitors as a whole; however, the result was nonsignificant when methodological variables were controlled. The effect size for exposure was not significantly different from the effect size for combined exposure and selective serotonin re-uptake inhibitors. Interestingly, dropout rates from behavior therapy were similar to those of any individual specific serotonin reuptake inhibitor.

The decision as to whether Obsessive-compulsive disorder sufferers are best treated with behavior therapy alone or in combination with pharmacological agents rests with the clinician and the sufferer. A number of reports in the literature suggest that a combined approach is the most favorable. There is, however, little evidence to support such recommendations for the majority of sufferers. As stated earlier, the notion that the addition of behavior therapy to pharmacological treatment may prevent the relapse associated with cessation of medication has not been specifically addressed in any study to date. Gradually tapering the medication as a method of reducing the high relapse rate has also not been tested in any controlled fashion.

However, anecdotal evidence from our clinic suggests that medication reduction and eventual discontinuation is possible in individuals who have had a good response and remained stable for a 6-month period. Any attempt at reduction of medication is undertaken very gradually (over a 6- to 8-month period) and patients are carefully monitored so that emergence of symptoms can be dealt with in behavior therapy booster sessions. Nevertheless, given the current absence of knowledge regarding the possible superiority of a combined versus individual approach as well as the side-effects that, although variable across the medications, are nonetheless present, the decision to include medication as part of treatment should be made on the basis of such factors as severity of associated depression, the patient’s willingness to undertake a behavioral program, failure to respond to exposure techniques, or the patient’s choice on the matter.

Psychosurgical techniques, such as anterior cingulotomy, anterior cap-sulotomy, or subcaudate tracheotomy procedures that interrupt connections between the basal ganglia and frontal cortex have been shown to be of benefit in the treatment of severe, intractable Obsessive-compulsive disorder that has not responded to traditional treatments. However, it is recommended that following such intervention a comprehensive program of behavior therapy and pharmacotherapy be utilized, as surgical intervention, rather than being curative, tends to restore the patient to a status that is more amenable to such techniques.