[Value of fluoxetine in obsessive-compulsive disorder in the adult: review of the literature]

Abstract

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) with demonstrated efficacy in the treatment of major depressive episodes. Since 1985, it has been evaluated for the treatment of obsessive-compulsive disorder (OCD). The orbitofrontal cortex and caudate nucleus are cerebral structures believed to be involved in the pathogenesis of OCD, since hyperactivation of these territories in the basal state is corrected upon remission of symptoms induced by therapy with an SSRI or by behavioral psychotherapy. Furthermore, several studies have found abnormalities in serotoninergic transmission in the orbitofrontal cortex and SSRIs can increase serotonin release by desensitizing 5HTID autoreceptors. OCD is a severe, chronic psychiatric disorder frequently complicated by depressive episodes. Here we review the clinical trials of fluoxetine listed in the Medline and Embase computerized databases. Fluoxetine was found to be effective in OCD in all the published open-label studies as well as in placebo-controlled trials with an effective dose range of 40 to 60 mg daily. Clinical evaluation was carried out by using specific scales such as the Y-BOCS or NIMH-OC and improvement was observed after several weeks of therapy. These studies comprising an extended phase showed that efficacy was maintained--for three years in the longest study--resulting in a higher percentage of responders relative to the treatment initiation phase. A comparison of fluoxetine and clomipramine showed comparable efficacy and a superior safety profile, both in terms of anticholinergic side effects and cardiotoxicity or overdosage. The relapse rate was similar with both drugs. In the four meta-analyses appearing in the databases, two studies found similar efficacy for clomipramine and fluoxetine. There are few studies which directly compare the different SSRIs, apart from a comparison of fluoxetine and sertraline showing that both drugs have similar efficacy. With clomipramine, the SSRIs represent the first-line treatment recommended by the experts, in association with behavioral therapy to improve and maintain the clinical response over the long term. The guidelines recommend an optimal fluoxetine dose of 40 to 60 mg daily with a minimum treatment duration of 1 to 2 years. Efficacy should not be evaluated before 8 weeks to allow for onset of the therapeutic effects. Fluoxetine was found to have a good safety profile in these studies and the adverse effects described (insomnia, headache, diminished libido) rarely led to discontinuation of the treatment. Adverse effects such as nervousness or insomnia at the start of therapy were predictors of a good response to fluoxetine, as were the presence of remissions, the absence of prior pharmacologic therapy and a high impulsiveness score. A long history of the disorder, severity of the symptoms, collection obsessions, washing compulsions, obsessional slowness and comorbidity with a schizotypic personality or vocal or motor tics were associated with a poorer response. Fluoxetine also alleviates collateral depressive symptoms by significantly reducing suicidal ideation and impulsiveness in OCD patients. Our study indicates that fluoxetine is effective and well tolerated in OCD, placing it among the first-line treatments recommended by consensus conference guidelines.