FLUOXETINE - AN OVERVIEW OF ITS PHARMACODYNAMIC AND PHARMACOKINETIC PROPERTIES AND REVIEW OF ITS THERAPEUTIC EFFICACY IN OBSESSIVE-COMPULSIVE DISORDER

Fluoxetine is a bicyclic monoamine whose primary pharmacological actio n is selective inhibition of serotonin (5-hydroxytryptamine; 5-HT) reu ptake; this action appears to be necessary for bur does not fully expl ain, its efficacy in the treatment of obsessive-compulsive disorder (O CD). It inhibits the reuptake of other neurotransmitters to a much les ser extent and has little affinity for a number of neurotransmitter bi nding sites. The mean elimination half-lives of fluoxetine and its act ive metabolite norfluoxetine are 2 to 7 and 7 to 15 days, respectively , after multiple doses. Results of several short term clinical trials indicate that fluoxetine 20 to 80 mg/day is superior to placebo in red ucing OCD symptom scores, with significant effects seen in both obsess ive and compulsive subscores. Response rates of 32 to compared with re sponse rates of 8 and 26% for patients treated with placebo have been reported. Significant improvement in symptoms compared with placebo we re reported after 4 to 8 weeks of treatment. While adequate comparativ e trials are not available, meta-analysis of data from large placebo-c ontrolled trials found fluoxetine to be similarly effective to fluvoxa mine and sertraline, but less effective than clomipramine. Studies in patients with OCD and concurrent depression or Gilles de la Tourette's syndrome have also found fluoxetine to be effective in reducing OCD s ymptoms. Fluoxetine has been used in combination with a variety of age nts including buspirone, lithium, clomipramine and fenfluramine in an attempt to augment the response in patients with treatment-refractory OCD, although adequate data to support this approach are lacking. In c omparison with tricyclic antidepressants, fluoxetine causes less sedat ion, fewer anticholinergic or cardiac adverse effects and is less harm ful in overdose, effects (insomnia, anxiety, anorexia) and gastrointes tinal effects (nausea, diarrhoea) are more frequent with fluoxetine. T he overall evidence presently suggests that fluoxetine is an effective agent in the treatment of OCD, although its relative efficacy and tol erability compared with other pharmacological treatments remain to be established. While several questions concerning its ultimate role in t he treatment of OCD remain unresolved, fluoxetine should currently be considered as a rueful treatment option with a iallv attractive for pa tients less likely to tolerate the anticholinergic and cardiac adverse effects of clomipramine.