Fluoxetine tenth anniversary update: the progress continues

This tenth anniversary review/update of fluoxetine concentrates on the past 5 years of its clinical application. The mechanism of action of fluoxetine; its metabolism; its efficacy in patients with various diagnostic subgroups of depression, patients with coincident medical disease, children and adolescents with depression, patients with eating disorders, and patients with obsessive-compulsive disorder (OCD); its long-term (maintenance) efficacy; its side effects and toxicity; and pharmacoeconomic considerations are reviewed. Pharmacotherapy is currently the only proven method for treating major depressive disorder that is applicable to all levels of severity of major depressive illness. Since its introduction 10 years ago, fluoxetine has been available to psychiatrists, primary care physicians, and other nonpsychiatric physicians as full-dose effective pharmacotherapy for patients with depression. Fluoxetine has been widely prescribed by physicians knowledgeable in pharmacology and in the treatment of depression because of its proven efficacy (ie, equal to that of tricyclic antidepressants [TCAs]), its ease of administration (with full therapeutic dosing usually starting from day 1), its generally benign side-effect profile, its remarkable safety in over-dose, and its proven effectiveness in the most common depressed patient population--anxious, agitated, depressed patients--as well as in patients with various subtypes and severities of depression. In more recent years it has also proved effective in the treatment of bulimia, an entity for which only limited or inadequate treatment options had been previously available. In OCD, fluoxetine, with its more acceptable side-effect profile and greater ease of dosing, presents a favorable alternative to previous drug therapy and is useful in treating both obsessions and compulsions. Fluoxetine is currently recognized among clinicians as efficacious in treating anxiety disorders and is being used successfully in special depressed populations such as patients with medical comorbidity, elderly patients, adolescents, and children. Rapid discontinuation or missed doses of short-half-life selective serotonin reuptake inhibitors, TCAs, and heterocyclic antidepressants are associated with withdrawal symptoms of a somatic and psychological nature, which cannot only be disruptive, but can also be suggestive of relapse or recurrence of depression. In striking contrast to these short-half-life antidepressants, fluoxetine is rarely associated with such sequelae on sudden discontinuation or missed doses. This preventive effect against withdrawal symptoms on discontinuation of fluoxetine is attributed to the unique extended half-life of this antidepressant. Current studies show that the overall increased effectiveness of fluoxetine in treating depression compensates for its higher cost, compared with older drugs, by reducing the need for physician contact because of increased compliance and less need of titration, and by reducing premature patient discontinuation, thereby yielding fewer relapses, less recurrence, and less reutilization of mental health services.