Clinical Information

Fluoxetine is a selective serotonin reuptake inhibitor approved for treatment of bulimia, obsessive-compulsive behavior, panic disorders, premenstrual dysphoria, and major depressive disorder, with a variety of off-label uses. Both fluoxetine and its major metabolite, norfluoxetine, are pharmacologically active and are reported together in this assay. Most individuals respond optimally when combined serum concentrations for both parent and metabolite are in the therapeutic range (120-500 ng/mL) at steady state. Due to the long half-life of the parent and metabolite (1-6 days), it may take several weeks for patients to reach steady-state concentrations. Fluoxetine is a potent inhibitor of the metabolic enzyme cytochrome P450 (CYP) 2D6, with lesser inhibitory effects on CYP2C19 and CYP3A. Therapy with fluoxetine is, therefore, subject to numerous drug interactions, which are compounded by wide interindividual variability in fluoxetine pharmacokinetics. Measurement of the drug is useful for managing comedications, dose or formulation changes, and in assessing compliance. Side effects are milder for fluoxetine than for older antidepressants, such as tricyclic antidepressants. The most common side effects of fluoxetine therapy include nausea, nervousness, anxiety, insomnia, and drowsiness. Anticholinergic and cardiovascular side effects are markedly reduced compared to tricyclic antidepressants. Fatalities from fluoxetine overdose are extremely rare.