The safety profile of nefazodone

Abstract

Comprehensive review of safety data from approximately 3500 patients who received nefazodone in premarketing clinical trials demonstrates the drug to be very well tolerated, with a favorable side effect profile compared with other antidepressant drugs. Nefazodone treatment was associated with fewer side effects than were the control drugs. The incidence of side effects was generally low, and treatment discontinuations for adverse effects were less frequent with nefazodone than with imipramine and comparable with fluoxetine. No late-appearing side effects or toxicity emerged during the long-term treatment (1 year or longer) of several hundred patients. There were no drug-related fatalities and no evidence that nefazodone caused specific organ toxicity, although some cardiovascular side effects were noted (e.g., asymptomatic reduced systolic blood pressure, asymptomatic sinus bradycardia). Experience in 488 elderly patients treated with nefazodone yielded no evidence of increased susceptibility of older patients to nefazodone-associated adverse experiences, including those pertaining to the cardiovascular system. However, treatment should be initiated at a reduced dose in elderly patients because of reduced hepatic clearance of nefazodone in this age group. Final dose range may be similar in healthy younger and older patients. Although nefazodone may interact with some other medications (e.g., increases at steady state in AUC: alprazolam, twofold; triazolam, fourfold), drug-drug interactions involving patients have been clinically minor. On the basis of the inhibition of cytochrome P450 3A4 isoenzyme by nefazodone in vitro, coadministration of terfenadine or astemizole with nefazodone is contraindicated because nefazodone can increase the plasma levels of these two drugs. Extensive clinical experience provides substantial evidence that nefazodone is an extremely safe and effective treatment for depression, with important advantages over existing therapies. Therapeutic benefits include a low incidence of clinically troublesome side effects and lack of unwanted psychic activation, sexual dysfunction, weight change, and the cardiotoxicity of other antidepressants.