THE SAFETY PROFILE OF NEFAZODONE

Comprehensive review of safety data from approximately 3500 patients w ho received nefazodone in premarketing clinical trials demonstrates th e drug to be very well tolerated, with a favorable side effect profile compared with other antidepressant drugs. Nefazodone treatment was as sociated with fewer side effects than were the control drugs. The inci dence of side effects was generally low, and treatment discontinuation s for adverse effects were less frequent with nefazodone than with imi pramine 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 an d no evidence that nefazodone caused specific organ toxicity, although some cardiovascular side effects were noted (e.g., asymptomatic reduc ed systolic blood pressure, asymptomatic sinus bradycardia). Experienc e 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 e lderly 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 medi cations (e.g., increases at steady state in AUC: alprazolam, twofold; triazolam, four-fold), drug-drug interactions involving patients have been clinically minor. On the basis of the inhibition of cytochrome P4 50 3A4 isoenzyme by nefazodone in vitro, coadministration of terfenadi ne 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 extrem ely safe and effective treatment for depression, with important advant ages over existing therapies. Therapeutic benefits include a low incid ence of clinically troublesome side effects and lack of unwanted psych ic activation, sexual dysfunction, weight change, and the cardiotoxici ty of other antidepressants.