title: 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.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT 06492, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: Robinson
authors.forename: D L
authors.initials: DL
authors.lastname: Roberts
authors.forename: J M
authors.initials: JM
authors.lastname: Smith
authors.forename: J C
authors.initials: JC
authors.lastname: Stringfellow
authors.forename: S B
authors.initials: SB
authors.lastname: Kaplita
authors.forename: J A
authors.initials: JA
authors.lastname: Seminara
authors.forename: R N
authors.initials: RN
authors.lastname: Marcus
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects* / Q000627:therapeutic use; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects; D002986:Clinical Trials as Topic; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects; D003866:Depressive Disorder / Q000188:drug therapy / Q000523:psychology; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D005473:Fluoxetine / Q000009:adverse effects; D006801:Humans; D007099:Imipramine / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000187:drug effects; D010879:Piperazines; D010919:Placebos; D020018:Sexual Dysfunctions, Psychological / Q000139:chemically induced; D016896:Treatment Outcome; D014230:Triazoles / Q000009:adverse effects* / Q000627:therapeutic use; D015430:Weight Gain
chemical_list: D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D010879:Piperazines; D010919:Placebos; D014230:Triazoles; D005473:Fluoxetine; C051752:nefazodone; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; D007099:Imipramine