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ABSTRACT
Nefazodone is an antidepressant medication which received approval from the Food and Drug Administration for treatment of major depressive disorder in 1994. This article summarizes the pharmacodynamics, pharmacokinetics, adverse effects, and drug interactions of nefazodone as well as its administration and dosing schedule. The potential efficacy of nefazodone in treating anxiety, premenstrual syndrome, chronic pain conditions, and sleep disturbances also is summarized. Nefazodone has a favorable side effects profile which makes it an attractive alternative option for patients who withdraw from treatment when they develop adverse effects to other available antidepressants.
Nefazodone (Serzone, Bristol-Myers Squibb Company) is an antidepressant medication which received Food and Drug Administration (FDA) approval in the United States in December 1994 (Hemrick-Luecke, Snoddy, & Fuller, 1994). Nefazodone is related structurally to trazodone (Desyrel) but is unrelated to the traditional tricyclic antidepressants (TCAs) and tetracyclics, the monoamine oxidase inhibitors (MAOIs), serotonin-specific (selective) reuptake inhibitors (SSRIs), and other available antidepressants (e.g., bupropion, venlafaxine, mirtazapine) (DeMeIIo, 1999; Nemeroff, 1994).
CHEMICAL STRUCTURE AND PHARMACODYNAMICS
Nefazodone hydrochloride is a phenylpiperazine. It blocks postsynaptic serotonergic 2A (5HT,A) receptors and to a lesser extent inhibits presynaptic serotonin reuptake (Eison, Eison, Torrente, Wright, & Yocca, 1990; Hemrick-Luecke et al., 1994). This dual serotonergic action distinguishes nefazodone from the SSRIs (Eison et al., 1990; Nemeroff, 1994). In addition, the predominant affinity for serotonergic modulation separates nefazodone from the TCAs and venlafaxine, which possess varying degrees of serotonergic and noradrenergic modulation (Nemeroff, 1994).
The mechanism of action of nefazodone is thought to be related to its postsynaptic serotonin receptor downregulation coupled with enhanced presynaptic serotonergic (5HT]A) neurotransmission (Eison et al., 1990; Hemrick-Luecke et al., 1994). Because of the inhibitory effects of 5HT, ? on 5HT1 ? receptor activity, nefazodone's 5HT,. blockade results in an enhancement of 5HT1 ? receptor activity (Eison et al., 1990; Fontaine, 1993). Nefazodone has no affinity for dopamine (D,), muscarinic, benzodiazepine, cholinergic, histamine, gammaaminobutyric, and calcium channel receptors (Eison et al., 1990). Therefore, it lacks significant anticholinergic and antihistamine side effects and is less likely to cause excessive sedation and weight gain (Fontaine, 1993).
Nefazodone does not inhibit monoamine oxidase and has a much lower affinity for alpha-adrenergic receptors than trazodone, which results in less potential for orthostatic hypotension and priapism (Eison et al., 1990)....