Nefazodone

Nefazodone (sold as Serzone, Nefadar) is a psychoactive drug and antidepressant marketed by Bristol-Myers Squibb. Its sale was discontinued in 2003 in some countries due to the rare incidence of hepatotoxicity (liver damage), which could lead to the need for a liver transplant, or even death. The incidence of severe liver damage is approximately 1 in every 250,000 to 300,000 patient-years. On May 20, 2004, Bristol-Myers Squibb discontinued the sale of Serzone in the United States and Canada. Several generic formulations of nefazodone are still available.

Pharmacology

Nefazodone acts primarily as a potent antagonist at the 5-HT₂ receptors (26 nM). It also has moderate affinity for the α₁-adrenergic receptor (48 nM) and 5-HT_1A receptor (80 nM), and very low affinity for the α₂-adrenergic receptor (640 nM) and D₂ receptor (910 nM). It acts as an antagonist at all of these sites. Nefazodone has low affinity for the serotonin (200 nM), norepinephrine (360 nM), and dopamine (360 nM) transporters as well, and therefore acts as a weak serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI). It has negligible affinity for the H₁ receptor (24,000 nM) or muscarinic acetylcholine receptors (11,000 nM), and accordingly lacks any antihistamine or anticholinergic side effects.

Dosing

Nefazodone doses for adults typically start at 50 mg twice daily uptitrated by 100 mg/day per week to a maximum of 600 mg (300 mg twice daily), according to Food and Drug Administration (FDA) regulations. Some patients with severe depression were treated with more than 600 mg/day. Most patients were treated with 300 mg–600 mg daily.

Side effects

Unlike most serotonin reuptake inhibitors, Nefazodone usually has no negative effects on libido or sexual functioning, and is actually sometimes used as an antidote to SSRI or SNRI induced impotence and anorgasmia in men. More serious side effects include an allergic reaction, fainting, or painful/prolonged erection. Less serious reactions of nefazodone include dizziness, lightheadedness, fatigue, upset stomach, insomnia; dry mouth; constipation; or blurred/abnormal vision.

Interactions

Nefazodone is a potent inhibitor of CYP3A4, an isozyme of the cytochrome P450 system, and may therefore interact adversely with many commonly-used medications that are metabolized by CYP3A4.

Advantages

Nefazodone's claimed advantages over other antidepressants include reduced possibility of disturbed sleep or sexual dysfunction, and ability to treat some patients who did not respond to other antidepressant drugs.

Nefazodone, though an antidepressant, may also be beneficial in the prophylaxis of migraines due to its antagonistic effects on the 5-HT2A and 5-HT2C receptors It has a more favorable side effect profile than amitriptyline, a tricyclic antidepressant commonly used for migraine prophylaxis.

Translation of "Nefazodone"

German: Nefazodon, Swedish: Nefazodon.