Section 3.2.1.3

NEFAZODONE

General Description

Nefazodone (Serzone) is a phenylpiperazine analogue of trazodone (see entry for trazodone).

Indications for Medication

Nefazodone is indicated in the treatment of depression.

Clinical Guidelines

It is recommended that treatment begin at 100 mg twice a day. For some patients dosages as low as 50 mg twice a day may be effective. After one week the dosage may be increased since tolerance to adverse effects develops rapidly. The optimal therapeutic range is between 300 and 500 mg a day administered in two equally divided dosages. The maximum therapeutic dose is 600 mg a day.

In the elderly the starting dose is 100 mg a day given in two equally divided doses. The therapeutic dosage range is between 200 and 400 mg a day, although the final target dose may be similar in healthy younger and older patients.

Adverse Effects

The incidence of dry mouth, nausea, drowsiness, dizziness, constipation, asthenia, and postural hypotension range from 25 to 40 percent in patients treated with 300 to 600 mg of nefazodone a day, respectively. There was a low frequency of insomnia, agitation, anxiety and tremor. Sexual side effects were comparable to placebo. Nefazodone may increase REM sleep, an effect unlike any other antidepressant currently in use.

Drug-Drug Interactions

Because nefazodone is an inhibitor of both serotonin and norepinephrine reuptake, it is recommended that nefazodone not be used in combination with an MAOI, or within 14 days of disconituing treatment with an MAOI. At least one week should be allowed after stopping nefazodone before starting an MAOI. Severe reactions have been reported when MAOIs have been combined with serotonin-specific reuptake inhibitors?please review the PDR for additional information.

Nefazodone strongly inhibits Cytochrome P450 3A4, a trait in common with many SSRIs. Drugs metabolized by CYP3A4 include alprazolam (Xanax), triazolam (Halcion), midazolam (Versed), carbamazepine (Tegretol), sertraline (Zoloft), TCAs, calcium channel blockers, cyclosporine, erythromycin, steroids, quinidine, and lidocaine.

Alprazolam or triazolam coadministered with nefazodone should be given in reduced dosage, but there is no change in the pharmacokinetics of nefazodone.

The coadministration of astemizole (Hismanal) with nefazodone is contraindicated because of QT prolongation and the risk of torsade de pointes.

Digoxin levels may increase during coadministration with nefazodone, and should be monitored.

Propranolol levels may decrease with coadministration, but no change in initial dose of either drug is necessary.

The consent form for this medication is "Antidepressants (SSRI's & Dopaminergic Acting Medications)."