Nefazodone hydrochloride

Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Serzone (Bristol-Myers Squibb)
100 mg, 200 mg and 300 mg tablets

Indication: major depression
This drug inhibits the reuptake of serotonin, but its structure is different to that of the selective serotonin reuptake inhibitors (SSRIs).

Nefazodone is completely absorbed from the gut, but food reduces its bioavailability. Most of the drug is eliminated by a complex metabolism. Some of the metabolites are active and one of these has a half-life of up to 9 hours compared with the 2-4 hours of the parent compound. As the metabolites are excreted in the urine and the faeces, extra caution is needed if the drug is prescribed to a patient with renal or hepatic failure. There is a potential for interaction with drugs metabolised by cytochrome P450 3A4 as this isoenzyme is inhibited by nefazodone. Examples of these drugs include triazolam, alprazolam, calcium channel antagonists, terfenadine, astemizole, ketoconazole and erythromycin.

Treatment starts with 100 mg twice a day. It is increased by 100 mg or 200 mg at weekly intervals depending on the patient's response. Although it may take several weeks for a depressed patient to respond to therapy, the effectiveness of nefazodone has not been systematically evaluated beyond
6-8 weeks.

In short-term clinical trials, nefazodone has comparable efficacy to imipramine. Its efficacy is also said to be similar to that of the SSRIs.
While the drug may be ineffective if the dose is increased too slowly, a rapid increase can cause adverse effects. The adverse effects of nefazodone include nausea, dry mouth, constipation, somnolence, dizziness and postural hypotension.

On currently available short-term data, it appears that nefazodone has no obvious advantages over SSRIs and is unlikely to be a first-line drug for depression.