NEFAZODONE - A REVIEW OF ITS PHARMACOLOGY AND CLINICAL EFFICACY IN THE MANAGEMENT OF MAJOR DEPRESSION

Nefazodone hydrochloride is a phenylpiperazine antidepressant with a m echanism of action that is distinct from those of other currently avai lable drugs. It potently and selectively blocks postsynaptic serotonin (5-hydroxytryptamine; 5-HT) 5-HT2A receptors and moderately inhibits serotonin and noradrenaline (norepinephrine) reuptake. In short term c linical trials of 6 or 8 weeks' duration, nefazodone produced clinical improvements that were significantly greater than those with placebo and similar to those achieved with imipramine, and the selective serot onin reuptake inhibitors (SSRIs) fluoxetine, paroxetine and sertraline . The optimum therapeutic dosage of nefazodone appears to be between 3 00 and 600 mg/day. Limited long term data suggest that nefazodone is e ffective in preventing relapse of depression inpatients treated for up to 1 year. Analyses of pooled clinical trial results indicate that ne fazodone and imipramine produces similar and significant improvements on anxiety- and agitation-related rating scales compared with placebo inpatients with major depression. Short term tolerability data indicat e that nefazodone has a lower incidence of adverse anticholinergic, an tihistaminergic and adrenergic effects than imipramine. Compared with SSRIs, nefazodone causes fewer activating symptoms, adverse gastrointe stinal effects (nausea, diarrhoea, anorexia) and adverse effects on se xual function, but is associated with more dizziness dry mouth, consti pation, visual disturbances and confusion. Available data also suggest that nefazodone is not associated with abnormal weight gain, seizures , priapism or significant sleep disruption, and appears to be relative ly safe in overdosage. Nefazodone inhibits the cytochrome P450 3A4 iso enzyme and thus has the potential to interact with a number of drugs. Further long term and comparative studies will provide a more accurate assessment of the relative place of nefazodone in the management of m ajor depression. Nonetheless, available data suggest that nefazodone i s a worthwhile treatment alternative to tricyclic antidepressants and SSRls inpatients with major depression.