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Editor, – The 'New drugs' information on nefazodone (Aust Prescr 1997;20:77-8) was based on the material available in early 1997. As the views are 'regarded as tentative', Bristol-Myers Squibb Pharmaceuticals appreciates the opportunity to update the information.
Nefazodone's primary action is potent post-synaptic 5-HT2 antagonism, although it does have weak serotonin reuptake inhibition, hence its designation as a serotonin antagonist and reuptake inhibitor.1 Data available indicate that food does not alter nefazodone's bioavailability.2 Treatment doses may be started at less than 100 mg twice daily (50 mg twice daily) in most people, particularly the elderly. This tends to reduce the occurrence of adverse effects; although if they do occur, they usually tail off in the first 6 weeks of therapy. The gradual increase to the median long-term dose of 400 mg/day will also reduce or prevent emergence of adverse effects.3
The anxiolytic effect and restoration of sleep quality often commences in the first week of therapy, with depression lifting usually between 10-21 days, even if therapy has been initiated slowly. Clinical trial and pooled data comparing nefazodone to SSRIs, imipramine and placebo have indicated efficacy in depression and prevention of relapse up to 12 months.3,4
M.D. Anderson-Hunt
Medical Practitioner and
Medical Affairs Manager (Neurosciences)
Bristol-Myers Squibb Pharmaceuticals
Noble Park, Vic.
The Editor comments:
Observant readers will notice that some of the new information provided is at variance with the approved product information (PI). For example, the PI informs us that food delays absorption and decreases systemic exposure by 20%. Reference 2 confirms this finding. The study found that food significantly reduces the area under the curve for nefazodone by 18%, although the rate of absorption was not significantly altered. In practice, these effects may not be clinically significant.
In the PI, the recommended starting dose for most patients is 100 mg twice daily and 50 mg twice daily for the elderly. Reference 3 suggests that some adverse effects will resolve with time. It does not say that adverse events are reduced by starting at a lower dose, although clinical practice suggests that this may be the case. Starting at a low dose and increasing too slowly may delay the response to treatment. (Consideration should be given to discontinuing nefazodone if no response occurs after 4-6 weeks of treatment).
Reference 4 is a review of long-term treatment with antidepressants, not specifically nefazodone. Part of the review discusses the 139 patients who continued to take nefazodone for a year after completing studies of acute efficacy. Their rate of relapse was 9% compared with 8% in patients taking imipramine and 25% in those given placebo. Approximately 11% of patients will discontinue long-term use of nefazodone because of adverse effects, compared with 16% for tricyclic antidepressants and 9% for placebo.
