Possible interaction of zopiclone and nefazodone

OBJECTIVE: To describe a case in which concurrent treatment with nefazodone was associated with an elevation in the plasma concentration of zopiclone, possibly resulting in enhanced hypnosedative efficacy. CASE REPORT: An 86-year-old white woman was treated with nefazodone for dep ression. Zopiclone was also introduced for the management of insomnia, but she subsequently experienced morning drowsiness. The concentration of zopic lone in plasma was subsequently measured eight hours after administration o n two occasions, during nefazodone therapy and after its withdrawal. After discontinuation of nefazodone, the plasma concentration of the S-enantiomer of zopiclone decreased from 107 to 16.9 ng/mL, while the R-enantiomer plas ma concentration decreased from 20.6 to 1.45 ng/mL. DISCUSSION: Nefazodone is a relatively potent inhibitor of CYP3A4, a hepati c isoenzyme thought to play a major role in the metabolic elimination of zo piclone. The substantial decrease in the plasma zopiclone concentrations ob served after withdrawal of nefazodone likely reflects a drug interaction. D espite the normally short elimination half-life of zopiclone, the residual sedation initially observed in this case suggests that the interaction may have clinical significance. CONCLUSIONS: The features observed in this case suggest the possibility of a drug-drug interaction between nefazodone and zopiclone. Further prospecti ve investigation is required to elucidate the nature and magnitude of this effect.