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.