Cytochrome P450 2D6 and treatment of codeine dependence

Oral opioid analgesics such as codeine are used extensively worldwide and a re frequently misused. Codeine is a substrate of CYP2D6, a genetically poly morphic P450 enzyme, and is metabolized to the more potent drug morphine. C YP2D6 activity can be inhibited by fluoxetine, and the inhibition of morphi ne formation may help individuals reduce their use of codeine, Fourteen lon gterm users of oral opiates (principally codeine) were assessed for an open -label pilot treatment study of fluoxetine 20 mg/day combined with a brief behavioral intervention and structured tapering of the opiate. Eight subjec ts entered and completed the 8-week treatment. Opiate use decreased by 30% to 100% of baseline use (p < 0.0001) in parallel with a decrease in CYP2D6 activity. Fluoxetine may have a role in the treatment of opiate dependence by decreasing opiate reinforcing properties.