title: Cytochrome P450 2D6 and treatment of codeine dependence.
abstract: Oral opioid analgesics such as codeine are used extensively worldwide and are frequently misused. Codeine is a substrate of CYP2D6, a genetically polymorphic P450 enzyme, and is metabolized to the more potent drug morphine. CYP2D6 activity can be inhibited by fluoxetine, and the inhibition of morphine formation may help individuals reduce their use of codeine. Fourteen long-term 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 subjects 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.
authors.affiliation: Department of Psychiatry, Centre for Research in Women's Health, University of Toronto, Ontario, Canada. myroslava.romach@utoronto.ca
authors.forename: M K
authors.initials: MK
authors.lastname: Romach
authors.forename: S V
authors.initials: SV
authors.lastname: Otton
authors.forename: G
authors.initials: G
authors.lastname: Somer
authors.forename: R F
authors.initials: RF
authors.lastname: Tyndale
authors.forename: E M
authors.initials: EM
authors.lastname: Sellers
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000493:pharmacokinetics* / Q000652:urine; D000704:Analysis of Variance; D003061:Codeine / Q000493:pharmacokinetics* / Q000652:urine; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009293:Opioid-Related Disorders / Q000188:drug therapy* / Q000523:psychology; D010865:Pilot Projects; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*
chemical_list: D000701:Analgesics, Opioid; D003061:Codeine; D019389:Cytochrome P-450 CYP2D6; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors