title: Dextromethorphan and quinidine combination for heroin detoxification.
abstract: Dextromethorphan (DM) is a low-affinity, non-competitive NMDA receptor antagonist that has shown promise in preclinical and preliminary clinical studies for the reduction of opioid withdrawal symptoms, but when used at higher doses, it is associated with deleterious side effects attributed to its metabolite, dextrorphan. A clinical trial was therefore conducted to test the withdrawal-suppressant effect of a combination of dextromethorphan with quinidine (DM/Q). Quinidine inhibits the metabolism of dextromethorphan, reducing dextrorphan levels. Opioid-dependent patients were admitted to an inpatient unit, stabilized for three days on morphine (25 mg, sc, every six hours), and randomly assigned on day 2 to DM/Q (30 mg/30 mg, twice a day) (n = 22) or matching placebo (n = 9) prior to the discontinuation of morphine on day 4. Withdrawal symptoms, measured with the Modified Himmelsbach Opioid Withdrawal Scale (MHOWS), increased significantly on days 4 and 5 (Z = 3.70, p = .0002), and by day 6, 90% of the sample (28/31) had dropped out of the study. There were no differences between treatment groups on either outcome measure. The combination of dextromethorphan and quinidine appears ineffective as a primary treatment for opioid withdrawal. Future studies should examine dextromethorphan as an adjunct to other anti-withdrawal medications and focus more on the relationship between dextrorphan levels and withdrawal suppression.
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians & Surgeons, New York, New York, USA.
authors.forename: Evaristo
authors.initials: E
authors.lastname: Akerele
authors.forename: Adam
authors.initials: A
authors.lastname: Bisaga
authors.forename: Maria A
authors.initials: MA
authors.lastname: Sullivan
authors.forename: Fatima
authors.initials: F
authors.lastname: Garawi
authors.forename: Sandra D
authors.initials: SD
authors.lastname: Comer
authors.forename: Anil A
authors.initials: AA
authors.lastname: Thomas
authors.forename: Edward V
authors.initials: EV
authors.lastname: Nunes
authors.forename: Herbert D
authors.initials: HD
authors.lastname: Kleber
mesh_terms: D000328:Adult; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D003915:Dextromethorphan / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D018691:Excitatory Amino Acid Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D003932:Heroin / Q000633:toxicity*; D006556:Heroin Dependence / Q000534:rehabilitation*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D010352:Patient Dropouts / Q000523:psychology / Q000706:statistics & numerical data; D011802:Quinidine / Q000009:adverse effects / Q000627:therapeutic use*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013375:Substance Withdrawal Syndrome / Q000175:diagnosis / Q000523:psychology / Q000534:rehabilitation*
chemical_list: D065690:Cytochrome P-450 CYP2D6 Inhibitors; D018691:Excitatory Amino Acid Antagonists; D018727:Muscarinic Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D003932:Heroin; D003915:Dextromethorphan; D011802:Quinidine