title: Lack of efficacy of dextromethorphan in managing alcohol withdrawal: a preliminary report of a randomized, double-blind, placebo-controlled trial.
abstract: Alcohol withdrawal syndrome is associated with increased central N-methyl-D-aspartate (NMDA) glutamate transmission. Medications that reduce glutamate release or block NMDA overactivation have shown efficacy for treating alcohol withdrawal syndrome. Dextromethorphan (DXM), a widely used antitussive drug, is a low-affinity, noncompetitive NMDA antagonist with potential neuroprotective properties. This study, using a randomized, double-blind, placebo-controlled study design, examined the benefit of DXM in the management of acute alcohol withdrawal. Alcohol-dependent patients admitted for detoxification treatment and experiencing moderate alcohol withdrawal, as measured by a score greater than 10 on the revised Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar), were randomly assigned to receive either DXM 360 mg/d or an identical placebo for 7 days in a double-blind manner. All subjects received a concurrent dose of lorazepam 2 mg along with the initial administration of DXM or placebo and were given additional lorazepam (1 mg) as a rescue medication according to the symptom-triggered detoxification protocol. Outcome measures consisted of the mean total dose of lorazepam received, the sequential scores on the CIWA-Ar, and craving assessed by the Obsessive-Compulsive Drinking Scale. Forty subjects completed the study, 18 in the DXM group and 22 in the placebo group. We found that compared with placebo, DXM use was not associated with lower lorazepam doses to control alcohol withdrawal symptoms. The progression in CIWA-Ar and Obsessive-Compulsive Drinking Scale scores was also comparable between the 2 groups. Our preliminary results do not support the efficacy of high-dose DXM in reducing the need of benzodiazepines to treat withdrawal symptoms in alcohol-dependent patients.
authors.affiliation: From the *Department of Psychiatry, Taipei City Psychiatric Center, Taipei City Hospital; †Department of Psychiatry, School of Medicine, Taipei Medical University; ‡Department of Psychiatry, Taipei Medical University-Wan-Fang Hospital; and §Department of Psychology, National Chengchi University, Taipei, Taiwan.
authors.forename: Ming-Chyi
authors.initials: MC
authors.lastname: Huang
authors.forename: Chun-Hsin
authors.initials: CH
authors.lastname: Chen
authors.forename: Chun-Hung
authors.initials: CH
authors.lastname: Pan
authors.forename: Shih-Ku
authors.initials: SK
authors.lastname: Lin
mesh_terms: D000328:Adult; D064829:Alcohol Abstinence; D000428:Alcohol Drinking / Q000517:prevention & control* / Q000523:psychology; D000437:Alcoholism / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003915:Dextromethorphan / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D018691:Excitatory Amino Acid Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008140:Lorazepam / Q000627:therapeutic use; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000175:diagnosis / Q000378:metabolism / Q000523:psychology / Q000628:therapy*; D013624:Taiwan; D013997:Time Factors; D017211:Treatment Failure
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D003915:Dextromethorphan; D008140:Lorazepam