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Background . Dextromethorphan is a noncompetitive N-methyl D-aspartate receptor antagonist that is clinically feasible for relieving the opioid withdrawal symptoms. This study compares the efficacy of a combination therapy with dextromethorphan and clonidine to treatment with clonidine alone.  Methods and Materials . In this double-blind randomized clinical trial, patients were selected from inpatients of detox and rehabilitation ward of Razi Hospital, Tabriz, Iran. They were randomly allocated to two groups receiving either clonidine (0.4–1.2 mg/day) or clonidine and dextromethorphan (300 mg/day). Withdrawal symptoms were evaluated in the first day of admission and again 24, 48, and 72 hours later.  Results . Thirty male patients completed the trial in each group. Withdrawal symptoms began to decrease in the second day in patients receiving dextromethorphan and clonidine while patients receiving clonidine experienced the more severe symptoms in 72 hours. Analysis of variance of the symptom severity score revealed a significant group × time interaction ( F  = 14.25;  P  < 0.001), so that patients receiving dextromethorphan plus clonidine had milder symptoms during three days in all of the measurements compared to clonidine group.  Conclusion . Combination therapy of dextromethorphan and clonidine would result in milder opioid withdrawal symptoms compared to clonidine alone with a reduction beginning at the second day.

The Therapeutic Effect of Adding Dextromethorphan to Clonidine for Reducing Symptoms of Opioid Withdrawal: A Randomized Clinical Trial