Memantine as an add-on therapy in alcohol withdrawal syndrome

Abstract

Objective: NMDA receptor antagonists were found to be effective treating alcohol withdrawal syndrome, preventing seizures, and decreasing daily alcohol intake in preclinical studies. But there were only few studies on the efficacy of NMDA receptor antagonists in humans. In this current study, we evaluated the effects of memantine, an NMDA receptor antagonist on alcohol withdrawal syndrome. Methods: The study was planned as a prospective, randomized; doubleblind study. In total, 32 patients enrolled in study. 16 patients were randomized to benzodiazepine plus memantine group and 16 were randomized to benzodiazepine plus placebo group. Memantine was administered to patients as 10 mg/day in first week of study and 20 mg/day in second week of study. Severity of alcohol withdrawal was measured by Revised Clinical Institute Withdrawal Assessment for Alcohol scale (CIWA-AR). Mean Corpuscular Volume (MCV), Gama Glutamyl transferase (GGT), Carbohydrate Deficient Transferrine (CDT), and Alcohol Using Disorders Identity Test (AUDIT) tests were also administered to evaluate patients. CIWA-AR scores of the two groups were compared with Mann-Whitney U test at 1st, 4th, 7th, 10 th, and 15th days of treatment. P values were corrected for multiple comparisons. Results: Two groups were identical on age, sex, marital status, education and employment. There were also no differences in AUDIT, CDT, MCV, and GGT scores between two groups at the beginning of the study. Mean CIWA-AR score of the memantine group was 23.63±7.24 and mean CIWA-AR score of the placebo group was 22.94±7.47 at the beginning of the study. The difference between two groups was not statistically significant. CIWA-AR scores of the memantine group were 7.88±4,37, 2.44±2.03, 0.94±0.99, and 0.25±0.44 respectively on the 4th, 7th, 10th and 15th measurement days. CIWA-AR scores of the placebo group were 8.63±4,79, 4.19±2.10, 2.50±1.82, and 1.13±0.96 respectively on the 4th, 7th, 10th and 15th measurement days. Although the decline in CIWA-AR scores was higher in memantine group, there was no statistically significant difference between memantine and placebo group. Memantine group had better improvement in tremor and sweating subscales of CIWA-AR but this difference was not statistically significant. Discussion: Despite the previous results that were mentioning that memantine was effective in alcohol withdrawal syndrome, we could not find statistically significant difference between two groups. Although memantine was not superior to placebo in our setting, randomized placebo controlled studies with more subjects and no extra medication might be helpful for showing efficacy of memantine and other antiglutamatergic agents in alcohol withdrawal syndrome.