A pilot double-blind treatment trial of memantine for alcohol dependence.
BACKGROUND
There is growing evidence that N-methyl-d-aspartate (NMDA) receptor antagonists may have potential for the treatment of alcohol disorders. Memantine is a selective noncompetitive NMDA receptor antagonist that has been shown to decrease alcohol craving in moderate drinkers. This 16-week double-blind outpatient pilot clinical trial determined if memantine was more effective than placebo at reducing alcohol use in actively drinking alcohol-dependent patients.


METHODS
Forty-four treatment-seeking alcohol-dependent individuals were enrolled, with 34 patients stratified to either the memantine group (n=19; maximum dose of 40 mg/d) or the placebo (PBO; n=15) group. The primary outcome measures were related to alcohol use (average drinks per day, average drinks per drinking day, percentage of heavy drinking days, and percentage of days abstinent) based on the timeline follow-back (TLFB). Secondary outcome measures included the Obsessive Compulsive Drinking Scale, Clinical Global Impression ratings, and gamma-glutamyltransferase (GGT), a biomarker of recent alcohol use. To enhance retention, patients received voucher incentives for clinic attendance.


RESULTS
Of those randomized, approximately 80% (27) completed the entire 16-week trial. Longitudinal analysis of drinks per day and drinks per drinking day showed a significant reduction in alcohol use, but no difference between the 2 groups. Further, the percentage of heavy drinking days indicated that both groups showed a significant decrease in drinking behavior, but there was significant treatment effect in favor of the PBO group. Similarly, for the percentage of days abstinent, the PBO group achieved a significantly greater percentage of days abstinent at a faster rate than the memantine group. Lastly, the memantine group reported a greater number of side effects compared with the PBO group, such that 26% of patients had their drug dose decreased or discontinued due to memantine-related side effects.


CONCLUSIONS
The results of this double-blind placebo-controlled pilot trial do not support the use of memantine for the treatment of actively drinking alcohol-dependent patients. However, voucher incentives did facilitate retention.
Evans
Suzette M
SM
New York State Psychiatric Institute, New York, New York 10032, USA. se18@columbia.edu
Levin
Frances R
FR
Brooks
Daniel J
DJ
Garawi
Fatima
F
D000328:Adult; D000339:Affect / Q000187:drug effects; D000437:Alcoholism / Q000188:drug therapy* / Q000523:psychology; D003627:Data Interpretation, Statistical; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008111:Liver Function Tests; D008297:Male; D008559:Memantine / Q000009:adverse effects / Q000627:therapeutic use*; D001523:Mental Disorders / Q000150:complications / Q000523:psychology; D008875:Middle Aged; D010349:Patient Compliance; D010865:Pilot Projects; D011569:Psychiatric Status Rating Scales; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012959:Socioeconomic Factors; D013695:Temperance; D016896:Treatment Outcome
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D008559:Memantine