A double-blind, placebo-controlled trial assessing the efficacy of levetiracetam extended-release in very heavy drinking alcohol-dependent patients.
BACKGROUND
Despite advances in the development of medications to treat alcohol dependence, few medications have been approved by the U.S. Food and Drug Administration. The use of certain anticonvulsant medications has demonstrated potential efficacy in treating alcohol dependence. Previous research suggests that the anticonvulsant levetiracetam may be beneficial in an alcohol-dependent population of very heavy drinkers.


METHODS
In this double-blind, randomized, placebo-controlled clinical trial, 130 alcohol-dependent patients who reported very heavy drinking were recruited across 5 clinical sites. Patients received either levetiracetam extended-release (XR) or placebo and a Brief Behavioral Compliance Enhancement Treatment intervention. Levetiracetam XR was titrated during the first 4 weeks to 2,000 mg/d. This target dose was maintained during weeks 5 through 14 and was tapered during weeks 15 and 16.


RESULTS
No significant differences were detected between the levetiracetam XR and placebo groups in either the primary outcomes (percent heavy drinking days and percent subjects with no heavy drinking days) or in other secondary drinking outcomes. Treatment groups did not differ on a number of nondrinking outcomes, including depression, anxiety, mood, and quality of life. The only difference observed was in alcohol-related consequences. The levetiracetam XR treatment group showed significantly fewer consequences than did the placebo group during the maintenance period (p = 0.02). Levetiracetam XR was well tolerated, with fatigue being the only significantly elevated adverse event, compared with placebo (53% vs. 24%, respectively; p = 0.001).


CONCLUSIONS
This multisite clinical trial showed no efficacy for levetiracetam XR compared with placebo in reducing alcohol consumption in heavy drinking alcohol-dependent patients.
Division of Treatment and Recovery Research, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, USA. jfertig@mail.nih.gov
Joanne B
JB
Fertig
Megan L
ML
Ryan
Daniel E
DE
Falk
Raye Z
RZ
Litten
Margaret E
ME
Mattson
Janet
J
Ransom
William J
WJ
Rickman
Charles
C
Scott
Domenic
D
Ciraulo
Alan I
AI
Green
Nassima A
NA
Tiouririne
Bankole
B
Johnson
Helen
H
Pettinati
Eric C
EC
Strain
Eric
E
Devine
Mary F
MF
Brunette
Kyle
K
Kampman
David
D
A Tompkins
Robert
R
Stout
D000328:Adult; D000339:Affect / Q000187:drug effects; D000368:Aged; D000437:Alcoholism / Q000188:drug therapy* / Q000523:psychology; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001007:Anxiety / Q000523:psychology; D001944:Breath Tests; D003692:Delayed-Action Preparations; D003863:Depression / Q000523:psychology; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000077287:Levetiracetam; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010349:Patient Compliance; D010889:Piracetam / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011788:Quality of Life; D012959:Socioeconomic Factors; D016896:Treatment Outcome
D000927:Anticonvulsants; D003692:Delayed-Action Preparations; D000077287:Levetiracetam; D010889:Piracetam