Ondansetron reduces the craving of biologically predisposed alcoholics.
BACKGROUND
Early onset alcoholics (EOA) differ from late onset alcoholics (LOA) by having greater serotonergic abnormality, familial history, and a range of antisocial behaviors. Previously, we showed that ondansetron, a selective 5-HT3 antagonist, effectively treated EOA. Proximate motivational drives such as craving could have determined drinking behavior. We therefore investigated whether ondansetron treatment would reduce alcohol craving significantly among EOA.


OBJECTIVE
We tested the hypothesis that the craving outcomes of EOA, compared with LOA, would be differentially improved by ondansetron. We also tested the prediction that craving would be significantly correlated with drinking behavior.


METHODS
We studied a cohort of 253 out of 321 enrolled alcohol dependent subjects. These 253 subjects were entered into a 1-week lead-in single-blind placebo period followed by 11 weeks of double-blind outpatient treatment. Study design was a 2 (EOA versus LOA)x 4 medication dose (placebo, or ondansetron 1, 4, or 16 microg/kg b.i.d)x 13 (visits) factorial analysis of variance. Craving was measured at each visit using seven visual analogue scales. Subjects received 12 weekly sessions of standardized group cognitive behavioral therapy.


RESULTS
Data reduction by factor analysis of the visual analog scale items yielded one dimension, overall craving. Ondansetron 4 microg/kg b.i.d. reduced overall craving significantly among EOA. In contrast, ondansetron (1 microg/kg b.i.d.) increased craving significantly in LOA. Decreased overall craving was positively correlated with reduced drinking and negatively associated with increased abstinence.


CONCLUSIONS
Compared with placebo, ondansetron (4 microg/kg b.i.d.) was associated with significant reductions in overall craving in EOA but not LOA, presumably by ameliorating serotonergic abnormality.
Johnson
Bankole A
BA
Department of Psychiatry, University of Texas, Health Science Center at San Antonio, 7703 Floyd Curl Drive, Mail Stop 7792, San Antonio, TX 78229-3900, USA. bjohnson@uthscsa.edu
Roache
John D
JD
Ait-Daoud
Nassima
N
Zanca
Nursen A
NA
Velazquez
Madeline
M
D000328:Adult; D000437:Alcoholism / Q000188:drug therapy* / Q000235:genetics* / Q000523:psychology; D000704:Analysis of Variance; D016739:Behavior, Addictive / Q000188:drug therapy* / Q000235:genetics / Q000523:psychology; D016009:Chi-Square Distribution; D004311:Double-Blind Method; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D017294:Ondansetron / Q000627:therapeutic use*; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016037:Single-Blind Method
D012702:Serotonin Antagonists; D017294:Ondansetron