Prediction of serotonergic treatment efficacy using age of onset and Type A/B typologies of alcoholism.
BACKGROUND
Previously, we reported that ondansetron was efficacious at treating early-onset (< or =25-years old) but not late-onset (> or =26-years old) alcoholics in a double-blind, randomized, placebo-controlled clinical trial (n = 321 enrolled patients, 271 of them randomized). Randomized participants underwent 11 weeks of treatment with ondansetron (1, 4, or 16 microg/kg twice daily; n = 67, 77, and 71, respectively) or identical placebo (n = 56), plus weekly standardized group cognitive behavioral therapy.


METHODS
For this study, we reanalyzed the original sample to determine whether the Type A/B typological classification predicts ondansetron treatment response. In this comparative analysis, k-means clustering was applied to 19 baseline measures of drinking behavior, psychopathology, and social functioning, similar to those used by Babor in the original typological derivation. A 2-factor solution described robustly 2 groups phenomenologically consistent with Type A/B classification. Subjects were subdivided into early- and late-onset alcoholics.


RESULTS
Seventy-two percent of Type B subjects had early-onset alcoholism (EOA); 67% of Type A subjects had late-onset alcoholism (LOA). The A/B typology better discriminated 2 clusters based upon baseline severity of alcoholism. There was a significant effect (p < 0.05) for Type B alcoholics to respond to ondansetron (4 microg/kg); however, Type A alcoholics receiving ondansetron showed no beneficial effect. Early-onset vs. late-onset classification predicted ondansetron response substantially better than Type A/B classification, which did not add to the prediction of treatment outcome. Further analyses showed that ondansetron was effective in the 33% of Type A alcoholics with EOA but ineffective in the 28% of Type B alcoholics with LOA.


CONCLUSIONS
Type A/B classification best discriminates alcoholic subtypes based upon baseline severity. Early- vs. late-onset classification is, however, a better predictor of response to ondansetron treatment because it might be more closely related to fundamental neurobiological processes associated with the underlying pathophysiology of alcoholism.
Roache
John D
JD
Department of Psychiatry, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, Mailstop 7792, San Antonio, Texas 78229, USA. roache@uthscsa.edu
Wang
Yanmei
Y
Ait-Daoud
Nassima
N
Johnson
Bankole A
BA
D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D000428:Alcohol Drinking / Q000523:psychology; D000437:Alcoholism / Q000145:classification* / Q000188:drug therapy* / Q000523:psychology; D000987:Antisocial Personality Disorder / Q000523:psychology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D017294:Ondansetron / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D018490:Serotonin Agents / Q000627:therapeutic use*; D012720:Severity of Illness Index; D012919:Social Behavior; D016896:Treatment Outcome
D018490:Serotonin Agents; D017294:Ondansetron