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.
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
John D
JD
Roache
Yanmei
Y
Wang
Nassima
N
Ait-Daoud
Bankole A
BA
Johnson
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