Drug is last call for some early-onset alcoholism

Ondasetron helps some early-onset alcoholics stop drinking, according to a professor of psychiatry and pharmacology at the University of Texas, San Antonio.

In a randomized, placebo-controlled study of 321 alcoholics, ondasetron, a 5-HT3 antagonist, increased abstinence in earl-onset alcoholics by 40 percent and reduce the intensity of drinking in this subgroup by 39 percent over late-onset alcoholics and those not treated with ondasetron, as reported at the 23rd Congress of the Collegium Internationale Psychopharmacologicum. Ondasetron can be given to alcoholics while they are still drinking, providing help early in the treatment cycle. Onset of alcoholism before age 25 is a clinical subtype in which genetically pre-disposed patients have a strong family history of alcoholism, increased propensity for antisocial behaviors, and a more stable and severe disease state than those with late onset alcoholism. Early-onset alcoholism account for approximately one quarter of all alcoholics and is considered the most difficult to treat. The 12-week dose-ranging trial showed that ondasetron – marketed as the antinausea drug Zofran for chemotherapy patients – in concert with cognitive – behavioral therapy had a positive therapeutic effect only among the early-onset alcoholics. A dosage of 4 ug/kg two times per day. The drug appears to minimize alcohol cravings by correcting an underlying diequilibrium in the serotonergic brain system.

A significant reduction of plasma carbohydrate-deficient transferin, a bio-chemical market, corroborated the self-reported drinking outcomes. The investigators used platelet analyses to identify variations in serotonin transporter functionality among the different alcoholic subgroups. The results validated the hypothesis that different subtypes of alcoholism are associated with specific serotonergic behavior and may have unique treatment responses to pharmacologic agents. Serotonin has long been implicated in alcoholic-drinking behavior, especially in regard to the serotonin-3 receptor and its effect on dopamine. In alcoholics, it has been hypothesized that reduced serotonergic function results in hightened sensitivity of the serotonin-3 receptor. However, selective serotonin reuptake inhibitors have been used with only limited success to decrease the resultant alcohol-induced dopamine release and the associated alcoholic-drinking behavior. The new study results indicate that early-onset alcoholism differs from late-onset alcoholism in its underlying chemical mechanism. It is not caused by a singular serotonergic deficiency, but rather, is the result of a complex chemical interaction among the serotonin, glutamate, and opioid systems in the brain.

In biologic alcoholics, ondasetron appears to be more effective than therapies involving serotonin reuptake inhibition because it targets and alters specific neurotransmitters associated with this alcoholic subtype. The ability to identify, target, and alter selected neurotransmitters offers significant hope for developing new therapies for all types of alcoholism. Because they have been able to identify the basis of what type of serotonergic agent works as a treatment for early-onset alcoholism and study results showed an opposite serotonergic response in late-onset alcoholics, it is reasonable to predict that nonbiologic alcoholism would benefit from treatment with serotonergic agents with perhaps a functionally opposite effect to ondasetron. Genetic testing and brain imaging will in the near future allow determination of the appropriate serotonergic agent for specific types of alcoholics. Our goal is to identify the exact types of genes involved in alcoholic subtypes. If our ongoing studies are successful, we may have a useful marker for understanding specific treatment responsiveness.