|
|
New developments in alcohol dependence treatments |
The aversive agent disulfiram was for a long time the only drug used to treat alcohol dependence. More recently the use of naltrexone and acamprosate have increased interest in the treatment of alcohol dependence.
The study of ondansetron is a direct outgrowth of an ambitious medications development program. This study shows a differential effect on alcohol consumption of the selective 5-HT3 (serotonin) antagonist as a function of age of alcoholism onset. This underscores the clinical relevance of a growing literature on the biological basis of alcohol dependence and its relationship to clinical subtypes. Second, the study exemplifies a potential role in alcoholism treatment for a medication with a well-defined mechanism of action, reinforcing the rational effort to identify medications to treat the disorder.
Consistent with a literature review supporting a role for serotonergic neurotransmission in the pathophysiology of alcohol dependence, particularly among patients with early onset of the disorder (ie. at age 25 years or younger), Johnson et al found a selective beneficial effect of ondansetron in this subgroup. Specifically, they found that a dosage of 4 ug/kg twice per day, ondansetron was superior to placebo on the proportion of days abstinent (an increase of nearly 40% over placebo) and on the intensity of alcohol intake (a decrease of more than 39%) among the study patients with early-onset alcoholism. The effects of carbohydrate-deficient transferrin, an objective measure of alcohol consumption, validated these findings.
Early onset alcoholism is characterised by a greater familial loading of alcoholism, a severe progression of the disorder, and a greater severity of comorbid psychiatric disorders, particularly antisocial personality disorder. Managing the care of such patients can be difficult for the GP. Based on these findings, ondansetron could be used to treat patients with early onset alcoholism, whereas a selective serotonin reuptake inhibitor might be used in patients with low-risk or low-severity alcohol abuse.
Large-scale family studies of alcohol dependence have identified genetic loci that are linked to the disorder in humans, and the process of fine mapping these genomic regions is underway. Candidate gene studies in alcohol dependence, other than those involving alcohol-metabolising enzymes, have yielded equivocal findings. However, the sequencing of the human genome and the push for its annotation will provide continued impetus to identify genes that contribute to alcoholism (and perhaps other forms of addiction) risk and pharmacological response.
Gareth Daniels is the D&A project officer for the Northern Rivers and Tweed Valley divisions of general practice, based in Lismore, NSW, Australia.
|
|
|
|
