Medications Acting on the Serotonergic System for the Treatment of Alcohol Dependent Patients

George      A. Kenna

Abstract

Research suggests that alcoholics show comparatively lower levels of serotonin (5-HT) than non-alcoholics. Medications aimed at increasing synaptic 5-HT have long been studied as potential treatments for alcoholism. Studies with selective serotonin reuptake inhibitors (SSRI) in a heterogeneous population of non-depressed alcoholics have produced inconsistent results. Further exploration involved whether or not treatment of co-morbid alcoholism and depression was a more practical approach. However, even in the presence of co-occurring depression, antidepressants in general lack the power to demonstrate a significant reduction of alcohol use among alcohol dependent patients with carefully diagnosed major depression. Further statistical analysis has also determined that perhaps genotypic and phenotypic variations differ for persons with alcohol dependence including those with or without comorbid alcohol dependence and depression suggesting important subgroups might respond differently to treatments. Clinical trials have also used the anxiolytic buspirone, a 5-HT1A partial agonist, as many alcoholics suffer from anxiety. When controlling for baseline anxiety, buspirone was no more effective than placebo for alcoholic patients. Another serotonergic drug, ritanserin, did not demonstrate effectiveness in relapse prevention in alcohol dependence. However, research on the use of the 5-HT3 antagonist ondansetron for alcohol dependence continues to provide promising results, particularly for patients with early onset alcoholism. As demonstrated by the studies with serotonergics, responses based on individual variables suggest that alcoholics may respond differentially based on various serotonin 5-HT subtypes. Of course, future studies need to further delineate and confirm the differences between these alcoholic subtypes.

Keywords: Serotonin, alcohol dependence, alcoholism, SSRI, fluoxetine, sertraline, ondansetron, busiprone, ritanserin