Serotonergic aspects on high consumption of alcohol in humans. Experimental and clinical studies

Sammanfattning: In animal studies an association between alcohol intake and central serotonergic function has been demonstrated. There are also evidence for altered serotonergic neurotransmission in subgroups of alcohol-dependent subjects.The aim of the thesis was to investigate the effect of SSRIs (selective serotonin reuptake inhibitors) on alcohol intake, in relation to biological markers for alcoholism, in men with long-term high alcohol consumption but without social, psychiatric or somatic complications due to their alcohol intake. The subjects were approximately 50 years old, had a history of daily alcohol consumption of about 100 g since 10 years. Despite that 70% fulfilled DSM-IV criteria for alcohol dependence only 30% had earlier experiences from health care or voluntary organizations due to their alcohol problem. They had few social, medical or other complications related to their alcohol intake. They may therefore represent a group of patients not well known in traditional treatment programs.Compared to a norm group they had lower levels of mental well-being but no anxious or depressive symptoms as assessed by rating scales. The lower moods were most marked in the group of subjects who discontinued the study. Reduction in alcohol consumption of about 60% did not affect moods. Treatment with an SSRI did not increase moods although a trend was observed. On the other hand, participating in the study program increased mood levels to that of a norm group.The subjects were found to have signs of impaired central serotonergic neurotransmission as assessed by the fenfluramine challenge test, but platelet monoamine oxidase B (MAO-B) activity was of the same magnitude as in a reference group. The presence of the dopamine receptor D2 (DRD2) A1 allele was about 20%, as could be expected from the prevalence in the general population. Subjects with the DRD2 A1 allele had lower platelet MAO-B activity than those with the DRD2 A2/A2 alleles.The present studies suggest that treatment with an SSRI during a period of alcohol consumption can reduce alcohol intake by about 20% compared to placebo for at least 2 weeks. This finding is more of a theoretical interest than of clinical usefulness. Predictors for an alcohol-reducing effect of SSRIs may be a mean daily pure alcohol consumption between 60 and 100 g, presence of the DRD2 A2/A2 alleles and high prolactin response to fenfluramine.