Serotonin-altering medications and desire, consumption and effects of alcohol-treatment implications

Abstract

SummaryThe relationship between serotonin neurotransmission and alcohol consumption (AC) was first determined in preclinical studies. AC generally increases following treatments which decrease serotonin activity, and levels of 5-HT and metabolites are low in some brain regions of alcohol-preferring rats. Pharmacological treatments which enhance serotonergic neurotransmission (uptake inhibitors, releasers, agonists) consistently reduce AC in rats. Serotonin uptake inhibitors (SUI; e.g., citalopram, fluoxetine) have been studied extensively in humans. In several double-blind randomized, placebo-controlled trials, SUI consistently decreased short-term (2-4 weeks) AC by averages of 15% to 20% in nondepressed mildly/moderately dependent alcoholics who received no other treatment. Some subjects decreased AC by up to 60%. The effects of SUI on AC were dose-dependent and not related to side effects (few and mild) or changes in anxiety or depression (not observed). SUI decreased desire to drink and liking for alcohol, suggesting a mechanism of action, to be considered in the development of treatments to reduce AC and prevent relapse. However, while an adjunctive brief psychosocial intervention enhanced the short-term effect of a SUI, the long-term (l2-week) effects of SUI and placebo were similar. Other drugs acting on the 5-HT system have been tested in humans, but results are inconclusive. For example, buspirone, a 5-HT IA receptor partial agonist, reduced anxiety and alcohol craving, but not AC; a 5-HT partial agonist, m-CPP, increased craving in abstinent alcoholics; modest reductions in AC were observed with a 5-HT) antagonist, ondansetron (0.5 mg/day, but not 4 mg/day). Ritanserin, a 5-HT2 antagonist, reduced desire to drink and prevented relapse in a small (n=5) study, and there was some indication that it reduced desire to drink and enhanced alcohol effects without reducing AC, in another study. The therapeutic potential of these medications is being studied. SUI and other serotonin-altering medications are promising new neuropharmacological treatments for AC.

Effects of Chronic Ethanol Consumption and Aging on Dopamine, Serotonin, and Metabolites

“…The importance of DA in the rewarding properties of ethanol is well known (Gessa et al, 1985;Koob and Weiss, 1990;Lewis and June, 1990;McBride et al, 1990;Samson et al, 1990;Caine and Koob, 1993;Laurier et al, 1994;Schwartz et a!., 1994). The additional potential involvement of mesocorticolimbic 5-HT neurons comes from studies dem-onstrating that ethanol consumption is altered by administration of certain 5-HT receptor agonists and antagonists (Panocka and Massi, 1992;Hodge et al, 1993;Panocka et al, 1993;Singh et al, 1993;Naranjo and Bremner, 1994). The effects of DA and 5-HT may be related because ethanol increases the release of both DA and 5-HT in the NA (Yoshimoto et al, 1992a,b).…”

“…The nigrostriatal DA regions are of interest because of their involvement in motor function (Morelli et al, 1990), and the mesocorticolimbic DA areas were examined because of their role in the rewarding properties of ethanol and other drugs of abuse (Gessa et al, 1985;Koob and Weiss, 1990;Lewis and June, 1990;McBride et al, 1990;Samson et al, 1990;Koob, 1992;Caine and Koob, 1993;Laurier et al, 1994;Schwartz et al, 1994). The potential involvement of mesocorticolimbic 5-HT neurons in the rewarding properties of ethanol comes from studies demonstrating that ethanol consumption is altered by administration of certain drugs that act at 5-HT receptors or reuptake sites (Naranjo et al, 1992;Panocka and Massi, 1992;Samson et al, 1992;Hodge et al, 1993;Panocka et al, 1993;Singh et al, 1993;Naranjo and Bremner, 1994).…”

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

“…While several antidepressants have been tested for alcohol dependence, because of their mild side effect profile, SSRIs have been the most studied. In all, despite reductions in drinking in lab studies with experimental animals [31], in human drinking sessions [31,32], and in alcoholics with major depression [33], most double-blind placebo controlled studies using SSRIs have not consistently reduced drinking or had a robust effect on any other measures of alcohol consumption. Of course, alcohol treatment research seeks a significant change in alcohol consumption as the primary marker for study success.…”

“…In summary, despite reductions in drinking shown in lab studies with experimental animals [31], in human drinking sessions [31,32], and in some alcoholics with major depression [33], most double-blind placebo controlled studies using SSRIs including fluoxetine [38][39][40][41][42], citalopram [51,52], or sertraline [45,46], have not reduced drinking or any other measures of alcohol consumption across a varied population of alcoholics. As a result, clinical trials using SSRIs in general are considered inconclusive [18].…”

Drug Therapy for Alcohol Dependence

“…81,82 Patients who are taking one of these drugs report a decreased desire and liking for alcohol. 83 However, the results in patients with diagnosed alcohol dependence have been less impressive. In a three-week prospective study of fluoxetine, alcohol intake decreased only during the first week, 84 and in a double-blind study comparing fluoxetine treatment with placebo in 101 patients, in which both groups received cognitive-behavioral psy-chotherapy, there was no difference in drinking between the groups.…”