Update on neuropharmacological treatments for alcoholism: Scientific basis and clinical findings

Abstract

The past decade has seen an expansion of research and knowledge on pharmacotherapy for the treatment of alcohol dependence. The Food and Drug Administration (FDA)-approved medications naltrexone and acamprosate have shown mixed results in clinical trials. Oral naltrexone and naltrexone depot formulations have generally demonstrated efficacy at treating alcohol dependence, but their treatment effect size is small, and more research is needed to compare the effects of different doses on drinking outcome. Acamprosate has demonstrated efficacy for treating alcohol dependence in European trials, but with a small effect size. In U.S. trials, acamprosate has not proved to be efficacious. Research continues to explore which types of alcohol-dependent individual would benefit the most from treatment with naltrexone or acamprosate. The combination of the two medications demonstrated efficacy for treating alcohol dependence in one European study but not in a multi-site U.S. study. Another FDA-approved medication, disulfiram, is an aversive agent that does not diminish craving for alcohol. Disulfiram is most effective when given to those who are highly compliant or who are receiving their medication under supervision. Of the non-approved medications, topiramate is among the most promising, with a medium effect size in clinical trials. Another promising medication, baclofen, has shown efficacy in small trials. Serotonergic agents such as selective serotonin reuptake inhibitors and the serotonin-3 receptor antagonist, ondansetron, appear to be efficacious only among certain genetic subtypes of alcoholic. As neuroscientific research progresses, other promising medications, as well as medication combinations, for treating alcohol dependence continue to be explored.

The Effects of Naltrexone on Subjective Response to Methamphetamine in a Clinical Sample: a Double-Blind, Placebo-Controlled Laboratory Study

“…Further, elevated frontal/temporal cortical μ-opioid receptor binding has been observed in cocaine dependence, the degree of which was shown to positively correlate with self-reported cocaine craving (Gorelick et al, 2005), and relate to relapse following treatment (Ghitza et al, 2010;Gorelick et al, 2008). NTX has been shown to block ethanol-induced β-endorphin and subsequent dopamine release in the nucleus accumbens and provide a blockade of ethanol-induced β-endorphin inhibition of GABAergic inhibitory interneurons in the ventral tegmental area (Johnson, 2008;Zalewska-Kaszubska et al, 2006). The decrease in amphetamine-induced dopamine Figure 3 Subjective response scores (drug effects questionnaire (DEQ)), presented with standard errors, at baseline (BA) and change from baseline at 5,10,15,20,30,60,90, and 120 min following methamphetamine (MA) administration, during both placebo and naltrexone (NTX) conditions.…”

Cerebral serotonin transporter binding is inversely related to body mass index

“…Drugs that increase the extracellular 5-HT through inhibition of SERT also inhibit food intake both in animals (Blundell, 1984;Simansky, 1996) and in humans (Olausson et al, 2002;Halford et al, 2005;Johnson, 2008). In addition, studies of SERT knockout mice have uncovered SERT as a candidate gene for human obesity, e.g., SERT mutant (SCL6A4−/−) mice become obese (Murphy and Lesch, 2008) and in obese and overweight individuals, recent evidence points to a decreased expression of the gene encoding for SERT (Sookoian et al, 2007;Fuemmeler et al, 2008).…”

Ethanol–BDNF interactions: Still more questions than answers

“…In addition, the anticonvulsant topiramate has recently been shown to be effective in increasing abstinence rates among alcoholic patients (Johnson et al, 2007); the pharmacological mechanisms underlying this response are presumably related enhanced activity of GABA receptors and antagonism of glutamate receptors. This dual mechanism of action at both excitatory and inhibitory synapses is believed to mitigate the effects of chronic ethanol exposure on glutamatergic and GABAergic receptors in the mesocorticolimbic circuit (Johnson 2008). Interestingly, topiramate has also been investigated as a treatment for binge eating (Shapira et al, 2000, McElroy et al, 2003 suggesting that this compound may be effective in other appetitive disorders.…”

“…Interestingly, topiramate has also been investigated as a treatment for binge eating (Shapira et al, 2000, McElroy et al, 2003 suggesting that this compound may be effective in other appetitive disorders. None of these agents are particularly effective in alcoholism, however, only modestly increasing abstinence rates (reviewed by Mann 2004;Johnson 2008). …”