Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alcoholism and stress share some common neurobiological circuits, including the GABAergic system. In particular, the GABA(B) receptor seems to play an important role. The GABA(B) receptor agonist baclofen has been studied as a treatment for alcohol-dependent subjects. Baclofen administration in alcohol-dependent patients was able to promote abstinence, inducing the remission of withdrawal symptoms, reducing alcohol craving, and reducing alcohol intake. Baclofen also reduced anxiety in alcohol-dependent subjects, probably acting on brain stress circuitry and/or on other neuroendocrine systems. Baclofen also showed excellent safety and tolerability, even in alcohol-dependent patients with advanced liver disease (i.e., cirrhosis). Future studies should investigate which alcoholic subtype may better benefit of the administration of baclofen in the treatment of alcohol dependence.
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PMID:Role of the GABA(B) receptor system in alcoholism and stress: focus on clinical studies and treatment perspectives. 1991 1

Both preclinical and clinical research studies have shown the GABA(B) receptor agonist baclofen represents a promising treatment for alcohol dependence. Preliminary clinical studies indicate that baclofen is able to suppress withdrawal symptoms in alcohol-dependent patients affected by the alcohol withdrawal syndrome. Moreover, baclofen has shown efficacy and safety in promoting alcohol abstinence in alcohol dependent patients in two placebo-controlled trials including one in alcohol-dependent patients with liver cirrhosis. These trials also demonstrated that baclofen was associated with reductions in withdrawal-related anxiety and alcohol craving. However, more work is needed to clearly demonstrate the efficacy of baclofen and to ascertain whether efficacy is limited to certain subtypes of alcoholic patients. For example, a recent US trial failed to demonstrate a robust effect of baclofen in treating alcohol-dependent patients though the relative moderate severity of alcohol-dependence in that trial has been suggested as one factor that may have contributed to the finding. In the present review, the authors will summarize the published clinical studies on the role of baclofen in alcohol dependence and will also present some unpublished secondary analyses. Finally, the authors will discuss possible future directions to further investigate the role of baclofen in alcohol dependence (e.g., baclofen's biobehavioral mechanisms, different baclofen doses, differences in severity and in alcoholic subtypes, different formulations of baclofen, possible combination of baclofen with other medications).
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PMID:Effectiveness and safety of baclofen in the treatment of alcohol dependent patients. 2020 13

Preclinical studies show that antagonism of the GABA(B) receptor may represent an effective neuropharmacological approach to treat alcohol dependence. Consistent with preclinical evidence, the majority of the human studies have demonstrated that the prototype GABA(B) receptor antagonist baclofen may represent an effective mediation to treat alcohol-dependent individuals. Specifically, baclofen has shown to reduce alcohol withdrawal symptoms, as well as to reduce alcohol craving and intake, and to promote alcohol abstinence. Notably, baclofen has shown a safe profile when administered to alcoholics, including those with liver cirrhosis. In summary, baclofen represents a safe and effective medication to treat alcohol dependence, thus holding promise as a new pharmacotherapy. However, large studies are needed to confirm the present findings.
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PMID:Safety and efficacy of baclofen in the treatment of alcohol-dependent patients. 2048 7

The pharmacological properties of baclofen, a GABA(B) receptor agonist, have led to investigation of its use for the off-label treatment of alcohol dependence. Literature examining the role of baclofen in alcohol dependence suggests that it may be a useful medication in the treatment armamentarium with an additional benefit of promoting abstinence and reducing alcohol-associated cravings and anxiety. We conducted a systematic review of prospective, randomized controlled trials comparing baclofen with placebo for the treatment of alcohol dependence. Four randomized controlled trials were identified but only three met criteria for inclusion. The excluded trial was a post hoc analysis of data collected from an original trial whose primary outcome did not fit our inclusion criteria and was terminated prior to completion. Compared with placebo, subjects randomized to baclofen experienced higher rates of abstinence and lower anxiety scores; the effect of baclofen was statistically significant in two trials assessing patients with more severe alcohol dependence and non-significant in a trial of outpatients receiving concomitant manualized psychotherapy. Baclofen appeared to be safe, well tolerated and to have low addiction liability even in the setting of moderate-to-severe liver cirrhosis, a known complication of alcohol dependence. Though baclofen may hold promise, the different outcomes and sample populations of the three studies highlight the need for more research to better understand the appropriate target patient population to benefit from this medication. Questions still remain about optimal dosing and duration. There is not enough evidence to support the use of baclofen as a first-line treatment option, except for those alcohol-dependent patients with moderate-to-severe liver cirrhosis in whom other pharmacological treatments are not safe or practical.
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PMID:Defining the role of baclofen for the treatment of alcohol dependence: a systematic review of the evidence. 2214 7

Hepatitis C virus (HCV) and alcoholic liver disease (ALD), either alone or in combination, count for more than two thirds of all liver diseases in the Western world. There is no safe level of drinking in HCV-infected patients and the most effective goal for these patients is total abstinence. Baclofen, a GABA(B) receptor agonist, represents a promising pharmacotherapy for alcohol dependence (AD). Previously, we performed a randomized clinical trial (RCT), which demonstrated the safety and efficacy of baclofen in patients affected by AD and cirrhosis. The goal of this post-hoc analysis was to explore baclofen's effect in a subgroup of alcohol-dependent HCV-infected cirrhotic patients. Any patient with HCV infection was selected for this analysis. Among the 84 subjects randomized in the main trial, 24 alcohol-dependent cirrhotic patients had a HCV infection; 12 received baclofen 10mg t.i.d. and 12 received placebo for 12-weeks. With respect to the placebo group (3/12, 25.0%), a significantly higher number of patients who achieved and maintained total alcohol abstinence was found in the baclofen group (10/12, 83.3%; p=0.0123). Furthermore, in the baclofen group, compared to placebo, there was a significantly higher increase in albumin values from baseline (p=0.0132) and a trend toward a significant reduction in INR levels from baseline (p=0.0716). In conclusion, baclofen was safe and significantly more effective than placebo in promoting alcohol abstinence, and improving some Liver Function Tests (LFTs) (i.e. albumin, INR) in alcohol-dependent HCV-infected cirrhotic patients. Baclofen may represent a clinically relevant alcohol pharmacotherapy for these patients.
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PMID:Baclofen promotes alcohol abstinence in alcohol dependent cirrhotic patients with hepatitis C virus (HCV) infection. 2224 7