Alcoholism has turned to be a difficult problem due to the association with several health issues. The treatment for alcoholism from long time was focused mainly on detoxification and use of drugs during rehabilitation period. In the recent years naltrexone has been proposed for treatment of alcohol dependence. Naltrexone is a synthetic compound which acts as an antagonist for opioid receptor. Alcohol consumption is a chronic disorder which results in severe economical impact on the country. The alcoholism is associated with craving for alcohol, repeated drinking and heavy drinking. The effectiveness of treatment for alcohol dependence measured with reduced heavy drinking.
Naltrexone drug is an antagonist of opioid receptor which is used as a pharmacological agent for relapse prevention for the treatment of alcohol dependence. Naltrexone is also used in opioid addictions as it is antagonist for Mu-opioid receptors which is receptor of opioid ligands such as heroine, morphine, and cocaine. The reinforcing action of alcohol drinking is associated with opioid activity after alcohol consumption. The opioid activity is blocked by the antagonist, which reduces the craving and hence encourages longer abstinence from alcohol drinking. When the patients consume the naltrexone drug daily, the drug appears to reduce the number of drinks by the patients and further it also reduces the quantity of alcohol consumed during the drinking period by the patients when they do occasionally. Naltrexone is the drug which has been used in the relapse preventing drug for the patients who are in rehabilitative counseling for alcohol dependence. The naltrexone treatment success increases when combined with counseling for cognitive coping skills. Naltrexone drug once administrated either as oral or injection undergoes a rapid and extensive metabolism in liver through enzymatic reduction to 6-beta-naltrexol. The metabolite 6-beta-naltrexol is a much weaker antagonist than naltrexone.
The consumption of alcohol results in the release of the beta-endorphin and encephalin endogenous opioids which leads to alcohol induced high pleasure, intoxication, and more craving and repeated consumption. Naltrexone treatment which blocks opioid receptor inhibits the pleasure that is experienced upon alcohol consumption. Naltrexone drug is an effective in treatment for alcohol dependence, but does not results in always positive outcome with everyone. The variation Asn40Asp in the OPRM1 (Mu opioid receptor) results in the varied capability of the receptor to bind its ligands and also associated with the different responses for the naltrexone treatment for alcohol dependence. The amino acid substitution of asparagine to aspartic acid at the 40 position is the result of Adenine to Guanine single nucleotide substitution at 118 position of OPRM1 gene (single nucleotide polymorphism rs1799971). This amino acid change in the protein results in the structural change in the receptor extracellular domain thereby causing the increased binding of the ligands which culminates into the enhanced activity of the receptor. The patients who carry the Asp40 allele has been shown associated with higher response to alcohol. The patients who carry at least one copy of Asp40 allele responded better to naltrexone treatment than the patients who are without this allele. Increased trend of abstinent days, lesser heavy drinking days were observed in patients who are carriers of at least one copy of Asp40 allele and treated with naltrexone, while those lacking Asp40 allele were associated with decreased abstinent days, increased heavy drinking days over the treatment period.
Naltrexone (both oral and injectable forms) is one of the several medications which are approved by the Food and Drug Administration (FDA) for the treatment of alcohol dependence. It is one among the few pharmacotherapies which are currently approved in United States for the treatment of alcoholism. Naltrexone belongs to class of opioid antagonist, which acts by a competitive antagonism for the mu-opioid receptor which inhibits the release of alcohol induced dopamine, resulting in reduced effects of alcohol. Naltrexone drug has been associated with reducing relapse, reduced number of drinks consumed at any time point and reduced carving for alcohol and has been associated with more number of abstinence from drinking alcohol. Further naltrexone drug has been associated with higher retention rate. There are two possible hypotheses for explaining the benefits of naltrexone for treatment of alcohol dependence. The first possible explanation may be that it increases the time elapsed before the first drink consumed by subjects. The second possible explanation may be that it influence on control of alcohol consumption upon drug treatment, which might results in delay in relapse. Which might enhances the subject's faith in naltrexone treatment.
Several studies have shown the positive effectiveness of naltrexone in alcohol treatment. The relapsing of heavy drinking and consumption of alcohol was reduced during naltrexone treatment. The patients having higher baseline craving were shown robust response to naltrexone treatment. The observed clinical benefits of naltrexone treatment for alcohol dependence are associated with alcohol craving, patients with a positive familial history of alcoholism, the age at which the alcoholism onset, the variation in the opiate receptor for the 118G allele and the association between sweet preference and naltrexone less efficacy. The patients with less sweet preferences are associated with the better outcome of naltrexone treatment.
The successful withdrawal of alcohol patient is associated with short psychosocial rehabilitation counseling programme, which aims to eliminate or reduce the craving for alcohol. Though the psychosocial counseling are much effective in decreasing the alcohol consumption and encouraging abstinence in many patients, a larger fraction of patients enters the drinking phase within couple of months after counseling. Hence psychosocial counseling is coupled with pharmacological treatment to obtain the higher success rate. Naltrexone treatment success are indicated as reduced relapse rates, less quantity of alcohol consumption during the treatment, and increased number of abstinence rates though they don't directly correlates with long term effect of reducing alcohol intake, but are indicative of success of naltrexone treatment in long term for patients. Several studies have shown the results in favour of naltrexone treatment and few variations observed may be due to the sample size, ethnicity, and duration of treatment and also may be due the variation in the opioid receptor gene.
In few patients the naltrexone treatment results in few side effects such as nausea and abdominal cramps, which ends with discontinuation and withdrawal from the treatment for alcohol dependence. Overall, naltrexone appears to be the most useful drug in a therapeutic treatment to lessen and control alcohol consumption. Naltrexone can be administered effectively and safely to patients without detoxification phase. Though naltrexone is safe to be prescribed to the patients, there are numerous areas requiring further research which includes, the need of combination of specific psychosocial therapy with naltrexone drug, the probable genotypes of patients with whom the drug is more effective, the best possible duration for treatment, its safety during pregnancy period and finally the search for the best measures which increases adherence to treatment by patients.
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