Comparison of naltrexone vs other drugs for alcohol dependence

A recent study published in the Indian Journal of Psychiatry, conducted by Arun Kumar et al compared the 3 drugs, namely: acamprosate, baclofen, and naltrexone, 1. To treat patients suffering from alcohol dependence and 2. To prevent its relapse. It was found that naltrexone was most effective in decreasing cravings and preventing relapse while baclofen has the best safety profile.

Alcohol dependence is a cluster of physiological, behavioral, and cognitive phenomena in which the use of alcohol takes on a much higher priority for a given individual than other behaviors that once had greater value. Dependence syndrome is the desire (often strong, sometimes overpowering) to take alcohol.

Most of alcohol-dependent patients require an initial period of detoxification. Benzodiazepines are commonly and very successfully used in the management of the symptoms of acute withdrawal, along with other adjunctive options such as beta-blockers, carbamazepine, clonidine, and antipsychotics occasionally.

Naltrexone is a competitive nonspecific opioid antagonist with the highest affinity for the µ-receptors. In addition to its role in opioid dependence, it was approved by the FDA for alcohol dependence in 1994. Naltrexone, is thought to help in attenuating the reinforcing effects of alcohol. As a result, alcohol consumption while taking naltrexone leads to lesser intoxicating effects of alcohol and therefore a decrease in desire to drink more. This ultimately leads to decreased craving and control over the drinking habits.

Acamprosate has been a proven safe and well-tolerated treatment modality for alcohol dependence since 1989. It tends to promote abstinence by counteracting or diminishing the physiological response to chronic alcohol exposure.

Baclofen is a prototypic GABA-B receptor agonist and it serves as the possible mechanism by which baclofen suppresses alcohol-induced dopamine release and the consequent dopamine-mediated alcoholism reinforcement and other associated alcoholism-related motivated behaviors. In addition, it is found to be effective in counterbalancing alcohol withdrawal syndrome, (AWS)-associated and N-methyl-D-aspartate-mediated glutamate excitatory neurotransmission.

30 patients were included in this study under each drug regimen and patients were selected using ICD-10 criteria for alcohol dependence. 3 scales used were:

(a) Obsessive Compulsive Drinking Scale (OCDS) -a self-reporting questionnaire for assessing the obsession and compulsivity related to craving and drinking behaviour.

(b) Advance Warning of Relapse (AWARE) questionnaire 3.0- applied to evaluate the risk for relapse. A higher score indicated more warning signs of relapse.

(c) Hogan Drug Attitude Inventory- applied to study the attitude of individuals toward medication adherence. A positive total score meant a compliant response, whereas a negative total score meant a noncompliant response.

Naltrexone dose was started at 50mg/day as per guidelines but due to frequent reporting of side effects it was started on 25mg/day & then titrated up. Acamprosate was started at dose of 333 mg thrice a day which was gradually titrated up to 4–6 tablets per day. Baclofen was started with 20 mg tablet once a day & the dose was increased to twice a day after a week.

During the weekly follow-up visits in the 1 st month, and bi-weekly follow-up visits for the next 5 months, the participants were assessed for craving, relapse risk, and medication adherence using the respective scales and questionnaires. Relapse was defined as taking four drinks for women or five drinks for men on an occasion or a single day. Side-effects if any were documented (Table).

It was found that in terms of OCDS score decline, the drop seen in the naltrexone group (26.72 ± 13.05) was maximum, followed by baclofen and acamprosate. In terms of decreasing AWARE questionnaire score, again naltrexone was most effective, with the maximum decline in AWARE score (64.72 ± 45.65), followed by baclofen and acamprosate. The attitude toward treatment with all three medications was positive, as per the Hogan Drug Attitude Inventory score.

It was concluded that naltrexone was most effective in terms of decreasing craving as well as decreasing the risk of relapse. In terms of safety profile, baclofen fared better than the other two drugs. Naltrexone was associated with the majority of side effects, while acamprosate was associated with the majority of dropouts.

All these factors should be weighed upon while opting for the anti-craving agent in the treatment of alcohol dependence.

source: Indian Journal of Psychiatry:: Kumar A, Sharma A, Bansal PD, Bahetra M, Gill HK, Kumar R. A comparative study on the safety and efficacy of naltrexone versus baclofen versus acamprosate in the management of alcohol dependence. Indian J Psychiatry 2020;62:650-8