Background

Patients prescribed opioid agonist therapy (OAT) for opioid dependence are known to have increased risk of multiple substance addiction, including alcohol.1 Benzodiazepines are commonly used to treat alcohol withdrawal syndrome (AWS); however, given their sedative effects, increased risk of misuse, and accidental overdose, an alternative therapy is warranted for OAT patients undergoing alcohol detoxification. Baclofen is an emerging treatment for alcohol detoxification as it can reduce the craving to drink and can suppress AWS symptoms. Currently, there is a lack of evidence for its effectiveness in OAT patients. A 2021 study therefore investigated baclofen’s effectiveness and patient acceptability in treating AWS in OAT patients.2 

Methods

In total, 23 alcohol-dependent patients attending Dublin OAT addiction clinics were invited to take part in this proof-of-concept study. The study was non-blinded (i.e. the participants knew what drug they were taking), with no control group as the sample size was limited, with the key aim to determine baclofen’s acceptability. Patients were assessed for alcohol intake and had a physical assessment, including liver and cardiac function. The Clinical Institute Withdrawal Assessment for Alcohol Scale Revised (CIWA-Ar) was used to monitor alcohol withdrawal symptoms during detoxification. The Treatment Satisfaction Questionnaire for Medication version 1.4 (TSQM 1.4) was undertaken once the detoxification period was completed to assess the participants’ satisfaction with baclofen. Data were gathered on side-effects, effectiveness, convenience, and global satisfaction with the treatment. A baclofen treatment regime was administered while the patients attended a daily clinic during the 11-day detoxification period.2 

Data analysis

An intention-to-treat analysis was carried out to compare alcohol intake and withdrawal symptoms before and after the detoxification using baclofen. An intention-to-treat analysis includes all available data from participants, with data from those who dropped out also included in the analysis.3 Appropriate statistical tests were applied to compare results among participants who completed the study and those who dropped out. 

Results

Of the 23 participants invited to take part, three dropped out before the trial commenced, reducing the study to 14 males and six females. A further three participants had dropped out by Day 4 of the trial. Approximately, one-half of the participants were homeless and alcohol intake was deemed very high. As this was an intention-to-treat study, any available data from the participants who dropped out were included in the analysis. The mean age was 37.6 years (males 38.7 yrs vs females 35.1 yrs). All participants had positive urinalysis for benzodiazepines, most (n=16/20) had abnormal liver findings, and one-half tested positive for hepatitis C. Following detoxification with baclofen, a statistically significant difference in median alcohol intake (interquartile range (IQR)) per day was observed, falling from 26.5 units (20.8–37.3) to 6.0 units (3.9–8.0), with a median reduction of 21.0 units (13.8–27.0). There was no difference observed between genders. Substantial reductions were also seen in AWS as measured by the CIWA-Ar, as median CIWA-Ar were also observed. Female participants were more likely to experience moderate withdrawal symptoms than males at the beginning of the study. Patient satisfaction with baclofen therapy was excellent across the four domains (side-effects, effectiveness, convenience, and global satisfaction) on the TSQM. Female participants scored slightly higher than males across the four scales, yet males still scored very high in relation to global satisfaction. 

Discussion

The baclofen therapy for AWS saw a large decline in alcohol units consumed per day over a detoxification period of 11 days in both male and female opioid-dependent participants on OAT recruited in this proof-of-concept study. Combined with the CIWA-Ar results, baclofen appeared to effectively suppress withdrawal effects. Participants considered baclofen to be effective, convenient to take with few side-effects, and gave very high satisfaction scores, suggesting acceptability. The authors state that this study is the first of its kind to show that a non-addictive drug (baclofen) may work in the opioid-dependent population requiring alcohol detoxification. 

However, the major weakness of the study was the positive benzodiazepine urinalysis observed in all patients, as no participant was known to have been prescribed benzodiazepines. This indicates illicit use, with the type and dose of benzodiazepines not known or regulated. Therefore, the reduction in withdrawal effects could be attributed to benzodiazepines rather than baclofen.

Another weakness was the small study numbers, which meant that a blinded controlled study could not be conducted. With no control group, a direct link to baclofen as an effective treatment of AWS in OAT patients undergoing alcohol detoxification is not possible. The authors noted that the mean alcohol consumption did not reach zero units by the end of the study. However, baclofen may be a suitable therapy for AWS in high-risk groups of relapses or developing benzodiazepine addiction, and further study is warranted.
 

1  Soyka M (2015) Alcohol use disorders in opioid maintenance therapy: prevalence, clinical correlates and treatment. Eur Addict Res, 21(2): 78–87.

2  Gibbons Z, McCarron P, Santlal K, McCarthy R and Keenan E (2021) Baclofen in the treatment of alcohol withdrawal syndrome in opioid-dependent patients. Heroin Addict Relat Clin Probl, Early online. https://www.drugsandalcohol.ie/35053/

3  Elkins MR and Moseley AM (2015) Intention-to-treat analysis. J Physiother, 61(3): 165–167.