When it comes to effective interventions for alcohol-dependent patients who recently underwent detox, primary care specialists will come up high and dry, according to a systematic review and network analysis.
In the study, with an outcome of continuous abstinence from alcohol at least 12 weeks after start of intervention in the primary care setting, the median probability of abstinence across placebo arms was 25% in 64 trials (43 interventions), reported David Kessler, MBBS, MD, of the University of Bristol in England, and co-authors.
Additionally, acamprosate was the only intervention linked with an increased probability of abstinence, or effectiveness, but with “moderate certainty evidence” (odds ratio 1.86, 95% CI 1.49 to 2.33), which corresponded to an absolute probability of 38%, they wrote in BMJ.
For the study’s second primary outcome – all cause dropouts at least 12 weeks after start of intervention – acamprosate was tied to a reduced number of dropouts versus placebo (probability 50%), the authors stated, adding that it was “uncertain” if other interventions — naltrexone and acamprosate plus naltrexone — “can help maintain abstinence and reduce dropouts because of low confidence in the evidence.”
“More evidence from high quality randomized controlled trials is needed, as are strategies using combined interventions (combinations of drug interventions or drug and psychosocial interventions) to improve treatment of alcohol dependency in primary care,” Kessler’s group concluded.
In the U.K., “much of the burden of alcohol related disease is borne by hospitals, not least because there is little alcohol treatment available in primary care,” explained Jim McCambridge, PhD, of the University of York in England, and Duncan Stewart, PhD, of London Metropolitan University, in an editorial accompanying the study.
They noted that society at large has a “paradoxical, and indeed pathological, relation with alcohol,” – Kessler’s group stated that over half a million people in the U.K. alone contend with alcohol dependence — and argued that “if [alcohol dependence] was any other major health problem, we would likely think harder, act faster, and explore more than the most visible manifestations of the problem.”
In primary care in particular, the focus could shift from intervention to prevention, according to McCambridge and Stewart, who pointed out that “The authors recommend pragmatic trials of drugs plus interventions such as home visits to help expand primary care involvement in alcohol treatment.”
However, “Prescribing is just one possible component of integrated patient centered care,” they stated. “We must find smarter ways to explore how much alcohol lurks below the surface of common presenting problems.”
Other interventions that have shown potential are psychosocial treatment, such as cognitive behavioral therapy (CBT) and motivational enhancement therapy. McCambridge and Stewart noted that Kessler’s group “almost entirely excluded the large literature on counselling and other psychosocial treatments… mainly because these interventions start earlier.”
The authors sought out randomized controlled trials of any treatment intervention — drug, psychological, or both — for maintaining abstinence in alcohol-dependent adults who had undergo detoxification a minimum of 4 weeks before randomization. The included studies were published from 1986 to 2020. The majority of the patients were men, age around 40, who presented with mild to moderate mental health issues, such as anxiety and depression.
Kessler and co-authors explained that “We were unable to conduct several preplanned sub-group and meta-regression analyses (length of intervention, optional psychosocial interventions, dosing and schedule of interventions, psychiatric comorbidity, severity of alcohol dependence, and social background) because of inconsistent or poorly reported data on these characteristics across studies.”
Additionally, the included studies lacked information on the methods and settings of detoxification, but benzodiazepines were most commonly used, they stated. Finally, 30 of 64 studies were deemed as presenting “some concerns” of bias, while 27 had a “high risk” of bias. Reasons for bias included a paucity of data on the randomization process, missing data between the groups, missing outcome data, and potential contamination because of open-label designs.
In terms of intervention effectiveness, Kessler’s group reported the following:
- Acamprosate: OR 0.73 (95% CI 0.62 to 0.86).
- Naltrexone: OR 0.70 (95% C 0.50 to 0.98).
- Acamprosate-naltrexone: OR 0.30 (95% CI 0.13 to 0.67).
Based on the network meta analysis and confidence in the evidence, the authors also found that the median probability of dropout across placebo arms was 48%, “although for interpretational convenience we set it at 50% for computation of corresponding absolute risks for each intervention,” they stated.
They also reported that only a few other interventions were associated with reduced dropouts versus placebo:
- Topiramat: OR 0.45 (95% CI 0.24 to 0.83.
- Home visits: OR 0.32 (95% CI 0.11 to 0.95).
- Short-form CBT: OR 0.06 (95% 0.01 to 0.33).
- Acamprosate and nurse visits: OR 0.21 (95% CI 0.07 to 0.57).
However, flupenthixol (OR 2.37, 95% CI 1.27 to 4.40), fluvoxamine (OR 2.15, 95% CI 1.30 to 3.55), and carbamazepine (OR 12.00, 95% CI 1.22 to 118.42) were tied to increased odds of dropout versus placebo.
Study limitations were the exclusion of studies that led to a reduction in alcohol dependence rather than abstinence, the definitions of detoxification was not clear across the various studies, the fact that most of the studies were done in the U.S. and Europe, and, lastly, “all cause dropout as a proxy for acceptability was driven primarily by practical considerations because dropouts often occur in these patients and are well reported across studies,” the authors stated.
Nonetheless, Kessler and co-authors said the findings are in line with previous systematic reviews in terms of support for acamprosate in detoxified patients with alcohol dependency, and are also in keeping with recommended guidelines, such as those from the U.K.’s National Collaborating Centre for Mental Health. In the U.S., the Substance Abuse and Mental Health Services Administration does back acamprostate as a medication-assisted treatment for alcohol use disorder (AUD), and it is one of four agents approved by the FDA for AUD.
There is a lack of evidence on the benefits of interventions that could be implemented in primary care settings to support alcohol abstinence in alcohol-dependent adults.
Acamprosate was the only intervention associated with increased probability of abstinence, but with moderate certainty evidence, compared with placebo.
Shalmali Pal, Contributing Writer, BreakingMED™
The study was funded by the School for Primary Care Research, National Institute for Health Research (NIHR).
Kessler reported support from the NIHR Bristol Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol. Co-authors reported support from the NIHR Bristol Biomedical Research Centre, NIHR Applied Research Collaboration West (ARC West) at University Hospitals Bristol and Weston NHS Foundation Trust, NIHR Health Research Health Protection Research Unit (HPRU), and the HPRU in Evaluation of Interventions at University of Bristol.
McCambridge and Stewart reported no relationships relevant to the contents of this paper to disclose.
Cat ID: 192
Topic ID: 86,192,192,144,925