Seminal and key studies and reviews on the effectiveness of medical interventions and treatment in medical settings.
S Seminal studies K Key studies R Reviews G Guidance more Search for more studies
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S Handing patients responsibility matches extended treatment (1977). Effectiveness Bank essay includes an analysis of a mould-breaking study in London which found a brief session handing responsibility to the couple to overcome the husband’s dependent drinking worked as well as extended treatment (which generally involved medications). See also this retrospective (2015) from a study researcher. Similar Scottish study later found (1988) more evidence for extended treatment, but still no statistically significant advantage over brief advice. For discussion and scroll down to highlighted heading.
S Offenders prefer disulfiram-enforced abstinence to a return to prison (1966). Conducted in early-’60s USA, the first test of whether problem-drinking offenders can be pressured to take a drug which enforces abstinence by generating deterrent reactions to alcohol. Among offenders for whom sanctions had repeatedly proved ineffective, the prospect of yet another spell in prison provided the motivation to take the medication witnessed by their probation officers, which seems to have provided about 6 in 10 with the prop they needed to avoid drinking. For related discussion and scroll down to highlighted heading.
S Disulfiram only works with compliant patients (1986). Despite overall negative findings, from the USA the first rigorous trial of the medication which causes deterrent physical reactions after drinking found that it helped some older and more socially stable patients who completed the study to drink less frequently after lapsing. The study became seen as confirming the need to supervise disulfiram’s administration so more patients took more of the pills. For discussions click and and scroll down to highlighted heading or text.
S Impressive results from first clinical trial of acamprosate (1985). Three months later the success rate among alcohol-dependent patients detoxified and discharged from a French inpatient unit was 61% if they had been randomly allocated to acamprosate versus 32% on placebo. It was a notable result among severely dependent patients with a record of failed treatments.
S Benzodiazepines best withdrawal treatment (1969). Study which clarified the dangerous confusion over how to prevent the life-threatening complications of alcohol withdrawal.
K Acamprosate fails for UK patients (2000). Despite positive findings elsewhere, large UK trial did not find acamprosate prevented relapse among detoxified alcoholics. The findings highlighted the importance of an accompanying support programme to help keep patients in treatment and taking the pills, and also perhaps the type of patients – steady drinkers rather than the study’s ‘bingers’ – who respond best to the acamprosate. For discussion and scroll down to highlighted passage.
K Supervised disulfiram works in Britain (1992). In the major UK trial, disulfiram significantly reduced drinking by nearly 10 UK units a day relative to a vitamin-pill placebo, though effects waned over the prescribing period. For the researchers their results showed the importance of supervising consumption and making patients aware of the potential consequences of drinking while taking disulfiram. For discussion and scroll down to highlighted passage. For related discussion and scroll down to highlighted heading.
K Naltrexone works in the UK among patients who take the pills (2000). Among patients randomly allocated to naltrexone versus a placebo in conditions typical of British alcohol treatment clinics, the active medication was associated with reduced drinking, craving, and need for treatment at the end of the 12-week prescribing period, but these results were rarely statistically significant. Naltrexone’s advantages were more clear among the ‘compliant’ minority (just 40%) who stayed in the study and in treatment and took at least 8 in 10 of their active or dummy tablets. For discussion and scroll down to highlighted passage.
K In the USA, naltrexone boosted the impact of primary care treatment (2006). In the large US ‘COMBINE’ trial, supplementing medication plus primary care-style care with psychological therapy elevated drinking outcomes on a placebo to those of the most effective trial medications. Without therapy, naltrexone boosted outcomes to about the same degree, but acamprosate was not found to improve outcomes. Results of this and another US trial supported prescribing naltrexone in primary care-based treatment with relatively compliant patients but also suggested that psychological therapy can match medication’s effects. Partial replication in Germany . For discussion and scroll down to highlighted heading.
K In Germany, naltrexone was not shown to boost the impact of primary care treatment (2012). Closely replicated the US COMBINE trial but did not test psychological therapy. Unlike in the USA, did not find that supplementing primary care with naltrexone (or acamprosate) improved on a placebo, perhaps because the patients in Germany were more severely dependent, came directly from inpatient detoxification wards, and were already about 20 days abstinent. Supported by long-term outpatient medical care, they may have been progressing as well as they would do, regardless of medication. For discussion and scroll down to highlighted heading.
R Full range of medical treatment expertly assessed (2017; free source at the time of writing). A review from a task force of the World Federation of Societies of Biological Psychiatry offers a well-evidenced overview of psychosocial, pharmacological and other medical treatments for alcohol dependence and also for co-occurring psychiatric conditions.
R The power of the placebo (2013; free source at time of writing). Across relevant trials, end-of-treatment improvements in alcohol patients randomly allocated to an inactive placebo preparation on average dwarfed estimates (for which see following reviews) of additional benefits due to the preparation being an active medication. For related discussion and scroll down to highlighted heading.
R Evidence strongest for acamprosate and oral naltrexone (2014; also available as a journal article). Report amalgamates findings from 123 trials of the full range of medications when prescribed for at least 12 weeks. Evidence for reduced drinking was strongest for acamprosate and oral naltrexone, though health improvements were unclear. The few head-to-head comparisons yielded no significant differences between the two medications, but other reviews have found minor differences. Confined to ‘double-blind’ trials, the review did not offer a practice-relevant evaluation of disulfiram, which requires the patient knows what they have been prescribed; instead see review .
R Prescribing in primary care and general medicine (2011). Based on studies offering minimal psychosocial support, recommends oral naltrexone, topiramate or (with abstinent patients) acamprosate – and given supervised consumption and motivated, abstinent patients, also disulfiram. Medication should be accompanied by support to promote compliance with treatment. However, not too much can be expected; even when little other support was provided, improvements due to medication were “modest”. For related discussion and scroll down to highlighted heading.
R Who benefits most from naltrexone versus acamprosate? (2013). Amalgamated findings from randomised trials comparing each to a placebo or to each other indicated that overall naltrexone was best for patients who want to reduce heavy drinking, acamprosate for those seeking abstinence, findings confirmed by a different kind of analysis (2014; free source at time of writing). Another review (2015) did not find evidence that the medications’ impacts differed between European and (mainly) US caseloads. In all three reviews, differences between the medications were slight as were their effects compared to placebo, and individual trials often failed to find benefits. For related discussion and scroll down to highlighted heading.
R Authoritative analysis finds modest benefits from UK’s most commonly prescribed medication for dependent drinking (2010). Amalgamated findings on acamprosate (the most popular pharmacotherapy for alcohol dependence in the UK; 1 2) from the Cochrane collaboration, whose work is often relied on to inform national policy and guidelines. Found that the medication offers worthwhile if modest benefits in preventing drinking after detoxification. Another Cochrane review on naltrexone (2010) and allied medications found inconsistent and generally small effects. For related discussion and scroll down to highlighted heading.
R Disulfiram needs supervised consumption and patient awareness (2014). Amalgamated findings indicate that disulfiram substantially improves on alternatives or a placebo when (and on average, only when) compliance is bolstered by supervising administration and patients know they are taking a drug which causes unpleasant reactions if they drink. Given the careful patient selection typical of research trials, disulfiram has not been associated with excess deaths or serious adverse events. Different kind of analysis (2011) confirmed findings on supervised consumption. For related discussions click and and scroll down to highlighted headings.
R Antiepileptic medication more effective than standard pharmacotherapies (2014; free source at time of writing). Amalgamating the limited research on topiramate suggests it reduces drinking more than naltrexone and acamprosate. Review agrees, but highlights topiramate’s undesirable side effects, said to (2014; free source at time of writing) limit its clinical utility. However, a textbook (2014) on addiction medication says these are generally mild or moderate, and that topiramate is among “the most promising agents that directly reduce alcohol consumption”. In the UK topiramate is not licensed for treating dependent drinking.
R How to help ensure patients take the pills (2004). Because the reasons why alcohol treatment patients skip their medication are varied, so too must be ways to address this, from reducing side-effects and adjusting dose to compliance-enhancing counselling and enrolling the family. For discussion and scroll down to highlighted heading.
R Benzodiazepines make withdrawal safer and easier (2010). Rigorous review and synthesis of randomised trials confirms the superiority of benzodiazepines for controlling the potentially serious medical consequences (especially seizures) of withdrawing from dependent drinking.
R Motivational interviewing is for medics too (2013). Reviews randomised trials of this popular counselling style (which importantly for non-specialist settings, lends itself to brevity) as applied typically for patients seeking treatment for physical illnesses affected by the behaviours (such as substance use) targeted by counselling. Concludes that “if you can devote a small amount of extra time with your patients to build relationship and evoke change talk, you can expect 10–15% additional improvement”. Impacts on problem drinking were among the strongest. Related review (2014; free source at time of writing) focused on primary care. Overall motivational interviewing generated positive behaviour change (mostly in substance use) relative to usual care.
R Psychological therapies improve on usual care for depressed drinkers (2014). Amalgamated findings show that psychological therapies based on cognitive-behavioural principles and/or motivational interviewing modestly but significantly improve on usual care (typically counselling and/or medication) for depressed problem drinkers, further ameliorating both depression and drinking.
G Official English guidelines on treating harmful drinking and alcohol dependence (National Institute for Health and Care Excellence [NICE], 2011). Britain’s gatekeeper to the public provision of health care interventions recommends considering acamprosate or naltrexone after withdrawal, but relegates disulfiram to a second-line option. Treatment and care should take account of the individual’s needs and preferences. See also Scottish primary care guidelines (2004). For discussions click and and scroll down to highlighted headings.
G Treating withdrawal (Royal College of Physicians, 2010). Guidance developed for the UK’s National Institute for Health and Care Excellence (gatekeeper to the public provision of health care interventions) on medical care of patients suffering alcohol-related ill-health conditions, including acute withdrawal.
G Assessment and management of alcohol use disorders (2015). Focuses on practical aspects from the perspective of the non-specialist hospital doctor or general practitioner. Structured around clinical guidelines developed by the National Institute for Health and Care Excellence, the UK’s gatekeeper to the public provision of health care interventions. Authorship team led by the substance use treatment specialist later to become the UK government’s ‘recovery champion’. For discussion and scroll down to highlighted text.
G US consensus clinical guidelines ([US] Substance Abuse and Mental Health Services Administration, 2009). From experts convened by the US health department, how approved medications in both the USA and the UK (acamprosate; oral and injectable naltrexone; disulfiram) can be incorporated into medical practice, including choosing suitable patients.
G Treating severe mental illness and co-occurring substance use (National Institute for Health and Care Excellence [NICE], 2016). Guidelines from the UK’s gatekeeper to the public provision of health care interventions on how to improve services for people aged 14 and above diagnosed with both severe mental illness and substance use problems. Another guideline (NICE, 2011) has dealt specifically with psychosis and substance use problems. Both are reflected in NICE quality standards (NICE, 2019).
G Treating substance use service clients with mental health problems ([Australian] National Drug and Alcohol Research Centre, 2016). Funded by the Australian government; recommends services screen all patients for mental health problems and that mental illness should not be a barrier to treating substance use problems. Research shows these patients can benefit as much as others from routine treatments for problem drinking.