Drug and Alcohol Findings home page. Opens new window Effectiveness Bank bulletin 25 July 2013

The entries below are our accounts of documents collected by Drug and Alcohol Findings as relevant to improving outcomes from drug or alcohol interventions in the UK. The original documents were not published by Findings; click on the Titles to obtain copies. Free reprints may also be available from the authors. If displayed, click prepared e-mail to adapt the pre-prepared e-mail message or compose your own message. The Summary is intended to convey the findings and views expressed in the document. Below may be a commentary from Drug and Alcohol Findings.


Contents

Spotlight on naltrexone and acamprosate, the two major anti-relapse medications for alcohol dependence treatment, digging deeper in to who they work for and who they may hinder. In respect of acamprosate it seems women respond as well as men. Women too are the focus for an assessment of the value of on-site parenting support. Last, away from treatment to prevention and whether two targets (sex and drugs) can be hit with one programme.

Largest US study yet favours naltrexone as alcoholism medication ...

Acamprosate as effective for alcohol-dependent women as for men ...

Integrating parenting support with treatment helps mums help the children ...

The same prevention programme can affect both sexual and substance use risks ...


Naltrexone and combined behavioral intervention effects on trajectories of drinking in the COMBINE study.

Gueorguieva R., Wu R. Donovan D. et al.
Drug and Alcohol Dependence: 2010, 107, p. 221–229.
Unable to obtain a copy by clicking title? Try asking the author for a reprint by adapting this prepared e-mail or by writing to Dr Gueorguieva at ralitza.gueorguieva@yale.edu. You could also try this alternative source.

Reanalysis of the largest US study of medication-based alcoholism treatment confirms that either naltrexone or psychological therapy improved outcomes more than medical care and placebos, while the two in combination or acamprosate added little. It also revealed previously invisible benefits when certain types of patients received certain treatments.

Summary The featured report used a more sophisticated and sensitive methodology to re-analyse outcomes from the US COMBINE trial which reported its original outcomes in 2006. This new analysis looked for patterns in drinking over the 16 weeks the study's treatments were offered to alcohol-dependent patients, and assessed the degree to which the trial's treatment combinations affected the chances that a patient would exhibit preferable patterns (such as consistent low drinking) rather than those which represent a poorer outcome (such as daily heavy drinking).

As described in an earlier Findings analysis, 11 clinics screened nearly 5000 applicants who had answered trial ads or had been referred to the trial by their clinicians. Of these, 1383 were dependent on alcohol, achieved at least an initial four days without drinking, agreed to join the study, and were randomly allocated to one of nine combinations of abstinence-oriented pharmacological and psychosocial treatments. Though more socially integrated and less severely dependent than some UK alcohol treatment caseloads, they were heavy drinkers, averaging 21 UK units (each 8g alcohol) most days.

Over the 16 weeks of treatment the core psychosocial support was nine appointments intended to represent a medical management programme deliverable by non-specialist primary care staff given adequate training and supervision. Typically sessions lasted under 20 minutes and focused on assessing, monitoring and feeding back the medical consequences of the patient's drinking, and promoting adherence to pharmacotherapy. Most of the staff delivering this care were nurses.

For half the patients, this medical care was supplemented by typically 10 sessions of psychological therapy incorporating motivational interviewing and cognitive behavioural and 12-step elements.

All the patients were also randomly allocated to pharmacotherapy consisting of dummy placebo pills, acamprosate, naltrexone, or both active medications.

The key question was how far the extra therapies improved on the study's most basic intervention – medical management with inactive placebo pills. Adding psychological therapy improved drinking outcomes to the point where medication failed to create further improvements. But roughly the same gains resulted from adding naltrexone, even without psychological therapy. These were the only supplements which created significant gains. Combining them and even also adding acamprosate did not further improve outcomes, and acamprosate alone did not augment outcomes from the basic intervention. For example, across the 16 weeks of treatment, 58% of patients receiving basic care achieved a "good clinical outcome" – drinking at most moderately with few adverse consequences – compared to 71–78% when either naltrexone or psychological therapy were added. Abstinence and relapse outcomes followed the same pattern as did outcomes a year after treatment, though by this time the differences had faded to the point where none were statistically significant.

Main findings: drinking

The featured analysis broadly replicated these findings with some significant nuances. Based on drinking records assessed by researchers at nine points during the 16 weeks, the patients clearly fell in to six patterns; three () were considered good outcomes and three () poor:
Abstainers: 37% of patients were very unlikely to drink on any of the days of the 16-weeks treatment period;
Infrequent drinkers: 24% of patients were consistently unlikely (between about 1 in 10 and 1 in 5) to drink on any of the days;
Frequent to infrequent: 12% of patients started the treatment period with around a 50% chance of drinking on any particular day but gradually drank less often, ending up drinking on around 30% of days;
Increasing to frequent drinkers: 11% of patients started being unlikely to drink (around a 1 in 10 chance on any day) but gradually drank more frequently until they drank on average about every other day;
Increasing to near daily drinkers: 8% of patients started the treatment period unlikely to drink but escalated until by the end they drank nearly every day;
Near daily drinkers: apart from a small dip at the start of the treatment period, 7% of patients drank virtually every day and by the end remained the most frequent drinkers in the study.

As in the original report, adding acamprosate to the care package made no difference to the chances that a patient would fall in to one or other category, but adding either naltrexone, psychological therapy, or both, increased the chances of a good outcome. However, they did so in different ways. Psychological therapy particularly helped prevent patients who started well escalating to near daily drinkers. In the absence of psychological therapy, naltrexone helped more patients sustain near abstinence. The two together (ie, psychological therapy plus naltrexone) particularly helped more patients decrease the frequency of their drinking over the 16-week period. Compared to medical care and placebo, it also reduced the numbers who escalated to near daily drinking but also the numbers who consistently abstained.

Main findings: heavy drinking

"Heavy" drinking was defined as any day on which a man drank five or more US standard drinks (nearly 9 UK units) or a woman four or more drinks (7 UK units). The featured analysis focused on a three-way classification:
Abstainers from heavy drinking: 60% of patients consistently almost never drank heavily;
Sporadic heavy drinkers: 30% of patients were consistently unlikely (about a 1 in 4 chance) to drink heavily;
Consistent heavy drinkers: another 10–11% of patients started treatment unlikely But still more likely than the other two categories. to drink heavily but then deteriorated until from the middle of the treatment period they had about an 8 in 10 chance of drinking heavily on any given day.

As in the original report, adding acamprosate to the care package made no difference to the chances that a patient would fall in to one or other category, but adding either naltrexone, psychological therapy, or both, increased the chances that a patient would almost never drink heavily. Though preferable to doing without both, combining naltrexone and psychological therapy was in one respect worse than doing either one or the other, slightly raising the chances of a patient being a sporadic heavy drinker.

The authors' conclusions

Compared to medical care and placebo tablets, this re-analysis of data from the COMBINE trial confirmed that naltrexone and the study's psychological therapy increased the probability of lower risk drinking trajectories during the 16-week treatment period, and also that acamprosate had no impact either alone or in combination with other treatments. The analysis also threw up some new findings, suggesting that there are subgroups of patients who derive greater benefit from specific treatment combinations.

In the absence of psychological therapy, naltrexone particularly reduced the probability of consistent near daily drinking and of escalating to frequent drinking. With or without naltrexone, psychological therapy reduced the numbers who escalated yet more sharply to near daily drinking, but did not increase the chances that a patient would consistently abstain.

Conceivably these findings reflect naltrexone's ability to blunt the rewarding effects of alcohol and the role psychological therapy played in preventing relapse in the face of high-risk situations. But this relapse-prevention effect is undermined if relapse occurs early before these skills have been learnt and practised. Such patients then potentially discontinue therapy, meaning they never benefit from its skills-acquisition phases.

The puzzle remains of why adding psychological therapy to naltrexone weakened the drug's ability to prevent consistent near daily drinking. Set against this however, it also decreased the numbers in the next worst category who escalated to near daily drinking, meaning that overall the combination did as well as naltrexone alone in preventing resumption of near daily drinking The same combination also led to the greatest chance that patients drinking on about half the days at the start of treatment would decrease the number of days on which they drank, perhaps consistent with gradually learning that drinking is (due to naltrexone) less rewarding and developing the skills to act on this by cutting back. Such an effect was invisible to the original analysis, which found the combination effectively equivalent to either of its components on its own.

It should be remembered that strict inclusion/exclusion criteria in the COMBINE study resulted in a relatively homogeneous sample of potentially more capable and compliant patients, who were able to achieve four days of abstinence before treatment started. In a more severe population, the drinking patterns identified by the featured analysis and the impact of the treatments on these might differ.


Findings logo commentary For these relatively stable and compliant patients, well structured but straightforward medical care plus naltrexone (in this case, 100mg a day) seemed at least as likely to achieve good outcomes as specialist psychological therapy. A similar message emerged from another US study which used the more typical 50mg a day dose: with naltrexone, primary care-style consultations were as effective as specialist cognitive-behavioural therapy; without the drug, cognitive-behavioural therapy was the more effective option.

Seemingly contradicting the featured study, several studies have found that naltrexone improves outcomes from cognitive-behavioural therapy. However, none compared this combination against naltrexone plus a systematic, compliance-promoting medical management programme.

Other studies have also found naltrexone effective in caseloads of the kind who might be treated in primary care, including one in which non-specialist nurses (who also formed the majority of the medical care staff in the featured study) delivered both medication and counselling. The featured study also confirms findings that acamprosate plus naltrexone at best only marginally betters naltrexone alone, which is generally more effective than acamprosate alone.

Now licensed for this purpose in the UK, the implications of these studies are that naltrexone can be a valuable supplement to medical counselling (by GPs or nurses) of dependent drinkers of the kind who might be treated in primary care, especially when specialist alcohol therapy is refused or unavailable. It is likely to be more effective than acamprosate, though more limited in its application due to contraindications and side-effects. However the featured study's medical counselling was possibly more structured and extensive in content (motivational support, compliance management, and education) and in time commitment than typical primary care approaches. In terms of which patients are suitable, level of consumption seems less important than whether they have retained sufficient stability to comply with treatment and are not so multiply problematic that more intensive care is required.

More comment and citations in the Findings analysis of the original results of the trial.

More on the featured study

Though an advanced study and a sophisticated analysis, the featured report's findings were often based on tests which the researchers decided to do after they had seen the results emerging from their new methodology. 'Post-hoc' analyses of this kind are best seen as generating hypotheses for testing in a study specially designed for this purpose. The main problem is that they can produce 'statistically significant' results by capitalising on what may in fact be chance variations in the effectiveness of the intervention between different subsamples or on different measures.

Other reanalyses of the COMBINE data have also used the methodology of the featured study. One applied it to drinking patterns in the three months As recalled by patients at the study baseline interview. before the patients entered the study to explore whether some types of drinkers may have responded better to the different treatments. Most notably this analysis suggested that acamprosate did have an impact, but a negative one, making some of most heavily dependent near daily drinkers (in particular, the ones able to stop drinking for the longest time – about 12 days – prior to starting treatment) more likely to drink heavily at the end of treatment than if they had been prescribed a dummy placebo tablet. An extended period of abstinence before treatment was also thought one of the reasons why the British acamprosate trial found no beneficial impacts Skip to UK acamprosate trial below.

In the featured study this negative impact of acamprosate on some patients was counterbalanced by positive impacts on other types of patients, especially intermediate severity patients who had drunk frequently before treatment but not nearly every day. These same intermediate patients also particularly benefited from naltrexone, being nearly twice as likely to sustain abstinence than if they had been prescribed a placebo. Another kind of analysis also spotlighted intermediate severity patients who before preparing for treatment had been drinking on 25% to 55% of days as particularly benefiting on the same yardsticks from acamprosate and naltrexone.

In contrast to the drugs, there was no sign that the study's psychological therapy was differentially effective for different types of pre-treatment drinkers. Like the featured analysis, these findings too were often based on 'post-hoc' analyses, so are best seen as generating hypotheses for testing in a study specially designed for this purpose.

A further analysis was similar to the one above, but divided patients up on the basis of their heavy drinking patterns before treatment. This time there was no indication that different types of patient benefited more or less from different treatments. However, it did confirm the previous report's finding that the very dependent near daily drinkers and heavy drinkers who stopped drinking on average 12 days before treatment started – several days longer than other patients – had very good drinking outcomes, almost as good as the low severity patients who were drinking or drinking heavily relatively All were dependent frequent drinkers. infrequently before treatment started. These were also the patients When pre-treatment drinking rather than heavy drinking was the criterion for identifying them. for whom acamprosate seemed counterproductive. Despite their very frequent heavy drinking before treatment and other indicators of severity of dependence, these patients were also the ones most likely to say they were committed to abstinence and demonstrated this by abstaining in the fortnight leading up to treatment entry.

Lastly the same methodology has been used to divide patients up on the basis of trends in how many of their prescribed tablets they took and how many therapy sessions they attended. Unsurprisingly, the most diligent patients also cut down their drinking and heavy drinking most, while those who early on started missing pills or sessions did worst. More interesting was that patients who missed sessions early (often due to dissatisfaction with their therapist) could substantially be 'rescued' from very poor heavy drinking outcomes if they had been prescribed one of the active medications rather than a placebo. Likewise patients who early on started to skip their prescribed acamprosate tablets could partially be 'rescued' in the same way by psychological therapy. It seemed that patients who effectively rejected either therapy or acamprosate could nevertheless be helped if they received a different kind of treatment.

Other studies of naltrexone and acamprosate

European studies of acamprosate have on average been more favourable than the featured analysis. Head-to-head trials (1 2) have found naltrexone somewhat more effective than acamprosate in reducing drinking. Naltrexone may also be the better option for people who are not aiming for or find it hard to stop drinking altogether, and for those with a strong desire to drink in order to achieve what they experience as a pleasurable state of intoxication. However, side effects are more common and more severe (though usually few patients have to stop taking the drug) than with acamprosate, and the drug is contraindicated in patients with certain liver problems or who are also dependent on opiates. There is also the complication that in a medical emergency, patients who have recently taken naltrexone will find that opiates fail to control pain, one reason why some prefer not to take the drug.

Without being conclusive either way, in line with the international literature, two major British studies provided greater support for naltrexone than for acamprosate. The negative UK findings on acamprosate may have been related to the fact that nearly a third of the patients in the study did not remain abstinent for the week before starting the treatment, a requirement in some other studies. Outcomes in the British study may also have suffered from not starting It was commenced on average 24 days after the start of detoxification, with an interval of over five weeks in some patients. the drug in the immediate post-withdrawal period, when theory suggests the drug's effectiveness should be at its height. This too may have been the reason why acamprosate appeared to worsen outcomes in the featured study for those heavily dependent patients who had been able to stop drinking on average 12 days before starting treatment.

Both UK studies suffered from high drop-out rates and poor compliance with treatment, but in the naltrexone study, patients who did complete the study and largely comply with treatment drank substantially less on naltrexone than on placebo tablets. One lesson from both studies seems to be that among typical British alcohol clinic caseloads, the support available from the staff and/or from families and friends is often insufficient to enable patients to sustain their commitment to treatment.

Given no overriding effectiveness differences, the decision between the two drugs can largely be a matter of individual choice and contraindications, licensing authorisation, and familiarity of the prescriber with the respective treatments.

For more details see these Findings analyses of an omnibus review of medical treatments for alcohol dependence, and of reviews focused on naltrexone and acamprosate. Another review has focused on the main alternative to these types of medications, disulfiram, which aims to enforce abstinence due to the aversive effects of drinking while the drug is active in the body.

UK policy and practice

In the last few years naltrexone has been licensed in the UK for the treatment of alcohol dependence, supplementing acamprosate and disulfiram. The delay seems merely to have been due to no company seeking a licence rather than any misgivings on the part of the authorities.

With the field now opened up, naltrexone may in this guise (as opposed to its established role in the treatment of opiate dependence) gain a greater UK profile, commensurate with the more positive UK and to a degree international findings compared to the main alternative, acamprosate. Whatever the balance between these two medications, disulfiram continues to have different role as an enforcer of abstinence rather than to promote reduced drinking, playing a major part in the pharmacotherapy offered by specialist centres in particular.

On the basis of the evidence, acamprosate, disulfiram and naltrexone are all endorsed in national guidance for Scotland and England and Wales. The guidance envisages a more routine and/or first-line post-detoxification role for acamprosate than for disulfiram, the latter coming with the caution that total abstinence is required to avoid unpleasant and potentially dangerous reactions, and that the positive evidence derives from situations where consumption has been supervised. Naltrexone is seen as fulfilling a similar role to acamprosate, but at the time the guidance was drafted it had no UK licence for the treatment of alcohol dependence, so the Scottish advisers felt they could not commend it for use in the NHS.

Though the positive US trials are acknowledged in the guidance for England and Wales, and despite its authorisation in the USA, injectable long-acting naltrexone is not recommended in either that or in the Scottish guidance. Greater risks due to administration by injection and its irreversibility, higher costs, and especially its non-approved status in the UK, mean this option will for the time being best be seen as a possible reserve for patients who have not done well with other therapies and who cannot be supported to consistently comply with oral naltrexone, especially if when they have taken the tablets, they have responded well to the medication.

Statistics for England in 2012 show that doctors in general have forefronted acamprosate, prescribed 117,405 times compared to 60,842 for disulfiram, figures dominated by GP prescribing. However, in hospitals disulfiram is prescribed slightly more often. In these settings patients are likely to be so severely dependent that at least initial abstinence is the preferred objective, and there is the support for patients and the expertise to handle the risks of prescribing disulfiram.

Thanks for their comments on this entry in draft to David Harding-Price, Council Member of the Royal College of Nursing of the United Kingdom. Commentators bear no responsibility for the text including the interpretations and any remaining errors.

Last revised 26 July 2013. First uploaded 15 July 2013

Comment/query to editor
Back to contents list at top of page
Give us your feedback on the site (one-minute survey)
Open Effectiveness Bank home page
Add your name to the mailing list to be alerted to new studies and other site updates


Top 10 most closely related documents on this site. For more try a subject or free text search

STUDY 2006 Naltrexone aids primary care alcohol treatment

STUDY 2005 'Real-world' studies show that medications do suppress heavy drinking

REVIEW 2011 Medical treatment of alcohol dependence: a systematic review

REVIEW 2011 Alcohol-use disorders: diagnosis, assessment and management of harmful drinking and alcohol dependence

STUDY 2013 Modeling the impact of alcohol dependence on mortality burden and the effect of available treatment interventions in the European Union

STUDY 2004 Naltrexone helps GPs and practice nurses manage alcohol dependence

STUDY 2010 Initial preference for drinking goal in the treatment of alcohol problems: II. Treatment outcomes

STUDY 2011 Modeling the cost-effectiveness of health care systems for alcohol use disorders: how implementation of eHealth interventions improves cost-effectiveness

REVIEW 2013 Metaanalysis of naltrexone and acamprosate for treating alcohol use disorders: when are these medications most helpful?

REVIEW 2012 Acamprosate for alcohol dependence: a sex-specific meta-analysis based on individual patient data





Acamprosate for alcohol dependence: a sex-specific meta-analysis based on individual patient data.

Mason B.J., Lehert P.
Alcoholism: Clinical and Experimental Research: 2012, 36(3), p. 497–508.
Unable to obtain a copy by clicking title? Try asking the author for a reprint by adapting this prepared e-mail or by writing to Dr Mason at mason@scripps.edu. You could also try this alternative source.

The first comprehensive analysis of whether acamprosate treatment works as well for alcohol-dependent women as for men definitively concludes that across 22 mainly European trials it has had a virtually identical impact. The analysis also reports the drug's overall impact, finding that it helps prevent heavy drinking as well as fostering abstinence.

Summary Traditionally alcohol dependence has been seen as a man's disease, and much of our understanding derives from studies largely of men. In particular, little is known about the efficacy of medications for alcohol dependence in women, including disulfiram, naltrexone, and acamprosate.

The featured analysis addresses this gap in respect of acamprosate, an oral prescription medication for the maintenance of abstinence in individuals with alcohol dependence. Acamprosate normalises neurotransmitter systems disrupted when alcohol-dependent individuals stop drinking, helping prevent this disruption from prompting relapse. In 23 trials in 18 countries which randomly allocated over 6000 patients to placebo or acamprosate, the drug has been shown to significantly increase the rate of abstinence relative to placebo without causing serious adverse effects. It is the most widely prescribed alcohol dependence medication in the United States.

However, only 22% of participants in acamprosate trials have been women, and outcomes have not been reported separately across these trials for men versus women, leaving it unclear whether the drug is equally effective and safe for both sexes.

The featured analysis searched for high quality trials available up to February 2011 which had randomly allocated patients to placebo or acamprosate. They had to have hidden this allocation from both patients and research assessors and reported impacts on some measure of drinking. The search included as yet unpublished trials and a request for trial data from the drug's developers.

Of the 22 such studies of adult patients, 17 had been conducted in Europe including one from the UK. In all, the trials involved 1317 women patients and 4794 men. Typically the trials excluded patients suffering significant psychiatric or medical disorders or dependent on other substances except tobacco. In all but three trials patients had to have stopped drinking for at least two days before being allocated to their medications. As well as medications, generally they received the alcoholism counselling offered at the participating clinics.

Compared to the men, the women in these trials were significantly more likely to be divorced or widowed and to also have suffered from drug abuse, anxiety, depression, and nonspecific psychiatric problems, and 22% versus 13% had attempted suicide. Despite being alcohol dependent for fewer years and drinking less, women exhibited significantly worse signs of impaired liver functioning.

Main findings

Outcomes were amalgamated across the trials using meta-analytic A study which uses recognised procedures to combine quantitative results from several studies of the same or similar interventions to arrive at composite outcome scores. Usually undertaken to allow the intervention's effectiveness to be assessed with greater confidence than on the basis of the studies taken individually. techniques. In analysing drinking outcomes, patients who had left trials early were considered to have been drinking through to the end of the trial unless the reason was clearly unrelated, such as moving out of the area. In general, relative to placebo the results showed acamprosate to have curbed drinking and heavy drinking about equally and to have caused no more adverse effects in women versus men.

Specifically, compared to placebo (average 43% days abstinent) acamprosate led to an extra 10% of days of non-drinking. Across placebo and acamprosate patients, women and men were abstinent on virtually the same proportions of days (48% and 47%), and the extra impact of taking acamprosate was about the same for both sexes (11% for women and 10% for men). Similarly, the 19% of placebo patients who sustained non-drinking throughout the trials was improved to 28% by acamprosate and improved roughly equally among women (from 17% to 25%) and men (from 19% to 28%).

Days when patients had drunk 'heavily' were defined as consuming at least 56g alcohol (seven UK units) for women and at least 70g (about nine UK units) for men. Across the trials placebo patients managed not to drink heavily on 53% of days, a figure improved by 11% by acamprosate. The extra impact of taking acamprosate was about the same among women (increased from 55% to 65%) and men (52% to 62%). Results were similar for the proportions of patients who avoided heavy drinking altogether, increased among women from 15% on placebo to 24% on acamprosate, and among men from 32% to 43%.

Compared to placebo, across both sexes acamprosate was associated with significantly higher rates of treatment completion (56% v. 52%) and compliance with taking medication (76% v. 72%). Acamprosate patients were no more likely than placebo patients to experience adverse events (and in particular, gastrointestinal, the main type associated with acamprosate) or as a result to leave the trials, and this was equally the case for women and men. However, across placebo and acamprosate patients, women reported significantly more at least moderately severe adverse events than men – 28% v. 20%.

Impacts of acamprosate on drinking outcomes varied substantially across the trials, particularly among male patients.

The authors' conclusions

The analysis shows that, compared to a placebo, acamprosate significantly improves rates of abstinence and no heavy drinking in both women and men with alcohol dependence, and also leads to significantly more patients completing treatment and taking their medication as intended. Women and men tolerated the drug equally well. The implication is that treatment providers may routinely consider acamprosate for treating alcohol dependence in both women and men, taking into account the patient's treatment goals and preferences as well as safety considerations specific to that individual.

In this, the largest trial-based dataset of women seeking treatment for alcohol dependence to date, despite a history of significantly more anxiety, depression, suicide attempts, drug abuse, interpersonal loss, and greater liver impairment than men, women responded comparably well to alcoholism treatment.

The results of this analysis are likely to be applicable to routine clinical practice because generally the clinics' routine counselling was provided and patients entered treatment in the normal way. However, some categories of patients were excluded. Selection of only rigorous trials suggests the amalgamated results can be relied on. However, results did vary substantially across the trials. Causes of this variation may include the recruitment of non-dependent patients to one of the trials, among whom acamprosate would not have been able to exert its normalising impact on neural systems because these would not have been disrupted by dependence and withdrawal; this trial was the only to have found acamprosate counterproductive among women. Similarly, results of a British trial which found negative effects of acamprosate among men could have been due to the recruitment of patients who were still drinking when they started treatment, so were yet to experience the neural disruption which acamprosate helps reverse.


Findings logo commentary The distinctive contribution of the featured analysis is to definitively confirm that on the evidence to date, alcohol-dependent women seeking treatment respond as well to acamprosate as men. In both sexes it typically made a modest but worthwhile contribution to sustaining abstinence and avoiding heavy drinking.

The analysis also offers a valuable update on the overall effectiveness of acamprosate across the sexes. With respect to abstinence, the results accord with a review conducted for the Cochrane Collaboration. This found that across all trials acamprosate reduced the risk of a return to drinking after detoxification to 86% of the risk with a placebo and increased the average time patients sustained abstinence by 11%. However, results differed in respect of heavy drinking. In the Cochrane analysis, across the six trials which yielded this data acamprosate made virtually no difference to the proportion of patients who returned to heavy drinking, though across seven trials, a biochemical marker indicative of heavy drinking was lower on acamprosate than on placebo, a finding which just failed to reach statistical significance. In contrast, with many more trials (about 20) to draw on, and a uniform and more precise definition of heavy drinking as excessive consumption on a single day, the featured analysis did find a significant improvement with acamprosate about as large as that found for the abstinence outcomes.

The Cochrane analysis agreed with the featured analysis that patients on acamprosate were slightly less likely (9% fewer) to drop out of treatment, but did find they were much more likely (35% more) to drop out early due to side effects and other adverse events, of which diarrhoea was the only one reported significantly more often on acamprosate. However, the numbers involved were generally few and the great majority of patients on either acamprosate or placebo completed the early phases of treatment.

The featured analysis attributes acamprosate's poor record in the major British trial to patients not having stopped drinking when they started the medication. Indeed, nearly a third 155 + 33 for whom no data and assumed to be drinking. of patients did not remain abstinent for the week before being randomised into the study, a requirement in some other studies. Outcomes in the British study may also have suffered from not starting It was commenced on average 24 days after the start of detoxification, with an interval of over five weeks in some patients. the drug in the immediate post-withdrawal period, when theory suggests its effectiveness should be at its height, the reason why UK guidance stipulates that acamprosate should be started "As soon as possible after assisted withdrawal". Also, many of the patients were episodic heavy drinkers and high drop-out and non-compliance rates meant that just a third of the sample completed the study, and by the end fewer than 30% were taking at least 90% of their tablets.

In contrast, in the major UK naltrexone trial, patients who completed the study and largely complied with treatment drank substantially less on naltrexone than on placebo tablets. One lesson from both trials seems to be that among typical British alcohol clinic caseloads, the support available from the staff and/or from families and friends is often insufficient to enable patients to sustain their commitment to treatment.

UK policy and practice

On the basis of the evidence, acamprosate, disulfiram and naltrexone are all endorsed in national guidance for Scotland and England and Wales. The guidance envisages a more routine and/or first-line post-detoxification role for acamprosate than for disulfiram, the latter coming with the caution that total abstinence is required to avoid unpleasant and potentially dangerous reactions, and that the positive evidence derives from situations where consumption has been supervised. Naltrexone is seen as fulfilling a similar role to acamprosate, but at the time the guidance was drafted it had no UK licence for the treatment of alcohol dependence, so the Scottish advisers felt they could not commend it for use in the NHS.

Statistics for England in 2012 show that doctors in general have forefronted acamprosate, prescribed 117,405 times compared to 60,842 for disulfiram, figures dominated by GP prescribing. However, in hospitals disulfiram is prescribed slightly more often. In these settings patients are likely to be so severely dependent that at least initial abstinence is the preferred objective, and there is the support for patients and the expertise to handle the risks of prescribing disulfiram.

For more on alcohol treatment medications see these Findings analyses of an omnibus review, and of reviews focused on acamprosate and the main alternative, naltrexone. Another review has focused on disulfiram, a different type of medication which aims not to help patients cut back but to enforce abstinence due to the aversive effects of drinking while the drugs is active in the body.

Last revised 17 July 2013. First uploaded 10 July 2013

Comment/query to editor
Back to contents list at top of page
Give us your feedback on the site (one-minute survey)
Open Effectiveness Bank home page
Add your name to the mailing list to be alerted to new studies and other site updates


Top 10 most closely related documents on this site. For more try a subject or free text search

REVIEW 2015 The efficacy of acamprosate and naltrexone in the treatment of alcohol dependence, Europe versus the rest of the world: a meta-analysis

REVIEW 2015 Risks and benefits of nalmefene in the treatment of adult alcohol dependence: a systematic literature review and meta-analysis of published and unpublished double-blind randomized controlled trials

STUDY 2005 'Real-world' studies show that medications do suppress heavy drinking

REVIEW 2010 Acamprosate for alcohol dependence

REVIEW 2013 Metaanalysis of naltrexone and acamprosate for treating alcohol use disorders: when are these medications most helpful?

REVIEW 2002 Convincing evidence that acamprosate and naltrexone help prevent alcohol relapse

STUDY 2012 Audit of alcohol detoxification at Leeds Addiction Unit

STUDY 2010 Naltrexone and combined behavioral intervention effects on trajectories of drinking in the COMBINE study

REVIEW 2010 Opioid antagonists for alcohol dependence

STUDY 2015 High-dose baclofen for the treatment of alcohol dependence (BACLAD study): A randomized, placebo-controlled trial





Integrated programs for mothers with substance abuse issues: a systematic review of studies reporting on parenting outcomes.

Niccols A., Milligan K., Sword W. et al.
Harm Reduction Journal: 2012, 9:14.
Unable to obtain a copy by clicking title? Try asking the author for a reprint by adapting this prepared e-mail or by writing to Dr Niccols at niccols@hhsc.ca. You could also try this alternative source.

The first systematic review of whether integrated substance use/parenting programmes improve the parenting of problem substance using mothers found remarkably few quality studies, but enough to suggest that such programmes can improve the prospects of often highly at-risk children.

Summary Treatment for mothers with substance use problems may be an important opportunity to improve parenting and break the intergenerational cycle of addiction and dysfunction. However, such women find it difficult to use conventional systems of care (for reasons including fear of losing custody of children, guilt, stigma, and lack of transportation), and prefer comprehensive services provided in a caring, 'one-stop' setting. Researchers, clinicians, and policymakers also recommend that substance use treatment programmes address women's needs and those of their children through comprehensive, integrated services at the same site.

The result has been the development of numerous programmes integrating addiction treatment with on-site pregnancy, parenting, or child-related services. Typically these provide individual addiction treatment, maternal mental health services, trauma treatment, parenting education and counselling, life skills training, prenatal education, medical and nutrition services, education and employment assistance, child care, children's services, and aftercare.

However, no review has yet systematically assessed the impact of these programmes on the quality of parenting. The featured review aimed to fill this gap, specifically by seeking evidence on whether integrated programmes are more effective than usual addiction treatment, and whether some features of integrated programmes are associated with better parenting outcomes than others.

The analysts searched databases for studies published in English from 1990 to May 2011 and conducted other searches to ensure as far as possible that all relevant studies were identified. Of the 31 studies which reported on the quality of parenting, just four were randomised trials; three involved mothers with children and one pregnant women. The women averaged 29–36 years of age. Most had experienced trauma and mental health problems, and were unemployed, single mothers. The children ranged from infants to adolescents. Programmes lasted three to 12 months and had a high dropout rate.

Main findings

Three of the trials addressed whether integrated programmes improve parenting more than usual addiction treatment by randomly allocating women and their children to one or the other. One assessed the involvement of the children with child protection services and found no differences attributable to integrated residential or outpatient programmes versus usual outpatient substance use treatment. The other two studies used standard interviews or questionnaires to assess the quality of parenting and/or the child-parent relationship as reported by the mother. Both involved methadone patients offered standard treatment (in one case plus recovery training) versus this plus group maternal psychotherapy. On a variety of measures they found typically small extra parenting improvements among mothers assigned to the psychotherapy.

The issue of whether some types of integrated programmes are more effective than others was addressed by examining all 31 studies with parenting outcome data, most of which simply assessed mothers in integrated programmes without comparing them with equivalent mothers not offered integrated treatment. Across these residential programmes seemed more effective than non-residential, and programmes which included a maternal mental health service more effective than those which did not.

One study randomly assigned mothers (of children under three) in outpatient substance abuse treatment to an attachment-based parenting intervention, or a parenting programme featuring case management and child guidance pamphlets. Immediately after these three-month programmes the attachment-based option had led to slightly greater improvements on some parenting measures, which six weeks later were no longer statistically significant.

In one study, as during treatment mothers became less depressed their parenting scores improved; in another, when their children had stayed with them in a residential facility, mothers were five times more likely to have custody of their children at the end of treatment.

The authors' conclusions

From the few randomised trials it seems that compared to usual addiction treatment, integrated programmes lead to small extra improvements in parenting. The one trial to assess involvement with child protection services found no differences, and no randomised comparisons assessed parenting attitudes, knowledge, or whether mothers retained or regained custody of their children. In three studies parenting improvements were associated respectively with an attachment-based parenting intervention, children residing in the treatment facility, and improvements in maternal mental health.

Even if the advantage of integrated programmes is small, this could have a large impact on the associated financial and human burden in this vulnerable population, for example by reducing the need for foster care, treatment of the child, psychiatric admissions, or by reducing crime.

A weakness of the randomised trials was that none directly observed the mother's parenting, perhaps a more objective and valid method than the mother's own accounts. Also, the studies comparing integrated to usual treatment did not assess some important areas of maternal functioning possibly impacted by substance use, such as maternal responsiveness, sensitivity, and reflective functioning, nor did they assess cost-effectiveness.


Findings logo commentary Given the importance of the issue, this was a remarkably sparse and weak set of studies, partly because of the restriction to mothers. It meant, for example, the exclusion of an important Australian study of methadone treatment patients caring for children; most but not all were mothers. On all the measures of parenting, child welfare risk, and child behaviour, patients allocated to a specially designed programme involving ten home visits over three months had improved substantially, while generally the others had not.

This study however was unable to tell whether the improvements were simply due to adding an extra intensive intervention, or due specifically to the parenting focus. Relevant to this issue, the featured review included two studies of methadone patients offered standard treatment or this plus recovery training, versus standard treatment plus group maternal psychotherapy. Where the same measures were used, the impacts of maternal psychotherapy seem to have been far greater compared to usual treatment rather than this plus recovery training, suggesting that doing something extra which was therapeutic was at least as much of an active major ingredient as focusing on parenting.

Partially set against this is the study cited in the review (1 2) which equalised the time mothers were offered in two forms of parenting interventions, one focused on emotions and attachment and the relationship with the child, the other on accessing external services (a 'case management' approach) and parenting education. The former generally led to greater improvements, but some were slight and with a small sample, few were statistically significant. These results do however suggest that content can matter, and perhaps too where services are provided (see below).

The studies found by the featured review leave us almost entirely in the dark on whether offering parenting support on-site as one of (as far as the patient is concerned) the services provided by the substance use treatment agency is preferable to referring patients to external support. Perhaps the critical factor will be the patients' feeling of safety at a familiar service not directly linked to statutory child protection, likely to increase the chances that they will admit to being in need of support and accept it. Another factor is the inevitable degree of attrition when patients are required to make another appointment and go somewhere else for services; even the willing will sometimes not get there. At US methadone treatment services just 10% of the children of patients who had aroused concern completed child development assessments off-site, but 85% when the assessment team visited the clinics and appointments were arranged to coincide with the patient's supervised consumption visit to the clinic. These considerations could be why (see previous paragraph) a case management approach to parenting support has been found less effective than direct on-site provision.

While the featured review uses the label 'integrated', the programmes it evaluated seem best described as on-site add-ons to substance use treatment rather than integrated with it in the manner of some programmes for mentally ill substance users, when the substance use treatment and the psychiatric components are both adjusted to the patient's condition and to each other.

The population addressed by the featured review – problem substance using parents – are a major concern for the UK where well over a million children have parents with a drug or alcohol problem. Across the UK, national targets, service standards and policy statements have embodied the perspective that their welfare is a core concern for services in contact with problem drug users, a contention featuring strongly in the latest Scottish and English drug strategies. In England it formed a specific workstream of the National Treatment Agency for Substance Misuse (NTA), which produced guidance on how authorities responsible for drug and alcohol services can work more closely with children and family services. In 2010 Scotland produced new child protection guidance which more fully addressed the issue of children affected by parental substance misuse.

For more see this Findings hot topic.

Thanks for their comments on this entry in draft to research author Alison Niccols of McMaster University in Canada. Commentators bear no responsibility for the text including the interpretations and any remaining errors.

Last revised 10 August 2013. First uploaded 22 July 2013

Comment/query to editor
Back to contents list at top of page
Give us your feedback on the site (one-minute survey)
Open Effectiveness Bank home page
Add your name to the mailing list to be alerted to new studies and other site updates


Top 10 most closely related documents on this site. For more try a subject or free text search

STUDY 2009 The Drug Treatment Outcomes Research Study (DTORS): final outcomes report

STUDY 2011 Monitoring and evaluation of family intervention services and projects between February 2007 and March 2011

STUDY 2012 An evaluation of the Option 2 intensive family preservation service

STUDY 2008 Final report on the evaluation of 'Option 2'

STUDY 2010 What works? A 15-year follow-up study of 85 young people with serious behavioral problems

STUDY 2012 The forgotten carers: support for adult family members affected by a relative's drug problems

STUDY 2014 Promoting supportive parenting in new mothers with substance use problems: a pilot randomized trial of residential treatment plus an attachment-based parenting program

REVIEW 2012 BAP updated guidelines: evidence-based guidelines for the pharmacological management of substance abuse, harmful use, addiction and comorbidity: recommendations from BAP

REVIEW 2011 Integrated substance abuse and child welfare services for women: a progress review

STUDY 2005 Abused women gain more from holistic counselling





An overview of prevention of multiple risk behaviour in adolescence and young adulthood.

Jackson C.A., Henderson M., Frank J.W. et al.
Journal of Public Health: 2012, 34(S1), p. i31–i40.
Unable to obtain a copy by clicking title? Try asking the author for a reprint by adapting this prepared e-mail or by writing to Dr Jackson at caroline.jackson@scphrp.ac.uk. You could also try this alternative source.

Different youth 'problem' behaviours overlap and share common causes, so it should make sense to implement programmes which affect several at once. That was the thesis of this Scottish review, which looked at studies reporting on both substance use and risky or underage sex. The literature was scarce but did give some reasons for optimism.

Summary Substance (alcohol, tobacco and illicit drug) use and sexual risk behaviour share some common underlying determinants. This 'rapid review' sought to synthesise the international evidence on 'what works' to prevent these overlapping risk behaviours, focusing largely on the 'microenvironment' rather than broader social and legal issues, and on universal approaches addressing whole youth populations rather than selected 'high-risk' groups or individuals.

The reviewers found no previous reviews of intervention studies which had reported multiple risk-behaviour outcomes, so instead they identified reviews focused on single risk-behaviours, and also looked for individual evaluation studies which reported both substance use and sexual risk behaviour outcomes. The latter had to be based on the young people's behaviour at age 11 to 25 and the impacts of interventions implemented between the ages of about five and 25.

Main findings

The featured article reported its findings separately based on its 'review of reviews' (broken down by type of intervention, eg, school-based versus parenting) and on its analysis of individual multi-outcome studies. It also included substantial consideration of the influences on risk behaviour beyond the type of specific interventions it reviewed. This account is based on the article's summary conclusions.

Reviews of studies addressing single risk behaviours indicated that evidence for the effectiveness of most approaches was mixed or limited due to few studies. Policy interventions and mass-media approaches, such as those which have focused on smoking, have had some success. School-based curriculum-focused programmes appear insufficient on their own to prevent risk behaviour, but whole-school approaches which also address the school's ethos and environment show some promise. Family/parenting programmes have also had mixed success, with the most promising intervention being the Strengthening Families Program for Parents and Youth 10–14 [Editor's note: described in this Findings review]. Maintaining family connectedness into the adolescent years, an aim of this programme, may help to reinforce and strengthen some of the protective factors needed to prevent risk behaviour. Multi-domain interventions have also had some success in reducing risk behaviour, though again, evidence is mixed.

The review of individual studies found that the common feature of interventions which affected both substance use and sexual risk behaviour was their multi-component nature, addressing influences on risk behaviour at individual, school and family and community levels [Editor's note: see for example this review of the impact of such interventions on drinking]. This pattern is consistent with the findings of the review of reviews, suggesting that complex interventions may be more effective than more traditional curriculum-only school programmes. [Editor's note: the same authors have produced a more extended analysis of the same studies.]

The authors' conclusions

On the evidence to date, the most promising interventions for reducing several risk behaviours simultaneously are those which address multiple domains of risk and protective factors, perhaps because they match the multi-faceted nature of the causes of risk behaviour. Such interventions largely aim to bolster young people's resilience, supported by promoting positive parental/family influences and/or healthy school environments which foster positive social and emotional development.

Timing is likely to be very important, particularly in relation to periods of transition in young people's lives. Programmes were commonly implemented at ages 11–12, during transition into adolescence, or at ages 13–14, when risk behaviours, or experimentation with them, may already have started. The Seattle Social Development Project was the only identified programme implemented in the pre-adolescent early years of primary school. Its success, especially in reducing sexual risk behaviour, suggests that intervening in early mid-childhood can have an impact on later risk behaviour. It may not be too late to intervene during teenage years, but addressing underlying determinants of risk behaviour early in childhood may have a greater impact than only intervening in adolescence.

Although substance use and sexual risk behaviour share common underlying determinants, the contribution of these factors varies. For example, a survey of a sample of Scottish schools found that differences between schools in the prevalence of smoking was related to school-level characteristics such as the school's focus on caring and inclusiveness, while underage sex was related to individual and neighbourhood socioeconomic factors. Such findings provide further support for a holistic approach to preventing several risk behaviours at once.

The main limitation of our review of reviews was that it depended on what has previously been reviewed and the way those reviews classified interventions. This hampered the identification of common features (such as duration or use of booster sessions) which might characterise successful interventions for different risk behaviours.

Methodological differences between individual studies also made it difficult to identify elements of successful interventions. The studies also tended to suffer from methodological limitations and short follow-ups. They also were rarely replicated in other populations or countries and often did not assess whether the intervention was equally effective for both sexes and for people at different socioeconomic levels. In turn this made it difficult to determine the interventions' impacts on health inequality. However, it seems likely that health equality considerations will mandate a combination of universal approaches and those targeted at higher risk groups.

Beyond specific interventions

As well as appropriate intervention programmes, steps are needed to reduce the exposure of young people to negative influences, and to increase opportunities for engaging in activities that nurture positive development. Policymakers should be act on the evidence that broader social change is needed to reduce negative societal influences and marginalisation, social exclusion and the vulnerability of young people during periods of transition in their lives. Further consideration below.

Among these broader influences are those exerted during very early childhood, which affect health and wellbeing throughout the life course, influencing literacy and numeracy, mental health, heart disease, criminality, and social participation. Although pre-school interventions can improve child development and life success, they are not always effective in preventing risk behaviour in young people [Editor's note: see this Findings hot topic on early years interventions].

Regulatory and legislative measures that increase price and impose marketing restrictions can help to reduce smoking by young people may also reduce drinking. However, these measures may be circumvented, so should be considered part of a larger package of preventive measures and thoroughly evaluated. Media ads and portrayals also affect a variety of health behaviours. The media industry could take more responsibility for the role they play, and parents need to be more aware of the role of media in their children's development and how to minimise it. Other dimensions of the social context also play a role, including cultural norms, access to attractive leisure and social facilities, and opportunities for engaging in health-enhancing activities.

Early childhood through to young adulthood includes various transition periods, each with the potential for increasing young people's vulnerability. Recent studies of young people in transition to adulthood highlighted the importance of social mobility, education, personal competence and resilience, as well as gender, neighbourhood deprivation and family support.

Last revised 18 July 2013. First uploaded 18 July 2013

Comment/query to editor
Back to contents list at top of page
Give us your feedback on the site (one-minute survey)
Open Effectiveness Bank home page
Add your name to the mailing list to be alerted to new studies and other site updates


Top 10 most closely related documents on this site. For more try a subject or free text search

REVIEW 2015 Prevention of addictive behaviours

DOCUMENT 2011 European drug prevention quality standards: a manual for prevention professionals

REVIEW 2014 Interventions to reduce substance misuse among vulnerable young people

HOT TOPIC 2015 It’s magic: prevent substance use problems without mentioning drugs

STUDY 2006 Effective delivery and positive message works for school-based media campaigns

STUDY 2009 Evaluating mediators of the impact of the Linking the Interests of Families and Teachers (LIFT) multimodal preventive intervention on substance use initiation

STUDY 2011 Effects of the Positive Action programme on problem behaviours in elementary school students: a matched-pair randomised control trial in Chicago

STUDY 2008 Substance use outcomes 5½ years past baseline for partnership-based, family-school preventive interventions

DOCUMENT 2012 The government's alcohol strategy

STUDY 2009 Blueprint drugs education: the response of pupils and parents to the programme





L10 Web Stats Reporter 3.15 LevelTen Hit Counter - Free PHP Web Analytics Script
LevelTen dallas web development firm - website design, flash, graphics & marketing