Drug and Alcohol Findings home page in a new window EFFECTIVENESS BANK BULLETIN 28 March 2012

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.


Motivational interviewing helps heavy drinking US students cut down ...

Inform and exhort not enough to improve hospital screening rate ...

How therapists can engage parents in family therapy ...

Month-long opiate-blocking injections help Russian addicts stay off heroin ...

A review of motivational interviewing-based interventions targeting problematic drinking among college students.

Branscum P., Sharma M.
Alcoholism Treatment Quarterly: 2010, 28, p. 63–77.
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 Branscum at branscpw@mail.uc.edu.

Studies published in the mid-2000s confirm that counselling based on motivational interviewing helps heavy drinking US college students control their drinking and reduce related problems.

Summary The Task Force on College Drinking established by the US National Institute on Alcohol Abuse and Alcoholism (NIAAA) considers motivational interviewing to be one of the few interventions clearly shown to reduce drinking in the college setting. Motivational interviewing is a counselling approach which avoids explicit confrontation and seeks to engender motivation by highlighting the client's own reasons for changing substance use.

This review aimed to summarise new findings for motivational interviewing interventions for college students and derive implications for research and health-promoting interventions. A search was conducted for English-language research articles documenting studies of motivational interviewing in colleges published from 2003–2008.

Eleven such studies were found. In these, five interventions targeted heavy-drinking college students and four 'adjudicated' students who had to attend because they had broken college rules regarding alcohol. The remaining two targeted underage In the USA 21 years of age is the legal drinking age. students and men in their first week of classes. Interventions typically lasted about an hour.

Main findings

Across these studies it appears that motivational interventions consistently reduced drinking and related problems among college students and high-risk subgroups. However, only three studies used the research design (a randomised controlled trial) best able to determine whether the intervention actually caused the reductions, and all three targeted heavy drinkers. Four studies had no comparison or control A group of people, households, organisations, communities or other units who do not participate in the intervention(s) being evaluated. Instead, they receive no intervention or none relevant to the outcomes being assessed, carry on as usual, or receive an alternative intervention (for the latter the term comparison group may be preferable). Outcome measures taken from the controls form the benchmark against which changes in the intervention group(s) are compared to determine whether the intervention had an impact and whether this is statistically significant. Comparability between control and intervention groups is essential. Normally this is best achieved by randomly allocating research participants to the different groups. Alternatives include sequentially selecting participants for one then the other group(s), or deliberately selecting similar set of participants for each group. groups against which to benchmark changes associated with the intervention, including two of the four of adjudicated students. Given that the students in these studies tended to be unusually heavy drinkers, lack of control/comparison groups makes them vulnerable to the tendency for atypical behaviour to normalise over time even without intervention ('regression to the mean'). It is also possible that adjudicated students cut back due to the sanctions imposed by the college and the wish to avoid being caught again. Studies which did feature a comparison intervention rarely described in sufficient detail what that intervention consisted of. On the plus side, most studies had adequate follow-up assessments of at least three months.

Many of the studies do not appear to have been based on a theory of how the intervention might lead to changes in drinking and related problems, though implicit in several was the idea that motivational interviewing could stimulate the desire to change in initially unmotivated students.

The authors' conclusions

Interventions based on motivational interviewing reduce drinking and related problems among college students, but analysis of the reviewed studies suggests their effectiveness might be improved by:
• using a standard calendar-based assessment of how much and when the student has been drinking as part of the counselling process;
• offering personalised feedback on their drinking and related problems;
• counselling which features open questions that invite elaboration by the student, and responses by the counsellor which elaborate on and then reflect back their own comments to the student ('complex reflections').

Findings logo commentary As with motivational interviewing for young people in general rather than just college students, lack of adequate comparison interventions raises doubts over whether the motivational nature of the interviews was the active ingredient, or whether any acceptable and feasible intervention would have been just as effective.

One riposte to such doubts is that among people not seeking help, motivational interventions (which do not confront or insist that participants accept a clinical label or a pre-determined outcome) are among the few which are acceptable to the participants and feasible – feasible partly because they are acceptable, and partly because they can be quite brief. Another is that we have evidence – from studies of young people among others – that what happens during motivational sessions does matter. In particular, from a British study of further education students and others from Switzerland, it seems that it is important to embody the overall spirit of the approach and, in finer detail, to use (as the featured review concluded) the skill of reflective listening to 'play back' to the client an elaborated version of their own comments.

The issue of whether other counselling/information-giving styles might have been just as effective as motivational interviewing was also addressed in a review which aggregated results from 62 studies evaluating attempts to curb risky drinking among college students. In line with the featured review's conclusions, among the interventions with the strongest research backing were individual, face-to-face discussions which adopted a motivational interviewing style, and which featured personalised feedback on the individual's drinking profile – in particular, 'normative' feedback setting their drinking and/or risks alongside national or local norms.

Most if not all the reviewed studies were conducted in the USA, where drinking is illegal below age 21 and attitudes to drink and youth drinking differ from those in the UK. However, a UK study which also tested motivational interviewing among college students found that in the short term this did reduce smoking, drinking and cannabis use among further education students already using stimulants and/or regularly using cannabis.

Last revised 15 March 2012

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STUDY 2009 What makes group MET work? A randomized controlled trial of college student drinkers in mandated alcohol diversion

STUDY 2010 Clinical outcomes of a brief motivational intervention for heavy drinking mandated college students: a pilot study

REVIEW 2014 Interventions to reduce substance misuse among vulnerable young people

STUDY 2009 Thinking about drinking: need for cognition and readiness to change moderate the effects of brief alcohol interventions

STUDY 2009 Dismantling motivational interviewing and feedback for college drinkers: a randomized clinical trial

REVIEW 2012 Efficacy of brief alcohol screening intervention for college students (BASICS): a meta-analysis of randomized controlled trials

STUDY 2011 Fidelity to motivational interviewing and subsequent cannabis cessation among adolescents

REVIEW 2015 Prevention of addictive behaviours

REVIEW 2011 Effectiveness of motivational interviewing interventions for adolescent substance use behavior change: a meta-analytic review

STUDY 1999 Students respond to brief alcohol intervention

Does implementation of clinical practice guidelines change nurses' screening for alcohol and other substance use?

Tran D.T., Stone A.M., Fernandez R.S. et al.
Contemporary Nurse: 2009, 33(1), p. 13–19.
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 Tran at Danielle.tran@swsahs.nsw.gov.au. You could also try this alternative source.

Hospital nurses in Sydney in Australia were trained to implement a new screening and intervention policy aiming to upgrade the identification of hazardous drinkers and other substance users among medical and surgical inpatients. Disappointing results highlight the need to do more than inform and exhort if practice is to change.

Summary To improve nurses' screening of patients for substance use problems during routine admission procedures, a large metropolitan health service in Sydney in Australia developed a clinical guideline titled Substance Use Screen Policy which was distributed to all its facilities and implemented through an in-service education programme. Half-day workshops covered topics such as managing withdrawal, intoxication and overdose. Training in brief interventions included 'safe' levels of smoking or drinking, smoking cessation techniques, illicit drug use, access to needle exchange programmes, and patient education pamphlets. Nurses who could not attend were given education packages with workshop handouts. The featured study investigated the effectiveness of this dissemination effort.

Data for the study was derived from medical record audits conducted in selected medical and surgical wards of two metropolitan hospitals prior to and three months following implementation of the guideline. According to the new policy, records for newly admitted patients should document whether they had been asked about smoking, drinking and drug use, their substance use, withdrawal symptoms, any related treatment given, and whether any further actions or plans had been agreed. A preliminary audit found that only 20% of admission records had complete substance use histories. Implementation of the guideline was expected to raise this to 50%.

Main findings

Audits were completed on 79 pre-implementation and 84 post-implementation patient records. Respectively, these documented screening for alcohol use in 28% and 29% of cases which resulted in 14 and 5 patients being identified as drinkers. Corresponding figures for smoking were 29% and 23% and 11 and 8. Further evaluation of these medical records demonstrated no differences in the assessment of smoking habits and quitting between pre- and post-implementation audits. Screening for illicit drug use was more commonly documented after guideline implementation than before (16% v 8%), but no patients screened positive. Before or after implementation, none of the records documented interventions such as brief advice or referral to substance use services.

The authors' conclusions

This study highlighted the difficulties of introducing and sustaining change amongst health professionals. Implementation of the policy of substance use screening via in-service education was ineffective in changing the substance use screening practice of nurses. Computerised reminders which automatically alert nurses to the need to screen may have improved implementation. Also, the workshops and education packages simply gave nurses information rather than involving them in interactive learning, a sub-optimal teaching strategy, and follow-up consultation was left to the trainees (who sought little further advice) rather than actively pursued. Lacking too were management structures to monitor and promote implementation and to refresh training to cater for staff turnover.

Uptake of screening may also depend upon the nature of what was being asked. A companion study found that nurses and other health professionals often felt it was not easy to broach and discuss alcohol and other substance misuse, especially illicit drug use, due to social, cultural, legal and emotional reasons. They may consider substance use as personal issues, be reluctant to obtain information about criminal activities, or lack adequate skills in asking about substance misuse.

Findings logo commentary Guidance from Britain's National Institute for Health and Clinical Excellence (NICE) insists that health service commissioners and managers "must" provide the required training, resources and time to implement alcohol screening and brief intervention, including on general hospital wards. Reflecting this advice, the 2012 national UK alcohol strategy called for programmes to identify hazardous drinkers in NHS services. It was specific about how this will be done in primary care by GPs and pharmacists, where alcohol identification and any subsequent brief advice will be incorporated in the NHS Health Check for adults aged 40 to 75 from April 2013. Accident and emergency departments and hospitals in general were also encouraged to check for and offer brief advice about hazardous drinking, drawing on the services of alcohol liaison nurses who will also manage patients with alcohol problems, liaise with community alcohol and other specialist services, and support other healthcare workers in the hospital.

However, the evidence that brief advice on hospital wards cuts drinking is patchy, and for Britain in particular, unconvincing. Alcohol liaison nurses now seem common in hospitals, but are often diverted from identifying and advising hazardous drinkers and focus as much or more on managing alcohol-dependent patients. Findings has analysed this literature and offered a fuller account of UK studies and policy and practice.

For more on implementing screening and brief intervention run this Findings search. Among the retrieved analyses is a UK-focused review for Britain's National Institute for Health and Clinical Excellence of what impedes or promotes the implementation of brief alcohol interventions.

Last revised 08 April 2012

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STUDY 2013 Screening and brief intervention for alcohol and other drug use in primary care: associations between organizational climate and practice

STUDY 2014 The effectiveness of alcohol screening and brief intervention in emergency departments: a multicentre pragmatic cluster randomized controlled trial

STUDY 2011 An evaluation to assess the implementation of NHS delivered alcohol brief interventions: final report

DOCUMENT 2011 Services for the identification and treatment of hazardous drinking, harmful drinking and alcohol dependence in children, young people and adults

DOCUMENT 2009 Screening and brief interventions (SBI) for unhealthy alcohol use: a step-by-step implementation guide for trauma centers

STUDY 2012 Alcohol screening and brief intervention in emergency departments

DOCUMENT 2011 Alcohol dependence and harmful alcohol use quality standard

STUDY 2010 Cluster-randomized controlled trial of dissemination strategies of an online quality improvement programme for alcohol-related disorders

STUDY 2012 Alcohol screening and brief intervention in primary health care

STUDY 2013 Effectiveness of screening and brief alcohol intervention in primary care (SIPS trial): pragmatic cluster randomised controlled trial

Therapist behavior as a predictor of black and white caregiver responsiveness in multisystemic therapy.

Foster S.L., Cunningham P.B., Warner S.E. et al.
Journal of Family Psychology: 2009, 23(5), p. 626–635.
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 Foster at sfoster@alliant.edu. You could also try this alternative source.

How to get parents more engaged in becoming a positive influence over their seriously delinquent drug abusing teenagers through family therapy integrated in to a US juvenile drug court. Some of the therapist tactics expected to work did deepen engagement, others did not.

Summary Multisystemic Therapy (MST) is an intensive family-and community-based treatment programme which focuses on the entire world of chronic and violent young offenders – homes, families, schools, teachers, neighbourhoods and friends – in the attempt to reduce antisocial and undesirable behaviour including problem substance use. It targets severe and intractable offenders aged 12–17 with very long arrest histories. MST clinicians are always on call, and work intensively in the home and elsewhere with parents or other caregivers to improve parenting and help focus the child on school and gaining job skills. Therapist and caregivers also introduce the child to sports and recreational activities as an alternative to 'hanging out'. Each therapist has a small caseload of one to five families. On average, treatment lasts four months and the therapist spends several hours a week with the child and/or their family.

The featured study addressed two gaps in research on this approach. First, whether therapist comments and responses expected to deepen the engagement of caregivers and make them feel more positive about the treatment process actually do have this effect. Secondly, whether such skills were more or less important for black families and whether matching these families with a black therapist would deepen engagement and make caregivers feel more positive.

Data for this analysis were drawn from audiotapes of mid-therapy Months two and three, chosen to capture the period when engagement is likely to be the most difficult because therapists are most likely to be making demands of caregivers in the attempt to improve parenting. sessions involving 89 The ones with decipherable audiotapes. of the 94 families/children allocated to Multisystemic Therapy as part of a study of the effectiveness of integrating this approach into a court specialising in young drug-related offenders. The youngsters aged 12–17 were randomly allocated to be sentenced and supervised by this court with or without also being offered Multisystemic Therapy, which was for some randomly selected children also combined with rewards and sanctions contingent on urine test results ('contingency management'). The original study concluded that in respect of substance use reductions, adding Multisystemic Therapy improved the effectiveness of the court. In this study, two thirds of primary caregivers identified themselves as black or African-American. Of these, 85% were living at or below the poverty level compared to 25% of white caregivers.

In consultation with MST therapists, scales were developed to identify therapist behaviours thought to contribute to treatment success with families in general and black families in particular. For families in general, these were:
• teach: the therapist directs the session, instructs, or educates the client, but not in an authoritarian manner;
• problem solve/collaborate: the therapist suggests an idea or plan of action;
• validate/empathy: the therapist legitimises the client's point of view or feelings; and
• reinforce: the therapist comments positively on a specific client behaviour or statement.

Four other behaviours were deemed especially relevant for black families:
• instrumental support: the therapist offers specific help with practical needs;
• strength focus: the therapist highlights something positive about the client, family, or situation;
• takes responsibility: eg, the therapist admits lack of understanding or acknowledges their possible contribution to a problem in therapy; and
• storytelling: the therapist uses a story or an example to illustrate a point.

The other side of the therapeutic interaction is the caregiver's responses. These were classified along two dimensions:
• positive responses: the proportion of caregiver comments which expressed agreement with the therapist about strategies, plans, or outcomes, or positive opinions, feelings, judgments, or hope.;
• engagement: a general impression of the degree to which the caregiver was involved in sessions, embracing commitment to therapy and agreement on treatment.

These therapist and caregiver behaviours were rated for each of an average eight segments Therapy sessions were transcribed verbatim and segmented into thought units (sentences or phrases that expressed complete thoughts). Transcripts were then divided into segment groups of approximately 100 thought units per group to ensure that each session was divided into equal parts. Transcript lengths varied from two to 20 segment groups. of each audiotaped therapy session.

The key issue was whether generally, and for black caregivers in particular, these therapist and client behaviours were related in such a way as to provide guidance on how therapists can deepen caregiver engagement and promote positive responses to therapy. Relationships were assessed within the same segment of the session and across succeeding segments.

Main findings

Within the same segment of a therapy session, and regardless of race, race-match, or socioeconomic status, of the eight therapist behaviours thought related to better engagement, five actually were: teach; strength focus; problem solve; reinforce; and instrumental support.

Across all clients and therapists, all but the last were also related to more positive responses from the caregiver, but here the picture was complicated by different relationships for different categories of clients and the match with their therapists. For example, another therapist behaviour – expressing empathy/validation – was only related to more positivity when the caregiver was white and the therapist black or vice versa, not when they were the same colour. Storytelling too was associated with positivity only among the less poor and (once poverty had been taken in to account) the black families.

These relationships might as easily represent an effect of the client on the therapist as the reverse. More indicative of the direction of any causal effects are relationships between how the therapist behaved in one segment and differences That is, not just how the caregiver subsequently behaved, but how this differed from their behaviour in the previous segment. in how the client responded in the next. Across all clients and therapists, there was one significant relationship: the more directive ('teach') the therapist had been in one segment of the session, the less engaged the caregiver became in the next. But among the poorer families, being directive also led to more positive responses from the caregiver. The influence was two-way; how the client behaved also seemed Caregiver engagement increased the probability of therapist reinforcement later in the session. For white caregivers, caregiver positive responses increased the likelihood of later therapist storytelling. Caregiver positive response predicted increased strength focus for disadvantaged families. to influence the therapist.

Another analysis focused on whether therapists behaved differently with black versus white caregivers. Significant findings were that practical ('instrumental ') support was more often That is, present in more segments. offered to black caregivers, and a strength focus and reinforcing statements were more common when therapist and caregiver were not racially (ie, black v. white) matched.

The authors' conclusions

The findings suggest that in this form of family therapy, relationship-focused strategies (strength focus, reinforcing, instrumental/practical support) on the part of the therapist are associated with greater engagement and positive responses by the caregivers of highly antisocial children, and that some therapist behaviours are more important or felt more relevant for black versus white families.

However, black versus white differences should not be over-emphasised. Though a previous MST study linked therapist–caregiver ethnic match with improved youth outcomes, in the featured study such a match was not associated with caregiver engagement or positive responses. Once poverty had been taken in to account, generally black or white caregivers responded similarly to their therapists. Regardless of caregiver race, two therapist behaviours expected to be especially relevant to black families (instrumental support, strength focus) and three expected to be generally relevant (teach, problem solve, reinforce) were significantly related either to caregiver engagement quality and/or positive responses. These signals or expressions of warmth and genuineness seem influential across racial and socioeconomic divides.

Although many findings were similar for white and black caregivers, a few differences emerged. Among these were that therapists were more likely to offer black families practical support, and that therapist storytelling predicted positive responding from more economically advantaged caregivers and from black but not white caregivers. It could be that offering 'real-life' examples is most helpful with families from economic backgrounds similar to those of their therapists. When therapist and caregiver were not the same colour, therapists tended to (and perhaps needed to) work harder to establish rapport, evident in their greater reliance on a strength focus and reinforcement, and in the fact that expressing empathy or validating the caregiver's perspective was more influential than when both were either black or white.

In terms of deepening caregiver engagement, findings supported Multisystemic Therapy's focus on building caregiver skills by identifying family strengths, dealing with practical issues, and reinforcing attempts at improved parenting. Complex findings in respect of therapist directiveness (teaching and problem solving) appear to reinforce that done skilfully and in moderation these need not arouse resistance in the client and cause them to distance themselves from therapy, but that this is a risk, at least for some caregivers.

It should be borne in mind that these findings derived only from the middle phase of therapy, and that it is not known whether therapist behaviours which improved caregiver responses also helped achieve the ultimate objectives of the therapy – to improve family and youth functioning. Also, the analyses of matching therapists to caregivers involved mainly a relatively crude black versus white matching. Finally, the significant interactions found between the variables and categories measured by the study only slightly exceeded the number to be expected purely by chance, so the findings should be considered tentative and in need of replication.

Findings logo commentary The processes probed by the featured study are important partly to the degree to which they show how an effective intervention (one implemented in several parts of the UK) might work and be made more effective. Based on findings generally from child and adolescent psychotherapy, psychotherapy with adults, and couples and family therapy, if Multisystemic Therapy is effective, then deepening the family's engagement in the process in ways suggested by the study can be expected to improve ultimate outcomes. Multisystemic Therapy is widely considered to have one of the best records in fostering more pro-social behaviour among highly troubled and troubling teenagers, but this record is reliant mainly on studies conducted by the approach's developers, studies whose rigour has been challenged. Details below.

For Britain's National Institute for Health and Clinical Excellence (NICE), Multisystemic Therapy is one of a family of programmes which integrate intervention in to several aspects of a child's life and environment which it recommended for children and young people who misuse alcohol who also have other major problems and/or limited social support.

According to the independent US Coalition for Evidence-Based Policy, randomised controlled trials of MST have found sizeable decreases in the amount and severity of criminal behaviour by young offenders. However, they saw the approach as promising rather than proven, and qualified their endorsement by suggesting that effectiveness may depend critically on close adherence to the intervention's key features and the population or setting in which it is implemented. For this their main evidence was a Canadian trial in which the intervention was less well implemented than in other trials, and the sample was less poor and had access to more extensive social and health services than in US studies.

This verdict based on four randomised trials is to some extent challenged by a systematic review of eight randomised trials of the approach, which concluded that it has not been shown to have clinically significant advantages over usual services or other interventions for youngsters with social, emotional or behavioural problems. Though tending to favour MST, pooled results from the studies did not reveal statistically significant advantages in terms of children being removed from home, crime, arrests or convictions, child psychiatric symptoms or family functioning, and when all the sample was included in the analysis, no study found significant differences in substance use.

Referring to the Canadian study highlighted by the Coalition for Evidence-Based Policy, the reviewers suggested that it might have found MST was equalled by usual services not only because these were relatively extensive, but also because the study was an unusually rigorous test. Specifically, the reviewers saw it as the only trial conducted fully independently In several social research areas,1 programme developers and other researchers with an interest in the programme's success have been found to record more positive findings than fully independent researchers. In the case of the eight MST studies, six were conducted by the approach's developers.

1. See articles at the following web addresses:
of the developers of the approach, and in which results from all the randomised participants could included over a defined follow-up period. A methodological critique of MST studies from the lead author of the review has been contested by the approach's developers and researchers, a rejoinder in turn contested by the reviewer.

The featured study's finding that matching (in terms of black versus white) the race of the therapist and caregiver did not deepen caregiver engagement or positive responses is in line with general findings in couple and family therapy. According to a review commissioned by the American Psychological Association, across these approaches there is no evidence that therapist gender, race/ethnicity, or therapist-family ethnic match are significant factors in the strength of the alliance between therapist and client or affect the degree to which this is related to outcomes.

Last revised 27 March 2012

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STUDY 2009 Multidimensional Family Therapy for young adolescent substance abuse: twelve-month outcomes of a randomized controlled trial

REVIEW 2011 Evidence-based therapy relationships: research conclusions and clinical practices

STUDY 2011 Treatment of adolescents with a cannabis use disorder: Main findings of a randomized controlled trial comparing multidimensional family therapy and cognitive behavioral therapy in The Netherlands

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

REVIEW 2011 Evidence-based psychotherapy relationships: The alliance in child and adolescent psychotherapy

STUDY 2013 Multidimensional family therapy lowers the rate of cannabis dependence in adolescents: A randomised controlled trial in Western European outpatient settings

REVIEW 2006 Motivational arm twisting: contradiction in terms?

STUDY 2010 A randomized pilot study of the Engaging Moms Program for family drug court

DOCUMENT 2009 Management of cannabis use disorder and related issues: a clinician’s guide

REVIEW 2011 Evidence-based psychotherapy relationships: Alliance in couple and family therapy

Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomised trial.

Krupitsky E., Nunes E.V., Ling W. et al.
Lancet: 2011, 377, p. 1506–1513.
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 Krupitsky at kruenator@gmail.com. You could also try this alternative source.

In Russia, injecting detoxified opiate addicts with long-acting naltrexone which blocks opiates for a month meant more were able to stay off the drugs, findings which helped persuade US authorities to approve it for this role. Others argue this was precipitate given the lack of evidence on overdose protection.

Summary Naltrexone is an opiate antagonist which has no psychoactive effects of its own but blocks the effects of heroin and other opiate-type ('opioid') drugs. An implant form inserted under the skin lasts up to six months, but involves minor surgery with occasional adverse reactions at the injection site. An alternative long-acting formulation approved in the USA and Russia for medical use For treatment of alcohol dependence and, partly on the basis of the featured study, in the USA now too for treating dependence on opioid drugs. instead takes the form of an intramuscular depot injection which blocks the action of opiate-type drugs for a month or possibly longer. Both avoid the need to take the medication daily, in theory overcoming the main shortcoming of oral naltrexone – that patients usually stop taking the tablets and resume heroin use.

In this trial in Russia (where opiate substitute prescribing using drugs like methadone is not permitted), the long-acting injection was tested as a way of sustaining abstinence from opiate-type drugs among opiate addicts who had been withdrawn from these drugs at 13 inpatient centres. Of 335 screened for the study, 250 voluntary That is, not subject to justice system coercion. Patients also had to be free of major psychiatric problems and of dependence on other drugs and to have a close associate like a relative or partner who could supervise their compliance with therapy and the study's requirements. patients completing their detoxifications joined it and were randomly allocated to naltrexone injections or to injections of a similar looking but inactive placebo. Injections started within a week of the completion of detoxification and were then scheduled to be re-administered every four weeks until 24 weeks, after which patients were to be offered long-acting naltrexone for another year. During the 24 weeks of the study patients could attend fortnightly counselling sessions.

Patients were typically young men in their late twenties and early thirties who had already spent nearly three weeks in inpatient detoxification. Over 4 in 10 were HIV positive and about 9 in 10 infected with hepatitis C. Of primary interest was whether they were opioid-abstinent (according to urine tests and their own accounts) during each week of the final 20 weeks of the 24-week follow-up; before this, some were expected to 'test' whether the injections really did block the effects of heroin or other opioids.

Main findings

Results were analysed on the basis that missing urine tests would have revealed that the patient had used opiate-type drugs. Over 4 in 10 tests were missing, almost exclusively because treatment had been prematurely terminated. Retention was, however, significantly better on the active naltrexone injections. By the end of the study just over half (67 of 126) of these patients remained in the study and in treatment compared to just over a third (47 of 124) assigned to placebo injections. Nearly 60% of naltrexone patients had all six of their scheduled injections compared to just over 40% on placebos.

In either group only a minority were known to have been totally abstinent, but the key finding was that on average naltrexone patients could be shown to have sustained abstinence in 18 of the 20 weeks of the assessment period compared to just 7 for placebo patients, a highly statistically significant difference. The gap between the proportions of patients sustaining abstinence became apparent by the second week of the trial and remained to the final week, when just over half the naltrexone patients could be shown not to have used opiate-type drugs compared to just over a third on placebos. On the assumption that patients not re-assessed were continuing with their pre-treatment opioid use, according to their own accounts, over the full 24 weeks of the follow-up on virtually no days had naltrexone patients lapsed to opioid use compared to 40% on placebos. The severity of relapse was indicated by the fact that 17 placebo patients were known At the end of the study and if patients missed urine tests or discontinued treatment, where possible their dependence was tested by administering a short-acting opioid antagonist. to have become once again physically dependent on opioids compared to just one on naltrexone.

Compared to placebo patients, in each week of the follow-up period naltrexone patients on average reported On the assumption that craving was unaltered when records were missing. less intense craving for opiate-type drugs and their craving remained lower than at the start of the study. In contrast, the impulse to use remained high among placebo patients. More generally too, and much more so than placebo patients, naltrexone patients had reduced their risk of infection and improved their health and quality of life, on several measures to the point where they no longer scored substantially worse than Russian norms.

Though naltrexone patients were more likely (over a quarter did) to experience some adverse side effects thought due to the treatment, none were judged serious and just two patients stopped treatment as a result, the same as on placebos. No overdoses or deaths were documented and no patient experienced pain which could not be relieved. However, liver enzyme abnormalities were more commonly found among naltrexone patients.

The authors' conclusions

The results of this study suggest that extended release naltrexone offers a new approach – distinct from maintenance using opioid agonists Drugs which have opiate-type effects. like methadone – which helps patients abstain from opioids and prevents relapse to opioid dependence. It found that detoxified, opioid-dependent adults voluntarily seeking treatment who received naltrexone experienced more weeks free of opioid drugs than those who received a placebo, and did so regardless of age, sex, or duration of opioid dependence. Naltrexone patients experienced a persistent anti-craving effect, fewer confirmed relapses to dependence, and nearly double the typical retention in treatment of placebo patients. These benefits were rapid and persisting and more apparent than in studies which have used oral naltrexone, which patients have to take every day, and which less effectively maintains blood levels of the active ingredient.

Injectable extended release naltrexone was generally well tolerated by the patients and no new safety concerns were reported. Though more naltrexone than placebo patients adverse events, similar numbers stopped treatment as a result or experienced serious adverse events. Abnormal liver function tests occurred only in patients infected with hepatitis C. Pain at the injection site pain was more common when naltrexone was injected but was not severe. No patient suffered intractable pain, though those in pain or who might be were excluded from the trial.

The study took place where the main alternative pharmacotherapy for opioid dependence – substitute opioids like methadone – was unavailable; findings may not generalise to other jurisdictions. But even where methadone and allied agonist options are available, extended release naltrexone might attract patients whose employment prohibits opioid use, those early in their addiction careers, and those who want to secure their recovery after a successful course of agonist therapy.

Findings logo commentary In the UK, neither implants nor depot injections of naltrexone have been licensed for medical use; they can still be (and have been; 1 2 Revill J. "A Comparative study of the protective benefits of oral and implanted naltrexone in a British NHS general practice." Abstracts from 7th International Conference 2002. Stapleford Trust. 3 Daly M. "Implant progress blocked." Druglink: September/October 2004, p. 12–13. 4) used, but patient and doctor have to accept the added responsibility of a product which has not yet been shown to meet the safety and efficacy requirements involved in licensing.

A criticism of trials to date is that they included highly selected patients. However, in this they may have reflected normal practice. Patients will only opt for such procedures if they are prepared (irreversibly in the case of depot injections) to commit to possibly weeks or months without the effects of heroin or other opiate-type drugs. From the control groups in naltrexone implant/depot studies, we know that even in these caseloads, treatment drop-out and relapse are common. Long-acting naltrexone helps these highly motivated patients sustain their resolve.

The clearest candidates for the treatment are patients who are motivated (perhaps because due to employment or other pressures, they have to) to return to a life without opiate-type drugs including prescribed substitutes, have the resources, stability and support to sustain this, are unlikely to simply use other drugs instead, but who when free to experience heroin and allied drugs, cannot resist using them, possibly reflected in their poor compliance with oral naltrexone regimens. The treatment may also be considered for unstable patients at very high risk of overdose, but who will not accept or do poorly in substitute prescribing programmes.

Naltrexone implants and depot injections impede opiate-based pain relief. This is a greater problem with the irreversible long-acting naltrexone injection than with implants which can be removed. Possible adverse effects of naltrexone on liver function – seen in the featured study among patients infected with hepatitis C – are also a concern based on early studies, but not one confirmed in several later studies.

About the study

The featured study demonstrated both the advantages and the limitations of an opiate-blocking agent which patients have to be motivated enough to renew every four weeks. The sample seem relatively promising: their major drug problems were limited to opiate-type drugs, they were in relatively good psychological health, had voluntarily submitted themselves to several weeks inpatient detoxification, completed this, remained opiate-free and stable enough to about a week later commence longer term treatment, had someone close and supportive enough to supervise them, and were prepared to take a 50-50 chance of being injected with a drug which would extend by four weeks the period during which they would not experience opiate effects. Even those assigned to placebo avoided opiate use on most days during the 24-week follow-up and – after on average 10 years of dependence – over a third could be shown to be abstinent from opioids in the final week.

This performance was achieved with the support of one counselling session a fortnight and an inactive injection. More active and structured aftercare (for example, regular monitoring, continued well organised care from the initial service, or active referral) might have narrowed the differences between the groups. However, highly motivated patients and imperfect aftercare arrangements probably reflect the conditions in which the injections would be deployed in normal practice. Set against this backdrop of perhaps inadequate aftercare, active injections substantially elevated opioid use outcomes and substantially improved general health and welfare. Yet it seems these benefits were concentrated in about half the patients who took all their injections, completed the study, and were abstinent from opioids in the final week. For the other half, four-weekly naltrexone injections and infrequent counselling were insufficient.

As with any abstinence-based treatment, relapse risking overdose due to lost tolerance to opiate-type drugs is a serious concern. Criticism of the trial has focused on the apparent lack of comprehensive enquiries to establish whether patients who dropped out of the study had died. The few studies to date of naltrexone implants suggest these protect against overdose while they are active, and that in caseloads prepared to undertake these procedures, opiate overdose reductions can outlast the active period of the implants. However, implants last up to six months while injections last four weeks, offering more opportunity to discontinue the treatment, re-experience opiate-type drugs, and risk taking too much.

Given excess drop-out on placebos, some of the advantage found for the naltrexone injections must have been due to the assumption that drop-outs were still using opiate-type drugs and doing so at the same rate as before treatment. Though the 'worst case' is a common and defensible assumption in research, it also seems possible that some of these motivated patients, discovering they had been allocated to placebo, discontinued treatment and participation in the trial yet managed well without treatment, or found alternative sources of support for their recovery.

Another issue is less a criticism of the trial, than of its acceptance in the process of approving the injections for the treatment of opioid dependence in the USA, where opiate substitute prescribing is available and has a proven lifesaving record. The argument is that in such countries the issue is not whether depot naltrexone is better than an inactive placebo, but whether it at least matches methadone maintenance, the standard pharmacotherapy, an argument which would apply also to the UK. In response, US authorities have pointed out that even where methadone treatment is available, many patients do not or cannot enter it, and that naltrexone is intended for a different caseload – one which has already overcome physical dependence on heroin and allied drugs and wishes to sustain this without dependence on similar-acting medications.

The study was sponsored and (with the researchers and others) designed, analysed and interpreted by the pharmaceutical company which manufactures depot naltrexone. The first author was a consultant to the company and the only author to have had full access to the original data without having to make a specific request. He also made the final decisions on all parts of the featured report. Three other authors were full-time employees of the company. This degree of involvement raises concerns over the independence of the study from pharmaceutical industry influences with a strong interest in finding positive results. Studies have found that industry-sponsored research is significantly more likely to reach conclusions favourable to the sponsor than studies not sponsored by the pharmaceutical industry. This seems partly because industry-sponsored trials are more likely to compare their products with an inactive placebo than an active alternative treatment.

Other similar trials

Another randomised trial of the same long-acting form of naltrexone has been conducted in the USA. Compared to placebo, this injection lasting four weeks nearly doubled the time heroin dependent patients were retained in aftercare following inpatient detoxification. On the credible assumption that drop-outs relapsed, there was a similar impact on heroin use. At the four-week choice point when the naltrexone patients could have refused the second set of injections, few did so, most committing themselves to another period without (or with reduced) opiate effects. Though encouraging, multiple exclusions (such as psychiatric conditions or dependence on other drugs) and the recruitment procedures (partly through newspaper ads) meant the patients may not have been typical of usual caseloads.

Results echoed those of a similar study in Norway, where – though permitted – access to substitute prescribing programmes is restricted, particularly for people unwilling to contract to forgo not just heroin, but persistent substance use of any kind. There a randomised trial used a naltrexone implant whose opiate-blocking effects last about six months. Over these six months, usual-care patients leaving inpatient detoxification recalled using opiate-type drugs on average on 97 days, implant patients on just 37. By the end, 18 out of 27 usual-care patients but just 9 of 29 implant patients continued to meet criteria for opioid dependence. As in the featured study, patients assigned to long-acting naltrexone were much less likely to experience craving. Again in this study, implants were compared against relatively weak The usual aftercare against which the implants were compared does not appear to have been a continued service from the clinics, but external counselling and other services which (if necessary with help from the clinics) patients would have had to arrange for themselves. aftercare arrangements.

Though in Russia methadone is not an alternative treatment, oral naltrexone is and might have been used as a comparator instead of placebo. The chances are however that the long-acting formulation would still have proved superior. This was the case in an Australian study of patients who had completed outpatient detoxification and were assigned either to naltrexone tablets or to an implant thought to block opiate effects for several months. By the end of the six months of treatment, a range of alternative measures confirmed that the implants had helped prevent relapse to heroin use, despite the fact that for the last half of this period the implants would have partially or altogether lost their potency.

For more Findings analyses of long-acting naltrexone treatment for opiate dependence click here.

Last revised 19 March 2012

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