Drug and Alcohol Findings home page in a new window EFFECTIVENESS BANK Bulletin 28 November 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.


These additions to the Effectiveness Bank all concern the treatment of drug and alcohol problems, contrasting the primacy of psychosocial therapies and the failures of drugs in the treatment of stimulant dependence, with virtually the reverse in the treatment of dependence on opiate-type drugs. Last entry confirms that motivational interviewing, the all-purpose Swiss army knife of therapy, may be more compact than other tools, but no more effective.

PROMETA drug protocol does not help treat methamphetamine dependence ...

Retention universal marker of successful opiate addiction treatment ...

No quick way out of treatment for prescription opioid addicts ...

Motivational interviewing works but no better than other therapies ...

Double-blind placebo-controlled evaluation of the PROMETATM protocol for methamphetamine dependence.

Ling W., Shoptaw S., Hillhouse M. et al.
Addiction: 2012, 107(2), p. 361–369.
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 Hillhouse at hillhous@ucla.edu. You could also try this alternative source.

The US company which owns and markets the controversial PROMETA proprietary combination of drugs for methamphetamine dependence funded a rigorous trial by independent researchers; the result was a no-better-than-placebo verdict, another negative in the search for drugs to counter stimulant dependence.

Summary After cannabis, the powerful stimulant methamphetamine is the most abused illicit drug worldwide, with 15–16 million regular users, yet there are no approved medications for the treatment of methamphetamine dependence.

A proprietary system of treatment for methamphetamine dependence, the PROMETATM protocol, combines medications purported to normalise brain systems altered by chronic stimulant use along with psychosocial treatment designed to minimise withdrawal symptoms, prevent relapse and reduce cravings. Of the three medications in the protocol, flumazenil is the principal element. Among other effects, the drug works via the GABA neurotransmitter system to block the action of benzodiazepine tranquilisers and sleeping pills. Medically it is used to reverse deep sedation and as an antidote to benzodiazepine overdose. A second element is gabapentin, an anti-convulsant which also acts on the GABA system and which has been used as an analgesic. It has been reported to reduce craving and other subjective effects of cocaine. Last is hydroxyzine hydrochloride, an anti-anxiety drug which has been widely used in the management of withdrawal from substance dependence.

The featured study was conducted when this protocol was being heavily publicised and was subject to a great deal of debate and controversy in drug abuse, investment and news media circles. Proponents were buoyed by anecdotal reports and uncontrolled studies, while opponents cited the lack of data from placebo-controlled trials. In just such a trial, the study aimed to evaluate the efficacy and safety of this protocol in the treatment of methamphetamine dependence. It was funded by the company which owns the protocol, which also referred people seeking treatment via its call centre to the researchers and trained the researchers in the protocol to ensure their implementation matched the company's specification. The company played no other part in the study.

The study recruited adults seeking treatment for methamphetamine abuse or dependence and who had used the drug on at least four of the last 30 days. The 120 eligible for and who agreed to join the study were allocated to one of three clinics which offered a 40-day medication regimen beginning with five infusions (at two clinics on an inpatient basis) plus 14 weekly sessions of cognitive-behavioural therapy over the roughly 15 weeks of the trial. For a randomly selected half of the patients, the medication was the PROMETATM protocol; the other half were given identical but inactive placebo preparations (except that they too were offered the anti-anxiety agent hydroxyzine hydrochloride, not considered a key element of the protocol). The study based its findings on the 111 patients who at least began the medication/placebo regimens. Typically they were white single men in employment who on average had used methamphetamine more than every other day and had used for about 10 years. Over 8 in 10 were on probation or parole and most had a history of physical and sexual abuse.

Main findings

Just half the 60 patients allocated to the protocol stayed in the study until the end of the 40-day medication phase and 18 to the end of the study. Corresponding figures for placebo patients were 42 and 26. At no point (until the end of the medication infusion phase, of all medication, or of the study) were there any statistically significant differences between PROMETATM and placebo patients in the proportions of weekly urine tests which indicated no methamphetamine use, or in the proportions of patients with three consecutive methamphetamine-free tests. Proportions of methamphetamine-free urine tests increased over the course of the study, but to the same degree regardless of whether the active protocol was administered or a placebo.

This general picture was replicated by the patients' own accounts of their methamphetamine use, by the end of the study among retained patients averaging just four to five days a month, regardless of whether real mdeication had been taken. Craving for methamphetamine too fell roughly equally over the course of the study and retention or compliance with taking medication did not significantly differ. Safety concerns were few. No adverse occurrences or experiences were deemed definitely related to the study drugs, and only one One participant in the PROMETATM group who neglected to report a history of seizures, experienced a generalised tonic clonic seizure during the first infusion. was probably related.

The authors' conclusions

Under the conditions of this study, treatment with the combination medication protocol was no more effective than placebo in reducing methamphetamine use or craving or keeping patients in treatment. The results were negative and clear: active medication and placebo groups showed no statistically significant differences in drug use as measured by urine testing or self-report, or in self-reported craving. Both groups substantially reduced their reported methamphetamine use. The placebo group remained in the study for on average about 17 days longer than the medication group, not a statistically significant difference after age had been taken in to account. There were no clinically relevant differences in the pattern or severity of adverse events that would imply a greater risk in either group.

These findings differ from those of another randomised and placebo-controlled trial of a similar medication combination, which did find reductions in methamphetamine use associated with the protocol. A possible explanation could be the influence of the marketing campaign which occurred during the featured trial, which may have elevated Editor's note: Presumably by elevating patients' expectations of benefit. the placebo effect. Inpatient hospitalisation for infusion at two of the sites may have also contributed to a strong placebo effect. Consistent with this explanation, at the end of treatment at one of the clinics twice as many patients believed they had received active medication as believed they had received a placebo. Regardless of whether they actually did receive active medication, these patients were twice as likely to be abstinent at the end of the study. Perhaps too the psychosocial components of the treatment were stronger in the featured study.

Findings logo commentary These findings, which do not even hint at a positive impact from a (in the USA) fairly widely implemented treatment, represent another blow to attempts to find pharmacological solutions to dependence on stimulant drugs. At the same time, among the minority of patients who stayed in the study to be assessed, they are a testament to the power of the patient's desire to get better and the impact of psychological and social influences – in particular, the belief that they are receiving a treatment which works, even if in reality it is an inactive placebo.

The more positive earlier trial referred to by the authors lasted just 30 days, and even then, by the end the gains associated with the active medication had nearly evaporated. In the final week patients who had received active medication said they had used methamphetamine on 41% of days, those given placebo, 44%, a minimal difference. After day six of the trial urine test results did not significantly differ between the two sets of patients. The report on the study says it was "double-blind', presumably meaning that both investigators and patients did not know which patient was in which group, but how blinding was achieved is not detailed, nor whether it successfully hid who got what, and whether medical staff too were blinded is unclear. From the featured study, it seems that anything which enabled patients to deduce or guess whether they had been given active medication could have accounted for the positive results. Possibly too, the fact that in the featured study the great majority of patients were under criminal justice supervision gave those who could get better such a strong incentive to do so that the drugs made no further difference. How many might have been in this position in the earlier trial was not reported.

The one seizure in the featured study is consistent with the warning from a commentator on the study that "the adverse effects of this medication combination, especially the risk of seizures associated with flumazenil, merits caution, especially in view of the frequent comorbidity of seizures in methamphetamine users".

The evaluated protocol has been the subject of considerable controversy in the USA. Attempts have also been made to gain a foothold in the UK. The confidential protocol is marketed by a US healthcare services management company which does not manufacture or distribute the medications. Rather than a new drug, it combines in what the company describes as "a unique dosing algorithm" several medications approved by US authorities, but not for the treatment of substance dependence. According to the company, the treatment programme it markets which features the protocol is "the only outpatient program to uniquely combine medical and psychosocial therapy into one integrated program". Apparently Though elsewhere it is said that rather than having changed its name, "Hythiam operates through a wholly owned subsidiary Catasys Health".
the company changed its name (1 2) in March 2011 from Hythiam to Catasys which now markets a similar treatment under the trade name OnTrakTM.

Last revised 26 November 2012. First uploaded 22 December 2012

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

REVIEW 2008 The search for medications to treat stimulant dependence

STUDY 2011 Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomised trial

STUDY 2010 Ultra-rapid opiate detoxification followed by nine months of naltrexone maintenance therapy in Iran

STUDY 2010 An open trial of gabapentin in acute alcohol withdrawal using an oral loading protocol

STUDY 2010 Randomized controlled trial of dexamphetamine maintenance for the treatment of methamphetamine dependence

REVIEW 2008 Treating pregnant women dependent on opioids is not the same as treating pregnancy and opioid dependence: a knowledge synthesis for better treatment for women and neonates

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

STUDY 2009 Naltrexone implants after in-patient treatment for opioid dependence: randomised controlled trial

STUDY 2006 Long-acting depot naltrexone extends opiate abstinence

STUDY 2008 Maintenance treatment with buprenorphine and naltrexone for heroin dependence in Malaysia: a randomised, double-blind, placebo-controlled trial

A review of opioid dependence treatment: pharmacological and psychosocial interventions to treat opioid addiction.

Veilleux J.C., Colvin P.J., Anderson J. et al.
Clinical Psychology Review: 2010, 30, p. 155–166.
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 Veilleux at jcveille@uark.edu.

This wide-ranging review uniquely draws together findings from authoritative reviews of rigorous research conducted for the Cochrane collaboration and later studies concerned with the pharmacological and psychosocial treatment of dependence on opiate-type drugs like heroin, concluding that retention is the common key to success.

Summary This wide-ranging review uniquely draws together findings from authoritative reviews of rigorous research conducted for the Cochrane collaboration and later studies concerned with the treatment of dependence on opioids Drugs with opiate-type effects (including analgesia and the capacity for producing euphoria and dependence) derived from the opium poppy like opium, heroin, and morphine (know as opiates) and synthetic drugs with similar effects like methadone and buprenorphine. – opiate-type drugs like heroin. The review covers pharmacological treatments aimed at withdrawing patients from these drugs altogether, substituting less damaging opiate-type drugs, and maintaining abstinence, plus psychosocial approaches like counselling and therapy. Studies on minors or pregnant women were excluded, as pharmacological treatments for these populations often follow different trajectories

Main findings


Detoxification aims at stopping opioid use altogether and withdrawing opioids from the body in a controlled and humane fashion, maximising retention and detoxification success rates while minimising discomfort. The two broad approaches are:
• abrupt termination of opioid use, after which withdrawal is sometimes precipitated by an 'antagonist' drug which blocks the action of opiate-type drugs and/or sometimes ameliorated by administration of the alpha2 adrenergics lofexidine and clonidine, which help reduce withdrawal symptoms;
• gradually reducing doses ('tapering') of opiate-type drugs such as buprenorphine or methadone.

After dealing with the options in detail, the review concludes that any pharmacological treatment confers benefits. If using an antagonist to precipitate withdrawal, clonidine and lofexidine may reduce the intensity of the withdrawal syndrome. However, tapering doses of methadone and buprenorphine seem to be associated with longer retention and fewer side effects. Psychological and social therapy or support may promote adherence to the treatment regimen and bolster social support variables known to promote positive outcomes. For example, compared to pharmacological treatments alone, supplementing this with contingency management, The systematic application of rewards and sanctions for desired behaviour such as not using drugs or complying with treatment. positive engagement of the patient's social network, psychotherapeutic counselling, or family therapy, results in higher rates of treatment compliance and completion, more patients abstinent at follow-up, and less opioid use.

Abstinence-focused long term interventions

Following detoxification many opioid addicts want to sustain a complete divorce from an opioid-dependent lifestyle. This relapse prevention phase is aimed at the long-term maintenance of an opioid-free life, typically (in pharmacological treatment programmes) by administering the opioid antagonist naltrexone which blocks the action of opiate-type drugs. Some of the advantages of naltrexone are that it decreases opioid craving and can be administered in a non-specialist medical outpatient setting.

However, naltrexone has been used only minimally in the past 20 years, primarily because patients refuse (or refuse to comply with) the treatment. Related to poor retention (most studies end with less than half the original sample), data on effectiveness is not encouraging. A recent systematic review found no statistically significant differences between naltrexone and placebo in treatment retention or relapse rates, even when naltrexone was supplemented by psychosocial support. It is important to note that rates of relapse in such studies are already skewed, because naltrexone cannot be used long-term without initial detoxification, and many patients are unable to endure withdrawal.

Despite poor treatment completion rates, naltrexone can confer benefits, such as leading to lower heroin use during treatment and decreased criminal activity compared to placebo. For patients strongly motivated to remain opioid-free, such as health professionals, business executives, and legally mandated addicts, naltrexone may be an effective option. However, several benefits are only apparent in programmes which achieve high long-term retention rates. Moreover, there is evidence that low compliance with naltrexone can actually have deleterious long-term effects. One study found that patients who use naltrexone effectively for a short period and subsequently return to opioid use are more likely to drop out of treatment completely and return to a fully dependent lifestyle.

Sustained-release depot naltrexone injections and implants require less frequent administration because their effects last much longer. In 2008 a systematic review of trials of these forms of the drug found only one methodologically rigorous study, which concluded that higher doses of sustained-release naltrexone were associated with lengthened treatment and less self-reported need for heroin. The review also assessed less rigorous studies which suggested that adverse effects from sustained-release naltrexone were similar to those from oral naltrexone, though both result in more adverse effects than a placebo.

Adding supplementary treatment components may reduce drop-out rates and increase naltrexone's effectiveness. Examples include combination buprenorphine/naltrexone treatment, inclusion of psychosocial therapies and supports, and incorporating families into the treatment process.

Maintenance/harm-reduction strategies

Long-term maintenance prescribing of opiate-type drugs is aimed at reducing the intensity, frequency, and length of relapse to use of non-prescribed opioids, promoting psychosocial adjustment, and limiting overdose risk, criminal activity, and HIV infection. The principal mechanisms are reducing craving for opioids, preventing negative withdrawal symptoms, and blocking euphoric effects if opioids are used. Though patients are still physically dependent on the substitution medication, maintenance treatments result in less time spent on drug-related activities and may allow dependent individuals to transition to abstinence-based programmes.

The four most frequently studied medications are methadone, LAAM, buprenorphine, and heroin itself (diacetylmorphine). After assessing each, the review concludes that though questions remain regarding their comparative efficacy, all are preferable to no treatment. Treatment retention and suppression of opioid use are the usual outcomes measured, but a recent systematic review revealed that entrance into any maintenance programme also curbs HIV risk behaviours including injection drug use, needle sharing, and number of sexual partners, and prevents HIV infection.

In particular, the most widely studied medication, methadone, has been found superior to treatments which do not involve substitute prescribing (detoxification, wait-list controls, abstinent-focused rehabilitation, and placebo controls) in terms of treatment retention and opioid use as assessed by self-report and urinalysis. Effects are dose-dependent; higher dosages are more effective than lower doses in retaining patients, reducing heroin and cocaine use, and preventing withdrawal symptoms.

Comparisons between the medications suggest that methadone should remain the first line of treatment, although buprenorphine may be a viable alternative when high doses of methadone are unavailable or medically contraindicated. One shortcoming of buprenorphine is that it may not be as cost-effective as methadone, though the cost difference may be offset by the fact that buprenorphine requires less monitoring and appears to have a better safety profile than either methadone or LAAM.

Psychosocial treatments

Psychosocial treatments may also be important ways to improve retention and prevent relapse. Two systematic reviews have investigated their role in the long-term treatment of opioid dependence. The first compared stand-alone psychosocial treatments with pharmacological maintenance treatments, concluding that there was insufficient evidence to support psychosocial treatments without medication. Two of the psychosocial treatments (reinforcement based intensive outpatient treatment and enhanced outreach counselling) seemed to be beneficial compared to pharmacological treatment alone, but the small sample sizes did not support a robust conclusion.

The second systematic review [Editor's note: since materially updated] compared agonist treatment alone to agonist treatment with an adjunct psychosocial component. It found that the only benefit of adding psychosocial treatment was to increase the number of people who remained abstinent at follow-up. Since the typical standard of care in pharmacological maintenance treatments already includes counselling, this analysis was looking specifically at additional structured psychosocial treatments, not the role of any psychosocial component compared to medication only.

Crisis management

Fatal overdoses are one of the most common causes of death for heroin addicts. The first line of treatment for overdose is the short-acting opioid antagonist naloxone; it has no effect on non-opioid dependent individuals and has no abuse potential, is ideally suited to reverse the respiratory depression that typically accompanies opioid overdose, and may prevent hypoxic brain injury in non-fatal overdoses.

Few studies have systematically investigated training programmes on managing overdose, though some recent studies have found that training increased opioid addicts' knowledge of overdose and the correct administration of naloxone, and produced preliminary evidence that prescription of take-home naloxone can reduce overdose fatalities.

The authors' conclusions

The systematic reviews synthesised by the featured review focused on several key outcome variables: treatment retention, duration of treatment, opioid use, adverse effects, and in studies of detoxification, severity of withdrawal. Of these, treatment retention is significant regardless of treatment strategy. Drop-out is associated with negative outcomes, such as greater risk of overdose, return to opioid dependence, increased HIV rates, criminal behaviour, and general strain on medical and social service systems. Whether the goal is detoxification, abstinence, or long-term maintenance on a substitute medication, keeping patients in treatment longer is often appropriately considered a primary goal.

All the psychopharmacological medications discussed in this review appear to have a place in the treatment of opioid dependence. Alpha2-adrenergic agents are helpful for completion of opioid detoxification, particularly when precipitated by the opioid antagonist naltrexone. Burgeoning evidence however suggests that buprenorphine may be more effective as a detoxification agent. As a partial agonist, buprenorphine maintains heightened levels of opioids in the brain, but a ceiling on its opiate-type effects also helps prevents overdose and abuse.

At first blush, methadone appears to be more effective than LAAM, heroin, or buprenorphine for long-term maintenance treatments, but it should be remembered that methadone enjoys greater longevity than the other treatments, both in terms of research and patient acceptance. As patients become more accustomed to a variety of options, and as subgroups of patients are identified (eg, heroin maintenance for people with an unsuccessful history of methadone treatment), the predominance of methadone may weaken. In particular, the fact that buprenorphine can be administered in routine outpatient settings will probably become paramount as the case-mix shifts from patients dependent on illegal heroin to those using medical opioids [Editor's note: see this example].

A pessimistic reading of the research reviewed is that psychosocial therapies administered with or without pharmacological treatment confer few benefits, particularly when supplementing long-term maintenance. However, in detoxification programmes, psychosocial components clearly help improve adherence to treatment and reduce opioid use, and the implications of other findings may not be as bleak as they initially appear. Some psychosocial therapies (outreach counselling and brief outpatient therapy plus contingency management) have resulted in lower relapse rates and higher treatment retention, although the benefits were not sustained. Because most maintenance programmes include some psychosocial services already, it is unclear exactly which psychosocial components augment pharmacological treatment. Also, the reviews on which the featured review was largely based excluded a variety of studies that lacked rigorous controls but which may provide useful data. For instance, a meta-analysis 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. of contingency management programmes added to methadone maintenance found these reduced opioid-positive urine rates during treatment. In the future more detailed research may find certain psychosocial approaches work with certain pharmacotherapies or help in respect of certain clients or outcomes. For example, the possibility remains that psychosocial treatments improve quality of life and physical health, or decrease risk behaviours related to HIV, all clinically and socially significant outcomes.

Findings logo commentary See these Effectiveness Bank entries for more on the reviews included in the featured review:
Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence
International review and UK guidance weigh merits of buprenorphine versus methadone maintenance
Heroin maintenance for chronic heroin-dependent individuals
Substitution treatment of injecting opioid users for prevention of HIV infection
Psychosocial combined with agonist maintenance treatments versus agonist maintenance treatments alone for treatment of opioid dependence
Psychosocial and pharmacological treatments versus pharmacological treatments for opioid detoxification
Lofexidine safe and effective in opiate detoxification
Oral naltrexone maintenance treatment for opioid dependence

Last revised 20 November 2012. First uploaded 10 November 2012

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DOCUMENT 2009 Guidelines for the psychosocially assisted pharmacological treatment of opioid dependence

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

DOCUMENT 2015 American Society of Addiction Medicine (ASAM) national practice guideline for the use of medications in the treatment of addiction involving opioid use

REVIEW 2009 Pharmacotherapies for the treatment of opioid dependence: efficacy, cost-effectiveness and implementation guidelines

STUDY 2015 Impact of treatment for opioid dependence on fatal drug-related poisoning: a national cohort study in England

HOT TOPIC 2016 Are the drugs enough? Counselling and therapy in substitute prescribing programmes

MATRIX CELL 2016 Drug Matrix cell A3: Interventions; Medical treatment

STUDY 2004 Opiate antagonist treatment risks overdose

DOCUMENT 2014 Consolidated guidelines on HIV prevention, diagnosis, treatment and care for key populations

STUDY 2010 Risk of death during and after opiate substitution treatment in primary care: prospective observational study in UK

Adjunctive counseling during brief and extended buprenorphine-naloxone treatment for prescription opioid dependence.

Weiss R.D., Potter J.S., Fiellin D.A. et al.
Archives of General Psychiatry: 2011, 68(12), p. 1238–1246.
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 Weiss at rweiss@mclean.harvard.edu. You could also try this alternative source.

From the USA, the first large study to randomly allocate patients dependent on prescription opioids to different treatments found that despite wanting to detoxify, all but a few relapsed after withdrawal from substitute medication; more intensive and specialist counselling did not help.

Summary Editor's introduction: In this study treatment was based on prescribing buprenorphine-naloxone tablets. Buprenorphine is the main alternative to methadone for substitute prescribing treatments for opiate addiction. Like methadone it offers the opiate-type effects patients have become dependent on in a way which enables them to get on with their lives rather than dominating them. It can be taken daily or once every two or three days and fatal overdose is much less likely than with either heroin or methadone, making it particularly suitable for non-specialist settings such as primary care. Adding the opiate blocking drug naloxone to buprenorphine (the combination marketed as Suboxone) is intended to reduce the risk of the tablets being crushed and injected rather than absorbed under the tongue as intended. When injected but not when absorbed under the tongue, naloxone blocks the opiate-type effects of buprenorphine, reducing the incentive to inject. For this reason the combined medication is considered particularly suitable for non-specialist settings and where supervising consumption is not possible or desirable.

In the USA many patients dependent on opiate-type drugs use not illegal drugs like heroin but opioid Drugs with opiate-type effects (including analgesia and the capacity for producing euphoria and dependence) derived from the opium poppy like opium, heroin, and morphine (know as opiates) and synthetic drugs with similar effects like methadone and buprenorphine. painkillers produced for medical use. How these patients will react to more or less provision of counselling in opiate substitute prescribing programmes is unclear, as is whether their generally better prognosis means they can more quickly be withdrawn from substitute medications. The featured study addressed these questions at outpatient substance abuse treatment clinics prescribing buprenorphine-naloxone (Suboxone) as a substitute medication. It planned to stabilise patients on the medication and then withdraw them over a short period, offering more extended stabilisation and withdrawal to those who did not succeed at the first attempt. The aim was to test the kind of 'stepped' treatment strategy which might be applied in routine practice, and at the same time to test whether offering additional specialist substance misuse counselling would improve on the kind of counselling/medical care available in primary care settings.

At the ten clinics 653 adult patients dependent Not just reliant on them to relieve pain or for some other medical reason. on prescription opioids joined the study. They had to be willing to be detoxified and have clearance from their doctor if the prescription was for pain. People with an appreciable history of heroin use or dependence, who had injected the drug, or were dependent on other drugs, could not join the study. Nine in 10 of the patients were white and nearly two thirds were employed full time. On average they had taken opioid analgesics nearly every day in the last month and had used these drugs for five years. A third had previously been treated for their opioid dependence. Very few were using cocaine. Four in ten reported chronic pain.

Initial detoxification treatment consisted of induction on to buprenorphine-naloxone, two weeks of stabilisation, then two weeks over which doses were reduced to zero. Patients were then followed up for eight weeks. Medication was dispensed weekly to be taken daily. Patients who completed this entire programme successfully Defined as after the first 15 days reporting opioid use on no more than four days in a month, registering no consecutive opioid-positive urine tests and no more than one missing test, and no additional substance use disorder treatment. with minimal continuing opioid use simply ended their treatment. But as soon as this became apparent, patients who were not going to complete successfully were offered more extended treatment consisting of 12 weeks (rather than two) stabilisation on buprenorphine-naloxone and reduction to zero over four (rather than two) weeks. As before, they were then followed up for another eight weeks. To be considered to have responded well to this extended treatment, patients had to have not used opioids Missing urine samples were considered positive for opioids. during their final week of stabilisation and in at least two of the previous three weeks. Additionally, these patients were assessed against a similar yardstick at the end of the eight-week follow-up.

During each phase patients were randomly allocated to (usually brief) weekly sessions of primary care-style counselling/care from their doctors, or to this plus longer sessions of specialist substance misuse counselling initially twice a week. These sessions were offered while substitute medication was being prescribed and at the start of the initial eight-week follow-up period. Using a skills-based format with interactive exercises and take-home assignments, the more specialist counselling covered a wider range of relapse prevention issues in greater depth, including coping with high-risk situations, managing emotions, and dealing with relationships. Both approaches were based on manuals from an earlier study of buprenorphine-naloxone treatment in primary care.

Main findings

As defined by the study, just 43 of the 653 patients – about 7% – successfully completed initial stabilisation/detoxification chart. These outcomes were assessed eight weeks after buprenorphine-naloxone had been withdrawn. In contrast, while still being prescribed maintenance doses of the drug, and even though they had 'failed' the initial treatment, half (49.2%) the 360 patients who took up the offer of further treatment were successful, meaning they used virtually no other opioid drugs. But these patients too generally responded poorly after their substitute medication was withdrawn; just 31 or about 9% could be shown to have virtually avoided opioid use eight weeks later, a statistically significant difference from when they were still being prescribed maintenance doses. At none of these measurement points had those offered extended and specialist counselling done better than those just offered primary care consultations with their doctors.

Treatment phases and success rates

Similar results were found when 'success' was defined as complete abstinence from opioid use in the previous four weeks. Among patients offered extended treatment, over the last four weeks after being withdrawn from buprenorphine-naloxone, and virtually regardless of the counselling option, just 6–7% had been abstinent, significantly fewer than the 36% over the last four weeks week of being prescribed maintenance doses. Urine tests corroborated The rate of opioid-positive urine tests among patients offered extended treatment was significantly higher (58% v. 39%) during the combined taper and post-taper periods than while patients were being maintained on buprenorphine-naloxone these results.

Chronic pain at the start of the study made no difference to outcomes or the impact of the counselling options, and nor in the first phase did a history of heroin use. However, in the extended treatment phase patients who had ever used heroin were less likely to be more or less opioid-free (37% v. 54%) while maintained on buprenorphine-naloxone.

Nearly all the medication doses were taken and most counselling sessions of whatever kind were attended, ranging from nearly 82% of primary care visits in the first phase to 64% of drug counselling sessions in the second. Most patients experienced some adverse effects possibly related to the medication, but very few left treatment as a result. Psychiatric symptoms were the most common serious adverse events, particularly (in five cases) depression leading to hospitalisation, all soon after completion of medication withdrawal.

The authors' conclusions

While maintained on full doses of substitute buprenorphine-naloxone many patients stopped using other opioids, but even after 12 weeks of stabilisation, over 90% continued or resumed opioid use after the medication had been withdrawn. Consistent with an earlier study of heroin users prescribed buprenorphine-naloxone in primary care, offering even (compared to that study) fairly intensive drug counselling in addition to medical visits did not help. This high rate of unsuccessful detoxification is notable given the promising nature of the caseload: largely employed, well educated, with relatively brief opioid use histories, and little other current substance use. The contrast with the maintenance phase substantiates research which has consistently demonstrated the benefit of longer-term opioid substitute treatment.

On the positive side, the study shows that primary care doctors can successfully treat many patients dependent on prescription opioids, with or without chronic pain, by prescribing buprenorphine-naloxone on a maintenance basis plus relatively brief weekly medical management visits; half the patients who started this treatment did well while it lasted. However, when tapered off this medication, relapse to opioid use or treatment drop-out was overwhelmingly the most likely result. Though serious incidents were few, physicians should monitor psychiatric symptoms when tapering such patients from opioids.

Though chronic pain did not affect opioid use outcomes, it was of relatively moderate intensity overall; patients whose doctors deemed their pain severe enough to require ongoing opioid therapy were excluded from the study. It is not known Also unknown is whether less than weekly medical visits would have sufficed or whether yet more intensive drug counselling, a longer period of stabilisation, or a different type of therapy such as contingency management, might have improved outcomes during maintenance phases and/or after withdrawal. whether these findings can be generalised to patients with severe pain or those seeking treatment for pain rather than for opioid dependence. For reasons yet to be clarified, patients with even minimal lifetime heroin use more often used other opioids while maintained on buprenorphine-naloxone.

Findings logo commentary For a relatively unresearched caseload dependent on pharmaceutical opioids, and despite their relatively high stock of 'recovery capital' and willingness to try detoxification, these findings confirm the verdict of World Health Organization guidelines that compared to maintenance treatment, opioid withdrawal results in poor outcomes in the long term.

In retrospect, the attempt at rapid detoxification at the start of the study appears to have created a discontinuity in treatment which contributed to the fact that 250 of the 653 patients were lost touch with, while gaining just 43 successful detoxification completions. This attrition in turn meant that though half the patients who resumed maintenance treatment then substantially reduced their use of other opioids, they constituted just 27% of the patients who started the study. If virtual cessation of non-medical opioid use is the yardstick of success, it seems likely that many more patients would have attained this if from the start they had been prescribed maintenance doses rather than rapidly transitioned to detoxification.

From another perspective, the study illustrates the well-known high failure rate of outpatient detoxification, and the high relapse rate after any form of detoxification when not immediately and seamlessly followed by residential care. But since most of the sample were employed full time, it could be that only a minority would have been able to spend months in residential detoxification and rehabilitation. Offering instead fairly intensive outpatient drug counselling seemed largely futile, as most appointments were missed.

Lack of impact of extra counselling is also a general finding across studies of adding psychosocial therapy to opiate substitute prescribing – a testament to the power of routine methadone and buprenorphine maintenance.

While the rationale for substituting pharmaceutical opioids for illegal heroin seems clear – including preventing crime and injecting-related damage and infection, and making sure pure drugs are taken – the rational for substituting one pharmaceutical opioid for others is less clear, especially since the criminal activity involved is less worrying to the general public. One answer is the dramatic increase in US overdose deaths related to the non-medical use of opioid painkillers, deaths which in the USA now outnumber those due to heroin and cocaine combined, and which substantially contribute to overdose deaths from prescription drugs which by 2008 had approached the number of deaths from motor vehicle crashes (1 2). For patients dependent on painkillers, substituting methadone might be seen as a counterproductive escalation in the intensity of the opiate-type effects they experience. Buprenorphine is generally felt to leave patients less sedated and more able to function normally, and to be easier to withdraw from.

Guidance is available for UK general practitioners on the treatment of opioid dependence.

Last revised 22 November 2012. First uploaded 16 November 2012

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STUDY 2010 Unobserved versus observed office buprenorphine/naloxone induction: a pilot randomized clinical trial

STUDY 2013 A randomized trial of cognitive behavioral therapy in primary care-based buprenorphine

DOCUMENT 2011 Guidance for the use of substitute prescribing in the treatment of opioid dependence in primary care

DOCUMENT 2011 Buprenorphine/naloxone for opioid dependence: clinical practice guideline

STUDY 2010 Risk of death during and after opiate substitution treatment in primary care: prospective observational study in UK

STUDY 2010 Home- versus office-based buprenorphine inductions for opioid-dependent patients

STUDY 2015 Risk of mortality on and off methadone substitution treatment in primary care: a national cohort study

STUDY 2012 Randomized trial of standard methadone treatment compared to initiating methadone without counseling: 12-month findings

DOCUMENT 2009 Buprenorphine: a guide for nurses

STUDY 2011 Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomised trial

Motivational interviewing for substance abuse.

Smedslund G., Berg R.C., Hammerstrøm K.T. et al.
Cochrane Database of Systematic Reviews: 2011, 5, Art.No.:CD008063.

Across the most rigorous studies, this synthesis of the research finds therapies based on motivational interviewing better than doing nothing, but no more effective than usual/other treatments for problem drinkers and drugtakers – powerful further support for the 'Dodo bird' verdict that all bona fide therapies are equivalent.

Summary Motivational interviewing is a widespread (Editor's note: including in Britain) and influential approach to counselling intended to work through four main principles. As explained on the Motivational Interviewing web site, expressing empathy involves seeing the world through the client's eyes. Supporting self-efficacy means clients are held responsible for choosing how to change and implementing these plans. The third principle, rolling with resistance, means the counsellor does not fight or challenge client resistance, but uses the client's 'momentum' to further explore their views. Lastly, motivation for change occurs when people perceive a discrepancy between where they are and where they want to get to. Counsellors seek to generate this perception by helping clients examine discrepancies between their current behaviour and future goals. When clients appreciate their behaviour is not consonant with some important future goal, they become more motivated to make significant life changes.

Several reviews have already assessed the evidence for interventions based on this approach. The featured review for the Cochrane collaboration extended these by exhaustively searching for relevant research on individual face-to-face counselling for problems related to alcohol and/or other drugs. It assured a degree of rigour in the studies by limiting itself to those which tried to eliminate bias by randomly allocating clients (or groups of clients) to motivational interviewing or not, and which checked session recordings to make sure that what was intended to be a motivational interviewing The motivational interviewing intervention might have been a standalone treatment or a prelude to or part of other treatment, and it might be compared with no intervention or another active therapy. approach actually was. Patients had to have been identified as not just 'misusing' but actually experiencing a problem with drugs or alcohol warranting at least a diagnosis (if not formally) of 'abuse'. Because there is already a Cochrane review on motivational interviewing for smoking, tobacco was excluded. So too were studies which provided one session based on motivational interviewing during an emergency department visit.

A search updated in November 2010 identified 59 studies (of which 55 could supply relevant data) covering 13,342 participants. In 29 studies the clients seemed to be have problems only with alcohol, in eight cannabis, and four cocaine. In the remaining 18, problems were being experienced with several substances. The USA accounted for 44 studies. Other developed western nations accounted for the remainder.

Main findings

In 24 studies motivational interviewing interventions were compared with no corresponding treatment – either none at all, or only the treatment to which the motivational interviewing sessions were added. Across Assessed through meta-analysis, 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. the four relevant studies, measures taken at the end of treatment registered the largest comparative reduction in substance use. Much smaller but still statistically significant was the comparative reduction assessed up to six months later across 15 studies and 612 months later across 12 studies. Just one study had a longer follow-up; it found no statistically significant comparative reduction in substance use. Across the studies readiness to change substance use behaviour – the degree to which someone feels they need to change and is taking steps to do so – was not significantly affected.

Often interventions based on motivational interviewing incorporate feedback of the results of an assessment of the patient's substance use and related problems. Seven studies compared interventions based on motivational interviewing against those amounting only to assessment or assessment plus feedback. Motivational interviewing approaches led to a small and not statistically significant extra reduction in substance use assessed up to six months later, and a larger and this time statistically significant reduction across two studies which assessed outcomes 6–12 months later.

Nine studies compared interventions based on motivational interviewing against 'treatment as usual'. Across these there were no statistically significant differences in substance use reductions at any follow-up point, nor was retention in treatment significantly affected.

In another 13 studies the comparison was with a specific therapy. At no follow-up point was there a substantial or statistically significant difference in substance use between clients allocated to motivational interviewing rather than another approach. Nor across the two studies to assess this did motivational interviewing significantly bolster readiness to change, and across five studies there was no impact on retention in treatment.

The authors' conclusions

Across these studies people who have participated in a motivational interviewing approach reduced their substance use more than people not offered treatment. However, it seems that motivational interviewing approaches are not consistently more effective than other active treatments, treatment as usual, or being assessed and given feedback. Data was insufficient to conclude about impacts on retention in treatment, readiness to change, or criminality. The certainty of these conclusions is limited by the quality of the research, and new research may change them.

For practitioners the implication is that those comfortable with this style of working should feel confident that despite its typical brevity (one to four sessions) it will be more effective than doing nothing. But if, for example, they prefer cognitive-behavioural therapy, the evidence is too weak to conclude that this will be more or less effective than motivational interviewing.

These results are consistent with motivational interviewing and other approaches sharing common therapeutic factors such as empathic attention from and a therapeutic relationship with a helper. Clinicians and researchers may have overemphasised treatment method as opposed to the individual who delivers the treatment and the client who receives it, and some studies may have failed to pay sufficient attention to whether the patient and/or therapist feel positive towards the treatment and whether they like and respect each other. Such factors may have a much greater influence on outcome than the contribution made by a specific approach or technique.

Findings logo commentary The featured review adds its considerable weight to the common conclusion that any well structured therapy is as good as any other – a conclusion reached in another recent review and meta-analysis 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. of motivational interviewing. The same conclusion has been reached in respect of the main alternative psychological approach, cognitive-behavioural therapy. Another analysis found that the equivalent-impact finding also applied specifically to comparisons between cognitive-behavioural therapy and motivational interviewing, though the latter took less time. In respect of psychological therapy for drinking problems, any structured approach grounded in an explicit model seems as effective in curbing drinking as any other. The fact that the featured analysis confirmed these findings after minimising the risk of bias by selecting only randomised trials, and ensuring the study assessed whether motivational interviewing actually characterised the therapy, means the conclusion that on average interventions based on motivational interviewing are no more effective than alternative therapies can be considered well established.

An important distinction not explicitly made by the featured analysis is whether participants were seeking treatment for the problems addressed by the interventions, or had been identified by screening programmes while, for example, routinely visiting their GPs. The motivational state of people who decide they have a problem and seek help is likely to be very different from those not seeking help for this issue at all, but (from their point of view) unexpectedly find it investigated and are told they have an actual or potential problem. The featured study's stipulation that clients warrant an abuse diagnosis did not exclude several studies of clients identified by screening and/or not seeking help for substance use problems.

Not even better than usual treatment?

It is particularly disappointing that in the featured analysis even 'treatment as usual' proved as effective as structured, theory-driven programmes featuring a widely respected approach, seemingly justifying a 'carry on as we are' policy. This was not the case in a broader recent review of motivational interviewing, which included studies not just of substance use but diet, exercise, safe sex, gambling, and engagement in treatment, and was not confined Though included studies did have to feature a no- or alternative-treatment comparison group against which to benchmark the motivational intervention. to randomised controlled trials. Also, examined in detail, the negative findings in the featured review were far from definitive, and motivational interviewing did improve on usual treatment in some of the most appropriate and generalisable trials.

For example, of the ten short-term follow-up studies in the featured analysis, half were of people seeking treatment in the normal way. Of these, two shared a particularly rigorous and appropriate design (1 2) in that they substituted outpatient counselling sessions based on motivational interviewing for the same number of usual-counselling sessions. Both studies found similar reductions in substance use during treatment whichever type of counselling was offered, but also that after treatment these reductions were sustained significantly better among motivational interviewing patients. Of the remaining three studies, one was of a very special population – pregnant women – and in another the comparison was arguably not treatment as usual, consisting of a manualised, 12-session, skills-based treatment package developed by researchers. The remaining study led by Bill Miller himself, architect of motivational interviewing, seems an example of the over-constricting manualisation of motivational interviewing which has been found to weaken its impact. Also the motivational interviewing was a minor addition to the overall treatment and one which was often offered too late to perform an induction role.

Are all specific interventions really equivalent?

Though well established as an average across groups of patients, for at least three reasons, the 'it doesn't matter what you do' message does not necessarily apply to individual patients or different types of patients:
• Across psychological therapies (including those for substance use problems), implementing the client's informed choice of their preferred therapy nearly halves drop-out rates and significantly if modestly improves outcomes.
• Relative to treatment as usual or directive advice consonant with their decisions, motivational sessions When Findings analysed these studies, we spotlighted the inflexible manualised motivational programmes which insisted that patients re-examine the pros and cons of whether they really did want to stop using drugs or commit to treatment and aftercare, when they had already decided to do so and started the process. can worsen outcomes for patients who already see themselves as committed to and engaged in a process of change. For less committed patients, motivational interviewing has been more consistently beneficial.
• While the specific therapeutic programme may not be directly relevant, some programmes are more conducive to certain interpersonal styles than others, and these styles suit some patients Directiveness has, for example, emerged as an important factor; clients who need 'a push' or like to be led respond well to directive therapists; those who react against being led, respond badly. True-to-type motivational interviewing, when not unduly constrained by a set, manualised programme, encourages a non-directive style; cognitive-behavioural therapy, with its emphasis on training and skills, encourages greater directiveness. In the large US Project MATCH alcohol treatment trial, motivational therapists were significantly less directive than those implementing cognitive-behavioural therapy, and it was this difference in style which accounted for how different types of patients reacted. Complicating this formulation is the fact that whether therapists feel the need to be and/or come across as directive depends at least partly on what feels 'natural' in that culture. more than others.

Without being able to make these fine distinctions, when analyses like those in the featured study find an overall equivalence between different therapies, this probably masks the fact that different therapies have done better or worse with different types of clients, the ups and downs evening out to the 'equivalent' verdict. Also not to be dismissed is the fact that motivational interviewing lends itself to relatively brief programmes of therapy, possibly a benefit in terms of cost-effectiveness if not effectiveness as such.

For a discussion of these issues and one-click access to all relevant Effectiveness Bank entries see this hot topic. See in particular these Findings reviews (1 2).

Thanks for their comments on this entry in draft to Geir Smedslund of the Norwegian Knowledge Centre for the Health Services. Commentators bear no responsibility for the text including the interpretations and any remaining errors.

Last revised 26 November 2012. First uploaded 13 November 2012

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

REVIEW 2010 A meta-analysis of motivational interviewing: twenty-five years of empirical studies

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

STUDY 2012 Brief intervention for drug-abusing adolescents in a school setting: outcomes and mediating factors

STUDY 2012 Motivational interviewing: a pilot test of active ingredients and mechanisms of change

REVIEW 2011 Effectiveness of e-self-help interventions for curbing adult problem drinking: a meta-analysis

STUDY 2011 Extended telephone-based continuing care for alcohol dependence: 24-month outcomes and subgroup analyses

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

REVIEW 2011 Adapting psychotherapy to the individual patient: Preferences

HOT TOPIC 2015 Computerising therapy and advice increases access – but is effectiveness sacrificed?

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

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