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Treatment options for opioid users

This page refers to the current evidence on the effectiveness of the available treatment options for opioid users. We refer here to the broad family of opioids including heroin, fentanyl, morphine, etc. Information on the methodology used and the definition of terms can be found on the methodology page.

Date of last update: 06.2016     Next update:  12.2016

Available treatments for opioid users – evidence base

Note: The GRADE symbol GRADE symbol indicates that a GRADE profile is available for the intervention. Learn more about GRADE.

Beneficial

Buprenorphine substitution to retain patients in treatment

Buprenorphine substitution treatment was found to be more effective than placebo in a synthesis of evidence (WHO, 2009) and more recenlty in a systematic review (Mattick et al., 2014) in:

  • improving retention in treatment
    • at low doses (2-6mg) (RR 1.50, 95 % CI 1.19 to 1.88, 5 studies, N=1131);
    • at medium doses (7-15mg) (RR 1.50, 95 % CI 1.19 to 1.88, 4 studies, N=887);
    • at high doses (≥ 16mg) (RR 1.82, 95 % CI 1.15 to 2.90, 5 studies, N=1001)
  • reducing the number of morphine-positive urines only at high doses (SMD –1.17, 95 % CI –1.85 to –0.49, 3 studies, N=729)

GRADE symbol View the GRADE profile for this intervention (reproduced with permission from WHO).

Buprenorphine vs methadone substitution treatment

Methadone maintenance therapy was found to be statistically more effective than Buprenorphine maintenance therapy in a systematic review (Mattick et al., 2014) in:

  • improving retention in treatment
    • in flexible doses studies (RR 0.83, 95 % CI 0.72 to 0.95, 5 studies, N=788);
    • in low doses studies (MMT ≤ 40mg , BUP 2-6mg) (RR 0.67, 95 % CI 0.52 to 0.87, 3 studies, N=253);
  • no difference was observed in reduction of opioid use as measured by urinalysis (SMD -0.11; 95 % CI -0.23 to 0.02, 8 studies, N=1027) or self-reported (SMD -0.11; 95 % CI -0.28 to 0.07, 4 studies, N=501)

However, at medium doses (MMT 40-85mg, BUP 7-15mg) and high doses (MMT ≥ 16mg, BUP ≥ 85mg) no difference was found between Methadone and Buprenorphine treatment in:

  • improving retention in treatment
    • medium doses (RR 0.87, 95 % CI 0.69 to 1.10, 7 studies, N=780)
    • high doses (RR 0.79, 95 % CI 0. 02 to 3.16, 1 study, N=134)
  • reducing opioid use as measured by urinalysis or self-reported

Case management for reducing drug use

Case management proved to be more effective than psycho-education and drug counselling in reducing drug use in a systematic review including one trial of around 500 patients (RR 0.24, 95 % CI 0.06 to 0.42) (Hesse et al., 2007).

Methadone substitution treatment vs opioid withdrawal

Methadone substitution treatment was found in a systematic review of three RCTs (N=505) (WHO, 2009) to be more effective than opioid withdrawal followed by placebo in:

  • increasing retention in treatment (RR 3.05, 95 % CI 1.75 to 5.35);
  • reducing illicit opioid use (RR 0.32, 95 % CI 0.23 to 0.44).

Observational studies found the mortality rate in methadone treatment to be approximately one-third the rate out of treatment (RR 0.37, 95 % CI 0.29 to 0.48).

Methadone was found in one RCT (N=253) to reduce the risk of HIV infection by approximately 50 % (RR 0.45, 95 % CI 0.35 to 0.59) and a similar reduction in seroconversion rates was found in 3 observational studies (N=43 035) (RR 0.36, 95 % CI 0.19 to 0.66) when compared to withdrawal or no treatment.

GRADE symbol View the GRADE profile for this intervention (reproduced with permission from WHO).

Naltrexone for patients forced to adhere to treatment

Pharmacologycal treatment with Naltrexone was found in a sub-analysis of patients forced to adhere to treatment (Minozzi et al., 2011) effective in:

  • achieving retention in treatment and abstinence (RR 2.93, 95 % CI 1.66 to 5.18, 3 RCTs, N=230).

Opioid assisted withdrawal with buprenorphine

Buprenorphine for opioid assisted withdrawal was found WHO (2009) in a pooled analysis of eight studies (N=884 participants) to be effective in:

  • achieving higher completion rates than alpha-2 agonists (RR 1.67, 95 % CI 1.24 to 2.25, moderate-quality evidence);
  • lowering the peak of objective withdrawal scores (SMD –0.61, 95 % CI –0.86 to –0.36, moderate-quality evidence);
  • lowering overall self-reported levels of opioid withdrawal (SMD –0.59, 95 % CI –0.79 to –0.39, high-quality evidence).

Psychosocial interventions with substitution treatment to reduce use and mortality

Methadone treatment plus psychosocial intervention compared with methadone treatment only was found in a systematic review of three studies (WHO, 2009, N=388) to be more effective in:

  • reducing heroin use (RR 0.69, 95 % CI 0.53 to 0.91)

Patients who received opioid agonist pharmacotherapy with psychological support were found in a national cohort study (Pierce et al., 2015, N=151 983) to be:

  • less at risk for fatal drug-related poisoning when compared to those enrolled only in psychological intervention (adjusted hazard ratio for only psychological support, aHR = 2.07, 95 % CI 1.75 – 2.46)

Psychosocial assistance in addition to pharmacological assistance for opioid withdrawal

WHO (2009) found combined psychosocial (contingency management, community reinforcement, psychotherapeutic counselling and family therapy) and pharmacological assistance were found to be effective in a systematic review of five randomised control trials (N=184 participants) in:

  • increasing rates of completion of treatment (RR 1.68, 95 % CI 1.11 to 2.55, moderate quality evidence);
  • reducing rates of relapse at follow-up (RR 0.41, 95 % CI 0.27 to 0.62, moderate-quality evidence).

GRADE symbol View the GRADE profile for this intervention (reproduced with permission from WHO).

Substitution agonist treatments for opiate dependent pregnant women for treatment and obstetrical outcomes

Evidence-based international guidelines (WHO, 2014) strongly recommend to advise opioid dependent pregnant women to start or continue substitution treatment with either methadone or buprenorphine.

Substitution treatment for pregnant women was found effective in 2 systematic review (EMCDDA 2014, Minozzi et al., 2013) in:

  • reducing drop-out rates, especially in the methadone group (buprenorphine vs methadone: RR 0.64, 95 % CI 0.41 to 1.01, 3 studies, N=223)
  • higher birth weight, especially in the buprenorphine group (buprenorphine vs methadone: MD = -365.45g, 95 % CI -673.84 to -57.07, 2 studies, N= 150)
  • reducing use during pregnancy, especially in the oral slow morphine group (oral slow morphine vs methadone: RR 2.40, 95 % CI 1.00 to 5.77, 1 study, N=48)

Substitution agonist treatments for opiate dependent pregnant women over detoxification

Evidence-based international guidelines (WHO, 2014) strongly recommend to advise opioid dependent pregnant women to use substitution treatment rather than attempt opioid detoxification.

Likely to be beneficial

Alpha2-adrenergic agonists for the management of opioid withdrawal

Alpha2-adrenergic agonists (Clonidine and lofexidine) were found in a systematic review (Gowing et al., 2016, 26 RCT, N=1 728) to be more effective than placebo in:

  • ameliorating withdrawal in terms of the likelihood of severe withdrawal (risk ratio (RR) 0.32, 95 % CI 0.18 to 0.57, 3 studies, N=148)
  • increasing completion of treatment (RR 1.95, 95 % CI 1.34 to 2.84, 3 studies, N=148)

When compared to reducing doses of methadone

  • duration of treatment was significantly longer with reducing doses of methadone (SMD -1.07, 95 % CI -1.31 to -0.83, 3 studies, N=310)
  • hypotensive or other adverse effects were significantly more likely with alpha2-adrenergic agonists (RR 1.92, 95 % CI 1.19 to 3.10, 6 studies, N=464)
  • no significant difference in rates of completion of withdrawal treatment were found (RR 0.85, 95 % CI 0.69 to 1.05, 9 studies, N=659)

Heroin maintenance treatment for chronic heroin users

Heroin plus methadone prescription for maintenance treatment in adult chronic opioid users who failed previous methadone treatment attempts was found to be effective in a systematic review (Ferri et al., 2011) of eight randomised control trials (N=2.007) in:

  • remaining in treatment until the end of the study (RR 1.44, 95 % CI 1.19 to1.75);
  • probably reducing the risk of death (RR 0.65,  95 % CI 0.25 to1.69).

The risk of adverse events was coherently high in all the seven studies providing comparable data (RR 13.50, 95 % CI 2.55 to 71.53).

Opioid substitution treatment to improve mental health outcomes in the short-term

Opioid substitution treatment was found to be effective in a systematic review, without meta-analysis, (Fingleton et al., 2015, N=22 studies, 19 RCTs and 3 national cohort studies), in:

  • improving mental health outcomes, eg. psychiatric, depressive and psychopathology symptoms, anxiety and stress (significant positive outcomes in 14 out of the 22 studies). Improvements were greatest in the first six months and studies with a longer follow-up reported no further improvement or that the improvements   were not sustained.

Psychosocial interventions to retain patients in treatment

Psychosocial interventions in addition to Methadone maintenance treatment were found in a systematic review (WHO (2009) of three RCTs (N=500) to be no different from methadone maintenance treatment only in:

  • retaining patients in treatment (RR 0.94, 95 % CI 0.85 to 1.02).

Substitution treatment for people dependent on pharmaceutical opioids

Methadone or buprenorphine appeared equally effective to treat pharmaceutical opioid dependent patients as presented in a systematic review (Nielsen et al., 2016, 6 RCT, N= 607). The review found no difference between methadone and buprenorphine in:

  • reducing opioid use
    • self-reported opioid use (risk ratio (RR) 0.37, 95 % confidence interval (CI) 0.08 to 1.63)
    • opioid positive urine drug tests (RR 0.81, 95 % CI 0.56 to 1.18)
  • retaining people in treatment (RR 0.69, 95 % CI 0.39 to 1.22)
  • adverse effects (RR 1.10, 95% CI 0.64 to 1.91)

Trade-off between benefits and harms

No interventions met the criteria for this category.

Unknown effectiveness

Assisted opioid withdrawal with methadone or buprenorphine

In a pooled analysis (two studies, N=63 participants) (WHO, 2009), there was no significant difference in:

  • completion of treatment between methadone and buprenorphine (RR 0.88, 95 % CI 0.67 to 1.15).

GRADE symbol View the GRADE profile for this intervention (reproduced with permission from WHO).

Naltrexone treatment for opioid dependence

In an updated version of a systematic review of 13 RCTs (N=1158) (Minozzi et al., 2011), pharmacologycal treatment with Naltrexone versus placebo or no pharmacological treatment in all patients was found to be not significantly different in:

  • retaining patients in treatment (RR 1.18, 95 % CI 0.72 to 1.91, 2 studies, N=88 participants);
  • achieving retention and abstinence (combined outcome) (RR 1.43, 95 % CI 0.72 to 2.82, 6 RCTs, N= 393 participants);
  • achieving abstinence (RR 1.39, 95 % CI 0.61 to 3.17,4 RCTs, N=143 participants);
  • achieving abstinence at follow up (RR 1.28, 95 % CI 0.80 to 2.08, 3 RCTs, N= 116 participants);
  • reducing side effects (RR 1.29, 95 % CI 0.54 to 3.11, 4 RCTs, N=159 participants).

Naltrexone with psychotherapy versus psychotherapy alone

In an updated version of a systematic review (Minozzi et al., 2011), pharmacologycal treatment with Naltrexone was compared with psychotherapy only and was found not significantly different in:

  • achieving abstinence at follow up (RR 1.63, 95 % CI 0.62 to 4,26, 1 RCT, N=38 participants);
  • avoiding reincarceration (RR 0.65, 95 % CI 0.26 to 1.65, 1 RCT, N=38 participants).

Naltrexone with psychotherapy versus Benzodiazepines with psychotherapy

In an updated version of a systematic review (Minozzi et al., 2011), pharmacologycal treatment with Naltrexone in association with psychotherapy was compared with Benzodiazepines associated with psychotherapy and was found not significantly different in:

  • achieving retention and abstinence (combined outcome) (RR 1.67, 95 % CI 0.96 to 2.89, 1 RCT, N=140 participants);
  • reducing side effects (RR 3.00, 95 % CI 0.63 to 14.36, 1 RCT, N=140 participants).

Naltrexone with psychotherapy versus Buprenorphine with psychotherapy

In an updated version of a systematic review (Minozzi et al., 2011), pharmacologycal treatment with Naltrexone in association with psychotherapy was compared with Buprenorphine treatment associated with psychotherapy and was found not significantly different in:

  • achieving retention and abstinence (combined outcome) (RR 0.37, 95 % CI  0.13 to 1.08, 1 RCT, N=87 participants).

Opioid withdrawal with antagonists under heavy sedation

Opioid withdrawal with antagonists under heavy sedation or anaesthesia was compared to withdrawal managed with reducing doses of methadone in a systematic review of 9 studies (8 RCTs N=1109) (Gowing 2010) and no difference was found:

  • in heroin use after 6 months (RR 0.97, 95 % CI 0.88 to 1.08);
  • rates of retention in treatment at 12 months (RR 0.95, 95 % CI 0.69 to 1.30).

Opioid withdrawal with antagonists under minimal sedation

In a systematic review of 4 studies (N=394) (Gowing 2009), there was no significant difference in:

Pharmacological detoxification treatment for adolescent opioid users

Detoxification treatment alone or in combination with psychosocial intervention compared to no intervention, other pharmacological intervention or psychosocial interventions was assessed in a systematic review of two RCT (involving 190 participants between 13–18 years of age) (Minozzi et al., 2014a) finding no conclusive results on:

  • completion of treatment;
  • reducing the use of substances; and
  • improving health and social status.

Among the studies enclosed in the review, one (N=152) compared buprenorphine detoxification with Buprenorphine-Naloxone substitution and found that:

  • the detox group group had more patients dropping out (RR 2.67, 95 % CI 1.85 to 3.86);
  • but no differences were found for opioid use (RR 1.03, 95 % CI 0.82 to 1.28).

Pyschosocial interventions versus comprehensive standard care for pregnant women for treatment and obstetrical outcomes

Psychosocial interventions were found in a systematic review (Terplan et al., 2015) to have no statistically significant different effect than other interventions in:

  • improving retention in treatment (RR 0.99, 95 % CI 0.93 to 1.06, 9 studies, N=743)
  • improving abstincence (RR 1.14, 95 % CI 0.75 to 1.73, 3 studies, N=367)
  • reducing pre-term birth (RR 0.71, 95 % CI 0.34 to 1.51, 3 studies, N=264)
  • reducing low birth weight (RR 0.72, 95 % CI 0.36 to 1.43, 1 study, N=160)

Substitution treatment for adolescent opioid users

Maintenance treatment with different medications was assessed in a systematic review (Minozzi et al., 2014b, 2 studies, N=189 aged 14-21) finding no conclusive results on:

  • completion of treatment;
  • reducing the use of substances; and
  • improving health and social status.

Among the studies, one (N=152) compared Buprenorphine-Naloxone maintenance with buprenorphine detoxification and found:

  • the maintenance treatment group had fewer drop out (RR 0.37, 95 % CI 0.26 to 0.54);
  • but no differences were found for opioid use (RR 0.97, 95 % CI 0.78 to 1.22)

Evidence of ineffectiveness

Opioid withdrawal with antagonists under heavy sedation

Opioid withdrawal with antagonists under heavy sedation or anaesthesia was compared to withdrawal managed with reducing doses of methadone in a systematic review of 9 studies (8 RCTs N=1109) (Gowing 2010) and:

  • heavy sedation or anaesthesia increased adverse effects (RR 3.21, 95%CI 1.13 to 9.12);
  • heavy sedation groups showed higher risk of life threatening than the non-heavy sedation groups (RR 14, 95%CI 0.74 to 264).

References and definitions

List of references

Explanation of terms used

Below you can find definitions and further explanation for some of the terms used in this section of the Best practice portal. A more general glossary for the best practice portal is also available.

Affective-focused prevention intervention

A type of prevention intervention which aims to they aim to modify inner qualities (personality traits such as self-esteem and self-efficacy, and motivational aspects such as the intention to use drugs).

BA

Before-after (BA) study design

BAL

Blood alcohol level (BAL)

Beneficial

Interventions for which precise measures of the effects in favour of the type of intervention were found in systematic reviews of relevant studies. An intervention ranked as ‘beneficial’ is suitable for most patients/contexts. See the relevant module methodology page for further information.

CBA

Controlled before-after (CBA) study design. UCBA stands for Uncontrolled before-after study design.

CBT

Cognitive behavioral therapy is an individual based intervention occurring in three stages. Phase 1 is aimed at determining and prioritizing the patient’s problems and constructing the treatment contract. Phase 2 is aimed at increasing coping competence and reducing risky behaviors. Phase 3 focuses on relapse prevention. Each session is administered once per week over a period of 4-6 months with 60- to 90-minute sessions (Beck AT, Wright FW, Newman CF, Liese B. Cognitive Therapy of substance abuse. New York: Guilford Press, 1993).

CCT

Controlled clinical trials (CCT)

Cohort study

A cohort study is a type of observational study that follows a group of people (i.e. a cohort) over time. In a prospective cohort study, the cohort is formed and then followed over time. In a retrospective cohort study, data is gathered for a cohort that was formed sometime in the past.

Confidence Interval (CI)

The Confidence Interval (CI) is a measure of the precision (or uncertainty) of study results. It is the interval that most likely includes the true value of the parameter we are calculating, where 'most likely' is taken by common usage to be a 95% probability. Thus the current expression of '95 % CI'. A wide CI indicates less precise estimates of effect and vice versa.

Practical interpretation

  • If the RR (the relative risk) = 1, or the CI (the confidence interval) = 1, then there is no significant difference between treatment and control groups
  • If the RR > 1, and the CI does not include 1, events are significantly more likely in the treatment than the control group
  • If the RR < 1, and the CI does not include 1, events are significantly less likely in the treatment than the control group
CPS

Current population survey (CPS)

Cross-sectional study

A cross-sectional study is a study employing a single point of data collection for each participant or system being studied.They are usually conducted to estimate the prevalence of the outcome of interest for a given population at a given point in time.

Evidence of ineffectiveness

Interventions that gave negative results if compared with a standard intervention or no intervention, for example. See the relevant module methodology page for further information.

Additional information for prevention
For ethical reasons this category in prevention should be considered as interventions with negative and undesired (iatrogenic) effect.

IP

Individual psychotherapy is a standard individual treatment based on counseling and motivational interviewing and focused on substance use triggers and strategies for relapse prevention. It includes elements of cognitive-behavioral therapy (CBT).

IQR

Interquartile range (IQR) - also called the midspread or middle fifty - is a measure of statistical dispersion. It is a trimmed estimator, defined as the 25% trimmed mid-range, and is the most significant basic robust measure of scale.

ITS

Intermittent time series design (ITS)

Knowledge-focused prevention intervention

A type of prevention intervention which aims to to enhance knowledge of drugs, and drug effects, and consequences.

Likely to be beneficial

Interventions that were shown to have limited measures of effect, that are likely to be effective but for which evidence is limited. An intervention ranked as ‘likely to be beneficial’ is suitable for most contexts/patients, with some discretion. See the relevant module methodology page for further information.

Number Needed to Treat (NNT)

The Number Needed to Treat (NNT)indicates the number of patients that needs to be treated to obtain one respondent patient. Numerically the NNT is the reciprocal of the difference between the proportion of events in the experimental and the comparison group (absolute risk reduction). Taking into consideration that the ideal NNT would be 1 (the unreal situation in which every single patient succeeded) it is easily understood that a NNT value close to 3 or 4 would be very good.

Adjusted Odds Ratio (AOR)

The Adjusted Odds Ratio is a way of comparing whether the probability of a certain event is the same between two groups, yet they are calculated adjusting for or controlling for other possible contributions from other variables (tipically demographic variables) in the model. An AOR equal to 1 implies that the the event is equally probable in both groups. An AOR greater than 1 implies that the event is more likely in the first group. An AOR less than 1 implies that the event is less likely in the first group.

Odds Ratio (OR)

The Odds Ratio is a way of comparing whether the probability of a certain event is the same between two groups. Like the Relative Risk, an OR equal to 1 implies that the the event is equally probable in both groups. A OR greater than 1 implies that the event is more likely in the first group. A OR less than 1 implies that the event is less likely in the first group. In medical research, the odds ratio is commonly used for case-control studies, as odds, but not probabilities, are usually estimated. Relative risk is used in randomized controlled trials and cohort studies.

p value

A p-value is a measure of how much evidence we have against the null hypothesis. The null hypothesis represents the hypothesis of no change or no effect. The smaller the p-value, the more evidence we have against the null hypothesis thus it is more likely that our sample result is true. Traditionally, researchers will reject a null hypothesis if the p-value is less than 0.05.

RBS

Responsible beverage service (RBS)

RCT

Randomised controlled trial (RCT)

Relative Risk (RR)

The Relative Risk (RR) is used to compare the risk in the two different groups of people, i.e. treated and control groups to see if belonging to one group or another increases or decreases the risk of developing certain outcomes. This measure of effect will tell us the number of times an outcome is more likely (RR > 1) or less likely (RR < 1) to happen in the treatment group compared with the control group.

Practical interpretation

  • If the RR (the relative risk) = 1, or the CI (the confidence interval) = 1, then there is no significant difference between treatment and control groups
  • If the RR > 1, and the CI does not include 1, events are significantly more likely in the treatment than the control group
  • If the RR < 1, and the CI does not include 1, events are significantly less likely in the treatment than the control group
Trade-off between benefits and harms

Interventions that obtained measures of effects in favour of the intervention, but that showed some limitations or unintended effects that need to be assessed before providing them. See the relevant module methodology page for further information.

 
Unknown effectiveness

Interventions for which there are not enough studies or where available studies are of low quality (with few patients or with uncertain methodological rigour), making it difficult to assess if they are effective or not. Interventions for which more research should be undertaken are also grouped in this category.

Additional information for prevention
For prevention interventions,  this  is also known as 'zero effect'.

Skill-focused prevention intervention

A type of prevention intervention which aims to enhance students’ abilities in generic skills, refusal skills and safety skills.

Standardised Mean Difference (SMD)

The Standardised Mean Difference (SMD) is the difference in means divided by a standard deviation. Note that it is not the standard error of the difference in means (a common confusion). The standardized mean difference has the important property that its value does not depend on the measurement scale. It may be useful if there are several trials assessing the same outcome, but using different scales.

z score (Standard Score)

The z-score (aka, a standard score) indicates how many standard deviations an element is from the mean of the population.

 

 

 

 

 

About opioid use

Case definition

Opioids, mainly heroin, continue to be cited as the principal drug by the majority of those seeking treatment in Europe. Considerable differences exist across Europe in the proportion of drug users entering treatment. Of the approximately 300 000 treatment entries for which the primary drug is known, 49 % cited heroin as their primary drug.

Aetiology

The mean age of clients entering outpatient treatment for primary opioid use is 33 years, and almost all countries have reported an increase since 2003.

Almost all opioid users entering treatment report initiation before the age of 30 and about half before the age of 20. An average time lag of about eight years is reported between first use of opioids and first contact with drug treatment (EMCDDA, 2009).

Prevalence

The average prevalence of problem opioid use in the countries providing data is estimated to be between four and five cases per 1 000 of the population aged 15–64. Injecting is frequently reported as the usual mode of administration by opioid users entering treatment, accounting for over half of opioid clients in most countries.

Treatment

In Europe, many opioid users are enrolled in programmes providing long-term care. Treatment is mostly conducted in outpatient settings, which can include specialist centres, general practitioners and low-threshold facilities.

Outcomes

Treatments may not be effective in achieving all the desired outcomes, these outcomes are prioritised.

Primary outcomes

  • Retention in treatment (observational studies* showed that people in treatment are less likely to take risks, and to be involved in crimes).
  • Mortality.
  • Relapse to use.
  • Criminal activity.

* studies such as National Treatment Outcome Research Study – NTORS, Australian Treatment Outcome Study – ATOS

Prognosis

Opioid use leads to tolerance, and after a period of use to dependence (National Institute Drug Abuse, 2008). Opioid dependence has been considered a chronic medical illness, benefiting from the same kind of long-term treatment and supportive care (McLellan, 2000). Untreated patients can have a relapse rate >90 % (McLellan, 1983).

References

American Psychiatric Association (2000), Diagnostic and statistical manual of mental  disorders, 4th edition, text revision, American Psychiatric Association, Washington, DC.

Cochrane systematic reviews

National Institute of Drug Abuse 2008

EMCDDA statistical bulletin

EMCDDA , Annual report: the state of the drugs problem in Europe, EMCDDA, Lisbon

McLellan, A. T., Luborsky, L., Woody, G. E., O’Brien, C. P. and Druley, K. A. (1983), Predicting response to alcohol and drug abuse treatments: role of psychiatric severity, Archives of General Psychiatry 40 (6), pp. 620–5.

McLellan, A. T., Lewis, D. C., O’Brien, C. P. and Kleber, H. D. (2000), Drug dependence, a chronic medical illness: Implications for treatment, insurance, and outcomes evaluation, Journal of the American Medical Association 284 (13), pp. 1689–95.

Ongoing trials

Related ongoing trials (PDF, updated January 2011)

Observational studies

Related observational studies (PDF, updated June 2011)

Page last updated: Thursday, 23 June 2016