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: 12.2016 Next update: 04.2017
Note: The GRADE symbol indicates that a GRADE profile is available for the intervention. Learn more about GRADE.
Methadone maintenance therapy was found to be statistically more effective than Buprenorphine maintenance therapy in a systematic review (Mattick et al., 2014) in:
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:
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 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.
Pharmacologycal treatment with Naltrexone was found in a sub-analysis of patients forced to adhere to treatment (Minozzi et al., 2011) effective in:
Buprenorphine for opioid assisted withdrawal was found WHO (2009) in a pooled analysis of eight studies (N=884 participants) to be effective in:
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:
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:
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:
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.
A systematic review with meta-analysis (Zedler et al, 2016, 3 RCTs, N= 223 and 15 observational studies, N=1 923), compared buprenorphine with methadone to treat pregnant women with opioid use disorder and found:
Evidence-based international guidelines (WHO, 2014) strongly recommend to advise opioid dependent pregnant women to use substitution treatment rather than attempt opioid detoxification.
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:
When compared to reducing doses of methadone
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:
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:
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:
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:
No interventions met the criteria for this category.
In a pooled analysis (two studies, N=63 participants) (WHO, 2009), there was no significant difference in:
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:
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:
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:
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:
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 a systematic review of 4 studies (N=394) (Gowing 2009), there was no significant difference in:
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:
Among the studies enclosed in the review, one (N=152) compared buprenorphine detoxification with Buprenorphine-Naloxone substitution and found that:
Psychosocial interventions were found in a systematic review (Terplan et al., 2015) to have no statistically significant different effect than other interventions in:
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:
Among the studies, one (N=152) compared Buprenorphine-Naloxone maintenance with buprenorphine detoxification and found:
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:
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.
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).
Before-after (BA) study design
Blood alcohol level (BAL)
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.
Controlled before-after (CBA) study design. UCBA stands for Uncontrolled before-after study design.
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).
Controlled clinical trials (CCT)
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.
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.
Current population survey (CPS)
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.
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.
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).
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.
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.
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.
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.
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.
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.
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.
Responsible beverage service (RBS)
Randomised controlled trial (RCT)
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.
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.
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'.
A type of prevention intervention which aims to enhance students’ abilities in generic skills, refusal skills and safety skills.
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.
The z-score (aka, a standard score) indicates how many standard deviations an element is from the mean of the population.
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.
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).
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.
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.
Treatments may not be effective in achieving all the desired outcomes, these outcomes are prioritised.
* studies such as National Treatment Outcome Research Study – NTORS, Australian Treatment Outcome Study – ATOS
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).
American Psychiatric Association (2000), Diagnostic and statistical manual of mental disorders, 4th edition, text revision, American Psychiatric Association, Washington, DC.
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.