Explore the most recent data on the drug situation in Europe provided by the EU Member States. These datasets underpin the analysis presented in the agency's work. Most data may be viewed interactively on screen and downloaded in Excel format.
We work closely with the 27 EU Member States plus Norway and Türkiye, candidates and potential candidates to the EU, the European Neighbourhood Policy countries and other third countries.
We have developed a systemic approach that brings together the human networks, processes and scientific tools necessary for collecting, analysing and reporting on the many aspects of the European drugs phenomenon.
We are your source of drug-related expertise in Europe. We prepare and share independent, scientifically validated knowledge, alerts and recommendations.
This database gives you access to the latest evidence on drug-related interventions. The information is based on systematic searches is updated regularly. To get started use the search boxes below.
Adding another formal psychotherapy, such as cognitive– behavioural therapy (CBT) or motivational enhancement therapy (MET), to contingency management (CM) was found in a systematic review with meta-analysis (Sheridan et al., 2020, 12 studies, N = 1654) to have no effect in:
improving both treatment end and at post-treatment follow-up compared with CM only
no evidence of a synergistic effect in PPA at treatment end (relative risk (RR) 0.97, 95% CI 0.85 to 1.09; p=0.57)
sensitivity analysis of studies featuring CBT/MET also found no evidence of an effect (RR 0.92; 95% CI 0.79 to 1.08; p=0.32)
none of the secondary outcomes showed any evidence of benefit.
Naloxone administration (intranasal/intramuscular) was assessed in a systematic review (Chou et al., 2017, 13 studies) and results showed that:
at the same dose (2 mg), 1 trial found similar efficacy between higher-concentration intranasal naloxone (2 mg/mL) and intramuscular naloxone,
1 trial found that lower-concentration intranasal naloxone (2 mg/5 mL) was less effective than intramuscular naloxone but was associated with decreased risk for agitation
Intranasal administration of naloxone was found in a review with meta-analysis (Yousefifard et al., 2020) to be as effective as intramuscular/intravenous administration in the pre-hospital management of opioid overdose:
the success rate (defined as the recovery of patients’ consciousness and spontaneous respiration) of the intranasal and intramuscular/intravenous administration of naloxone was 82.54% (95% CI: 57.97 to 97.89%) and 80.39% (95% CI: 57.38 to 96.04%) respectively with no difference between the two routes (OR=1.01; 95% CI: 0.42 to 2.43; P=0.98)
the prevalence of major side-effects was non-significant for both intranasal (0.00%) and intramuscular/intravenous (0.05%) routes and there was no difference in the prevalence of major (OR=1.18; 95% CI: 0.38 to 3.69; P=0.777) and minor (OR=0.64; 95% CI: 0.17 to 2.34; P=0.497) side-effects between the two routes.
The odds of needing a rescue dose were 2.17 times higher for intranasal naloxone than intramuscular/intravenous naloxone (OR=2.17; 95% CI: 1.53 to 3.09; P<0.0001), however since it does not require intravenous access and its re-administration does not cause serious complications, this limitation does not seem major enough to prevent its use.
Naloxone distribution was found in an umbrella review of systematic reviews (Razaghizad et al., 2021, 6 SR containing 87 unique studies) effective in:
reducing opioid-related mortality. High-concentration intranasal naloxone (> 2 mg/mL) was as effective as intramuscular naloxone at the same dose, whereas lower-concentration intranasal naloxone was less effective.
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)
Anti-alcohol/cannabis community interventions were analyzed in a review of reviews (McGrath et al., 2006, 29 reviews) and weak studies due to lack of control groups suggested a reduction in:
Mass-media campaign in combination with school-based, community-based or national programmes were found in a systematic review (Carson et al., 2017, 8 studies, N= 17 385) to be inconclusive regarding:
reduced smoking behaviour of young people (3 studies (n = 17,385) found some evidence but the remaining 5 studies (n = 72,740) did not detect a significant effect on smoking behaviour)
Unknown effectiveness
tobacco
improve behavioural life skills, reduce substance use
Coordinated, widespread, multi-component community interventions include age restrictions on tobacco purchase, programs for prevention of disease (like heart disease), mass media and school programs. Such interventions were found in a systematic review of 17 studies (Sowden and Stead, 2003) to:
reduce smoking prevalence when compared to no intervention control and to school-based programmes only;
reduce the rate of increase in smoking prevalence when compared to mass-media campaign alone.
A systematic review without meta-analysis (Penzenstadler et al 2019, 5 datasets) found no clear superiority of results of assertive community treatment (ACT) in reducing substance use (compared to control group).
ACT originally developed for patients with severe mental illness, providing personalized, high intensity, holistic and integrated multidisciplinary community care services.
Take home naloxone (THN) programs have been rapidly upscaled in response to increasing opioid-related mortality. One often cited concern is that naloxone provision could be associated with increased opioid use, due to the availability of naloxone to reverse opioid overdose.
A narrative systematic review (Tse et al., 2022, studies =7 - two quasi-experimental studies and five cohort studies, N= 2 578) investigated whether THN provision is associated with changes in substance use by participants enrolled in THN programs and found:
no evidence that THN provision was associated with increased opioid use or overdose.
Behavioural Activation (BA) interventions were found in a systematic review without meta-analysis (Matrínez-Vispo et al 2018, studies = 8, 6 of which RCTs) to potentially improve:
substance use (2 out of 6 RCTs reported statistically significant results in favour of BA)
depressive symptoms (6 out of 8 studies reported statistically significant results in favour of BA)
Unknown effectiveness
co-morbidity
improve mental health outcomes, reduce substance use
A narrative review (Fischer et al., 2015), without meta-analysis, concluded that, despite the fairly substantive body of largely controlled studies, there is:
mixed and short-term evidence, so not conclusive, on the effectiveness of targeted behavioural harm reduction measures, eg. peer-delivered intervention (‘EachOneTea-chOne’; EOTO), enhanced peer-delivered HIV education interventions, standard HIV prevention programs.
Behavioural therapies targeting specifically adolescents were analysed in a systematic review without meta-analysis (Hogue et al., 2014, 8 RCTs) and found that:
cognitive behavioural therapies (CBT) are well established but were outperformed by family-based treatments in several trials
cognitive behavioural therapies (CBT) at group level or at individual level are equally effective
A review of 29 reviews (McGrath et al., 2006) found evidence that booster sessions or similar extra components that aimed to reinforce the effects of a programme have a positive impact on the pre-specified outcomes. However, since the relationship between booster sessions and programme outcomes was not statistically examined, the link should be treated as hypothetical.
A systematic review with meta-analysis (Tanner-Smith et al., 2021, RCTs = 116, N= 64 439) investigated the effectiveness of brief interventions in patients of any age or severity level recruited in general medical settings. Analyses were conducted separately by brief intervention (BI) target substance: alcohol only or drugs. The overall conclusion was that when delivered in general medical settings, alcohol-targeted brief interventions may produce small beneficial reductions in drinking (equivalent to a reduction in 1 drinking day per month), however there is limited evidence regarding the effects of drug-targeted brief interventions on drug use.
Specific results of the analysis found that:
drug-targeted BIs yielded significant small improvements in multiple drug/mixed substance use (Hedges' g = 0.08; 95% CI = 0.002, 0.15), but after adjusting for multiple comparisons, they did not produce significant effects on cannabis use (g = 0.06; 95% CI = 0.001, 0.12), alcohol use (g= 0.08; 95% CI = -0.0003, 0.17), or consequences (g = 0.05; 95% CI = 0.01, 0.10)
drug-targeted BIs yielded larger improvements in multiple drug/mixed substance use when delivered by a general practitioner (g = 0.19; 95% CI = 0.187, 0.193)
alcohol-targeted BIs yielded small beneficial effects on alcohol use (g = 0.12; 95% CI 0.08, 0.16), but no evidence of an effect on consequences (g = 0.05; 95% CI = -0.04, 0.13). However, alcohol-targeted BIs only had beneficial effects on alcohol use when delivered in general medical settings (g = 0.17; 95% CI = 0.10, 0.24); the findings were inconclusive for those delivered in emergency department/trauma centers (g = 0.05; 95% CI = 0.00, 0.10)
Brief interventions (BIs) were analyzed analysed in a narrative systematic review and metanalysis for patients with comorbid substance misuse (Ghosh et al., 2023, 8 studies). The review found some positive but not conclusive effects on:
reducing substance use (Hedges g = 0.752, 95% confidence interval, 0.405–1.099) and alcohol consumption 3 months after the intervention.
More research is needed for robust results, due to the limited number of studies in the review.
Brief interventions for non-treatment seeking young adults (17-25 ys) were found in a systematic review with meta-analysis (Halladay et al., 2019) to have some promising but not conclusive effects when compared to no intervention or usual care in:
improving short-term abstinence - 3 months follow-up (OR 1.73, 95 % CI 1.13 to 2.66, 3 studies, N=666)
reducing the risk of cannabis use disorders (as measured by the CUPIT tool, a brief self-report screening instrument for detection of currently and potentially problematic cannabis use) (SMD -0.14, 95 % CI -0.26 to -0.01, 7 studies, N=1173)
The results were confirmed in a new systematic review with meta-analysis (Steele et al., 2020) that synthetised the evidence regarding the effects of brief behavioural interventions for adolescents (12–20 years) with problematic substance use. Brief interventions were categorized into motivational interviewing (MI), psychoeducation, and treatment as usual. The analysis found that:
use of MI did not reduce cannabis use days, with a net mean difference of 20.05 days per month (95% CrI: 20.26 to 0.14; moderate SoE)
while it confirmed the effectiveness of brief interventions, especially MI, in reducing heavy alcohol use and alcohol use days
Another narrative systematic review (Chazal et al., 2022, 8 studies, N= 2 199) assessed the effectiveness of brief interventions realized in primary care in reducing cannabis use for adolescents and emerging adults. Brief interventions were all based on motivational interviewing techniques or personalized feedback. The results found:
no significant reduction of cannabis use after brief intervention was found for most studies, especially in the long term.
Brief interventions (Bis) were found in a review with metanalysis (Schweer-Collins et al., 2023, k = 116, N= 12,074) to be more beneficial to treat alcohol use in the following target groups:
Females: The study found that among females, brief interventions (BIs) led to significant reductions in binge alcohol consumption (g = 0.09, 95% CI [0.03, 0.14]), frequency of alcohol consumption (g = 0.10, 95% CI [0.03, 0.17]), and alcohol-related consequences (g = 0.16, 95% CI [0.08, 0.25]). The study also found that BIs resulted in greater utilisation of substance use treatment (g = 0.25, 95% CI [0.21, 0.30]).
Individuals with less than a high school level education showed a significant decrease (g = 0.16, 95% CI [0.09, 0.22]) in the frequency of alcohol consumption at the 3-month follow-up.
Motivational interviewing was found to have no different effect than treatment as usual in a systematic review (Darker et al., 2015) in:
reducing use at any time intervals;
reducing drop-outs at any time intervals
A more recent systematic review with meta-analysis (Lynch at al., 2021,, studies = 8, n= 2071) investigated at the effectiveness of brief interventions in primary care compared to usual care. Results found promising yet very low quality (and thus not conclusive) evidence on:
discontinuation of BZRA use at 6 months (eight studies, RR = 2.73, 95% CI = 1.84-4.06) and 12 months post-intervention (two studies, RR = 3.41, 95% CI = 2.22-5.25)
Brief interventions delivered in healthcare settings targeting cannabis users were found in a systematic review with meta-analysis (Imtiaz et al., 2020) to have no conclusive effects when compared to minimal control interventions in:
improving cannabis-specific Alcohol, Smoking and Substance Involvement
Screening Test (ASSIST) scores in the short term (MD = 1.27 points, 95% CI 3.75 - 1.21)
reducing the number of days of cannabis use in the past 30 days in the short term (MD =0.22 days, 95% CI 2.27- 1.82) and long term (MD= 0.28 days, 95% CI 2.42- 1.86)
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)
A new systematic review with network meta-analysis (Lim et al., 2022, 79 RCTs) confirmed the results and found a significant overall effect of Buprenorphine compared to control in:
retaining people in treatment (RR 2.15, 95 % CI 1.76 to 2.69)
in the network analysis Methadone was the highest ranked intervention (Surface Under the Cumulative Ranking [SUCRA] = 0.901) with control being the lowest (SUCRA = 0.000). Methadone was superior to buprenorphine for treatment retention (RR = 1.22; 95% CI = 1.06-1.40) yet buprenorphine superior to naltrexone (RR = 1.39; 95% CI = 1.10-1.80).
Buprenorphine and methadone for opioid assisted withdrawal was found in a systematic review (Gowing et al., 2017, 27 RCTs, N = 3 048) to be equally effective in treatment outcomes and no difference between the two medications was detected in terms of:
completion rates (RR 1.04, 95% CI 0.91 to 1.20, RCTs = 5; N = 457, moderate quality)
average treatment duration (MD 1.30 days, 95% CI −8.11 to 10.72, RCTs = 2, N = 82, low quality)
Similarly, another systematic review (Baxley et al. 2022, 10 studies, N = 2468) also found that:
buprenorphine effectively reduced cravings
In three studies, there was a greater craving for buprenorphine than methadone. Both methadone and buprenorphine were effective, but this systematic review does not provide enough evidence to determine whether one is more effective than the other.
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
A new systematic review with network meta-analysis (Lim et al., 2022, 79 RCTs) confirmed the results and found a significant overall effect of Methadone in:
retaining people in treatment (RR 2.62, 95 % CI 2.09 to 3.33) compared to control
in the network analysis Methadone was the highest ranked intervention (Surface Under the Cumulative Ranking [SUCRA] = 0.901) with control being the lowest (SUCRA = 0.000). Methadone was superior to buprenorphine for treatment retention (RR = 1.22; 95% CI = 1.06-1.40) yet buprenorphine superior to naltrexone (RR = 1.39; 95% CI = 1.10-1.80).
In a more recent systematic review with meta-analysis (Degenhardt et al., 2023, 32 RCTs), the primary outcomes considered were retention in treatment, treatment adherence, and extra-medical opioid use; the following results were concluded:
For retention beyond one month, methadone had higher retention rates compared to buprenorphine (RR 0.76, 95% CI 0.67–0.85; I²=74.2%; 16 studies, N=3151)
For extra-medical opioid use, there is some evidence indicating lower rates of buprenorphine compared to methadone as measured by urinalysis (–0.20, 95% CI –0.29 to –0.11; I²=0.0%; 3 studies, N=841)
To summarise, the authors highlight that while methadone may have better treatment retention rates, there are few differences in other comparative outcomes. Therefore, it is important to consider other factors and take a client-centered approach when prescribing.
Beneficial
opioids
reduce substance use, retain patients in treatment
Case management was found in a systematic review with meta-analysis (Vanderplasschen et al., 2019) to be more effective than treatment as usual in:
improving treatment outcomes, including retention in treatment, linkages with services, satisfaction in treatment (SMD = 0.33, 95% CI 0.18–0.48). The largest effect size was found for retention in substance use treatment (SMD = 0.47, 95% CI 0.13 - 0.81) and linkage with substance use services (SMD = 0.23, 95% CI 0.11 - 0.35)
The analysis found a very small but statistically not significant effect on personal functioning outcomes (substance use, health status, legal involvement, risk behavior, and social functioning).
Case management is defined in the review as an intervention designed to enhance coordination and continuity of care and support, especially for persons with multiple, and complex needs.
A systematic review (Harada et al 2018) of two small RCTs (n=210) addressing the efficacy of cognitive-behavioural treatment (CBT) for people with amphetamine-type stimulants (ATS) use disorder found that there were insufficient data for conclusive assessment of CBT in the treatment of ATS use disorders (SMD -0.28, 95% CI -0.69 to 0.14).
The same result was confirmed by a systematic review of reviews (Ronsley et al., 2020, 29 systematic reviews examining eleven intervention modalities) that found no no significant benefit was identified for abstinence at 12 weeks, at the end of treatment, or at longest follow up.
Specifically for methamphetamine use disorder, a systematic review without meta-analysis (AshaRani et al., 2020) found that most of the behavioural interventions i.e., CBT, GCBT, MI and counselling demonstrated treatment some efficacy in reducing METH use in the participants however, a clear superiority of one over the other was not demonstrated. Moreover, while CM (contingency management) and CBT, both demonstrated positive outcomes individually, no clear synergism was observed when CM interventions were combined together with CBT.
Combined cognitive behavioral therapy (CBT) and pharmacotherapy was found in a systematic review with meta-analysis (Ray et al., 2020, 30 RCTs) to have:
increased benefits compared with usual care and pharmacotherapy
the effect for CBT on posttreatment frequency outcomes was small, homogeneous, and statistically significant (g=0.18 [95%CI, 0.01-0.35]; P = .04; τ2=0.00, Q > 0.05, I2 = 0%)
for quantity outcomes effects were small to moderate, homogenous, and significant (g=0.28 [95% CI, 0.03-0.54]; P = .03; τ2=0.03; Q > 0.05; I2 = 31%).
Outcomes included the following in the decisional hierarchy established by the authors: (1) biological assay measures, (2) measures of frequency or quantity in the form of means (SDs), (3) sample proportions, and (4) other outcomes (eg, diagnostic measures).
CBT did not perform better than another evidence-based modality (eg. contingency management, motivation enhancement therapy, 12-step facilitation, and interpersonal therapy) in this context or as an add-on to combined usual care and pharmacotherapy.
Combined enforcement checks and management training programmes were found in one study included in a systematic review (Bolier et al 2011) to be effective in:
reducing the service to under-age clients (relatively non-significant decrease in intervention group, from 46 % to 42 %).
Likely to be beneficial
alcohol
reduce risk behaviours
Police interventions, Responsible serving trainings and policies
Combined OST and high NSP coverage has been found to be effective in a systematic review with meta-analysis (Platt et al., 2017, 28 studies, N= 11 070 PWID) in:
reducing the risk of HCV acquisition by 74 % (RR 0.26 95% CI 0.07 to 0.89).
Another systematic review (Palmateer et al., 2022, 27 systematic review, 61 studies) confirmed the results and found sufficient evidence to support the combination of OST and NSP in:
the prevention of HCV transmission among PWID.
the prevention of injecting risk behaviour among PWID.
While there are still not enough studies to assess the effect on HIV, considering the positive effect on HCV, experts assume the same positive effect on HIV infections.
The Communities That Care (CTC) approach (i.e. community coalitions that develop a common strategy and mobilise communities in prevention and health promotion initiatives) was found in a systematic review (EMCDDA 2017, studies = 5) to be effective in:
reducing substance use and delinquency behaviours (USA trials)
Likely to be beneficial
not-drug specific
reduce disruptive behaviours, reduce substance use
Community-based interventions showed no significant impact in a systematic review (Stockings et al, 2018, 24 trials, n=249 125, samples subject to high-risk bias) in:
reducing binge-drinking (5 trials, RR 0.97, 95% CI 0.98 to 1.06); and
reducing 12 month marijuana use (2 trials, RR 0.98, 95% CI 0.86 to 1.11).
Community-based interventions showed some impact in a systematic review (Stockings et al, 2018, 24 trials, n=249 125, samples subject to high-risk bias) in:
reducing risky drinking (AUDIT ˃8, 3 trials, RR 0.78, 95% CI 0.62 to 0.99).
A systematic review comparing buprenorphine, methadone, and naltrexone in preventing relapse and promoting harm reduction among people with opioid addiction found that:
Methadone is considered the gold standard in MAT and can be started at any withdrawal stage. It requires titration to effective dose, which can be time-consuming and must be administered in specialized clinics.
Buprenorphine is the second most effective Medication-Assisted Treatment (MAT) for reducing harm and preventing relapse. It can be initiated and maintained in primary care settings, has low overdose risk but requires initiation during moderate withdrawal phase.
Naltrexone (Extended-Release, Intramuscular) in its oral form is ineffective due to low adherence, while the injectable extended-release form shown to reduce relapse and improve quality of life, but it requires 7–14 days of opioid abstinence before initiation.
Beneficial
opioids
reduce relapse rates, reduce substance use, retain patients in treatment
Comprehensive approaches involving community and school, were found effective in a systematic review (Jones et al., 2006, 222 studies - 14 systematic reviews; 103 RCTs; 52 Controlled non-randomized studies; 18 CBA; 35 BA) at preventing/delaying/reducing:
all substances when compared with community-only programmes and school-community programmes targeting high-risk youth (SMD = 0.38 and 0.36 respectively), and in high-risk individuals when compared with low-risk individuals (SMD = 0.42 and 0.08);
tobacco when compared with community-only programmes and school-community programmes targeting high-risk youth (SMD = 0.46 and 0.48), and in high-risk individuals when compared with low-risk individuals (SMD = 0.49 and 0.03);
alcohol when compared with community-only programmes and school-community programmes targeting high-risk youth (SMD = 0.49 and 0.49), and in high-risk individuals when compared with low-risk individuals (SMD = 0.56 and 0.05);
cannabis when compared with community-only programmes and school-community programmes targeting high-risk youth (SMD = 0.82 and 0.79), and in high-risk individuals when compared with low-risk individuals (SMD = 0.84 and 0.22);
all illicit drugs when compared with community-only programmes and school-community programmes targeting high-risk youth (SMD = 0.56 and 0.54), and in high-risk individuals when compared with low-risk individuals (SMD = 0.65 and 0.05).
There was no difference in effectiveness between ‘school-community’ programmes and ‘community-only’ programmes. Moreover, low risk population effect sizes were significantly greater across all types of interventions (‘comprehensive’, ‘school-community’, ‘community-only’) for tobacco (SMD = 0.05, SMD = 0.13); and cannabis (SMD = 0.04, SMD = 0.10). No other significant differences were reported.
Comprehensive family-oriented prevention, which includes training for parents, children and whole families, was found to be effective in one study included in a systematic review (Gates et al., 2006, 9 cluster randomised studies and 8 randomised studies, N = 1230) — although with some disagreement and methodological weaknesses — in:
reducing lifetime cannabis use and cannabis use in the past year in adolescents (RR = 0.55, 95 % CI 0.32–0.95 and RR = 0.44 95 % CI 0.20–0.96 respectively, at 6 year follow-up) .
Compulsory drug treatment (including drug detention facilities, short (i.e. 21-day) and long-term (i.e. 6 months) inpatient treatment, community-based treatment, group-based outpatient treatment, and prison-based treatment) was found in a systematic review without meta-analysis (Werb et al., 2016, 9 studies, N=10 699) was found to have no effect on:
drug use or criminal recidivism over other approaches (78% of the studies)
two studies (22 %) detected negative impacts of compulsory treatment on criminal recidivism compared with control arms
only two studies (22 %) observed a significant impact of long-term compulsory patient treatment on criminal recidivism: one reported a small effect size on recidivism after two years, and one found a lower risk of drug use within one week of release from compulsory treatment
Computer-based interventions targeting specifically recreational drug users were found in a systematic review (Wood et al., 2014) to have general positive results in:
reducing use of drugs both immediately and in the mid-term when targeting specifically recreational drug users
Contingency management (CM) interventions for people with HIV and substance use disorder were found in a systematic review with meta-analysis (Ribeiro et al. 2023, five studies) to have a more positive effect when compared to control conditions in:
adherence to antiretroviral therapy during the intervention period (improved patient adherence by 2.69 (95% confidence interval: [0.08, 0.51]; p = .007)).
Adherence to antiretroviral therapy was measured by counting the increase in CD4 (a type of white blood cell).
Contingency management in psychotic patients with Substance Use Disorders (SUD) was found in a systematic review with meta analysis (Destoop et al., 2021) to be effective compared to standard care in:
Improving abstinence rates of drug use, measured by:
self-reported lower number of days using substance (SMD = −0.52, 95% CI −0.98 to −0.06; p = 0.03
tendency to more negative breath or urine samples for substance use (OR 2.13, 95% CI 0.97 to 4.69; p = 0.06)
However no differences among retention in treatment (RR 1.15, 95% CI 0.90 to 1.45; p = 0.26).
Likely to be beneficial
not-drug specific
improve mental health outcomes, reduce substance use
A recent systematic review with meta-analysis (Bolivar et al., 2021, RCT= 74, N=10 444) found contingency management for patietns receiving medication for opioid use disorder to have:
medium-large effect size for abstinence from stimulants, Cohen d = 0.70 [95% CI, 0.49-0.92]; cigarette use, Cohen d = 0.78 [95% CI, 0.43-1.14]; illicit opioid use, Cohen d = 0.58 [95% CI, 0.30-0.86] and improved medication adherence, Cohen d = 0.75 [95% CI, 0.30-1.21]),
small-medium effect size for increased absitnence from polysubstance use, Cohen d = 0.46 [95% CI, 0.30-0.62] and improved therapy attendance, d = 0.43 [95% CI, 0.22-0.65]).
Collapsing across abstinence and adherence categories, contingency management was associated with medium effect sizes for abstinence (Cohen d = 0.58; 95% CI, 0.47-0.69) and treatment adherence (Cohen d = 0.62; 95% CI, 0.40-0.84) compared with controls.
Contingency management was found in a systematic review (EMCDDA 2016, studies = 20, N=1 676) to be effective in:
helping opioid users in substitution treatment to reduce cocaine use (10 out of 13 studies reported statistically significant results in favour of CM)
helping opioid users in substitution treatment to improve cocaine abstinence (8 out of 8 studies reported statistically significant results in favour of CM)
helping opioid users in detoxification to improve retention in treatment (2 out of 3 studies reported statistically significant results in favour of CM) as well as opioids and cocaine abstinence (7 out of 10 studies reported statistically significant results in favour of CM)
Reducing cannabis use for patients with comorbidities could improve clinical, cognitive, and psychosocial outcomes. Contingency management (CM) for patients with comorbid diagnoses was assessed in a narrative systematic review (Rodas et al., 2022, 6 studies, 4 focused on Schizophrenia and schizoaffective disorder, while the remaining two involved patients with major depressive disorder) and found to have an effect in:
decreasing cannabis use.
More research is needed to establish the implications of CM for improving psychiatric symptoms in patients with comorbidities. Several studies in the current review did not find significant results in reducing psychiatric symptom severity.
Unknown effectiveness
co-morbidity
improve mental health outcomes, reduce substance use
Contingency management (CM) involves participants receiving something of value such as a gift card, voucher or chance to win a prize as a reward for the achievement of a specific and measurable desired behaviour, most commonly a negative urine drug test for stimulants when implemented for the treatment of stimulant use disorder.
CM alone was found in a systematic review of reviews (Ronsley et al., 2020, 29 systematic reviews examining eleven intervention modalities) to be effective in improving:
abstinence at 12 weeks (Odds Ratio [OR] 2.29, 95% Confidence Interval [CI] 1.62, 3.24),
abstinence at the end of treatment (OR 2.22, 95% CI 1.59, 3.10),
dropout at 12 weeks (OR 1.39, 95% CI 1.09, 1.78),
and dropout at the end of treatment (OR 1.41, 95% CI 1.10, 1.82).
However the effect was not sustained at longest follow up (OR 1.10, 95% CI 0.83, 1.46).
Another more recent systematic review with meta-analysis (Bentzley et al., 2021) statistically compared all the different treatment options (157 studies comprising 402 treatment groups and 15 842 participants) looking for the interventions associated with an objective reductions in cocaine use among adults. Excluding other therapies, the largest treatment groups across all studies were psychotherapy (mean [SD] number of participants, 40.04 [36.88]) and contingency management programs (mean [SD] number of participants, 37.51 [25.51]). The analysis found that:
only contingency management programs were significantly associated with an increased likelihood of having a negative test result for the presence of cocaine (OR, 2.13; 95% CI, 1.62-2.80), and this association remained significant in all sensitivity analyses.
METHAMPHETAMINE
A systematic review without meta-analysis (Hayley et al., 2020) described the broad benefits of contingency management, including greater drug abstinence, higher utilization of other treatments and medical services, and reductions in risky sexual behaviour specifically for methamphetamine users.
Another systematic review without meta-analysis (AshaRani et al., 2020) confirmed that CM interventions among all the behavioural interventions consistently showed benefits (reduced drug use, better treatment retention, reduction in psychiatric symptoms and better quality of life) during the treatment period of METH use; however, the sustainability of the effect, post-intervention, is not well-studied. Moreover they found that although CM and CBT, both demonstrated positive outcomes individually, no clear synergism was observed when CM interventions were combined together with CBT.
Continuing care, i.e. interventions following the initial period of more intensive care aimed at manage and sustain recovery (including cognitive behavioural therapies (CBT), recovery management check-ups, 12-step or self-help and technology based interventions) was found in a systematic review with meta-analysis (Blodgett et al., 2014, 19 studies, N=3542) to be more effective than control conditions on:
at least one substance use outcome (Hedges’ g = 0.187, p< 0.001)
The same meta-analysis also found that
longer planned treatments did not have larger effects sizes than studies with shorter prescribed periods of treatment
there was no significant difference between treatments with protocol-specified intervention sessions and those without planned sessions per week
These results were confirmed by another systematic review without meta-analysis (Dennis et al., 2014) that looked specifically at the effects of different types of continuing care:
behavioural therapies showed promising results on use and retention in treatment outcomes, especially for moderate severity clients recovery managements check-ups are primarily effective in linking people back to treatment more robust evidence is still needed for self-help groups and technology-based interventions
Opioid substitution treatment was found in a systematic review (ECDC/EMCDDA, 2018) to be effective in:
reducing post-release mortality.
One cohort study (Degenhardt et al., 2014) enrolling N=16453 people released from prison 60161 times (all opioid dependent people who entered OST between 1985 and 2010 and were released from prison at least once between 2000 and 2012 in Australia) showed that those continuously retained in OST after being released from prison (continuity of care):
had a reduced risk of mortality by 75% (adjusted hazard ration=0.25, 95 % CI 0.12 to 0.53).
One RCT (Dolan et al., 2005, cited in EMCDDA, 2010) suggests that retention in MMT in prison settings is associated with:
reduced mortality from all causes (OR 0.54, 95 % CI 0.20 to 1.43);
Economic evaluations of the pharmacological treatment of opioid use disorder were analysed in a narrative systematic review (Onuoha et al., 2021, studies = 21 - 4 cost-offset studies and 17 cost-effectiveness/cost-benefit studies) that found:
strengthened evidence on the cost-effectiveness of buprenorphine and methadone, indicating that these treatments are both economically advantageous compared with no pharmacotherapy (no evidence was found supporting superior economic value between the two medications)
Four studies focused on the potential reductions in healthcare costs associated with pharmacological treatment of opioid use disorders and found that OST leads to lower healthcare resource utilization and expenditures than nonpharmacologic therapies. Also results from one population-level study indicate significantly lower criminal justice–related costs among participants who received methadone compared with those who received detoxification only.
Further economic research is needed on Naltrexone, as well as other emerging pharmacotherapies, treatment modalities, and dosage forms.
Culturally sensitive programs integrate positive youth development factors such as future orientation, problem-solving, communication, decision-making, and emotional regulation with specific cultural or ethnic factors related to socialisation, identity, and acculturation. Culturally sensitive prevention programs for substance use were assessed in a systematic review and meta-analysis (Bo et al., 2023, 30 studies) and found a small yet significant effect in:
Preventing and reducing substance use (Hedges’s g = - 0.20, 95% CI = [-0.24, -0.16])
Likely to be beneficial
improve knowledge, improve psychosocial functioning, reduce substance use
Culturally sensitive substance use treatment interventions for racial/ethnic minority youth were found in a systematic review with meta-analysis (Steinka-Fry et al., 2017) to have no significant effect in:
reducing use when compared to ‘treatment as usual’ and bona fide comparisons (i.e. intervetions that differed only on the culturally sensitive elements)
Customised Employment Supports (CES) is an employment counseling intervention tailored for clients in SUD treatment, emphasizing small caseloads, therapeutic alliance, rapid job search, vocational fieldwork and longterm support. CES is one of the interventions/programmes aimed at improving employment outcomes evaluated in a narrative review (Magura et Marshall, 2020, 14 studies).
CES is an adaptation from the Individual Placement and Support model (IPS). The main and significant differences between IPS and CES are that CES does not incorporate job development, but rather relies on available jobs in the community, and includes an emphasis on fieldwork— accompanying clients into the community for such things as looking for local job postings and making employer contacts.
The review concluded that CES had significant effect on:
improving employment outcomes (41% of individuals in CES obtained any paid employment vs. 26% of those in standard treatment (p < .05); 27% obtained informal employment vs. 14% of those in standard treatment (p < .05)
The other interventions reviewed are: Individual Placement and Support (IPS), Therapeutic Workplace (TW), Drug court employement intervention, Job Seekers Workshop (JSW).
Customised employment supports for methadone maintenance clients focusing on individualised interventions to promote vocational skills and reduction of non-vocational barriers (e.g. low self-efficacy) was found to be effective in one RCT (n = 168; Magura et al., 2007, cited in EMCDDA, 2012 - Online appendix):
41 % of intervention vs. 25.5 % of standard vocational counselling participants had paid employment (full or part time) during both follow-up periods;
regression analysis showed that having prior paid employment, full intervention and receiving the intervention rather than the control were significant predictors of having any paid employment at follow-up;
there was, however, no difference in mean income during the study period.
Digital interventions for substance were assessed in a narrative review (Boumparis and Shaub, 2022). Programmes considered were both add-on interventions or standalone interventions and substance-specific (mainly cannabis interventions), were found:
to have good feasibility among target groups
However most studies were underpowered to assess effectiveness.
Digital prevention and treatment interventions were found in a systematic review with meta-analysis (Boumparis et al., 2019, 30 studies, N=13 333) to have a small but significant effect in:
reducing Cannabis use at post-treatment in the prevention interventions (6 studies, N=2564, g=0.33; 95% CI 0.13 to 0.54, p= 0.001) and in the treatment interventions (17 comparisons, N=3813, g=0.12; 95% CI 0.02 to 0.22, p= 0.02) as compared with controls;
the effects of prevention interventions were maintained at follow-ups of up to 12 months (5 comparisons, N=2445, g=0.22; 95% CI 0.12 to 0.33,p < 0.001) but were no longer statistically significant for treatment interventions
Computerized interventions were confirmed to be effective, by an additional systematic review with meta-analysis (Olmos et al 2017, 9 RCTS; n=2963) in:
reducing cannabis use (self-reported or urine testing) at 6 months follow-up (SMD: -0.19; 85% CI: -0.26 to -0.11; ).
Computerized interventions included personalised online feedback, motivational interviewing, computer-delivered cognitive behavioural therapy and clinician-assisted computer-based interventions.
Digital interventions (internet- or computer-based interventions) were found in a systematic review with meta-analysis (Hoch et al., 2016, 4 studies, N=1 928) to be effective in:
reducing cannabis use (self-reported) after 3 month follow-up (MD – 4.07, 95 % CI -5.8 to -2.34). The largest treatment effects were found for the web-based online chat with a trained psychotherapist, plus online diary with weekly personalized, written feedback based on CBT/MI.
Online interventions, web or mobile-based, for young adults (defined as adolescents and young adults from 15 to 30 years), including peer-to-peer contact, patient-to-expert communication, or interactive psychoeducation/therapy to reduce cannabis use was found in a systematic review with meta-analysis (Beneria et al., 2021, 17 RCTs, N= 3 525) to have no effect in:
reducing cannabis consumption (Hedge's g = -0.061, 95% CI [-0.363] to [-0.242], p = .695)
However, some of the more recent studies out of the 17 used in the analysis, reported positive results. These trials used structured interventions, daily feedback, young adults centred designs, peer support, and specifically targeting cannabis use (as opposed to generic interventions) and showed promise as potentially effective approaches to address cannabis use in this population.
A narrative systematic review (Ramadas et al., 2023, 5 studies) assessed the effectiveness of digital interventions in providing ongoing support for individuals with alcohol use disorders (AUD). The review concluded that:
smartphone applications might be beneficial to provide continuous support for the treatment of AUD (Out of the 5 studies, 4 found the intervention to be clinically effective).
Due to the limited number of studies, more research is needed to provide robust conclusions.
A narrative review (Fischer et al., 2015), without meta-analysis, concluded that there is:
mixed and short-term evidence, so not conclusive, on the effectiveness of the distribution of crack use paraphernalia on morbidity and mortality outcomes.
Drink-driving service (free transport home - ‘Tipsy Taxi’ service (operated 24 hours a day, 365 days a year) providing a free ride home for persons too intoxicated to drive. Service offered by bar employee or request made to bar employee by patron. Control areas had no such service.) for intoxicated drinkers was found to be effective in a systematic review (Ker and Chinnock, 2008) in:
reducing injury in car crashes: 15 % reduction in the experimental area (reported as ‘highly significant’), with no change in the control.
reducing fatal crashes (ratio reduced from 0.78 to 0.60, P = 0.29 – not statistically significant).
DCRs were found to be effective in a systematic review without meta-analysis (Kennedy et al., 2017, 47 studies) in:
facilitating access and uptake of health care services, both addiction services (4 studies) and other health or social services (9 studies).
A systematic review (Potier et al., 2014), without meta-analysis, concluded that:
DCRs are effective in reaching the most marginalized and problematic injecting users.
Another systematic review and meta-synthesis of qualitative studies (McNeil et al., 2014, 21 studies, n>800) that looked specifically at the effects of three types of safer environment interventions (SEI - syringe exchange, peer-based approaches and drug consumption rooms) found that SEI:
provide refuge from street-based drug scene
enable safer injecting by reshaping social and environmental contexts
mediate access to resources and health care services
Drug consumption rooms were found in a systematic review without meta-analysis (Kennedy et al., 2017, 47 studies) to have a promising but not significant effect in:
reducing public disorders associated with illicit drug use (people injecting drugs in public, publicly discarded syringes and injection-related litter) (5 studies).
Results of 6 studies also found no change in drug-related offences (drug dealing, thefts or robbery incidents, drug possession) within the area of the DCRs.
Drug court programmes are among the interventions/programmes aimed at improving employment outcomes evaluated in a narrative review (Magura et Marshall, 2020, 14 studies). The drug court interventions included in the review consisted of 26 individual and group counseling sessions provided by an employment specialist with experience in both employment and SUD counseling.
The review showed no significant effect on:
increased number days of paid employment
increased income
The other interventions reviewed are: Individual Placement and Support (IPS), Customized Employment Supports (CES), Therapeutic Workplace (TW), Job Seekers Workshop (JSW).
Drug court programmes were found to be effective in a systematic review (Mitchell et al., 2012, 154 studies) in
reducing recidivism at three years follow-up for adult drug courts (3 studies; the mean effect size is analogous to a drop in recidivism from 50% for non-participants to approximately 38% for participants)
reducing recidivism for drunk-driving drug courts (DWI) (4 studies – 3 found sizeable reductions in recidivism, however, 1 experimental evaluation found a negative effect)
reducing recidivism for juvenile drug courts albeit with a smaller effect size (the mean effect size is analogous to a drop in recidivism from 50% for non-participants to roughly 43.5% for participants)
Ecological family-based treatments (including multidimensional family therapy) delivered in community settings were found in a systematic review without meta-analysis (Hogue et al., 2014, 8 RCTs) and a meta-analysis (Hartnett et al., 2016, 14 studies) to have significant effect in:
reducing adolescent drug use (mainly cannabis and alcohol)
reducing adolescent disruptive behaviours
Beneficial
alcohol, cannabis
reduce disruptive behaviours, reduce substance use
A systematic review was performed to examine whether the addition of naloxone to buprenorphine, bup/nx, has a clinical difference in a treatment setting and whether bup/nx is more effective than buprenorphine and methadone.
Overall, there was no statistically significant difference in treatment retention between bup/ nx and buprenorphine or bup/nx and methadone (OR 0.58, 95% CI 0.28,1.19), which showed that the addition of naloxone yields no clinical difference.
This suggests that bup/nx may be used as an alternative to methadone or buprenorphine and may allow patients the choice in opioid replacement therapy.
In a systematic review investigating the effectiveness of Dihydrocodeine in reducing illicit opiate use:
Two studies with 150 individuals compared DHC with buprenorphine for detoxification and found low-quality evidence of no significant difference between DHC and buprenorphine for detoxification at six-month follow-up (RR 0.59, 95% CI 0.25 to 1.39; P = 0.23) in the meta-analysis for the primary outcome of abstinence from illicit opiates. Similarly, low-quality evidence indicated no difference for treatment retention (RR 1.29, 95% CI 0.99 to 1.68; P = 0.06).
One study with 235 participants compared DHC to methadone for maintenance substitution therapy resulting in low quality evidence, and possibly no difference in effects between DHC and methadone for reported abstinence from illicit opiates (MD −0.01, 95% CI −0.31 to 0.29). For treatment retention at six months' follow-up in this single trial, the RR calculated with an intention-to-treat analysis also indicated that there may be no difference between DHC and methadone (RR 1.04, 95% CI 0.94 to 1.16).
It is premature to make any conclusive statements about the effectiveness of DHC and further high-quality studies are needed, especially in low- to middle-income countries.
Unknown effectiveness
opioids
reduce substance use, retain patients in treatment
In a systematic review investigating changes in retention over time for participants in buprenorphine and methadone programs in LMIC, retention was measured for participants by length of follow-up, type of medication-assisted treatment (MAT) and treatment dosage. It was found that in LMIC:
Overall average retention after 12 months was 54.3% (95% CI = 46.2, 63.7%).
Overall average retention was moderately good for both buprenorphine (48.3%, 95% CI = 22.1, 74.6%) and methadone (56.6%, 95% CI = 45.9%, 67.3%) after 12 months of treatment.
Among programs using methadone there was no statistically significant difference in average retention by dosage level, and the 10 highest and lowest dosage programs obtained similar average retention levels after 12 months.
These results are comparable to average retention rates seen among MAT participants in high-income countries. The study demonstrates the effectiveness of MAT in LMIC, underscoring that there is no justification for delaying its broader implementation in these settings.
Beneficial
opioids
reduce substance use, retain patients in treatment
Brief interventions in emergency settings were found in a systematic review without meta-analysis (EMCDDA, 2016, 16 studies, N=8 875) to have no effect in:
significantly decreasing substance use (mainly alcohol) and related harms
The same results were confirmed in a more recent narrative systematic review (Kaczorowski et al., 2020, 12 studies) that focused specifically on ER-initiated interventions for opioid users.
Buprenorphine initiation in emergency departments was found in a narrative systematic review (Kaczorowski et al., 2020) to have:
positive short-term effects on treatment outcomes (i.e. retention and use)
The review concluded that while EDs seems to be an appropriate setting for initiating opioid agonist treatment, in order to be sustained, it likely needs to be coupled with community-based follow-up and support to ensure longer-term retention.
Employer-led interventions (including employee education, drug testing (random, post-accident and reasonable suspicion), employee assistance programs (EAP), supervisor training, written workplace drug-free policy, and restructuring of employee health benefit plans) showed no significant difference in a narrative review (Akanbi et al., 2020, 27 studies) in:
reducing use
reducing the adverse effects of drug misuse in the workplace
Employment-based interventions (including substance use and vocational skills interventions (7 studies), supported employment (6 studies), and integrated supports including an employment component (6 studies)) were found to have mixed results in:
improving community reintegration
improving well-being outcomes
reducing substance use
Specifically:
Employment participation: only two out of the 12 studies reported a statistically significant increase in employment participation. The statistically significant studies involved interventions for individuals with substance use and/or concurrent disorders. Thus, interventions targeting substance use disorder or mental illnesses and housing interventions might lead to larger benefits.
Improvement of housing: Four studies in this review reported improved housing after the intervention. Determining the interventions’ impact on housing was complicated due to only half of the studies measuring housing outcomes.
Unknown effectiveness
not-drug specific
improve employability, improve mental health outcomes, improve psychosocial functioning, reduce substance use
A systematic review with meta-analysis (Tinner et al., 2022, 66 studies) assessed the effects of individual-, family- and school-based interventions to prevent multiple risk behaviours relating to alcohol, tobacco and drug use in young people aged 8-25 years.
There were too few family-level (n=4), individual-level (n=2) and combination level (n=5) studies to draw confident conclusions.
Multi-component programmes, with both family and schools interventions, for preventing smoking by children and adolescents were found in a systematic review (Thomas et.al., 2015, 27 RCTs), to be more effective than school-only intervention in:
reducing smokng in adolescents who never smoked at baseline (2 RCTs, N = 2 301) (RR = 0.85, 95 % CI 0.75–0.96)
reducing smoking in adolescents who were smokers at baseline (1 RCT, N = 1 096) (RR = 0.60, 95 % CI 0.38–0.94)
Family focused, psychosocial, preventive interventions targeting parents/carers at risk of, or experiencing, parental domestic violence and abuse, mental ill-health, and substance misuse were assessed in a systematic review (Allen et al., 2022, 37 studies, studies were included if they measured impacts on two or more of these issues). Results showed that:
none had a combined positive impact on all three outcomes and only one study demonstrated a combined positive impact on two outcomes.
The analysis also found studies that had combined adverse, mixed, or singular impacts.
A recent systematic review (MacArthur et al 2018) of 70 RCTs addressing two or more risk behaviours (with a follow-up period of at least six months) and targetting children up to 18 years of age found:
little or no effect of family- or individual-level multiple risk behaviour interventions to prevent alcohol use (moderate to low-quality evidence, with few studies available for comparisson, n≤ 4)
A recent systematic review (MacArthur et al 2018) of 70 RCTs addressing two or more risk behaviours (with a follow-up period of at least six months) and targetting children up to 18 years of age, found:
little or no effect of family- or individual-level multiple risk behaviour interventions to prevent cannabis use (moderate to low-quality evidence, with few studies available for comparisson, n≤ 4)
A recent systematic review (MacArthur et al 2018) of 70 RCTs addressing two or more risk behaviours (with a follow-up period of at least six months) and targetting children up to 18 years of age, found:
little or no effect of family- or individual-level multiple risk behaviour interventions to prevent illicit drug use (moderate to low-quality evidence, with few studies available for comparisson, n≤ 4)
A recent systematic review (MacArthur et al 2018) of 70 RCTs addressing two or more risk behaviours (with a follow-up period of at least six months) and targetting children up to 18 years of age found:
little or no effect of family- or individual-level multiple risk behaviour interventions to prevent tobacco use (moderate to low-quality evidence, with few studies available for comparisson, n≤ 4)
Family-based prevention programs (including development of parenting skills, parental support, nurturing behaviours, establishing clear boundaries or rules, parental monitoring, social and peer resistance skills, development of behavioural norms and positive peer affiliations) have shown to be effective in a systematic review (Foxcroft et al., 2011, 12 RCTs) in:
reducing alcohol misuse in adolescents, with persistence of effects over the medium and longer-term (in 9 of the 12 RCTs analysed)
Las directrices internacionales basadas en la evidencia (OMS, 2014) no recomiendan la farmacoterapia para el tratamiento rutinario de la dependencia de los estimulantes y del cannabis en mujeres embarazadas
Evidence of ineffectiveness
cannabis
improve treatment outcomes, retain patients in treatment
A systematic review with meta-analysis (Lo Coco et al 2019, 33 RCTs, n= 3951) of substance use treatment interventions in group settings found:
significant small effects on abstinence when compared to no treatment (SMD 0.28, 95% CI 0.04 to 0.52), individual therapy (SMD 0.34, 95% CI 0.06 to 0.62), and other treatments (SMD 0.29, 95% CI 0.07 to 0.50).
no significant effects on substance use frequency when compared to individual therapy (SMD 0.52, 95% CI -0.25 to 1.28), and other treatments (SMD 0.01, 95% CI -0.14 to 0.16).
significant moderately sized effects for mental state when compared to no treatment (SMD 0.64, 95% CI 0.38 to 0.90).
no difference in abstinence rates when compared to control groups.
Interventions addressed the use of alcohol, cocaine, heroin or opioids, and cannabis.
European guidelines (EASL, 2015) recommend to provide treatment to drug users on an individualized basis and delivering it within a multidisciplinary setting.
Opioid substitution treatment is not a contraindication to HCV treatment.
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, 8 RCT, 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).
A more recent systematic review and meta-analysis (McNair et al., 2023, eight studies n = 2331) found that supervised heroin-assisted treatment (HAT) leads to effective results in:
Heroin-assisted-treatment (HAT) effects on criminal activity were evaluated in a systematic review with meta-analysis (Smart and Reuter, 2022, 10 RCTs, N= 2 427). Results found:
significantly reduced criminal activity among HAT participants,
four trials found significantly larger reductions for HAT compared to control condition [median odds ratios (ORs) = 0.45].
Reductions in crime are concentrated in drug-related and property offenses (ORs range from 0.14 to 0.90 and from 0.12 to 1.89, respectively).
Home visitation for families composed of low-income unmarried women was found in a narrative review to be mildly effective at 15-year follow-up (Toumbourou et al., 2007, 1 study, N= 743) in reducing for the parent(s):
number of cigarettes smoked per day (1.50 versus 2.50, p = 0.10);
number of days having consumed alcohol in the past six months (1.09 versus 2.49, p = 0.03)
Individual Placement and Support (IPS) is based on eight principles aimed at helping individuals tofind and work in competitive jobs of their choosing. These principles are: competitive employment, systematic job development, rapid job search, integrated services, benefits planning, no client exclusion, worker preferences, and time-unlimited supports. IPS has been shown to be effective in improving employment of persons with serious mental disorders.
Individual Placement and Support interventions were found in a narrative systematic review (Harrison et al., 2019, 5 RCTs, 2 Cohort) to be effective in:
improving employment outcomes (employment rates, hours worked, wages earned) in individuals with substance use disorders.
IPS is one of the interventions/programmes aimed at improving employment outcomes evaluated in another narrative review (Magura et Marshall, 2020, 14 studies). The other interventions were: Customized Employment Supports (CES), Therapeutic Workplace (TW), Drug court employement intervention, Job Seekers Workshop (JSW).
The review concluded that IPS had significant effect on:
Information provision (e.g. prevention or harm reduction information material, such as brochures and pamphlets on intoxication and related harm) was not found to be an effective measure in a narrative review (EMCDDA, 2012) in:
Interventions aimed at improving engagement of PWID at any (or combination) of the following stages along the chronic HCV care cascade: a) linkage to care, defined as the clinical assessment of HCV infection or liver disease following diagnosis of HCV infection b) adherence to treatment, with regimens combining inter- feron/DAA or solely DAA were evaluated in a systematic review with meta-analysis (Schwarz et al., 2022, 14 studies).
Integrated care structures, where a variety of services are brought together, and nurse case management approaches that facilitate referral for HCV assessment and scheduling of specialist appointments for clients were found to be the most effective in:
improving engagement throughout the continuum of HCV care among people who inject drugs and people receiving OST
A systematic review without meta-analysis (Vold et al 2019, 7 RCT and 3 cohort studies, high risk of bias), found uncertain results on the effects of integrated care models on the treatment of infectious diseases in people with substance use disorders.
Intensive family-based programmes for preventing smoking by children and adolescents were found in a systematic review (Thomas et.al., 2015, 27 RCTs), to be effective in:
reducing cigarette use in adolescents (9 studies, N=4 810) (RR = 0.76, 95 % CI 0.68–0.84)
Programmes offering strong behavioural life skills development content, emphasised team-building, interpersonal communication methods, and introspective learning approaches focusing on self-reflection were found to be effective in a review of studies (Springer et al., 2004) in:
reducing 30-day tobacco, alcohol and herbal cannabis (‘marijuana’) use among vulnerable youth.
These programmes were based upon a clearly articulated and coherent programme theory, and provided quality contact with young people
School-based interactive programmes (i.e. those involving discussion) implemented in schools with predominantly special population, were found in a meta-analysis (Porath-Waller et al., 2010, 222 studies, N= 15 571) to be more effective than non-interactive programmes (i.e. a lecture) in:
reducing smoking or non-smoking tobacco use, alcohol use or drinking/driving, “cannabis” or other illicit drugs’ use (SMD 0.21 vs. -0.05, p < 0.000);
statistically significant delay in the onset of substance use;
Internet-based interventions (including unguided stand-alone internet interventions and internet interventions as an add-on to treatment as usual) were found in a systematic review with meta-analysis (Boumparis et al., 2017, 17 RCTs, N = 2 836) to have a small but significant effect in:
reducing drug use at post-treatment (pooled analysis of the 17 studies, g = 0.31; 95 % CI = 0.23-0.39, P < 0.001, N = 2 836) and at follow-up assessments (g = 0.22; 95 % CI = 0.07-0.37; P = .003, RCTs = 9, N = 1 906)
decreasing any illicit drug use at post-treatment (g = 0.35; 95 % CI = 0.24-0.45, P < 0.001, RCTs = 9, N= 1 749)
decreasing opioid use at post-treatment (g = 0.36; 95 % CI = 0.20-0.53, P < .001, RCTs = 4, N=606)
Digital interventions targeting opioid users were assessed in a different narrative review (Kiburi et al., 2023, 20 studies) and found some evidence of effect in:
retaining people in treatment (of 20 studies, 10 reported statistical significance for abstinence and four increased treatment retention)
Internet-based interventions (including unguided stand-alone internet interventions and internet interventions as an add-on to treatment as usual) were found in a systematic review with meta-analysis (Boumparis et al., 2017, 17 RCTs, N = 2 836) to have no significant effect in:
reducing stimulant use at post-treatment (P = 0.164, RCTs = 4, N = 481)
Different interventions targeting drug-using offenders with co-occurring mental illness (including interpersonal psychotherapy, multi‐systemic therapy, legal defence wrap‐around services, and motivational interviewing) were found in a systematic systematic review (Perry et al., 2019, 13 RTCs, N = 2 606) to have no significant effect in:
A narrative systematic review (Dalton et al., 2021) assessed the interventions for emerging adults (age 18 -25) showing more promise to retain these patients in treatment. The results indicate that the interventions with the most promise for retention in treatment were:
behavioural therapy such as cognitive behavioural therapy and contingency management for cannabis and alcohol use disorders
cognitive behavioural therapy paired with opioid-agonist-therapy for opioid use disorder
A narrative systematic review (Razaghizad et al., 2021, studies = 11 RCTs and 17 non-RCTs, N = 33,711 of 37,117 active research participants aged 15-25 yrs) investigated the effectiveness of prevention interventions for drugs-and-driving outcomes. The results found evidence to support the interventions that may improve drugs and driving knowledge, attitudes, and behaviours, specifically:
high quality evidence that cannabis packaging with health warnings increases the knowledge about drugged driving effects
moderate quality evidence that roadside drug testing can reduce drugs-and-driving among cannabis users
moderate quality evidence that for youth or previous offenders, motivational interviewing can prevent drug-and-driving and driver education programs can increase knowledge
The impact of such interventions on measures of drugs-and-driving morbidity and mortality outcomes is uncertain.
Interventions to reduce intimate partner violence perpetration by men who use substances (mainly CBT and MI therapies) were found in a systematic review with meta-analysis (Stephens-Lewis et al., 2021, 9 RCTs, N = 1 014 men) to have no effect compared to treatment as usual in:
reducing substance use or intimate violence partner violence
Interventions to reduce stigma about substance abuse aim to establish contact with vulnerable groups to avoid social isolation, protest and take action against prejudice, and foster education to replace myths with factual knowledge. A systematic review (Gür & Yilmaz, 2023, 10 studies) to assess the effectiveness of interventions reducing substance-related stigma found that:
interventions did not have a significant impact on reducing stigma (Hedges’ g = 0.301, 95% CI =-0.154 to 0.755, p = 0.195) nor social stigma (g=-0.198, 95% CI=-1.271 to 0.876).
interventions had a small significant impact on reducing structural stigma [0.360 (95% CI= 0.156-0.564), p = 0.00].
The Job Seekers Workshop (JSW) is a model that provides short-term, small group sessions focusing on locating available jobs, making “cold calls” to potential employers, and rehearsing job interview skills. JSW is among the interventions/programmes aimed at improving employment outcomes evaluated in a narrative review (Magura et Marshall, 2020, 14 studies).
The review showed no significant effect on:
improving employment outcomes
The other interventions reviewed are: Individual Placement and Support (IPS), Customized Employment Supports (CES), Therapeutic Workplace (TW), Drug court employment interventions.
Social influence approaches use normative education methods and anti-drugs resistance skills training. School-based programmes that implement the concepts of social influence and life skills were found in a large trial (Faggiano et al., 2010) to be effective in:
reducing overall drunkenness (OR 0.80, 95 % CI 0.67 to 0.97, 1 RCT, N= 7079);
reducing drunkenness in 3 or more episodes (OR 0.62, 95 % CI 0.47 to 0.81, 1 RCT, N= 7079)
Beneficial
alcohol
reduce substance use
Life skill and social influence–based school programmes
School programmes based on a combination of social competence and social influence approaches were found in a systematic review (Faggiano et al., 2014) to be more effective than usual curricula in:
reducing generic drug use at <12 months (RR 0.76, 95 % CI 0.64 to 0.89, 1 study, N=6362)
Beneficial
not-drug specific
reduce substance use
Life skill and social influence–based school programmes
School programmes based on a combination of social competence and social influence approaches were found in a systematic review (Faggiano et al., 2014) to be more effective than usual curricula in:
reducing cannabis use at 12+months follow-up (RR 0.83, 95 % CI 0.69 to 0.99, 6 studies, N=26 910);
Beneficial
cannabis
reduce substance use
Life skill and social influence–based school programmes
School programmes based on a combination of social competence (life skills-based) and social influence approaches were found in a systematic review (Faggiano et al., 2014) to have no different effect than usual school curricula or no intervention in:
reducing hard drug use at <12 months follow-up (conflicting results between dichotomous and continuous outcomes within 1 study, N=693)
reducing hard drug use at 12+ months follow-up (RR 0.86, 95 % CI 0.39 to 1.90, 2 studies, N=1066)
Unknown effectiveness
opioids
reduce substance use
Life skill and social influence–based school programmes
Manualised mindfulness-based interventions (i.e. structured programs of at least 8 sessions) were reviewed to assess the effets of different existing programs in a narrative review (Korecki et. al, 2020, 30 RCTs). The mindfulness-based programs analysed in the review were the following - from the most common and studied to the least:
Mindfulness-based relapse prevention (MBRP) - a manualized, structured protocol that integrates formal meditation practices with the cognitive behavioral approach of relapse prevention treatment.
Mindfulness oriented recovery enhancement (MORE) - is a protocol that integrates elements of mindfulness training, cognitive restructuring, and positive psychology to address the factors theorized to maintain a substance use disorder.
Mindful awareness in body-oriented therapy (MABT) - is a manualized, mindfulness-based approach that is designed to teach interoceptive skills for self-care. Interoception is the ability to process signals that originate in the body and is broadly described as the overall sensations, or state, of the body.
Mindfulness-based addiction treatment (MBAT) - is a protocol that closely follows the procedures and rationale of Mindfulness-Based Cognitive Therapy (MBCT) but with the depression focused content removed and replaced with information regarding substance use.
Mindfulness training for smoking cessation (MTS) - is a protocol built upon the foundational ideas outlined in both MBSR and MBRP, but was tailored specifically for individuals who are trying to stop smoking.
Moment-by-moment in Women’s recovery (MMWR) - developed as an adaptation of MBSR, specifically designed for low income, racially, and ethnically diverse women currently enrolled in residential SUD treatment.
Overall the review found structured mindfulness-based interventions to have beneficial effects on:
cue-reactivity and thus reducing cravings
reducing perceived stress
And promising effects on:
psychiatric outcomes, including depression and anxiety symptoms
A more recent narrative systematic review (Ramadas et al., 2021) confirmed that, despite some heterogeneity regarding the type of MBRP program used, results support the effectiveness of these interventions in the SUD population, especially in reducing cravings, decreasing the frequency of use, and improving depressive symptoms.
A more recent systematic review (Félix-Junior et al., 2022, 21 studies, 11 studies focused on therapeutic communities and 9 in residential treatment) confirmed the effectiveness of Mindfulness-Based Interventions to:
reduce cravings and improve treatment adherence
It is unclear whether the inpatient context could affect MBI. Only one study from 21 included showed data related to the impact of the context over the implementation. Future studies could further consider the influence of context on MBI.
According to three narrative reviews (Calafat, 2010; Calafat, Juan and Duch, 2009; Faggiano and Vigna-Taglianti, 2008) and one systematic review (Tay 2005), drink-driving mass media campaigns have proven:
to reduce alcohol-related crashes in the period during or after the campaign resulting in injury, by a median of 10 % (IQR 6 % to 15 %).
Mass-media campaigns in combination with school-based, community-based or national programmes were found in a systematic review (Ferri et al., 2013, 23 studies, N= 188 934) to have no statistically significant different effect in:
reducing substance use
pooled results of 5 RCTs (N = 5470) show no effect of media campaign intervention (standardised mean difference (SMD) -0.02; 95% confidence interval (CI) -0.15 to 0.12)
pooled results of 4 out of 5 ITS studies (N = 26 405) focusing on methamphetamine use showed a reduction only in past-year prevalence of methamphetamine use among 12 to 17 years old
a further 5 studies (N = 151 508), which could not be included in meta-analyses, reported a drug use outcome with varied results including a clear iatrogenic effect in one case)
Another systematic review (Stead et al 2019) of the effectiveness of mass-media campaigns to communicate public health messages found no evidence of impact on illicit drug behaviours.
MOUD to promote opioid abstinence (negative urine screens) and treatment retention in transition-age youth was investigated in a systematic review of four RCT, assessing a combination of buprenorphine (studies evaluated sublingual, short-term buprenorphine) plus cognitive behavioral therapy versus a comparison condition. It was found that buprenorphine or buprenorphine-naloxone was more effective than clonidine:
to promote abstinence at the 1-month follow-up, measured as percent of patients with negative urine screens (OR = 4.00, 95% CI: 1.00, 16.00),
when augmented by memantine at three months (OR 9.2 95% CI: 2.7, 31.5),
when tapered over longer rather than shorter durations (in two studies, OR 7.1 95%CI: 2.9 , 17.3; Cohen's d = 0.57, 95%CI: 0.02, 1.13.
Because of ethical challenges, few trials with young people exist, yet further long-term studies are urgently needed to assess relapse after treatment and social functioning.
Mentoring (intended as a supportive relationship in which one person offers support, guidance and concrete assistance to a partner) is based on the sharing of experience and expertise without expectation of personal gain by the mentor - Center for Substance Abuse Prevention 2000) was found in a systematic review (Thomas et al., 2011) more effective than no interventions in:
preventing alcohol use (3 RCTs) (RR 0.71, 95% CI 0.57 to 0.90, p = 0.005).
No pooled analysis could be done on mentoring (understood here to mean a supportive relationship in which one person offers support, guidance and concrete assistance to the partner, based on the sharing of experience and expertise without expectation of personal gain by the mentor — Center for Substance Abuse Prevention 2000) in a systematic review (Thomas et al., 2011) for:
Methadone substitution treatment was found in a systematic review (WHO, 2009, 3RCTs, N=505) 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.
Beneficial
opioids
reduce substance use, retain patients in treatment
Mobile health (mHealth) is defined as the use of mobile and wireless devices to deliver healthcare. mHealh interventions are divided between static interventions and connected interventions. Static interventions collect data from the individual (e.g., biologic or physiologic data, selfreported data (EMA), or geolocation) but do not provide dynamic feedback, rather use collected data after the fact to alter the treatment plan. Reactive or connected interventions, in contrast, collect data to provide customized responses to user input in real time.
Connected interventions were analysed in a narrative systematic review (Carreiro et al., 2020) and were defined as one that meets all of the following three criteria: 1) uses a wearable device and/or mobile phone/app, 2) collects data from a participant (e.g. biologic samples, physiologic data, geolocation, or self- report/Ecological Momentary Assessment), and 3) includes an intervention that was triggered based on data collected from the participant by the device.
The most commonly studied SUD was alcohol disorders (but 3 studies focused on cannabis and 1 on opioids). The most common intervention was some form of craving management and/or coping assistance (e.g. sending a mindfulness-oriented SMS text when a participant reports a craving).
Connected mHealth interventions were found to be effective in:
reducing craving and substance use while the interventions were in use, with a possible sustained behavior change at short term (3–9 month) follow up.
Motivational interviewing was found in a systematic review with meta-analysis (Li et al., 2016, 10 RCT, N=1 466) to have no statistically significant effect in:
changing drug use behaviours (d=0.05, 95% CI 0.06 - 0.17, p=0.36)
Multi-component prevention programs (intervention delivered in more than one setting) have shown in a systematic review (Foxcroft et al., 2011) of 20 RCTs to be effective in:
reducing alcohol misuse in adolescents (12 of the 20 trials showed some evidence of effectiveness).
Multi-substance interventions targeting both tobacco and cannabis were found in a systematic review with Bayesian meta-analysis (Walsh et al., 2020, 11 RCTs, N = 1117) to have a significant effect on:
cannabis cessation, (RR=1.48 [0.92,2.49], studies=8) and no clear effect on tobacco cessation (RR=1.10 [0.68,1.87], studies=9)
Subgroup analysis suggested multi-substance interventions might be more effective than cannabis targeted interventions on cannabis cessation (RR= 2.19 [1.10, 4.36] versus RR=1.39 [0.75,2.74]).
Interventions eamined consisted of nicotine replacement therapies alongside a behavioural component for tobacco and of mainly behavioural interventions for cannabis
The project STAD (Stockholm Prevents Alcohol and Drug Problems), a multicomponent programme that has been active for ten years based on community mobilisation, training in RBS for servers and stricter enforcement of existing alcohol laws, was found in two narrative reviews (Calafat, 2010; Calafat, Juan and Duch, 2009) to be effective in:
decreasing police-reported violent crimes by 29 % in the intervention area, compared with the control area.
decreasing alcohol-related problems at licensed premises (only narrative results).
increasing refusal of alcohol to intoxicated clients (from 5 % in 1996 to 47 % in 1999 and 70 % in 2001) in licensed premises and in increasing refusal to serve minors (from 55 % in 1996 to 59 % in 1999 and 68 % in 2001).
Beneficial
alcohol
reduce drug-related crimes, reduce public disorders, reduce risk behaviours
The Community Trials project including community mobilisation, media advocacy, RBS training, and enhanced enforcement efforts against drink-driving and under-age drinking was found to be effective in two narrative reviews (Calafat, 2010; Calafat, Juan and Duch, 2009) in:
reducing the rate of night time traffic injuries and the number of hospital admissions due to traffic accidents (116 fewer injury accidents in 38 months in the experimental site compared with the control community) .
The Sacramento Neighbourhood Alcohol Prevention Project was found effective in a narrative review (EMCDDA, 2012) and in two systematic reviews (Jones et al., 2010; Bolier et al 2011) in:
significantly reducing assaults and motor vehicle accidents (based on police and emergency medical service reports);
The 'A Matter of Degree' programme was found effective in a narrative review (EMCDDA, 2012) and in two systematic reviews (Jones et al., 2010; Bolier et al 2011) in:
significantly reducing alcohol consumption, alcohol-related harms and drink-driving at follow-up, based on self-reported outcomes (but only at five sites with the highest implementation of environmental programming).
The Sacramento Neighbourhood Alcohol Prevention Project (CCT focused on community mobilisation, community awareness, RBS and law enforcement in relation to under-age access to alcohol and intoxicated clients) showed no effects in a narrative review (EMCDDA, 2012) and in a systematic review (Joneset al 2010) in:
reduced sales to under-age and pseudo-intoxicated clients.
MDFT was compared to IP in one study (INCANT study- N= 450, Rigter et al., 2012, cited in EMCDDA 2014) and was found to be more effective in:
reducing the frequency of cannabis consumption in the high-severity MDFT group more than the corresponding IP group across assessments points (differential slope coefficient on treatment=3.8 [95% CI=1.4 to 7.6], p=0.002)
reducing the prevalence of cannabis use disorders at 12-month follow-up. Namely, 38% of MDFT adolescents met the criteria for cannabis dependence and 33% for cannabis abuse, with 18% no longer having a cannabis disorder. In IP, the corresponding numbers were 52%, 22%, and 15% (differential slope coefficient on treatment=0.9 [95 % CI=0.2 to 1.7], p=0.015).
decreasing the number of dependence symptoms from baseline to 12-month follow-up. The 12-month symptoms average was 2.4 for MDFT (SD=2.0) and 3.0 for IP (SD=2.0). The drop in symptoms was larger in MDFT than in IP (differential slope coefficient on treatment=0.27 [95 % CI=0.13 to 0.41], p<0.001).
retaining patients in treatment. A higher proportion (90%) of MDFT patients completed therapy in comparison to IP (48%) (OR=9.8 [95 % CI=5.7 to 16.7], p<0.001).
Another systematic review (Esteban et al. 2022, 18 studies, RCTs= 15), evaluated the effectiveness of different types of family therapy on substance use treatment among adolescents and adults and found that:
Multidimensional Family Therapy is as effective as Cognitive Behavioral Therapy in reducing consumption, with medium to large effect sizes observed for both treatments at the end of the intervention (7 studies focused on MDFT vs CBT).
Family therapy is effective in both reducing consumption and improving family functioning.
Family therapy might be suitable for adolescents with cases of higher severity of substance abuse, as it integrates family members in the treatment process.
Beneficial
cannabis
reduce substance use, retain patients in treatment
MDFT was compared to CBT in one study and was found to be more effective (Liddle 2008 cited in EMCDDA 2014) in:
reducing cannabis use (measured as number of days of use in previous 30) in the MDFT group (- 58.7%) than in the CBT group (- 46,1%) at the 12-month follow-up. However, both treatments showed statistically significant decreases across time in 30-day frequency of cannabis use (p=.001) and there were no significant differences between MDFT and CBT.
Naloxone is recommended in an evidence-based guidance (Neptune, 2018) to be used in case of suspected synthetic opioids, both in community and hospital settings.
Specificities with regard to fentanyls in comparison to heroin overdoses are the followings:
a more rapid administration of naloxone is warranted because of the rapid onset of fentanyls,
a more rapid escalation of additional doses for naloxone may be needed in comparison with heroin or other opioids,
overall, higher doses of naloxone may be needed for fentanyl patients in comparison with heroin patients,
Fentanyl patients may require a longer period of observation in hospital than heroin patients.
Likely to be beneficial
new psychoactive substances (NPS), opioids, prescription medicines
Brief training and standardised naloxone supply for individuals at risk of opioid overdose in prison has been found to be effective in a pre-post evaluation of a national policy (Bird et al.,2016) in:
reducing by 36 % the proportion of opioid-related deaths that occurred in the 4 weeks following release from prison (from 9.8 % of ORDs (193/1970) in 2006–10 to 6.3 % of ORDs (76/1212) in 2011–13).
Naltrexone (NTX), an antagonist pharmacological treatment for relapse prevention, reversibly blocks reward associated with opioid use, without possessing any opioid-like properties of its own. Extended-release NTX is available and administered through intramuscular injections every 4 weeks, eliminating the need for daily oral dosing.
Naltrexone was found in a systematic review wit meta-analysis (Bahji et al., 2020, 11 studies, N= 1 045) to be effective in:
improving retention in treatment (RR = 1.31; 95% confidence interval (CI) = 1.05, 1.63) - no difference between oral and extended release
reducing rates of re-incarceration (RR = 0.70, 95% CI = 0.54–0.92) - significant reduction for oral NTX
reducing opioid relapse (RR = 0.63, 95% CI = 0.53–0.76) - no difference between oral and extended release
and improved opioid abstinence (RR = 1.38, 95% CI = 1.16–1.65) - significant reduction for extended release NTX
However, Naltrexone was associated with a greater burden of adverse events overall (RR = 1.49, 95% CI = 1.13–1.95). Mild to moderate adverse events were more frequently reported by participants receiving extended release -NTX (rather than oral NTX) compared to TAU conditions, and these included dry mouth, colic, fatigue, anxiety, blurred vision, abdominal pain, vomiting, nausea and insomnia. The most common reported side effects with extended release-NTX were immediate injection site reactions (such as redness and soreness) and fatigue.
Serious adverse events (i.e. requiring discontinuation or hospitalization) were not statistically significant higher among those who received Naltrexone.
In an updated version of a systematic review (Minozzi et al., 2011, 13 RCTs, N=1158), pharmacological treatment with Naltrexone versus placebo or no pharmacological treatment in opioid dependent patients was found:
to have a statistically significant effect only when considering only the studies with patients forced to adhere to treatment which favoured naltrexone for retention and abstinence.
A new systematic review with network meta-analysis (Lim et al., 2022, 79 RCTs) however found a significant overall effect of Naltrexone compared to control in:
retaining patients in treatment (RR 1.54, CI 95% 1.26 - 1.90).
The network analysis showed that Buprenorphine and Methadone appear to have superior retention to naltrexone yet based on a small number of studies.
Another systematic review (Timko et al.,2016) covering five years (55 articles, 2010–2014) of research on MAT retention by opiate-dependent individuals suggests that:
in RCTs with a Medication Focus, the receipt of a naltrexone implant rather than placebo was associated with a higher 3-month retention rate (52.0% vs 28.0%), a higher 6-month retention rates (≥20%), and a longer duration of MAT.
in RCTs with a Behavioral Therapy Focus compared to naltrexone-only patients, patients receiving naltrexone and contingency management were more likely to be retained at 6 months (16.0% vs 54.0%).
NSP programmes were found to be effective in a systematic review (Aspinall et al., 2014), in:
reducing the transmission of HIV among people who inject drugs (pooled effect size 0.66 (95 % CI 0.43 to -1.01) across all studies, and 0.42 (95 % CI 0.22 to 0.81) across six higher quality studies)
A review of reviews (MacArthur et al., 2014, N=25 reviews), without meta-analysis, concluded that there is:
sufficient evidence to support the effectiveness of NSPs in reducing self-reported injecting risk behaviour among IDUs (N=43 studies, 39 positive, 1 negative, 3 no association).
Needle and syringe programmes implemented in prison were found in a systematic review (Palmateer et al., 2022, 27 systematic review, 61 studies) to have insufficient evidence to either support or discount the intervention in:
High NSP coverage (defined as regular attendance at an NSP or all injections being covered by a new needle/syringe) has been found to be effective in a a systematic review with meta-analysis (Platt et al., 2017, 28 studies, N= 11 070 PWID) in:
reducing the risk of HCV acquisition by 76 % only in studies in Europe (RR 0.24, 95 % CI 0.09 to 0.62).
Another systematic review (Palmateer et al., 2022, 27 systematic review, 61 studies) confirmed the results and found sufficient evidence to support the effectiveness of OST in:
the prevention of HCV transmission among PWID.
the prevention of HIV transmission among PWID.
reducing self-reported injecting risk behaviour among PWID
Transcranial magnetic stimulation and transcranial direct current stimulation were found in a narrative review (without meta-analysis) (Rachid, 2018, 10 clinical studies, n=195) to have:
no significant effect on reducing substance use.
There were some indications of positive results in safety and reduction of cocaine cravings.
A systematic review of randomised controlled trials (Soni et al. 2022, 10 studies, N=1431) assessed the effectiveness of deprescribing interventions used to discontinue long-term use of benzodiazepines. The review reported that:
Non-pharmacological interventions were more effective than routine care in facilitating benzodiazepine withdrawal (n=189; RR 3.26, 95% CI 2.36-4.51, low quality).
Deprescribing benzodiazepines with a non-pharmacological intervention was more effective than gradual tapering alone both in the short term (n=124; RR 2.02; 95%CI 1.41, 2.89, low quality), and long term (n=123; RR 2.45; 95%CI 1.56, 3.85, low quality).
Postpartum nonpharmacological adjunctive treatments for women with opioid use disorder were analysised in a narrative systematic review (Martinez and Allen, 2020). Four studies were identified by the review and while they all reported improvements, overall it was not possible to draw conclusions on their effect on:
reducing opioid use
Postpartum nonpharmacological adjunctive treatments included group or individual counseling or employemnt interventions.
Occupation-based interventions are those programmes in which an occupation is performed, and occupations are defined as those activities a person engages in to structure time and create meaning in their life. In the addiction field, occupation-based interventions are typically in the areas of work, leisure, and social participation. Those interventions were found in a systematic review without meta-analysis (Wasmuth et al., 2016, 26 studies) to have no significant effect in:
improving recovery short and long-term recovery outcomes (ASI scores)
One cohort study (Larney et al., 2014) enrolling N=16 715 opioid dependent people who were in prison between 2000 and 2012 showed that:
being in OST was associated with a 74% lower hazard of dying in prison (adjusted HR (AHR) 0.26; 95% CI 0.13 to 0.50), compared to time not in OST
being in OST was associated with a 87% lower hazard of unnatural death (adjusted HR (AHR) 0.13; 95% CI 0.05 to 0.35), compared to time not in OST
being in OST was associated with a 94% lower all-cause mortality hazard during the first 4 weeks of incarceration (adjusted HR (AHR) 0.06; 95% CI 0.01 to 0.48), compared to time not in OST
being in OST was associated with a 93% lower hazard of unnatural death during the first 4 weeks of incarceration (adjusted HR (AHR) 0.07; 95% CI 0.01 to 0.59), compared to time not in OST
Opioid substitution therapies were found in a systematic review with meta-analysis (Strange et .a, 2022, 20 studies, N=30 119) to have a significant effect in:
reducing nonfatal overdoses (OR = 0.41 [0.18, 0.91], SE = 0.41, p < 0.05).
The same review however found a non-significant effect of OST in reducing fatal overdoses, yet the overall results suggests that those receiving OST had nearly 60% reduced odds of a nonfatal overdose and confirming it to be a very effective harm reduction intervention.
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., 2020 - 3RCTS methadone vs buprenorphine, 1 RCT methadone vs slow-release morphine) in:
reducing drop-out rates RR 0.66, 95 % CI 0.37 to 1.20, 3 studies, N=223 (no differences between OST medications)
higher birth weight (may be higher in the buprenorphine group)
reducing use during pregnancy (RR 1.81, 95 % CI 0.70 to 4.68, 2 studies, N=151)
new-borns treated for neonatal abstinence syndrome RR 1.19, 95% CI 0.87 to1.63 (no differences between OST medications)
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:
lower risk of preterm birth (RR =0.40, 95 % CI = 0.18-0.91)
greater birth weight (weighted mean difference (WMD) =277g, 95 % CI = 104-450)
larger head circumference (WMD=0.90cm, 95 % CI=0.14-1.66)
A systematic review (Link et al., 2020, 5 RCTS, N= 1 875) found that substitution treatment with buprenorphine-naloxone have similar pregnancy outcomes when compared to women undergoing treatment with other forms of OST.
A more recent systematic review (Ordean & Tubman-Broeren, 2023, 5 studies) confirmed that using buprenorphine-naloxone during pregnancy lead to:
reduced opioid use
similar gestation outcomes to those exposed to methadone, buprenorphine monotherapy, illicit opioids, or no opioids.
In a scientific review article commissioned by EBCOG (Vella et al, 2023) concerns have been raised, however, regarding current practices of initiating buprenorphine or buprenorphine/naloxone during pregnancy. It is noted that while substitution treatment with methadone and buprenorphine is widely accepted and recommended during pregnancy, the induction protocols used in some settings—particularly rapid induction methods used to initiate buprenorphine/naloxone—may carry unacknowledged risks, including potential miscarriage.
Opioid substitution treatment to treat pharmaceutical opioid dependent patients was evaluated in a systematic review (Nielsen et al., 2022, 8 RCT, N= 709). Results show that:
there is very low- to moderate-certainty evidence supporting the use of maintenance agonist pharmacotherapy for pharmaceutical opioid dependence.
Methadone or buprenorphine did not differ on some outcomes, however on the outcomes of retention and self-reported substance use some results favoured methadone.
Maintenance treatment with buprenorphine appears more effective than non-opioid treatments.
Opioid substitution treatment was found sufficiently supported by evidence in a synthesis of 4 narrative reviews (Malta et al.,2008; WHO, 2007b, Tilson et al., 2007, Lucas et al., 2006, cited in EMCDDA - ECDC 2011) in:
improving the effectiveness of anti-retro-viral treatment in HIV positive opioid users.
Opioid Substitution Treatment (OST) to increase compliance to HCV treatment and to to increase HCV treatment virological response were considered not possible to assess due to the lack of ad-hoc studies in a synthesis based on a narrative review (Hellard et al., 2009, cited in EMCDDA - ECDC 2011) including 30 observational studies with a total number of patients superior to 4,000.
OST has been found to be effective in a a systematic review with meta-analysis (Platt et al., 2017, 28 studies, N= 11 070 PWID) in:
reducing the risk of HCV acquisition by 50% (RR 0.50, 95 % CI 0.40 to 0.63).
Another systematic review (Palmateer et al., 2022, 27 systematic review, 61 studies) confirmed the results and found sufficient evidence to support the effectiveness of OST in:
the prevention of primary HCV infection and HCV reinfection among PWID
the prevention of HIV seroconversion, especially for those in continuous treatment
the prevention of the frequency of injection, the sharing of injecting equipment and injecting risk behaviour
Opioid substitution treatment (OST) implemented in prison was found in a systematic review (Palmateer et al., 2022, 27 systematic review, 61 studies) to have insufficient evidence to either support or discount the intervention in:
Opioid substitution provided in prison settings was found in a systematic review (ECDC/EMCDDA, 2018) to be effective in:
reducing injecting risk behaviour.
The result is confirmed in another systematic review (Palmateer et al., 2022, 27 systematic review, 61 studies) that found sufficient evidence to support the effectiveness of OST in:
the prevention of injecting risk behaviours and injecting frequency among PWID in prison settings.
Opioid substitution treatment (OST)/Opioid Agonist Treatment (OAT) was found to be effective in several systematic reviews (Mattick et al., 2009, Mathers et al., 2013, Sordo et al., 2017, Santo et al. 2021) in reducing the risk of death.
Sordo et al., (2017) conducted a systematic review and meta-analysis of cohort studies (19 eligible cohorts, following 122 885 people treated with methadone over 1.3-13.9 years and 15 831 people treated with buprenorphine over 1.1-4.5 years) and found:
all cause mortality rates were 11.3 and 36.1 per 1000 person years in and out of methadone treatment (unadjusted out-to-in rate ratio 3.20, 95% confidence interval 2.65 to 3.86) and reduced to 4.3 and 9.5 in and out of buprenorphine treatment (2.20, 1.34 to 3.61)
In pooled trend analysis, all cause mortality dropped sharply over the first four weeks of methadone treatment and decreased gradually two weeks after leaving treatment.
All cause mortality remained stable during induction and remaining time on buprenorphine treatment. Overdose mortality evolved similarly, with pooled overdose mortality rates of 2.6 and 12.7 per 1000 person years in and out of methadone treatment (unadjusted out-to-in rate ratio 4.80, 2.90 to 7.96) and 1.4 and 4.6 in and out of buprenorphine treatment.
Santo et al., (2021) analysed both observational studies ( 36 studies, N= 749 634) that collected data on all-cause or cause-specific mortality among people with opioid dependence while receiving and not receiving OAT as well as randomized clinical trials (15 RCTs, N = 3852). Results found that:
the rate of all-cause mortality during OAT was more than half of the rate seen during time out of OAT (RR, 0.47; 95% CI, 0.42-0.53). This association was consistent regardless of patient sex, age, geographic location, HIV status, and hepatitis C virus status and whether drugs were taken through injection. Associations were not different for methadone (RR, 0.47; 95% CI, 0.41-0.54) vs buprenorphine (RR, 0.34; 95% CI, 0.26-0.45).
There was lower risk of suicide (RR, 0.48; 95% CI, 0.37-0.61), cancer (RR, 0.72; 95% CI, 0.52-0.98), drug-related (RR, 0.41; 95% CI, 0.33-0.52), alcohol-related (RR, 0.59; 95% CI, 0.49-0.72), and cardiovascular-related (RR, 0.69; 95% CI, 0.60-0.79) mortality during OAT.
In the first 4 weeks of methadone treatment, rates of all-cause mortality and drug-related poisoning were almost double the rates during the remainder of OAT (RR, 2.01; 95% CI, 1.55- 5.09) but not for buprenorphine (RR, 0.58; 95% CI, 0.18-1.85).
All-cause mortality was 6 times higher in the 4 weeks after OAT cessation (RR, 6.01; 95% CI, 4.32-8.36), remaining double the rate for the remainder of time not receiving OAT (RR, 1.81; 95% CI, 1.50-2.18).
Opioid agonist treatment was associated with a lower risk of mortality during incarceration (RR, 0.06; 95% CI, 0.01-0.46) and after release from incarceration (RR, 0.09; 95% CI, 0.02-0.56)
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.
In a PEER umbrella systematic review of systematic reviews, a meta-analysis on three RCT found that:
Retention in treatment improves when OUD is treated in primary care (86% vs 67% in specialty care, risk ratio [RR] of 1.25, 95% CI 1.07 to 1.47)
Street opioid abstinence was also higher in primary care settings (53% vs 35%, RR = 1.50, 95% CI 1.12 to 2.01, I2 = 74%). However, heterogeneity was high and this included both self-reported and urine-confirmed data.
There is reasonable evidence that patients with OUD should be managed in the primary care setting.
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 (Minozzi et al., 2014, 2 RCTs, N= 190 between 13–18 years of age) 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).
Opioid withdrawal with antagonists under heavy sedation or anaesthesia was compared to withdrawal managed with reducing doses of methadone in a systematic review of (Gowing 2010, 8 RCTs, N=1109) 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).
Opioid withdrawal with antagonists under heavy sedation or anaesthesia was compared to withdrawal managed with reducing doses of methadone in a systematic review (Gowing 2010, 8 RCTs, N=1109) ) 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).
The overall authors' conclusion is that there is a significantly increased risk of serious adverse events with anaesthesia-assisted approaches. The lack of additional benefit, and increased risk of harm, suggest that this form of treatment should not be pursued.
Evidence of ineffectiveness
opioids
reduce substance use, retain patients in treatment
A review of reviews (MacArthur et al., 2014, N=25 reviews), without meta-analysis, concluded that there is:
tentative evidence to support the effectiveness of outreach including IEC activities in reducing injecting risk behaviour (N=28 studies, 18 positive, 10 no association).
A review of 29 reviews (McGrath et al., 2006) found evidence in favour of the effectiveness of peer educators in school-based drug prevention programmes in:
reducing all substances use at post-test (SMD = 0.24, 95 % CI 0.06–0.41, Z-test p < 0.01);
reducing tobacco smoking at post-test (SMD = 0.17, 95 % CI 0.05–0.21, Z-test p < 0.01).
However, this relative effectiveness did not extend to 1 or 2 year follow-ups (McGrath et al., 2006).
In a narrative systematic review (Kerman et al., 2021, studies = 35) harm reduction outcomes and practices in Housing First were examined in four domains: substance-related harms, viral health, sexual health, and harm reduction service use. Overall the review found that harm reduction outcomes in Housing First remain underexamined and any conclusions of the intervention's impacts in this domain would be premature. Effective harm reduction practices in Housing First require strong working relationships between staff and tenants.
Specific results of the analysis found that:
harm reduction outcome studies focused mostly on nonspecific substance use problems, with Housing First being found to have minimal effects in this domain.
More severe harms, such as delirium tremens and substance use-related deaths, have been minimally explored, though preliminary evidence is promising.
Viral health, sexual health, and harm reduction service use outcomes were the focus of few studies.
Permanent supportive housing has changed the sequence of treatment and housing, and access to housing is not contingent on adherence to treatment or abstinence. Permanent housing has become a strategy that is often combined with coordinated case management. Programmes such as Housing First and Pathways to Housing are examples of permanent supportive housing interventions.
Permanent supportive housing was found in a systematic review (Aubry et al., 2020, 35 studies - 15 on housing) to be effective in:
increasing long-term (6 year) housing stability for participants with moderate support needs as well as high support needs when compared with usual care
The review found small but promising evidence suggesting that recipients of permanent supportive housing report greater improvements in their subjective quality of life than those receiving standard care. Results also showed no evidence of any major harms associated with mental health, substance use, quality of life, and other outcomes of implementing housing interventions among homeless individuals.
Future research should focus on the long-term effects of housing interventions on physical, mental health and substance use as the review could not formulate conclusive statements on the effects of the intervention on those outcomes.
The same results were confirmed by a narrative systematic review of reviews (Miler et al., 2021).
In a systematic review, naloxone, nalmefene, and physostigmine emerged as effective in treating opioid overdose, whereas naltrexone showed evidence in preventing opioid overdose.
Opioid agonists were found to be effective in improving retention in treatment and in reducing illicit opioid use.
Evidence for a multidisciplinary approach involving harm reduction and addressing psychosocial barriers could be the topic of subsequent literature reviews.
Opium withdrawal presents significant symptoms, even if milder than heroin withdrawal. Pharmacologically assisted withdrawal was found to have no effect in a systematic review (Rahimi-Movaghar et al, 2018, 13 studies, N=1096) in:
improving treatment outcomes.
Tested medications include the following (individually or combined, and/or in different dosages): baclofen, clonidine, amantadine, buprenorphine, methadone, tramadol, gabapentin, tincure of opium.
While all these may be useful in alleviating the symptoms, there is no clear evidence as to whether any of the medications is more effective than the others in the management of opium withdrawal.
Pharmacological treatment (Buprenorphine) for female drug-using offenders was found in a systematic review (Perry et al., 2015) to have no different effect than placebo in:
reducing drug use - self-reported at three months follow-up (RR 0.58, 95 % CI 0.25 to 1.35, 1 study, N=36)
A Cochrane systematic review with meta-analysis (Zankl et al., 2021, studies= 16, N= 1 110) investigated the efficacy and safety of using an opioid as compared to a sedative or non-pharmacological treatment for the treatment of neonatal abstinence syndrome (NAS) due to withdrawal from opioids. The results found:
moderate quality evidence that treatment failure is reduced by the use of an opioid compared to the use of the sedatives phenobarbital (RR 0.51, 95% CI 0.35 to 0.74; 6 studies, 458 infants) or chlorpromazine (RR 0.08, 95% CI 0.01 to 0.62; 1 study, 90 infants). There was little or no difference in treatment failure according to the type of opioid used (morphine, methadone or buprenorphine)
moderate quality evidence that the use of sublingual buprenorphine reduces duration of treatment (morphine vs bup MD 12.79, 95% CI 7.57 to 18.00; 3 studies, 112 infants) and hospitalisation (morphine vs bup MD 11.45, 95% CI 5.89 to 17.01; 3 studies, 113 infants) compared to the use of morphine
There is insufficient evidence to determine the effectiveness and safety of non-pharmacological interventions alone compared to non-pharmacological interventions plus a pharmacological agent (drug such as opioid or sedative).
The current literature on pharmacological interventions of SUD in ADHD patients involves norepinephrine, dopamine, and nicotinic acetylcholine receptors as prime neurotransmitters. The same neurotransmitters are addressed purposefully at stabilizing ADHD symptoms. The mindset is that medications that manage ADHD symptoms should also help to decrease the risk of developing SUD.
Pharmacological treatment of attention deficit hyperactivity disorder (ADHD) was found in a systematic review with meta-analysis (Fluyau et al., 2020, 17 studies, N = 2155) to have small but positive pooled effect compared to placebo in:
reducing in substance use (SMD = 0.405, 95% confidence interval [CI]: [0.252, 0.557], P < .001),
decrease in the severity of ADHD symptoms (SMD = 0.533, 95% CI: [0.393, 0.672], P < .001),
reduction in the frequency of ADHD symptoms (SMD = 0.420, 95% CI: [0.259, 0.582], P < .001).
The pooled effect was moderate for the management of withdrawal symptoms (SMD = 0.577, 95% CI: [0.389, 0.764], P = .001]) and the decrease in the severity of ADHD symptoms (SMD = 0.533, 95% CI: [0.393, 0.672], P < .001).
There were differences among different substances (tobacco, cocaine, amphetamine or cannabis) in the different outcomes when considered individually and not pooled together.
Likely to be beneficial
co-morbidity
improve mental health outcomes, reduce substance use
Agonist pharmacological treatments for drug-using offenders were found in a systematic review (Perry et al., 2015) to have no different effect than non-pharmacological interventions in:
reducing drug use
measured (RR 0.72, 95 % CI 0.51 to 1.00, 2 studies, N=237)
arrests (RR 0.60, 95 % CI 0.32 to 1.14, 1 study, N=62)
re-incarceration (RR 0.77, 95 % CI 0.36 to 1.64, 3 studies, N=472)
Antagonist pharmacological treatments (Naltrexone) were found in the same review (Perry et al., 2015) to also have no different effect than non-pharmacological interventions in:
reducing drug use (measured) (RR 0.69, 95 % CI 0.28 to 1.70, 1 study, N=63)
When comparing the drugs no significant differences between comparisons (methadone versus buprenorphine, diamorphine and naltrexone) on any of the outcome measures.
Unknown effectiveness
not-drug specific
reduce re-incarceration rates, reduce substance use
Pharmacotherapies with different medications (i.e. preparations containing tetrahydro-cannabinol (THC), selective serotonin reuptake inhibitor (SSRI) antidepressants, mixed action antidepressants, anticonvulsants and mood stabilisers, atypical antidepressant, anxiolytic, norepinephrine reuptake inhibitor, glutamatergic modulator) for cannabis dependent users were assessed in a systematic review (Marshall et al., 2014, 14 RCTs, N= 958) finding no conclusive results on:
completion of treatment;
reducing the use of substances; and
improving withdrawal symptoms and craving.
An update to Marshall et al 2014 (Nielsen et al 2019, 21 RCTs, N= 1 755) also found no conclusive results.
A narrative systematic review (Kondo et al., 2020, 26 RCTs - 14 trials more than the first Marshall et al. review) included trials with cannabinoids, hormones, fatty acid amide hydrolase inhibitor and galantamine. The results confirm the previous systematic reviews, that there is largely insufficient evidence to draw conclusions about the effectiveness of any drug classes tested so far. The review actually found low- to moderate-strength evidence that buspirone, cannabinoids, and SSRIs were ineffective for decreasing cannabis use or improving abstinence.
A more recent systematic review (Bahji et al., 2021, 24 RCTs) performed a network meta-analysis of the different medications tested with individuals diagnosed with cannabis use disorder. The results confirm the previous systematic reviews, that there is largely insufficient evidence to support any particular pharmacological treatment.
Two narrative systematic reviews (Vuilleumier et al., 2022, 8 RCTs, N= 667; Paulus et al., 2022, 40 studies, 24 animal and 16 human studies) assessed the use of cannabinoids for the treatment of cannabis use disorder. Results found promising effects for cannabidiol (CBD) and endocannabinoid modulation, however overall there is insufficient evidence to draw conclusions.
Unknown effectiveness
cannabis
reduce substance use, retain patients in treatment
Pharmacotherapies were found in a systematic review of reviews (Ronsley et al., 2020, 29 systematic reviews examining eleven intervention modalities) to have no effect in:
reducing stimulant use
improving abstinence
The pharmacotherapies evaluated are:
antidepressants
disulfiram
dopamine agonists
antipsychotics
anticonvulsants - with a focus on Topimarate
opioid agonists
N-acetylcysteine
Treatment with psychostimulants was found to have promising results and warrants further investigation (see separate entry).
Population characteristics of the included reviews showed a higher proportion of males in most studies, and predominantly cocaine users, with few studies focusing on methamphetamine use or stimulant use more broadly.
Pharmacotherapies (namely 23 different medications, including anticonvulsants, antidepressants, antipsychotics, dopamine agonists, medications for OUD, medications approved by the FDA for other substance use disorders (SUDs), psychostimulants, and various other pharmacotherapies) were found in a systematic review (Chan et al., 2020, 34 RCTs) to have no effect in:
reducing stimulant use
improving abstinence
The review found moderate-strength evidence that antidepressants (desipramine, bupropion, and fluoxetine) worsened retention. There was moderate- strength evidence that disulfiram worsened treatment retention (N = 605, RR 0.86, 95 % CI 0.77 to 0.95).
Treatment with psychostimulants warrant further study as the review found promising results that it may reduce cocaine use.
The majority of studies used methadone concurrently with the study medication, three studies used buprenorphine, and one study used diacetylmorphine. Also the majority of the studies enrolled participants who were already receiving opioid maintenance treatment.
A systematic review (Siefried et al., 2020, 43 RCTs, N = 4065) addressing 23 different types of pharmacotherapies for amphetamine and/or methamphetamine use, alone or in combination, found:
no evidence of effectiveness of any pharmacotherapy in treating amphetamine and/or methamphetamine dependence. While some drugs demonstrated results that were statistically significantly better than placebo outcomes, the studies were generally small and the samples biased and study protocol completion was low making it impossible to recommend any intervention.
Some weak but positive findings have been demonstrated with stimulant agonist treatment (dexamphetamine and methylphenidate), naltrexone and topiramate.
Future research should address the heterogeneity of AMPH/MA dependence (e.g. coexisting conditions, severity of disorder, differences between MA and AMPH dependence) and the role of psychosocial intervention.
Treatment of amphetamine and methamphetamine use disorder with mirtazepine was found in a systematic review with meta-analysis (Naji et al., 2022, 2 RCTs) to have no effect against placebo to improve:
retention in treatment (RR=1.01, 95% CI: 0.91, 1.12; n = 180; moderate certainty evidence)
Different pharmacotherapy options for methamphetamine withdrawal were assessed in a systematic reivew with meta-analysis (Acheson et al., 2022, 9 RCTS of 6 medications, N= 242). Results found that:
Amineptine may reduce discontinuation rates (RR 0.22, 95% confidence interval [CI] 0.07, 0.72, p = 0.01), and improve global state (MD -0.49, 95% CI -0.80, -0.17), compared with placebo, however, this medication is no longer approved.
No other medications improved any domain when compared with placebo.
A narrative review (Fischer et al., 2015), without meta-analysis, concluded that, despite the availability of a numerous body of studies and agents tested:
no pharmacological option has proven to date to be effective.
Pharmacy-based needle and syringe programmes (NSPs) were found in a systematic review with meta-analysis (Sawangjit et al., 2016, 14 observational studies, N= 7 035 PWID) to be effective in:
reducing risk behaviours among people who inject drugs when compared to those with no NSP available (OR = 0.50, 95 % CI = 0.34–0.73) and sensitivity analyses, excluding studies with a serious risk of bias (OR = 0.52, 95 % CI = 0.32–0.84).
Physical exercise (and/or activity) was found in a systematic review (Thompson et al., 2020, 32 studies) to have no conclusive effects in:
improving substance use outcomes
reducing the risk of progression to alcohol and other drug use
supporting individuals to reduce alcohol and other drug use for harm reduction
promote abstinence and relapse prevention during and after treatment of alcohol and other drug use
A more specific but limited systematic review (Jake-Schoffman et al., 2020, 3 studies) analysed the effects of aerobic exercise interventions as adjunctive treatment for patients in opioid substitution treatment and also found no significant effects on substance use outcomes.
Physical exercise for substance use disorders patients (both aereobic programs and body–mind activities such as tai chi, yoga, or qigong) was found in a systematic review with meta-analysis (Giménez-Meseguer et al., 2020, 59 studies) to be effective in:
improving stress (SMD = 1.11 (CI: 0.31, 1.91); z = 2.73; p = 0.006)
depression (SMD = 0.63 (CI: 0.34, 0.92); z = 4.31; p < 0.0001).
All the studies included resulted in improvements in physical conditions expressed in terms of VO2, heart rate or performance in indirect tests that measure aerobic capacity.
When comparing the effects of aerobic-strength exercise with oriental practices, no relevant di fferences were found about the overall value of quality of life and mental health.
The results also showed a trend towards a positive effect on craving (SMD = 0.89 (CI: -0.05, 1.82); z = 1.85, p = 0.06) but not statistically significant.
Another systematic review with meta-analysis (Liu et al., 2020, 7 studies, N = 772) investigated specifically the effects of tai chi and Qigong exercise and found the latter (Qigong) effective in:
improving anxiety compared to that of medication (SMD = -1.12[− 1.47, − 0.78]), and no treatment control (SMD = -0.52[− 0.77, − 0.27]).
The effect of Tai Chi was comparable to treatment as usual (TAU) on depression (standardized mean difference (SMD) = − 0.17[− 0.52, 0.17]).
The role of physical activity in opioid substitution therapy was assessed in a narrative systematic review (Alpers et al., 2022) and results confirmed that:
physical activity has beneficial effects on physical fitness and mental health for patients in opioid substitution therapy
Likely to be beneficial
not-drug specific
improve mental health outcomes, improve psychosocial functioning
Police interventions encompassing regular enforcement and visits by plain clothes officers aimed at promoting responsible alcohol service and at preventing driving while under the influence, and targeting servers in nightlife settings and licensed premises were found in a systematic review (Bolier et al 2011) to lead to:
Bar tenders serving alcohol less often to pseudo-clients acting as though they were intoxicated (variation of results across three studies ranging from significant to not statistically significant results).
Evidence for the effectiveness of police intervention or increased enforcement of licensing laws in reducing alcohol-related incidents was found in two systematic reviews (Jones et al 2010; Bolier et al 2011) and in a narrative review (EMCDDA, 2012) to be inconclusive regarding:
Police interventions aimed at reducing the movement of clients between bars, the overall alcohol consumption of clients and contain that consumption within safer settings was found to be effective in a systematic review (Ker and Chinnock, 2008) in:
reducing assault rates: pre-intervention serious assault rate in the experimental area was 52 % higher than the rate in the control area. After intervention, the serious assault rate in the experimental area was 37 % lower than in the control area.
Police interventions in licensed premises, with uniformed police officers visiting pubs two to three times a week was found in a narrative review (Calafat, Juan and Duch, 2009) to lead to:
a 20 % reduction in recorded public disorders offences in the intervention area, compared with no reduction in the control area.
Police intervention in high-risk premises was found in a systematic review (Jones et al 2010) and in a narrative review (EMCDDA, 2012) to be a more effective strategy than ‘low level’ policing in:
Police-based diversion measures defined as measures involving “the police initiating and leading the intervention and the [people who use drugs] receiving a diversionary scheme to avoid a criminal record and any consequences that may result from continued formal contact with the criminal justice system”, have been evaluated in a narrative systematic review (Blais et al., 2022, 27 studies, US =17, Portugal = 5, Australia = 5) and were found to be effective in:
preventing criminal offending or future contacts with the criminal justice system
The analysis also showed promising results for improving participants' health and diminishing social costs as well as costs associated with processing drug-related offenses.
There was insufficient evidence to draw conclusions about the effect of police-based diversion measures on drug use, drug accessibility, or changes in participants’ socioeconomic conditions.
Findings from qualitative studies suggest that program acceptance by police officers, constructive intersectoral collaboration, clear eligibility criteria, and timely access to services seem to facilitate the implementation and delivery of police-based diversion measures.
The review solely focused on diversion measures that offered an alternative to a formal arrest (i.e., measures where arrest and criminal prosecution were only replaced by an administrative fine were not considered) and included
the Commissions for the Dissuasion of Drug Addiction (CDDA) in Portugal where drug use is decriminalized,
police-based diversion programs implemented in jurisdictions where drug use is still a criminal offense, such as the Law Enforcement Assisted Diversion (LEAD) program, which creates a de facto decriminalization of drug use and is implemented in several US cities,
police-based diversion programs rest on a mixture of de jure and de facto decriminalization implemented in Australia where the most common type of program is “cannabis cautioning”, where minor cannabis offenders are diverted away from the criminal justice system into education or treatment programs
Police-based diversion measures defined as measures involving “the police initiating and leading the intervention and the [people who use drugs] receiving a diversionary scheme to avoid a criminal record and any consequences that may result from continued formal contact with the criminal justice system”, have been evaluated in a narrative systematic review (Blais et al., 2022, 27 studies, US =17, Portugal = 5, Australia = 5) and found insufficient evidence to draw conclusionson:
on drug use, drug accessibility, or changes in participants’ socioeconomic conditions.
However police-based interventions were found to be effective in preventing criminal offending or future contacts with the criminal justice system. The analysis also showed promising results for improving participants' health and diminishing social costs as well as costs associated with processing drug-related offenses.
Findings from qualitative studies suggest that program acceptance by police officers, constructive intersectoral collaboration, clear eligibility criteria, and timely access to services seem to facilitate the implementation and delivery of police-based diversion measures.
The review solely focused on diversion measures that offered an alternative to a formal arrest (i.e., measures where arrest and criminal prosecution were only replaced by an administrative fine were not considered) and included
the Commissions for the Dissuasion of Drug Addiction (CDDA) in Portugal where drug use is decriminalized,
police-based diversion programs implemented in jurisdictions where drug use is still a criminal offense, such as the Law Enforcement Assisted Diversion (LEAD) program, which creates a de facto decriminalization of drug use and is implemented in several US cities,
police-based diversion programs rest on a mixture of de jure and de facto decriminalization implemented in Australia where the most common type of program is “cannabis cautioning”, where minor cannabis offenders are diverted away from the criminal justice system into education or treatment programs
Positive youth development (PYD) interventions i.e. programmes that favour the promotion of positive assets were found in a systematic review with meta-analysis (Melendez-Torres et al., 2016, 10 studies) to have no significant effect in:
Pre-exposure prophylaxis of HIV in adults at high risk was found in an evidence review (NHS, 2016) to be effective in:
reducing the relative risk of acquiring HIV infection by the following amounts in men or transgender women who have sex with men,
44 % compared with placebo (1RCT ‘iPrEx’, n=2 441; Truvada given daily; number needed to treat [NNT] 62 per year)
86 % compared with no prophylaxis (1 RCT ‘PROUD’, n=523; Truvada given daily; NNT 13 per year)
86 % compared with placebo (1 RCT ‘IPERGAY’, n=400; Truvada given 'on demand'; NNT 18 per year)
reducing the relative risk of acquiring HIV infection in serodiscordant heterosexual couples by 75 % compared with placebo (1 RCT ‘Partners PreP’, n=3 136, once-daily Truvada, mITT population; NNT 68 per year).
Behavioural interventions (face-to-face or group counselling, print materials, interactive computer-based tools designed for patient use, and clinician training and quality improvement programs) implemented in primary care settings and targeting youth not seeking or identified as needing special treatment were found in a systematic review with meta-analysis (O'Connor E. et al., 2020, 29 studies, N=18 353) to have no significant effect in:
preventing or reducing illicit drug use (SMD= - 0.08, 95% CI = -0.16, p<0.001, 24 studies, N=12 801).
The majority of intervention showed no clear evidence of benefit, and 2 reported increased illicit drug use in youth participating in the interventions for at least 1 drug-related outcome.
However a few showed a benefit for some outcomes in some subgroups, especially the combination of a clinician interview and an electronic-based intervention (e.g. computer-based interventions targeting young female adolescents or the computer-based version of the Familias Unidas intervention).
Primary care-based models for opioid substitution treatment were analysed in a systematic review (Legisetty et al., 2017, 35 studies) to identify models' structures and processes associated
with improved patient outcomes. While some models, namely multidisciplinary and coordinated care delivery models were common to most studies and showed positive association with some outcomes, overall the review could not find a significant correlation between models and/or components in:
Promotion of sensible alcohol consumption and/or prevention injuries policy were found in narrative review (Calafat Juan and Duch, 2009) and in a systematic review (Ker and Chinnock, 2008) including 23 studies (RCT, 10 non-randomised controlled trials and 5 CBA) to be more effective than no intervention in:
reducing Single Vehicle Night crashes 4 % after six months, 11 % after 12 months, 18 % after 24 months, and 23 % after 36 months.
A review of reviews (MacArthur et al., 2014, N=25 reviews), without meta-analysis, concluded that there is:
tentative evidence to support the effectiveness of the provision of sterile injecting paraphernalia in reducing injecting risk behaviour (N=15 studies, 10 positive, 5 no association).
A narrative review (Fischer et al., 2015), without meta-analysis, concluded that there is:
some evidence to support the effectiveness of contingency management in outcomes such as retention in treatment and behavioural outcomes, eg, reduce use, abstinence yet mixed evidence in relation to social outcomes, eg, housing and employment albeit in the short-term of treatment.
Likely to be beneficial
cocaine
reduce substance use, retain patients in treatment
Psychosocial interventions delivered to people affected by someone else's addiction (problematic alcohol use, substance use, gambling or gaming) were assessed in a systematic review with meta-analysis ((Merkouris et al., 2022). Interventions included therapist interventions, delivered individually, in group and/or self-directed; cognitive–behavioural programmes based on CRAFT methodology that helps affected others to engage treatment-resistant addicted individuals into treatment and improve the affected other’s quality of life; coping skills training and other type of interventions. The results found beneficial intervention effects over control groups at post-intervention:
on some affected other
depressive symptomatology (SMD = -0.48, 95% CI = -0.67, -0.29),
life satisfaction (SMD = -0.37, 95% CI = -0.71, -0.03)
and coping style (SMD = -1.33, 95% CI = -1.87, -0.79)
on the addicted person
treatment entry (RR = 0.86, 95% CI = 0.75-0.98)
on relationship functioning outcomes
marital discord, SMD = -0.40, 95% CI = -0.61, -0.18)
No beneficial intervention effects were identified at short-term follow-up (4-11 months post-treatment). The beneficial intervention effects identified at post-treatment remained when limiting to studies of alcohol use and therapist-delivered interventions.
Likely to be beneficial
not-drug specific
improve behavioural life skills, improve mental health outcomes, improve psychosocial functioning
Psychosocial interventions for Amphetamine-type stimulants (ATS - meth/amphetamine and ecstasy) use were found in review of reviews with meta-analysis (Tran et al., 2021) that:
membership of a psychological intervention group was associated with an important reduction in drug usage (risk ratio (RR) 0.80, 95% CI: 0.75 to 0.85, high-quality evidence)
the combination of therapies reduced 1.51 day using drugs in the preceding 30 days (95% CI: −2.36 to −0.67) compared to cognitive behavioural therapy intervention alone (high-quality evidence)
compared to usual care, cognitive behavioural therapy was less likely to be retained at follow-up (RR 0.89, 95% CI: 0.82 to 0.97; high-quality evidence). However, the additional of contingency management strategy can make an important improvement upon retention (RR 1.42, 95%CI: 1.25 to 1.62)
Psychosocial interventions considered in the analysis were:
Psychosocial interventions for Amphetamine-type stimulants (ATS - meth/amphetamine and ecstasy) use were found in review of reviews with meta-analysis (Tran et al., 2021) that:
patients in psychological interventions used injectables substantially less (odds ratio (OR) 0.35, 95% CI: 0.24 to 0.49, low quality evidence)
the risk of unsafe sex in the psychosocial intervention group was lower than in the control group (RR 0.49, 95% CI: 0.34 to 0.71, moderate quality evidence)
Psychosocial interventions considered in the analysis were:
Psychosocial interventions for family members affected of other members’ substance abuse were found in a systematic review with meta-analysis (Rushton et al., 2023, 19 studies, 10 incl. metanalysis) to have a significant effect on:
reducing depression (RTCs = 3, SMD= 0.50, 95% CI 0.21 to 0.79) and in non-RTCs (d =0.50, 95% CI 0.17 to 0.82)
decreasing distress (SMD=0.28, 95% CI 0.03, 0.54) and in non-RTC (d = 0.44, 95% CI 0.13, 0.75)
improving family functioning (d = 0.51, 95% CI 0.28, 0.73) and coping (d = 0.81, 95% CI 0.29, 1.33).
Likely to be beneficial
not-drug specific
improve mental health outcomes, improve psychosocial functioning
Psychosocial interventions involving information, education, counselling and/or skills training (IECS) were found in a systematic review (Palmateer et al., 2022, 27 systematic review, 61 studies) to have insufficient evidence for:
Psychosocial interventions involving information, education, counselling and/or skills training (IECS) were found in a systematic review (Palmateer et al., 2022, 27 systematic review, 61 studies) to have sufficient evidence in:
the prevention of injecting risk behaviours and injecting frequency among PWID.
A Cochrane systematic review with meta-analysis (McGovern et al., 2021 a, studies=22, N= 2 274) assessed complex psychosocial interventions targeting substance use in parents of children under the age of 21 years. Interventions were found to be effective in:
reducing the frequency at which parents use alcohol and drugs
low-quality evidence that psychosocial interventions targeting substance use only may not reduce the frequency of alcohol (6 months: SMD −0.35, 95% CI −0.86 to 0.16; 2 studies, 89 participants and 12 months: SMD −0.09, 95% CI −0.86 to 0.61; 1 study, 34 participants) or drug use (6 months: SMD 0.01, 95% CI −0.42 to 0.44; 2 studies; 87 participants and 12 months: SMD −0.08, 95% CI −0.81 to 0.65; 1 study, 32 participants)
Integrated psychosocial interventions which combine parenting skills interventions with a substance use component may show the most promise (low quality evidence)
integrated interventions which combined both parenting- and substance use- targeted components may reduce alcohol misuse with a small effect size (6 months: SMD −0.56, 95% CI −0.96 to −0.16 and 12 months: SMD −0.42, 95% CI −0.82 to −0.03; 2 studies, 113 participants) and drug use (6 months: SMD −0.39, 95% CI −0.75 to −0.03 and 12 months: SMD −0.43, 95% CI −0.80 to −0.07; 2 studies, 131 participants)
Authors also found
that whilst it appears that mothers may benefit less than fathers from intervention, caution is advised in the interpretation of this evidence, as the interventions provided to mothers alone typically did not address their substance use and other related needs.
low-quality evidence from few studies that interventions involving children are not beneficial.
A more comprehensive narrative review (McGovern et al., 2021 b, studies=58) investigating the adverse health and social outcomes derived by the the substance use of a close relative, found behavioural interventions to be effective in:
improving the social wellbeing of family members (reducing intimate partner violence, enhancing relationship satisfaction and stability and family functioning) when delivered conjointly with the substance user and the affected family members.
Also an affected adult family members may derive psychological benefit from an associated individually focused therapeutic intervention component.
However no interventions fully addressed the complex multidimensional adversities experienced by many families affected by substance use and further research is needed to determine the effect of a multi-component psychosocial intervention, which seeks to support both the substance user and the affected family member.
Likely to be beneficial
alcohol, not-drug specific
improve behavioural life skills, improve psychosocial functioning, improve recovery outcomes
A systematic review (Klimas et al, 2018, 7 trials, n= 825, low to very-low quality evidence) comparing different types of psychosocial interventions did not find clear superiority results in:
reducing alcohol use among people who use illicit drugs (mostly opioids and stimulants).
Compared psychosocial interventions included among others 12-steps programmes, educational interventions only, motivational interviewing, and treatment as usual.
Behavioural therapies (including cognitive behavioural therapies (CBT), motivational interviewing (MI) and contingency management) were found in a systematic review with meta-analysis (Gates et al., 2016, 23 RCTs, N=4 045) to be more effective than control conditions on:
completing of treatment (effect size (ES) 0.71, 95 % CI 0.63 to 0.78, 11 studies, N=1 424)
reducing use (MD 5.67, 95 % CI 3.08 to 8.26, six studies, N=1 144)
improving abstinence (RR 2.55, 95 % CI 1.34 to 4.83, six studies, N=1 166)
reducing symptoms of dependence (standardised mean difference (SMD) 4.15, 95 % CI 1.67 to 6.63, four studies, N=889)
reducing cannabis-related problems (SMD 3.34, 95 % CI 1.26 to 5.42, six studies, N=2 202)
The same meta-analysis also found that:
Interventions of more than four sessions delivered over longer than one month (high intensity) produced consistently improved outcomes (particularly in terms of cannabis use frequency and severity of dependence) in the short term as compared with low-intensity interventions
The most consistent evidence supports the use of cognitive-behavioural therapy (CBT), motivational enhancement therapy (MET) and particularly their combination for assisting with reduction of cannabis use frequency and severity of dependence at early follow-up
Data from five out of six studies supported the utility of adding voucher-based incentives for cannabis-negative urines to enhance treatment effect on cannabis use frequency
Evidence of drug counselling, social support, relapse prevention and mindfulness meditation was weak because identified studies were few, information on treatment outcomes insufficient and rates of treatment adherence low.
Behavioural therapies targeting specifically adolescents were analysed in a systematic review without meta-analysis (Hogue et al., 2014, 8 RCTs) arriving at the same conclusions: see comment for the rest of the text
CBT is well established but was outperformed by family-based treatments in several trials
CBT at group level or at individual level are equally effective
MI as a standalone approach has given mixed results
Integrated models uniformly performed well
Likely to be beneficial
cannabis
improve psychosocial functioning, reduce substance use
Psychosocial interventions for female drug-using offenders were found in a systematic review (Perry et al., 2015a) to have no significant effect (in different types of comparisons) in:
reducing drug use
Interventions examined included collaborative case management, interpersonal psychotherapy, cognitive behavioural skills, single computerised intervention, dialectic behavioural therapy and case management and therapeutic community.
Cognitive behavioural therapy was found in a systematic review (Perry et al., 2019a) to be more effective than therapeutic communities (one study of low quality) in:
reducing criminal activity, i.e. arrested (not for parole) violations at six months follow-up (RR 0.43, 95 % CI 0.25 to 0.77, N=314)
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, WHO 2009) 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).
Methadone treatment plus psychosocial intervention compared with methadone treatment only was found in a systematic review of (WHO, 2009, 3 RCTs, 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 interventions in addition to Methadone maintenance treatment were found in a systematic review (WHO 2009, 3 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).
Psychosocial treatments (delivered alone or in combination with pharmacotherapy) were analysed in a systematic review (Hides et al., 2020) that found no significant effect compared with no treatment or treatment as usual in:
the treatment of comorbid depression and substance use disorders.
Although some significant effects were found between different phychotherapies, these were inconsistent and small and the evidence of poor quality.
Unknown effectiveness
co-morbidity
improve mental health outcomes, reduce substance use
Substitution therapy has already proved to be effective for smoking and opioid use. Evidence is emerging around the effectiveness of pychostimulants prescription for stimulants related problems.
Psychostimulants, namely modafinil, methylphenidate, or amphetamines (mixed amphetamine salts, lisdexamphetamine, and dextroamphetamine) were found in a systematic review (Tardelli et al., 2020, 38 RCTs, N = 2889) to be effective in:
increasing rates of sustained abstinence [risk ratio (RR) = 1.45, 95% confidence interval (CI) = (1.10, 1.92)] and duration of abstinence [mean difference (MD) = 3.34, 95%CI = (1.06, 5.62)], particularly in patients with cocaine use disorder (although very low-quality evidence).
Prescription amphetamines were particularly beneficial in promoting sustained abstinence in patients with cocaine use disorder [RR = 2.44, 95% CI = (1.66, 3.58)], and
higher doses of PPs (eg. >60 mg/dose of dextroamphetamine) were particularly efficacious for treatment of cocaine use disorder [RR = 1.95, 95% CI = (1.38, 2.77)].
Treatment with prescription amphetamines also yielded more cocaine-negative urines [MD = 8.37%, 95% CI = (3.75, 12.98)].
There was no effect of PPs on the retention in treatment.
Psychotherapy interventions (individual (CBT, IPSRT, family focused therapy) and group interventions) were found in a systematic review (Crowe et al., 2021, 7 studies) to have no conclusive effects in:
improving mental health and treatment outcomes (i.e. improving mood outcomes and reducing use)
Unknown effectiveness
not-drug specific
improve mental health outcomes, reduce substance use
Psychosocial interventions were found in a systematic review (Terplan et al., 2015) to have no statistically significant different effect than other standard care 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)
Replacement of pint glasses with toughened glassware was found in two systematic reviews (Jones et al, 2010; Ker and Chinnock, 2008) to cause even more harm:
experimental glass caused more injury than the control (only narrative results).
Residential treatment was found in a systematic review without meta-analysis (Reif et al., 2014, 8 review and 21 studies) mixed results when compared to other interventions in:
A systematic review of a small number of studies assessing the acceptance and feasibility of safe tattooing and body piercing programmes in prison (ECDC/EMCDDA, 2018) suggests these bear no significant effect in:
A systematic review with no meta-analysis (Esrick et al 2018, 17 studies) found that scare tactics and fear-based messages may be effective in preventing substance misuse. The studies focused on campaigns addressing the use of tobacco, alcohol, cannabis, or methamphetamine.
School health services were found in a systematic review with meta-analysis (Montgomery et al., 2021) to be effective (moderate quality evidence) in:
reducing drinking alcohol (60.1% vs. 70.5%, p < .001),
reducing using drugs (28.0% vs. 38.3%, p < .001)
School health services were also found to be associated with reductions in suicide planning (male: 7.1% vs. 7.7%, p < .01), hospitalization (relative risks 3.403, 95% confidence interval [CI] 1.536 to 8.473, p < .05), emergency department visits (odds ratio .85, 95% CI .75 to .95, p ¼ .006), school absence (odds ratio .78, 95% CI .69 to .87, p < .0001), carrying weapons (male: 16.1% vs. 25.1%, p < .01), fighting (male: 32.6% vs. 43.1%, p < .01), sexual activity (53.5% vs. 60.5%, p < .05) and physical activity (female: 57.4% vs. 50.4%, p < .01).
School-based brief interventions were found in a systematic review (Carney et al., 2016, 6 RCT, N=1 176) to have no different effect than information-only interventions (eg. general health promotion materials and harm reduction information) in:
reducing alcohol and cannabis use
reducing delinquent-type behaviours
There was very low-quality evidence that brief school-based interventions may be more effective in reducing alcohol and cannabis use than no-intervention (i.e when compared to assessment-only) and that these reductions were sustained at long-term follow-up, however it is premature to make a definitive statement.
Multiple health behaviour change interventions target risk factors in combination and are a promising method to improve lifelong health. This approach capitalises on evidence that changing one lifestyle behaviour could increase self-efficacy to improve others. Given that teaching time is often restricted, interventions that simultaneously address multiple risk behaviours are particularly advantageous in school settings. eHealth interventions (delivered via the internet, computers, tablets, mobile technology, or tele-health) offer increased student engagement, fidelity, and scalability, and internet technology is becoming increasingly embedded in school education.
School-based eHealth multiple health behaviour change interventions were found in a systematic review with meta-analysis (Champion et al., 2019, 18 studies, N = 18 873 students) to have no effect in:
reducing alcohol use or smoking
The interventions significantly increased fruit and vegetable intake (standard mean difference 0·11, 95% CI 0·03 to 0·19; p=0·007) and both accelerometer-measured (0·33, 0·05 to 0·61; p=0·02) and self-reported (0·14, 0·05 to 0·23; p=0·003) physical activity, and reduced screen time (–0·09, –0·17 to –0·01; p=0·03) immediately after the intervention; however, these effects were not sustained at follow-up when data were
available.
School-based generic prevention programs (not including life/social skills approaches, see above in the Beneficial category) have not shown enough evidence to be effective in a systematic review (Foxcroft et al., 2011) of 53 RCTs in:
reducing alcohol misuse in adolescents (no statistically significant outcomes in 24 out of 39 generic trials).
School-based multicomponent positive psychology interventions aim at increasing well-being indicators of mental health (i.e., subjective and psychological well-being) and reducing the most common psychological distress indicators (i.e., depression, anxiety, and stress) in adolescents. Positive psychology interventions originated as scientifically-based interventions that focus on strengthening positive emotions, thoughts, and behaviors through activities that can be easily implemented in daily routines. Multicomponent positive psychology interventions are based on a variety of individual exercises targeting two or more theoretically relevant well-being components and are conducted within an integral program, decreasing the risk of relapse and increasing the probability of spill-over effects and synergy between activities, thus being more likely to provide long-term effects.
School-based multicomponent positive psychology interventions were found in a systematic review with meta-analysis (Tejada-Gallardo et al., 2020, 9 studies, N= 4 898) to be effective in improving:
subjective well-being (g = 0.24, 95% CI 0.11–0.38, p = 0.000),
psychological wellbeing (g = 0.25, 95% CI 0.01–0.51, p <0.05),
and depression symptoms (g = 0.28, 95% CI 0.13–0.43, p = 0.000).
Removing low-quality studies led to a slight decrease in the effect sizes for subjective well-being and a considerable increase for psychological well-being and depression symptoms.
Beneficial
not-drug specific
improve behavioural life skills, improve mental health outcomes, improve psychosocial functioning
A recent systematic review (MacArthur et al 2018) of 70 RCTs addressing two or more risk behaviours (with a follow-up period of at least six months) and targetting children up to 18 years of age, found that:
universal school-based multiple risk behaviour interventions were beneficial in preventing alcohol use (OR 0.72, 95% CI 0.56 to 0.92; n=8 studies; 8751 participants; bothmoderate-quality evidence) at up to 12 months' follow-up
A recent systematic review (MacArthur et al 2018) of 70 RCTs addressing two or more risk behaviours (with a follow-up period of at least six months) and targetting children up to 18 years of age found:
no certain effects of universal school-based multiple risk behaviour interventions in preventing cannabis use (OR 0.79, 95% CI 0.62 to 1.01; P= 0.06; n=6 studies; 4140 participants; I² = 0%; moderate-quality evidence)
A recent systematic review (MacArthur et al 2018) of 70 RCTs addressing two or more risk behaviours (with a follow-up period of at least six months) and targetting children up to 18 years of age, found that:
universal school-based multiple risk behaviour interventions may be effective in preventing illicit drug use (OR 0.74, 95% CI 0.55 to 1.00; n=5 studies; 11,058 participants; low-quality evidence) at up to 12 months' follow-up
A recent systematic review (MacArthur et al 2018) of 70 RCTs addressing two or more risk behaviours (with a follow-up period of at least six months) and targetting children up to 18 years of age, found that:
universal school-based multiple risk behaviour interventions were beneficial in preventing tobacco use (OR 0.77, 95% CI 0.60 to 0.97; n=9 studies; 15,354 participants) at up to 12 months' follow-up.
School-based anti-bullying programmes were found in a systematic review with meta-analysis (Ng et al., 2020, 17 studies, N= 35 694 adolescents) to have very small to small yet significant effect in:
reducing traditional bullying and cyberbullying perpetration (traditional:SMD -0.30 and cyber: SMD - 0.16)
reducing traditional bullying and cyberbullying victimization (traditional: SMD - 0.18 and cyber: SMD - 0.13)
Type of intervention (i.e., whole school–based or classroom-based), program duration, and presence of parental involvement did not moderate program effectiveness, but cyberbullying programs were more effective when delivered by technology-savvy content experts compared to teachers.
The results of a second systematic review with meta-analysis (Fraguas, et al. 2020, 69 RCTs, N = 111 659) support the feasibility of implementing anti-bullying programs in schools and suggest their potential effectiveness. School anti-bullying interventions were found to have small but significant effect in:
improving mental health problems (ES, −0.205; 95%CI, −0.277 to −0.133) at study end point,
with PINs -Population Impact Number - for universal interventions that target the total student population of 147 (95%CI, 113-213) and 107 (95%CI, 73-173), respectively. In other words, for an estimated bullying prevalence of 15% (a conservative estimate considering prevalence rates reported in previous studies), an average anti-bullying intervention needs to include 147 (95% CI, 113-213) people to prevent 1 case of bullying and 107 (95% CI, 73-173) people to improve mental health problems. We also found a substantial population impact (PIN, 167; 95%CI, 100-360) for interventions targeting cyberbullying (ie, 167 young people on average need to receive the intervention to prevent 1 case of cyberbullying perpetration or exposure). To put these results into context, the PIN is 35 450 for taking aspirin to avoid 1 death during the 6 months after a first nonhemorrhagic stroke, and the PIN is 324 for human papillomavirus vaccination in girls to prevent cervical cancer.
The duration of intervention was not statistically significantly associated with intervention effectiveness (mean [range] duration of interventions, 29.4 [1 to 144] weeks). The effectiveness of anti-bullying programs did not diminish over time during follow-up (mean [range] follow-up, 30.9 [2-104] weeks).
Shared decision-making (SDM) as means to involve patients in medical decision- making and matching patients’ preferences to treatments were found in a systematic review without meta-analysis (Friedrichs et al., 2016, 25 studies, N=8 729) to have no effect in:
Spiritual/religious (S/R) interventions for substance use disorders were found in a systematic review and meta-analysis (Hai et al 2019) to have
no significant effect when compared to inactive controls such as no treatment (6 studies, d =0.537, 95% CI = -0.316 to 1.390);
significant effect when compared to other interventions (16 studies, all comparing 12-step-oriented interventions to other interventions, d =0.176, 95% CI = -0.001 to 0.358).
There is evidence from a narrative review including results of one RCT (N=326) (Velleman 2009) that specific training given to young people in order to make them influence each other is not effective in:
reducing alcohol and tobacco use;
increasing knowledge and attitudes towards alcohol and tobacco
Knowledge focused programs were found in a systematic review (Faggiano et al, 2014) to have no different effect than usual school curricula or no intervention in:
improvinge participants’ knowledge of illicit drugs (SMD 0.91, 95 % CI 0.42–1.39, 1 study, N=165);
Standalone mass-media campaigns (not associated with other components such as school-based, community-based or national programmes) were found to be not effective in reducing tobacco consumption in a review of reviews of mass-media campaigns (Bühler and Kröger, 2006).
Overall, standalone mass-media campaigns for alcohol consumption were found to be ineffective in a narrative review (Wakefield 2010) based on the following outcomes:
warnings on drinks bottles, as a standalone measure have no effect on alcohol consumption. Campaigns to lessen alcohol intake have had little success. Most have been targeted towards young people but the potential effects have generally been overshadowed by widespread unrestricted alcohol marketing strategies and the view of drinking as a social norm.
safe drinking campaigns sponsored by alcohol companies have been ineffective in changing drinking behaviour, because the messages are viewed as ambiguous by recipients
School programmes based on social competence approaches were found in a systematic review (Faggiano et al., 2014) to be more effective than usual curricula in:
reducing use of cannabis at <12 months follow-up (RR 0.88, 95 % CI 0.72 to 1.07, 3 studies, N=10 716);
reducing use of cannabis at 12+ months follow-up (RR 0.95, 95 % CI 0.81 to1.13, 1 study, N=5 862)
reducing use of hard drugs (just one study not providing data for meta-analysis found a significant protective effect)
Street-level law enforcement approaches (including community-wide policing, problem-oriented policing, hot spots policing and standard model of policing) were found in a systematic review (EMCDDA 2017 - not published, based on Mazerolle et al., 2007) to be effective in:
reducing drug offences (OR 1.53, 95% CI 0.75 to 3.13)
problem-oriented policing (OR 2.44, 95% CI 1.30 to 4.60)
community-wide policing (OR 1.85, 95% CI 1.53 to 2.22)
reducing drug-related calls for service (OR 1.33, 95% CI 1.07 to 1.65)
problem-oriented policing (OR 1.44, 95% CI 1.16 to 1.77)
Evidence-based international guidelines (WHO, 2014) strongly recommend to advise opioid dependent pregnant women to use substitution treatment rather than attempt opioid detoxification.
Evidence does not support detoxification as a recommended treatment intervention as a result of low detoxification completion rates, high rates of relapse, and limited data regarding the effect of detoxification on maternal and neonatal outcomes beyond delivery (Dashe et al, 2018).
Maintenance treatment with different medications was assessed in a systematic review (Minozzi et al., 2014, 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)
There is evidence from a narrative review including results (Faggiano 2008, 1 RCT, N=271) that such interventions in the short to medium term can be effective at improving young people’s:
A review of reviews (MacArthur et al., 2014, N=25 reviews), without meta-analysis, concluded that there is:
insufficient evidence to support the effectiveness of pharmacy based NSP in preventing HIV infections (N=4 studies, 4 positive)
insufficient evidence to support the effectiveness of syringe provision through vending machine in preventing HIV infections (N=1 study, 1 no association) and reducing injecting risk behaviours (N=3 studies, 1 positive, 2 no association)
insufficient evidence to support the effectiveness of syringe provision through mobile vans in preventing HIV infections (N=1 study, 1 negative)
Community distribution of naloxone was the focus of a systematic reviews of economic evaluations (Cherrier et al., 2022, 10 studies, one cost-effectiveness analysis, eight cost-utility analyses, and one cost-benefit analysis) and results showed that:
all studies concluded that community distribution of naloxone was cost effective, with an incremental cost-utility ratio range of $US111-58,738 (year 2020 values) per quality-adjusted life-year gained.
Education and naloxone distribution was found in an umbrella review of systematic reviews (Razaghizad et al., 2021, 6 SR containing 87 unique studies) effective in:
Education and naloxone distribution was found in an umbrelal review of systematic reviews (Razaghizad et al., 2021, 6 SR containing 87 unique studies) effective in:
reducing opioid-related mortality. High-concentration intranasal naloxone (> 2 mg/mL) was as effective as intramuscular naloxone at the same dose, whereas lower-concentration intranasal naloxone was less effective.
Educational and training interventions complemented by take-home naloxone has been found to be effective in systematic review of 21 studies (EMCDDA, 2015) in:
A systematic review with meta-analysis (Tinner et al., 2022, 66 studies) assessed the effects of individual-, family- and school-based interventions to prevent multiple risk behaviours relating to alcohol, tobacco and drug use in young people aged 8-25 years. Results found that:
for targeted school-level interventions, there was low quality evidence of no or a small short-term benefit: alcohol use (OR 0.90, 95% CI: 0.74-1.09), tobacco use (OR 0.86, 95% CI: 0.66, 1.11), cannabis use (OR 0.84, 95% CI: 0.66-1.07) and other illicit drug use (OR 0.79, 95% CI 0.62-1.02).
Technology-based interventions for women between 18 and 44 years old were found in a systematic review with meta-analysis (Hai et al., 2019, 15 studies, N = 3 488) to have an effect when compared to control conditions in:
reducing substance use (alcohol and/or drugs) in the short term (follow-up ranged from 2 to 6 months) (d = 0.19, 95% CI = 0.02, 0.35, 13 studies)
The effect size estimates calculated separately for alcohol use and illicit drug use were 0.13 and 0.30 respectively and neither was statistically significant possibly due to low power of the studies.
Interventions examined included brief interventions modeled after the motivational interviewing approach or involving periodically sending participants text messages to provide educational information to reduce substance use.
Technology-based (web or computer) motivational and psycho-education interventions and cognitive enhancement therapy were found in a systematic review without meta-analysis (Tatar et al, 2020, 8 studies) to have no significant effect in:
reducing cannabis use, abstinence or dependence severity in patients with psychosis
A systematic review without meta-analysis (Lin et al 2019, 13 studies) found no evidence of effect of telemedicine-delivered treatment (psychotherapy or pharmacotherapy) interventions for substance use disorders.
Studies examined suggest this type of intervention is an effective alternative, particularly where face-to-face treatment is less available, but more research is needed on their effectiveness.
When compared to treatment as usual therapeutic communities in prison and aftercare were found in a systematic review (Perry et al., 2019, 13 RTCs, N = 2 606) to have a moderate effect in:
reducing re-incarceration rates (RR 0.40, 95% CI 0.24 - 0.67)
reducing involvement in subsequent criminal activity (RR 0.67, 95% CI 0.53 - 0.84)
Therapeutic communities in prison (including aftercare or transitional programs and drug-free wings) were found in a systematic review without meta-analysis (Galassi et al., 2015, 14 studies, N =8245) to be more effective than control conditions in:
reducing re-incarceration rates (5 studies out of 7 found significant results)
reducing or preventing drug misuses relapse (7 studies out of 9 found positive results)
Therapeutic communities were analysed in a narrative systematic review (Vanderplasschen et al., 2013). While the review found some positive impact of TC on legal outcomes, overall it did not find any significant effects in:
The Therapeutic Workplace (TW) is a motivational intervention that uses access to employment and wages to promote therapeutic behavioral changes. TW is one of the interventions/programmes aimed at improving employment outcomes evaluated in a narrative review (Magura et Marshall, 2020, 14 studies).
The review showed no significant effect on:
average monthly days employed and employment outcomes in general
The other interventions reviewed are: Individual Placement and Support (IPS), Customized Employment Supports (CES), Drug Court employment interventions, Job Seekers Workshop (JSW).
Drink-driving programmes targeting recreational settings encompassing compulsory training for all alcohol servers and owners/managers were found in a narrative review (Calafat, Juan and Duch, 2009) to lead to:
statistically significant reductions in single-vehicle night-time traffic accidents (those with high percentages of alcohol involvement).
Mandated server training was found in two systematic reviews (Jones et al 2010; Ker and Chinnock, 2008) and in a narrative review (EMCDDA, 2012), to lead to:
reductions in Single Vehicle Night crashes and alcohol-related crashes (23 % by the end of the third year).
Alcohol server interventions were found in a systematic review (Bolier et al 2011) to have significant effects in:
Face to face server training, when accompanied by strong and active management support, assessed in two narrative and two systematic review (Calafat, Juan and Duch, 2009; EMCDDA, 2012; Bolier et al, 2011; Jones et al 2010) was found effective in:
reducing the level of intoxication in bar clients (only narrative results).
reducing the percentage of clients with BALs ≥ 0.08 (reported by the authors as significant, only narrative results).
In a meta-analysis including 8 randomized clinical trials which evaluated the effect of tramadol for the treatment of opioid withdrawal and used an opioid withdrawal scale to assess the change in opioid withdrawal symptoms was found:
no significant difference between tramadol and comparators like placebo (SMD: -1.12; 95%CI: -2.69 to 0.45) buprenorphine (SMD: -0.21; 95%CI: -0.43 to 0.01), clonidine (SMD: -0.26; 95%CI: -0.55 to 0.02) and methadone (SMD: -0.84; 95%CI: -1.78 to 0.10).
There were no significant differences in treatment retention at the end of studies between tramadol and comparators.
The efficacy of tramadol in reducing opioid withdrawal symptoms is not significantly different from comparators with low certainty of evidence against placebo, moderate against methadone, whereas with high certainty of evidence against buprenorphine and clonidine.
A narrative systematic review (Özgen et al., 2021) investigated the treatment options of adolescents with attention-deficit/hyperactivity disorder (ADHD) and comorbid substance use disorders (SUD) and overall found that there is very limited evidence of treatments for this comorbidity and does not allow for strong recommendations. Specifically:
pharmacological treatment - none of the trials in this comorbid adolescent population showed a robust between-group effect of treatment on either ADHD or SUD
psychosocial treatment - no randomized trials or meta-analyses have been conducted to date in youth with concurrent ADHD and SUD
Unknown effectiveness
co-morbidity, not-drug specific
improve mental health outcomes, improve treatment outcomes
A systematic review with meta-analysis (Tinner et al., 2022, 66 studies) assessed the effects of individual-, family- and school-based interventions to prevent multiple risk behaviours relating to alcohol, tobacco and drug use in young people aged 8-25 years. Results show that:
universal school-based interventions are likely to have little or no short-term benefit (up to 12 months) in relation to alcohol use (OR 0.94, 95% CI: 0.84, 1.04), tobacco use (OR 0.98, 95% CI: 0.83, 1.15), cannabis use (OR 1.06, 95% CI: 0.86, 1.31) and other illicit drug use (OR 1.09, 95% CI: 0.85, 1.39)
Virtual Reality was found in a narrative systematic review (Segawa et al., 2020) to have heterogenous results and no conclusive effect in:
reducing craving (studies focused on nicotine, cocaine, alcohol, cannabis, gambling)
However the same review found VR applications to be an effective alternative to in-vivo techniques in triggering cue-reactivity in adult individuals in both substance use disorders and behavioural addictions. In addition, the authors concluded that including coping mechanisms to VR-based interventions may add efficacy in terms of craving reduction.
Virtual Reality is identified in the review as a Human-Computer Interaction platform based on immersive simulations of realistic environments.
A more recent narrative systematic review (Taubin et al., 2022, 5 studies, focus on tobacco) assessed the effect of virtual reality therapies on substance use disorder and arrived at the same conclusions:
no clear evidence of effect in reducing craving, mood outcomes, anxiety and depression.
Work-based interventions were evaluated in a narrative systematic review (Morse et al., 2022, 39 studies) and found no evidence of effect in treating and preventing substance use. More specifically:
Workplace health promotion interventions could reduce alcohol consumption, but the quality of the evidence is low: out of seven interventions on health promotion, five found statistical significance. However, more research is needed due to the low quality of the studies and the lack of a control group.
Workplace-based psychosocial and e-health interventions might not be effective. Most studies reported weak statistical evidence.
The authors discussed that the main difficulties of implementing workplace interventions are a lack of engagement in online interventions, male employees' hesitation to seek help, and confidentiality issues.
