Psychosocial and pharmacologic interventions to reduce harmful alcohol use in low‐ and middle‐income countries

M Claire Greene; Jeremy Kane; Michelle Alto; Ali Giusto; Kathryn Lovero; Melissa Stockton; Jasmine McClendon; Terriann Nicholson; Milton L Wainberg; Renee M Johnson; Wietse Anton Tol

doi:10.1002/14651858.CD013350.pub2

. 2023 May 9;2023(5):CD013350. doi: 10.1002/14651858.CD013350.pub2

Psychosocial and pharmacologic interventions to reduce harmful alcohol use in low‐ and middle‐income countries

M Claire Greene ^1,^2,^✉, Jeremy Kane ², Michelle Alto ³, Ali Giusto ⁴, Kathryn Lovero ⁵, Melissa Stockton ⁴, Jasmine McClendon ⁶, Terriann Nicholson ⁴, Milton L Wainberg ⁴, Renee M Johnson ², Wietse Anton Tol ^2,⁷

Editor: Cochrane Drugs and Alcohol Group

PMCID: PMC10167787 PMID: 37158538

Abstract

Background

Harmful alcohol use is defined as unhealthy alcohol use that results in adverse physical, psychological, social, or societal consequences and is among the leading risk factors for disease, disability and premature mortality globally. The burden of harmful alcohol use is increasing in low‐ and middle‐income countries (LMICs) and there remains a large unmet need for indicated prevention and treatment interventions to reduce harmful alcohol use in these settings. Evidence regarding which interventions are effective and feasible for addressing harmful and other patterns of unhealthy alcohol use in LMICs is limited, which contributes to this gap in services.

Objectives

To assess the efficacy and safety of psychosocial and pharmacologic treatment and indicated prevention interventions compared with control conditions (wait list, placebo, no treatment, standard care, or active control condition) aimed at reducing harmful alcohol use in LMICs.

Search methods

We searched for randomized controlled trials (RCTs) indexed in the Cochrane Drugs and Alcohol Group (CDAG) Specialized Register, the Cochrane Clinical Register of Controlled Trials (CENTRAL) in the Cochrane Library, PubMed, Embase, PsycINFO, CINAHL, and the Latin American and Caribbean Health Sciences Literature (LILACS) through 12 December 2021. We searched clinicaltrials.gov, the World Health Organization International Clinical Trials Registry Platform, Web of Science, and Opengrey database to identify unpublished or ongoing studies. We searched the reference lists of included studies and relevant review articles for eligible studies.

Selection criteria

All RCTs comparing an indicated prevention or treatment intervention (pharmacologic or psychosocial) versus a control condition for people with harmful alcohol use in LMICs were included.

Data collection and analysis

We used standard methodological procedures expected by Cochrane.

Main results

We included 66 RCTs with 17,626 participants. Sixty‐two of these trials contributed to the meta‐analysis. Sixty‐three studies were conducted in middle‐income countries (MICs), and the remaining three studies were conducted in low‐income countries (LICs). Twenty‐five trials exclusively enrolled participants with alcohol use disorder. The remaining 51 trials enrolled participants with harmful alcohol use, some of which included both cases of alcohol use disorder and people reporting hazardous alcohol use patterns that did not meet criteria for disorder.

Fifty‐two RCTs assessed the efficacy of psychosocial interventions; 27 were brief interventions primarily based on motivational interviewing and were compared to brief advice, information, or assessment only. We are uncertain whether a reduction in harmful alcohol use is attributable to brief interventions given the high levels of heterogeneity among included studies (Studies reporting continuous outcomes: Tau² = 0.15, Q =139.64, df =16, P<.001, I² = 89%, 3913 participants, 17 trials, very low certainty; Studies reporting dichotomous outcomes: Tau²=0.18, Q=58.26, df=3, P<.001, I² =95%, 1349 participants, 4 trials, very low certainty). The other types of psychosocial interventions included a range of therapeutic approaches such as behavioral risk reduction, cognitive‐behavioral therapy, contingency management, rational emotive therapy, and relapse prevention. These interventions were most commonly compared to usual care involving varying combinations of psychoeducation, counseling, and pharmacotherapy. We are uncertain whether a reduction in harmful alcohol use is attributable to psychosocial treatments due to high levels of heterogeneity among included studies (Heterogeneity: Tau² = 1.15; Q = 444.32, df = 11, P<.001; I²=98%, 2106 participants, 12 trials, very low certainty).

Eight trials compared combined pharmacologic and psychosocial interventions with placebo, psychosocial intervention alone, or another pharmacologic treatment. The active pharmacologic study conditions included disulfiram, naltrexone, ondansetron, or topiramate. The psychosocial components of these interventions included counseling, encouragement to attend Alcoholics Anonymous, motivational interviewing, brief cognitive‐behavioral therapy, or other psychotherapy (not specified). Analysis of studies comparing a combined pharmacologic and psychosocial intervention to psychosocial intervention alone found that the combined approach may be associated with a greater reduction in harmful alcohol use (standardized mean difference (standardized mean difference (SMD))=‐0.43, 95% confidence interval (CI): ‐0.61 to ‐0.24; 475 participants; 4 trials; low certainty).

Four trials compared pharmacologic intervention alone with placebo and three with another pharmacotherapy. Drugs assessed were: acamprosate, amitriptyline, baclofen disulfiram, gabapentin, mirtazapine, and naltrexone. None of these trials evaluated the primary clinical outcome of interest, harmful alcohol use.

Thirty‐one trials reported rates of retention in the intervention. Meta‐analyses revealed that rates of retention between study conditions did not differ in any of the comparisons (pharmacologic risk ratio (RR) = 1.13, 95% CI: 0.89 to 1.44, 247 participants, 3 trials, low certainty; pharmacologic in addition to psychosocial intervention: RR = 1.15, 95% CI: 0.95 to 1.40, 363 participants, 3 trials, moderate certainty). Due to high levels of heterogeneity, we did not calculate pooled estimates comparing retention in brief (Heterogeneity: Tau² = 0.00; Q = 172.59, df = 11, P<.001; I² = 94%; 5380 participants; 12 trials, very low certainty) or other psychosocial interventions (Heterogeneity: Tau² = 0.01; Q = 34.07, df = 8, P<.001; I² = 77%; 1664 participants; 9 trials, very low certainty). Two pharmacologic trials and three combined pharmacologic and psychosocial trials reported on side effects. These studies found more side effects attributable to amitriptyline relative to mirtazapine, naltrexone and topiramate relative to placebo, yet no differences in side effects between placebo and either acamprosate or ondansetron.

Across all intervention types there was substantial risk of bias. Primary threats to validity included lack of blinding and differential/high rates of attrition.

Authors' conclusions

In LMICs there is low‐certainty evidence supporting the efficacy of combined psychosocial and pharmacologic interventions on reducing harmful alcohol use relative to psychosocial interventions alone. There is insufficient evidence to determine the efficacy of pharmacologic or psychosocial interventions on reducing harmful alcohol use largely due to the substantial heterogeneity in outcomes, comparisons, and interventions that precluded pooling of these data in meta‐analyses. The majority of studies are brief interventions, primarily among men, and using measures that have not been validated in the target population. Confidence in these results is reduced by the risk of bias and significant heterogeneity among studies as well as the heterogeneity of results on different outcome measures within studies. More evidence on the efficacy of pharmacologic interventions, specific types of psychosocial interventions are needed to increase the certainty of these results.

Keywords: Humans, Male, Acamprosate, Alcoholism, Alcoholism/prevention & control, Amitriptyline, Developing Countries, Disulfiram, Mirtazapine, Naltrexone, Ondansetron, Topiramate

Plain language summary

Interventions to reduce harmful alcohol use in low‐ and middle‐income countries

Why is this review important?

Harmful alcohol use is one of the main contributors to the global burden of disease. In low‐ and middle‐income countries, harmful alcohol use is increasing. However, services to prevent and treat harmful alcohol use are limited. One contributor to the lack of available services is the limited information about which intervention approaches are effective in reducing harmful alcohol use and whether these approaches are feasible and acceptable in low‐resource settings. In order to prevent the physical, psychological, and societal burden of harmful alcohol use, it is important that effective interventions are available to reduce alcohol‐related harm.

What is the goal of this review?

The goal of this review is to summarize evidence on whether psychosocial and pharmacologic interventions are able to reduce harmful alcohol use in low‐ and middle‐income countries. We also aim to evaluate the safety of treatments and how many people remain in treatment until its completion.

What does the research say?

We identified 66 randomized controlled trials that evaluated the effect of interventions on reducing harmful alcohol use. Most of these studies assessed psychosocial interventions (n = 52 studies), six assessed pharmacologic interventions alone, and eight assessed combined pharmacologic and psychosocial interventions.

The majority of included trials were funded by government agencies (36 trials) followed by multiple public and private funders (8 trials) or private foundations (5 trials). Seventeen trials did not report the funding source.

We are uncertain whether brief psychosocial interventions and other psychosocial interventions reduce harmful alcohol use. Combined pharmacologic and psychosocial interventions may reduce harmful alcohol use relative to psychosocial interventions combined with placebo, yet the certainty of the evidence has been assessed as low. No studies were found that looked at the effect of pharmacologic interventions alone on harmful alcohol use. We did not find evidence that rates of retention differed between study conditions for any of the intervention types.

Certainty of evidence: The certainty of evidence on the effect of brief and other psychosocial interventions on harmful alcohol use was very low due to lack of masking, differential attrition and missing data, selective outcome reporting, high heterogeneity, and differences in patient populations. The certainty of evidence on the effect of combined pharmacologic and psychosocial interventions on harmful alcohol use was low due to lack of blinding, incomplete outcome data, and heterogeneity in the pharmacologic interventions under investigation. No studies evaluated the effect of pharmacologic interventions alone on harmful alcohol use.

The evidence is current to 12 December 2021.

What are the next steps?

Future research on interventions to reduce harmful alcohol use is needed to address some of the limitations described in this review. Studies evaluating similar interventions across studies and contexts are needed to improve generalizability and understand the necessary characteristics of and conditions for effective intervention. Studies must utilize measurement tools that are valid in the population they are studying. Lastly, studies must be designed to reduce the risk of bias leading to the high degree of uncertainty in the results reported in this review.

Summary of findings

Summary of findings 1. Pharmacologic intervention compared to placebo for individuals with alcohol use disorder.

Pharmacologic intervention compared to placebo for individuals with alcohol use disorder
Patient or population: individuals with alcohol use disorder Setting: Low‐ and middle‐income countries Intervention: Pharmacologic intervention Comparison: placebo
Outcomes	№ of participants (studies) Follow‐up	Certainty of the evidence (GRADE)	Relative effect (95% CI)	*Anticipated absolute effects^ (95% CI)**
				Risk with placebo	Risk difference with Pharmacologic intervention
Harmful alcohol use	0 (0 RCTs)	‐	not estimable	Study population
				0 per 1,000	0 fewer per 1,000 (0 fewer to 0 fewer)
Retention	247 (3 RCTs)	⊕⊕⊝⊝ Low ^{1 2}	RR 1.13 (0.89 to 1.44)	Study population
				562 per 1,000	73 more per 1,000 (62 fewer to 247 more)
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).  CI: confidence interval; RR: risk ratio.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

Pharmacologic intervention along with psychosocial intervention compared to psychosocial intervention alone for individuals with alcohol use disorder
Patient or population: individuals with alcohol use disorder Setting: Low‐ and middle‐income countries Intervention: Pharmacologic intervention along with psychosocial intervention Comparison: psychosocial intervention alone
Outcomes	№ of participants (studies) Follow‐up	Certainty of the evidence (GRADE)	Relative effect (95% CI)	*Anticipated absolute effects^ (95% CI)**
				Risk with psychosocial intervention alone	Risk difference with Pharmacologic intervention along with psychosocial intervention
Harmful alcohol use (continuous)	475 (4 RCTs)	⊕⊕⊝⊝ Low ^{1 2}	‐	The mean harmful alcohol use (continuous) was 0 SD	SMD 0.43 SD lower (0.61 lower to 0.24 lower)
Harmful alcohol use (dichotomous)	102 (1 RCT)	⊕⊝⊝⊝ Very low ^{1 3}	RR 0.62 (0.16 to 2.47)	Study population
				96 per 1,000	37 fewer per 1,000 (81 fewer to 141 more)
Retention	363 (3 RCTs)	⊕⊕⊕⊝ Moderate ³	RR 1.15 (0.95 to 1.40)	Study population
				491 per 1,000	74 more per 1,000 (25 fewer to 196 more)
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).  CI: confidence interval; RR: risk ratio.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

Brief interventions compared to brief advice, information, or assessment only for individuals with hazardous or harmful alcohol use
Patient or population: individuals with hazardous or harmful alcohol use Setting: Low‐ and middle‐income countries Intervention: Brief interventions Comparison: brief advice, information, or assessment only
Outcomes	№ of participants (studies) Follow‐up	Certainty of the evidence (GRADE)	Relative effect (95% CI)	*Anticipated absolute effects^ (95% CI)**
				Risk with brief advice, information, or assessment only	Risk difference with Brief interventions
Harmful alcohol use (continuous)	3913 (17 RCTs)	⊕⊝⊝⊝ Very low ^{1 2 3}	‐	The mean harmful alcohol use (continuous) was 0 SD	see comment
Harmful alcohol use (dichotomous)	1349 (4 RCTs)	⊕⊝⊝⊝ Very low ^{1 2 3}	not pooled	Study population
				not pooled	not pooled
Retention	5380 (12 RCTs)	⊕⊝⊝⊝ Very low ^{1 2 3}	not pooled	Study population
				not pooled	not pooled
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).  CI: confidence interval; RR: risk ratio.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

Other psychosocial intervention compared to usual care, brief intervention, or wait list for individuals with hazardous or harmful alcohol use
Patient or population: individuals with hazardous or harmful alcohol use Setting: Low‐ and middle‐income countries Intervention: Other psychosocial intervention Comparison: usual care, brief intervention, or wait list
Outcomes	№ of participants (studies) Follow‐up	Certainty of the evidence (GRADE)	Relative effect (95% CI)	*Anticipated absolute effects^ (95% CI)**
				Risk with usual care, brief intervention, or wait list	Risk difference with Other psychosocial intervention
Harmful alcohol use	2106 (12 RCTs)	⊕⊝⊝⊝ Very low ^{1 2 3}	‐	The mean harmful alcohol use was 0	see comment
Retention	1664 (9 RCTs)	⊕⊝⊝⊝ Very low ^{1 2 3 4}	not pooled	Study population
				not pooled	not pooled
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).  CI: confidence interval;RR: risk ratio.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

Medication	Administration	Indication	Intended effect
Acamprosate	Oral (3 times daily)	Maintenance of abstinence from alcohol	Reduces symptoms of protracted abstinence (e.g. anxiety, craving)
Disulfiram	Oral (once daily)	Promote abstinence from alcohol	Produces adverse effects when alcohol is consumed
Naltrexone	Oral (once daily) Injection (once monthly)	Prevent alcohol craving	Reduces the euphoric effects of alcohol

Adverse events
Study	Heading 1	Heading 2
Baltieri 2003	Experimental: 13% diarrhea, 10% pruritis, 7% polyuria, 10% headache	Control: 11% diarrhea, 4% pruritis, 11% polyuria, 4% headache

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Remission	1	75	Risk Ratio (M‐H, Random, 95% CI)	2.12 [1.00, 4.52]
1.2 Retention	3	247	Risk Ratio (M‐H, Random, 95% CI)	1.13 [0.89, 1.44]
1.3 Adverse events	0		Other data	No numeric data

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
2.1 Harmful alcohol use (continuous)	4	475	Std. Mean Difference (IV, Random, 95% CI)	‐0.43 [‐0.61, ‐0.24]
2.2 Harmful alcohol use (dichotomous)	1	102	Risk Ratio (M‐H, Random, 95% CI)	0.62 [0.16, 2.47]
2.3 Alcohol consumption	1	71	Std. Mean Difference (IV, Random, 95% CI)	0.34 [‐0.13, 0.81]
2.4 Remission	4	462	Risk Ratio (M‐H, Random, 95% CI)	1.19 [1.01, 1.40]
2.5 Retention	3	363	Risk Ratio (M‐H, Random, 95% CI)	1.15 [0.95, 1.40]
2.6 Adverse events	0		Other data	No numeric data

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3.1 Remission	2	171	Risk Ratio (M‐H, Random, 95% CI)	0.58 [0.42, 0.79]
3.2 Retention	2	190	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.76, 1.19]
3.3 Adverse events	0		Other data	No numeric data

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
4.1 Remission	2	200	Risk Ratio (M‐H, Random, 95% CI)	1.78 [1.40, 2.25]
4.2 Retention	2	200	Risk Ratio (M‐H, Random, 95% CI)	1.02 [0.96, 1.08]

Outcome or subgroup title	No. of studies	Statistical method	Effect size
5.1 Harmful alcohol use (continuous)	17	Std. Mean Difference (IV, Random, 95% CI)	Totals not selected
5.2 Harmful alcohol use (dichotomous)	4	Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
5.3 Alcohol consumption	9	Std. Mean Difference (IV, Random, 95% CI)	Totals not selected
5.4 Remission	5	Risk Ratio (M‐H, Random, 95% CI)	Totals not selected
5.5 Retention	12	Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

Adverse events
Study	Heading 1	Heading 2
Ahmadi 2004	Experimental (n=58): 20 nausea, 13 lethargy, 5 nightmares, 7 dizziness, 10 insomnia, 14 headache, 14 anxiety	Control (n=58): 9 nausea, 0 nighmares, 1 dizziness, 4 insomnia, 6 headache, 10 anxiety
Correa Filho 2013	Experimental (n=50): 26 reported side effects (52%)	Control (n=52): 26 reported side effects (50%)
Likhitsathian 2013	Experimental (n=53): 3.8% headache, 1.9% fatigue, 1.9% somnolence, 0% back pain, 0% tremor, 0% dizziness, 0% numbness, 45.3% parasthesia, 15.1% taste perversion, 17.0% poor appetite, 17.0% impaired concentration, 20.7% pruritus, 1.9% psychomotor retardation, 1.9% joint pain, 0% nervousness, 0% tongue numbness, 0% flushed face	Control (n=53): 0% headache, 1.9% fatigue, 5.7% somnolence, 1.9% back pain, 3.8% tremor, 1.9% dizziness, 1.9% numbness, 17.0% parasthesia, 5.7% taste perversion, 9.4% poor appetite, 11.3% impaired concentration, 15.1% pruritus, 0% psychomotor retardation, 0% joint pain, 1.9% nervousness, 3.8% tongue numbness, 1.9% flushed face

*Study characteristics*
Methods	Study design: Rrandomized controlled trial Country: Iran Setting: outpatient clinic Eligibility criteria: included were adult males with a current diagnosis of alcohol dependence and between 3‐30 days abstinent prior to enrollment. Excluded were individuals with other substance use disorders; current use of opioids, neuroleptics, or disulfiram; bilirubin level and alanine aminotransferase greater than five times normal levels. Duration of follow‐up: 36 weeks Informed consent: all participants provided informed consent Ethical approvals: not listed
Participants	Sample size: 116 (58 intervention, 58 control) Description of the target population: males in outpatient treatment for alcohol use disorder Age: 42.97 years (SD = 9.17) Sex: 100% male Race/Ethnicity: Not listed Marital status: 87.07% married, 12.93% single Harmful alcohol use (baseline): not listed Co‐occurring disorders: not listed
Interventions	Type: pharmacologic + non‐pharmacologic Description: naltrexone and alcohol counseling (consequences and relapse prevention) Duration and frequency: 50 mg/day of naltrexone and 12 weekly 30‐minute counseling sessions Delivery and provider: not listed Comparison group: placebo and alcohol counseling (consequences and relapse prevention)
Outcomes	Primary outcome(s): abstinence/remission, relapse Primary outcome measurement tool(s): Timeline follow‐back Secondary outcome(s) :Retention in Treatment,Adverse events Secondary outcome measurement tool(s): not listed Time points: 4, 8, 12, 16, 20, 24, 28, 32, 36 weeks
Notes	Study funding and conflicts of interest: none listed Linked study records: none
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Subjects were allocated randomly to receive either naltrexone 50mg/day or an identical placebo capsule for 36 weeks." Pg. 35
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote:"Patients and research staff were blind to the capsule prescribed" Pg. 35
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote:"Patients and research staff were blind to the capsule prescribed" Pg. 35
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Not described
Selective reporting (reporting bias)	Unclear risk	No protocol available

*Study characteristics*
Methods	Study design: randomized controlled trial Country: Russia Setting: health facility Eligibility criteria: included were males who reported weekly consumption of 250 mL or more of ethanol over the past year as well as extended periods of binge drinking (i.e., Zapoi) in the last year, using drinking surrogates (i.e. non‐beverage alcohol) in the last year, excessive drunkenness, and/or going to sleep clothed due to being drunk twice or more per week on average over the past year. Excluded were males who refused to have a baseline health check or refused at baseline to be re‐interviewed for follow‐up. Duration of follow‐up: 3‐months Informed consent: men randomized to intervention received an information sheet and provided consent for participating in the intervention and follow‐up. Men randomized to control provided general consent to be followed up Ethical approvals: not listed
Participants	Sample size: 441 (221 intervention, 220 control) Description of the target population: working age men with hazardous alcohol use Age: 30‐59 years Sex: 100% male Race/Ethnicity: not listed Marital status: not listed Harmful alcohol use (baseline): 71.6% self‐reported hazardous alcohol use; 93.9% proxy‐reported hazardous alcohol use Co‐occurring disorders: not listed
Interventions	Type: non‐pharmacologic Description: brief motivational interviewing Duration and frequency: 2 required and 2 optional sessions Delivery and provider: narcologist (specialists in treating alcohol and other drug use disorders), psychiatrists, social workers, school psychologists Comparison group: general health promotion and feedback sent by mail after general health check
Outcomes	Primary outcome(s): hazardous and harmful drinking Primary outcome measurement tool(s): Defined as 1+ occurrences of zapoi in the past month, use of alcohol surrogates in the past month, hangover on average twice or more per week in past month, or 250 mL or more of ethanol in the past week Secondary outcome(s): Aalcohol consumption, Treatment compliance Secondary outcome measurement tool(s): average consumption ‐ average weekly consumption of ethanol in past month >250 mL; Treatment compliance ‐ Both MI sessions before 3 months follow‐up Time points: 3‐months
Notes	Study funding and conflicts of interest: Wellcome Trust Linked study records: none
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Data collected at the baseline re‐interview were sent to the randomisation service in London, allowing participants to be allocated in a 1:1 ratio to MI intervention or no MI. Minimisation criteria (age, surrogate use in past year, and living alone status) were used to ensure a reasonable balance of confounding factors. An online randomisation program was used to generate the random allocation." Pg. 3
Allocation concealment (selection bias)	Low risk	Quote:"At the end of the health check, the doctor undertaking the physical examination opened a sealed envelope containing the allocation." Pg. 3
Blinding of participants and personnel (performance bias) All outcomes	High risk	Participants and personnel cannot be blinded for this type of intervention Quote:"Telling the control group about the alcohol‐specific MI intervention and the alcohol‐specific outcomes, would have sensitised the control group to our primary research interest and thereby in itself may have altered behaviour. This could have also diluted any effect of the MI intervention" Pg. 3
Blinding of outcome assessment (detection bias) All outcomes	High risk	Outcomes reported by participant not blind to intervention
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote:"Follow up at 3 months was very high (97% of those having a health check), and similar in the two trial arms (183 in the intervention and 187 in the control)." Pg. 5
Selective reporting (reporting bias)	Unclear risk	No protocol available

*Study characteristics*
Methods	Study design: randomized controlled trial Country: Turkey Setting: hospital specialized addiction unit Eligibility criteria: individuals who were 18‐65 years of age, met criteria for alcohol dependence and depressive disorder, were experiencing a current depressive episode, but had no serious physical illness. Female participants also needed to be adequately protected against pregnancy. Excluded were individuals with another major psychiatric disorder, a history of psychiatric problems other than depressive disorder, the presence of organic brain disease, a history of hypersensitivity to mirtazapine or amitriptyline, pregnant or breastfeeding, other substance (non‐alcohol, tobacco, or caffeine) use disorder, and having consumed alcohol during the study. Duration of follow‐up: 56 days Informed consent: all participants provided written informed consent Ethical approvals: all procedures were approved by Ege University Ethics Committee
Participants	Sample size: 36 (20 mirtazapine, 16 amitriptyline) Description of target population: patients seeking primary healthcare with alcohol dependence and depression Age: 44.0 years (range 18‐65) Sex: 8.3% female Race/Ethnicity: not reported Marital status: 63.9% married Harmful alcohol use (baseline): Michigant Alcoholism Screening Test (MAST): 38.9 (SD=6.1) Co‐occurring disorders: 100% major depressive disorder and current depressive episode
Interventions	Type: pharmacologic Description: mirtazapine following alcohol detoxification with diazepam taper and vitamin B Duration and frequency: started with 15 mg/day. On the third day patients were increased to 30 mg/day. At the end of the first week dose was increased to 45 mg to 60 mg/day if severity of symptoms persisted Delivery and provider: clinician delivered capsules consumed orally Comparison group: amitriptyline (50 mg/day increased to 100 mg/day on third day and 125‐150 mg/day at end of first week if severity of symptoms persisted) following detoxification with diazepam taper and vitamin B
Outcomes	Primary outcome(s): alcohol craving Primary outcome measurement tool(s): alcohol craving questionnaire developed by study investigators Secondary outcome(s): State anxiety, trait anxiety, Depression Secondary outcome measurement tool(s): Spielberger State‐Trait Anxiety Inventory (STAI); Hamilton Depression Rating Scale (HDRS) Time points: 0, 7, 14, 28, 42, 56 days
Notes	Study funding and conflicts of interest: not reported Linked study records: none
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "At the end of the alcohol detoxification treatment with diazepam (approximately 10–14 days), the patients with HDRS scores 14 were included in the study and they were randomly allocated to mirtazapine or amitriptyline treatment groups." Pg. 315
Allocation concealment (selection bias)	Unclear risk	Drugs were administered in identical looking opaque capsules, but unclear if allocation was concealed
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "Both the clinicians and patients were blind to the treatment." Pg. 315
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not described
Incomplete outcome data (attrition bias) All outcomes	High risk	Quote: "Initially, 97 patients were enrolled in the study but after the detoxification period there were only 44 patients meeting the criteria for current major depressive disorder. Eight of the patients dropped out (three of the patients dropped out due to adverse effects of drugs, one of them dropped out due to an another psychiatric disorder emerged during the study, two patients dropped out due to alcohol consumption in the treatment setting, and two patients decided not to remain in the study). Thirty‐six patients completed the study. Dropouts were not included in the analysis due to missing data." Pgs. 315‐316
Selective reporting (reporting bias)	Unclear risk	No protocol available

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
6.1 Harmful alcohol use	12		Std. Mean Difference (IV, Random, 95% CI)	Totals not selected
6.2 Alcohol consumption	7		Std. Mean Difference (IV, Random, 95% CI)	Totals not selected
6.3 Remission	7	1519	Risk Ratio (M‐H, Random, 95% CI)	1.44 [1.19, 1.76]
6.4 Retention	9		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

*Study characteristics*
Methods	Study design: randomized controlled trial Country: India Setting: inpatient substance use treatment center Eligibility criteria: included were patients admitted to the addiction treatment center with addiction to tobacco and alcohol, having a high level of tobacco dependence (Fagerstrom scale>5), and agreed to stay as inpatients in the treatment center for 25‐30 days. Excluded were participants with addiction only to alcohol and/or other substances and not tobacco, who were undergoing pharmacological interventions during the study period, who had known drug hypersensitivities, patients with epilepsy, pregnant, lactation, serious physical comorbidities, or low levels of dependence. Duration of follow‐up: 2 months Informed consent: not reported Ethical approvals: not reported
Participants	Sample size: 83 (27 reading‐writing therapy, 28 games‐narrative therapy, 28 motivational intervention only) Description of the target population: patients in inpatient treatment with alcohol and tobacco dependence Age: 32.2 years (SD=9.12) Sex: 100% male Race/Ethnicity: not reported Marital status: not reported Harmful alcohol use (baseline): practice: 2.89 (SD = 1.56) Co‐occurring disorders: 100% tobacco dependence
Interventions	Type: non‐pharmacologic Description: A) Reading‐writing therapy + motivational intervention: use of self‐help materials to motivate and guide behavior change. In each group session participants were given autobiographies of previous patients who had successful substance use treatment outcomes to read. In writing therapy, participants were given a diary and pen. They were asked to express their experience with substance use, adverse consequences, and potential benefits of reducing their substance use in these diaries; B) Games‐narrative therapy + motivational intervention: Cognitive, behavioral and motivational approaches to promote interaction between patients and divert participant's attention to rigorous activity to mask craving and withdrawal symptoms. The games included short mind games and puzzles. The narrative/story therapy consisted of sharing stories related to their personal life and addiction, including the relationship between their substance use and personal life circumstances. Delivery and frequency: A) not reported, group‐based; B) 2 hours per day for 25‐30 days of inpatient treatment, group or individual sessions Duration and provider: A) trained counselors Comparison group: motivational interviewing consisting of group counseling, individual counseling, and Anonymous meetings over the course of 25‐30 days of inpatient treatment; Provider was a trained counselor
Outcomes	Primary outcome(s): alcohol practice Primary outcome measurement tool(s): Knowledge, Attitudes, and Practices related to alcohol Secondary outcome(s): none Secondary outcome measurement tool(s): N/A Time points: 1, 2 months
Notes	Study funding and conflicts of interest: not reported Linked study records: none
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	Quote: "The randomization and group allocation were done on a quota basis in the de‐addiction center by the center in charge. The first five eligible participants admitted to the de‐addiction center were allotted to Group A, and then, the next five eligible participants to Group B and Group C, respectively. This group allocation strategy was followed as it was convenient to administer the intervention. The group code was entered on the assessment form of the participant following randomization and the information on the actual intervention offered to different groups was concealed from the investigator to ensure blinding in the study." Pg. 3
Allocation concealment (selection bias)	High risk	Quote: "The randomization and group allocation were done on a quota basis in the de‐addiction center by the center in charge. The first five eligible participants admitted to the de‐addiction center were allotted to Group A, and then, the next five eligible participants to Group B and Group C, respectively. This group allocation strategy was followed as it was convenient to administer the intervention. The group code was entered on the assessment form of the participant following randomization and the information on the actual intervention offered to different groups was concealed from the investigator to ensure blinding in the study." Pg. 3
Blinding of participants and personnel (performance bias) All outcomes	High risk	Participants and personnel cannot be blinded for this type of intervention
Blinding of outcome assessment (detection bias) All outcomes	High risk	Outcomes reported by participant not blind to intervention Quote: "The randomization and group allocation were done on a quota basis in the de‐addiction center by the center in charge. The first five eligible participants admitted to the de‐addiction center were allotted to Group A, and then, the next five eligible participants to Group B and Group C, respectively. This group allocation strategy was followed as it was convenient to administer the intervention. The group code was entered on the assessment form of the participant following randomization and the information on the actual intervention offered to different groups was concealed from the investigator to ensure blinding in the study." Pg. 3.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Not described
Selective reporting (reporting bias)	Unclear risk	Protocol not available

*Study characteristics*
Methods	Study design: cluster‐randomized controlled trial Country: Zimbabwe Setting: HIV clinics Eligibility criteria: adults living with HIV on combination antiretroviral therapy with hazardous or harmful alcohol use and without cognitive impairment. Duration of follow‐up: 6 months Informed consent: all participants will provide informed consent (specified in study protocol) Ethical approvals: study procedures were approved by the Medical Research Council of Zimbabwe, Stellenbosch University Human Research Ethics Committee, the Harare Hospital Ethics Committee, and the Ministry of Health Permanent Secretary of Zimbabwe.
Participants	Sample size: 234 (108 intervention, 126 control) Description of the target population: Adult HIV‐positive individuals on HAART in HIV care clinics in Zimbabwe with hazardous alcohol use Age: 43 years Sex: 79% male Race/Ethnicity: not reported Marital status: 62% married Harmful alcohol use (baseline): mean AUDIT score was 14.9 (SD = 6.3) in intervention group and 14.7 (SD = 6.2) in control group Co‐occurring disorders: not reported
Interventions	Type: non‐pharmacologic Description: motivational interviewing and cognitive behavioral therapy Duration and frequency: up to 10 sessions lasting 45‐60 minutes each and integrated into usual care Delivery and provider: registered general nurse Comparison group: mhGAP Intervention Guide Alcohol Module including personalized feedback and psychoeducation
Outcomes	Primary outcome(s): hazardous alcohol use Primary outcome measurement tool(s): AUDIT Secondary outcome(s): viral load, CD4, functionality, quality of life Secondary outcome measurement tool(s): blood samples were collected to measure viral load and CD4 count, WHODAS, WHOQoL HIV Time points: 0, 6 months
Notes	Study funding and conflicts of interest: Fogary International Center, National Institute of Nursing Research, National Institute of Mnetal Health, National Institute of Dental and Craniofacial Research, National Institute of Neurological Disorders and STroke, National Heart, Lung and Blood Institute, African Academy of Sciences, New Partnership for Africa's Development Planning and Coordinating Agency, Wellcome Trust, King's College London Partnership Fund Linked study records: Madhombiro 2017
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "We used a computer‐generated randomization schedule to allocate clusters to MI‐CBT and EUC arms in a 1:1 ratio." Pg. 2
Allocation concealment (selection bias)	Unclear risk	Not reported
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote: "Second, participants were not and could not be blinded to the allocation which was a limitation of our study." Pg. 8
Blinding of outcome assessment (detection bias) All outcomes	High risk	Quote: "However, the outcome assessors were blinded to the arm of the facility." Pg. 8 Outcome assessment based on self report by unblinded participant
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Quote: "Third, our study had differential loss to follow‐up (which was, however, not statisti‐ cally significant) with more participants lost in the control arm, which is a limitation. The loss to follow‐up was greater in the EUC arm than in the MI‐CBT arm. The effect of the MI‐CBT intervention on reduction in alcohol use and in viral load was greater than the effect of the EUC intervention, although this was only significant at the 0.05 level for alcohol use and was non‐significant in the case of viral load. If the follow‐up had been more equal, we might have been able to demonstrate a stronger effect of the intervention on alcohol use and even on viral load." Pg. 8
Selective reporting (reporting bias)	Low risk	Study outcomes align with those reported in study protocol (Madhombiro 2017)

*Study characteristics*
Methods	Study design: cluster ‐ controlled trial Country: Thailand Setting: outpatient hospital setting Eligibility criteria: Included were patients between 18‐60 years of age, able to participate at 3‐ and 6‐month follow‐up, able to give contract details for 2‐3 other people, having a permanent address, without pending incarceration in next 3 months, absence of cognitive impairment or severe behavior problems, not intoxicated or going through withdrawal, not currently in alcohol or nicotine treatment, and with moderate risk of alcohol and tobacco problems. Excluded were individuals with low or high risk of alcohol problems, or who had frequently injected drugs in the past 3 months. Duration of follow‐up: 6‐months Informed consent: all participants provided informed consent Ethical approvals: Mahidol University Research and Ethics Committee
Participants	Sample size: 620 (215 joint alcohol and tobacco brief intervention, 199 tobacco only brief intervention, 206 control alcohol only brief intervention) Description of the target population: patients seeking care in outpatient hospital department with moderate risk for problematic tobacco and alcohol use Age: 33.7 years Sex: 2.3% female Race/Ethnicity: not reported Marital status: 79.4% married Harmful alcohol use (baseline): Alcohol ASSIST = 16.8 Co‐occurring disorders: Tobacco ASSIST = 20.1
Interventions	Type: non‐pharmacologic Description: ASSIST‐linked brief intervention for heavy drinking smokers with feedback, discussion on the relationship between drinking and smoking, the potential effects of alcohol on smoking cessation, an emphasis on personal responsibility for behavior change, advice to avoid or minimize drinking during smoking cessation, strategies to carry out behavior change, use of empathy, and encouragement of self‐efficacy Duration and frequency: 3 sessions within a 3‐week period Delivery and provider: trained counselors Comparison group: 1) Three sessions of ASSIST‐linked intervention focusing on alcohol use, 2) Three sessions of ASSIST‐linked intervention focusing on tobacco use
Outcomes	Primary outcome(s): hazardous alcohol use Primary outcome measurement tool(s): ASSIST Alcohol Scores Secondary outcome(s): alcohol consumption, non‐problematic/low‐risk drinking (remission) Secondary outcome measurement tool(s): ASSIST, Timeline Followback Time points: 0‐, 3‐, 6‐months
Notes	Study funding and conflicts of interest: The Thai Health Promotion Foundation Linked study records: None
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Randomisation was conducted using a secure remote randomization service. The 4 out of 8 district hospitals were randomly assigned to the treatment (co‐joint intervention) and control arms (alcohol only or tobacco only interventions). Patients moderately at risk for conjoint alcohol and tobacco use were randomized to either the treatment or control groups." Pg. 3
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote: "Participants (clinic staff members and patients) were not blind to their intervention status." Pg. 3
Blinding of outcome assessment (detection bias) All outcomes	High risk	Outcomes reported by participant not blind to intervention "However, to protect against information biases in the reporting of substance use, the data collection team who assessed the outcomes were blind to the hospital’s status as intervention." Pg. 3
Incomplete outcome data (attrition bias) All outcomes	High risk	Quote: "Researchers used an intent‐to‐treat analysis by including all participants who completed baseline assessments and who were randomized to intervention conditions." Pg. 5 "Listwise deletion (i.e., using complete cases only) in the context of generalized estimating equations (GEE) was used with missing data. The extent of the missing component was 27.4 % at six months." Pg. 5 High levels and poor handling (complete case analysis) of missing data
Selective reporting (reporting bias)	Unclear risk	Protocol not available

*Study characteristics*
Methods	Study design: Cluster randomized controlled trial Country: India Setting: Chennai City zones where TB investigations and treatment are offered through the Revised National Tuberculosis Control Programme (RNTCP) Eligibility criteria: Included were zones with TB investigations and treatment offered through the RNTCP in Chennai. Participants were included if they were new TB patients, 18 years and older who were registered for an anti‐tuberculosis treatment. Duration of follow‐up: 6‐months Informed consent: All participants provided written informed consent Ethical approvals: Study procedures were approved by the National Institute for Research in Tuberculosis, the Indian Council of Medical Research, and Chennai Corporation
Participants	Sample size: 298 (113 alcohol counseling, 185 usual care) Description of the target population: Patients with tuberculosis Age: 44 years Sex: Not reported Race/Ethnicity: Not reported Marital status: 72% married Harmful alcohol use (baseline): 37% hazardous alcohol use, 20% harmful use, 33% dependence Co‐occurring disorders: 76% were new cases of tuberculosis, 24% were retreatment cases
Interventions	Type: Non‐pharmacologic Description: Alcohol counseling including discussion of the relationship between alcohol and tuberculosis, and the effect of alcohol on physical health, family and society. Duration and frequency: Four 45‐60 minute sessions at 0, 2, 4, and 6 months Delivery and provider: Trained lay counselor Comparison group: Usual care for tuberculosis without alcohol counseling
Outcomes	Primary outcome(s): Alcohol consumption Primary outcome measurement tool(s): AUDIT Secondary outcome(s): Adherence to anti‐tuberculosis treatment Secondary outcome measurement tool(s): Regular adherence, irregular adherence, or lost to follow‐up Time points: 0 and 6 months
Notes	Study funding and conflicts of interest: UNAIDS Linked study records: None
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"This was a pilot, two‐arm, parallel‐cluster randomised trial carried out in four zones (TB units) where TB investigations and treatment are offered through the Revised National Tuberculosis Control Programme (RNTCP). The four zones were divided into two strata, two of which were high‐prevalence and two were low‐prevalence zones. Within each stratum, one zone was allocated to the intervention arm and the other to the control arm. Here the zones were the units of randomisation (clusters)" Pg. 948
Allocation concealment (selection bias)	High risk	"For administrative purposes, Chennai City is divided into 10 corporation zones and 155 divisions. This was a pilot, two‐arm, parallel‐cluster randomised trial carried out in four zones (TB units) where TB investigations and treatment are offered through the Revised National Tuberculosis Control Programme (RNTCP). The four zones were divided into two strata, two of which were high‐prevalence and two were low‐prevalence zones. Within each stratum, one zone was allocated to the intervention arm and the other to the control arm. Here the zones were the units of randomisation (clusters)" Pg. 948
Blinding of participants and personnel (performance bias) All outcomes	High risk	Participants and personnel cannot be blinded for this type of intervention
Blinding of outcome assessment (detection bias) All outcomes	High risk	Outcomes reported by participant not blind to intervention
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	"Information on overall treatment adherence was available for 104 (92%) intervention group participants and for 173 (94%) control group participants." Pg. 950
Selective reporting (reporting bias)	High risk	Does not provide quantitative results by alcohol risk level.

Study	Reason for exclusion
Aira 2013	Wrong population ‐ study included some non‐drinkers and non‐problematic drinkers. There was no subgroup analysis that included only people with unhealthy alcohol use
Burnhams 2015	Wrong population ‐ study included some non‐drinkers and non‐problematic drinkers. There was no subgroup analysis that included only people with unhealthy alcohol use
Chaudhury 2016	Wrong population ‐ majority of sample were non‐drinkers or non‐problematic drinkers
Dawson 2012	Wrong intervention ‐ universal community education program
Holla 2020	Wrong intervention ‐ transcranial direct current stimulation (tDCS)
Kalichman 2007	Wrong population ‐ majority of sample were non‐problematic drinkers
Kalichman 2008	Wrong population and outcomes ‐ not all participants met criteria for hazardous alcohol use. The authors did conduct a moderation analysis by heavy drinking, but the primary outcomes were related to high‐risk sexual behaviors as opposed to alcohol use.
Kalichman 2011	Wrong population ‐ study included non‐drinkers. There is a moderation analysis that evaluates the effect of intervention on sexual risk outcomes for light and heavy drinkers, but this analysis is not available for alcohol outcomes.
Mertens 2014	Wrong population ‐ included participants with non‐alcohol substance use and did not include a subgroup analysis of participants with problematic alcohol use
Myers 2016	Wrong population ‐ included participants with non‐alcohol substance use and did not include a subgroup analysis of participants with problematic alcohol use
Rongkavilit 2013	Wrong population ‐ included non‐drinkers
Rotheram‐Borus 2015	Wrong population ‐ included non‐drinkers and non‐problematic drinkers
Sorsdahl 2015	Wrong population ‐ included participants with non‐alcohol substance use and did not include a subgroup analysis of participants with problematic alcohol use
Thapinta 2014	Wrong intervention ‐ intervention was aimed at treating depression, not alcohol use disorder
Ward 2015	Wrong population ‐ included participants with non‐alcohol substance use and did not include a subgroup analysis of participants with problematic alcohol use
Wechsberg 2006	Wrong population ‐ eligibility criteria focused on cocaine, not alcohol use
Wechsberg 2008	Wrong population ‐ included participants with non‐alcohol substance use and did not include a subgroup analysis of participants with problematic alcohol use
Wechsberg 2016	Wrong population ‐ inclusion criteria included men reporting that they frequented shebeens and drank alcohol, not necessarily that they displayed problematic alcohol use

Methods	Cluster randomized controlled trial
Participants	767 non‐pregnant women at risk for an alcohol‐exposed pregnancy in OB/GYN clinics in Russia
Interventions	Two face‐to‐face 5‐minute sessions incorporated into routine clinical OB/GYN care visits
Outcomes	Alcohol consumption, alcohol patterns (latent transition analysis)
Notes	Conference abstract only; Author also published abstracts in 2012, 2013, 2014, and 2015 that appear to report on same trial; Authors contacted for full report on November 7, 2019 Linked study records (Balachova 2012, Balachova 2013, Balachova 2014, Balachova 2015)

Methods	Randomized controlled trial
Participants	220 inpatients with alcohol dependence in Russia
Interventions	Psychoanalysis two times per week for one month (90‐minute sessions) vs. psycho‐evacuation sessions with elements of behavioral therapy
Outcomes	Alcohol dependence symptoms, Quality of life, remission
Notes	Abstract only; Emailed author on April 9, 2020

Methods	TBD
Participants	1336 clients from 18 Beichuan count village hospitals in Sichuan, China
Interventions	15‐30 minute brief intervention + general health education vs. general health education alone
Outcomes	Unhealthy alcohol use, substance use knowledge, depression, anxiety, well‐being
Notes	Conference abstract only; Unable to locate author's contact information

Methods	TBD
Participants	908 patients in primary care in Russia
Interventions	Advice by a narcologist vs. preventive counseling vs. no counseling
Outcomes	Alcohol consumption
Notes	Abstract only; Unable to locate author's contact information

PERMALINK

Psychosocial and pharmacologic interventions to reduce harmful alcohol use in low‐ and middle‐income countries

M Claire Greene

Jeremy Kane

Michelle Alto

Ali Giusto

Kathryn Lovero

Melissa Stockton

Jasmine McClendon

Terriann Nicholson

Milton L Wainberg

Renee M Johnson

Wietse Anton Tol

Abstract

Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

Plain language summary

Summary of findings

Summary of findings 1. Pharmacologic intervention compared to placebo for individuals with alcohol use disorder.

Summary of findings 2. Pharmacologic intervention along with psychosocial intervention compared to psychosocial intervention alone for individuals with alcohol use disorder.

Summary of findings 3. Pharmacologic intervention compared to another pharmacologic intervention for individuals with alcohol use disorder.

Summary of findings 4. Pharmacologic intervention compared to another pharmacologic intervention in addition to psychosocial intervention for individuals with alcohol use disorder.

Summary of findings 5. Brief interventions compared to brief advice, information, or assessment only for individuals with hazardous or harmful alcohol use.

Summary of findings 6. Other psychosocial intervention compared to usual care, brief intervention, or wait list for individuals with hazardous or harmful alcohol use.

Background

Description of the condition

Description of the intervention

Pharmacologic treatments

1. Summary of medication assisted treatment approved for harmful alcohol use.

Psychosocial interventions

Combined pharmacologic and psychosocial interventions

How the intervention might work

Why it is important to do this review

Objectives

Methods

Criteria for considering studies for this review

Types of studies

Types of participants

Types of interventions

Types of outcome measures

Primary outcomes

Secondary outcomes

Search methods for identification of studies

Electronic searches

Searching other resources

Data collection and analysis

Selection of studies

Data extraction and management

Assessment of risk of bias in included studies

Measures of treatment effect

Continuous data

Dichotomous data

Unit of analysis issues

Dealing with missing data

Assessment of heterogeneity

Assessment of reporting biases

Data synthesis

Qualitative data synthesis

Quantitative data synthesis

Subgroup analysis and investigation of heterogeneity

Sensitivity analysis

Summary of findings and assessment of the certainty of the evidence

Summary of findings tables

Grading of evidence

Results

Description of studies

Results of the search

1.

Included studies

Setting

Participants

Interventions and comparators

Outcomes

Excluded studies

Studies awaiting classification

Study name	EFICO
Methods	Randomized controlled trial
Participants	Adults scheduled for surgery who are current smokers or risky alcohol drinkers
Interventions	Brief counseling
Outcomes	Behavior change; Risky drinking; Smoking
Starting date	2018
Contact information
Notes	ClinicalTrials.gov Identifier: NCT03521622

Study name	Computer‐based alcohol reduction intervention
Methods	Randomized controlled trial
Participants	Females ages 21‐45 years receiving HIV medical care (including antiretroviral therapy) with HCV infection and recent alcohol use
Interventions	Computer‐based alcohol reduction intervention including cognitive behavioral therapy modules vs. usual care
Outcomes	Alcohol use (EtG), PEth, HIV viral load, CD4 cell count, liver damage (FibroTest), liver stiffness
Starting date	January 3, 2018
Contact information	Ralph DiClemente
Notes	Study expected to end in 2020

Study name	Alcohol Use Disorders ‐ Mobile Based Brief Intervention Treatment (AMBIT)
Methods	Randomized controlled trial
Participants	Adults in educational institutions and male adults in workplaces/primary health centers who have a mobile phone and are hazardous drinkers (India)
Interventions	Mobile‐based intervention involving messages and calls 2‐3 times per week over 8 weeks. Messages cover topics related to self‐awareness, self‐reflection, motivational messages, safe drinking, alcohol reduction, drinking management, risk management, craving management, drinking alternatives, health education, personalized feedback and information, help‐seeking resources, and goal setting vs. face‐to‐face mhGAP single‐session brief intervention vs. active control involving an educational leaflet
Outcomes	Frequency of drinking (TLFB), quantity of drinking, heavy drinking, intensity of drinking
Starting date	September 17, 2019
Contact information	Danielle Fernandes
Notes	Study expected to end April 30, 2020

Study name	KISOBOKA
Methods	Randomized controlled trial
Participants	HIV‐positive adults working in the fishing industry who have been on antiretroviral therapy for at least 6 months, have an HIV viral load greater than 200 or less than 90% adherence in the past 2 weeks, consume 5 or more drinks per occasion two or more times per month, have a mobile phone, and are not planning on moving outside of the study area (Wakiso District, Uganda) within the next 6 months
Interventions	KISOBOKA intervention (combination of behavioral components ‐ alcohol screening, financial literacy, goal‐setting, alcohol counseling, HIV care engagement ‐ and structural components ‐ changing the mode of work payment from cash to mobile money) vs. screening and referral
Outcomes	Frequency of heavy/binge drinking, HIV care engagement, ART adherence, PEth, HIV viral load
Starting date	September 2019
Contact information	Susan M. Kiene
Notes	Study expected to end July 2021

Study name	Comunica
Methods	Randomized cross‐over study
Participants	Gay/bisexual males 16+ years in Romania who reported 3 or more acts of condomless anal sex with an HIV‐positive or status‐unknown partner in the prior 3 months, 15 or more days of heavy drinking the past 3 months, own a mobile device, and are HIV‐negative
Interventions	Comunica: a 60‐minute live chat session delivered by a trained psychologist on a mobile platform that focuses on sexual health, motivation to change their HIV risk behaviors and alcohol use, and behavioral skills necessary for reducing their risk vs. education attention control
Outcomes	Sexual behavior, alcohol use (TLFB), hazardous alcohol use (AUDIT), depression, anxiety, HIV knowledge, alcohol effects, readiness for change, motivation to use condoms, safer‐sex self‐efficacy, confidence in reducing alcohol use, rejection sensitivity, sexual orientation concealment, assertiveness, sexual minority identity, LGBT victimization, perceived social support
Starting date	May 13, 2019
Contact information	Corina Lelutiu‐Weinberger; John Pachankis
Notes	Study expected to end July 2024

Study name	ASF in the treatment of patients with alcohol dependence
Methods	Randomized placebo‐controlled trial
Participants	Adults (18‐65 years) diagnosed with alcohol dependence without obvious withdrawal symptoms
Interventions	ASF (a compound of traditional Chinese medicine)
Outcomes	Alcohol consumption, abstinence
Starting date
Contact information
Notes

Study name	Drinkers' Intervention to Prevent Tuberculosis (DIPT Study)
Methods	Randomized controlled trial
Participants	HIV‐positive adults prescribed antiretroviral therapy for at least 6 months, a positive tuberculin skin test, AST and ALT less than twice the upper limit of normal, no history of active TB or TB treatment/preventive therapy who report heavy alcohol use and live within 2 hours from the study site in Uganda
Interventions	Escalating economic incentives (EtG tests) vs. Escalating incentives (IsoScreen tests) vs. Escalating incentives (EtG + IsoScreen tests) vs. not intervention
Outcomes	Non‐heavy drinking (AUDIT‐C + PEth), isoniazid treatment adherence
Starting date	April 16, 2018
Contact information	Nneka Emenyonu
Notes	Study expected to end February 2022

Study name	PRACT
Methods	Adaptive randomized trial
Participants	Adults seeking care at an emergency department for acute injury who are not clinically intoxicated and have either disclosed alcohol use prior to the injury, screened positive for hazardous or harmful alcohol use, or test positive for alcohol consumption on a breathalyzer.
Interventions	Variations of a brief intervention involving a one‐time nurse‐led motivational interview (MI) session in the emergency department vs. one MI session with weekly standard text boosters vs. one MIsession with weekly personalized boosters
Outcomes	Binge drinking, frequency of alcohol use, quantity of alcohol use, alcohol‐related harms, alcohol use disorder, depression
Starting date	2020
Contact information
Notes

Study name	Project MIND
Methods	Cluster‐randomized controlled trial
Participants	Adults with hazardous alcohol use and receiving treatment for diabetes or HIV, but not currently receiving treatment for alcohol use
Interventions	Motivational interviewing (MI) and problem solving therapy (PST) delivered in 3 sessions over 6 weeks with 1 optional booster session
Outcomes	Psychosocial functioning, Depression, Hazardous alcohol use (AUDIT)
Starting date	2017
Contact information	Ms. Vimbayi Mutyambizi‐Mafunda
Notes	Study expected to end in 2020

Study name	AMBIT
Methods	Randomized controlled trial
Participants	Adults in educational institutions, workplaces, and primary health centers who report hazardous drinking and own a mobile phone
Interventions	Mobile‐based brief intervention (AMBIT)
Outcomes	Percent days abstinent, quantity of alcohol use, percent days heavy drinking, intensity of drinking
Starting date	2019
Contact information
Notes	Clinical Trials identifier: NCT04078360