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

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Health Organization International Clinical Trials Registry Platform, Web of Science, and Opengrey database to identify unpublished or ongoing studies.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.

Primary-level and community worker interventions for the prevention of mental disorders and the promotion of well-being in low- and middle-income countries.

BACKGROUND: There is a significant research gap in the field of universal, selective, and indicated prevention interventions for mental health promotion and the prevention of mental disorders. Barriers to closing the research gap include scarcity of skilled human resources, large inequities in resource distribution and utilization, and stigma. OBJECTIVES: To assess the effectiveness of delivery by primary workers of interventions for the promotion of mental health and universal prevention, and for the selective and indicated prevention of mental disorders or symptoms of mental illness in low- and middle-income countries (LMICs). To examine the impact of intervention delivery by primary workers on resource use and costs. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, Global Index Medicus, PsycInfo, WHO ICTRP, and ClinicalTrials.gov from inception to 29 November 2021. SELECTION CRITERIA: Randomized controlled trials (RCTs) of primary-level and/or community health worker interventions for promoting mental health and/or preventing mental disorders versus any control conditions in adults and children in LMICs. DATA COLLECTION AND ANALYSIS: Standardized mean differences (SMD) or mean differences (MD) were used for continuous outcomes, and risk ratios (RR) for dichotomous data, using a random-effects model. We analyzed data at 0 to 1, 1 to 6, and 7 to 24 months post-intervention. For SMDs, 0.20 to 0.49 represented small, 0.50 to 0.79 moderate, and ≥ 0.80 large clinical effects. We evaluated the risk of bias (RoB) using Cochrane RoB2. MAIN RESULTS: Description of studies We identified 113 studies with 32,992 participants (97 RCTs, 19,570 participants in meta-analyses) for inclusion. Nineteen RCTs were conducted in low-income countries, 27 in low-middle-income countries, 2 in middle-income countries, 58 in upper-middle-income countries and 7 in mixed settings. Eighty-three RCTs included adults and 30 RCTs included children. Cadres of primary-level workers employed primary care health workers (38 studies), community workers (71 studies), both (2 studies), and not reported (2 studies). Interventions were universal prevention/promotion in 22 studies, selective in 36, and indicated prevention in 55 RCTs. Risk of bias The most common concerns over risk of bias were performance bias, attrition bias, and reporting bias. Intervention effects 'Probably', 'may', or 'uncertain' indicates 'moderate-', 'low-', or 'very low-'certainty evidence. *Certainty of the evidence (using GRADE) was assessed at 0 to 1 month post-intervention as specified in the review protocol. In the abstract, we did not report results for outcomes for which evidence was missing or very uncertain. Adults Promotion/universal prevention, compared to usual care: - probably slightly reduced anxiety symptoms (MD -0.14, 95% confidence interval (CI) -0.27 to -0.01; 1 trial, 158 participants) - may slightly reduce distress/PTSD symptoms (SMD -0.24, 95% CI -0.41 to -0.08; 4 trials, 722 participants) Selective prevention, compared to usual care: - probably slightly reduced depressive symptoms (SMD -0.69, 95% CI -1.08 to -0.30; 4 trials, 223 participants) Indicated prevention, compared to usual care: - may reduce adverse events (1 trial, 547 participants) - probably slightly reduced functional impairment (SMD -0.12, 95% CI -0.39 to -0.15; 4 trials, 663 participants) Children Promotion/universal prevention, compared to usual care: - may improve the quality of life (SMD -0.25, 95% CI -0.39 to -0.11; 2 trials, 803 participants) - may reduce adverse events (1 trial, 694 participants) - may slightly reduce depressive symptoms (MD -3.04, 95% CI -6 to -0.08; 1 trial, 160 participants) - may slightly reduce anxiety symptoms (MD -2.27, 95% CI -3.13 to -1.41; 1 trial, 183 participants) Selective prevention, compared to usual care: - probably slightly reduced depressive symptoms (SMD 0, 95% CI -0.16 to -0.15; 2 trials, 638 participants) - may slightly reduce anxiety symptoms (MD 4.50, 95% CI -12.05 to 21.05; 1 trial, 28 participants) - probably slightly reduced distress/PTSD symptoms (MD -2.14, 95% CI -3.77 to -0.51; 1 trial, 159 participants) Indicated prevention, compared to usual care: - decreased slightly functional impairment (SMD -0.29, 95% CI -0.47 to -0.10; 2 trials, 448 participants) - decreased slightly depressive symptoms (SMD -0.18, 95% CI -0.32 to -0.04; 4 trials, 771 participants) - may slightly reduce distress/PTSD symptoms (SMD 0.24, 95% CI -1.28 to 1.76; 2 trials, 448 participants). AUTHORS' CONCLUSIONS: The evidence indicated that prevention interventions delivered through primary workers - a form of task-shifting - may improve mental health outcomes. Certainty in the evidence was influenced by the risk of bias and by substantial levels of heterogeneity. A supportive network of infrastructure and research would enhance and reinforce this delivery modality across LMICs.