Combined pharmacological and psychosocial interventions for alcohol use disorder.

Abstract

Background: Alcohol use disorder (AUD) is a mental disorder characterised by a strong desire to consume alcohol and impaired control of alcohol use, with devastating consequences. Many people with AUD do not respond to psychosocial or pharmacological interventions when these are provided alone. Combining these interventions may improve the response to treatment, though evidence remains limited.

Objectives: To assess the effects of combined pharmacological and psychosocial interventions for the treatment of AUD in adults.

Search methods: We searched CENTRAL, MEDLINE, Embase, three other databases, and two trials registers in November 2023, without language restrictions.

Selection criteria: We included randomised controlled trials (RCTs) comparing combined pharmacological and psychosocial interventions versus pharmacological or psychosocial interventions alone, or no intervention/treatment as usual (TAU), in adults with AUD. Our primary outcomes were continuous abstinent participants, frequency of use (measured as heavy drinkers, percentages of abstinent days, heavy-drinking days), amount of use (number of drinks per drinking day), adverse events, serious adverse events, dropouts from treatment, and dropouts due to adverse events.

Data collection and analysis: We assessed risk of bias using Cochrane's RoB 1 tool, performed random-effects meta-analyses, and evaluated the certainty of evidence according to the GRADE approach.

Main results: We included 21 RCTs (4746 participants). The most studied pharmacological and psychosocial interventions were naltrexone (81.0%) and cognitive behavioural therapy (66.7%), respectively. Most participants were men (74%), aged about 44 years, with AUD, without comorbid mental disorders or other substance use disorders; 15 RCTs detoxified participants before treatment. We judged 28.5% of the studies as at low risk of bias for random sequence generation, allocation concealment, performance bias for objective and subjective outcomes, and detection bias for subjective outcomes; all studies were at low risk of detection bias for objective outcomes; 85.7% of studies were at low risk of attrition bias; 14.2% of studies were at low risk of reporting bias. 1) Compared to psychosocial intervention alone, combined pharmacological and psychosocial interventions probably reduce the number of heavy drinkers (above the clinically meaningful threshold (MID) of 2%; absolute difference (AD) -10%, 95% confidence interval (CI) -18% to -2%; risk ratio (RR) 0.86, 95% CI 0.76 to 0.97; 8 studies, 1609 participants; moderate-certainty evidence). They may increase continuous abstinent participants (MID 5%; AD 5%, 95% CI 1% to 11%; RR 1.17, 95% CI 1.02 to 1.34; 6 studies, 1184 participants; low-certainty evidence). They probably have little to no effect on: • the rate of abstinent days (MID 8%; mean difference (MD) 4.16, 95% CI 1.24 to 7.08; 10 studies, 2227 participants); • serious adverse events (MID 1%; AD -2%, 95% CI -3% to 0%; RR 0.20, 95% CI 0.03 to 1.12; 4 studies; 524 participants); • dropouts from treatment (MID 10%; AD -3%, 95% CI -5% to 0%; RR 0.89, 95% CI 0.79 to 1.01; 15 studies, 3021 participants); and • dropouts due to adverse events (MID 5%; AD 2%, 95% CI 0% to 5%; RR 1.91, 95% CI 1.04 to 3.52; 8 studies, 1572 participants) (all moderate-certainty evidence). They may have little to no effect on: • heavy-drinking days (MID 5%; MD -3.49, 95% CI -8.68 to 1.70; 4 studies, 470 participants); • number of drinks per drinking day (MID 1 drink; MD -0.57, 95% CI -1.16 to 0.01; 7 studies, 805 participants); and • adverse events (MID 30%; AD 17%, 95% CI -5% to 46%; RR 1.25, 95% CI 0.93 to 1.68; 4 studies, 508 participants) (all low-certainty evidence). 2) Compared to pharmacological intervention alone, combined pharmacological and psychosocial interventions may have little to no effect on: • the rate of abstinent days (MID 8%; MD -1.18, 95% CI -4.42 to 2.07; 2 studies, 1158 participants); and • dropouts from treatment (MID 10%; AD 1%, 95% CI -10 to 14%; RR 0.98, 95% CI 0.65 to 1.47; 3 studies, 1246 participants) (all low-certainty evidence). We are uncertain about their effect on: • continuous abstinent participants (MID 5%; AD 3%, 95% CI -5% to 18%; RR 1.22, 95% CI 0.62 to 2.40; 1 study, 241 participants); • the number of heavy drinkers (MID 2%; AD 2%, 95% CI -4% to 8%; RR 1.03, 95% CI 0.94 to 1.12; 1 study, 917 participants); • the number of drinks per drinking day (MID 1 drink; MD -2.40, 95% CI -3.98 to -0.82; 1 study, 241 participants); and • dropouts due to adverse events (MID 5%; AD -1%, 95% CI -3% to 6%; RR 0.61, 95% CI 0.14 to 2.72; 2 studies, 1165 participants) (all very low-certainty evidence). 3) We are uncertain about the effect of combined pharmacological and psychosocial interventions, when compared to TAU, on: • the number of heavy drinkers (MID 2%; AD -5%, 95% CI -13% to 2%; RR 0.93, 95% CI 0.83 to 1.03; 1 study, 616 participants); • the rate of abstinent days (MID 8%; MD 3.43, 95% CI -1.32 to 8.18; 1 study, 616 participants); • dropouts from treatment (MID 10%; AD 0%, 95% CI -10% to 15%; RR 0.98, 95% CI 0.58 to 1.65; 2 studies, 696 participants); and • dropouts due to adverse events (MID 5%; AD 3%, 95% CI 0% to 15%; RR 2.97, 95% CI 0.70 to 12.67; 1 study, 616 participants) (all very low-certainty evidence). The certainty of evidence ranged from moderate to very low, downgraded mainly due to risk of bias and imprecision.

Authors' conclusions: As implications for practice, our findings indicate that adding pharmacological to psychosocial interventions is safe and helps people with AUD recover. These conclusions are based on low- to moderate-certainty evidence. Given the few studies and very low-certainty evidence, any benefits of adding psychosocial to pharmacological interventions or comparing the combined intervention to TAU are less clear. As implications for research, further studies should investigate the effects of the combined intervention compared to pharmacotherapy or TAU.