Patient-centered care interventions for the management of alcohol use disorders: a systematic review of randomized controlled trials

Figures & data

Figure 1 (A) Study flow chart and (B) quality assessment.

Abbreviation: ITT, intention-to-treat.

Table 1 Single-session patient-centered counseling – no active comparator

Study	Intervention	Patients	Follow-up duration	Outcomes reported	Key findings
Bazargan-Hejazi et al^Citation29 2005, USA	1. BI 2. Usual treatment in the ED	• N=295 • ED attendants with CAGE score ≥1	3 months	• Changes in AUDIT category from baseline to follow-up  ○ Low risk: 0–6  ○ At-risk/moderate risk: 7–18  ○ High risk: 19–40	• 48% reduced their AUDIT risk category in the intervention group vs 38% in the control group. Differences were not statistically significant • In the subgroup of moderate risk, 34% of the intervention group had a risk reduction vs 13% in the control group (P=0.0099)
Bischof et al^Citation30 2008, Germany	1. Full care: personalized feedback at baseline + MI + BCC on the phone at baseline, 1, 3, and 6 months in 30-minute sessions 2. Stepped care: if no improvement reported, then patients received personalized feedback at baseline + MI + BCC (as above) 3. Control: booklet on health behavior	• N=408 • Subjects attending 81 general practices in North Germany • AUDIT score ≥5, or LAST score ≥2 • Individuals who screened positive were then assessed to identify AD, AA, AR, and HED with the lifetime version of the M-CIDI	12 months	• Average daily alcohol consumption • HED	Grams of alcohol per day: • Intervention groups reduced from 46.9 (49.3) and 49.0 (51.3) to 35.7 (48.1); control group reduced from 41.0 (50.3) to 34.9 (48.9). Differences not significant (P=0.883) Percent binge drinkers at follow-up: • For alcohol-dependent patients: intervention group 54.5%; control group 50.0% (P=0.694) • For patients with alcohol abuse or at risk drinking: intervention group 25.0%; control group 41.3% (P=0.039) • For HED only patients: intervention group 32.9%; control group 27.5% (P=0.672)
Brown et al^Citation31 2010, Canada	1. One 30-minute brief MI session, adapted for DWI offenders 2. Control	• N=92 • Adult drivers convicted of at least 2 DWI offences within the last 15 years • AUDIT score >8 • Residence within a 100 km radius of Montreal • No current DWI intervention involvement	12 months	• Percent of risky drinking days in the last 180 days (defined as ≥42 g of alcohol for males) and ≥2 standard drinks (≥28 g of alcohol) for females	• Group × time interaction not statistically significant • No differences between groups at either time • Significant reduction from 6 to 12 months in risky drinking days for intervention group (mean reduction (SD) =6.1 (20.2) to 12.2 (25.0) for intervention group; 8.5 (22.4) to 7.5 (22.7); P<0.02) • Greater reduction of MCV for intervention group at 3 months in MCV (mean (SD) =9.6 (34.3) vs 1.75 (23.9); P<0.005)
Carey et al^Citation32 2006, USA	1. TLFB + BMI enhanced with decisional balance 2. BMI enhanced with decisional balance 3. TLFB + basic BMI 4. Basic BMI 5. TLFB 6. Control: initial assessment only 7. Control: brochure	• N=615 • Adult university students reporting >1 episode of heavy drinking in a week, or four heavy drinking episodes in the last month	12 months	• Drinks/week • Drinks/drinking day • Heavy drinking frequency	• Reduction in all drinking outcomes in all groups (significance not reported) • Between groups effect sizes at 1 month were medium for intervention vs control group in drinks per drinking day, peak BAC and RAPI (0.41; 0.44 and 0.52) • At 12 months also medium for intervention vs control group in peak BAC and RAPI (0.57 and 0.50) • All other outcomes resulted in small effect sizes
Chang et al^Citation33 2011, USA	1. BI 2. Control	• Outpatient women with hypertension, diabetes, osteoporosis, or infertility • T-ACE alcohol screen-positive; and/or typically consuming ≥7 drinks a week or ≥2 drinks at a time	12 months	• Drinks per drinking day • Percent drinking days • Number of binge episodes, with binges defined as ≥4 drinks per occasion	Drinks per drinking day: • Intervention group reduced from 2.1 (1.4) to 2.0 (2.0); control group reduced from 2.2 (1.5) to 1.9 (1.6). Differences not significant (P=0.60) Percent drinking days: • Intervention group reduced from 26% to 22%; control group reduced from 21% to 20%. Differences not significant (P=0.52) Binge episodes: • Intervention group reduced from 7.4 (24) to 6.0 (21); control group reduced from 5.7 (17) to 3.8 (13). Differences not significant (P=0.17)
Cherpitel et al^Citation34 2010, Poland	1. 20 minutes of BNI 2. Assessment only 3. Screening only	• N=446 • Patients attending the ED • Positive on any one of the four RAPS4 items during the last year, or reported ≥11 standard drinks per week for men (≥6 for women), or reported ≥4 drinks on a typical drinking day for men (≥3 for women) in the last year	12 months	• Percent at risk drinking • Drinking days per week • Drinks per drinking day • Maximum drinks per occasion last month	At risk drinking: • Intervention group reduced from 87.5% to 63.8%; control groups reduced from 87.4% and 88.7% to 54.0% and 64.9%, respectively. No significant differences between groups. Within group differences significant for all groups (P<0.01) Drinking days per week: • Intervention group reduced from 2.5 (0.2) to 1.8 (0.2); control groups reduced from 2.3 (0.2) and 2.3 (0.2) to 2.0 (0.2) and 2.1 (0.2), respectively. Differences between groups not significant. Within group differences only statistically significant for intervention group (P<0.01) Drinks per drinking day: • Intervention group reduced from 5.6 (0.4) to 4.1 (0.4); control groups reduced from 5.0 (0.4) and 5.3 (0.4) to 3.5 (0.3) and 4.2 (0.4), respectively. Within group differences significant for all groups (P<0.01). No differences between groups Maximum drinks per occasion last month: • Intervention group reduced from 9.3 (0.8) to 7.4 (0.6); control groups reduced from 6.7 (0.5) and 7.8 (0.5) to 6.1 (0.6) and 7.7 (0.6), respectively. No differences between groups. Within group differences only significant for intervention group (P<0.05)
Daeppenet al^Citation35 2007, Switzerland	1. BAI (15-minute session) 2. Control with assessment 3. Control with no assessment	• N=987 • Patients admitted to the ED for an injury • Hazardous drinking, defined as men aged <65 years who drank >14 drinks per week or five drinks on a single occasion in the past 30 days, or men aged >65 years and women who drank >7 drinks per week or four drinks on a single occasion	12 months	• Percentage of patients changing from high- to low-risk drinking	Drinks per week among binge drinkers: • Intervention group baseline to follow-up difference −1.5 (13.2), control group 0.8 (10.8). Differences statistically significant (P=0.004) Binge drinking occasions per month among binge drinkers: • Intervention group baseline to follow-up difference −1.5 (3.4), control group −0.8 (3.2). Differences statistically significant (P=0.04)
Daeppenet al^Citation36 2011, Switzerland	1. BMI (15–45 minutes) 2. Control	• N=271 • 20-year old men entering military service who were binge drinkers (typical drinking episodes of 60 g pure alcohol at least once a month)	6 months	• Typical number of drinks per week (standard drink containing ~10 g of pure alcohol) • Typical number of binge drinking episodes per month • AUDIT score • Number of drinks per occasion • Number of drinking days per week	Hazardous drinkers: • Intervention group reduced from 100% to 64.4%, control groups reduced from 100% to 66.0% and 63.0%, respectively. Differences not significant (P=0.71) Binge drinking episodes last month: • Intervention group reduced from 4.2 (6.1) to 3.7 (5.8); control groups reduced from 4.0 (6.2) and 3.7 (6.1) to 3.6 (6.1) and 3.6 (6.4), respectively. Differences not significant (P=0.46) Number of drinks in last 7 days: • Intervention group reduced from 13.4 (12.8) to 10.3 (11.3); control groups reduced from 13.3 (14.7) to 11.1 (11.9) and 10.9 (14.2). Differences not significant (P=0.65) AUDIT score: • Intervention group reduced from 9.7 (5.2) to 7.8 (5.0), control groups reduced from 8.7 (4.1) to 7.2 (4.3) and 7.3 (4.7). Differences not significant (P=0.27) Number of drinks per occasion: • Intervention group reduced from 4.0 (2.6) to 3.7 (2.9), control groups reduced from 3.8 (2.4) and 3.7 (2.8) to 3.5 (2.6) and 3.4 (2.6). Differences not significant (P=0.28) Number of days drinking per week: • Intervention group reduced from 3.5 (2.3) to 3.0 (2.2), control groups reduced from 3.5 (2.4) and 3.6 (2.3) to 3.2 (2.4) and 3.1 (2.4). Differences not significant (P=0.52)
D’Onofrio et al^Citation37 2008, USA	1. BNI 2. BNI + booster 3. Standard care	• N=494 • Patients presenting to an ED	12 months	• Number of standard drinks per week • Number of binge episodes (>4 drinks for women and >5 drinks for men) in the past 30 days • Percent of participants in each treatment condition who exceeded NIAAA low-risk drinking limits in the past month	Drinks per week: • Intervention group reduced from 13.6 (11.6) to 9.8 (14.3); control group reduced from 12.4 (8.7) to 9.8 (10.9). Differences not significant Binge episodes last month: • Intervention group reduced from 6.0 (6.8) to 4.0 (6.7); control group reduced from 5.4 (5.4) to 3.9 (6.2). Differences not significant Proportion of patients over NIAAA guidelines (with previous outcomes combined): • Intervention group reduced from 99.2% to 62.0%; control group reduced from 98.0% to 65.4%. Differences not significant
Emmen et al^Citation38 2005, the Netherlands	1. Dutch Motivational Drinker’s Check-Up 2. Control	• N=123 • Patients from a general internal medicine outpatient department • Positive answer to one of three questions: 1) Have you ever felt the need to cut down on your drinking? 2) Do you ever drink to forget your worries? 3) Do close relatives ever worry or complain about your drinking?	6 months	• Change in self-reported alcohol consumption in units/day • Change in CDT	• Overall, patients reduced their alcohol consumption over time from 3.9 (2.42) units/day to 3.11 (2.29) units/day; P<0.001 • Intervention group reduced from 4.16 (2.15) to 0.81 (2.0), control group from 3.70 (2.67) to 0.84 (2.61). Differences not significant • No significant differences in the reduction of % CDT values
Gaume et al^Citation39 2011, Switzerland	1. BMI 2. Control	• N=446 • Swiss army conscripts, who were heavy episodic users, defined as having ≥1 episode per month of ≥6 drinks on a single occasion	6 months	• Number of standard drinks (~10 g of pure alcohol) per week and number of heavy drinking episodes (≥6 drinks on a single occasion) per month	Among heavy episodic users: Drinks per week: • Baseline to 6-month difference −0.4 (13.1) for the intervention group; 0.7 (19.1) for the control group. Differences not statistically significant (P=0.90) Heavy drinking episodes per month: • Baseline to 6-month difference −0.7 (3.2) for the intervention group; −0.8 (3.8) for the control group. Differences not statistically significant (P=0.61)
Hansen et al^Citation40 2012, Denmark	1. BMI (10 minutes) and a brief telephone booster session 4 weeks later 2. Control	• N=772 • Patients attending a health examination, after completing an online survey • Weekly alcohol consumption above the Danish National Board of Health limits (14 drinks =168 g of alcohol for women, 21 drinks =252 g for men) • Dependent drinkers included	12 months	• Number of drinks per week	• The difference in the number of drinks per week between intervention and control group in change over time was 1.0 favoring intervention • Difference not significant (95% CI: −2.15 to 0.23; P=0.114)
Lee et al^Citation41 2011, USA	1. CAMI 2. MI (1.5 hours)	• N=54 • Hazardous drinking (≥5/4 drinks/occasion for men/women or ≥14/7 drinks/week for men/women) • Hispanic nationality	6 months	• Heavy drinking days/month • Drinking days/month • DrInC	• Significant within groups decline for both groups on drinking days/month; heavy drinking days/month, and DrInC (numbers not reported), with no between groups differences at 6 months • At 2 months, CAMI had a greater reduction than MI in drinking days/month • Trend favoring CAMI (PCC) in reduction of heavy drinking days (P=0.08) • Significant time by treatment interaction on the DrInC Impulse scale at 6 months favoring CAMI
Murphy et al^Citation42 2001, USA	1. Basics: MI (50 minutes) 2. Education: 30-minutes of video watching and individual discussion 3. Control: assessment only	• N=54 • University undergraduate students on the upper third of the screening sample in terms of drinks per week, as measured by the DDQ • Endorsed ≥2 alcohol-related problems on the RAPI	9 months	• Drinks per week • Binge drinking days per week, drinking days per week, RAPI score, ADS score	Drinks per week: • The intervention group reduced from 22.38 (12.04) to 16.63 (9.29); the control groups reduced from 21.29 (10.06) and 20.76 (10.75) to 15.72 (7.75) and 18.46 (14.17), respectively Drinking days per week: • The intervention group reduced from 3.90 (1.35) to 3.17 (1.21); the control groups reduced from 3.75 (1.45) and 3.92 (1.46) to 3.37 (1.14) and 3.89 (1.93), respectively Binge drinking days per week: • The intervention group reduced from 2.57 (1.38) to 1.87 (1.11); the control groups reduced from 2.67 (1.05) and 2.44 (1.23) to 1.90 (1.33) and 1.93 (1.54), respectively • Not significant multivariate effect of group (P=0.22)
Murphy et al^Citation43 2004, USA	1. PDF + plus 30–50 minute MI session 2. PDF alone	• N=54 • College students who consumed at least 13 drinks per week and endorsed one or more alcohol-related problems in the past month on the RAPI	6 months	• Drinks per week • Frequency of heavy drinking in the past month	• In general, both the groups showed moderate drinking reductions • Within-group effect size across the three drinking measures was 0.48 for intervention group (PDF + MI) and 0.42 for control group (PDF alone) • No significant differences between groups
Senft et al^Citation44 1997, USA	1. Intervention: delivered in two parts: a 30-second message from the primary care clinician and a 15-minute MI session 2. Control: usual care	• N=524	12 months	• Drinking amount in units • Usual drinking amount per occasion • Health care utilization	At 12 months: • Intervention patients reported fewer drinking days per week (2.7 vs 3.1; P=0.04) than controls, but similar numbers of standard drinks (157 vs 179; P=0.13) and drinks per drinking day (3.6 vs 3.3; P=0.20) • Intervention patients were more likely than controls to report drinking within daily recommended limits (≤3 for men, ≤2 for women) (80% vs 73%; P=0.07) • No significant differences in other drinking outcomes (percent abstinent, frequency of drinking ≥6 drinks per drinking occasion, estimated peak blood alcohol concentration), or use of medical care in the year following intervention
Soderstrom et al^Citation45 2007, USA	1. Personalized MI 2. BIA	• N=497 • Patients attending a trauma center • Any positive response to an item of the CAGE, or • Drinking >2 times per week with total weekly drinking of ≥8 drinks for women and ≥15 for men, or • Drinking 2–4 times a month with typical daily consumption of ≥4 drinks for women and ≥5 drinks for men, or • Drinking ≥6 drinks on one occasion, weekly, daily, or almost daily	12 months	• Number of drinks within the past 90 days • Number of binges within the last 90 days	• Within group significant declines in number of binge episodes during the last 90 days and number of drinks during the last 90 days • No statistical significance between groups (final numbers not reported)

Abbreviations: AA, alcohol abuse; AD, alcohol dependence; ADS, Alcohol Dependence Scale; AR, at-risk drinking; AUDIT, alcohol use disorders identification test; BAC, blood alcohol content; BAI, brief alcohol intervention; BCC, behavioral change counseling; BI, brief intervention; BIA, brief intervention and advice; BMI, brief motivational interviewing; BNI, brief negotiated interview; CAGE, Cut down, Annoyed, Guilty, Eye-opener; CAMI, culturally adapted motivational intervention; CDT, carbohydrate deficient transferrin; DrInC, Drinker Inventory of Consequences; DWI, driving while intoxicated; ED, emergency department; HED, heavy episodic drinking; LAST, Luebeck alcohol dependence and abuse screening test; M-CIDI, Munich composite international diagnostic interview; MCV, mean cell volume; MI, motivational interviewing; NIAAA, National Institute on Alcohol Abuse and Alcoholism; PCC, patient-centered care; PDF, personalized drinking feedback; RAPI, Rutgers alcohol problem index; SD, standard deviation; TLFB, time line follow back.

Table 2 More than one session patient-centered counseling – no active comparator

Study	Intervention	Patients	Follow-up times	Outcomes reported	Key findings
Aalto et al^Citation46 2000, Finland	1. BI sessions at 0, 2, 6, 12, 18, 24, and 30 months (10–20 minutes based on FRAMES) 2. BI sessions at 0, 12, and 24 months 3. Control: patients were advised to reduce drinking and contact GP in the event of health problems	• N=118 • Female patients consecutively attending four primary care health clinics and one occupational health care clinic • Heavy drinker with self-reported alcohol consumption ≥190 g of absolute ethanol per week • And/or ≥2 affirmative answers on CAGE	36 months	• Drinking amount per week • Drinking frequency per week • Drinking amount per occasion • CDT • GGT	• No differences between or within groups at 3 years in alcohol consumption variables • Significant reductions within all groups in MCV • GGT decreased in intervention groups, while not in the control group (difference not statistically significant)
Aalto et al^Citation47 2001, Finland	1. BI sessions at 0, 2, 6, 12, 18, 24, and 30 months (10–20 minutes based on FRAMES) 2. BI sessions at 0, 12, and 24 months 3. Control: patients were advised to reduce drinking and contact GP in the event of health problems	• N=296 • Male patients • Heavy drinker with self-reported alcohol consumption ≥280 g of absolute ethanol per week • And/or ≥3 affirmative answers on CAGE	36 months	• Drinking amount per week • Drinking frequency per week • Drinking amount per occasion • CDT • GGT	Grams of alcohol per week: • Intervention groups decreased from 270 (251) and 284 (262) to 272 (302) and 290 (273), respectively; control group decreased from 308 (337) to 338 (371). Differences not significant Drinking frequency per week: • Intervention groups increased from 2.0 (1.6) and 2.4 (1.6) to 2.0 (1.8) and 2.6 (1.8), respectively; control group increased from 2.3 (1.8) to 2.4 (1.9). Differences not significant Usual drinking amount per occasion in grams: • Intervention groups decreased from 154 (86) and 131 (80) to 151 (89) and 125 (76), respectively. Control group increased from 130 (83) to 137 (82). Differences not significant Significant decreases within groups for all groups in MCV: • Intervention groups from 94.5 (4.2) and 94.2 (4.2) to 93.7 (4.1) and 93.2 (4.2); control group from 94.5 (4.0) to 93.2 (3.9)
Allen et al^Citation48 2011, Russia	1. MI up to four sessions 2. Control	• N=441 • Male patients aged 25–54 years recruited from a longitudinal observational study (the Izhevsk Family Study II) • Criteria for hazardous and harmful drinking were:  ○ Zapoi in the last year (behavior resulting in ≥2 days of continuous drunkenness)  ○ Drinking surrogates (nonbeverage alcohols) in the last year  ○ Hangover and/or excessive drunkenness and/or going to sleep clothed due to being drunk twice or more per week on average over the past year  ○ Weekly consumption of 250 mL or more of ethanol (from beverages) over the past year	3 months	• Self-report of hazardous and harmful drinking	Hazardous drinking over previous month: • Intervention group decreased from 70.5% to 47.5%, control group reduced from 73.8% to 54.0%. Differences not significant (AOR 0.64, 95% CI 0.39–1.06)
Beich et al^Citation49 2007, Denmark	1. BI (10-minute session and follow-up session with GP) 2. Control – no intervention	• N=906 • Listed patients aged 18–64 years, scheduled to see their GP • AUDIT score ≥8	12–14 months	• Drinking frequency • Drinking diary • Binge drinking • AUDIT score • Compliance	Units of alcohol per week: • Intervention group increased from 12.8 (8.7) to 13.5 (11.1); control group increased from 12.9 (9.0) to 13.6 (11.7) • Differences not significant
Brown et al^Citation50 2007, USA	1. Male intervention MI (six sessions) 2. Male control 3. Female intervention MI (six sessions) 4. Female control	• N=897 • Patients (21–59 years) who exceeded recommendations on low-risk drinking • DSM-IV criteria for alcohol abuse or dependence • No alcohol treatment in the past 3 months • Men who exceeded 56 standard drinks in 28 days and men who had >4 standard drinks in any 1 day • Women who exceeded 44 drinks in 28 days and women who had >3 drinks in any 1 day	3 months	• Number of drinks per month • Risky drinking days per month	Men in the intervention group: • 17.3% decrease in 28-day alcohol consumption in standard drinks (from 69.4 to 57.4; P<0.001) • 30% decrease in number of risky drinking days (from 6.2 to 4.3; P<0.001) Men in the control group: • 12.9% decrease in 28-day alcohol consumption in standard drinks (from 82.1 to 71.5; P=0.002) • 8.3% decrease in number of risky drinking days (from 7.2 to 6.6; P=0.009) • Decreases in the intervention group significantly larger Women in the intervention group: • 15.7% decrease in 28-day alcohol consumption in standard drinks (from 50.4 to 42.5; P<0.001) • 20.7% decrease in number of risky drinking days (from 5.8 to 4.6; P<0.001) Women in the control group: • 13.5% decrease in 28-day alcohol consumption in standard drinks (P<0.001) • 15.4% decrease in number of risky drinking days (P<0.001) • No differences between groups
Curry et al^Citation51 2003, USA	1. BI 2. Control	• N=307 • Outpatients visiting their primary care provider • Consuming an average of ≥2 alcoholic drinks per day in the past month (chronic drinking) • ≥2 episodes of binge drinking (defined as consuming ≥5 drinks on a single occasion) in the past month • ≥1 episode of driving after consuming ≥3 drinks	12 months	• Prevalence of at-risk drinking practices and weekly alcohol consumption	Any at risk drinking pattern reported at 12 months: • Intervention group 57%, control group 43% (P=0.003) Drinks per week: • Intervention group reduced from 14.93 (0.82) to 9.3; control group reduced from 13.56 (0.83) to 9.5. Differences not statistically significant (P=0.40)
D’Onofrio et al^Citation52 2012, USA	1. BNI 2. BNI + booster phone call at 1 month 3. Standard care (screening with health questionnaire)	• N=889	12 months	• Past 7-day alcohol consumption • Number of binge-drinking episodes in the past 28 days (>4 drinks per occasion for men and >3 drinks per occasion for women)	Mean number of drinks in the past 7 days: • Intervention groups reduced from 20.4 (18.8–22.0) and 19.8 (18.3–21.4) to 13.0 (10.5–15.5) and 14.3 (11.9–16.8); control group reduced from 20.9 (18.7–23.2) to 17.6 (14.1–21.2). Differences statistically significant (P=0.045) Mean number of binge days in past 28 days: • Intervention groups reduced from 7.5 (6.8–8.2) and 7.2 (6.5–7.9) to 4.7 (3.9–5.6) and 5.1 (4.2–5.9); control group reduced from 7.2 (6.2–8.2) to 5.8 (4.6–7.0) • Differences statistically significant (P=0.03)
Hermansson et al^Citation53 2010, Sweden	1. Comprehensive intervention: patients were offered ≤3 sessions (BI + TLFB + drinking diary over 4 weeks) 2. BI (one 15-minute session) 3. Control: no feedback on screening or verbal counseling	• N=194 • Adults presenting to an ED	12 months	• Change in percentage of patients with AUDIT positive	Change in AUDIT status: • Overall, 51.3% of patients tested positive at baseline, and 22.8% at follow-up (−56% reduction, P<0.0001) • No significant differences between groups intervention groups reduced 1.55 (2.47) and 1.11 (1.95) points, respectively; controls reduced 1.11 (2.12) points (P=0.57)
Longabaugh et al^Citation54 2001, USA	1. BI (40 minutes in ED) + booster MI session 2. BI (single 40-minute session) 3. Standard care	• N=539 • Adults attending an ED • Assessed as a hazardous or harmful drinker; defined by one of three criteria  ○ Breath alcohol positive (BAC >0.003 mg/dL)  ○ Reported having ingested alcohol in the 6 hours prior to their injury  ○ AUDIT score ≥8	12 months	• Number of heavy drinking days • Negative consequences from drinking (DrInC) • Alcohol-related injuries (IBC-R)	Number of heavy drinking days: • BI with booster session had a mean of 1.68 (1.15), BI of 1.72 (1.23) and standard care 1.70 (1.09) • Differences between groups not significant DrInC inventory: • BI with booster had the lowest score, with 2.24 (0.082). BI was 2.40 (0.078) and standard care was 2.52 (0.076) • Differences between groups statistically significant (P=0.005)
Maisto et al^Citation55 2001, USA	1. MET (30–45 minutes session + two booster sessions) 2. BI (1×10–15 minutes session) 3. Standard care	• N=301 • Adults attending a primary care clinic • AUDIT score ≥8 • Or ≥16 standard (0.6 oz ethanol) drinks per week for men and ≥12 drinks for women	12 months	• Number of drinks in past 30 days • Drinks per drinking days, past 30 days • Number of days in the past month in which patients had between 1–6 drinks	Days abstinent: • Motivational enhancement therapy group showed the greatest reduction in the difference between baseline to 12-month follow-up: −3.58 (−5.57, −1.58). BI reduced −2.54 (−4.56, −0.53), and standard care −1.16 (−2.67, −0.34) • Regression models showed no significant differences between either MET or BI vs SC Number of drinks: • Motivational enhancement therapy group showed a reduction in the difference between baseline to 12-month follow-up of 22 drinks (11.65, 32.32). BI reduced 33.20 (18.21, 48.19), and standard care reduced 14.24 (4.21, 24.26) • Regression models showed no significant differences between MET vs SC. BI showed a regression coefficient of −1.27 (P<0.05) Drinks per drinking day: • Motivational enhancement therapy group showed a reduction in the difference between baseline to 12-month follow-up of 1.30 (0.64, 1.96). BI reduced 1.55 (0.79, 2.32), and standard care 1.48 (0.85, 2.11) • Regression models showed no significant differences between either MET or BI vs SC
Mello et al^Citation56 2013, USA	1. BMI 2. Standard care	• N=285 • Patients attending the ED • ≥14 drinks/week for male subjects, ≥7 drinks/week for female subjects • Or ≥5 drinks/occasion for males, ≥4 drinks/occasion for females	12 months	• Changes in AUDIT-C • Alcohol-related injuries • DrInC score	AUDIT-C score AUDIT-1: • The intervention group decreased from 2.76 (0.89) to 2.33 (0.94); the control group decreased from 2.74 (0.83) to 2.31 (1.07). Differences at 12 months not statistically significant (P=0.87) AUDIT-2: • The intervention group decreased from 1.53 (1.14) to 1.15 (1.03); the control group decreased from 1.59 (1.12) to 1.16 (1.14). Differences at 12 months not statistically significant (P=0.0.97) AUDIT-3: • The intervention group decreased from 1.84 (1.16) to 1.41 (1.13); the control group decreased from 1.88 (1.01) to 1.51 (1.16). Differences at 12 months not statistically significant (P=0.52) Alcohol-related injuries: • Significant decrease favoring the intervention group (difference between baseline and 12-month: −0.33 (0.74) vs −0.16 (0.60); P=0.04) DrInC score: • Intervention group reduced from 3.54 (1.77) to 2.54 (1.72); the control group reduced from 3.38 (1.85) to 2.65 (1.86). Differences between baseline and 12-month score were −1.00 (1.50) for the intervention group and −0.74 (1.70) for the control group • Differences not statistically significant (P=0.09)
Monti et al^Citation57 2007, USA	1. MI (30–40 minutes) + 2× telephone booster sessions 2. Feedback only	• N=198 • Adults attending a level 1 trauma center • Blood alcohol concentration >0.01% • Reported drinking alcohol in the 6 hours prior to the event that caused their visit • Or AUDIT score ≥8	12 months	• Number of days drinking • Number of heavy drinking days • Average drinks per week	Number of days drinking in the last month: • The intervention group reduced from 8.27 (6.35) to 4.52 (5.70); the control group reduced from 7.31 (6.27) to 6.54 (6.24). Differences statistically significant in the treatment × time interaction (P<0.001) Number of heavy drinking days in the last month: • The intervention group reduced from 5.49 (5.94) to 2.72 (4.70); the control group reduced from 4.01 (4.48) to 3.53 (4.28). Differences statistically significant in the treatment × time interaction (P<0.01) Number of drinks per week in the last month: • The intervention group reduced from 13.07 (11.59) to 6.10 (8.33); the control group reduced from 10.77 (10.73) to 8.83 (9.67). Differences statistically significant in the treatment × time interaction (P<0.01) • No differences in RAPI scores at 12 months
Noknoy et al^Citation58 2010, Thailand	1. MET (3×15-minute sessions) 2. Control: assessment only	• N=117 • Consecutive primary care attenders • AUDIT score ≥8 • Patients with alcohol dependence excluded	6 months	• Amount of alcohol consumption during previous week • Binge drinking episodes during previous week • GGT levels	Drinks per drinking day in the last week: • The intervention group reduced from 5.19 (4.30) to 2.26 (2.70); the control group reduced from 4.31 (4.23) to 4.02 (4.00). Difference at 6 months statistically significant between groups (P=0.018) Drinks per week in the last week: • The intervention group reduced from 13.27 (15.40) to 4.72 (8.34); the control group reduced from 10.55 (16.96) to 11.24 (17.74). Difference at 6 months statistically significant between groups (P=0.04) Episodes of binge drinking in the last week: • The intervention group reduced from 1.00 (1.49) to 0.45 (1.38); the control group reduced from 0.88 (1.54) to 0.32 (0.72). Difference at 6 months not statistically significant between groups (P=0.139)
Sellman et al^Citation59 2001, New Zealand	1. MET (four sessions) 2. NDRL (four sessions) 3. Control: received feedback at initial session	• N=122 • Alcohol-dependent patients (according to DSM-IV criteria) of a community alcohol service	6 months	• Abstinence • Heavy drinking (drinking ≥10 standard drinks ≥6 times in the 6-month follow-up period)	• Abstinence: no differences between groups (MET 11.9%, NDRL 10%, control 7.5%; P=0.51) • Heavy drinking: MET 42.9%, NDRL 62.5%, control 65%; differences between groups significant (P=0.04)
Sommers et al^Citation60 2013, USA	1. BI (2×20-minute sessions + one face to face in ED + one telephone visit) 2. Contact control group (20-minute assessment interview) 3. No-contact control group: patients were asked for contact information only and were not interviewed	• N=476 • Young drivers (18–44 years) at a level I trauma center • Positive on two risky driving and two hazardous drinking items in a 3-minute screening	12 months	• Self-reported risky driving behaviors • Alcohol consumption	6 months period: • Absolute risk reduction for maximum number of drinks within a 6-hour period for intervention relative to control group of 0.81 (95% CI, 0.67–0.97). Intervention group decreased two drinks, control only one • Odds ratio for drinking >4 drinks in a day at 6 months for intervention relative to control group of 0.41 (95% CI, 0.17–0.98) • Significance lost at 12-month follow-up

Notes: AUDIT-1, -2, or -3 refers to the first, second, or third AUDIT question; AUDIT-C is the short version of AUDIT.

Abbreviations: AOR, adjusted odds ratio; AUDIT, Alcohol Use Disorders Identification Test; BAC, blood alcohol content; BI, brief intervention; BMI, brief motivational interviewing; BNI, brief negotiated interview; CAGE, Cut down, Annoyed, Guilty, Eye-opener; CDT, carbohydrate deficient transferrin; CI, confidence interval; DrInC, Drinker Inventory of Consequences; DSM-IV, Diagnostic and statistical manual of mental disorders, fourth edition; FRAMES, Feedback, Responsibility, Advice, Menu, Empathy, Self-efficacy; ED, emergency department; GGT, gamma glutamil transpeptidase; GP, general practitioner; IBC-R, Injury behavior check-list; MCV, mean cell volume; MET, motivational enhancement therapy; MI, motivational interviewing; NDRL, nondirective reflective listening; RAPI, Rutgers alcohol problem index; SC, standard care; TLFB, time line follow back.

Table 3 Patient-centered counseling – active comparator

Study	Intervention	Patients	Follow-up times	Outcomes reported	Key findings
Project MATCH^Citation61 1997, USA	12 weeks therapy: 1. MET 2. CBT 3. 12-step facilitation	• N=648 • Outpatients with a current DSM III-R diagnosis of alcohol abuse or dependence; active drinking for the 3 months before enrollment	15 months	• % days abstinent in last month • Drinks per drinking day in last month	• No consistent and clinically meaningful differences in efficacy between treatments • In the outpatient arm, there was a tendency for CBT patients to have a slightly higher rate of drinking days over time than the other two groups
Shakeshaft et al^Citation63 2002, Australia	1. One or multiple BI sessions (<90 minutes) based on FRAMES 2. Face-to-face counseling for six consecutive weekly sessions, organized around specific themes	• N=295 • Patients attending a free, community-based, drug and alcohol counseling service • At least one of four inclusion criteria needed:  1. To be attending for their own concerns with alcohol  2. Consumption of ≥280 g (males) or 140 g (females) of alcohol per week  3. Consumption of ≥60 g of alcohol on one occasion at least weekly or in the 7 days prior to completing the questionnaire  4. AUDIT score ≥8	6 months	• Weekly alcohol consumption • Binge alcohol consumption • Alcohol-related problems (APQ) • AUDIT score • Cost-effectiveness	• Intervention group reduced weekly consumption from 32.7 to 24.9 drinks (P<0.01); and binge occasions last 30 days 20.9 to 15.4 (P<0.01) • No statistical significance when compared to control group on both outcomes (P=0.78 and P=0.98)
UKATT Research Team^Citation62 2005, UK	1. MET 3×50 minutes sessions over 8–12 weeks 2. SBNT: 8×50-minute sessions over 8–12 weeks	• N=742 • Patients who would normally receive an offer of treatment from British treatment sites for alcohol problems	12 months	• Number of drinks per drinking day • Percent of days abstinent • Alcohol dependence, measured by the Leeds dependence questionnaire • Alcohol-related problems over the past 3 months, measured by the alcohol problems questionnaire and GGT levels	• Improvement for the whole sample in all drinking outcomes at 3 and 12 months (significance not reported) • No significant difference in percentage of days abstinent (MET 45.4% vs SBNT 46.6; difference −1.19; 95% CI [−4.50 to 6.88]) • No significant difference in number of drinks per drinking day (MET 18.7 vs SBNT 19.8; difference 1.14; 95% CI [−0.95 to 3.22])

Abbreviations: BI, brief intervention; BNI, brief negotiated interview; CBT, cognitive behavioral therapy; CI, confidence interval; DSM-III, Diagnostic and statistical manual of mental disorders, third edition; FRAMES, Feedback, Responsibility, Advice, Menu, Empathy, Self-efficacy; GGT, gamma glutamil transpeptidase; MET, motivational enhancement therapy; SBNT, social behavioral network therapy; UKATT, UK Alcohol Treatment Trial.

Table 4 Patient-centered pharmacological interventions

Study	Intervention	Patients	Follow-up times	Outcomes reported	Key findings
Gual et al^Citation65 2013, Southern urope	1. Nalmefene: as-needed dosing of nalmefene 18 mg, 1–2 h before anticipated drinking. Patients also received BRENDA 2. Control: placebo and BRENDA	• N=718 • Adults with a primary diagnosis of alcohol dependence	24 weeks	• Heavy drinking days • Total alcohol consumption (g/day)	Mean number of heavy drinking days per month: • The nalmefene group decreased from 19.8 (6.8) to 6.6 (8.9), the placebo group decreased from 18.3 (7.0) to 7.5 (9.2). • The group difference at month 6 was −1.7 days/month favoring nalmefene (95% CI −3.1 to −0.4; P=0.012) Total alcohol consumption in grams per day: • The nalmefene group decreased from 93 (46) to 30 (36), the placebo group decreased from 89 (48) to 33 (38) • The group difference at month 6 was −5.0 g/day favoring nalmefene (95% CI −10.6 to 0.7; P=0.08)
Heinala et al^Citation67 2001, Finland	1. Coping + naltrexone: coping group therapy at weeks 1, 2, 5, and 12 +50 mg of daily naltrexone for 12 weeks, then targeted naltrexone for 20 weeks 2. Coping + placebo 3. Supportive + naltrexone: supportive therapy at weeks 1, 2, 5, and 12 (emphasis on abstinence) +50 mg of daily naltrexone for 12 weeks, then targeted naltrexone for 20 weeks 4. Supportive + placebo	• N=121 • DSM IV diagnosis of alcohol dependence • Average consumption in the last 30 days of ≥5 drinks per day	32 weeks	• Relapse to heavy drinking (defined as ≥5 drinks on one occasion, having ≥5 drinking occasions in 1 week, or arriving at a visit intoxicated)	Grams per week (with SD) in the last 8 weeks of the study: • Coping + naltrexone 231 (40); coping + placebo 354 (62); supportive + naltrexone 357 (81); supportive-placebo 326 (80), coping + naltrexone significantly better than the rest of the groups, P=0.05) • Differences not significant prior to this point, with coping + naltrexone tending to do better • Overall comparison in survival analysis significant, with coping + naltrexone doing better in preventing relapses to heavy drinking. In the coping group, naltrexone was better than placebo (P=0.008). Naltrexone did better in the coping group compared to the supportive group (P=0.041).
Karhuvaara et al^Citation66 2007, Finland	1. Nalmefene: as-needed dosing patients also received limited elements of BRENDA 2. Control: placebo and limited elements of BRENDA	• N=403 • ≥18 heavy drinking days and no more than 14 consecutive abstinence days during the last 12 weeks • Sober at inclusion visit and with no withdrawal symptoms	28 weeks	• Decrease in heavy drinking days per month (≥5 drinks/day in man, ≥4 in women)	Heavy drinking days per month: • The nalmefene group decreased from 15.5 (6.9) in the first month to 8.8 (7.3) in the last month; the control group reduced from 16.2 (6.9) to 10.6 (8.3). Differences between groups statistically significant (P=0.0065) Heavy drinking days during the study period of 28 weeks: • The nalmefene group had 58.2, the control group had 86.1 (risk of heavy drinking 32.4% smaller in the nalmefene group [95% CI 14.2%–46.8%; P=0.0013]) Drinks per week: • The nalmefene group reduced from 43.2 (22.4) in the first month to 23.2 (20.8) in the last month; the control group reduced from 45.0 (23.3) to 28.5 (23.7). Differences between groups statistically significant (P=0.0018) Drinks per drinking day: • The nalmefene group reduced from 9.6 (4.8) in the first month to 6.3 (3.9) in the last month; the control group reduced from 9.5 (4.0) to 7.3 (3.7). Differences between groups statistically significant (P=0.0134)
Kranzler et al^Citation68 2009, USA	1. Targeted naltrexone 2. Targeted placebo 3. Daily naltrexone 4. Daily placebo	• N=163 • Average weekly alcohol consumption ≥24 standard drinks for men and ≥18 for women	12 weeks	• Number of standard drinks per day	Mean number of drinks consumed per day: • Targeted naltrexone group drank 16.5% less than other groups. Differences not statistically significant. Exact numbers not reported • Among men, at week 12 the targeted naltrexone group drank less than the other groups (P=0.027; exact numbers not reported)
Mann et al^Citation64 2013, Northern Europe	1. Nalmefene: as-needed dosing of nalmefene 18 mg, 1–2 hours before anticipated drinking. Patients also received BRENDA 2. Control: placebo and BRENDA	• N=598 • Adults with a primary diagnosis of alcohol dependence	24 weeks	• Heavy drinking days • Total alcohol consumption (g/day)	Mean number of heavy drinking days per month: • Nalmefene group decreased from 19 to 8, placebo group decreased from 20 to 11. Adjusted change from baseline to month 6 was −11.2 (0.6) for nalmefene, −8.9 (0.6) for placebo. Group difference of −2.3 days (95% CI −3.8 to –0.8) statistically significant (P=0.0021) Total alcohol consumption in grams per day: • The nalmefene group decreased from 84 to 33, the placebo group decreased from 85 to 45 • Adjusted change from baseline to month 6 was −50.7 (2.4) for nalmefene, −39.7 (2.2) for placebo. Group difference of −11.0 g/day (95% CI −16.8 to −5.1) statistically significant (P=0.0003)

Abbreviations: BRENDA, Biopsychosocial evaluation, Report to the patient on assessment, Empathic understanding of the patient’s situation, Needs collaboratively identified by the patient and treatment provider, Direct advice to the patient on how to meet those needs, Assess reaction of the patient to advice and adjust as necessary for best care; DSM-IV, Diagnostic and statistical manual of mental disorders, fourth edition; SD, standard deviation.

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