Intervention | Population | Comparator | Outcome | Timeframe | Effect size (method: effect (95% CI)) | I2 | Publication bias | Number of RCTs | Quality assessment of RCTs |
---|---|---|---|---|---|---|---|---|---|
Anticonvulsants | |||||||||
Anticonvulsants [90] | Alcohol dependence | Placebo | Drinks/drinking day | 11.9 weeks | MD: -1.49 (-2.32, -0.65) | 31% | NR | 11 | NR |
Mean heavy drinking | 11.2 weeks | MD: -0.35 (-0.51, -0.19) | 34% | NR | 12 | NR | |||
Abstinence | 15.5 weeks | MD: 1.21 (0.97, 1.52) | 7% | NR | 8 | Moderate | |||
Gabapentin [73] | AUD | Placebo | Alcohol consumption | NR | Hedge’s g: 0.14 (-0.35, 0.63) | 82.2% | NR | 4 | NR |
Percentage heavy drinking days | NR | Hedge’s g: 0.55 (0.01, 1.08) | 89% | NR | 7 | NR | |||
Percentage abstinent days | NR | Hedge’s g: 0.50 (-0.17, 1.16) | 81.9% | NR | 3 | NR | |||
Abstinence rate | NR | OR: 1.47 (0.82, 2.65) | 2% | NR | 4 | NR | |||
Gabapentin 300–3600 mg/day [80] | Alcohol dependence or AUD (aged > = 18 years) | Placebo | Drink per day | NR | MD: -0.15 (-0.64, 0.35) | 89% | None | 5 | Good |
Relapse of heavy drinking | NR | RR: 0.80 (0.57, 1.13) | 65% | None | 6 | Good | |||
Percentage of heavy drinking days | NR | MD: -0.64 (-1.22, -0.06) | 92% | None | 7 | Good | |||
Abstinence | NR | RR: 1.33 (0.84, 2.10) | 44% | None | 6 | Good | |||
Percentage of days abstinent | NR | MD: 0.26 (-0.16, 0.69) | 69% | None | 4 | Good | |||
Carbamazepine [103] | Alcohol dependence or AUD | Placebo | Continuous abstinence | 84–365 days | OR: 0.55 (0.08, 3.90) | NR | NR | 64 | Very low |
Levetiracetam [103] | Alcohol dependence or AUD | Placebo | Continuous abstinence | 84–365 days | OR: 1.03 (0.46, 2.34) | NR | NR | 64 | Low |
Oxcarbazepine [103] | Alcohol dependence or AUD | Placebo | Continuous abstinence | 84–365 days | OR: 2.46 (0.91, 6.61) | NR | NR | 64 | Very low |
Pregabalin [103] | Alcohol dependence or AUD | Placebo | Continuous abstinence | 84–365 days | OR: 1.97 (0.58, 6.74) | NR | NR | 64 | Low |
Topiramate [103] | Alcohol dependence or AUD | Placebo | Continuous abstinence | 84–365 days | OR: 1.88 (1.06, 3.34) | NR | NR | 64 | Very low |
Topiramate [89] | Alcohol dependence or AUDs | Placebo | Total alcohol consumption | 3–52 weeks | SMD: -0.77 (-1.12, -0.42) NMD: -0.79 (-1.21, -0.36) | 0%, 51.5% | Yes | 2 | Very low |
Non-drinking days | 3–52 weeks | SMD: 0.45 (0.15, 0.75) NMD: 0.42 (0.19, 0.66) | 62.9% 41.2% | Yes | 3 | NR | |||
Drinks per drinking day | 3–52 weeks | SMD: -0.40 (-0.88, 0.09) NMD: -0.39 (-0.83, 0.04) | 79.1% 61.5% | Yes | 2 | NR | |||
Drinking days | 3–52 weeks | SMD: -0.75 (-1.46, -0.05) NMD: -0.75 (-1.53, 0.02) | NA 46.4% | Yes | 1 | NR | |||
Heavy drinking day | 3–52 weeks | SMD: -0.59 (-0.96, -0.22) NMD: -0.49 (-0.71, -0.27) | 73.8% 38.4% | Yes | 4 | Very low | |||
Mortality | 3–52 weeks | OR: 0.14 (0, 7.01) | NA | Yes | 3 | NR | |||
Antidepressants | |||||||||
SSRI-based [96] | Alcohol disorder and major depressive disorder | Placebo | Alcohol abstinence | NR | OR: 1.26 (0.06, 2.56) | 30% | NR | 3 | NR |
Nefazodone [96] | Alcohol disorder and major depressive disorder | Placebo | Alcohol abstinence | NR | OR: 2.18 (0.68, 7.07) | 0% | NR | 2 | NR |
Mirtazapine [76] | AUD; comorbid depression/depressive symptoms | Control | AUD remission rate | NR | MD: -0.95 (-86.65, 83.82) SMD: -0.78 (-1.69, 0.13) | NR | No | NR | Low-moderate quality (all outcomes) |
SARI [76] | AUD; comorbid depression/depressive symptoms | Control | AUD remission rate | NR | OR: 1.85 (0.62, 5.66) MD: 19.49 (-6.59, 45.62) SMD: -0.23 (-1.38, 0.92) | NR | No | NR | Low-moderate quality (all outcomes) |
NRI | AUD remission rate | NR | OR: 1.60 (0.2, 12.0) | NR | No | NR | |||
SSRI | AUD remission rate | NR | OR: 1.53 (0.46, 5.0) | NR | No | NR | |||
Tricyclic antidepressants | AUD remission rate | NR | OR: 1.12 (0.3, 5.2) | NR | No | NR | |||
NRI [76] | AUD; comorbid depression/depressive symptoms | Control | AUD remission rate | NR | OR: 1.15 (0.21, 6.31) SMD: -2.44 (-3.53, -1.36) | NR | No | NR | Low-moderate quality (all outcomes) |
SSRI | AUD remission rate | NR | OR: 0.96 (0.2, 5.3) | NR | No | NR | |||
Tricyclic antidepressants | AUD remission rate | NR | OR: 0.70 (0.1, 5.1) | NR | No | NR | |||
SSRI [76] | AUD; comorbid depression/depressive symptoms | Control | AUD remission rate | NR | OR: 1.21 (0.78, 1.92) MD: 0.45 (-6.35, 7.36) SMD: -0.33 (-0.90, 0.24) | NR | No | NR | Low-moderate quality (all outcomes) |
Tricyclic antidepressants | AUD remission rate | NR | OR: 0.73 (0.2, 2.3) | NR | No | NR | |||
SSRI [70] | AUD; depression patients | Placebo | Drinks per drinking days | NR | MD: -1.42 (-2.58, -0.26) | 15% | Yes | 3 | Moderate |
Number of abstinent participants | NR | RR: 1.66 (1.02, 2.68) | 20% | Yes | 4 | Moderate | |||
Tricyclic antidepressants [76] | AUD; comorbid depression/depressive symptoms | Control | AUD remission rate | NR | OR: 1.65 (0.57, 4.73) MD: 2.50 (-21.44, 26.40) SMD: -0.31 (-1.11, 0.49) | NR | No | NR | Low-moderate quality (all outcomes) |
5-HT2 antagonist [70] | AUD; depression patients | Placebo | Drinks per drinking days | NR | MD: -1.06 (-2.00, -0.11) | 0% | Yes | 3 | Moderate |
Citalopram/ escitalopram [103] | Alcohol dependence or AUD | Placebo | Continuous abstinence | 84–365 days | OR: 1.03 (0.33, 3.16) | NR | NR | 64 | Low |
Fluoxetine [103] | Alcohol dependence or AUD | Placebo | Continuous abstinence | 84–365 days | OR: 2.97 (0.97, 9.05) | NR | NR | 64 | Very low |
Fluvoxamine [103] | Alcohol dependence or AUD | Placebo | Continuous abstinence | 84–365 days | OR: 1.03 (0.57, 1.88) | NR | NR | 64 | Low |
Nefazodone [103] | Alcohol dependence or AUD | Placebo | Continuous abstinence | 84–365 days | OR: 0.57 (0.19, 1.76) | NR | NR | 64 | Very low |
Tianeptine [103] | Alcohol dependence or AUD | Placebo | Continuous abstinence | 84–365 days | OR: 1.22 (0.58, 2.57) | NR | NR | 64 | Low |
Tiapride [103] | Alcohol dependence or AUD | Placebo | Continuous abstinence | 84–365 days | OR: 0.56 (0.3, 1.05) | NR | NR | 64 | Moderate |
Trazodone [103] | Alcohol dependence or AUD | Placebo | Continuous abstinence | 84–365 days | OR: 0.61 (0.2, 1.84) | NR | NR | 64 | Very low |
Antipsychotics | |||||||||
Antipsychotics [76] | AUD; comorbid depression/depressive symptoms | Control | AUD remission rate | NR | OR: 0.97 (0.30, 3.22) MD: 9.56 (-13.88, 32.99) SMD: -0.03 (-1.42, 1.36) | NR | No | NR | Low-moderate quality (all outcomes) |
Baclofen | AUD remission rate | NR | OR: 0.56 (0.2, 2.1) | NR | No | NR | |||
Bromocriptine | AUD remission rate | NR | OR: 2.65 (0.4, 22.0) | NR | No | NR | |||
Buspirone | AUD remission rate | NR | OR: 0.57 (0.1, 3.2) | NR | No | NR | |||
Disulfiram | AUD remission rate | NR | OR: 0.19 (0.04, 0.9) | NR | No | NR | |||
Lithium | AUD remission rate | NR | OR: 1.40 (0.4, 6.3) | NR | No | NR | |||
Memantine | AUD remission rate | NR | OR: 0.86 (0.1, 5.2) | NR | No | NR | |||
Naltrexone | AUD remission rate | NR | OR: 0.70 (0.2, 2.5) | NR | No | NR | |||
Naltrexone + disulfiram | AUD remission rate | NR | OR: 0.38 (0.1, 2.2) | NR | No | NR | |||
Naltrexone + SSRI | AUD remission rate | NR | OR: 0.44 (0.1, 1.7) | NR | No | NR | |||
SARI | AUD remission rate | NR | OR: 0.53 (0.1, 2.7) | NR | No | NR | |||
NRI | AUD remission rate | NR | OR: 0.85 (0.1, 6.7) | NR | No | NR | |||
SSRI | AUD remission rate | NR | OR: 0.81 (0.2, 2.8) | NR | No | NR | |||
Tricyclic antidepressant | AUD remission rate | NR | OR: 0.59 (0.1, 22.9) | NR | No | NR | |||
Antipsychotics (all) [79] | Alcohol dependence | Placebo | Relapse | 2–52 weeks | RR: 1.05 (0.95, 1.16) | 68% | No | 9 | High |
Abstinence/drinking days | 12—52 weeks | RR: 0.17 (0.01, 0.33) | 29% | No | 5 | High | |||
Aripiprazole [79] | Alcohol dependence | Placebo | Relapse | 2–12 weeks | RR: 1.07 (0.92, 1.24) | 70% | NR | 2 | High |
Quetiapine [79] | Alcohol dependence | Placebo | Relapse | 12 weeks | RR: 0.87 (0.65, 1.17) | 78% | NR | 2 | High |
Tiapride [79] | Alcohol dependence | Placebo | Relapse | 24–26 weeks | RR: 1.07 (0.67, 1.71) | 88% | NR | 2 | High |
Amisulpride [103] | Alcohol dependence or AUD | Placebo | Continuous abstinence | 84–365 days | OR: 0.39 (0.09, 1.64) | NA | NR | 64 | Low |
Aripiprazole [103] | Alcohol dependence or AUD | Placebo | Continuous abstinence | 84–365 days | OR: 1.49 (0.43, 5.18) | NA | NR | 64 | Low |
Flupentixol [103] | Alcohol dependence or AUD | Placebo | Continuous abstinence | 84–365 days | OR: 0.44 (0.2, 0.95) | NA | NR | 64 | Very low |
Quetiapine [103] | Alcohol dependence or AUD | Placebo | Continuous abstinence | 84–365 days | OR: 6.75 (1.2, 38.05) | NA | NR | 64 | Low |
Aversive agents | |||||||||
Disulfiram [76] | AUD; comorbid depression/depressive symptoms | Control | AUD remission rate | NR | OR: 5.00 (1.97, 12.95) MD: 17.03 (3.83, 30.47) SMD: 0.31 (-0.99, 1.61) | NR | No | NR | Low-moderate quality (all outcomes) |
Lithium | AUD remission rate | NR | OR: 7.19 (2.2, 27.0) | NR | No | NR | |||
Memantine | AUD remission rate | NR | OR: 4.44 (0.8, 23.0) | NR | No | NR | |||
Naltrexone | AUD remission rate | NR | OR: 3.62 (1.4, 9.3) | NR | No | NR | |||
Naltrexone + disulfiram | AUD remission rate | NR | OR: 1.94 (0.4, 8.0) | NR | No | NR | |||
Naltrexone + SSRI | AUD remission rate | NR | OR: 2.25 (0.7, 6.9) | NR | No | NR | |||
SARI | AUD remission rate | NR | OR: 2.74 (0.6, 12.0) | NR | No | NR | |||
NRI | AUD remission rate | NR | OR: 4.36 (0.6, 30.0) | NR | No | NR | |||
SSRI | AUD remission rate | NR | OR: 4.16 (1.5, 12.0) | NR | No | NR | |||
Tricyclic antidepressant | AUD remission rate | NR | OR: 3.04 (0.7, 13.0) | NR | No | NR | |||
Disulfiram [77] | AUD; adult | Placebo or another medication | Return to any drinking | NR | RD: -0.04 (-0.11 to 0.03) | 0% | NR | 2 | Moderate |
Disulfiram [78] | Alcohol dependent patients | Other treatment | Abstinence | 12 months | OR: 1.83 (1.02, 3.29) | 94% | NR | 2 | NR |
Placebo | Abstinence | 12 month | OR: 1.48 (0.98, 2.23) | 0% | NR | 2 | NR | ||
Other or no treatment | Abstinence | NR | OR: 2.24 (1.69, 2.97) | 77% | NR | 9 | NR | ||
Supervised disulfiram [78] | Alcohol dependent patients | Other or no treatment | Abstinence | NR | OR: 3.89 (2.66, 5.58) | 84% | NR | 7 | NR |
Unsupervised disulfiram [78] | Alcohol dependent patients | Other or no treatment | Abstinence | NR | OR: 1.59 (1.07, 2.37) | 34% | NR | 3 | NR |
Disulfiram [94] | Alcohol abuse or dependent | Control | Combined measure | 8—52 weeks | Hedges' g: 0.58 (0.35, 0.82) | 72% | Yes | 22 | NR |
No disulfiram | Combined measure | NR | Hedges' g: 0.43, (0.17, 0.69) | 44% | NR | 8 | NR | ||
Disulfiram [103] | Alcohol dependence or AUD | Placebo | Continuous abstinence | 84–365 days | OR: 0.93 (0.48, 1.79) | NR | NR | 64 | Low |
Baclofen | |||||||||
Baclofen [71] | Alcohol dependence | Placebo | Amount of drinking | NR | SMD: 0.28 (0.00, 0.56) | 71.9% | No | 10 | high |
Baclofen [76] | AUD; comorbid depression/depressive symptoms | Control | AUD remission rate | NR | OR: 1.75 (0.97, 3.29) MD: 10.42 (1.70, 19.33) SMD: -0.25 (-1.03, 0.54) | NR | No | NR | Low-moderate quality (all outcomes) |
Bromocriptine | AUD remission rate | NR | OR: 4.76 (0.8, 30.0) | NR | No | NR | |||
Buspirone | AUD remission rate | NR | OR: 1.03 (0.3, 4.1) | NR | No | NR | |||
Disulfiram | AUD remission rate | NR | OR: 0.35 (0.1, 1.1) | NR | No | NR | |||
Lithium | AUD remission rate | NR | OR: 2.49 (0.96, 7.6) | NR | No | NR | |||
Memantine | AUD remission rate | NR | OR: 1.54 (0.3, 6.9) | NR | No | NR | |||
Naltrexone | AUD remission rate | NR | OR: 1.26 (0.6, 2.8) | NR | No | NR | |||
Naltrexone + disulfiram | AUD remission rate | NR | OR: 0.68 (0.2, 2.9) | NR | No | NR | |||
Naltrexone + SSRI | AUD remission rate | NR | OR: 0.78 (0.3, 2.0) | NR | No | NR | |||
SARI | AUD remission rate | NR | OR: 0.95 (0.3, 3.3) | NR | No | NR | |||
NRI | AUD remission rate | NR | OR: 1.52 (0.3, 9.2) | NR | No | NR | |||
SSRI | AUD remission rate | NR | OR: 1.44 (0.7, 3.1) | NR | No | NR | |||
Tricyclic antidepressant | AUD remission rate | NR | OR: 0.22 (0.03, 1.6) | NR | No | NR | |||
Baclofen [82] | Alcohol-dependent patients | Placebo | Percentage abstinent patients | 4–12 weeks | RR: 2.79 (1.79, 4.34) | 0% | No | 3 | Low |
Mean abstinent days | 4–12 weeks | SMD: 3.69 (0.74, 8.11) | 96% | No | 3 | Low | |||
Baclofen [85] | Alcohol use disorder | Placebo | Relapse: return to any drinking | 4–52 weeks | RR: 0.88 (0.74, 1.04) | 76.65% | NR | 5 | Moderate |
Percentage of heavy drinking days | NR | MD: 0.25 (-1.25, 1.76) | 0% | NR | 3 | Moderate | |||
Drinks per drinking day | NR | MD: 1.55 (1.32, 1.77) | 0% | NR | 2 | Low | |||
Percentage days abstinent | NR | MD: 0.39 (-11.51, 12.29) | 96% | NR | 6 | Low | |||
Baclofen [89] | Alcohol dependence or AUDs | Placebo | Total alcohol consumption | 3–52 weeks | SMD: -1.00 (-1.80, -0.19) NMD: -1.00 (-1.86, -0.13) | NA | Yes | 1 | Very low |
Non-drinking days | 3–52 weeks | SMD -0.08 (-0.44, 0.27) NMD -0.09 (-0.50, 0.32) | 0%, 41.2% | Yes | 2 | NR | |||
Heavy drinking days | 3–52 weeks | SMD 0.03 (-0.33, 0.39) NMD 0.03 (-0.37, 0.44) | 0%, 38.4% | Yes | 2 | Very low | |||
Baclofen [91] | AUD with heavy drinking, craving, anxiety and depression | Placebo | Heavy drinking days | 3–26 weeks | SMD: -0.26 (-0.68, 0.15) | 95% | Yes | 6 | Acceptable |
Abstinent days | 3–26 weeks | SMD: 0.03 (-0.10, 0.15) | 23% | Yes | 6 | Acceptable | |||
Baclofen [103] | Alcohol dependence or AUD | Placebo | Continuous abstinence | 84–365 days | OR: 4.63 (1, 21.48) | NA | NR | 64 | Low |
Benzodiazepine | |||||||||
Glutamate antagonist | |||||||||
Acamprosate [72] | Alcohol dependence | Placebo | Abstinence rate | 1 – 12 months | OR: 1.88 (1.57, 2.25) | NR | Yes | 11 | NR |
Cumulative abstinence duration | 3 – 12 months | WMD: 26.55 (17.56, 35.54) | NR | NR | 7 | NR | |||
Acamprosate [74] | Alcohol dependence or harmful alcohol use/alcohol abuse | Placebo | Abstinence | 6 months | RR: 0.83 (0.78,0.89) | 64% | Yes | 17 | Moderate |
Acamprosate [76] | AUD; comorbid depression/depressive symptoms | Control | AUD remission rate | NR | OR: 1.66 (0.89, 3.05) MD: 6.79 (-2.30, 16.19) SMD: -0.4 (-1.45, 0.60) | NR | No | NR | Low-moderate quality (all outcomes) |
Antiepileptics | AUD remission rate | NR | OR: 0.65 (0.3, 1.6) | NR | No | NR | |||
Antipsychotics | AUD remission rate | NR | OR: 1.72 (0.4, 6.4) | NR | No | NR | |||
Baclofen | AUD remission rate | NR | OR: 0.96 (0.3, 3.8) | NR | No | NR | |||
Bromocriptine | AUD remission rate | NR | OR: 4.55 (0.8, 28.0) | NR | No | NR | |||
Buspirone | AUD remission rate | NR | OR: 0.98 (0.3, 3.8) | NR | No | NR | |||
Disulfiram | AUD remission rate | NR | OR: 0.33 (0.1, 0.9) | NR | No | NR | |||
Lithium | AUD remission rate | NR | OR: 2.39 (0.1, 0.9) | NR | No | NR | |||
Memantine | AUD remission rate | NR | OR: 1.48 (0.3, 6.5) | NR | No | NR | |||
Naltrexone | AUD remission rate | NR | OR: 1.21 (0.6, 2.4) | NR | No | NR | |||
Naltrexone + disulfiram | AUD remission rate | NR | OR: 0.65 (0.2, 2.6) | NR | No | NR | |||
Naltrexone + SSRI | AUD remission rate | NR | OR: 0.75 (0.3, 1.8) | NR | No | NR | |||
SARI | AUD remission rate | NR | OR: 0.91 (0.3, 3.1) | NR | No | NR | |||
NRI | AUD remission rate | NR | OR: 1.45 (0.2, 8.6) | NR | No | NR | |||
SSRI | AUD remission rate | NR | OR: 1.39 (0.6, 2.9) | NR | No | NR | |||
Tricyclic antidepressants | AUD remission rate | NR | OR: 0.99 (0.3, 3.4) | NR | No | NR | |||
Acamprosate [77] | AUD; adult | Placebo or another medication | Return to any drinking | NR | RD: -0.09 (-0.14, -0.04) | 80.8% | NR | 16 | Low and moderate |
Return to heavy drinking | NR | RD: -0.01 (-0.04, 0.03) | 0% | NR | 7 | Low and moderate | |||
% Drinking Days | NR | WMD: -8.8 (-12.8, -4.8) | NR | NR | 13 | Moderate | |||
Acamprosate [83] | Alcohol dependence | Placebo | Continuous abstinence | 3 months | RR: 1.33 (1.20, 1.47) | NR | NR | NR | NR |
6 months | RR: 1.47 (1.29, 1.69) | NR | No | 17 | Moderate | ||||
12 months | RR: 1.95 (1.58, 2.42) | NR | NR | 5 | NR | ||||
Acamprosate [84] | Alcohol dependence | Placebo | Mean percentage abstinent days | NR | MD: 10.38 (7.10, 13.65) | NR | NR | NR | NR |
Abstinence: Abstinence rate | NR | OR: 1.87 (1.57, 2.23) | NR | NR | NR | NR | |||
Acamprosate [95] | Adults with alcohol dependence | Placebo | Cumulative abstinence duration | 3 months | RR: 1.76 (1.14, 2.39) | NR | NR | 9 | Good |
6 months | RR: 1.16 (1.03, 1.16) | NR | NR | 8 | Good | ||||
12 months | RR: 1.11 (1.01, 1.21) | NR | NR | 6 | Good | ||||
Acamprosate [103] | Alcohol dependence or AUD | Placebo | Continuous abstinence | 84–365 days | OR: 1.86 (1.49, 2.33) | NR | NR | 64 | Moderate |
Acamprosate [92] | Adults with alcohol dependence | Placebo | Return to any drinking | 12 months | RR: 0.86 (0.81, 0.91) | 79.11% | No | 24 | NR |
Placebo | Cumulative abstinence duration | 12 months | MD: 10.94 (5.08, 16.81) | 94.32% | No | 19 | NR | ||
Opioid antagonist | |||||||||
Nalmefene [88] | Alcohol dependence | Placebo | Total alcohol consumption | 6 months | SMD: -0.2 (-0.3, -0.1) | NR | NR | 5 | NR |
Monthly number of heavy drinking days | 6 months | MD: − 1.65 (− 2.41, − 0.89) | NR | NR | 5 | NR | |||
Mortality | 6 months | RR: 0.43 (0.08, 2.38) | 0% | NR | 4 | NR | |||
Nalmefene [89] | Alcohol dependence or AUDs | Placebo | Total alcohol consumption | 3–52 weeks | SMD: -0.19 (-0.29, -0.10) NMD: -0.18 (-0.35, -0.02) | 0%, 51.5% | Yes | 7 | Moderate |
Non-drinking days | 3–52 weeks | SMD: 0.09 (-0.01, 0.19) NMD: 0.10 (-0.05, 0.25) | 0%, 38.4% | Yes | 8 | NR | |||
Drinks per drinking day | 3–52 weeks | SMD: -0.26 (-0.48, -0.05) NMD: -0.24 (-0.65, 0.18) | 0% 61.5% | Yes | 3 | NR | |||
Heavy drinking days | 3–52 weeks | SMD: -0.22 (-0.32, -0.12) NMD: -0.18 (-0.35, -0.02) | 0%, 51.5% | Yes | 7 | Moderate | |||
Mortality | 3–52 weeks | SMD: 0.41 (0.08, 2.11) | 0% | Yes | 9 | NR | |||
Naltrexone [89] | Alcohol dependence or AUDs | Placebo | Total alcohol consumption | 3–52 weeks | SMD: -0.11 (-0.40, 0.18) NMD: -0.09 (-0.29, 0.11) | 75.6% 51.5% | Yes | 5 | Very low |
Non-drinking days | 3–52 weeks | SMD: -0.28 (-0.95, 0.40) NMD: -0.21 (-0.52, 0.10) | 82.8% 41.2% | Yes | 3 | NR | |||
Drinks per drinking day | 3–52 weeks | SMD: -0.04 (-0.31, 0.23) NMD: -0.05 (-0.30, 0.21) | 66.1% 61.5% | Yes | 8 | NR | |||
Drinking day | 3–52 weeks | SMD: -0.16 (-0.35, 0.04) NMD: -0.16 (-0.35, 0.04) | 46.4% | Yes | 6 | NR | |||
Heavy drinking days | 3–52 weeks | SMD -0.03 (-0.21, 0.16) NMD -0.04 (-0.19, 0.12) | 51%, 38.4% | Yes | 8 | Very low | |||
Naltrexone [103] | Alcohol dependence or AUD | Placebo | Continuous abstinence | 84–365 days | OR: 1.36 (0.97, 1.91) | NR | NR | 64 | Low |
Naltrexone [76] | AUD; comorbid depression/depressive symptoms | Control | AUD remission rate | NR | OR: 1.38 (0.88, 2.18) MD: 4.76 (-3.59, 13.13) SMD: 0.11 (-0.68, 0.89) | NR | No | NR | Low-moderate quality (all outcomes) |
Naltrexone + disulfiram | AUD remission rate | NR | OR: 0.54 (0.1, 1.9) | NR | No | NR | |||
Naltrexone + SSRI | AUD remission rate | NR | OR: 0.62 (0.3, 1.3) | NR | No | NR | |||
SARI | AUD remission rate | NR | OR: 0.75 (0.2, 2.4) | NR | No | NR | |||
NRI | AUD remission rate | NR | OR: 1.20 (0.2, 6.8) | NR | No | NR | |||
SSRI | AUD remission rate | NR | OR: 1.15 (0.62, 2.0) | NR | No | NR | |||
Tricyclic antidepressant | AUD remission rate | NR | OR: 0.84 (0.3, 2.7) | NR | No | NR | |||
Naltrexone, 50 mg oral [77] | AUD; adults | Placebo or another medication | Return to any drinking | NR | RD: -0.05 (-0.10, -0.002) | 46.4% | NR | 16 | Low and moderate |
Return to heavy drinking | NR | RD: -0.09 (-0.13, -0.04) | 43.7% | NR | 19 | Low and moderate | |||
% Drinking Days | NR | WMD: -5.4 (-7.5, -3.2) | NR | NR | 15 | Moderate | |||
% Heavy Drinking Days | NR | WMD: -4.1 (-7.6, -0.61) | NR | NR | 6 | Moderate | |||
Drinks per Drinking Day | NR | WMD: -0.49 (-0.92, -0.06) | NR | NR | 9 | Low | |||
Naltrexone, 100 mg oral [77] | AUD; adults | Placebo or another medication | Return to any drinking | NR | RD: -0.03 (-0.08, 0.02) | 0% | NR | 3 | Low to moderate |
Return to heavy drinking | NR | RD: -0.05 (-0.11, 0.01) | 0% | NR | 2 | Low to moderate | |||
% Drinking Days (DDs) | NR | WMD: -0.9 (-4.2, 2.5) | NR | NR | 2 | Low | |||
% Heavy Drinking Days | NR | WMD: -3.1 (-5.8, -0.3) | NR | NR | 2 | Low | |||
Naltrexone injection [77] | AUD; adults | Placebo or another medication | Return to any drinking | NR | RD: -0.04 (-0.10, 0.03) | 58.5% | NR | 2 | moderate |
Return to heavy drinking | NR | RD: -0.01 (-0.14, 0.13) | 72.2% | NR | 2 | moderate | |||
% Heavy Drinking Days (HDDs) | NR | WMD: -4.6 (-8.5, -0.56) | NR | NR | 2 | Low | |||
Naltrexone [93] | AUD | Placebo | Drinking days | NR | MD: -3.89 (-5.75, -2.04) | 94.4% | NR | 26 | NR |
Heavy drinking days | NR | MD: -3.25 (-5.51, -0.99) | 81% | NR | 15 | NR | |||
Naltrexone [72] | Alcohol dependence | Placebo or reference group | Drinking days | 12 weeks | WMD: -4.49 (-5.22, -3.77) | NR | Yes | 7 | NR |
Drinks/ drinking days | 12 weeks | WMD -0.75 (-1.2, -0.29) | NR | Yes | 5 | NR | |||
Total alcohol consumption (g/ week) | 12 weeks | WMD -100 (-107, -109) | NR | Yes | 2 | NR | |||
Heavy drinking days | Min: 12 weeks; Max: 9 months | WMD -1.1 (-2.0, -0.21) | NR | Yes | 2 | NR | |||
Abstinence rate | Min: 12 weeks; Max: 9 months | OR: 1.26 (0.97, 1.64) | NR | Yes | 10 | Good quality | |||
Relapse rate | Min: 12 weeks; Max: 9 months | OR: 0.62 (0.52, 0.75) | NR | Yes | 14 | Good quality | |||
Naltrexone [95] | Adults with alcohol dependence | Placebo | Cumulative abstinence duration (CAD) | 3 months | RR: 1.23 (1.00 1.78) | NR | NR | 8 | Good |
Relapse rate | 3 months | RR: 1.2 (1.17, 1.47) | NR | NR | 18 | Good | |||
Naltrexone [97] | Alcohol dependence or abuse (aged > = 18 years) | Placebo | Mean percentage of drinking days | 12 weeks | MD: –2.8 (–5.8, –0.2) | NR | NR | 5 | NR |
Abstinence rate | 12 weeks | RR: 1.28 (1.08, 1.52) | NR | NR | 7 | NR | |||
Other | |||||||||
Alpha-blocker [98] | AUD: adult | Placebo | Drink/ day or week | 6–13 week | SMD: -0.32 (-0.56, -0.07) | 15% | No | 6 | NR |
Heavy drinking days | NR | SMD: -0.44 (-0.94, 0.06) | 76% | No | 5 | NR | |||
Antiepileptic [76] | AUD; comorbid depression/depressive symptoms | Control | AUD remission rate | NR | OR: 2.55 (1.26, 5.22) MD: 16.94 (-0.80,34.58) SMD: -0.70 ( -2.05, 0.65) | NR | No | NR | Low-moderate quality (all outcomes) |
Antipsychotics | AUD remission rate | NR | OR: 2.63 (0.7, 10.0) | NR | No | NR | Low-moderate quality (all outcomes) | ||
Baclofen | AUD remission rate | NR | OR: 1.47 (0.6, 3.7) | NR | No | NR | |||
Bromocriptine | AUD remission rate | NR | OR: 6.98 (1.2, 45.0) | NR | No | NR | |||
Buspirone | AUD remission rate | NR | OR: 1.51 (0.4, 6.2) | NR | No | NR | |||
Disulfiram | AUD remission rate | NR | OR: 0.51 (0.2, 1.6) | NR | No | NR | |||
Lithium | AUD remission rate | NR | OR: 3.67 (1.3, 11.0) | NR | No | NR | |||
Memantine | AUD remission rate | NR | OR: 2.26 (0.5, 10.0) | NR | No | NR | |||
Naltrexone | AUD remission rate | NR | OR: 1.85 (0.8, 4.1) | NR | No | NR | |||
Naltrexone + disulfiram | AUD remission rate | NR | OR: 0.99 (0.2, 4.3) | NR | No | NR | |||
Naltrexone + SSRI | AUD remission rate | NR | OR: 1.14 (0.4, 3.0) | NR | No | NR | |||
SARI | AUD remission rate | NR | OR: 1.39 (0.4, 5.1) | NR | No | NR | |||
NRI | AUD remission rate | NR | OR: 2.22 (0.4, 14.0) | NR | No | NR | |||
SSRI | AUD remission rate | NR | OR: 2.13 (0.9, 4.8) | NR | No | NR | |||
Tricyclic antidepressant | AUD remission rate | NR | OR: 1.55 (0.4, 5.5) | NR | No | NR | |||
Atenolol [103] | Alcohol dependence or AUD | Placebo | Continuous abstinence | 84–365 days | OR: 0.85 (0.25, 2.95) | NA | NR | 64 | Very low |
Bromocriptine [76] | AUD; comorbid depression/depressive symptoms | Control | AUD remission rate | NR | OR: 1.70 (0.50, 5.65) MD: 7.51 (-4.83, 19.91) SMD: -0.48 (-2.44, 1.48) | NR | No | NR | Low-moderate quality (all outcomes) |
Buspirone | AUD remission rate | NR | OR: 0.22 (0.03, 1.7) | NR | No | NR | |||
Disulfiram | AUD remission rate | NR | OR: 0.07 (0.01, 0.5) | NR | No | NR | |||
Lithium | AUD remission rate | NR | OR: 0.53 (0.01, 3.4) | NR | No | NR | |||
Memantine | AUD remission rate | NR | OR: 0.32 (0.04, 2.7) | NR | No | NR | |||
Naltrexone | AUD remission rate | NR | OR: 0.27 (0.05, 1.5) | NR | No | NR | |||
Naltrexone + disulfiram | AUD remission rate | NR | OR: 0.14 (0.02, 1.2) | NR | No | NR | |||
Naltrexone + SSRI | AUD remission rate | NR | OR: 0.16 (0.03, 0.96) | NR | No | NR | |||
SARI | AUD remission rate | NR | OR: 0.20 (0.03, 1.4) | NR | No | NR | |||
NRI | AUD remission rate | NR | OR: 0.32 (0.03, 3.3) | NR | No | NR | |||
SSRI | AUD remission rate | NR | OR: 0.30 (0.05, 1.7) | NR | No | NR | |||
Tricyclic antidepressant | AUD remission rate | NR | OR: 0.22 (0.03, 1.6) | NR | No | NR | |||
Buspirone [76] | AUD; comorbid depression/depressive symptoms | Control | AUD remission rate | NR | OR: 0.37 (0.07, 1.89) MD: 4.29 (-24.62, 33.18) SMD: -0.14 (-2.11, 1.83) | NR | No | NR | |
Disulfiram | AUD remission rate | NR | OR: 0.34 (0.07, 1.5) | NR | No | NR | |||
Lithium | AUD remission rate | NR | OR: 2.44 (0.6, 11.0) | NR | No | NR | |||
Memantine | AUD remission rate | NR | OR: 1.50 (0.2, 9.1) | NR | No | NR | |||
Naltrexone | AUD remission rate | NR | OR: 0.82 (0.2, 3.5) | NR | No | NR | |||
Naltrexone + disulfiram | AUD remission rate | NR | OR: 0.66 (0.1, 3.8) | NR | No | NR | |||
Naltrexone + SSRI | AUD remission rate | NR | OR: 0.76 (0.2, 3.0) | NR | No | NR | |||
SARI | AUD remission rate | NR | OR: 0.92 (0.2, 4.7) | NR | No | NR | |||
NRI | AUD remission rate | NR | OR: 1.48 (0.2, 12.0) | NR | No | NR | |||
SSRI | AUD remission rate | NR | OR: 1.41 (0.4, 5.0) | NR | No | NR | |||
Tricyclic antidepressant | AUD remission rate | NR | OR: 0.97 (0.2, 5.1) | NR | No | NR | |||
Galantamine [103] | Alcohol dependence or AUD | Placebo | Continuous abstinence | 84–365 days | OR: 0.31 (0.11, 0.87) | NR | NR | 64 | Low |
Sodium oxybate (GHB) [103] | Alcohol dependence or AUD | Placebo | Continuous abstinence | 84–365 days | OR: 2.31 (1.22, 4.36) | NR | NR | 64 | Very low |
GHB 50 mg [81] | Alcohol dependent patients receiving therapy to prevent or to treat alcohol withdrawal symptom (AWS) | Naltrexone | Relapse to heavy drinking | 3 months | RR: 3.23 (0.57, 18.33) | NR | NR | 2 | Very low |
Abstinence | 3 months | RR: 2.59 (1.35, 4.98) | NR | NR | 2 | Very low | |||
Lisuride [103] | Alcohol dependence or AUD | Placebo | Continuous abstinence | 84–365 days | OR: 0.38 (0.13, 1.12) | NR | NR | 64 | Very low |
Lithium [103] | Alcohol dependence or AUD | Placebo | Continuous abstinence | 84–365 days | OR: 1.43 (0.39, 5.23) | NR | NR | 64 | Low |
Lithium [76] | AUD; comorbid depression/depressive symptoms | Control | AUD remission rate | NR | OR: 0.70 (0.29, 1.52) MD: 4.98 (-7.23, 17.41) SMD: 0.01 (-1.35, 1.37) | NR | No | NR | Low-moderate quality (all outcomes) |
Memantine | AUD remission rate | NR | OR: 0.62 (0.1, 2.9) | NR | No | NR | |||
Naltrexone | AUD remission rate | NR | OR: 0.51 (0.2, 2.1) | NR | No | NR | |||
Naltrexone + disulfiram | AUD remission rate | NR | OR: 0.27 (0.1, 1.2) | NR | No | NR | |||
Naltrexone + SSRI | AUD remission rate | NR | OR: 0.31 (0.1, 0.9) | NR | No | NR | |||
SARI | AUD remission rate | NR | OR: 0.38 (0.1, 1.4) | NR | No | NR | |||
NRI | AUD remission rate | NR | OR: 0.60 (0.1, 3.8) | NR | No | NR | |||
SSRI | AUD remission rate | NR | OR: 0.58 (0.2, 1.4) | NR | No | NR | |||
Tricyclic antidepressants | AUD remission rate | NR | OR: 0.42 (0.1, 1.5) | NR | No | NR | |||
Lithium, naltrexone/ disulfiram, imipramine [96] | Alcohol addiction and major depressive disorder | Placebo | Alcohol abstinence | NR | OR: 1.59 (0.84, 3.01) | 32% | NR | 3 | NR |
Memantine [76] | AUD; comorbid depression/depressive symptoms | Control | AUD remission rate | NR | OR: 1.10 (0.29, 4.60) SMD: -0.50 (-2.51, 1.50) | NR | No | NR | Low-moderate quality (all outcomes) |
Naltrexone | AUD remission rate | NR | OR: 0.82 (0.2, 3.5) | NR | No | NR | |||
Naltrexone + disulfiram | AUD remission rate | NR | OR: 0.44 (0.1, 2.9) | NR | No | NR | |||
Naltrexone + SSRI | AUD remission rate | NR | OR: 0.51 (0.1, 2.2) | NR | No | NR | |||
SARI | AUD remission rate | NR | OR: 0.62 (0.1, 36) | NR | No | NR | |||
NRI | AUD remission rate | NR | OR: 0.98 (0.1, 8.8) | NR | No | NR | |||
SSRI | AUD remission rate | NR | OR: 0.94 (0.3, 3.5) | NR | No | NR | |||
Tricyclic antidepressant | AUD remission rate | NR | OR: 0.69 (0.1, 4.0) | NR | No | NR | |||
Modafinil [103] | Alcohol dependence or AUD | Placebo | Continuous abstinence | 84–365 days | OR: 2.48 (0.72, 8.53) | NR | NR | 64 | Low |
Paroxetine [75] | Anxiety and comorbid alcohol use disorders | Placebo | Drinks per drinking day | 12 – 16 weeks | MD: -2.42 (-4.97, 0.14) | 0.0% | NR | 2 | Very low quality |
Proportion of days abstinent | 12 – 16 weeks | MD: 0.08 (-0.26, 0.43) | 68% | NR | 2 | Very low quality | |||
Varenicline [87] | Patients people with problematic alcohol use | Placebo | Heavy drinking days | NR | SMD: -0.14 (-0.33, 0.05) | 15% | No | 5 | NR |
Alcohol consumption (number of standard drinks over time) | NR | SMD: -0.37 (-0.66, -0.07) | 49% | NR | 3 | High quality | |||
All pharmacological interventions | |||||||||
Pharmacological treatments [96] | Alcohol addiction and mood disorders | Placebo | Alcohol consumption | NR | SMD: -0.10 (-0.24, 0.04) | 0% | NR | 9 | NR |
Alcohol addiction and mood disorders in bipolar disorder | Placebo | Alcohol consumption | NR | SMD: -0.07 (-0.25, 0.11) | 0% | NR | 4 | NR | |
Alcohol addiction and mood disorders in major depressive disorder | Placebo | Alcohol consumption | NR | SMD: -0.15 (-0.38, 0.08) | 0% | NR | 5 | NR | |
Alcohol addiction and major depressive disorder, no bipolar disorder | Placebo | Alcohol abstinence | NR | OR: 1.46 (1.02, 2.11) | 0% | NR | 8 | NR | |
Pharmacotherapy [107] | AUD | Control | Abstinent rate, during treatment | ≥ 12 weeks | OR: 1.18 (0.88, 1.60) | 67.3% | NR | 60 | NR |
Abstinent rate, after treatment | ≥ 12 weeks | OR: 0.68 (0.4, 1.16) | 67.3% | NR | 60 | NR | |||
Pharmacotherapy + BI | Abstinent rate, during treatment | ≥ 12 weeks | OR: 1.95 (1.18, 3.18) | 67.3% | NR | 60 | NR | ||
Abstinent rate, after treatment | ≥ 12 weeks | OR: 1.02 (0.50, 2.14) | 67.3% | NR | 60 | NR | |||
Pharmacotherapy + psychotherapy | Abstinent rate, during treatment | ≥ 12 weeks | OR: 1.49 (0.97, 2.34) | 67.3% | NR | 60 | NR | ||
Abstinent rate, after treatment | ≥ 12 weeks | OR: 0.93 (0.40, 2.21) | 67.3% | NR | 60 | NR | |||
Psychotherapy | Abstinent rate, during treatment | ≥ 12 weeks | OR: 1.27 (0.84, 1.96) | 67.3% | NR | 60 | NR | ||
Abstinent rate, after treatment | ≥ 12 weeks | OR: 1.44 (0.70, 3.01) | 67.3% | NR | 60 | NR | |||
Psychotherapy + BI | Abstinent rate, during treatment | ≥ 12 weeks | OR: 1.54 (0.72, 3.28) | 67.3% | NR | 60 | NR | ||
Abstinent rate, after treatment | ≥ 12 weeks | OR: 3.20 (1.08, 9.55) | 67.3% | NR | 60 | NR | |||
Combination interventions | |||||||||
Naltrexone + disulfiram [76] | AUD; comorbid depression/depressive symptoms | Control | AUD remission rate | NR | OR: 2.60 (0.71, 10.15) MD: 10.72 (-6.11, 27.65) SMD: 0.30 (-1.37, 1.98) | NR | No | NR | Low-moderate quality (all outcomes) |
Naltrexone + SSRI | AUD remission rate | NR | OR: 1.15 (0.3, 5.1) | NR | No | NR | |||
SARI | AUD remission rate | NR | OR: 1.40 (0.3, 8.0) | NR | No | NR | |||
NRI | AUD remission rate | NR | OR: 2.25 (0.3, 19.0) | NR | No | NR | |||
SSRI | AUD remission rate | NR | OR: 2.14 (2.5, 8.8) | NR | No | NR | |||
Tricyclic antidepressant | AUD remission rate | NR | OR: 1.57 (0.3, 8.8) | NR | No | NR | |||
Naltrexone + SSRI [76] | AUD; comorbid depression/depressive symptoms | Control | AUD remission rate | NR | OR: 2.24 (1.15, 4.50) MD: 10.01 (-4.32, 24.42) SMD: -0.19 (-1.07, 0.68) | NR | No | NR | |
SARI | AUD remission rate | NR | OR: 1.22 (0.3, 4.4) | NR | No | NR | |||
NRI | AUD remission rate | NR | OR: 1.94 (0.3, 12.0) | NR | No | NR | |||
SSRI | AUD remission rate | NR | OR: 1.86 (1.0, 3.6) | NR | No | NR | |||
Tricyclic antidepressant | AUD remission rate | NR | OR: 1.36 (0.4, 4.8) | NR | No | NR | |||
Acamprosate + nurse visit [103] | Alcohol dependence or AUD | Placebo | Continuous abstinence | 84–365 days | OR: 4.59 (1.47, 14.36) | NR | NR | 64 | Very low |
Acamprosate + Naltrexone [103] | Alcohol dependence or AUD | Placebo | Continuous abstinence | 84–365 days | OR: 3.68 (1.5, 9.02) | NR | NR | 64 | Low |
GHB + Escitalopram [103] | Alcohol dependence or AUD | Placebo | Continuous abstinence | 84–365 days | OR: 5.13 (0.53, 49.92) | NR | NR | 64 | Low |
GHB + Naltrexone [103] | Alcohol dependence or AUD | Placebo | Continuous abstinence | 84–365 days | OR: 12.64 (2.77, 57.78) | NR | NR | 64 | Very low |
Naltrexone + Escitalopram [103] | Alcohol dependence or AUD | Placebo | Continuous abstinence | 84–365 days | OR: 2.57 (0.25, 25.85) | NR | NR | 64 | Low |
Naltrexone + GHB + Escitalopram [103] | Alcohol dependence or AUD | Placebo | Continuous abstinence | 84–365 days | OR: 25.65 (2.13, 309.46) | NR | NR | 64 | Low |
Combination interventions (psychosocial and pharmacological) | |||||||||
XR-naltrexone + psychosocial intervention [86] | AUD | Placebo + psychosocial intervention | Drinking days per month | < 6 weeks | MD: -2.00 (-3.39, -0.61) | 0% | No | 5 | NR |
XR-naltrexone + psychosocial intervention [86] | AUD | Placebo + psychosocial intervention | Heavy drinking days per month | < 6 weeks | MD: -1.16 (-2.1, -0.23) | 0% | No | 7 | NR |
Intensive perioperative cessation programme (disulfiram, chlordiazepoxide, motivational counselling, brief interview on alcohol intake, B vitamins) [106] | Hazardous drinkers undergoing all types of surgical procedures | Treatment as usual | Abstinence (self-report/ interview) | Min: 4 weeks Max: 3 months | RR: 8.22 (1.67, 40.44) | 47% | NR | 3 | Moderate (GRADE) |
Naltrexone (50 mg) plus psychotherapy [109] | Alcohol-dependent patients | Placebo plus psychotherapy | Percentage of drinking days | 12–16 weeks | MD: -4.30 (-6.16, -2.44) | NR | NR | 4 | High |
Naltrexone (50 mg) plus psychotherapy [109] | Alcohol-dependent patients | Placebo plus psychotherapy | Abstinence rate (AR) | 12—16 weeks | OR: 1.46 (1.07, 2.00) | NR | Yes | 9 | High |
Naltrexone (50 mg) plus psychotherapy [109] | Alcohol-dependent patients | Placebo plus psychotherapy | Number of drinks per drinking days | 12–16 weeks | MD: -0.28 (-0.50, -0.07) | NR | NR | 6 | High |
Naltrexone (50 mg) plus psychotherapy [109] | Alcohol-dependent patients | Placebo plus psychotherapy | Abstinence rate (AR) | 24—36 weeks | Not significant | NR | NR | 2 | High |
Naltrexone (50 mg) plus psychotherapy [109] | Alcohol-dependent patients | Placebo plus psychotherapy | Relapse rate | 12—16 weeks | OR: 0.48 (0.36, 0.64) | NR | Yes | 13 | High |
Pharmacotherapy + psychotherapy [107] | AUD | Control | Abstinent rate, during treatment | ≥ 12 weeks | OR: 1.76 (1.17, 2.73) | 67.3% | NR | 1 | NR |
Pharmacotherapy + psychotherapy [107] | AUD | Control | Abstinent rate, after treatment | ≥ 12 weeks | OR: 0.63 (0.32, 1.31) | 67.3% | NR | 0 | NR |
Phamacotherapy + Psychotherapy [107] | AUD | Psychotherapy | Abstinent rate, during treatment | ≥ 12 weeks | OR: 0.86 (0.63, 1.14) | 67.3% | NR | 25 | NR |
Phamacotherapy + Psychotherapy [107] | AUD | Psychotherapy | Abstinent rate, after treatment | ≥ 12 weeks | OR: 1.56 (0.94, 2.56) | 67.3% | NR | 4 | NR |
Phamacotherapy + Psychotherapy [107] | AUD | Psychotherapy + BI | Abstinent rate, during treatment | ≥ 12 weeks | OR: 1.03 (0.48, 2.19) | 67.3% | NR | 1 | NR |
Phamacotherapy + Psychotherapy [107] | AUD | Psychotherapy + BI | Abstinent rate, after treatment | ≥ 12 weeks | OR: 3.47 (1.26, 9.52) | 67.3% | NR | 0 | NR |