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Table 9 Summary results of included systematic reviews, for pharmacological interventions

From: Which interventions for alcohol use should be included in a universal healthcare benefit package? An umbrella review of targeted interventions to address harmful drinking and dependence

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

  1. ASI Alcohol severity index, AUD Alcohol use disorder, AUDIT AUD identification test, BI Brief intervention, CI Confidence interval, CM Contingency management, GHB Gamma hydroxybutyric acid, MD Mean difference, NMD Network mean difference, NR Not reported, NRI Noradrenaline reuptake inhibitor, OR Odds ratio, RAPI Rutgers Alcohol Problems Index, RCT Randomized controlled trial, RR Relative risk, SARI Serotonin receptor antagonist reuptake inhibitor, SMD Standard mean difference, SSRI Selective serotonin reuptake inhibitor, WMD Weighted mean difference, XR Extended release