1 Dropout Show forest plot

6

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.1 All studies

6

406

Risk Ratio (M‐H, Fixed, 95% CI)

1.15 [0.88, 1.51]

1.2 Studies with low risk of bias

4

325

Risk Ratio (M‐H, Fixed, 95% CI)

1.40 [1.00, 1.96]

2 Severity of depression dichotomous measures Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 "very much" or "much" improved on the Clinical Global Impression Scale

2

183

Risk Ratio (M‐H, Fixed, 95% CI)

1.92 [1.26, 2.94]

2.2 >50% reduction in depressive severity from baseline (HDRS score)

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.54, 1.71]

3 Severity of depression continuous measures Show forest plot

7

Std. Mean Difference (IV, Random, 95% CI)

Subtotals only

3.1 HDRS total score at the end of the treatment

5

346

Std. Mean Difference (IV, Random, 95% CI)

‐0.31 [‐0.64, 0.01]

3.2 MADRS score at the end of the treatment

1

49

Std. Mean Difference (IV, Random, 95% CI)

0.18 [‐0.39, 0.74]

3.3 POMS score at the end of the treatment

1

44

Std. Mean Difference (IV, Random, 95% CI)

‐0.50 [‐1.12, 0.11]

3.4 AUSSI at the end of the treatment

1

49

Std. Mean Difference (IV, Random, 95% CI)

0.32 [‐0.24, 0.89]

3.5 Global Improvement Rating at the end of the treatment

1

29

Std. Mean Difference (IV, Random, 95% CI)

‐0.52 [‐1.26, 0.22]

3.6 BDI score at the end of the treatment

2

68

Std. Mean Difference (IV, Random, 95% CI)

‐0.58 [‐2.30, 1.14]

4 Adverse events Show forest plot

5

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

4.1 Withdrawn for medical reasons

4

311

Risk Ratio (M‐H, Fixed, 95% CI)

2.90 [1.23, 6.86]

4.2 Nausea/stomach discomfort

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

0.68 [0.40, 1.17]

4.3 Dry mouth

2

171

Risk Ratio (M‐H, Fixed, 95% CI)

1.63 [0.74, 3.62]

4.4 Drowsiness

1

76

Risk Ratio (M‐H, Fixed, 95% CI)

1.8 [0.66, 4.88]

4.5 Sluggishness/fatigue

2

171

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.51, 1.99]

4.6 Dizziness

2

171

Risk Ratio (M‐H, Fixed, 95% CI)

0.76 [0.18, 3.29]

4.7 Increased sweating

1

76

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.33, 27.57]

4.8 Headache

2

171

Risk Ratio (M‐H, Fixed, 95% CI)

1.97 [0.89, 4.39]

4.9 Jitteriness

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

1.46 [0.61, 3.51]

4.10 Constipation

2

171

Risk Ratio (M‐H, Fixed, 95% CI)

1.39 [0.49, 3.95]

4.11 Weight gain

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

1.70 [0.43, 6.72]

4.12 Insomnia

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

7.15 [0.38, 134.67]

4.13 Diarrhea

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

1.79 [0.56, 5.71]

4.14 Libido loss

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

2.55 [0.52, 12.52]

4.15 Memory problems

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

4.09 [0.47, 35.21]

5 Drug use dichotomous measure Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5.1 >50% reduction in substance use from baseline

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.60, 1.57]

5.2 >50% urine negative for substance of abuse

1

32

Risk Ratio (M‐H, Fixed, 95% CI)

1.57 [0.82, 3.00]

5.3 Continuous abstinence (4 of 4 weeks abstinent at the end of the study)

1

84

Risk Ratio (M‐H, Fixed, 95% CI)

6.0 [0.75, 47.71]

6 Drug use continuous measures Show forest plot

4

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

6.1 Use of heroin or cocaine at the end of treatment (proportion of days of use in the past 30 days)

1

95

Mean Difference (IV, Fixed, 95% CI)

‐0.06 [‐0.16, 0.04]

6.2 Use of any drug or alcohol at the end of treatment (proportion of days of use in the past 30 days)

1

95

Mean Difference (IV, Fixed, 95% CI)

‐0.1 [‐0.23, 0.03]

6.3 Polydrug use at the end of treatment (Opiate Treatment Index)

1

49

Mean Difference (IV, Fixed, 95% CI)

0.21 [‐0.69, 1.11]

6.4 Frequency of use of any drug (days of use per week)

1

137

Mean Difference (IV, Fixed, 95% CI)

‐1.17 [‐1.90, ‐0.44]

6.5 Use of cocaine at the end of treatment (days of use in the past 30 days)

1

44

Mean Difference (IV, Fixed, 95% CI)

‐2.10 [‐5.74, 1.54]

6.6 Use of heroin at the end of treatment (days of use in the past 30 days)

1

44

Mean Difference (IV, Fixed, 95% CI)

‐1.3 [‐4.83, 2.23]

6.7 Use of drugs at the end of the treatment (ASI drug composite score)

1

44

Mean Difference (IV, Fixed, 95% CI)

‐0.04 [‐0.09, 0.01]

7 Psychiatric symptoms/psychological distress: Functional health and well‐being at the end of treatment (SF‐36 Health Survey score) Show forest plot

1

49

Mean Difference (IV, Fixed, 95% CI)

‐2.5 [‐13.76, 8.76]

1 Dropout Show forest plot

4

322

Risk Ratio (M‐H, Fixed, 95% CI)

1.20 [0.88, 1.64]

2 Severity of depression dichotomous measures Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 "very much" or "much" improved on the Clinical Global Impression scale

1

137

Risk Ratio (M‐H, Fixed, 95% CI)

2.03 [1.17, 3.53]

2.2 >50% reduction in depressive severity from baseline (HDRS score)

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.54, 1.71]

3 Severity of depression continuous measures Show forest plot

4

Std. Mean Difference (IV, Random, 95% CI)

Subtotals only

3.1 HDRS total score at the end of the treatment

3

276

Std. Mean Difference (IV, Random, 95% CI)

‐0.23 [‐0.69, 0.23]

3.2 Global Improvement Rating at the end of the treatment

1

29

Std. Mean Difference (IV, Random, 95% CI)

‐0.52 [‐1.26, 0.22]

3.3 BDI score at the end of the treatment

1

44

Std. Mean Difference (IV, Random, 95% CI)

0.26 [‐0.33, 0.85]

4 Adverse events Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

4.1 Withdrawn for medical reasons

3

276

Risk Ratio (M‐H, Fixed, 95% CI)

3.03 [1.20, 7.68]

4.2 Nausea/stomach discomfort

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

0.68 [0.40, 1.17]

4.3 Dry mouth

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

3.06 [0.33, 28.41]

4.4 Sluggishness/fatigue

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

0.91 [0.38, 2.15]

4.5 Dizziness

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.15, 6.95]

4.6 Headache

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

1.90 [0.83, 4.33]

4.7 Jitteriness

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

1.46 [0.61, 3.51]

4.8 Constipation

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

1.79 [0.56, 5.71]

4.9 Weight gain

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

1.70 [0.43, 6.72]

4.10 Insomnia

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

7.15 [0.38, 134.67]

4.11 Diarrhea

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

1.79 [0.56, 5.71]

4.12 Libido loss

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

2.55 [0.52, 12.52]

4.13 Memory problems

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

4.09 [0.47, 35.21]

5 Drug use dichotomous measure Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5.1 >50% reduction in substance use from baseline

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.60, 1.57]

5.2 Continuous abstinence (4 of 4 weeks abstinent at the end of the study)

1

84

Risk Ratio (M‐H, Fixed, 95% CI)

6.0 [0.75, 47.71]

6 Drug use continuous measures Show forest plot

3

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

6.1 Use of heroin or cocaine at the end of treatment (proportion of days of use in the past 30 days)

1

95

Mean Difference (IV, Fixed, 95% CI)

‐0.06 [‐0.16, 0.04]

6.2 Use of any drug or alcohol at the end of treatment (proportion of days of use in the past 30 days)

1

95

Mean Difference (IV, Fixed, 95% CI)

‐0.1 [‐0.23, 0.03]

6.3 Frequency of use of any drug (days of use per week)

1

137

Mean Difference (IV, Fixed, 95% CI)

‐1.17 [‐1.90, ‐0.44]

6.4 Use of cocaine at the end of treatment (days of use in the past 30 days)

1

44

Mean Difference (IV, Fixed, 95% CI)

‐2.10 [‐5.74, 1.54]

6.5 Use of heroin at the end of treatment (days of use in the past 30 days)

1

44

Mean Difference (IV, Fixed, 95% CI)

‐1.3 [‐4.83, 2.23]

6.6 Use of drugs at the end of the treatment (ASI drug composite score)

1

44

Mean Difference (IV, Fixed, 95% CI)

‐0.04 [‐0.09, 0.01]

1 Drupout Show forest plot

6

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.1 Tricyclics versus placebo

3

218

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.74, 1.37]

1.2 SSRI versus placebo

3

188

Risk Ratio (M‐H, Fixed, 95% CI)

1.53 [0.91, 2.56]

2 Severity of depression dichotomous measures Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 Tricyclics versus placebo: "very much" or "much" improvement on the Clinical Global Impression scale

2

183

Risk Ratio (M‐H, Fixed, 95% CI)

1.92 [1.26, 2.94]

2.2 SSRI versus placebo:>50% reduction in depressive severity from baseline (HDRS score)

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.54, 1.71]

3 Severity of depression continuous measures Show forest plot

7

Std. Mean Difference (IV, Random, 95% CI)

Subtotals only

3.1 HDRS total score at the end of the treatment: Tricyclics versus placebo

3

207

Std. Mean Difference (IV, Random, 95% CI)

‐0.57 [‐0.85, ‐0.29]

3.2 HDRS total score at the end of the treatment: SSRI versus placebo

2

139

Std. Mean Difference (IV, Random, 95% CI)

‐0.01 [‐0.34, 0.32]

3.3 MADRS score at the end of the treatment: SSRI versus placebo

1

49

Std. Mean Difference (IV, Random, 95% CI)

0.18 [‐0.39, 0.74]

3.4 POMS score at the end of the treatment: Tricyclics versus placebo

1

44

Std. Mean Difference (IV, Random, 95% CI)

‐0.50 [‐1.12, 0.11]

3.5 AUSSI at the end of the treatment: SSRI versus placebo

1

49

Std. Mean Difference (IV, Random, 95% CI)

0.32 [‐0.24, 0.89]

3.6 Global Improvement Rating at the end of the treatment: Tricyclic versus placebo

1

29

Std. Mean Difference (IV, Random, 95% CI)

‐0.52 [‐1.26, 0.22]

3.7 BDI score at the end of the treatment: Tricyclics versus placebo

1

24

Std. Mean Difference (IV, Random, 95% CI)

‐1.50 [‐2.43, ‐0.57]

3.8 BDI score at the end of the treatment: SSRI versus placebo

1

44

Std. Mean Difference (IV, Random, 95% CI)

0.26 [‐0.33, 0.85]

4 Adverse events Show forest plot

5

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

4.1 Withdrawn for medical reasons: Tricyclics versus placebo

2

172

Risk Ratio (M‐H, Fixed, 95% CI)

3.11 [1.06, 9.12]

4.2 Withdrawn for medical reasons: SSRI versus placebo

2

139

Risk Ratio (M‐H, Fixed, 95% CI)

2.55 [0.61, 10.75]

4.3 Nausea/stomach discomfort: Tricyclic versus placebo

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

0.68 [0.40, 1.17]

4.4 Dry mouth: Tricyclic versus placebo

1

76

Risk Ratio (M‐H, Fixed, 95% CI)

1.43 [0.61, 3.36]

4.5 Dry mouth: SSRI versus placebo

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

3.06 [0.33, 28.41]

4.6 Drowsiness: Tricyclic versus placebo

1

76

Risk Ratio (M‐H, Fixed, 95% CI)

1.8 [0.66, 4.88]

4.7 Sluggishness/fatigue: Tricyclic versus placebo

1

76

Risk Ratio (M‐H, Fixed, 95% CI)

1.2 [0.40, 3.60]

4.8 Sluggishness/fatigue: SSRI versus placebo

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

0.91 [0.38, 2.15]

4.9 Dizziness: Tricyclic versus placebo

1

76

Risk Ratio (M‐H, Fixed, 95% CI)

0.5 [0.05, 5.28]

4.10 Dizziness: SSRI versus placebo

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.15, 6.95]

4.11 Increased sweating: Tricyclic versus placebo

1

76

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.33, 27.57]

4.12 Headache: Tricyclic versus placebo

1

76

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.13, 71.40]

4.13 Headache: SSRI versus placebo

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

1.90 [0.83, 4.33]

4.14 Jitteriness: SSRI versus placebo

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

1.46 [0.61, 3.51]

4.15 Constipation: Tricyclic versus placebo

1

76

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.01, 7.93]

4.16 Constipation: SSRI versus placebo

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

1.79 [0.56, 5.71]

4.17 Weight gain: SSRI versus placebo

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

1.70 [0.43, 6.72]

4.18 Insomnia: SSRI versus placebo

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

7.15 [0.38, 134.67]

4.19 Diarrhea: SSRI versus placebo

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

1.79 [0.56, 5.71]

4.20 Libido loss: SSRI versus placebo

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

2.55 [0.52, 12.52]

4.21 Memory problems: SSRI versus placebo

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

4.09 [0.47, 35.21]

5 Drug use dichotomous measure Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5.1 Tricyclic versus placebo

1

32

Risk Ratio (M‐H, Fixed, 95% CI)

1.57 [0.82, 3.00]

5.2 SSRI versus placebo

1

95

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.60, 1.57]

6 Drug use continuous measures Show forest plot

4

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

6.1 Use of heroin or cocaine at the end of treatment (proportion of days of use in the past 30 days): SSRI versus placebo

1

95

Mean Difference (IV, Fixed, 95% CI)

‐0.06 [‐0.16, 0.04]

6.2 Use of any drug or alcohol at the end of treatment (proportion of days of use in the past 30 days): SSRI versus placebo

1

95

Mean Difference (IV, Fixed, 95% CI)

‐0.1 [‐0.23, 0.03]

6.3 Polydrug use at the end of treatment (Opiate Treatment Index): SSRI versus placebo

1

49

Mean Difference (IV, Fixed, 95% CI)

0.21 [‐0.69, 1.11]

6.4 Frequency of use of any drug (days of use per week): Tricyclics versus placebo

1

137

Mean Difference (IV, Fixed, 95% CI)

‐1.17 [‐1.90, ‐0.44]

6.5 Use of cocaine at the end of treatment (days of use in the past 30 days): SSRI versus placebo

1

44

Mean Difference (IV, Fixed, 95% CI)

‐2.10 [‐5.74, 1.54]

6.6 Use of heroin at the end of treatment (days of use in the past 30 days): SSRI versus placebo

1

44

Mean Difference (IV, Fixed, 95% CI)

‐1.3 [‐4.83, 2.23]

6.7 Use of drugs at the end of the treatment (ASI drug composite score): SSRI versus placebo

1

44

Mean Difference (IV, Fixed, 95% CI)

‐0.04 [‐0.09, 0.01]

7 Psychiatric symptoms/psychological distress: Functional health and well‐being at the end of treatment (SF‐36 Health Survey score): SSRI versus placebo Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only