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Study flow diagram.
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Figure 1

Study flow diagram.

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Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
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Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

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Comparison 1 Short‐term Efficacy Studies: opioid vs placebo, Outcome 1 Pain intensity post‐opioid/placebo.
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Analysis 1.1

Comparison 1 Short‐term Efficacy Studies: opioid vs placebo, Outcome 1 Pain intensity post‐opioid/placebo.

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Comparison 1 Short‐term Efficacy Studies: opioid vs placebo, Outcome 2 % Pain reduction post‐opioid/placebo.
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Analysis 1.2

Comparison 1 Short‐term Efficacy Studies: opioid vs placebo, Outcome 2 % Pain reduction post‐opioid/placebo.

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Comparison 2 Intermediate‐term Efficacy Studies: Opioid vs. Placebo, Outcome 1 Number of participants with at least 33% pain relief.
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Analysis 2.1

Comparison 2 Intermediate‐term Efficacy Studies: Opioid vs. Placebo, Outcome 1 Number of participants with at least 33% pain relief.

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Comparison 2 Intermediate‐term Efficacy Studies: Opioid vs. Placebo, Outcome 2 Number of participants with at least 50% pain relief.
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Analysis 2.2

Comparison 2 Intermediate‐term Efficacy Studies: Opioid vs. Placebo, Outcome 2 Number of participants with at least 50% pain relief.

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Comparison 2 Intermediate‐term Efficacy Studies: Opioid vs. Placebo, Outcome 3 Pain intensity post‐opioid/placebo.
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Analysis 2.3

Comparison 2 Intermediate‐term Efficacy Studies: Opioid vs. Placebo, Outcome 3 Pain intensity post‐opioid/placebo.

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Comparison 2 Intermediate‐term Efficacy Studies: Opioid vs. Placebo, Outcome 4 Evoked pain intensity post‐opioid/placebo.
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Analysis 2.4

Comparison 2 Intermediate‐term Efficacy Studies: Opioid vs. Placebo, Outcome 4 Evoked pain intensity post‐opioid/placebo.

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Comparison 2 Intermediate‐term Efficacy Studies: Opioid vs. Placebo, Outcome 5 SF‐36 Health Survey.
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Analysis 2.5

Comparison 2 Intermediate‐term Efficacy Studies: Opioid vs. Placebo, Outcome 5 SF‐36 Health Survey.

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Comparison 2 Intermediate‐term Efficacy Studies: Opioid vs. Placebo, Outcome 6 Brief Pain Inventory: Pain Interference items.
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Analysis 2.6

Comparison 2 Intermediate‐term Efficacy Studies: Opioid vs. Placebo, Outcome 6 Brief Pain Inventory: Pain Interference items.

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Comparison 2 Intermediate‐term Efficacy Studies: Opioid vs. Placebo, Outcome 7 Beck Depression Inventory.
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Analysis 2.7

Comparison 2 Intermediate‐term Efficacy Studies: Opioid vs. Placebo, Outcome 7 Beck Depression Inventory.

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Comparison 3 Intermediate‐term Efficacy Studies: opioid vs active control, Outcome 1 Number of participants with at least 33% pain relief.
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Analysis 3.1

Comparison 3 Intermediate‐term Efficacy Studies: opioid vs active control, Outcome 1 Number of participants with at least 33% pain relief.

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Comparison 3 Intermediate‐term Efficacy Studies: opioid vs active control, Outcome 2 Number of participants with at least 50% pain relief.
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Analysis 3.2

Comparison 3 Intermediate‐term Efficacy Studies: opioid vs active control, Outcome 2 Number of participants with at least 50% pain relief.

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Comparison 3 Intermediate‐term Efficacy Studies: opioid vs active control, Outcome 3 Pain intensity post‐opioid/active control.
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Analysis 3.3

Comparison 3 Intermediate‐term Efficacy Studies: opioid vs active control, Outcome 3 Pain intensity post‐opioid/active control.

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Comparison 3 Intermediate‐term Efficacy Studies: opioid vs active control, Outcome 4 SF‐36 Health Survey.
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Analysis 3.4

Comparison 3 Intermediate‐term Efficacy Studies: opioid vs active control, Outcome 4 SF‐36 Health Survey.

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Comparison 3 Intermediate‐term Efficacy Studies: opioid vs active control, Outcome 5 Beck Depression Inventory.
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Analysis 3.5

Comparison 3 Intermediate‐term Efficacy Studies: opioid vs active control, Outcome 5 Beck Depression Inventory.

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Comparison 4 Adverse Events from Intermediate‐term Studies: opioid vs placebo, Outcome 1 Participants reporting constipation.
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Analysis 4.1

Comparison 4 Adverse Events from Intermediate‐term Studies: opioid vs placebo, Outcome 1 Participants reporting constipation.

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Comparison 4 Adverse Events from Intermediate‐term Studies: opioid vs placebo, Outcome 2 Participants reporting dizziness.
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Analysis 4.2

Comparison 4 Adverse Events from Intermediate‐term Studies: opioid vs placebo, Outcome 2 Participants reporting dizziness.

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Comparison 4 Adverse Events from Intermediate‐term Studies: opioid vs placebo, Outcome 3 Participants reporting drowsiness/somnolence.
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Analysis 4.3

Comparison 4 Adverse Events from Intermediate‐term Studies: opioid vs placebo, Outcome 3 Participants reporting drowsiness/somnolence.

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Comparison 4 Adverse Events from Intermediate‐term Studies: opioid vs placebo, Outcome 4 Participants reporting nausea.
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Analysis 4.4

Comparison 4 Adverse Events from Intermediate‐term Studies: opioid vs placebo, Outcome 4 Participants reporting nausea.

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Comparison 4 Adverse Events from Intermediate‐term Studies: opioid vs placebo, Outcome 5 Participants reporting vomiting.
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Analysis 4.5

Comparison 4 Adverse Events from Intermediate‐term Studies: opioid vs placebo, Outcome 5 Participants reporting vomiting.

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Comparison 4 Adverse Events from Intermediate‐term Studies: opioid vs placebo, Outcome 6 Particpants withdrawing due to adverse events.
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Analysis 4.6

Comparison 4 Adverse Events from Intermediate‐term Studies: opioid vs placebo, Outcome 6 Particpants withdrawing due to adverse events.

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Comparison 4 Adverse Events from Intermediate‐term Studies: opioid vs placebo, Outcome 7 Participants withdrawing due to lack of efficacy.
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Analysis 4.7

Comparison 4 Adverse Events from Intermediate‐term Studies: opioid vs placebo, Outcome 7 Participants withdrawing due to lack of efficacy.

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Comparison 5 Adverse Events from Intermediate‐term Studies: opioid vs active control, Outcome 1 Participants reporting constipation.
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Analysis 5.1

Comparison 5 Adverse Events from Intermediate‐term Studies: opioid vs active control, Outcome 1 Participants reporting constipation.

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Comparison 5 Adverse Events from Intermediate‐term Studies: opioid vs active control, Outcome 2 Participants reporting dizziness.
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Analysis 5.2

Comparison 5 Adverse Events from Intermediate‐term Studies: opioid vs active control, Outcome 2 Participants reporting dizziness.

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Comparison 5 Adverse Events from Intermediate‐term Studies: opioid vs active control, Outcome 3 Participants reporting drowsiness/somnolence.
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Analysis 5.3

Comparison 5 Adverse Events from Intermediate‐term Studies: opioid vs active control, Outcome 3 Participants reporting drowsiness/somnolence.

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Comparison 5 Adverse Events from Intermediate‐term Studies: opioid vs active control, Outcome 4 Participants reporting nausea.
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Analysis 5.4

Comparison 5 Adverse Events from Intermediate‐term Studies: opioid vs active control, Outcome 4 Participants reporting nausea.

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Comparison 5 Adverse Events from Intermediate‐term Studies: opioid vs active control, Outcome 5 Participants reporting vomiting.
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Analysis 5.5

Comparison 5 Adverse Events from Intermediate‐term Studies: opioid vs active control, Outcome 5 Participants reporting vomiting.

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Comparison 5 Adverse Events from Intermediate‐term Studies: opioid vs active control, Outcome 6 Participants withdrawing due to adverse events.
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Analysis 5.6

Comparison 5 Adverse Events from Intermediate‐term Studies: opioid vs active control, Outcome 6 Participants withdrawing due to adverse events.

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Comparison 5 Adverse Events from Intermediate‐term Studies: opioid vs active control, Outcome 7 Participants withdrawing due to lack of efficacy.
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Analysis 5.7

Comparison 5 Adverse Events from Intermediate‐term Studies: opioid vs active control, Outcome 7 Participants withdrawing due to lack of efficacy.

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Comparison 1. Short‐term Efficacy Studies: opioid vs placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Pain intensity post‐opioid/placebo Show forest plot

6

180

Mean Difference (IV, Random, 95% CI)

‐15.81 [‐22.54, ‐9.07]

1.1 Peripheral Pain

4

138

Mean Difference (IV, Random, 95% CI)

‐15.01 [‐22.97, ‐7.06]

1.2 Central Pain

2

42

Mean Difference (IV, Random, 95% CI)

‐17.81 [‐30.48, ‐5.15]

2 % Pain reduction post‐opioid/placebo Show forest plot

2

38

Mean Difference (IV, Random, 95% CI)

25.78 [16.91, 34.65]
Figuras y tablas -
Comparison 1. Short‐term Efficacy Studies: opioid vs placebo
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Comparison 2. Intermediate‐term Efficacy Studies: Opioid vs. Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Number of participants with at least 33% pain relief Show forest plot

6

727

Risk Difference (M‐H, Random, 95% CI)

0.25 [0.13, 0.37]

2 Number of participants with at least 50% pain relief Show forest plot

5

305

Risk Difference (M‐H, Random, 95% CI)

0.17 [0.02, 0.33]

3 Pain intensity post‐opioid/placebo Show forest plot

9

725

Mean Difference (IV, Random, 95% CI)

‐12.01 [‐15.40, ‐8.62]

4 Evoked pain intensity post‐opioid/placebo Show forest plot

2

148

Mean Difference (IV, Random, 95% CI)

‐23.73 [‐34.50, ‐12.96]

5 SF‐36 Health Survey Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Subtotals only

5.1 Physical functioning

2

142

Mean Difference (IV, Random, 95% CI)

3.16 [‐5.46, 11.77]

5.2 Role‐physical

2

142

Mean Difference (IV, Random, 95% CI)

9.62 [‐7.73, 26.97]

5.3 Bodily pain

2

142

Mean Difference (IV, Random, 95% CI)

6.78 [0.08, 13.48]

5.4 General health

2

142

Mean Difference (IV, Random, 95% CI)

‐0.62 [‐8.08, 6.85]

5.5 Vitality

2

142

Mean Difference (IV, Random, 95% CI)

1.62 [‐5.82, 9.07]

5.6 Social functioning

2

142

Mean Difference (IV, Random, 95% CI)

3.40 [‐5.09, 11.88]

5.7 Role‐emotional

2

142

Mean Difference (IV, Random, 95% CI)

7.97 [‐5.06, 21.00]

5.8 Mental health

2

142

Mean Difference (IV, Random, 95% CI)

3.09 [‐3.05, 9.23]

6 Brief Pain Inventory: Pain Interference items Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Subtotals only

6.1 General activity

2

245

Mean Difference (IV, Random, 95% CI)

‐0.91 [‐1.67, ‐0.14]

6.2 Mood

2

245

Mean Difference (IV, Random, 95% CI)

‐0.62 [‐1.31, 0.07]

6.3 Walking

2

245

Mean Difference (IV, Random, 95% CI)

‐0.54 [‐1.28, 0.20]

6.4 Normal work

2

245

Mean Difference (IV, Random, 95% CI)

‐0.82 [‐1.59, ‐0.05]

6.5 Social relations

2

245

Mean Difference (IV, Random, 95% CI)

‐0.71 [‐1.25, ‐0.16]

6.6 Sleep

2

245

Mean Difference (IV, Random, 95% CI)

‐1.74 [‐2.42, ‐1.06]

6.7 Enjoyment of life

2

245

Mean Difference (IV, Random, 95% CI)

‐1.18 [‐1.91, ‐0.44]

7 Beck Depression Inventory Show forest plot

3

273

Mean Difference (IV, Random, 95% CI)

0.21 [‐2.29, 2.71]
Figuras y tablas -
Comparison 2. Intermediate‐term Efficacy Studies: Opioid vs. Placebo
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Comparison 3. Intermediate‐term Efficacy Studies: opioid vs active control

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Number of participants with at least 33% pain relief Show forest plot

3

243

Risk Difference (M‐H, Random, 95% CI)

0.17 [0.04, 0.31]

1.1 opioid vs gabapentin

1

88

Risk Difference (M‐H, Random, 95% CI)

0.18 [‐0.01, 0.37]

1.2 opioid vs tricyclic antidepressant

1

63

Risk Difference (M‐H, Random, 95% CI)

0.02 [‐0.22, 0.26]

1.3 opioid vs antiarrythmic

1

92

Risk Difference (M‐H, Random, 95% CI)

0.28 [0.08, 0.48]

2 Number of participants with at least 50% pain relief Show forest plot

2

155

Risk Difference (M‐H, Random, 95% CI)

0.07 [‐0.20, 0.33]

2.1 opioid vs tricyclic antidepressant

1

63

Risk Difference (M‐H, Random, 95% CI)

‐0.07 [‐0.30, 0.15]

2.2 opioid vs antiarrythmic

1

92

Risk Difference (M‐H, Random, 95% CI)

0.20 [0.01, 0.39]

3 Pain intensity post‐opioid/active control Show forest plot

4

388

Mean Difference (IV, Random, 95% CI)

‐7.19 [‐13.13, ‐1.25]

3.1 opioid vs gabapentin

1

88

Mean Difference (IV, Random, 95% CI)

‐5.0 [‐14.40, 4.40]

3.2 opioid vs tricyclic antidepressant

2

208

Mean Difference (IV, Random, 95% CI)

‐3.30 [‐13.48, 6.89]

3.3 opioid vs antiarrythmic

1

92

Mean Difference (IV, Random, 95% CI)

‐13.0 [‐19.12, ‐6.88]

4 SF‐36 Health Survey Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Subtotals only

4.1 Physical functioning

2

144

Mean Difference (IV, Random, 95% CI)

‐5.09 [‐13.81, 3.63]

4.2 Role‐physical

2

144

Mean Difference (IV, Random, 95% CI)

‐5.38 [‐19.05, 8.29]

4.3 Bodily pain

2

144

Mean Difference (IV, Random, 95% CI)

‐3.11 [‐9.91, 3.70]

4.4 General health

2

144

Mean Difference (IV, Random, 95% CI)

‐4.44 [‐11.75, 2.86]

4.5 Vitality

2

144

Mean Difference (IV, Random, 95% CI)

‐6.60 [‐13.63, 0.44]

4.6 Social functioning

2

144

Mean Difference (IV, Random, 95% CI)

‐6.04 [‐14.44, 2.35]

4.7 Role‐emotional

2

144

Mean Difference (IV, Random, 95% CI)

‐6.39 [‐19.37, 6.60]

4.8 Mental health

2

144

Mean Difference (IV, Random, 95% CI)

‐6.24 [‐14.06, 1.57]

5 Beck Depression Inventory Show forest plot

3

276

Mean Difference (IV, Random, 95% CI)

1.40 [‐0.38, 3.17]

5.1 opioid vs gabapentin

1

88

Mean Difference (IV, Random, 95% CI)

0.30 [‐2.46, 3.06]

5.2 opioid vs tricyclic antidepressant

2

188

Mean Difference (IV, Random, 95% CI)

2.17 [‐0.14, 4.49]
Figuras y tablas -
Comparison 3. Intermediate‐term Efficacy Studies: opioid vs active control
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Comparison 4. Adverse Events from Intermediate‐term Studies: opioid vs placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Participants reporting constipation Show forest plot

10

1114

Risk Difference (M‐H, Random, 95% CI)

0.25 [0.18, 0.33]

2 Participants reporting dizziness Show forest plot

10

1114

Risk Difference (M‐H, Fixed, 95% CI)

0.14 [0.10, 0.18]

3 Participants reporting drowsiness/somnolence Show forest plot

8

738

Risk Difference (M‐H, Random, 95% CI)

0.14 [0.03, 0.25]

4 Participants reporting nausea Show forest plot

10

1114

Risk Difference (M‐H, Random, 95% CI)

0.16 [0.08, 0.25]

5 Participants reporting vomiting Show forest plot

7

813

Risk Difference (M‐H, Random, 95% CI)

0.08 [0.01, 0.15]

6 Particpants withdrawing due to adverse events Show forest plot

7

867

Risk Difference (M‐H, Random, 95% CI)

0.08 [0.04, 0.12]

7 Participants withdrawing due to lack of efficacy Show forest plot

5

723

Risk Difference (M‐H, Random, 95% CI)

‐0.09 [‐0.12, ‐0.05]
Figuras y tablas -
Comparison 4. Adverse Events from Intermediate‐term Studies: opioid vs placebo
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Comparison 5. Adverse Events from Intermediate‐term Studies: opioid vs active control

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Participants reporting constipation Show forest plot

4

397

Risk Difference (M‐H, Random, 95% CI)

0.29 [0.21, 0.38]

2 Participants reporting dizziness Show forest plot

4

397

Risk Difference (M‐H, Random, 95% CI)

‐0.01 [‐0.05, 0.03]

3 Participants reporting drowsiness/somnolence Show forest plot

4

397

Risk Difference (M‐H, Random, 95% CI)

0.13 [0.06, 0.20]

4 Participants reporting nausea Show forest plot

4

393

Risk Difference (M‐H, Random, 95% CI)

0.13 [‐0.01, 0.26]

5 Participants reporting vomiting Show forest plot

1

97

Risk Difference (M‐H, Random, 95% CI)

0.0 [‐0.04, 0.04]

6 Participants withdrawing due to adverse events Show forest plot

1

75

Risk Difference (M‐H, Random, 95% CI)

0.06 [‐0.06, 0.19]

7 Participants withdrawing due to lack of efficacy Show forest plot

1

75

Risk Difference (M‐H, Random, 95% CI)

0.0 [‐0.05, 0.05]
Figuras y tablas -
Comparison 5. Adverse Events from Intermediate‐term Studies: opioid vs active control
Ir a la tabla de la revisión