28. Serious adverse events summary of findings.
| Estimates of effects, credible intervals, and certainty of the evidence for serious adverse events with antidepressants in people with chronic pain | |||||||
| Bayesian network meta‐analysis summary of findings table | |||||||
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Patient or population: people with chronic pain Interventions: desvenlafaxine high dose (> 50 mg); duloxetine low dose (< 60 mg), standard dose (60 mg), and high dose (> 60 mg); esreboxetine standard dose (4‐8 mg) and high dose (> 8 mg); milnacipran standard dose (100 mg), high dose (> 100 mg), and dose unable to be categorised; mirtazapine standard dose (30 mg) Comparator (reference): placebo Outcome: serious adverse events (events that are life‐threatening or resulting in: hospitalisation, persistent or significant disability, or death) as reported per study Direction: lower is better (i.e. fewer people having serious adverse events) | |||||||
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Total studies: 71 Total participants: 19304 |
Relative effect (OR and 95% CI) |
Anticipated absolute effect (event rate)* | Certainty of the evidence (GRADE) |
Ranking** (2.5% to 97.5% credible interval) |
Interpretation of findings | ||
| With placebo | With intervention | Difference | |||||
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Desvenlafaxine high dose RCTs: 2 Participants: 912 |
0.51 (‐0.27 to 1.29) |
12/221 54 per 1000 |
20/691 28 per 1000 |
26 fewer per 1000 | Very lowa,b,c | 11 (4 to 24) |
Not significantly different from placebo |
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Milnacipran dose unable to be categorised RCTs: 3 Participants: 272 |
0.66 (‐0.95 to 2.27) |
3/69 43 per 1000 |
5/203 29 per 1000 |
14 fewer per 1000 | Very lowa,b,c | 15 (2 to 36) |
Not significantly different from placebo |
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Duloxetine low dose RCTs: 4 Participants: 935 |
0.89 (‐0.05 to 1.83) |
11/462 24 per 1000 |
9/473 21 per 1000 |
3 fewer per 1000 | Very lowa,b,c | 19 (6 to 32) |
Not significantly different from placebo |
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Duloxetine high dose RCTs: 12 Participants: 3404 |
0.92 (0.43 to 1.41) |
33/1601 21 per 1000 |
40/1803 19 per 1000 |
2 fewer per 1000 | Very lowa,b,c | 19 (9 to 29) |
Not significantly different from placebo |
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Milnacipran standard dose RCTs: 7 Participants: 2474 |
0.94 (0.31 to 1.57) |
22/1234 18 per 1000 |
21/1240 17 per 1000 |
1 fewer per 1000 | Very lowa,b,c | 19 (9 to 31) |
Not significantly different from placebo |
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Mirtazapine standard dose RCTs: 3 Participants: 484 |
0.99 (‐0.83 to 2.81) |
3/241 12 per 1000 |
3/243 12 per 1000 |
0 fewer per 1000 | Very lowb,c | 10 (3 to 38) |
Not significantly different from placebo |
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Milnacipran high dose RCTs: 7 Participants: 2826 |
1.08 (0.55 to 1.61) |
28/1257 22 per 1000 |
35/1569 24 per 1000 |
2 more per 1000 | Very lowa,b,c | 22 (11 to 32) |
Not significantly different from placebo |
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Duloxetine standard dose RCTs: 15 Participants: 4589 |
1.16 (0.71 to 1.61) |
34/1082 16 per 1000 |
52/2507 19 per 1000 |
3 more per 1000 | Very lowa,b,c | 23 (13 to 32) |
Not significantly different from placebo |
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Esreboxetine standard dose RCTs: 1 Participants: 833 |
2.25 (‐0.69 to 5.19) |
1/277 4 per 1000 |
3/556 8 per 1000 |
4 more per 1000 | Very lowa,b,c,e | 27 (4 to 41) |
Not significantly different from placebo |
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Esreboxetine high dose RCTs: 1 Participants: 558 |
2.75 (‐0.35 to 5.85) |
1/277 4 per 1000 |
2/281 10 per 1000 |
6 more per 1000 | Very lowa,b,c,e | 28 (4 to 41) |
Not significantly different from placebo |
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Network meta‐analysis‐summary of findings table definitions * Anticipated absolute effect. Anticipated absolute effect compares two risks by calculating the difference between the risk of the intervention group with the risk of the control group. ** Mean rank and credible intervals are presented. CI: confidence interval; OR: odds ratio; RCT: randomised controlled trial The number of participants for each antidepressant reflects the total number of participants taking the antidepressant or placebo from the studies in the network meta‐analysis. | |||||||
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GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect. | |||||||
aDowngraded due to within‐study bias. bDowngraded due to imprecision in the estimate. cDowngraded due to heterogeneity in the estimate. dDowngraded due to incoherence in the network. eDowngraded due to a small number of trials and participants; we cannot draw reliable conclusions.