Inhibidores de la recaptación de serotonina y noradrenalina (IRSN) para la fibromialgia
Appendices
Appendix 1. Search strategies and hits retrieved
Randomized controlled trials (RCTs) with serotonin and noradrenaline reuptake inhibitors (SNRIs) in fibromyalgia (updated search 8 August 2017)
| Database (access) and date of search | Search strategy and hits retrieved |
|---|---|
| CENTRAL (the Cochrane Library) 2017, Issue 7 | #1 MeSH descriptor Fibromyalgia explode all trees 823 #2 (fibromyalgi$):ti,ab,kw or (fibrositis):ti,ab,kw 62 #3 (#1 OR #2), from 2010 to 2012 38 #4 (cymbalta):ti,ab,kw or (savella):ti,ab,kw or (ixel):ti,ab,kw or (pristiq):ti,ab,kw or (effexor):ti,ab,kw 31 #5 (desvenlaxafine):ti,ab,kw or (duloxetine):ti,ab,kw or (milnacipran):ti,ab,kw or (venlaxafine):ti,ab,kw1011 #6 (#4 OR #5), from 2010 to 2017 106 #7(#3 AND #6) 2 |
| MEDLINE (PubMed) 8 August 2017 | #1 Search Fibromyalgia"[Mesh] OR fibromyalgi*[ti] OR fibrositis[ti] 6497 #2 Search (randomized controlled trial[pt] OR controlled clinical trial[pt] OR randomized[tiab] OR placebo[tiab] OR drug therapy[sh] OR randomly[tiab] OR trial[tiab] OR groups[tiab]) NOT (animals[mh] NOT (humans[mh] AND animals[mh])) 3521493 #3 Search cymbalta OR savella OR ixel OR pristiq OR effexor OR desvenlafaxine OR duloxetine OR venlafaxine 6258 # 4 Search ((#1) AND #2) AND #3 Filters: Publication date from 2015/08/01 to 2017/08/07 7 |
| Embase via SCOPUS 8 August 2017 | ( ( ( TITLE‐ABS‐KEY ( cymbalta ) OR TITLE‐ABS‐KEY ( savella ) OR TITLE‐ABS‐KEY ( ixel ) OR TITLE‐ABS‐KEY ( pristiq ) OR TITLE‐ABS‐KEY ( effexor ) OR TITLE‐ABS‐KEY ( desvenlaxafine ) OR TITLE‐ABS‐KEY ( duloxetine ) OR TITLE‐ABS‐KEY ( venlaxafine ) AND ( ( ( TITLE‐ABS‐KEY ( fibromyalgia ) OR TITLE‐ABS‐KEY ( fibrositis ) OR TITLE‐ABS‐KEY ( fms ) ) ) AND ( ( TITLE‐ABS‐KEY ( randomizedcontrolledtrial ) OR TITLE‐ABS‐KEY ( controlledtrial ) OR TITLE‐ABS‐KEY ( placebo ) OR TITLE‐ABS‐KEY ( singleblind ) OR TITLE‐ABS‐KEY ( doubleblind ) ) ) ) ) AND ( PUBYEAR > 2015 ) 18 |
| US National Institutes of Health 31 November 2015 to 8 August 2017 | 1 fibromyalgia and desvenlafaxine 0 2 fibromyalgia and duloxetine 3 3 fibromyalgia and milnacipran 0 4 fibromyalgia and venlafaxine 1 5 SNRI and fibromyalgia 21 |
| World Health Organization Inception to 8 August 2017 | 1 fibromyalgia and desvenlafaxine 3 2 fibromyalgia and duloxetine 10 3 fibromyalgia and milnacipran 10 4 fibromyalgia and venlafaxine 1 5 SNRI and fibromyalgia 0 |
RCTs with SNRIs in fibromyalgia (search 30 November 2015)
| Database (access) and date of search | Search strategy and hits retrieved |
|---|---|
| CENTRAL (the Cochrane Library) 2015, Issue 11 | #1 fibromyalgi$ or fibrositis:ti,ab,kw (Word variations have been searched) 61 #2 MeSH descriptor: [Fibromyalgia] explode all 675 #3 #1 or #2 723 #4 cymbalta or savella or ixel or pristiq or effexor or desvenlaxafine or duloxetine or venlaxafine:ti,ab,kw (Word variations have been searched) 816 #5 #3 AND #4 in Trials 31 #6 #5 Publication Year from 2012 to 2015 7 |
| MEDLINE (PubMed) 30 November 2015 | #1 Search Fibromyalgia"[Mesh] OR fibromyalgi*[ti] OR fibrositis[ti] 5713 #2 Search (randomized controlled trial[pt] OR controlled clinical trial[pt] OR randomized[tiab] OR placebo[tiab] OR drug therapy[sh] OR randomly[tiab] OR trial[tiab] OR groups[tiab]) NOT (animals[mh] NOT (humans[mh] AND animals[mh])) 3125777 #3 Search cymbalta OR savella OR ixel OR pristiq OR effexor OR desvenlafaxine OR duloxetine OR venlafaxine 5544 # 4 Search ((#1) AND #2) AND #3 Filters: Publication date from 2012/09/01 to 2015/11/30 42 |
| Embase via SCOPUS 30 November 2015 | ( ( ( TITLE‐ABS‐KEY ( cymbalta ) OR TITLE‐ABS‐KEY ( savella ) OR TITLE‐ABS‐KEY ( ixel ) OR TITLE‐ABS‐KEY ( pristiq ) OR TITLE‐ABS‐KEY ( effexor ) OR TITLE‐ABS‐KEY ( desvenlaxafine ) OR TITLE‐ABS‐KEY ( duloxetine ) OR TITLE‐ABS‐KEY ( venlaxafine ) AND ( ( ( TITLE‐ABS‐KEY ( fibromyalgia ) OR TITLE‐ABS‐KEY ( fibrositis ) OR TITLE‐ABS‐KEY ( fms ) ) ) AND ( ( TITLE‐ABS‐KEY ( randomizedcontrolledtrial ) OR TITLE‐ABS‐KEY ( controlledtrial ) OR TITLE‐ABS‐KEY ( placebo ) OR TITLE‐ABS‐KEY ( singleblind ) OR TITLE‐ABS‐KEY ( doubleblind ) ) ) ) ) AND ( PUBYEAR > 2011 ) 104 |
| US National Institutes of Health 30 November 2015 | 1 fibromyalgia and desvenlafaxine 1 2 fibromyalgia and duloxetine 1 3 fibromyalgia and milnacipran 2 3 fibromyalgia and venlafaxine 1 4 SNRI and fibromyalgia 10 |
RCTs with SNRIs in fibromyalgia (updated search 11 September 2012)
| Database (access) and date of search | Search strategy and hits retrieved |
|---|---|
| CENTRAL (the Cochrane Library) 2012, Issue 9 | #1MeSH descriptor Fibromyalgia explode all trees 510 #2 (fibromyalgi$):ti,ab,kw or (fibrositis):ti,ab,kw 62 #3 (#1 OR #2), from 2010 to 2012 107 #4 (cymbalta):ti,ab,kw or (savella):ti,ab,kw or (ixel):ti,ab,kw or (pristiq):ti,ab,kw or (effexor):ti,ab,kw 17 #5 (desvenlaxafine):ti,ab,kw or (duloxetine):ti,ab,kw or (milnacipran):ti,ab,kw or (venlaxafine):ti,ab,kw 454 #6 (#4 OR #5), from 2010 to 2012 77 #7 (#3 AND #6) 17 |
| MEDLINE (PubMed) 11 September 2012 | #1"Fibromyalgia"[MeSH] OR fibromyalgi*[ti] OR fibrositis[ti] 6070 #2 (randomized controlled trial[pt] OR controlled clinical trial[pt] OR randomized[tiab] OR placebo[tiab] OR drug therapy[sh] OR randomly[tiab] OR trial[tiab] OR groups[tiab]) NOT (animals[mh] NOT (humans[mh] AND animals[mh])) 2600091 #3 Search cymbalta OR savella OR ixel OR pristiq OR effexor OR desvenlafaxine OR duloxetine OR milnacipran OR venlafaxine 4353 #4 Search ((#1) AND #2) AND #3 Filters: Publication date from 2010/10/01 to 2012/09/10 42 |
| Embase via SCOPUS 11 September 2012 | 1 (TITLE‐ABS‐KEY(random) OR TITLE‐ABS‐KEY(placebo) OR TITLE‐ABS‐KEY(double‐blind)) AND DOCTYPE(ar) AND PUBYEAR > 2009 97115 2 (TITLE‐ABS‐KEY(expfibromyalgia/) OR TITLE‐ABS‐KEY(fibrositis) OR TITLE‐ABS‐KEY(fibromyalgia)) AND DOCTYPE(ar) AND PUBYEAR > 2009 1265 3 (TITLE‐ABS‐KEY(cymbalta) OR TITLE‐ABS‐KEY(savella) OR TITLE‐ABS‐KEY(ixel) OR TITLE‐ABS‐KEY(pristiq) OR TITLE‐ABS‐KEY(effexor) OR TITLE‐ABS‐KEY(desvenlaxafine) OR TITLE‐ABS‐KEY(duloxetine) OR TITLE‐ABS‐KEY(venlaxafine) OR TITLE‐ABS‐KEY(milnacipran)) AND DOCTYPE(ar) AND PUBYEAR > 2009 1051 4 ((TITLE‐ABS‐KEY(expfibromyalgia/) OR TITLE‐ABS‐KEY(fibrositis) OR TITLE‐ABS‐KEY(fibromyalgia)) AND DOCTYPE(ar) AND PUBYEAR > 2009) AND ((TITLE‐ABS‐KEY(random) OR TITLE‐ABS‐KEY(placebo) OR TITLE‐ABS‐KEY(double‐blind)) AND DOCTYPE(ar) AND PUBYEAR > 2009) AND ((TITLE‐ABS‐KEY(cymbalta) OR TITLE‐ABS‐KEY(savella) OR TITLE‐ABS‐KEY(ixel) OR TITLE‐ABS‐KEY(pristiq) OR TITLE‐ABS‐KEY(effexor) OR TITLE‐ABS‐KEY(desvenlaxafine) OR TITLE‐ABS‐KEY(duloxetine) OR TITLE‐ABS‐KEY(venlaxafine) OR TITLE‐ABS‐KEY(milnacipran)) AND DOCTYPE(ar) AND PUBYEAR > 2009) 50 |
| US National Institutes of Health 11 September 2012 | 1 fibromyalgia 401 2 fibromyalgia and desvenlafaxine 4 3 fibromyalgia and duloxetine 25 4 fibromyalgia and milnacipran 27 5 fibromyalgia and venlafaxine 0 |
RCTs with SNRIs in fibromyalgia (updated search November 2010)
| Database (access) and date of search | Search strategy and hits retrieved |
|---|---|
| CENTRAL (the Cochrane Library) 2010, Issue 10 | #1MeSH descriptor Fibromyalgia explode all trees 449 #2 fibromyalgi* 755 #3 fibrositis 50 #4 #1 OR #2 OR #3 774 #5 (#1 OR #2 OR #3), from 2009 to 2010 137 (69 in clinical trials) |
| MEDLINE (PubMed) 4 November 2010 | #1"Fibromyalgia"[MeSH] OR fibromyalgi*[ti] OR fibrositis[ti] 5248 #2 (randomized controlled trial[pt] OR controlled clinical trial[pt] OR randomized[tiab] OR placebo[tiab] OR drug therapy[sh] OR randomly[tiab] OR trial[tiab] OR groups[tiab]) NOT (animals[mh] NOT (humans[mh] AND animals[mh])) 2309479 #3 #1 AND #2 1682 #4 (#2) AND #1 Limits: Publication Date from 2009 312 |
| Embase (Ovid) 4 November 2010 | 1 exp Fibromyalgia/ 8833 2 fibromyalgia.ti,ab. 6702 3 exp Fibromyalgia/ 8833 4 fibrositis.ti. 271 5 1 or 2 or 3 or 4 9482 6 random:.tw. or placebo:.mp. or double‐blind:.mp. 776985 7 5 and 6 1417 8 limit 7 to yr="2009 ‐Current" 405 |
| ClinicalStudyResults.org 31 December 2010 | 1 fibromyalgia 19 2 fibromyalgia and cymbalta4 3 fibromyalgia and savella or ixel: no search possible 4 fibromyalgia and pristiq 4 5 fibromyalgia and effexor 0 |
| US National Institutes of Health 31 December 2010 | 1 fibromyalgia 326 2 fibromyalgia and desvenlafaxine 4 3 fibromyalgia and duloxetine 20 4 fibromyalgia and milnacipran 20 5 fibromyalgia and venlafaxine 0 |
RCTs with SNRIs in fibromyalgia (initial search February 2009)
| Database (access) and date of search | Search strategy and hits retrieved |
|---|---|
| CENTRAL (the Cochrane Library) 2009, Issue 1 | #1MeSH descriptor Fibromyalgia explode all trees 315 #2 fibromyalgi* 512 #3 fibrositis 36 #4 #1 OR #2 OR #3 526 |
| MEDLINE (PubMed) 9 February 2009 | #1"Fibromyalgia"[MeSH] OR fibromyalgi*[ti] OR fibrositis[ti] 4433 #2 (randomized controlled trial[pt] OR controlled clinical trial[pt] OR randomized[tiab] OR placebo[tiab] OR drug therapy[sh] OR randomly[tiab] OR trial[tiab] OR groups[tiab]) AND humans [mh] 1912816 #3 #1 AND #2 1316 |
| Embase (Ovid) 9 February 2009 | 1 exp Fibromyalgia/ 5537 2 fibromyalgia.ti,ab. 4304 3 exp Fibromyalgia/ 354 4 fibrositis.ti. 122 5 1 or 2 or 3 or 4 6046 6 random:.tw. or placebo:.mp. or double‐blind:.mp. 514373 7 5 and 6 886 |
Study flow diagram
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
Risk of bias summary: review authors' judgements about each risk of bias item for each included study
Comparison 1: SNRIs versus placebo in parallel and cross‐over design trials, Outcome 1: Self‐reported pain relief of 50% or greater
Comparison 1: SNRIs versus placebo in parallel and cross‐over design trials, Outcome 2: PGIC much or very much improved
Comparison 1: SNRIs versus placebo in parallel and cross‐over design trials, Outcome 3: Withdrawal due to adverse events
Comparison 1: SNRIs versus placebo in parallel and cross‐over design trials, Outcome 4: Serious adverse events
Comparison 1: SNRIs versus placebo in parallel and cross‐over design trials, Outcome 5: Self‐reported fatigue
Comparison 1: SNRIs versus placebo in parallel and cross‐over design trials, Outcome 6: Self‐reported sleep problems
Comparison 1: SNRIs versus placebo in parallel and cross‐over design trials, Outcome 7: Self‐reported health‐related quality of life
Comparison 1: SNRIs versus placebo in parallel and cross‐over design trials, Outcome 8: Self‐reported pain relief of 30% or greater
Comparison 1: SNRIs versus placebo in parallel and cross‐over design trials, Outcome 9: Self‐reported mean pain intensity
Comparison 1: SNRIs versus placebo in parallel and cross‐over design trials, Outcome 10: Self‐reported depression
Comparison 1: SNRIs versus placebo in parallel and cross‐over design trials, Outcome 11: Self‐reported anxiety
Comparison 1: SNRIs versus placebo in parallel and cross‐over design trials, Outcome 12: Self‐reported disability
Comparison 1: SNRIs versus placebo in parallel and cross‐over design trials, Outcome 13: Self‐reported cognitive disturbances
Comparison 1: SNRIs versus placebo in parallel and cross‐over design trials, Outcome 14: Tenderness
Comparison 1: SNRIs versus placebo in parallel and cross‐over design trials, Outcome 15: Withdrawal due to lack of efficacy
Comparison 1: SNRIs versus placebo in parallel and cross‐over design trials, Outcome 16: Nausea
Comparison 1: SNRIs versus placebo in parallel and cross‐over design trials, Outcome 17: Somnolence
Comparison 1: SNRIs versus placebo in parallel and cross‐over design trials, Outcome 18: Insomnia
| Serotonin noradrenaline reuptake inhibitors compared with placebo for fibromyalgia ‐ studies with parallel design | ||||||
| Patient or population: people with fibromyalgia Settings: study centers in North, Central and South America, Asia and Europe Intervention: serotonin noradrenaline reuptake inhibitors (duloxetine, milnacipran) Comparison: placebo | ||||||
| Outcomes | Probable outcome with intervention (95% CI) | Probable outcome with placebo | Relative effect SMD or risk difference | No of participants | Quality of the evidence | Comments |
|---|---|---|---|---|---|---|
| Self‐reported pain relief of 50% or greater | 309 per 1000 (282 to 344) | 210 per 1000 | RD 0.09 (0.07 to 0.11) | 6918 (15 studies) | ⊕⊕⊝⊝ | NNTB 11 (95% CI 9 to 14) |
| Patient Global Impression to be much or very much improved (PGIC) | 519 per 1000 (459 to 573) | 293 per 1000 | RD 0.19 (0.12 to 0.26) | 2918 (6 studies) | ⊕⊕⊝⊝ | NNTB 5 (95% CI 4 to 8) |
| Self‐reported fatigue (20‐100 scale) Higher scores indicate higher fatigue problem levels | Mean fatigue | Baseline mean score 69.4 (SD 12.3)3 | SMD ‐0.13 (‐0.18 to ‐0.08) | 6168 (12 studies) | ⊕⊕⊝⊝ | NNTB 18 (95% CI 12 to 29) |
| Self‐reported sleep problems (0‐100 scale) Higher scores indicate higher sleep problem levels | Mean sleep problems | Baseline mean score 68.0 (23.8)4 | SMD ‐0.07 (‐0.15 to 0.01) | 4547 (8 studies) | ⊕⊕⊝⊝ | NNTB not calculated due to lack of statistically significant difference |
| Self‐reported health‐related quality of life (0‐100 scale) Higher scores indicate higher burden of disease (lower quality of life) | Mean health‐related quality of life problems score was 3.9 points lower (2.3 to | Baseline mean score 57.9 (SD | SMD ‐0.20 (‐0.25 to ‐0.15) | 6861 (14 studies) | ⊕⊕⊝⊝ | NNTB 11 (95% CI 8 to 14) |
| Tolerability (withdrawal due to adverse events) | 191 per 1000 (172 to 210) | 102 per 1000 | RD 0.07 (0.04 to 0.10) | 7029 (15 studies) | ⊕⊕⊝⊝ | NNTH 14 (95% CI 10 to 25) |
| Safety (serious adverse events) | 18 per 1000 (16 to 20) | 21 per 1000 | RD ‐0.00 (‐0.01 to 0.00) | 6732 (13 studies) | ⊕⊝⊝⊝ | NNTH not calculated due to lack of statistically significant difference |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; FIQ: Fibromyalgia Impact Questionnaire; MFI: Multidimensional Fatigue Inventory; MOS‐Sleep problem index: Medical Outcome Study ‐ sleep problem index; NNTB: number needed to treat for an additional beneficial outcome; NNTH: number needed to treat for an additional harm; NRS: numerical rating scale; RD: risk difference; SMD: standardized mean difference; VAS: visual analog scale | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Downgraded once: indirectness: participants with major medical diseases and mental disorders except major depression excluded in > 50% of studies | ||||||
| Outcome | Number of participants (studies) | Effect size RD (95% CI) | Test for overall effect P value | Heterogeneity I² (%)
| Test of interaction: effect estimate and P value |
| Self‐reported pain relief 50% or greater |
|
|
|
| Z = 0.78; P = 0.43 |
| Only North American participants | 3935 (8) | 0.10 (0.08 to 0.13) | < 0.001 | 0 | |
| Only European participants | 960 (2) | 0.06 (0.01 to 0.12) | 0.02 | 0 |
|
| Withdrawal due to adverse events |
|
|
|
| Z = 1.14; P = 0.25 |
| Only North American participants | 3935 (8) | 0.08 (0.04 to 0.13) | < 0.0002 | 71 | |
| Only European participants | 960 (2) | 0.12 (0.08 to 0.17) | < 0.0001 | 0 |
|
| CI: confidence interval; RD: risk difference; SNRIs: serotonin and noradrenaline reuptake inhibitors | |||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 Self‐reported pain relief of 50% or greater Show forest plot | 15 | 6918 | Risk Difference (IV, Random, 95% CI) | 0.09 [0.07, 0.11] |
| 1.1.1 Duloxetine | 7 | 2582 | Risk Difference (IV, Random, 95% CI) | 0.10 [0.06, 0.14] |
| 1.1.2 Milnacipran | 8 | 4336 | Risk Difference (IV, Random, 95% CI) | 0.09 [0.06, 0.11] |
| 1.2 PGIC much or very much improved Show forest plot | 6 | 2918 | Risk Difference (M‐H, Random, 95% CI) | 0.19 [0.12, 0.26] |
| 1.2.1 Duloxetine | 1 | 530 | Risk Difference (M‐H, Random, 95% CI) | 0.35 [0.27, 0.42] |
| 1.2.2 Milnacipran | 5 | 2388 | Risk Difference (M‐H, Random, 95% CI) | 0.15 [0.11, 0.19] |
| 1.3 Withdrawal due to adverse events Show forest plot | 15 | 7029 | Risk Difference (IV, Random, 95% CI) | 0.07 [0.04, 0.10] |
| 1.3.1 Desvenlafaxine | 1 | 82 | Risk Difference (IV, Random, 95% CI) | ‐0.03 [‐0.09, 0.04] |
| 1.3.2 Duloxetine | 7 | 2642 | Risk Difference (IV, Random, 95% CI) | 0.05 [0.02, 0.07] |
| 1.3.3 Milnacipran | 7 | 4305 | Risk Difference (IV, Random, 95% CI) | 0.11 [0.07, 0.14] |
| 1.4 Serious adverse events Show forest plot | 13 | 6732 | Risk Difference (IV, Random, 95% CI) | ‐0.00 [‐0.01, 0.00] |
| 1.4.1 Desvenlafaxine | 1 | 82 | Risk Difference (IV, Random, 95% CI) | 0.00 [‐0.05, 0.05] |
| 1.4.2 Duloxetine | 6 | 2432 | Risk Difference (IV, Random, 95% CI) | ‐0.00 [‐0.01, 0.01] |
| 1.4.3 Milnacipran | 6 | 4218 | Risk Difference (IV, Random, 95% CI) | ‐0.00 [‐0.01, 0.01] |
| 1.5 Self‐reported fatigue Show forest plot | 12 | 6168 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.13 [‐0.18, ‐0.08] |
| 1.5.1 Duloxetine | 5 | 1954 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.12 [‐0.21, ‐0.03] |
| 1.5.2 Milnacpran | 7 | 4214 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.14 [‐0.21, ‐0.07] |
| 1.6 Self‐reported sleep problems Show forest plot | 8 | 4547 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.07 [‐0.15, 0.01] |
| 1.6.1 Duloxetine | 3 | 1382 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.20 [‐0.31, ‐0.10] |
| 1.6.2 Milnacipran | 5 | 3165 | Std. Mean Difference (IV, Random, 95% CI) | 0.02 [‐0.05, 0.10] |
| 1.7 Self‐reported health‐related quality of life Show forest plot | 14 | 6861 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.20 [‐0.25, ‐0.15] |
| 1.7.1 Duloxetine | 7 | 2604 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.22 [‐0.30, ‐0.13] |
| 1.7.2 Milnacipran | 7 | 4257 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.19 [‐0.25, ‐0.12] |
| 1.8 Self‐reported pain relief of 30% or greater Show forest plot | 15 | 6924 | Risk Difference (IV, Random, 95% CI) | 0.10 [0.08, 0.12] |
| 1.8.1 Duloxetine | 7 | 2588 | Risk Difference (IV, Random, 95% CI) | 0.11 [0.07, 0.15] |
| 1.8.2 Milnacipran | 8 | 4336 | Risk Difference (IV, Random, 95% CI) | 0.10 [0.07, 0.13] |
| 1.9 Self‐reported mean pain intensity Show forest plot | 16 | 7014 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.22 [‐0.27, ‐0.17] |
| 1.9.1 Desvenlafaxine | 1 | 82 | Std. Mean Difference (IV, Random, 95% CI) | 0.16 [‐0.27, 0.59] |
| 1.9.2 Duloxetine | 7 | 2619 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.26 [‐0.35, ‐0.18] |
| 1.9.3 Milncipran | 8 | 4313 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.20 [‐0.26, ‐0.13] |
| 1.10 Self‐reported depression Show forest plot | 14 | 6478 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.16 [‐0.21, ‐0.11] |
| 1.10.1 Duloxetine | 7 | 2264 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.25 [‐0.34, ‐0.17] |
| 1.10.2 Milnacipran | 7 | 4214 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.11 [‐0.17, ‐0.05] |
| 1.11 Self‐reported anxiety Show forest plot | 9 | 3533 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.08 [‐0.21, 0.05] |
| 1.11.1 Duloxetine | 4 | 1403 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.07 [‐0.17, 0.04] |
| 1.11.2 Milnacipran | 5 | 2130 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.11 [‐0.36, 0.13] |
| 1.12 Self‐reported disability Show forest plot | 13 | 6789 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.21 [‐0.26, ‐0.16] |
| 1.12.1 Duloxetine | 7 | 2602 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.29 [‐0.37, ‐0.21] |
| 1.12.2 Milnacipran | 6 | 4187 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.16 [‐0.22, ‐0.10] |
| 1.13 Self‐reported cognitive disturbances Show forest plot | 8 | 5444 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.16 [‐0.21, ‐0.10] |
| 1.13.1 Duloxetine | 3 | 1360 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.27 [‐0.38, ‐0.16] |
| 1.13.2 Milnacipran | 5 | 4084 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.12 [‐0.18, ‐0.05] |
| 1.14 Tenderness Show forest plot | 5 | 1444 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.21 [‐0.33, ‐0.09] |
| 1.14.1 Duloxetine | 4 | 1364 | Std. Mean Difference (IV, Random, 95% CI) | ‐0.23 [‐0.35, ‐0.12] |
| 1.14.2 Milnacipran | 1 | 80 | Std. Mean Difference (IV, Random, 95% CI) | 0.12 [‐0.31, 0.56] |
| 1.15 Withdrawal due to lack of efficacy Show forest plot | 14 | 6924 | Risk Difference (IV, Random, 95% CI) | ‐0.03 [‐0.04, ‐0.02] |
| 1.15.1 Desvenlafaxine | 1 | 82 | Risk Difference (IV, Random, 95% CI) | 0.07 [‐0.02, 0.16] |
| 1.15.2 Duloxetine | 7 | 2642 | Risk Difference (IV, Random, 95% CI) | ‐0.04 [‐0.06, ‐0.02] |
| 1.15.3 Milnacipran | 6 | 4200 | Risk Difference (IV, Random, 95% CI) | ‐0.02 [‐0.04, ‐0.01] |
| 1.16 Nausea Show forest plot | 12 | 6606 | Risk Difference (IV, Random, 95% CI) | 0.16 [0.14, 0.19] |
| 1.16.1 Desvenlafaxine | 1 | 82 | Risk Difference (IV, Random, 95% CI) | 0.04 [‐0.10, 0.18] |
| 1.16.2 Duloxetine | 6 | 2432 | Risk Difference (IV, Random, 95% CI) | 0.19 [0.15, 0.22] |
| 1.16.3 Milnacipran | 5 | 4092 | Risk Difference (IV, Random, 95% CI) | 0.15 [0.12, 0.18] |
| 1.17 Somnolence Show forest plot | 7 | 2514 | Risk Difference (IV, Random, 95% CI) | 0.05 [0.02, 0.08] |
| 1.17.1 Desvenlafaxine | 1 | 82 | Risk Difference (IV, Random, 95% CI) | ‐0.05 [‐0.17, 0.06] |
| 1.17.2 Duloxetine | 6 | 2432 | Risk Difference (IV, Random, 95% CI) | 0.06 [0.03, 0.09] |
| 1.18 Insomnia Show forest plot | 9 | 5387 | Risk Difference (M‐H, Random, 95% CI) | 0.03 [0.01, 0.04] |
| 1.18.1 Desvenlafaxine | 1 | 82 | Risk Difference (M‐H, Random, 95% CI) | ‐0.08 [‐0.18, 0.03] |
| 1.18.2 Duloxetine | 4 | 1684 | Risk Difference (M‐H, Random, 95% CI) | 0.04 [0.01, 0.07] |
| 1.18.3 Milnacipran | 4 | 3621 | Risk Difference (M‐H, Random, 95% CI) | 0.03 [0.01, 0.04] |
