Table 4.
Conditions for which antidepressants show inconclusive evidence for pain
| Condition by drug class | Treatment regimen: median (minimum-maximum) dose and duration | Outcome | Effect estimate (95% CI)* | No of trials (No of participants) | Certainty of evidence |
|---|---|---|---|---|---|
| SNRI | |||||
| Atypical chronic orofacial pain54 | Venlafaxine 37.5-75 mg for 4 weeks (1 trial) | Pain intensity | MD −13 (−26.1 to 0.1) | 1 (36) | Low† |
| Chronic migraine61 | Venlafaxine 75-150 mg for 10 weeks | Headache frequency (days) | MD −1.4 (−2.8 to −0.1) | 1 (49) | Low† |
| Sciatica32 | Duloxetine 120 mg for 4 weeks (1 trial); milnacipran 100 mg for 8 (6-10) weeks (2 trials) | Pain intensity | MD −17.8 (−45.5 to 9.9) | 3 (96) | Very low |
| Chronic tension-type headache50 | Venlafaxine 150 mg for 12 weeks (1 trial) | Headache frequency (days) | MD −2.3 (−7.3 to 2.7) | 1 (59) | Low |
| SSRI | |||||
| Chronic pelvic pain63 | Sertraline 100 mg for 6 weeks (1 trial) | Pain intensity | MD 0 (−6 to 6) | 1 (23) | Low† |
| Chronic prostatitis59 | Fluvoxamine 50-300 mg for 8 weeks (1 trial) | Pain intensity | MD −45 (−77.6, −12.4) | 1 (42) | Low† |
| Irritable bowel syndrome56 | Fluoxetine 20 mg for 9 (6-12) weeks (2 trials); paroxetine 40 mg for 12 weeks (1 trial) | Abdominal pain not improving | RR 0.6 (0.3 to 1.3) | 3 (167) | Very low† |
| Chronic migraine61 | S-fluoxetine 40 mg for 12 weeks (1 trial) | Headache frequency (days) | MD −1.4 (−2.7, −0.1) | 1 (33) | Low† |
| Postoperative pain16 | Escitalopram 10 mg for 7 days (including day of surgery) (1 trial) | Pain 24 hours post-surgery | MD 0 (−7.1 to 7.1) | 1 (114) | Low |
| Chronic tension-type headache50 | Citalopram 20 mg for 24 weeks (1 trial) | Headache frequency (days) | MD −0.2 (−3.9 to 3.5) | 1 (68) | Low |
| TCA | |||||
| Acute oral mucositis58 | Doxepin mouth rinse, single dose of 10 mg/mL×2.5 mL, diluted to 5 mL with 2.5 mL of sterile or distilled water (1 trial) | Pain intensity | MD −44 (−67 to −21) | 1 (140) | Low† |
| Atypical chronic orofacial pain54 | Amitriptyline 10 mg for 8 weeks (1 trial) | Pain intensity | MD −15.7 (−32.4 to 1.1) | 1 (42) | Low† |
| Back pain32 | Amitriptyline 15 (5-25) mg for 17 (8-26) weeks (2 trials); desipramine 60 mg for 12 weeks (2 trials); nortriptyline 100 mg for 8 weeks (1 trial); imipramine 75 mg for 4 weeks (1 trial); doxepin 300 mg for 6 weeks | Pain intensity | MD −10.3 (−18.8 to −1.9) | 7 (591) | Very low |
| Bladder pain syndrome55 | Amitriptyline 62.5 (25-100) mg for 14 (12-16) weeks | Pain intensity | MD −12.7 (−33.1 to 7.6) | 2 (279) | Very low† |
| Fibromyalgia49 | Amitriptyline 37.5 (25-50) mg for 8.5 (8-24) weeks | 50% pain reduction | RR 2.1 (1.2 to 3.6) | 4 (275) | Very low |
| Phantom limb pain60‡ | Amitriptyline 10-125 mg for 6 weeks (1 trial) | Pain intensity | MD 0 (−17.6 to 17.6) | 1 (39) | Low† |
| Rheumatoid arthritis64 | Amitriptyline 50 (25-75) mg for 6 (1 day to 12 weeks) weeks (3 trials); dothiepin 75-150 mg for 7-10 weeks (2 trial); imipramine 75 mg for 6 weeks (1 trial); trimipramine 75 mg for 12 weeks (1 trial) | Pain intensity | NE. No benefit of TCA in the descriptive analysis | 7 (482) | Very low |
| Sciatica32§ | Amitriptyline 50 mg for 26 weeks (1 trial); nortriptyline 100 mg for 9 weeks (1 trial) | Pain intensity | MD −16 (−31.5 to −0.4) | 2 (114) | Very low |
| Vulvodynia57 | Desipramine 25-150 mg for 12 weeks (1 trial) | Pain intensity | MD 8.2 (−11.8, 28.2) | 1 (112) | Low† |
| NDRI | |||||
| Back pain32 | Bupropion 300 mg for 7 weeks (1 trial) | Pain intensity | MD −1 (−12.2 to 10.2) | 1 (44) | Low |
| SARI | |||||
| Back pain32 | Trazodone 600 mg for 6 weeks (1 trial) | Pain intensity | MD −5.4 (−22.9 to 12.1) | 1 (40) | Low |
| Burning mouth syndrome53 | Trazodone 200 mg for 8 weeks (1 trial) | Pain intensity | MD −1.6 (−6.8 to 3.6) | 1 (37) | Low† |
| Tetracyclic/atypical | |||||
| Back pain32 | Maprotiline 150 mg for 8 weeks (1 trial) | Pain intensity | MD −4.5 (−20.4 to 11.4) | 1 (34) | Low |
| Fibromyalgia46 | Mirtazapine 30 (30-45) mg for 13 (7-13) weeks (3 trials) | Pain reduction ≥50% | RR 1.3 (0.9 to 1.9) | 3 (591) | Very low |
| Functional dyspepsia36 | Mirtazapine 15 mg for 8 weeks (1 trial) | Pain intensity | MD 1.7 (−21.2 to 24.6) | 1 (34) | Low† |
| MAOI | |||||
| Fibromyalgia48 | Pirlindole 150 mg for 4 weeks (1 trial); moclobemide 600 mg for 12 weeks (12 weeks) | Pain intensity | MD −14.5 (−27.1 to −2) | 2 (121) | Very low† |
CI=confidence interval; MAOI=monoamine oxidase inhibitors; MD=mean difference; NDRI=noradrenaline-dopamine reuptake inhibitors; NE=not estimable; RR=risk ratio; SARI=serotonin antagonist and reuptake inhibitors; SNRI=serotonin-norepinephrine reuptake inhibitors; SSRI=selective serotonin reuptake inhibitors; TCA=tricyclic antidepressants.
Pain intensity outcomes are on a 0-100 scale unless stated otherwise.
Grading of recommendations assessment, development, and evaluation determined by current authors (see supplementary file 5 for details of the assessment).
Phantom pain is a form of neuropathic pain, although the trial included in this review was not included in the meta-analysis estimates of either of the neuropathic pain reviews (Finnerup et al 201517; Caruso et al 201935).
Sciatica may be classified as a form of neuropathic pain; however, the sciatica review included substantially more trials (n=6) than previous reviews (eg, Finnerup et al 201517 only included one trial).