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Review
. 2023 May 10;5(5):CD014682.
doi: 10.1002/14651858.CD014682.pub2.

Antidepressants for pain management in adults with chronic pain: a network meta-analysis

Hollie Birkinshaw  1 , Claire M Friedrich  1 , Peter Cole  2 , Christopher Eccleston  3 , Marc Serfaty  4 , Gavin Stewart  5 , Simon White  6 , R Andrew Moore  7 , David Phillippo  8 , Tamar Pincus  1
Affiliations
Review

Antidepressants for pain management in adults with chronic pain: a network meta-analysis

Hollie Birkinshaw et al. Cochrane Database Syst Rev. .

Abstract

Background: Chronic pain is common in adults, and often has a detrimental impact upon physical ability, well-being, and quality of life. Previous reviews have shown that certain antidepressants may be effective in reducing pain with some benefit in improving patients' global impression of change for certain chronic pain conditions. However, there has not been a network meta-analysis (NMA) examining all antidepressants across all chronic pain conditions.

Objectives: To assess the comparative efficacy and safety of antidepressants for adults with chronic pain (except headache).

Search methods: We searched CENTRAL, MEDLINE, Embase, CINAHL, LILACS, AMED and PsycINFO databases, and clinical trials registries, for randomised controlled trials (RCTs) of antidepressants for chronic pain conditions in January 2022.

Selection criteria: We included RCTs that examined antidepressants for chronic pain against any comparator. If the comparator was placebo, another medication, another antidepressant, or the same antidepressant at different doses, then we required the study to be double-blind. We included RCTs with active comparators that were unable to be double-blinded (e.g. psychotherapy) but rated them as high risk of bias. We excluded RCTs where the follow-up was less than two weeks and those with fewer than 10 participants in each arm. DATA COLLECTION AND ANALYSIS: Two review authors separately screened, data extracted, and judged risk of bias. We synthesised the data using Bayesian NMA and pairwise meta-analyses for each outcome and ranked the antidepressants in terms of their effectiveness using the surface under the cumulative ranking curve (SUCRA). We primarily used Confidence in Meta-Analysis (CINeMA) and Risk of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN) to assess the certainty of the evidence. Where it was not possible to use CINeMA and ROB-MEN due to the complexity of the networks, we used GRADE to assess the certainty of the evidence. Our primary outcomes were substantial (50%) pain relief, pain intensity, mood, and adverse events. Our secondary outcomes were moderate pain relief (30%), physical function, sleep, quality of life, Patient Global Impression of Change (PGIC), serious adverse events, and withdrawal.

Main results: This review and NMA included 176 studies with a total of 28,664 participants. The majority of studies were placebo-controlled (83), and parallel-armed (141). The most common pain conditions examined were fibromyalgia (59 studies); neuropathic pain (49 studies) and musculoskeletal pain (40 studies). The average length of RCTs was 10 weeks. Seven studies provided no useable data and were omitted from the NMA. The majority of studies measured short-term outcomes only and excluded people with low mood and other mental health conditions. Across efficacy outcomes, duloxetine was consistently the highest-ranked antidepressant with moderate- to high-certainty evidence. In duloxetine studies, standard dose was equally efficacious as high dose for the majority of outcomes. Milnacipran was often ranked as the next most efficacious antidepressant, although the certainty of evidence was lower than that of duloxetine. There was insufficient evidence to draw robust conclusions for the efficacy and safety of any other antidepressant for chronic pain. Primary efficacy outcomes Duloxetine standard dose (60 mg) showed a small to moderate effect for substantial pain relief (odds ratio (OR) 1.91, 95% confidence interval (CI) 1.69 to 2.17; 16 studies, 4490 participants; moderate-certainty evidence) and continuous pain intensity (standardised mean difference (SMD) -0.31, 95% CI -0.39 to -0.24; 18 studies, 4959 participants; moderate-certainty evidence). For pain intensity, milnacipran standard dose (100 mg) also showed a small effect (SMD -0.22, 95% CI -0.39 to 0.06; 4 studies, 1866 participants; moderate-certainty evidence). Mirtazapine (30 mg) had a moderate effect on mood (SMD -0.5, 95% CI -0.78 to -0.22; 1 study, 406 participants; low-certainty evidence), while duloxetine showed a small effect (SMD -0.16, 95% CI -0.22 to -0.1; 26 studies, 7952 participants; moderate-certainty evidence); however it is important to note that most studies excluded participants with mental health conditions, and so average anxiety and depression scores tended to be in the 'normal' or 'subclinical' ranges at baseline already. Secondary efficacy outcomes Across all secondary efficacy outcomes (moderate pain relief, physical function, sleep, quality of life, and PGIC), duloxetine and milnacipran were the highest-ranked antidepressants with moderate-certainty evidence, although effects were small. For both duloxetine and milnacipran, standard doses were as efficacious as high doses. Safety There was very low-certainty evidence for all safety outcomes (adverse events, serious adverse events, and withdrawal) across all antidepressants. We cannot draw any reliable conclusions from the NMAs for these outcomes.

Authors' conclusions: Our review and NMAs show that despite studies investigating 25 different antidepressants, the only antidepressant we are certain about for the treatment of chronic pain is duloxetine. Duloxetine was moderately efficacious across all outcomes at standard dose. There is also promising evidence for milnacipran, although further high-quality research is needed to be confident in these conclusions. Evidence for all other antidepressants was low certainty. As RCTs excluded people with low mood, we were unable to establish the effects of antidepressants for people with chronic pain and depression. There is currently no reliable evidence for the long-term efficacy of any antidepressant, and no reliable evidence for the safety of antidepressants for chronic pain at any time point.

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Conflict of interest statement

Hollie Birkinshaw: none known

Claire Friedrich: none known

Peter Cole is a Consultant in anaesthesia and pain medicine and manages people with chronic pain.

Christopher Eccleston: none known

Andrew Moore: none known

David Phillippo: none known

Marc Serfaty is a Consultant Psychiatrist and manages people with mental health conditions.

Gavin Stewart: none known

Simon White: none known

Tamar Pincus had one consultancy advisory meeting with Reckitt Benckiser Group PLC in February 2020. Reckitt Benckiser Group PLC are a multinational company that produce consumer goods, including pharmacological products such as analgesics. Tamar Pincus was asked to deliver an advisory talk to the company about psychological factors that might compromise randomised controlled trials. The University of Southampton was paid for her time. This talk did not cover the use of antidepressants.

Figures

1
1
PRISMA flow diagram of studies found, screened, and included
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Risk of bias of included studies by domain
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Risk of bias of included studies by study
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Substantial pain relief network plot. NASSA: noradrenergic and specific serotonergic antidepressants; SNRI: serotonin noradrenalin reuptake inhibitors; SSRI: selective serotonin reuptake inhibitors; TCA: tricyclic antidepressants; nonad: non‐antidepressants
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Substantial pain relief forest plot (log odds ratio with credible intervals). NASSA: noradrenergic and specific serotonergic antidepressants; SNRI: serotonin noradrenalin reuptake inhibitors; SSRI: selective serotonin reuptake inhibitors; TCA: tricyclic antidepressants; nonad: non‐antidepressants
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Pain intensity network diagram. SNRI: serotonin noradrenalin reuptake inhibitors; SSRI: selective serotonin reuptake inhibitors; TCA: tricyclic antidepressants; nonad: non‐antidepressants
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Pain intensity forest plot (standardised mean difference with credible intervals). SNRI: serotonin noradrenalin reuptake inhibitors; SSRI: selective serotonin reuptake inhibitors; TCA: tricyclic antidepressants; nonad: non‐antidepressants
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8
Mood network diagram. NASSA: noradrenergic and specific serotonergic antidepressants; SNRI: serotonin noradrenalin reuptake inhibitors; SSRI: selective serotonin reuptake inhibitors; TCA: tricyclic antidepressants; nonad: non‐antidepressants
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Mood forest plot (standardised mean difference with credible intervals). NASSA: noradrenergic and specific serotonergic antidepressants; SNRI: serotonin noradrenalin reuptake inhibitors; SSRI: selective serotonin reuptake inhibitors; TCA: tricyclic antidepressants; nonad: non‐antidepressants
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Adverse events network diagram. MAOI_rev: monoamine oxidase inhibitors (reversible); NASSA: noradrenergic and specific serotonergic antidepressants; SNRI: serotonin noradrenalin reuptake inhibitors; SSRI: selective serotonin reuptake inhibitors; TCA: tricyclic antidepressants; TECA: tetracyclic antidepressants; nonad: non‐antidepressants
11
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Adverse events forest plot (log odds ratio with credible intervals). MAOI_rev: monoamine oxidase inhibitors (reversible); NASSA: noradrenergic and specific serotonergic antidepressants; SNRI: serotonin noradrenalin reuptake inhibitors; SSRI: selective serotonin reuptake inhibitors; TCA: tricyclic antidepressants; TECA: tetracyclic antidepressants; nonad: non‐antidepressants
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Moderate pain relief network diagram. NASSA: noradrenergic and specific serotonergic antidepressants; SNRI: serotonin noradrenalin reuptake inhibitors; TCA: tricyclic antidepressants; nonad: non‐antidepressants
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Moderate pain relief forest plot. NASSA: noradrenergic and specific serotonergic antidepressants; SNRI: serotonin noradrenalin reuptake inhibitors; TCA: tricyclic antidepressants; nonad: non‐antidepressants
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Physical function network diagram. NASSA: noradrenergic and specific serotonergic antidepressants; SNRI: serotonin noradrenalin reuptake inhibitors; SSRI: selective serotonin reuptake inhibitors; TCA: tricyclic antidepressants; nonad: non‐antidepressants
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15
Physical function forest plot (standardised mean difference with credible intervals). NASSA: noradrenergic and specific serotonergic antidepressants; SNRI: serotonin noradrenalin reuptake inhibitors; SSRI: selective serotonin reuptake inhibitors; TCA: tricyclic antidepressants; nonad: non‐antidepressants
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Sleep network diagram. SNRI: serotonin noradrenalin reuptake inhibitors; SSRI: selective serotonin reuptake inhibitors
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Sleep forest plot (standardised mean difference with credible intervals). SNRI: serotonin noradrenalin reuptake inhibitors; SSRI: selective serotonin reuptake inhibitors
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Quality of life network diagram. SNRI: serotonin noradrenalin reuptake inhibitors; SSRI: selective serotonin reuptake inhibitors; TCA: tricyclic antidepressants; nonad: non‐antidepressants
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Quality of life forest plot (standardised mean difference with credible intervals). SNRI: serotonin noradrenalin reuptake inhibitors; SSRI: selective serotonin reuptake inhibitors; TCA: tricyclic antidepressants; nonad: non‐antidepressants
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Patient Global Impression of Change much/very much improved network diagram. SNRI: serotonin noradrenalin reuptake inhibitors
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Patient Global Impression of Change much/very much improved forest plot. SNRI: serotonin noradrenalin reuptake inhibitors; SSRI: selective serotonin reuptake inhibitors; TCA: tricyclic antidepressants; nonad: non‐antidepressants
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Patient Global Impression of Change continuous network diagram. SNRI: serotonin noradrenalin reuptake inhibitors; nonad: non‐antidepressants
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Patient Global Impression of Change continuous forest plot (standardised mean difference with credible intervals). SNRI: serotonin noradrenalin reuptake inhibitors; nonad: non‐antidepressants
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Serious adverse events network diagram. NARI: noradrenaline reuptake inhibitors; NDRI: Noradrenaline and dopamine reuptake inhibitors; NASSA: noradrenergic and specific serotonergic antidepressants; SNRI: serotonin noradrenaline reuptake inhibitors; SSRI: selective serotonin reuptake inhibitors; TCA: tricyclic antidepressants; nonad: non‐antidepressants
25
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Serious adverse events forest plot (log odds ratio with credible intervals). NARI: noradrenaline reuptake inhibitors; NDRI: Noradrenaline and dopamine reuptake inhibitors; NASSA: noradrenergic and specific serotonergic antidepressants; SNRI: serotonin noradrenaline reuptake inhibitors; SSRI: selective serotonin reuptake inhibitors; TCA: tricyclic antidepressants; nonad: non‐antidepressants
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Withdrawal network diagram. MAOI_rev: monoamine oxidase inhibitors (reversible); NARI: noradrenaline reuptake inhibitors; NDRI: noradrenaline and dopamine reuptake inhibitors; NASSA: noradrenergic and specific serotonergic antidepressants; SNRI: serotonin noradrenaline reuptake inhibitors; SSRI: selective serotonin reuptake inhibitors; TCA: tricyclic antidepressants; TECA: tetracyclic antidepressants; nonad: non‐antidepressants
27
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Withdrawal forest plot (log odds ratio with credible intervals). MAOI_rev: monoamine oxidase inhibitors (reversible); NARI: noradrenaline reuptake inhibitors; NDRI: Noradrenaline and dopamine reuptake inhibitors; NASSA: noradrenergic and specific serotonergic antidepressants; SNRI: serotonin noradrenaline reuptake inhibitors; SSRI: selective serotonin reuptake inhibitors; TCA: tricyclic antidepressants; TECA: tetracyclic antidepressants; nonad: non‐antidepressants
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    1. Enomoto H, Yasuda H, Nishiyori A, Fujikoshi S, Furukawa M, Ishida M, et al. Duloxetine in patients with diabetic peripheral neuropathic pain in Japan: a randomized, doubleblind, noninferiority comparative study with pregabalin. Journal of Pain Research 2018;11:1857-68. [DOI: 10.2147/JPR.S170646] - DOI - PMC - PubMed
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Ginsberg 1998 {published data only}
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Hannonen 1998 {published data only}
    1. Hannonen P, Malminiemi K, Yli-Kerttula U, Isomeri R, Roponen P. A randomized, double-blind, placebo-controlled study of moclobemide and amitriptyline in the treatment of fibromyalgia in females without psychiatric disorder. British Journal of Rheumatology 1998;37(12):1279-86. [DOI: 10.1093/rheumatology/37.12.1279] - DOI - PubMed
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Iwaki 2020 {published data only}
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Rintala 2007 {published data only}
    1. Rintala DH, Holmes SA, Courtade D, Fiess RN, Tastard LV, Loubser PG. Comparison of the effectiveness of amitriptyline and gabapentin on chronic neuropathic pain in persons with spinal cord injury. Archives of Physical Medicine and Rehabilitation 2007;88(12):1547-60. [DOI: 10.1016/j.apmr.2007.07.038] - DOI - PubMed
Robinson 2004 {published data only}
    1. Robinson LR, Czerniecki JM, Ehde DM, Edwards WT, Judish DA, Goldberg ML, et al. Trial of amitriptyline for relief of pain in amputees: results of a randomized controlled study. Archives of Physical Medicine and Rehabilitation 2004;85(1):1-6. [DOI: 10.1016/s0003-9993(03)00476-3] - DOI - PubMed
Rowbotham 2004 {published data only}
    1. Rowbotham MC, Goli V, Kunz NR, Lei D. Venlafaxine extended release in the treatment of painful diabetic neuropathy: a double-blind, placebo-controlled study. Pain 2004;110(3):697-706. [DOI: 10.1016/j.pain.2004.05.010] - DOI - PubMed
Rowbotham 2005 {published data only}
    1. Rowbotham MC, Reisner LA, Davies PS, Fields HL. Treatment response in antidepressant-naïve postherpetic neuralgia patients: double-blind, randomized trial. Journal of Pain 2005;6(11):741‐6. [DOI: 10.1016/j.jpain.2005.07.001] - DOI - PubMed
Rowbotham 2012 {published data only}
    1. Rowbotham MC, Arslanian A, Nothaft W, Duan WR, Best AE, Pritchett Y, et al. Efficacy and safety of the alpha4β2 neuronal nicotinic receptor agonist ABT-894 in patients with diabetic peripheral neuropathic pain. Pain 2012;153(4):862-8. [DOI: 10.1016/j.pain.2012.01.009] - DOI - PubMed
Russell 2008 {published data only}
    1. Russell IJ, Mease PJ, Smith TR, Kajdasz DK, Wohlreich MM, Detke MJ, et al. Efficacy and safety of duloxetine for treatment of fibromyalgia in patients with or without major depressive disorder: results from a 6-month, randomized, double-blind, placebo-controlled, fixed-dose trial. Pain 2008;136(3):432-44. [DOI: 10.1016/j.pain.2008.02.024] - DOI - PubMed
Sarzi Puttini 1988 {published data only}
    1. Sarzi Puttini P, Cazzola M, Boccassini L, Ciniselli G, Santandrea S, Caruso I, et al. A comparison of dothiepin versus placebo in the treatment of pain in rheumatoid arthritis and the association of pain with depression. Journal of International Medical Research 1988;16(5):331-7. [DOI: 10.1177/030006058801600502] - DOI - PubMed
Schukro 2016 {published data only}
    1. Schukro RP, Oehmke MJ, Geroldinger A, Heinze G, Kress H-G, Pramhas S. Efficacy of duloxetine in chronic low back pain with a neuropathic component: a randomized, double-blind, placebo-controlled crossover trial. Anesthesiology 2016;124(1):150-8. [DOI: 10.1097/ALN.0000000000000902] - DOI - PubMed
Scudds 1989 {published data only}
    1. Scudds RA, McCain GA, Rollman GB, Harth M. Improvements in pain responsiveness in patients with fibrositis after successful treatment with amitriptyline. Journal of Rheumatology Supplement 1989;19:98-103. - PubMed
Sencan 2004 {published data only}
    1. Sencan S, Ak S, Karan A, Muslumanoglu L, Ozcan E, Berker E. A study to compare the therapeutic efficacy of aerobic exercise and paroxetine in fibromyalgia syndrome. Journal of Back and Musculoskeletal Rehabilitation 2004;17(2):57-61. [DOI: 10.3233/BMR-2004-17204] - DOI
Shakiba 2018 {published data only}
    1. Shakiba M, Moazen-Zadeh E, Noorbala AA, Jafarinia M, Divsalar P, Kashani L, et al. Saffron (Crocus sativus) versus duloxetine for treatment of patients with fibromyalgia: a randomized double-blind clinical trial. Avicenna Journal of Phytomedicine 2018;8(6):513-23. - PMC - PubMed
Sindrup 2003 {published data only}
    1. Sindrup SH, Bach FW, Madsen C, Gram LF, Jensen TS. Venlafaxine versus imipramine in painful polyneuropathy: a randomized, controlled trial. Neurology 2003;60(8):1284-9. - PubMed
Skljarevski 2009 {published data only}
    1. Skljarevski V, Ossanna M, Liu-Seifert H, Zhang Q, Chappell A, Iyengar S, et al. A double-blind, randomized trial of duloxetine versus placebo in the management of chronic low back pain. European Journal of Neurology 2009;16(9):1041-8. [DOI: 10.1111/j.1468-1331.2009.02648.x] - DOI - PubMed
Skljarevski 2010a {published data only}
    1. Skljarevski V, Desaiah D, Liu-Seifert H, Zhang Q, Chappell AS, Detke MJ, et al. Efficacy and safety of duloxetine in patients with chronic low back pain. Spine 2010;35(13):E578-85. [DOI: 10.1097/BRS.0b013e3181d3cef6] - DOI - PubMed
Skljarevski 2010b {published data only}
    1. Skljarevski V, Zhang S, Desaiah D, Alaka KJ, Palacios S, Miazgowski T, et al. Duloxetine versus placebo in patients with chronic low back pain: a 12-week, fixed-dose, randomized, double-blind trial. Journal of Pain 2010;11(12):1282-90. [DOI: 10.1016/j.jpain.2010.03.002] - DOI - PubMed
Smith 2013 {published data only}
    1. Smith EM, Pang H, Cirrincione C, Fleishman S, Paskett ED, Ahles T, et al. Effect of duloxetine on pain, function, and quality of life among patients with chemotherapy-induced painful peripheral neuropathy: a randomized clinical trial. Journal of the American Medical Association 2013;309(13):1359-67. [DOI: 10.1001/jama.2013.2813] - DOI - PMC - PubMed
Sofat 2017 {published data only}
    1. Sofat N, Harrison A, Russell MD, Ayis S, Kiely PD, Baker EH, et al. The effect of pregabalin or duloxetine on arthritis pain: a clinical and mechanistic study in people with hand osteoarthritis. Journal of Pain Research 2017;10:2437-49. [DOI: 10.2147/JPR.S147640] - DOI - PMC - PubMed
Spinhoven 2010 {published data only}
    1. Spinhoven P, Van der Does AJ, Van Dijk E, Van Rood YR. Heart-focused anxiety as a mediating variable in the treatment of noncardiac chest pain by cognitive-behavioral therapy and paroxetine. Journal of Psychosomatic Research 2010;69(3):227-35. [DOI: 10.1016/j.jpsychores.2010.02.005] - DOI - PubMed
Srinivasan 2021 {published data only}
    1. Srinivasan A, Dutta P, Bansal D, Chakrabarti A, Bhansali AK, Hota D. Efficacy and safety of low-dose naltrexone in painful diabetic neuropathy: a randomized, double-blind, active-control, crossover clinical trial. Journal of Diabetes 2021;13(10):770-8. [DOI: 10.1111/1753-0407.13202] - DOI - PubMed
Staud 2015 {published data only}
    1. Staud R, Lucas YE, Price DD, Robinson ME. Effects of milnacipran on clinical pain and hyperalgesia of patients with fibromyalgia: results of a 6-week randomized controlled trial. Journal of Pain 2015;16(8):750-9. [DOI: 10.1016/j.jpain.2015.04.010] - DOI - PubMed
Suttiruksa 2016 {published data only}
    1. Suttiruksa S, Yeephu S, Prateepavanich P, Suthisisang C. Effects of mirtazapine on quality of life of Thai patients with fibromyalgia syndrome: a double-blind, randomized, placebo-controlled trial. Asian Biomedicine 2016;10(5):435-45. [DOI: 10.5372/1905-7415.1005.506] - DOI
Talley 2008 {published data only}
    1. Talley NJ, Kellow JE, Boyce P, Tennant C, Huskic S, Jones M. Antidepressant therapy (imipramine and citalopram) for irritable bowel syndrome: a double-blind, randomized, placebo-controlled trial. Digestive Diseases and Sciences 2008;53(1):108-15. [DOI: 10.1007/s10620-007-9830-4] - DOI - PubMed
Tammiala‐Salonen 1999 {published data only}
    1. Tammiala-Salonen T, Forssell H. Trazodone in burning mouth pain: a placebo-controlled, double-blind study. Journal of Orofacial Pain 1999;13(2):83-8. - PubMed
Tanum 1996 {published data only}
    1. Tanum L, Malt UF. A new pharmacologic treatment of functional gastrointestinal disorder. A double-blind placebo-controlled study with mianserin. Scandinavian Journal of Gastroenterology 1996;31(4):318-25. [DOI: 10.3109/00365529609006404] - DOI - PubMed
Tasmuth 2002 {published data only}
    1. Tasmuth T, Härtel B, Kalso E. Venlafaxine in neuropathic pain following treatment of breast cancer. European Journal of Pain 2002;6(1):17-24. [DOI: 10.1053/eujp.2001.0266] - DOI - PubMed
Tesfaye 2013 {published data only}
    1. Tesfaye S, Wilhelm S, Lledo A, Schacht A, Tölle T, Bouhassira D, et al. Duloxetine and pregabalin: high-dose monotherapy or their combination? the "COMBO-DN study"— a multinational, randomized, double-blind, parallel-group study in patients with diabetic peripheral neuropathic pain. Pain 2013;154(12):2616-25. [DOI: 10.1016/j.pain.2013.05.043] - DOI - PubMed
Tétreault 2016 {published and unpublished data}
    1. Tétreault P, Mansour A, Vachon-Presseau E, Schnitzer TJ, Apkarian AV, Baliki MN. Brain connectivity predicts placebo response across chronic pain clinical trials. PLOS Biology 2016;14(10):e1002570. [DOI: 10.1371/journal.pbio.1002570] - DOI - PMC - PubMed
Trugman 2014 {published data only}
    1. Trugman JM, Palmer RH, Ma Y. Milnacipran effects on 24-hour ambulatory blood pressure and heart rate in fibromyalgia patients: a randomized, placebo-controlled, dose-escalation study. Current Medical Research and Opinion 2014;30(4):589-97. [DOI: 10.1185/03007995.2013.861812] - DOI - PubMed
Uchio 2018 {published data only}
    1. Uchio Y, Enomoto H, Alev L, Kato Y, Ishihara H, Tsuji T, et al. A randomized, double-blind, placebo-controlled phase III trial of duloxetine in Japanese patients with knee pain due to osteoarthritis. Journal of Pain Research 2018;11:809-21. [DOI: 10.2147/JPR.S164128] - DOI - PMC - PubMed
Urquhart 2018 {published data only}
    1. Urquhart DM, Wluka AE, Van Tulder M, Heritier S, Forbes A, Fong C, et al. Efficacy of low-dose amitriptyline for chronic low back pain: a randomized clinical trial. JAMA Internal Medicine 2018;178(11):1474-81. [DOI: 10.1001/jamainternmed.2018.4222] - DOI - PMC - PubMed
Vahedi 2005 {published data only}
    1. Vahedi H, Merat S, Rashidioon A, Ghoddoosi A, Malekzadeh R. The effect of fluoxetine in patients with pain and constipation-predominant irritable bowel syndrome: a double-blind randomized-controlled study. Alimentary Pharmacology and Therapeutics 2005;22(5):381-5. [DOI: 10.1111/j.1365-2036.2005.02566.x] - DOI - PubMed
Van Ophoven 2004 {published data only}
    1. Van Ophoven A, Pokupic S, Heinecke A, Hertle L. A prospective, randomized, placebo controlled, double-blind study of amitriptyline for the treatment of interstitial cystitis. Journal of Urology 2004;172(2):533-6. [DOI: 10.1097/01.ju.0000132388.54703.4d] - DOI - PubMed
Ventafridda 1987 {published data only}
    1. Ventafridda V, Bonezzi C, Caraceni A, De Conno F, Guarise G, Ramella G, et al. Antidepressants for cancer pain and other painful syndromes with deafferentation component: comparison of amitriptyline and trazodone. Italian Journal of Neurological Sciences 1987;8(6):579-87. [DOI: 10.1007/BF02333665] - DOI - PubMed
Vitton 2004 {published data only}
    1. Vitton O, Gendreau M, Gendreau J, Kranzler J, Rao SG. A double-blind placebo-controlled trial of milnacipran in the treatment of fibromyalgia. Human Psychopharmacology: Clinical and Experimental 2004;19 Suppl 1:S27-35. [DOI: 10.1002/hup.622] - DOI - PubMed
Vollmer 2014 {published data only}
    1. Vollmer TL, Robinson MJ, Risser RC, Malcolm SK. A randomized, double-blind, placebo-controlled trial of duloxetine for the treatment of pain in patients with multiple sclerosis. Pain Practice 2014;14(8):732-44. [DOI: 10.1111/papr.12127] - DOI - PubMed
Vranken 2011 {published data only}
    1. Vranken JH, Hollmann MW, Van der Vegt MH, Kruis MR, Heesen M, Vos K, et al. Duloxetine in patients with central neuropathic pain caused by spinal cord injury or stroke: a randomized, double-blind, placebo-controlled trial. Pain 2011;152(2):267-73. [DOI: 10.1016/j.pain.2010.09.005] - DOI - PubMed
Vrethem 1997 {published data only}
    1. Vrethem M, Boivie J, Arnqvist H, Holmgren H, Lindström T, Thorell LH. A comparison of amitriptyline and maprotiline in the treatment of painful polyneuropathy in diabetics and nondiabetics. Clinical Journal of Pain 1997;13(4):313-23. [DOI: 10.1097/00002508-199712000-00009] - DOI - PubMed
Wang 2017 {published data only}
    1. Wang G, Bi L, Li X, Li Z, Zhao D, Chen J, et al. Efficacy and safety of duloxetine in Chinese patients with chronic pain due to osteoarthritis: a randomized, double-blind, placebo-controlled study. Osteoarthritis Cartilage 2017;25(6):832-8. [DOI: 10.1016/j.joca.2016.12.025] - DOI - PubMed
Ward 1986 {published data only}
    1. Ward NG. Tricyclic antidepressants for chronic low-back pain. Mechanisms of action and predictors of response. Spine 1986;11(7):661-5. [DOI: 10.1097/00007632-198609000-00003] - DOI - PubMed
Ware 2010 {published data only}
    1. Ware MA, Fitzcharles M-A, Joseph L, Shir Y. The effects of nabilone on sleep in fibromyalgia: results of a randomized controlled trial. Anesthesia & Analgesia 2010;110(2):604-10. [DOI: 10.1213/ANE.0b013e3181c76f70] - DOI - PubMed
Watson 1992 {published data only}
    1. Watson PN, Chipman M, Reed K, Evans RJ, Birkett N. Amitriptyline versus maprotiline in postherpetic neuralgia: a randomized, double-blind, crossover trial. Pain 1992;48(1):29-36. [DOI: 10.1016/0304-3959(92)90128-X] - DOI - PubMed
Watson 1998 {published data only}
    1. Watson CP, Vernich L, Chipman M, Reed K. Nortriptyline versus amitriptyline in postherpetic neuralgia: a randomized trial. Neurology 1998;51(4):1166-71. [DOI: 10.1212/wnl.51.4.1166] - DOI - PubMed
Wernicke 2006 {published data only}
    1. Wernicke JF, Pritchett YL, D'Souza DN, Waninger A, Tran P, Iyengar S, et al. A randomized controlled trial of duloxetine in diabetic peripheral neuropathic pain. Neurology 2006;67(8):1411-20. [DOI: 10.1212/01.wnl.0000240225.04000.1a] - DOI - PubMed
Wolfe 1994 {published data only}
    1. Wolfe F, Cathey MA, Hawley DJ. A double-blind placebo controlled trial of fluoxetine in fibromyalgia. Scandinavian Journal of Rheumatology 1994;23(5):255-9. [DOI: 10.3109/03009749409103725] - DOI - PubMed
Yasuda 2011 {published data only}
    1. Yasuda H, Hotta N, Nakao K, Kasuga M, Kashiwagi A, Kawamori R. Superiority of duloxetine to placebo in improving diabetic neuropathic pain: results of a randomized controlled trial in Japan. Journal of Diabetes Investigation 2011;2(2):132-9. [DOI: 10.1111/j.2040-1124.2010.00073.x] - DOI - PMC - PubMed
Yeephu 2013 {published data only}
    1. Yeephu S, Suthisisang C, Suttiruksa S, Prateepavanich P, Limampai P, Russell IJ. Efficacy and safety of mirtazapine in fibromyalgia syndrome patients: a randomized placebo-controlled pilot study. Annals of Pharmacotherapy 2013;47(7-8):921-32. [DOI: 10.1345/aph.1R725] - DOI - PubMed
Yucel 2005 {published data only}
    1. Yucel A, Ozyalcin S, Koknel Talu G, Kiziltan E, Yucel B, Andersen OK, et al. The effect of venlafaxine on ongoing and experimentally induced pain in neuropathic pain patients: a double blind, placebo controlled study. European Journal of Pain 2005;9(4):407-16. [DOI: 10.1016/j.ejpain.2004.09.009] - DOI - PubMed
Zabihiyeganeh 2021 {published data only}
    1. Zabihiyeganeh M, Kadijani AA, Afshar SV, Janbozorgi M, Akbari A, Mirzaei A. The effect of cognitive-behavioral therapy versus duloxetine on the laboratory indices of inflammation in fibromyalgia: a randomized controlled trial. Journal of Rational-Emotive & Cognitive-Behavior Therapy 202s;40:512–26. [DOI: 10.1007/s10942-021-00426-y] - DOI
Zitman 1990 {published data only}
    1. Zitman FG, Linssen AC, Edelbroek PM, Stijnen T. Low dose amitriptyline in chronic pain: the gain is modest. Pain 1990;42(1):35-42. [DOI: 10.1016/0304-3959(90)91089-2] - DOI - PubMed

References to studies excluded from this review

Amelin 1991 {published data only}
    1. Amelin AV, Vasil'ev IN, Ignatov ID, Skoromets AA. The combined use of acupuncture and antidepressants for managing the spondylogenic lumbosacral pain syndrome. Farmakologiia i Toksikologiia [Pharmacology and Toxicology] 1991;54(5):12-3. - PubMed
Amr 2010 {published data only}
    1. Amr YM, Yousef AA. Evaluation of efficacy of the perioperative administration of venlafaxine or gabapentin on acute and chronic postmastectomy pain. Clinical Journal of Pain 2010;26(5):381-5. [DOI: 10.1097/AJP.0b013e3181cb406e] - DOI - PubMed
Arnold 2014 {published data only}
    1. Arnold L, Sarzi-Puttini P, Arsenault P, Khan T, Bhadra Brown P, Clair A, et al. Pregabalin is effective irrespective of antidepressant class in fibromyalgia patients currently receiving antidepressant medication for comorbid depression. Journal of Pain 2014;15(4 Suppl 1):S75. [DOI: 10.1016/j.jpain.2014.01.307] - DOI
Avan 2018 {published data only}
    1. Avan R, Janbabaei G, Hendouei N, Alipour A, Borhani S, Tabrizi N, et al. The effect of pregabalin and duloxetine treatment on quality of life of breast cancer patients with taxane-induced sensory neuropathy: a randomized clinical trial. Journal of Research in Medical Sciences 2018;23(1):52. [DOI: 10.4103/jrms.JRMS_1068_17] - DOI - PMC - PubMed
Beaumont 1980 {published data only}
    1. Beaumont G, Seldrup J. Comparative trial of clomipramine and placebo in the treatment of terminal pain. Journal of International Medical Research 1980;8 Suppl 3:67‐9. - PubMed
Braak 2011 {published data only}
    1. Braak B, Klooker TK, Wouters MM, Lei A, den Wijngaard RM, Boeckxstaens GE. Randomised clinical trial: the effects of amitriptyline on drinking capacity and symptoms in patients with functional dyspepsia, a double-blind placebo-controlled study. Alimentary Pharmacology and Therapeutics 2011;34(6):638-48. [DOI: 10.1111/j.1365-2036.2011.04775.x] - DOI - PubMed
Carette 1995 {published data only}
    1. Carette S, Oakson G, Guimont C, Steriade M. Sleep electroencephalography and the clinical response to amitriptyline in patients with fibromyalgia. Arthritis & Rheumatology 1995;38(9):1211-7. [DOI: 10.1002/art.1780380906] - DOI - PubMed
ChiCTR2000030195 {published data only}
    1. ChiCTR2000030195. Duloxetine reduces postoperative pain and improves quality of life after single-segment lumbar fusion procedures in centrally sensitized patients: a prospective randomized controlled study. https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR2000030195 (first received 25 February 2020).
ChiCTR‐TRC‐12001968 {published data only}
    1. ChiCTR-TRC-12001968. Epidemiology survey and the effects of low-dose amitriptyline on intractable functional dyspepsia: a prospective, randomized, controlled study. https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR-TRC-12001968 (first received 13 February 2012).
ChiCTR‐TRC‐12001969 {published data only}
    1. ChiCTR-TRC-12001969. Incidence of refractory irritable bowel syndrome and the effects of low dose amitriptyline in the patients: a prospective, randomized-controlled trial. https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR-TRC-12001969 (first received 29 February 2012).
Chitsaz 2009 {published data only}
    1. Chitsaz A, Janghorbani M, Shaygannejad V, Ashtari F, Heshmatipour M, Freeman J. Sensory complaints of the upper extremities in multiple sclerosis: relative efficacy of nortriptyline and transcutaneous electrical nerve stimulation. Clinical Journal of Pain 2009;25(4):281-5. [DOI: 10.1097/AJP.0b013e318190862b] - DOI - PubMed
CTRI/2015/05/005791 {published data only}
    1. CTRI/2015/05/005791. Treatment of irritable bowel syndrome (IBS) by a plant based Ayurvedic formulation [Ayurvedic formulation developed for the prevention and management of irritable bowel syndrome (IBS)]. https://trialsearch.who.int/Trial2.aspx?TrialID=CTRI/2015/05/005791 (first received 21 May 2015).
Daghaghzadeh 2015 {published data only}
    1. Daghaghzadeh H, Naji F, Afshar H, Sharbafchi MR, Feizi A, Maroufi M, et al. Efficacy of duloxetine add on in treatment of inflammatory bowel disease patients: a double-blind controlled study. Journal of Research in Medical Sciences 2015;20(6):595‐601. [DOI: 10.4103/1735-1995.165969] - DOI - PMC - PubMed
Dinat 2015 {published data only}
    1. Dinat N, Marinda E, Moch S, Rice AS, Kamerman PR. Randomized, double-blind, crossover trial of amitriptyline for analgesia in painful HIV-associated sensory neuropathy. PLOS One 2015;10(5):e0126297. [DOI: 10.1371/journal.pone.0126297] - DOI - PMC - PubMed
Ehrnrooth 2001 {published data only}
    1. Ehrnrooth E, Grau C, Zachariae R, Andersen J. Randomized trial of opioids versus tricyclic antidepressants for radiation-induced mucositis pain in head and neck cancer. Acta Oncologica 2001;40(6):745-50. [DOI: 10.1080/02841860152619179] - DOI - PubMed
EUCTR2005‐005555‐17‐NL {published data only}
    1. EUCTR2005-005555-17-NL. [S,S]-reboxetine add-on trial: a randomized, double-blind, placebo-controlled, multi-center trial of [S,S]-reboxetine in patients with postherpetic neuralgia (PHN) concomitantly treated with pregabalin. https://trialsearch.who.int/Trial2.aspx?TrialID=EUCTR2005-005555-17-NL (first received 5 October 2006).
EUCTR2006‐003656‐38‐GB {published data only}
    1. EUCTR2006-003656-38-GB. A double-blind, randomised, parallel groups investigation into the effects of pregabalin, duloxetine and amitriptyline on aspects of pain, sleep, and next day performance in patients suffering from diabetic peripheral neuropathy. https://trialsearch.who.int/Trial2.aspx?TrialID=EUCTR2006-003656-38-GB (first received 18 September 2006).
EUCTR2006‐005506‐32‐DK {published data only}
    1. EUCTR2006-005506-32-DK. Pain, anxiety and depression in neuropathic and non-neuropathic pain: effect of monoamine modulation. https://trialsearch.who.int/Trial2.aspx?TrialID=EUCTR2006-005506-32-DK (first received 12 January 2007).
EUCTR2009‐013061‐26‐FI {published data only}
    1. EUCTR2009-013061-26-FI. Efficacy, safety, tolerability and pharmacokinetics of concomitant administration of tramadol with duloxetine or pregabalin: a randomized controlled flexible-dose study in patients with neuropathic pain. https://trialsearch.who.int/Trial2.aspx?TrialID=EUCTR2009-013061-26-FI (first received 8 June 2009).
EUCTR2016‐003146‐89‐GB {published data only}
    1. EUCTR2016-003146-89-GB. Optimal pathway for treating neuropathic pain in diabetes mellitus [A multicentre, double-blind, centre-stratified multi-period crossover trial to evaluate the efficacy of the optimal pathway for treatIng neuropathic pain in diabetes mellitus (OPTION-DM)]. https://trialsearch.who.int/Trial2.aspx?TrialID=EUCTR2016-003146-89-GB (first received 10 September 2018). - PMC - PubMed
EUCTR2017‐003307‐21‐NL {published data only}
    1. EUCTR2017-003307-21-NL. Personalized treatment of functional dyspepsia with nortriptyline [Tailored treatment of functional dyspepsia with nortriptyline: a multi-center double-blind placebo-controlled trial (TENDER)]. https://trialsearch.who.int/Trial2.aspx?TrialID=EUCTR2017-003307-21-NL (first received 19 December 2017).
EUCTR2018‐000133‐12‐GB {published data only}
    1. EUCTR2018-000133-12-GB. Efficacy and safety of products containing trazodone and gabapentin in patients affected by painful diabetic neuropathy [Efficacy and safety of fixed-dose combination (FDC) products containing trazodone and gabapentin in patients affected by painful diabetic neuropathy: randomized, controlled, dose finding study]. https://trialsearch.who.int/Trial2.aspx?TrialID=EUCTR2018-000133-12-GB (first received 26 June 2018).
EUCTR2019‐003437‐42‐DK {published data only}
    1. EUCTR2019-003437-42-DK. The effect of duloxetine on pain sensitivity in patients with osteoarthritis [A mechanism based proof of concept study of the effects of duloxetine in the treatment of patients with osteoarthritic knee pain]. https://trialsearch.who.int/Trial2.aspx?TrialID=EUCTR2019-003437-42-DK (first received 30 August 2019).
Farshchian 2018 {published data only}
    1. Farshchian N, Alavi A, Heydarheydari S, Moradian N. Comparative study of the effects of venlafaxine and duloxetine on chemotherapy-induced peripheral neuropathy. Cancer Chemotherapy and Pharmacology 2018;82(5):787-93. [DOI: 10.1007/s00280-018-3664-y] - DOI - PubMed
Frank 1988 {published data only}
    1. Frank RG, Kashani JH, Parker JC, Beck NC, Brownlee-Duffeck M, Elliott TR, et al. Antidepressant analgesia in rheumatoid arthritis. Journal of Rheumatology 1988;15(11):1632-8. - PubMed
Gardela 1991 {published data only}
    1. Gardela G. Value of adjuvant treatment with imipramine for lumbosacral pain syndrome. Polski Tygodnik Lekarski 1991;46(30-31):544-6. - PubMed
Gelijkens 2014 {published data only}
    1. Gelijkens V, Van Zundert J, De Vooght P, Vander Laenen M, Heylen R, Vanelderen P. The effectiveness of amitriptyline in the treatment of subacute lumbar radicular pain. European Journal of Anaesthesiology 2014;31:232.
Ghadir 2011 {published data only}
    1. Ghadir MR, Habibinejad H, Heidari A, Vahedi H. Doxepin is more effective than nortriptyline and placebo for the treatment of diarrhea-predominant irritable bowel syndrome: a randomized triple-blind placebo-controlled trial. Tehran University Medical Journal 2011;69(6):352‐8.
Goldenberg 2010 {published data only}
    1. Goldenberg DL, Clauw DJ, Palmer RH, Mease P, Chen W, Gendreau RM. Durability of therapeutic response to milnacipran treatment for fibromyalgia. Results of a randomized, double-blind, monotherapy 6-month extension study. Pain Medicine 2010;11(2):180-94. [DOI: 10.1111/j.1526-4637.2009.00755.x] - DOI - PubMed
Gomez‐Perez 1985 {published data only}
    1. Gomez-Perez FJ, Rull JA, Dies H, Rodriquez-Rivera JG, Gonzalez-Barranco J, Lozano-Castañeda O. Nortriptyline and fluphenazine in the symptomatic treatment of diabetic neuropathy. A double-blind cross-over study. Pain 1985;23(4):395-400. [DOI: 10.1016/0304-3959(85)90010-7] - DOI - PubMed
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Henry 2018 {published data only}
    1. Henry NL, Unger JM, Schott A, Hansen L, Lew D, Wade JL, et al. A randomized placebo-controlled phase III study of duloxetine for treatment of aromatase inhibitor (AI)-associated musculoskeletal symptoms in women with early-stage breast cancer: SWOG S1202. Journal of Clinical Oncology 2014;32(15 Suppl 1):1.
    1. Henry NL, Unger JM, Schott AF, Fehrenbacher L, Flynn PJ, Prow D, et al. Randomized, placebo controlled trial of duloxetine for aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS) in early stage breast cancer (SWOG S1202). Cancer Research 2017;77(4 Suppl):S5-6. [DOI: 10.1158/1538-7445.SABCS16-S5-06] - DOI
    1. Henry NL, Unger JM, Schott AF, Fehrenbacher L, Flynn PJ, Prow DM, et al. Randomized, multicenter, placebo-controlled clinical trial of duloxetine versus placebo for aromatase inhibitor-associated arthralgias in early-stage breast cancer: SWOG S1202. Journal of Clinical Oncology 2018;36(4):326-32. - PMC - PubMed
    1. Henry NL, Unger JM, Till C, Schott AF, Crew KD, Lew DL, et al. Association between body mass index (BMI) and response to duloxetine for aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS). Cancer Research 2018;79(4 Suppl 1):1. - PMC - PubMed
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IRCT201506171647N4 {published data only}
    1. IRCT201506171647N4. The effect of mesalazine and nortriptyline in patients with irritable bowel syndrome with diarrhea: a randomized clinical trial [The effect of mesalazine and nortriptyline on improvement of severity and frequency of abdominal pain and stool frequency recorded daily in patients with irritable bowel syndrome with diarrhea: a randomized clinical trail]. https://trialsearch.who.int/Trial2.aspx?TrialID=IRCT201506171647N4 (first received 13 July 2015).
IRCT20170829035966N1 {published data only}
    1. IRCT20170829035966N1. Efficacy of laughter yoga and anti-anxiety drugs on irritable bowel syndrome. https://trialsearch.who.int/Trial2.aspx?TrialID=IRCT20170829035966N1 (first received 17 January 2018).
IRCT20191210045685N1 {published data only}
    1. IRCT20191210045685N1. Effectiveness of duloxetine in chronic low back pain [Effetiveness of duloxetine on severity of pain and quality of life in chronic low back pain in patients who had posterior spinal fixation (PSF)]. https://trialsearch.who.int/Trial2.aspx?TrialID=IRCT20191210045685N1 (first received 4 July 2020).
ISRCTN16086699 {published data only}
    1. ISRCTN16086699. MODULATE: a study to evaluate the effectiveness of either amitriptyline, ondansetron, loperamide, or dietary intervention (the low FODMAP diet) against standard dietary advice for the treatment of diarrhoea in patients with stable ulcerative colitis [Management of diarrhoea in ulcerative colitis: multi-arm multi-stage trial of low FODMAP diet, amitriptyline, ondansetron, or loperamide: MODULATE]. https://trialsearch.who.int/Trial2.aspx?TrialID=ISRCTN16086699 (first received 13 February 2020).
ISRCTN63671932 {published data only}
    1. ISRCTN63671932. Multicentre trial of combined cognitive behavioural therapy and antidepressant treatment in functional bowel disorders [Cognitive behavioural therapy and antidepressant treatment in functional bowel disorders: a multicentre randomised, parallel, three arm trial studying behavioural and medication impact]. https://trialsearch.who.int/Trial2.aspx?TrialID=ISRCTN63671932 (first received 30 January 2007).
Kaosombatwattana 2015 {published data only}
    1. Kaosombatwattana U, Pongprasobchai S, Limsrivilai J, Leelakusolvong S, Tanwandee T. Efficacy and safety of nortriptyline in functional dyspepsia in Asians: a randomized double-blind placebo-controlled trial. Gastroenterology 2015;148(4 Suppl 1):S822. - PubMed
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Khalilian 2021 {published data only}
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Khosrawi 2018 {published data only}
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Kieburtz 1998 {published data only}
    1. Kieburtz K, Simpson D, Yiannoutsos C, Max MB, Hall CD, Ellis RJ, et al. A randomized trial of amitriptyline and mexiletine for painful neuropathy in HIV infection. Neurology 1998;51(6):1682-8. [DOI: 10.1212/wnl.51.6.1682] - DOI - PubMed
Kishore‐Kumar 1990 {published data only}
    1. Kishore-Kumar R, Max MB, Schafer SC, Gaughan AM, Smoller B, Gracely RH, et al. Desipramine relieves postherpetic neuralgia. Clinical Pharmacology & Therapeutics 1990;47(3):305-12. [DOI: 10.1038/clpt.1990.33] - DOI - PubMed
Kreiter 2021 {published data only}
    1. Kreiter D, Drukker M, Mujagic Z, Vork L, Rutten BP, Os J, et al. Symptom-network dynamics in irritable bowel syndrome with comorbid panic disorder using electronic momentary assessment: a randomized controlled trial of escitalopram vs. placebo. Journal of Psychosomatic Research 2021;141:110351. [DOI: 10.1016/j.jpsychores.2020.110351] - DOI - PubMed
Kroenke 2006 {published data only}
    1. Kroenke K, Messina N 3rd, Benattia I, Graepel J, Musgnung J. Venlafaxine extended release in the short-term treatment of depressed and anxious primary care patients with multisomatoform disorder. Journal of Clinical Psychiatry 2006;67(1):72-80. [DOI: 10.4088/jcp.v67n0111] - DOI - PubMed
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    1. Kuiken SD, Tytgat GN, Boeckxstaens GE. The selective serotonin reuptake inhibitor fluoxetine does not change rectal sensitivity and symptoms in patients with irritable bowel syndrome: a double blind, randomized, placebo-controlled study. Clinical Gastroenterology and Hepatology 2003;1(3):219-28. - PubMed
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Li 2019 {published data only}
    1. Li W-D, Jia L, Jiang S-M, Ping L, Xu M. The therapeutic effect of low-dose amitriptyline on patients with refractory diarrhea-predominant irritable bowel syndrome and its 1-year follow-up study. International Journal of Clinical and Experimental Medicine 2019;12(1):891-8.
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    1. Matsuoka H, Ishiki H, Iwase S, Koyama A, Kawaguchi T, Kizawa Y, et al. Study protocol for a multi-institutional, randomised, double-blinded, placebo-controlled phase III trial investigating additive efficacy of duloxetine for neuropathic cancer pain refractory to opioids and gabapentinoids: the DIRECT study. BMJ Open 2017;7(8):e017280. [DOI: 10.1136/bmjopen-2017-017280] - DOI - PMC - PubMed
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    1. Mishra S, Bhatnagar S, Goyal GN, Rana SP, Upadhya SP. A comparative efficacy of amitriptyline, gabapentin, and pregabalin in neuropathic cancer pain: a prospective randomized double-blind placebo-controlled study. American Journal of Hospice and Palliative Medicine 2012;29(3):177-82. [DOI: 10.1177/1049909111412539] - DOI - PubMed
NCT00006157 {published data only}
    1. NCT00006157. Treatment of functional bowel disorders [Multicenter trial of functional bowel disorders]. https://clinicaltrials.gov/ct2/show/NCT00006157 (first received 9 August 2000).
NCT00189059 {published data only}
    1. NCT00189059. Effects of amitriptyline for the treatment of pain on driving performance and cognition [Effects of pain and the treatment of pain with amitriptyline on driving performance, attentional capacity and psychomotor performance in chronic neuropathic pain patients]. https://clinicaltrials.gov/show/NCT00189059 (first received 16 September 2005).
NCT00191919 {published data only}
    1. NCT00191919. A randomized double blind study evaluating duloxetine in outpatients with MDD and pain [A ten-week, randomized, double-blind study evaluating the efficacy of duloxetine 60mg once daily versus placebo in outpatients with major depressive disorder and pain]. https://clinicaltrials.gov/show/NCT00191919 (first received 19 September 2005).
NCT00283842 {published data only}
    1. NCT00283842. Study evaluating desvenlafaxine succinate sustained-release (DVS SR) in adult outpatients with pain associated with diabetic peripheral neuropathy [A multicenter, randomized, double-blind, placebo-controlled, parallel-group, 13-week, adaptive-design study of 4 fixed oral doses of DVS SR in adult outpatients with pain associated with diabetic peripheral neuropathy]. https://clinicaltrials.gov/show/NCT00283842 (first received 30 January 2006).
NCT00592384 {published data only}
    1. NCT00592384. Project to improve symptoms and mood in people with spinal cord injury (PRISMS) [A controlled trial of venlafaxine XR for major depression after spinal cord injury: a multi-site study]. https://clinicaltrials.gov/show/NCT00592384 (first received 14 January 2008).
NCT00610909 {published data only}
    1. NCT00610909. Paroxetine - controlled release in the treatment of irritable bowel syndrome (IBS) [Single-site, double-blind, flexible-dose, placebo-controlled study of the efficacy, tolerability, & safety of paroxetine - controlled release in the treatment of irritable bowel syndrome (IBS)]. https://clinicaltrials.gov/show/NCT00610909 (first received 8 February 2008).
NCT00619983 {published data only}
    1. NCT00619983. Three way interaction between gabapentin, duloxetine, and donepezil in patients with diabetic neuropathy. https://clinicaltrials.gov/show/NCT00619983 (first received 21 February 2008).
NCT00625833 {published data only}
    1. NCT00625833. A trial of [S,S]-reboxetine In patients with chronic painful diabetic peripheral neuropathy [A randomized, double-blind placebo controlled trial of [S,S]-reboxetine in patients with chronic painful diabetic peripheral neuropathy]. https://clinicaltrials.gov/show/NCT00625833 (first received 28 February 2008).
NCT00696787 {published data only}
    1. NCT00696787. A study evaluating desvenlafaxine sustained release (DVS SR) in adult female outpatients with fibromyalgia [A multicenter, randomized, double-blind, placebo-controlled, pregabalin-referenced, parallel-group, adaptive design study of DVS SR in adult female outpatients with fibromyalgia syndrome]. https://clinicaltrials.gov/show/NCT00696787 (first received 13 June 2008).
NCT00754793 {published data only}
    1. NCT00754793. Sinusitis and facial pain disorders anti-depression trial (SFPAT). https://clinicaltrials.gov/show/NCT00754793 (first received 18 September 2008).
NCT00945945 {published data only}
    1. NCT00945945. A study of duloxetine in patients with osteoarthritis knee pain [A phase 3b study to assess the efficacy of duloxetine 60 mg once daily compared with placebo on the reduction of pain caused by osteoarthritis of the knee, in a 13-week, double-blind, randomized study]. https://clinicaltrials.gov/ct2/show/NCT00945945 (first received 24 July 2009).
NCT01116531 {published data only}
    1. NCT01116531. Efficacy, safety, tolerability and pharmacokinetics of concomitant administration of tramadol with duloxetine or pregabalin [Efficacy, safety, tolerability and pharmacokinetics of concomitant administration of tramadol with duloxetine or pregabalin: a randomized controlled flexible-dose study in patients with neuropathic pain]. https://clinicaltrials.gov/show/NCT01116531 (first received 5 May 2010).
NCT01173055 {published data only}
    1. NCT01173055. A study to evaluate the effects of milnacipran on pain processing and functional MRI in patients with fibromyalgia [A randomized, double-blind,placebo-controlled, two-way crossover study to evaluate the effect of milnacipran on pain processing and functional magnetic resonance imaging activation patterns in patients with fibromyalgia]. https://clinicaltrials.gov/show/NCT01173055 (first received 30 July 2010).
NCT01268709 {published data only}
    1. NCT01268709. Effect of doxepin and nortriptyline on irritable bowel syndrome. https://clinicaltrials.gov/show/NCT01268709 (first received 31 December 2010).
NCT01288937 {published data only}
    1. NCT01288937. A placebo controlled, randomized, double blind trial of milnacipran for the treatment of idiopathic neuropathy pain. https://clinicaltrials.gov/show/NCT01288937 (first received 3 February 2011).
NCT01359514 {published data only}
    1. NCT01359514. Mechanism-based choice of therapy for neuropathic pain [Mechanism-based choice of therapy for neuropathic pain: can treatments success in neuropathic post-operative pain be coupled to psychophysical pain modulation profile?]. https://clinicaltrials.gov/show/NCT01359514 (first received 24 May 2011).
NCT01359826 {published data only}
    1. NCT01359826. The effect of milnacipran on fatigue and quality of life in lupus patients [The effect of milnacipran on fatigue and quality of life in a lupus cohort]. https://clinicaltrials.gov/show/NCT01359826 (first received 25 May 2011).
NCT01377038 {published data only}
    1. NCT01377038. OASIS: osteoarthritis sensitivity integration study (OASIS) [Central pain mechanisms in osteoarthritis: a longitudinal cohort]. https://clinicaltrials.gov/show/NCT01377038 (first received 20 June 2011).
NCT01451606 {published data only}
    1. NCT01451606. Duloxetine for the treatment of chronic pelvic pain [Evaluating duloxetine's analgesic effectiveness in chronic pelvic pain]. https://clinicaltrials.gov/show/NCT01451606 (first received 13 October 2011).
NCT01471379 {published data only}
    1. NCT01471379. Milnacipran (Savella) in irritable bowel syndrome (IBS) [A randomized, double-blind, placebo-controlled study to assess the efficacy of milnacipran in the treatment of irritable bowel syndrome]. https://clinicaltrials.gov/show/NCT01471379 (first received 16 November 2011).
NCT01579279 {published data only}
    1. NCT01579279. A study comparing the efficacy and safety of ABT-652 to placebo in subjects with diabetic neuropathic pain [A multicenter, randomized, double-blind, placebo- and active-controlled study comparing the analgesic efficacy and safety of ABT-652 to placebo in subjects with diabetic neuropathic pain]. https://clinicaltrials.gov/show/NCT01579279 (first received 17 April 2012).
NCT01869907 {published data only}
    1. NCT01869907. Effect of minocycline on pain caused by nerve damage (EMON) [Effect of minocycline on neuropathic pain]. https://clinicaltrials.gov/show/NCT01869907 (first received 5 June 2013).
NCT01910259 {published data only}
    1. NCT01910259. MS-SMART: multiple sclerosis-secondary progressive multi-arm randomisation trial (MS-SMART) [A multi-arm phase IIB randomised, double blind placebo-controlled clinical trial comparing the efficacy of three neuroprotective drugs in secondary progressive multiple sclerosis]. https://clinicaltrials.gov/show/NCT01910259 (first received 29 July 2013). - PMC - PubMed
NCT02650544 {published data only}
    1. NCT02650544. Efficacy and safety analyses of mirtazapine in NSCLC patients with depression [Efficacy and safety analyses of mirtazapine in the treatment of malignant tumor related depression: a phase II, placebo-controlled, randomized, double-blinded clinical trial in advanced non-small cell lung cancer patients]. https://clinicaltrials.gov/show/NCT02650544 (first received 8 January 2016).
NCT02970591 {published data only}
    1. NCT02970591. A comparison of three different treatment options for irritable bowel syndrome (CARIBS) [The role of carbohydrates in irritable bowel syndrome (CARIBS): protocol for a randomized controlled trial comparing three different treatment options]. https://clinicaltrials.gov/show/NCT02970591 (first received 22 November 2016).
NCT03364075 {published data only}
    1. NCT03364075. Genetic variants associated with low back pain and their response to treatment with duloxetine or propranolol [Genetic variants associated with the occurrence of localized low back pain or low back pain with widespread pain symptoms, and their response to treatment with duloxetine or propranolol]. https://clinicaltrials.gov/show/NCT03364075 (first received 6 December 2017).
NCT03522207 {published data only}
    1. NCT03522207. Accuracy and efficacy of trazodone (Desyrel) on sleep quality and pain management of TMD patient [Stabilisation de la qualité du sommeil chez le sujet en douleurs orofaciales chroniques - étude expérimentale en chassé croisé: trazodone/ placebo]. https://clinicaltrials.gov/show/NCT03522207 (first received 11 May 2018).
NCT04747314 {published data only}
    1. NCT04747314. Treating negative affect in low back pain patients (TNA-LBP) [Proof of concept study to treat negative affect in chronic low back pain]. https://clinicaltrials.gov/show/NCT04747314 (first received 10 February 2021).
Nickel 2005 {published data only}
    1. Nickel MK, Nickel C, Lahmann C, Mitterlehner FO, Tritt K, Leiberich PK, et al. Changes in instrumental activities of daily living disability after treatment of depressive symptoms in elderly women with chronic musculoskeletal pain: a double-blind, placebo-controlled trial. Aging Clinical and Experimental Research 2005;17(4):293-6. [DOI: 10.1007/BF03324613] - DOI - PubMed
Panerai 1990 {published data only}
    1. Panerai AE, Monza G, Movilia P, Bianchi M, Francucci BM, Tiengo M. A randomized, within-patient, cross-over, placebo-controlled trial on the efficacy and tolerability of the tricyclic antidepressants chlorimipramine and nortriptyline in central pain. Acta Neurologica Scandinavica 1990;82(1):34-8. [DOI: 10.1111/j.1600-0404.1990.tb01584.x] - DOI - PubMed
Parker 2003 {published data only}
    1. Parker JC, Smarr KL, Slaughter JR, Johnston SK, Priesmeyer ML, Hanson KD, et al. Management of depression in rheumatoid arthritis: a combined pharmacologic and cognitive-behavioral approach. Arthritis Care & Research 2003;49(6):766-77. [DOI: 10.1002/art.11459] - DOI - PubMed
Parkman 2013 {published data only}
    1. Parkman HP, Van Natta ML, Abell TL, McCallum RW, Sarosiek I, Nguyen L, et al. Effect of nortriptyline on symptoms of idiopathic gastroparesis: the NORIG randomized clinical trial. Journal of the American Medical Association 2013;310(24):2640-9. [DOI: 10.1001/jama.2013.282833] - DOI - PMC - PubMed
Pilowsky 1982 {published data only}
    1. Pilowsky I, Hallett EC, Bassett DL, Thomas PG, Penhall RK. A controlled study of amitriptyline in the treatment of chronic pain. Pain 1982;14(2):169‐79. [DOI: 10.1016/0304-3959(82)90097-5] - DOI - PubMed
Pilowsky 1995 {published data only}
    1. Pilowsky I, Spence N, Rounsefell B, Forsten C, Soda J. Out-patient cognitive-behavioural therapy with amitriptyline for chronic non-malignant pain: a comparative study with 6-month follow-up. Pain 1995;60(1):49-54. [DOI: 10.1016/0304-3959(94)00087-U] - DOI - PubMed
Poulsen 1987 {published data only}
    1. Poulsen DL, Hansen HJ, Langemark M, Olesen J, Bech P. Discomfort or disability in patients with chronic pain syndrome. Psychotherapy and Psychosomatics 1987;48(1‐4):60‐2. [DOI: 10.1159/000288032] - DOI - PubMed
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    1. Raja SN, Haythornthwaite JA, Pappagallo M, Clark MR, Travison TG, Sabeen S, et al. Opioids versus antidepressants in postherpetic neuralgia: a randomized, placebo-controlled trial. Neurology 2002;59(7):1015-21. [DOI: 10.1212/wnl.59.7.1015] - DOI - PubMed
Rajagopalan 1998 {published data only}
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Saxe 2009 {published data only}
    1. Saxe PA, Arnold LM, Gendreau RM, Spera A, Gendreau J, Wang Y. A randomized, double-blind, placebo-controlled clinical trial of milnacipran 100 mg/day for the management of fibromyalgia: results from a 2-week discontinuation phase. Arthritis and Rheumatism 2009;60:1421.
Seddighnia 2020 {published data only}
    1. Seddighnia A, Tadayon Najafabadi B, Ghamari K, Noorbala AA, Ebrahimi Daryani N, Kashani L, et al. Vortioxetine effects on quality of life of irritable bowel syndrome patients: a randomized, double-blind, placebo-controlled trial. Journal of Clinical Pharmacy and Therapeutics 2020;45(1):97-104. [DOI: 10.1111/jcpt.13032] - DOI - PubMed
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    1. Selvarajah D, Petrie J, White D, Julious S, Bortolami O, Cooper C, et al. Multicentre, double-blind, crossover trial to identify the optimal pathway for treating neuropathic pain in diabetes mellitus (OPTION-DM): study protocol for a randomised controlled trial. Trials 2018;19(1):578. [DOI: 10.1186/s13063-018-2959-y] - DOI - PMC - PubMed
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    1. Strauss DH, Santhanam DR, McLean SA, Beaudoin FL. Study protocol for a randomised, double-blind, placebo-controlled clinical trial of duloxetine for the treatment and prevention of musculoskeletal pain: altering the transition from acute to chronic pain (ATTAC pain). BMJ Open 2019;9(3):e025002. [DOI: 10.1136/bmjopen-2018-025002] - DOI - PMC - PubMed
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    1. Tondlova H, Bastecky J. Citalopram and dosulepine in adjuvant treatment of oncological pain. Bolest 2002;5(4):247-52.
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References to studies awaiting assessment

ACTRN12620000656932 {published data only}
    1. ACTRN12620000656932. Duloxetine and pregabalin for neuropathic cancer pain [A phase III, international, multi-centre, double-blind, dose increment, parallel-arm, randomised controlled trial of duloxetine versus pregabalin over 14 days for opioid unresponsive cancer-related neuropathic pain]. https://trialsearch.who.int/Trial2.aspx?TrialID=ACTRN12620000656932 (first received 5 June 2020). - PMC - PubMed
Brown 2015 {published data only}
    1. Brown TR, Slee A. A randomized placebo-controlled trial of duloxetine for central pain in multiple sclerosis. International Journal of MS Care 2015;17(2):83-9. [DOI: 10.7224/1537-2073.2014-001] - DOI - PMC - PubMed
Cánovas Martínez 2009 {published data only}
    1. Cánovas Martínez L, Gómez Gutiérrez I, Castro Bande M, Peralta Espinosa E, Prieto Gutiérrez JM, Segado Jiménez I. Analgesic efficacy of the association of duloxetine plus pregabalin in neuropathic pain: experience in 60 patients. Revista de la Sociedad Española del Dolor 2009;16(7):381‐5.
Chandra 2006 {published data only}
    1. Chandra K, Shafig N, Pandhi P, Gupta S, Malhotra S. Gabapentin versus nortriptyline in post-herpetic neuralgia patients: a randomized, double-blind clinical trial—The GONIP Trial. International Journal of Clinical Pharmacology and Therapeutics 2006;44(8):358-63. [DOI: 10.5414/cpp44358] - DOI - PubMed
Di 2019 {published data only}
    1. Di C, Xu D. Effect of concomitant administration of oxycontin and amitriptyline on patients with severe cancer pain and depression. Tropical Journal of Pharmaceutical Research 2019;18(1):129-34. [DOI: 10.4314/tjpr.v18i1.19] - DOI
Hammack 2002 {published data only}
    1. Hammack JE, Michalak JC, Loprinzi CL, Sloan JA, Novotny PJ, Soori GS, et al. Phase III evaluation of nortriptyline for alleviation of symptoms of cis-platinum-induced peripheral neuropathy. Pain 2002;98(1-2):195-203. [DOI: 10.1016/s0304-3959(02)00047-7] - DOI - PubMed
Jia 2006 {published data only}
    1. Jia H-Y, Li Q-F, Song D-P, Liu Y, Ran X. Effects of venlafaxine and carbamazepine for painful peripheral diabetic neuropathy: a randomized, double-blind and double-dummy, controlled multi-center trial. Chinese Journal of Evidence-Based Medicine 2006;6(5).
Keskinbora 2006 {published data only}
    1. Keskinbora K, Pekel AF, Aydinli I. Comparison of efficacy of gabapentin and amitriptyline in the management of peripheral neuropathic pain. Ağrı (Algoloji) Derneği'nin Yayın Organıdır [Journal of the Turkish Society of Algology] 2006;18(2):34-40. - PubMed
Riesner 2008 {published data only}
    1. Riesner H-J, Zeitler C, Schreiber H, Wild A. Additional treatment in chronic pain syndrome due to hip and knee arthritis with the selective serotonin reuptake inhibitor fluvoxamine (Fevarin) [Eine additive Therapie chronischer Schmerzen bei fortgeschrittener Gon-/Coxarthrose mit dem selektiven Serotonin-Reuptake-Hemmer Fluvoxamin (Fevarin®)]. Zeitschrift für Orthopädie und Unfallchirurgie 2008;146(6):742-6. [DOI: 10.1055/s-2008-1039038] - DOI - PubMed
Salehifar 2020 {published data only}
    1. Salehifar E, Janbabaei G, Hendouei N, Alipour A, Tabrizi N, Avan R. Comparison of the efficacy and safety of pregabalin and duloxetine in taxane-induced sensory neuropathy: a randomized controlled trial. Clinical Drug Investigation 2020;40(3):249-57. [DOI: 10.1007/s40261-019-00882-6] - DOI - PubMed
Shabbir 2011 {published data only}
    1. Shabbir B, Shafi F, Mahboob F. Amitriptyline vs pregabalin in painful diabetic neuropathy a randomised placebo-based study. Pakistan Journal of Medical and Health Sciences 2011;5(4):745-7.
Shlay 1998 {published data only}
    1. Shlay JC, Chaloner K, Max MB, Flaws B, Reichelderfer P, Wentworth D, et al, for the Terry Beirn Community Programs for Clinical Research on AIDS. Acupuncture and amitriptyline for pain due to HIV-related peripheral neuropathy: a randomized controlled trial. Journal of the American Medical Association 1998;280(18):1590-5. [DOI: 10.1001/jama.280.18.1590] - DOI - PubMed
Taghizadeh 2020 {published data only}
    1. Taghizadeh M, Elahabadi I, Kamiab Z, Zaydabadi Nejad N, Mortazavi Lahijani M, Vazirinejad R, et al. A comparative study on the effects of fluoxetine and tamoxifen on the treatment of mastalgia: a randomized clinical trial. KOOMESH 2020;22(4):574-80.
Xu 2006 {published data only}
    1. Xu J, Cheng YQ, Lv SP, Li XZ, Feng R, Cui RM. A controlled study of paroxetine and amitriptyline in the treatment of primary fibromyalgia syndrome. Chinese Mental Health Journal 2006;20(8):542‐4.
Zakerkish 2017 {published data only}
    1. Zakerkish M, Amiri F, Nasab NM, Ghorbani A. Comparative efficacy of duloxetine versus nortriptyline in patients with diabetic peripheral neuropathic pain: a double blind randomized controlled trial. Iranian Red Crescent Medical Journal 2017;19(8):e59995. [DOI: 10.5812/ircmj.59995] - DOI

References to ongoing studies

ACTRN12619000878178 {published data only}
    1. ACTRN12619000878178. Venlafaxine for pain reduction in patients with knee osteoarthritis [A randomised controlled trial of venlafaxine to treat patients with knee osteoarthritis pain]. https://trialsearch.who.int/Trial2.aspx?TrialID=ACTRN12619000878178 (first received 20 June 2019).
ACTRN12619001082190 {published data only}
    1. ACTRN12619001082190. Serotonin noradrenaline reuptake inhibitors (SNRI) medications for the treatment of osteoarthritis pain (STOP) trial [Venlafaxine compared to duloxetine for the treatment of osteoarthritis pain: a double-blind, randomised, non-inferiority trial]. https://trialsearch.who.int/Trial2.aspx?TrialID=ACTRN12619001082190 (first received 6 August 2019).
Ammitzboll 2021 {published data only}
    1. Ammitzbøll N, Arendt-Nielsen L, Bertoli D, Brock C, Olesen AE, Kappel A, et al. A mechanism-based proof of concept study on the effects of duloxetine in patients with painful knee osteoarthritis. Trials 2021;22(1):958. [DOI: 10.1186/s13063-021-05941-y] - DOI - PMC - PubMed
ChiCTR1900027038 {published data only}
    1. ChiCTR1900027038. Synergistic analgesia of duloxetine in phantom limb pain: a randomized controlled trial. https://trialsearch.who.int/Trial2.aspx?TrialID=ChiCTR1900027038 (first received 29 October 2019).
CTRI/2018/10/015944 {published data only}
    1. CTRI/2018/10/015944. A study of gabapentin and duloxetine in painful diabetic neuropathy [A comparative evaluation of duloxetine and gabapentin in painful diabetic neuropathy: a randomised control trial]. https://trialsearch.who.int/Trial2.aspx?TrialID=CTRI/2018/10/015944 (first received 8 October 2018).
CTRI/2018/10/015983 {published data only}
    1. CTRI/2018/10/015983. Vitamin D as an add on therapy in the treatment of diabetic peripheral neuropathy [Effectiveness of vitamin d as a supplement with conventional therapy in the treatment of diabetic peripheral neuropathy - a randomized controlled clinical trial]. https://trialsearch.who.int/Trial2.aspx?TrialID=CTRI/2018/10/015983 (first received 10 October 2018).
CTRI/2021/02/031068 {published data only}
    1. CTRI/2021/02/031068. Comparing the benefit of tablet pregabalin with tablet duloxetine and only tablet pregabalin in nerve pain in diabetes and relation with PPARG and Akt gene [A randomized double-blind comparative study evaluating the efficacy of a combination of pregabalin and duloxetine versus pregabalin alone and the modulation of mRNA expression of PPARG and Akt genes in patients of painful diabetic peripheral neuropathy]. https://trialsearch.who.int/Trial2.aspx?TrialID=CTRI/2021/02/031068 (first received 8 February 2021).
CTRI/2021/03/031875 {published data only}
    1. CTRI/2021/03/031875. Effect of duloxetine in central post-stroke pain [Efficacy of duloxetine in patients with central post-stroke pain: a randomised double blind placebo controlled study]. https://trialsearch.who.int/Trial2.aspx?TrialID=CTRI/2021/03/031875 (first received 10 March 2021).
EUCTR2019‐000243‐27‐DK {published data only}
    1. EUCTR2019-000243-27-DK. Bupropion for the treatment of nerve pain. A randomized, double-blind study [The effect of bupropion in peripheral neuropathic pain. A randomized, double-blind, placebo-controlled study]. https://trialsearch.who.int/Trial2.aspx?TrialID=EUCTR2019-000243-27-DK (first received 10 May 2021).
EUCTR2019‐000324‐17‐GB {published data only}
    1. EUCTR2019-000324-17-GB. Amitriptyline at low-dose and titrated for irritable bowel syndrome as second-line treatment (the ATLANTIS study): a double-blind placebo-controlled trial [Amitriptyline at low-dose and titrated for irritable bowel syndrome as second-line treatment (the ATLANTIS study): a double-blind placebo-controlled trial]. https://trialsearch.who.int/Trial2.aspx?TrialID=ISRCTN48075063 (first received 7 June 2019).
EUCTR2019‐001202‐14‐NL {published data only}
    1. EUCTR2019-001202-14-NL. Effect of an antidepressant on chest pain in patients with achalasia. https://trialsearch.who.int/Trial2.aspx?TrialID=EUCTR2019-001202-14-NL (first received 18 April 2019).
EUCTR2021‐002288‐24‐NL {published data only}
    1. EUCTR2021-002288-24-NL. Effect of citalopram on chest pain in patients with chest pain of unkown origin [Effect of citalopram on chest pain in patients with functional chest pain - Ci-FCP]. https://trialsearch.who.int/Trial2.aspx?TrialID=EUCTR2021-002288-24-NL (first received 27 July 2021).
IRCT20110413006186N13 {published data only}
    1. IRCT20110413006186N13. The effect of electric stimulation through skin and duloxetine on diabetic neuropathic pain [A comparison of the effectiveness of transcutaneous electrical nerve stimulation and duloxetine on diabetic peripheral neuropathic pain]. https://trialsearch.who.int/Trial2.aspx?TrialID=IRCT20110413006186N13 (first received 27 May 2019).
IRCT20200205046381N1 {published data only}
    1. IRCT20200205046381N1. Comparing the analgesic effect of fluoxetine and vitamin E with vitamin E only in breast pain due to fibrocystic breast disease. https://trialsearch.who.int/Trial2.aspx?TrialID=IRCT20200205046381N1 (first received 28 February 2020).
IRCT20200620047852N1 {published data only}
    1. IRCT20200620047852N1. Agomelatin in chronic low back pain [Comparing the analgesic effect of agomelatin versus placebo in combination with pregabalin in patients with chronic low back pain: a randomized, double-blinded study]. https://trialsearch.who.int/Trial2.aspx?TrialID=IRCT20200620047852N1 (first received 23 June 2020).
NCT00981149 {published data only}
    1. NCT00981149. Duloxetine for treatment of painful temporomandibular joint disorder. https://clinicaltrials.gov/show/NCT00981149 (first received 22 September 2009).
NCT03249558 {published data only}
    1. NCT03249558. Effect of combined morphine and duloxetine on chronic pain. https://clinicaltrials.gov/show/NCT03249558 (first received 15 August 2017).
NCT03324035 {published data only}
    1. NCT03324035. Treatment of neuropathic pain in leprosy. https://clinicaltrials.gov/show/NCT03324035 (first received 27 October 2017).
NCT04704453 {published data only}
    1. NCT04704453. Study to evaluate the interest of qutenza in patients with head and neck cancer in remission and with sequelae neuropathic pain. https://clinicaltrials.gov/show/NCT04704453 (first received 11 January 2021).
NCT04727502 {published data only}
    1. NCT04727502. Comparison of duloxetine versus pregabalin [Comparison of duloxetine versus pregabalin in post-mastectomy pain syndrome: a randomized controlled trial]. https://clinicaltrials.gov/show/NCT04727502 (first received 27 January 2021).
PACTR202001764151121 {published data only}
    1. PACTR202001764151121. Efficacy of clomipramine for chronic lumbar radicular pain: a randomized clinical trial. https://trialsearch.who.int/Trial2.aspx?TrialID=PACTR202001764151121 (first received 6 November 2019).
RBR‐6pqx4n {published data only}
    1. RBR-6pqx4n. Efficacy of duloxetine in chronic facial pain. https://trialsearch.who.int/Trial2.aspx?TrialID=RBR-6pqx4n (first received 3 September 2018).
Reckziegel 2017 {published data only}
    1. Reckziegel D, Bailey H, Cottam WJ, Tench CR, Mahajan RP, Walsh DA, et al. Imaging pain relief in osteoarthritis (IPRO): protocol of a double-blind randomised controlled mechanistic study assessing pain relief and prediction of duloxetine treatment outcome. BMJ Open 2017;7(6):e014013. [DOI: 10.1136/bmjopen-2016-014013] - DOI - PMC - PubMed
TCTR20190303001 {published data only}
    1. TCTR20190303001. A comparison of analgesic efficacy between amitriptyline and mianserin in chronic low back pain patients: a randomized double-blind controlled trial. https://trialsearch.who.int/Trial2.aspx?TrialID=TCTR20190303001 (first received 3 April 2023).
TCTR20210311009 {published data only}
    1. TCTR20210311009. Comparison effectiveness of nortriptyline and placebo in the treatment of chronic osteoarthritis knee. https://trialsearch.who.int/Trial2.aspx?TrialID=TCTR20210311009 (first received 11 March 2021).
Wluka 2021 {published data only}
    1. Wluka AE, Urquhart DM, Teichtahl AJ, Hussain SM, Forbes A, Arnold C, et al. Effect of low-dose amitriptyline on reducing pain in clinical knee osteoarthritis compared to benztropine: study protocol of a randomised, double blind, placebo-controlled trial. BMC Musculoskeletal Disorders 2021;22(1):826. [DOI: 10.1186/s12891-021-04690-y] - DOI - PMC - PubMed

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