Evidence-Based Reviews

Antidepressants for chronic pain

Current Psychiatry. 2019 February;18(2):8-16,21-22

References

1. Paoli F, Darcourt G, Cossa P. Preliminary note on the action of imipramine in painful states [in French]. Rev Neurol (Paris). 1960;102:503-504.
2. Fields HL, Heinricher MM, Mason P. Neurotransmitters in nociceptive modulatory circuits. Annu Rev Neurosci. 1991;14:219-245.
3. Hunt SP, Mantyh PW. The molecular dynamics of pain control. Nat Rev Neurosci. 2001;2(2):83-91.
4. Lamont LA, Tranquilli WJ, Grimm KA. Physiology of pain. Vet Clin North Am Small Anim Pract. 2000;30(4):703-728, v.
5. Fields HL, Basbaum AI, Heinricher MM. Central nervous system mechanisms of pain modulation. In: McMahon S, Koltzenburg M, eds. Wall and Melzack’s Textbook of Pain. 5th ed. Burlington, MA: Elsevier Health Sciences; 2005:125-142.
6. Marks DM, Shah MJ, Patkar AA, et al. Serotonin-norepinephrine reuptake inhibitors for pain control: premise and promise. Curr Neuropharmacol. 2009;7(4):331-336.
7. Baba H, Shimoji K, Yoshimura M. Norepinephrine facilitates inhibitory transmission in substantia gelatinosa of adult rat spinal cord (part 1): effects on axon terminals of GABAergic and glycinergic neurons. Anesthesiology. 2000;92(2):473-484.
8. Carter GT, Sullivan MD. Antidepressants in pain management. Curr Opin Investig Drugs. 2002;3(3):454-458.
9. Kawasaki Y, Kumamoto E, Furue H, et al. Alpha 2 adrenoceptor-mediated presynaptic inhibition of primary afferent glutamatergic transmission in rat substantia gelatinosa neurons. Anesthesiology. 2003;98(3):682-689.
10. McCleane G. Antidepressants as analgesics. CNS Drugs. 2008;22(2):139-156.
11. Ansari A. The efficacy of newer antidepressants in the treatment of chronic pain: a review of current literature. Harv Rev Psychiatry. 2000;7(5):257-277.
12. Egbunike IG, Chaffee BJ. Antidepressants in the management of chronic pain syndromes. Pharmacotherapy. 1990;10(4):262-270.
13. Fishbain DA. Evidence-based data on pain relief with antidepressants. Ann Med. 2000;32(5):305-316.
14. Fishbain DA, Detke MJ, Wernicke J, et al. The relationship between antidepressant and analgesic responses: findings from six placebo-controlled trials assessing the efficacy of duloxetine in patients with major depressive disorder. Curr Med Res Opin. 2008;24(11):3105-3115.
15. Harada E, Tokuoka H, Fujikoshi S, et al. Is duloxetine’s effect on painful physical symptoms in depression an indirect result of improvement of depressive symptoms? Pooled analyses of three randomized controlled trials. Pain. 2016;157(3):577-584.
16. Kehoe WA. Antidepressants for chronic pain: selection and dosing considerations. Am J Pain Med. 1993;3(4):161-165.
17. Damush TM, Kroenke K, Bair MJ, et al. Pain self-management training increases self-efficacy, self-management behaviours and pain and depression outcomes. Eur J Pain. 2016;20(2):1070-1078.
18. DeVeaugh-Geiss AM, West SL, Miller WC, et al. The adverse effects of comorbid pain on depression outcomes in primary care patients: results from the ARTIST trial. Pain Medicine. 2010;11(5):732-741.
19. Egloff N, Cámara RJ, von Känel R, et al. Hypersensitivity and hyperalgesia in somatoform pain disorders. Gen Hosp Psychiatry. 2014;36(3):284-290.
20. Goesling J, Clauw DW, Hassett AL. Pain and depression: an integrative review of neurobiological and psychological factors. Curr Psych Reports. 2013;15(12):421.
21. Kroenke K, Wu J, Bair MJ, et al. Reciprocal relationship between pain and depression: a 12-Month longitudinal analysis in primary care. J Pain. 2011;12(9):964-973.
22. Leo RJ. Chronic pain and comorbid depression. Curr Treat Options Neurol. 2005;7(5):403-412.
23. Bair MJ, Robinson RL, Eckert GJ, et al. Impact of pain on depression treatment response in primary care. Psychosom Med. 2004;66(1):17-22.
24. Karp JF, Scott J, Houck P, et al. Pain predicts longer time to remission during treatment of recurrent depression. J Clin Psychiatry. 2005;66(5):591-597.
25. Kroenke K, Shen J, Oxman TE, et al. Impact of pain on the outcomes of depression treatment: results from the RESPECT trial. Pain. 2008;134(1-2):209-215.
26. Mavandadi S, Ten Have TR, Katz IR, et al. Effect of depression treatment on depressive symptoms in older adulthood: the moderating role of pain. J Am Geriatr Soc. 2007;55(2):202-211.
27. Thielke SM, Fan MY, Sullivan M, et al. Pain limits the effectiveness of collaborative care for depression. Am J Geriatr Psychiatry. 2007;15(8):699-707.
28. Arnow BA, Hunkeler EM, Blasey CM, et al. Comorbid depression, chronic pain, and disability in primary care. Psychosom Med. 2006;68(2):262-268.
29. Demyttenaere K, Bonnewyn A, Bruffaerts R, et al. Comorbid painful physical symptoms and depression: Prevalence, work loss, and help seeking. J Affect Disord. 2006;92(2-3):185-193.
30. Nakao M, Barsky AJ. Clinical application of somatosensory amplification in psychosomatic medicine. Biopsychosoc Med. 2007;1:17.
31. Perez DL, Barsky AJ, Vago DR, et al. A neural circuit framework for somatosensory amplification in somatoform disorders. J Neuropsychiatry Clin Neurosci. 2015;27(1):e40-e50.
32. Fishbain DA, Cutler RB, Rosomoff HL, et al. Do antidepressants have an analgesic effect in psychogenic pain and somatoform pain disorder? A meta-analysis. Psychosom Med. 1998;60(4):503-509.
33. Kleinstäuber M, Witthöft M, Steffanowski A, et al. Pharmacological interventions for somatoform disorders in adults. Cochrane Database Syst Rev. 2014;(11):CD010628.
34. Collins SL, Moore RA, McQuay HJ, et al. Antidepressants and anticonvulsants for diabetic neuropathy and postherpetic neuralgia: a quantitative systematic review. J Pain Symptom Manage. 2000;20(6):449-458.
35. Saarto T, Wiffen PJ. Antidepressants for neuropathic pain: a Cochrane review. J Neurol Neurosurg Psychiatry. 2010;81(12):1372-1373.
36. Arnold LM, Keck PE, Welge JA. Antidepressant treatment of fibromyalgia. A meta-analysis and review. Psychosomatics. 2000;41(2):104-113.
37. O’Malley PG, Balden E, Tomkins G, et al. Treatment of fibromyalgia with antidepressants: a meta-analysis. J Gen Intern Med. 2000;15(9):659-666.
38. Tomkins GE, Jackson JL, O’Malley PG, et al. Treatment of chronic headache with antidepressants: a meta-analysis. Am J Med. 2001;111(1):54-63.
39. Jackson JL, O’Malley PG, Tomkins G, et al. Treatment of functional gastrointestinal disorders with antidepressant medications: a meta-analysis. Am J Med. 2000;108(1):65-72.
40. Lesbros-Pantoflickova D, Michetti P, Fried M et al. Meta-analysis: the treatment of irritable bowel syndrome. Aliment Pharmacol Ther. 2004;20(11-12):1253-1269.
41. Centre for Clinical Practice at NICE (UK). Neuropathic pain: the pharmacological management of neuropathic pain in adults in non-specialist settings. London, UK: National Institute for Health and Care Excellence, (UK); 2013.
42. O’Connor AB, Dworkin RH. Treatment of neuropathic pain: an overview of recent guidelines. Am J Med. 2009;122(suppl 10):S22-S32.
43. Moulin D, Boulanger A, Clark AJ, et al; Canadian Pain Society. Pharmacological management of chronic neuropathic pain: revised consensus statement from the Canadian Pain Society. Pain Res Manag. 2014;19(6):328-35.
44. Mu A, Weinberg E, Moulin DE, et al. Pharmacologic management of chronic neuropathic pain: Review of the Canadian Pain Society consensus statement. Can Fam Physician. 2017;63(11):844-852.
45. Finnerup NB, Otto M, McQuay HJ, et al. Algorithm for neuropathic pain treatment: an evidence based proposal. Pain. 2005;118(3):289-305.
46. Hempenstall K, Nurmikko TJ, Johnson RW, et al. Analgesic therapy in postherpetic neuralgia: a quantitative systematic review. PLoS Med. 2005;2(7):e164.
47. Sindrup SH, Jensen TS. Efficacy of pharmacological treatments of neuropathic pain: an update and effect related to mechanism of drug action. Pain. 1999;83(3):389-400.
48. Wu CL, Raja SN. An update on the treatment of postherpetic neuralgia. J Pain. 2008;9(suppl 1):S19-S30.
49. Kroenke K, Krebs EE, Bair MJ. Pharmacotherapy of chronic pain: a synthesis of recommendations from systematic reviews. Gen Hosp Psychiatry. 2009;31(3):206-219.
50. Hearn L, Moore RA, Derry S, et al. Desipramine for neuropathic pain in adults. Cochrane Database Syst Rev. 2014;(9):CD011003.
51. Hearn L, Derry S, Phillips T, et al. Imipramine for neuropathic pain in adults. Cochrane Database Syst Rev. 2014;(5):CD010769.
52. Derry S, Wiffen PJ, Aldington D, et al. Nortriptyline for neuropathic pain in adults. Cochrane Database Syst Rev. 2015;1:CD011209.
53. Moore R, Derry S, Aldington D, et al. Amitriptyline for neuropathic pain in adults. Cochrane Database Syst Rev. 2015;(7):CD008242.
54. Lunn MP, Hughes RA, Wiffen PJ. Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia. Cochrane Database Syst Rev. 2014;(1):CD007115.
55. Gallagher HC, Gallagher RM, Butler M, et al. Venlafaxine for neuropathic pain in adults. Cochrane Database Syst Rev. 2015;(8):CD011091.
56. Alviar MJ, Hale T, Dungca M. Pharmacologic interventions for treating phantom limb pain. Cochrane Database Syst Rev. 2016;10:CD006380.
57. Dinat N, Marinda E, Moch S, et al. 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.eCollection 2015.
58. Mehta S, McIntyre A, Janzen S, et al; Spinal Cord Injury Rehabilitation Evidence Team. Systematic review of pharmacologic treatments of pain after spinal cord injury: an update. Arch Phys Med Rehabil. 2016;97(8):1381-1391.e1.
59. Moore RA, Derry S, Aldington D, et al. Amitriptyline for neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev. 2012;(12):CD008242..
60. Walitt B, Urrútia G, Nishishinya MB, et al. Selective serotonin reuptake inhibitors for fibromyalgia syndrome. Cochrane Database Syst Rev. 2015;(6):CD011735.
61. Welsch P, Üçeyler N, Klose P, et al. Serotonin and noradrenaline reuptake inhibitors (SNRIs) for fibromyalgia. Cochrane Database Syst Rev. 2018;(2):CD010292.
62. VanderWeide LA, Smith SM, Trinkley KE. A systematic review of the efficacy of venlafaxine for the treatment of fibromyalgia. J Clin Pharm Ther. 2015;40(1):1-6.
63. Welsch P, Bernardy K, Derry S, et al. Mirtazapine for fibromyalgia in adults. Cochrane Database Syst Rev. 2018;(8):CD012708.
64. Lance JW, Curran DA. Treatment of chronic tension headache. Lancet. 1964;283(7345):1236-1239.
65. Jackson JL, William S, Laura S, et al. Tricyclic antidepressants and headaches: systematic review and meta-analysis. BMJ. 2010;341:c5222. doi: https://doi.org/10.1136/bmj.c5222
66. Xu XM, Liu Y, Dong MX, et al. Tricyclic antidepressants for preventing migraine in adults. Medicine. 2017;96(22):e6989. doi: 10.1097/MD.0000000000006989.
67. Banzi R, Cusi C, Randazzo C, et al. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) for the prevention of migraine in adults. Cochrane Database Syst Rev. 2015;(4):CD002919.
68. Banzi R, Cusi C, Randazzo C, et al. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) for the prevention of tension-type headache in adults. Cochrane Database Syst Rev. 2015;(5):CD011681.
69. Quartero AO, Meineche-Schmidt V, Muris J, et al. Bulking agents, antispasmodic and antidepressant medication for the treatment of irritable bowel syndrome. Cochrane Database Syst Rev. 2005;(2):CD003460.
70. Ford AC, Talley NJ, Schoenfeld PS, et al. Efficacy of antidepressants and psychological therapies in irritable bowel syndrome: systematic review and meta-analysis. Gut. 2009;58(3):367-378.
71. Coss-Adame E, Erdogan A, Rao SS. Treatment of esophageal (noncardiac) chest pain: an expert review. Clin Gastroenterol Hepatol. 2014;12(8):1224-1245.
72. Kelada E, Jones A. Interstitial cystitis. Arch Gynecol Obstet. 2007;275(4):223-229.
73. Leo RJ, Dewani S. A systematic review of the utility of antidepressant pharmacotherapy in the treatment of vulvodynia pain. J Sex Med. 2013;10(10):2497-2505.
74. McMillan R, Forssell H, Buchanan JA, et al. Interventions for treating burning mouth syndrome. Cochrane Database Syst Rev. 2016;11:CD002779.
75. Patel DN. Inconclusive results of a systematic review of efficacy of antidepressants on orofacial pain disorders. Evid Based Dent. 2013;14(2):55-56.
76. Wang W, Sun YH, Wang YY, et al. Treatment of functional chest pain with antidepressants: a meta-analysis. Pain Physician. 2012;15(2):E131-E142.
77. Lavis JN. How can we support the use of systematic reviews in policymaking? PLoS Med. 2009;6(11):e1000141. doi: 10.1371/journal.pmed.1000141.
78. Sorkin L. Nociceptive transmission within the spinal cord. Mt Sinai J Med. 1991;58(3):208-216.
79. Yokogawa F, Kiuchi Y, Ishikawa Y, et al. An investigation of monoamine receptors involved in antinociceptive effects of antidepressants. Anesth Analg. 2002;95(1):163-168, table of contents.
80. Lynch ME. Antidepressants as analgesics: a review of randomized controlled trials. J Psychiatry Neurosci. 2001;26(1):30-36.
81. Max MB. Treatment of post-herpetic neuralgia: antidepressants. Ann Neurol. 1994;35(suppl):S50-S53.
82. Max MB, Lynch SA, Muir J, et al. Effects of desipramine, amitriptyline, and fluoxetine on pain in diabetic neuropathy. N Engl J Med. 1992;326(19):1250-1256.
83. McQuay HJ, Tramèr M, Nye BA, et al. A systematic review of antidepressants in neuropathic pain. Pain. 1996;68(2-3):217-227.
84. Mochizucki D. Serotonin and noradrenaline reuptake inhibitors in animal models of pain. Hum Psychopharmacol Clin Exp. 2004;19(suppl 1):15-19.
85. Sussman N. SNRIs versus SSRIs: mechanisms of action in treating depression and painful physical symptoms. Primary Care Companion J Clin Psychiatry. 2003;5(suppl 7):19-26.
86. Bundeff AW, Woodis CB. Selective serotonin reuptake inhibitors for the treatment of irritable bowel syndrome. Ann Pharmacother. 2014;48(6):777-784.
87. Jung AC, Staiger T, Sullivan M. The efficacy of selective serotonin reuptake inhibitors for the management of chronic pain. J Gen Intern Med. 1997;12(6):384-389.
88. Xie C, Tang Y, Wang Y, et al. Efficacy and safety of antidepressants for the treatment of irritable bowel syndrome: a meta-analysis. PLoS One. 2015;10(8):e0127815. doi: 10.1371/journal.pone.0127815. eCollection 2015.
89. Zijlstra TR , Barendregt PJ , van de Laar MA. Venlafaxine in fibromyalgia: results of a randomized, placebo-controlled, double-blind trial. Arthritis Rheum. 2002;46(suppl 9):S105.
90. Bymaster FP, Dreshfield-Ahmad LJ, Threlkeld PG. Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors. Neuropsychopharmacology. 2001;25(6):871-880.
91. Thorpe J, Shum B, Moore RA, et al. Combination pharmacotherapy for the treatment of fibromyalgia in adults. Cochrane Database Syst Rev. 2018;(2):CD010585.
92. Gilron I, Chaparro LE, Tu D, et al. Combination of pregabalin with duloxetine for fibromyalgia: a randomized controlled trial. Pain. 2016;157(7):1532-1540.
93. Häuser W, Petzke F, Üçeyler N, et al. Comparative efficacy and acceptability of amitriptyline, duloxetine and milnacipran in fibromyalgia syndrome: a systematic review with meta-analysis. Rheumatology (Oxford). 2011;50(3):532-543.
94. Hossain SM, Hussain SM, Ekram AR. Duloxetine in painful diabetic neuropathy: a systematic review. Clin J Pain. 2016;32(11):1005-1010.
95. Riediger C, Schuster T, Barlinn K, et al. Adverse effects of antidepressants for chronic pain: a systematic review and meta-analysis. Front Neurol. 2017;8:307.

Fibromyalgia

As with the issues encountered in interpreting the effectiveness of antidepressants in neuropathic pain, interpreting results gleaned from clinical trials of antidepressants for treating FM are fraught with similar difficulties. Although amitriptyline has been a first-line treatment for FM for many years, the evidence upon which such recommendations were based consisted of low-level studies that had a significant potential for bias.⁵⁹ Large randomized trials would offer more compelling data regarding the efficacy of amitriptyline, but the prohibitive costs of such studies makes it unlikely they will be conducted. Amitriptyline (25 to 50 mg/d) was effective in mitigating FM-related pain in a small percentage of patients studied, with an estimated NNT of 4.⁵⁹ Adverse effects, often contributing to treatment discontinuation, were encountered more frequently among patients who received amitriptyline compared with placebo.

Selective serotonin reuptake inhibitors failed to demonstrate significant pain relief (estimated NNT of 10), or improvement in fatigue or sleep problems, even though the studies upon which such conclusions were based were low-level studies with a high potential for bias.⁶⁰ Although SSRIs have limited utility for mitigating pain, they are still quite useful for reducing depression among patients with FM.⁶⁰

By contrast, the SNRIs duloxetine and milnacipran provided clinically relevant benefit over placebo in the frequency of patients reporting pain relief of ≥30%, as well as patients’ global impression of change.⁶¹ These agents, however, failed to provide clinically relevant benefit over placebo in improving health-related quality of life, reducing sleep problems, or improving fatigue. Nonetheless, duloxetine and milnacipran are FDA-approved for managing pain in FM. Studies assessing the efficacy of venlafaxine in the treatment of FM to date have been limited by small sample sizes, inconsistent dosing, lack of a placebo control, and lack of blinding, which limits the ability to clearly delineate the role of venlafaxine in managing FM.⁶²

Mirtazapine (15 to 45 mg/d) showed a clinically relevant benefit compared with placebo for participant-reported pain relief of ≥30% and sleep disturbances. There was no benefit in terms of participant-reported improvement of quality of life, fatigue, or negative mood.⁶³ The evidence was considered to be of low quality overall.

Headache

Amitriptyline has been employed off-label to address headache prophylaxis since 1964.⁶⁴ Compared with placebo, it is efficacious in ameliorating migraine frequency and intensity as well as the frequency of tension headache.^65,66 However, SSRIs and SNRIs (venlafaxine) failed to produce significant reductions in migraine frequency or severity or the frequencies of tension headache when compared with placebo.^67,68

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Antidepressants for chronic pain

References

Fibromyalgia

Headache

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