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Antidepressant and Anticonvulsant Drugs as Adjuvant Analgesics in Chronic Pain

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Melatonin, Neuroprotective Agents and Antidepressant Therapy

Abstract

Adjuvant analgesics are defined as drugs with a primary indication ther than pain that have analgesic properties in some painful conditions. The group includes numerous drugs in diverse classes. Although the widespread use of these drugs as first-line agents in chronic nonmalignant pain syndromes suggests that the term “adjuvant” is a misnomer, they usually are combined with a less-than-satisfactory opioid regimen when administered for cancer pain. Some adjuvant analgesics are useful in several painful conditions and are described as multipurpose adjuvant analgesics (antidepressants, corticosteroids, α2-adrenergic agonists, neuroleptics), whereas others are specific for neuropathic pain (anticonvulsants, local anesthetics, N-methyl-D-aspartate receptor antagonists), bone pain (calcitonin, bisphosphonates, radiopharmaceuticals), musculoskeletal pain (muscle relaxants), or pain from bowel obstruction (octreotide, anticholinergics). This article reviews the evidence supporting the use of two class of adjuvant analgesic for the treatment of chronic pain, antidepressant ans anticonvulsivants, and provides a comprehensive outline of dosing recommendations, side effects, and drug interactions.

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References

  1. Abbass K. Efficacy of gabapentin for treatment of adults with phantom limb pain. Ann Pharmacother. 2012;46:1707–11.

    Article  CAS  PubMed  Google Scholar 

  2. Alamo C, López-Muñóz F, García-García P. Tratamiento farmacológico del dolor neuropático en el anciano. In: Sociedad Española de Geriatría y Gerontología, editor. Guía de buena práctica clínica en geriatría. Dolor neuropático en el anciano. Madrid: DL; 2012. p. 33–49.

    Google Scholar 

  3. Álamo C, López-Muñoz F, García-García P, García-Ramos S. Risk–benefit analysis of antidepressant drug treatment in the elderly. Psychogeriatrics. 2014;14:261–8.

    Article  PubMed  Google Scholar 

  4. Ángel-García D, Martínez-Nicolás I, Saturno-Hernández PJ. Clinical approach to fibromyalgia: synthesis of evidence-based recommendations, a systematic review. Reumatol Clin. 2015. doi:10.1016/j.reuma.2015.06.001.

    PubMed  Google Scholar 

  5. Attal N, Cruccu G, Baron R, Haanpää M, Hansson P, Jensen TS, Nurmikko T, European Federation of Neurological Societies. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. Eur J Neurol. 2010;17:1113–e88.

    Article  CAS  PubMed  Google Scholar 

  6. Backonja MM. Use of anticonvulsants for treatment of neuropathic pain. Neurology. 2002;59(5 Suppl 2):S14–7.

    Article  PubMed  Google Scholar 

  7. Bajwa ZH, Smith HS. Overview of the treatment of chronic pain. In: Post TW, editor. UpToDate. Waltham: Wolters Kluwer; 2013.

    Google Scholar 

  8. Bergouignan M. Heureuses des neuralgies faciales esentielles par diphenylhidantoinate de soide. Rev Laringol Otol Rhinol. 1942;63:34–1.

    Google Scholar 

  9. Berry DJ, Beran RG, Plunkeft MJ, Clarke LA, Hung WT. The absorption of gabapentin following high dose escalation. Seizure. 2003;12:28–36.

    Article  PubMed  Google Scholar 

  10. Beydoun A, Uthman BM, Sackellares JC. Gabapentin: pharmacokinetics, efficacy, and safety. Clin Neuropharmacol. 1995;18:469–81.

    Article  CAS  PubMed  Google Scholar 

  11. Birse F, Derry S, Moore RA. Phenytoin for neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev. 2012;5, CD009485. doi:10.1002/14651858.CD009485.pub2.

    Google Scholar 

  12. Bockbrader HN, Wesche D, Miller R, Chapel S, Janiczek N, Burger P. A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin. Clin Pharmacokinet. 2010;49:661–9.

    Article  CAS  PubMed  Google Scholar 

  13. Bril V, England J, Franklin GM, Backonja M, Cohen J, Del Toro D, et al. Evidence-based guideline: treatment of painful diabetic neuropathy: report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology. 2011;76:1758–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Burchiel K. Carbamazepine inhibits spontaneous activity in experimental neurones. Exp Neurol. 1988;102:249–53.

    Article  CAS  PubMed  Google Scholar 

  15. CADTH. CADTH rapid response reports. Gabapentin for adults with neuropathic pain: a review of the clinical efficacy and safety. Ottawa: Canadian Agency for Drugs and Technologies in Health; 2015.

    Google Scholar 

  16. Chang CY, Challa CK, Shah J, Eloy JD. Gabapentin in acute postoperative pain management. Biomed Res Int. 2014;2014:631756. doi: 10.1155/2014/631756. Epub 2014 Apr 14.

    Google Scholar 

  17. Citrome L, Weiss-Citrome A. A systematic review of duloxetine for osteoarthritic pain: what is the number needed to treat, number needed to harm, and likelihood to be helped or harmed? Postgrad Med. 2012;124:83–93.

    Article  PubMed  Google Scholar 

  18. Clarke H, Bonin RP, Orser BA, Englesakis M, Wijeysundera DN, Katz J. The prevention of chronic postsurgical pain using gabapentin and pregabalin: a combined systematic review and meta-analysis. Anesth Analg. 2012;115:428–42.

    Article  CAS  PubMed  Google Scholar 

  19. Cording M, Derry S, Phillips T, Moore RA, Wiffen PJ. Milnacipran for pain in fibromyalgia in adults. Cochrane Database Syst Rev. 2015;10:Cd008244. doi:10.1002/14651858.CD008244.pub3.

    Google Scholar 

  20. Couch JR, Ziegler DK, Hassanein R. Amitriptyline in the prophylaxis of migraine. Effectiveness and relationship of antimigraine and antidepressant effects. Neurology. 1976;26:121–7.

    Article  CAS  PubMed  Google Scholar 

  21. Cruz-Hernández JJ, Álamo C, de Castro J, Contreras J, Gálvez R, García J, et al. Monografía “Aula de dolor musculoesquelético”. Paciente oncológico. 2nd ed. Madrid: Mundipharma Pharmaceuticals, S.L; 2012.

    Google Scholar 

  22. Derry S, Phillips T, Moore RA, Wiffen PJ. Milnacipran for neuropathic pain in adults. Cochrane Database Syst Rev. 2015;7:CD011789. doi:10.1002/14651858.cd011789.

    Google Scholar 

  23. Derry S, Wiffen PJ, Aldington D, Moore RA. Nortriptyline for neuropathic pain in adults. Cochrane Database Syst Rev. 2015;1:Cd011209. doi:10.1002/14651858.CD011209.pub2.

    PubMed  Google Scholar 

  24. Dharmshaktu P, Tayal V, Kalra BS. Efficacy of antidepressants as analgesics: a review. J Clin Pharmacol. 2012;52:6–17.

    Article  CAS  PubMed  Google Scholar 

  25. Doleman B, Heinink TP, Read DJ, Faleiro RJ, Lund JN, Williams JP. A systematic review and meta-regression analysis of prophylactic gabapentin for postoperative pain. Anaesthesia. 2015;70:1186–204.

    Article  CAS  PubMed  Google Scholar 

  26. Dworkin RH, O’Connor AB, Audette J, Baron R, Gourlay GK, Haanpää ML, et al. Recommendations for the pharmacological management of neuropathic pain: an overview and literature update. Mayo Clin Proc. 2010;85(3 Suppl):S3–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Finnerup NB, Sindrup SH, Jensen TS. The evidence for pharmacological treatment of neuropathic pain. Pain. 2010;150:573–81.

    Article  PubMed  Google Scholar 

  28. Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015;14:162–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Gilron I, Bailey JM, Tu D, Holden RR, Weaver DF, Houlden RL. Morphine, gabapentin, or their combination for neuropathic pain. N Engl J Med. 2005;352:1324–34.

    Article  CAS  PubMed  Google Scholar 

  30. Giner J, Saiz Ruiz J, Bobes J, Zamorano E, López F, Hernando T, et al. Grupo para el Desarrollo de Recomendaciones sobre Salud Física en el Paciente con Depresión. Spanish consensus on the physical health of patients with depressive disorders. Rev Psiquiatr Salud Ment. 2014;7:195–207.

    Article  PubMed  Google Scholar 

  31. Godfrey RG. A guide to the understanding and use of tricyclic antidepressants in the overall management of fibromyalgia and other chronic pain syndromes. Arch Intern Med. 1996;156:1047–52.

    Article  CAS  PubMed  Google Scholar 

  32. Goldstein FJ. Adjuncts to opioid therapy. JAOA. 2002;102:S15–20.

    PubMed  Google Scholar 

  33. Häuser W, Walitt B, Fitzcharles MA, Sommer C. Review of pharmacological therapies in fibromyalgia syndrome. Arthritis Res Ther. 2014;16:201.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Hearn L, Derry S, Phillips T, Moore RA, Wiffen PJ. Imipramine for neuropathic pain in adults. Cochrane Database Syst Rev. 2014;5:Cd010769. doi:10.1002/14651858.CD010769.pub2.

    Google Scholar 

  35. Hearn L, Moore RA, Derry S, Wiffen PJ, Phillips T. Desipramine for neuropathic pain in adults. Cochrane Database Syst Rev. 2014;9:Cd011003. doi:10.1002/14651858.CD011003.pub2.

    Google Scholar 

  36. IASP. Pain terms: a list of definitions and notes on usage. Pain. 1979;6:249–52.

    Google Scholar 

  37. Jackson JL, Shimeall W, Sessums L, DeZee KJ, Becher D, Diemer M, et al. Tricyclic antidepressants and headaches: systematic review and meta-analysis. BMJ. 2010;341:c5222.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Knotkova H, Pappagallo M. Adjuvant analgesics. Med Clin N Am. 2007;91:113–24.

    Article  CAS  PubMed  Google Scholar 

  39. Kyle JA, Dugan BD, Testerman KK. Milnacipran for treatment of fibromyalgia. Ann Pharmacother. 2010;44:1422–9.

    Article  CAS  PubMed  Google Scholar 

  40. López-Muñoz F, Álamo C. Monoaminergic neurotransmission: the history of the discovery of antidepressants from 1950s until today. Curr Pharm Des. 2009;15:1563–86.

    Article  PubMed  Google Scholar 

  41. López Muñoz F, Álamo C. Antidepresivos y anticonvulsivantes. En: Máster Universitario de Especialista en el Tratamiento del Dolor (SED). Tratamiento del dolor: farmacológico, psicológico y psiquiátrico. Unidad 3, Módulo 15. Valladolid: Universidad Europea Miguel de Cervantes; 2012.

    Google Scholar 

  42. Lussier D, Huskey AG, Portenoy RK. Adjuvant analgesics in cancer pain management. Oncologist. 2004;9:571–91.

    Article  CAS  PubMed  Google Scholar 

  43. McCleane G. Antidepressants as analgesics. CNS Drugs. 2008;22:139–56.

    Article  CAS  PubMed  Google Scholar 

  44. McDonald AA, Portenoy RK. How to use antidepressants and anticonvulsants as adjuvant analgesics in the treatment of neuropathic cancer pain. J Support Oncol. 2006;4:43–52.

    CAS  PubMed  Google Scholar 

  45. Merskey H, Bogduk N, editors. Classification of chronic pain: descriptions of chronic pain syndromes and definitions of pain terms. 2nd ed. Seattle: IASP Press; 1994.

    Google Scholar 

  46. Moja L, Cusi C, Sterzi R, Canepari C Selective serotonin reuptake inhibitors (SSRIs) for preventing migraine and tensiontype headaches. Cochrane Database Syst Rev 2005 Jul 20;(3):CD002919:CD002919. http://dx.doi.org/10.1002/14651858.CD002919.pub2.

  47. Moore RA, Derry S, Aldington D, Cole P, Wiffen PJ. Amitriptyline for fibromyalgia in adults. Cochrane Database Syst Rev. 2015;7:Cd011824. doi:10.1002/14651858.cd011824.

    Google Scholar 

  48. Moore RA, Derry S, Aldington D, Cole P, Wiffen PJ. Amitriptyline for neuropathic pain in adults. Cochrane Database Syst Rev. 2015;7:Cd008242. doi:10.1002/14651858.CD008242.pub3.

    Google Scholar 

  49. Moore RA, Straube S, Wiffen PJ, Derry S, McQuay HJ. Pregabalin for acute and chronic pain in adults. Cochrane Database Syst Rev. 2009;3:Cd007076. doi:10.1002/14651858.CD007076.pub2.

    Google Scholar 

  50. Moore RA, Wiffen PJ, Derry S, Toelle T, Rice AS. Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev. 2014;4:Cd007938. doi:10.1002/14651858.CD007938.pub3.

    Google Scholar 

  51. Moulin DE, Boulanger A, Clark AJ, Clarke H, Dao T, Finley GA, et al. Pharmacological management of chronic neuropathic pain: revised consensus statement from the Canadian Pain Society. Pain Res Manag. 2014;19:328–35.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Onghena P, Van Houdenhove B. Antidepressant-induced analgesia in chronic non-malignant pain: a meta-analysis of 39 placebo-controlled studies. Pain. 1992;49:205–19.

    Article  CAS  PubMed  Google Scholar 

  53. Paoli F, Darcourt G, Cossa P. Note preliminaire sur l’action de l’imipramine dans les états douloureus. Rev Neurol (Paris). 1960;102:503–50.

    CAS  Google Scholar 

  54. Perrot S, Maheu E, Javier RM, Eschalier A, Coutaux A, LeBars M, et al. Guidelines for the use of antidepressants in painful rheumatic conditions. Eur J Pain. 2006;10:185–92.

    Article  CAS  PubMed  Google Scholar 

  55. Portenoy RK, McCaffery M. Adjuvant analgesics. In: McCaffery M, Pasero C, editors. Pain: a clinical manual. New York: Mosby; 1999. p. 300–61.

    Google Scholar 

  56. Rico-Villademoros F, Slim M, Calandre EP. Amitriptyline for the treatment of fibromyalgia: a comprehensive review. Expert Rev Neurother. 2015;15:1123–50.

    Article  CAS  PubMed  Google Scholar 

  57. Rogawski MA, Loscher W. The neurobiology of antiepileptic drugs for the treatment of nonepileptic conditions. Nat Med. 2004;10:685–92.

    Article  CAS  PubMed  Google Scholar 

  58. Rolan PE. Understanding the pharmacology of headache. Curr Opin Pharmacol. 2014;14:30–3.

    Article  CAS  PubMed  Google Scholar 

  59. Schreiber AK, Nones CFM, Reis RC, Chichorro JG, Cunha JM. Diabetic neuropathic pain: physiopathology and treatment. World J Diabetes. 2015;6:432–44.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Simpson DM, McArthur JC, Olney R, Clifford D, So Y, Ross D, et al. Lamotrigine for HIV-associated painful sensory neuropathies: a placebo-controlled trial. Neurology. 2003;60:1508–14.

    Article  CAS  PubMed  Google Scholar 

  61. Simpson DM, Olney R, McArthur JC, Khan A, Godbold J, Ebel-Frommer K. A placebo-controlled trial of lamotrigine for painful HIV-associated neuropathy. Neurology. 2000;54:2115–9.

    Article  CAS  PubMed  Google Scholar 

  62. Surges R, Feuerstein TJ. Mode of action of gabapentin in chronic neuropathic pain syndromes. A short review about its cellular mechanisms in nociceptive neurotransmission. Arzneimittelforschung. 2002;52:583–6.

    CAS  PubMed  Google Scholar 

  63. Titlic M, Jukic I, Tonkic A, Josipovic-Jelic Z, Boschi V, Mihalj M, Punda A. Lamotrigine in the treatment of pain syndromes and neuropathic pain. Bratisl Lek Listy. 2008;109:421–4.

    CAS  PubMed  Google Scholar 

  64. WHO. The essential adjuvant analgesics for neuropathic pain. Cancer Pain Release. 2002;15(2):45–59.

    Google Scholar 

  65. Wiffen PJ, Derry S, Moore RA, Kalso EA. Carbamazepine for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev. 2014;4, CD005451. doi:10.1002/14651858.CD005451.pub3.

    Google Scholar 

  66. Wiffen PJ, Derry S, Moore RA. Lamotrigine for acute and chronic pain. Cochrane Database Syst Rev. 2011;2:Cd006044. doi:10.1002/14651858.CD006044.pub3.

    Google Scholar 

  67. Wiffen PJ, Derry S, Moore RA. Lamotrigine for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev. 2013;12:Cd006044. doi:10.1002/14651858.CD006044.pub4.

    Google Scholar 

  68. Woolf CJ, Decosterd I. Implications of recent advances in the understanding of pain pathophysiology for the assessment of pain in patients. Pain. 1999;82(Suppl 6):S141–7.

    Google Scholar 

  69. Yu L, Ran B, Li M, Shi Z. Gabapentin and pregabalin in the management of postoperative pain after lumbar spinal surgery: a systematic review and meta-analysis. Spine. 2013;38:1947–52. doi:10.1097/BRS.0b013e3182a69b90.

    Article  PubMed  Google Scholar 

  70. Zakrzewska JM. Medical management of trigeminal neuropathic pains. Expert Opin Pharmacother. 2010;11:1239–54.

    Article  CAS  PubMed  Google Scholar 

  71. Zakrzewska JM, Chaudhry Z, Nurmikko TJ, Patton DW, Mullens EL. Lamotrigine (Lamictal) in refractory trigeminal neuralgia: results from a double-blind placebo controlled crossover trial. Pain. 1997;73:223–30.

    Article  CAS  PubMed  Google Scholar 

  72. Zhou M, Chen N, He L, Yang M, Zhu C, Wu F. Oxcarbazepine for neuropathic pain. Cochrane Database Syst Rev. 2013;3, CD007963. doi:10.1002/14651858.CD007963.pub2.

    Google Scholar 

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Authors and Affiliations

  1. Primary Care Administration of Soria, Soria, Spain

    Manuel Sebastián-Aldeanueva

  2. Faculty of Health Sciences, Camilo José Cela University, Villanueva de la Cañada, Madrid, Spain

    Francisco López-Muñoz

  3. Neuropsychopharmacology Unit, Hospital 12 de Octubre Research Institute (i+12), Madrid, Spain

    Francisco López-Muñoz

  4. Portucalense Institute of Neuropsychology and Cognitive and Behavioural Neurosciences, Portucalense University, Porto, Portugal

    Francisco López-Muñoz

  5. Department of Pharmacology, Pharmacy Faculty, Complutense University, Madrid, Spain

    José Antonio Guerra

  6. Department of Biomedical Sciences (Pharmacology Area), Faculty of Medicine and Health Sciences, University of Alcalá, Alcalá de Henares, Madrid, Spain

    Cecilio Álamo

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  1. Manuel Sebastián-Aldeanueva
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  2. Francisco López-Muñoz
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  3. José Antonio Guerra
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  4. Cecilio Álamo
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Correspondence to Francisco López-Muñoz .

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Editors and Affiliations

  1. Vice-Rectorate for Research and Sci, Camilo José Cela University Vice-Rectorate for Research and Sci, Madrid, Spain

    Francisco López-Muñoz

  2. International Medical Sciences Research Study Center, Sri Sathya Sai Medical Educational & Research Foundation, Coimbatore, India

    Venkataramanujam Srinivasan

  3. Department of Neurosciences and Ima, University of Chieti Department of Neurosciences and Ima, Italy, Italy

    Domenico de Berardis

  4. Department of Biomedical Sciences (Pharmacology Area), University of Alcalá, Madrid, Spain

    Cecilio Álamo

  5. Department of Neuropsychiatry, Kyushu University, Fukuoka, Japan

    Takahiro A. Kato

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Sebastián-Aldeanueva, M., López-Muñoz, F., Guerra, J.A., Álamo, C. (2016). Antidepressant and Anticonvulsant Drugs as Adjuvant Analgesics in Chronic Pain. In: López-Muñoz, F., Srinivasan, V., de Berardis, D., Álamo, C., Kato, T. (eds) Melatonin, Neuroprotective Agents and Antidepressant Therapy. Springer, New Delhi. https://doi.org/10.1007/978-81-322-2803-5_33

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