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The psychopharmacologic treatment of depression and anxiety in the context of chronic pain

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Abstract

Chronic pain afflicts millions of people, commonly causing depression and anxiety. These conditions must be treated to achieve a good functional outcome from pain treatment. Selective serotonin reuptake inhibitors, tricyclics, and newer antidepressants effectively treat both depression and selected anxiety disorders. Antidepressants with noradrenergic and serotinergic activity, and anticonvulsants, which may also stabilize mood, are effective in neuropathic pain. Other medications have limited but important pharmacotherapeutic roles.

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References and Recommended Reading

  1. Loeser JD, Melzack R: Pain: an overview. Lancet 1999, 353:1607–1609.

    Article  PubMed  CAS  Google Scholar 

  2. Fishbain DA: Approaches to treatment decisions for psychiatric comorbidity in management of chronic pain patient. Med Clin North Am 1999, 3:737–761. Clear exposition of decision making for treating comorbidity in chronic pain patients.

    Article  Google Scholar 

  3. Fishbain DA, Cutler RB, Rosomoff HL, et al.: Chronic pain associated depression: Antecedent or consequence of chronic pain? A review. Clin J Pain 1997, 13:116–137.

    Article  PubMed  CAS  Google Scholar 

  4. Romano JM, Turner JA: Chronic pain and depression: does the evidence support the relationship. Psychol Bull 1985, 97:18–34.

    Article  PubMed  CAS  Google Scholar 

  5. Fishbain DA: Current research on chronic pain and suicide. Am J Public Health 1996, 86:1320–1321.

    PubMed  CAS  Google Scholar 

  6. Gallagher RM: Integrating medical and behavioral treatment in chronic pain management. Med Clin North Am 1999, 83:823–849.

    Article  PubMed  CAS  Google Scholar 

  7. Richelson E: Pharmacology of antidepressants. Mayo Clinic Proc 2001, 76:511–527.

    CAS  Google Scholar 

  8. Mulrow CD, Williams JW Jr, Chiquette E, et al.: Efficacy of newer medications for treating depression in primary care patients. Am J Med 2000, 108:54–64.

    Article  PubMed  CAS  Google Scholar 

  9. Schulberg HC, Katon W, Simon GE, Rush AJ: Treating major depression in primary care practice: an update of the Agency for Health Care Policy and Research practice guidelines. Arch Gen Psychiatry 1998, 55:1121–1127.

    Article  PubMed  CAS  Google Scholar 

  10. Depression Guideline Panel. Depression in Primary Care. Clinical Practice Guideline, no. 5. Rockville, MD: Agency for Health Care Policy and Research; 1993.

  11. Beasley CM Jr, Dornseif BE, Pultz JA, et al.: Fluoxetine versus trazodone: efficacy and activating-sedating effects. J Clin Psychiatry 1991, 52:294–299.

    PubMed  Google Scholar 

  12. Tollefson GD, Holman SL, Sayler ME, Potvin JH: Fluoxetine, placebo, and tricyclic antidepressants in major depression with and without anxious features. J Clin Psychiatry 1994, 55:50–59.

    PubMed  CAS  Google Scholar 

  13. Simon GE, Heiligenstein JH, Grothaus L, et al.: Should anxiety and insomnia influence antidepressant selection: a randomized comparison of fluoxetine and imipramine. J Clin Psychiatry 1998, 59:49–55.

    PubMed  CAS  Google Scholar 

  14. Simon GE, Heiligenstein J, Revicki D, et al.: Long-term outcomes of initial antidepressant drug choice in a "real world" randomized trial. Arch Fam Med 1999, 8:319–325.

    Article  PubMed  CAS  Google Scholar 

  15. Jick SS, Dean AD, Jick H: Antidepressants and suicide. BMJ 1995, 310:215–218.

    PubMed  CAS  Google Scholar 

  16. Sawynok J, Esser MJ, Reid AR: Antidepressants as analgesics: an overview of central and peripheral mechanisms of action. J Psychiatry Neurosci 2001, 26:21–29. Good review of antidepressants and pain.

    PubMed  CAS  Google Scholar 

  17. Speigel K, Kalb R, Pasternak GW: Analgesic activity of tricyclic antidepressants. Ann Neurol 1983, 13:462–465.

    Article  Google Scholar 

  18. Sierralta F, Pinardi G Miranda HF: Effects of p-chlorophenylalnine and alpha-methyltyrosine on the antinociceptive effect of antidepressant drugs. Pharmacol Toxicol 1995, 77:276–280.

    PubMed  CAS  Google Scholar 

  19. Schreiber S, Backer MM, Weizaman R, Pick GG: The antinociceptive effects of fluoxetine. Pain Clin 1996, 9:349–356.

    Google Scholar 

  20. Hwang AS, Wilcox GL: Analgesic properties of intrathecally administered heterocyclics. Pain 1987, 28:343–355.

    Article  PubMed  CAS  Google Scholar 

  21. Iwashita T, Shimizu T: Imipramine inhibits intrathecal substance P-induced behaviour and blocks spinal cord substance P receptors in mice. Brain Res 1992, 581:59–66.

    Article  PubMed  CAS  Google Scholar 

  22. Eisenach JC, Gebhart GF: Intrathecal amitriptyline acts as a N-methyl-D-aspartate receptor antagonist in the presence of inflammatory hyperalgesia in rats. Anesthesiology 1995, 83:1046–1054.

    Article  PubMed  CAS  Google Scholar 

  23. Sawynok J, Esser MJ, Reid AR: Peripheral antinociceptive actions of desipramine and fluoxetine in an inflammatory and neuropathic pain test in the rat. Pain 1999, 82:149–158.

    Article  PubMed  CAS  Google Scholar 

  24. Sawynok J, Reid AR, Esser MJ: Peripheral antinociceptive action of amitriptyline in the rat formalin test: involvement of adenosine. Pain 1999, 80(1-2):45–55.

    Article  PubMed  CAS  Google Scholar 

  25. Scott MA, Letrent KJ, Hager KL, Burch JL: Use of transdermal amitriptyline gel in a patient with chronic pain and depression. Pharmacotherapy 1999, 19:236–239.

    Article  PubMed  CAS  Google Scholar 

  26. Gallagher RM, Verma S: Managing pain and co-morbid depression: a public health challenge. Semin Clin Neuropsychiatry 1999, 4:203–220. A detailed review of the relationship between pain and mood and the clinical management of pain and comorbid depression.

    PubMed  CAS  Google Scholar 

  27. Max M: Antidepressants As Analgesics. Progress in Pain Research and Management, vol 1. Seattle: IASP Press; 1994.

    Google Scholar 

  28. France RD: The future of antidepressants: treatment of pain. Psychopathology 1987, 20(suppl 1):99–113.

    Article  PubMed  Google Scholar 

  29. Blumer D, Heilbron M: Chronic pain as a variant of depressive disease: the pain-prone disorder. J Nerv Ment Dis 1982, 170:381–406.

    Article  PubMed  CAS  Google Scholar 

  30. Banks SM, Kerns RD: Explaining high rates of depression in chronic pain: a diathesis-stress framework. Psychol Bull 1996, 119:95–110.

    Article  Google Scholar 

  31. Dohrenwend B, Marbach J, Raphael K, Gallagher RM: Why is depression co-morbid with chronic facial pain? A family study test of alternative hypotheses. Pain 1999, 83:183–192. Methodologic advances in this study help establish that pain causes depression.

    Article  PubMed  CAS  Google Scholar 

  32. Aronoff GM, Evans WO: Doxepine as an adjunct in the treatment of chronic pain. J Clin Psychiatry 1982, 43(8/sec 2):42–45.

    PubMed  CAS  Google Scholar 

  33. Gallagher RM, Verma S: Treatment and rehabilitation of chronic orthopedic pain syndromes. In Psychiatric Care of the Medical Patient. Edited by Stoudemire A et al. New York: 2000.

  34. Gallagher RM, Woznicki M: Low back pain rehabilitation. In Medical Psychiatric Practice, vol 2. Edited by Stoudemire A, Fogel BS. Washington, DC: APA Press; 1993.

    Google Scholar 

  35. Botney M, Fields HL: Amitriptyline potentiates morphine analgesia by direct action on the central nervous system. Ann Neurol 1983, 13:160–164.

    Article  PubMed  CAS  Google Scholar 

  36. Lynch ME: Antidepressants as analgesics: a review of randomized controlled trials. J Psychiatry Neurosci 2001, 26:30–36.

    PubMed  CAS  Google Scholar 

  37. Kvinesdale B, Molin J, Forland A, Gram LF: Imipramine in treatment of painful diabetic neuropathy. JAMA 1984, 251:1727–1730.

    Article  Google Scholar 

  38. Max MB, Cunane M, Scahfer SC, et al.: Amitriptyline relieves diabetic neuropathy pain in patients with normal or depressed mood. Neurology 1987, 37:589–596.

    PubMed  CAS  Google Scholar 

  39. Max MB, Kishore-Kumar R, Schaffer SC, et al.: Efficacy of desipramine in painful diabetic neuropathy: a placebo-controlled trail. Pain 1991, 45:3–9.

    Article  PubMed  CAS  Google Scholar 

  40. Sindrup SH, Ejlertsen B, Forland A, et al.: Imipramine in the treatment of diabetic neuropathy; relief of subjective symptoms without change in peripheral and autonomic nerve function. Eur J Clin Phamacol 1989, 37:151–153.

    Article  CAS  Google Scholar 

  41. Joss JD: Tricyclic antidepressant use in diabetic neuropathy. Ann Pharmacother 1999, 33:996–1000.

    Article  PubMed  CAS  Google Scholar 

  42. Watson CP, Vernich L, Chipman M, Reed K: Nortriptyline versus amitriptyline in postherpetic neuralgia: a randomized trial. Neurology 1998, 51:1166–1167.

    PubMed  CAS  Google Scholar 

  43. Panerai AE, Monza G, Movilla P, et al.: A randomized, within patient, crossover, placebo-controlled trail on the efficacy and tolerability of tricyclics antidepressants chlorimipramine and desipramine in central pain. Acta Neurol Scand 1990, 82:34–38.

    Article  PubMed  CAS  Google Scholar 

  44. Leijon G, Boivie J: Central post-stroke pain: controlled trial of amitriptyline and carbamazepine. Pain 1989, 36:27–36.

    Article  PubMed  CAS  Google Scholar 

  45. Tomkins GE, Jackson JL, O’Malley PG, et al.: Treatment of chronic headache with antidepressants: a meta-analysis. Am J Med 2001, 111:54–63.

    Article  PubMed  CAS  Google Scholar 

  46. Bowsher D: The effects of pre-emptive treatment of post herpetic neuralgia with amitriptyline: a randomized double blind, placebo-controlled trial. J Pain Symptom Manage 1997, 13:327–331.

    Article  PubMed  CAS  Google Scholar 

  47. Levine JD, Gordon NC, Smith R, et al.: Desipramine enhances opiate postoperative analgesia. Pain 1986, 27:45–49.

    Article  PubMed  CAS  Google Scholar 

  48. Lindsay PG, Olsen RB: Maprotiline in pain-depression. J Clin Psychiatry 1985, 46:226–228.

    PubMed  CAS  Google Scholar 

  49. Pfeiffer RF: Drugs for pain in the elderly. Geriatrics 1982, 37:67–69.

    PubMed  CAS  Google Scholar 

  50. Atkinson JH, Slater MA, Wahlgren DR, et al.: Effects of noradrenergic and serotonergic antidepressants on chronic low back pain intensity. Pain 1999, 83:137–145.

    Article  PubMed  CAS  Google Scholar 

  51. Vrethem M, Boivie J, Arnqvist H, et al.: A comparison of amitriptyline and maprotiline in the treatment of painful polyneuropathy in diabetics and nondiabetics. Clin J Pain 1997, 13:313–323.

    Article  PubMed  CAS  Google Scholar 

  52. Watson CP, Chipman M, Reed K, et al.: Amitriptyline versus maprotiline in postherpetic neuralgia: a randomized, double-blind, crossover trial. Pain 1992, 48:29–36.

    Article  PubMed  CAS  Google Scholar 

  53. Eberhard G, von Knorring L, Nilsson HL, et al.: A double-blind randomized study of clomipramine versus maprotiline in patients with idiopathic pain syndromes. Neuropsychobiology 1988, 19:25–34.

    PubMed  CAS  Google Scholar 

  54. Jung AC, Staiger T, Sullivan M: The efficacy of selective serotonin reuptake inhibitors for the management of chronic pain. J Gen Intern Med 1997, 12:384–389.

    Article  PubMed  CAS  Google Scholar 

  55. Max MB, Lynch SA, Muir J, et al.: Effects of desipramine amitriptyline and fluoxetine on pain in diabetic neuropathy. N Engl J Med 1992, 326:1250–1256.

    Article  PubMed  CAS  Google Scholar 

  56. Sindrup SH, Bjerre U, Dejgaard A, et al.: The selective serotonin reuptake inhibitor citalopram relieves the symptoms of diabetic neuropathy symptoms. Clin Pharmacol Ther 1992, 52:547–552.

    Article  PubMed  CAS  Google Scholar 

  57. Sindrup SH, Gram LF, Brosen K, et al.: The selective serotonin reuptake inhibitor paroxetine is effective in the treatment of diabetic neuropathy symptoms. Pain 1990, 43:135–144.

    Article  Google Scholar 

  58. Lynch ME: Antidepressants as analgesics: a review of randomized controlled trials. J Psychiatry Neurosci 2001, 26:30–36. A good review of the literature.

    PubMed  CAS  Google Scholar 

  59. Sindrup SH, Jensen TS: Pharmacologic treatment of pain in polyneuropathy. Neurology 2000, 55:915–920.

    PubMed  CAS  Google Scholar 

  60. Fishbain DA, Cutler R, Rosomoff HL, Rosomoff RS: Evidencebased data from animal and human experimental studies on pain relief with antidepressants: a structured review. Pain Med 2000, 1:310–316. A systematic review of the animal and human data on the use of antidepressants in pain.

    Article  PubMed  CAS  Google Scholar 

  61. Onghena P, Van Houdenhove B: Antidepressant-induced analgesia in chronic non-malignant pain: a meta-analysis of 39 placebo controlled studies. Pain 1992, 49:205–209.

    Article  PubMed  CAS  Google Scholar 

  62. Semenchuk MR, Davis B: Efficacy of sustained-release bupropion in neuropathic pain: an open-label study. Clin J Pain 2000, 16:6–11.

    Article  PubMed  CAS  Google Scholar 

  63. Markowitz JS, Patrick KS: Venlafaxine-tramadol similarities. Med Hypotheses 1998, 51:167–168.

    Article  PubMed  CAS  Google Scholar 

  64. Songer DA, Schulte H: Venlafaxine for the treatment of chronic pain. Am J Psychiatry 1996, 153:737.

    PubMed  CAS  Google Scholar 

  65. Pernia A, Mico JA, Calderon E, Torres LM: Venlafaxine for the treatment of neuropathic pain. J Pain Symptom Manage 2000, 19:408–410.

    Article  PubMed  CAS  Google Scholar 

  66. Davis JL, Smith RL: Painful peripheral diabetic neuropathy treated with venlafaxine HCl extended release capsules. Diabetes Care 1999, 22:1909–1910.

    Article  PubMed  CAS  Google Scholar 

  67. Brannon GE, Stone KD: The use of mirtazapine in a patient with chronic pain. J Pain Symptom Manage 1999, 18:382–385.

    Article  PubMed  CAS  Google Scholar 

  68. Lascelles RG: Atypical facial pain and depression. Br J Psychiatry 1966, 112:651–659.

    Article  PubMed  CAS  Google Scholar 

  69. Schreiber S, Getslev V, Weizman A, Pick CG: The antinociceptive effect of moclobemide in mice is mediated by noradrenergic pathways. Neurosci Lett 1998, 253:183–186.

    Article  PubMed  CAS  Google Scholar 

  70. Menkes DB, Fawcett JP, Busch AF, Jones D: Moclobemide in chronic neuropathic pain: preliminary case reports. Clin J Pain 1995, 11:134–138.

    Article  PubMed  CAS  Google Scholar 

  71. Jacox A, Carr DB, Payne R: Management of Cancer Pain. Clinical Practice Guideline No. 9. Agency for Health Care Policy and Research. Rockville, MD: US Department of Health and Human Services, Public Health Service; 1994.

    Google Scholar 

  72. Christina MD: Antidepressant augmentation and combinations. Psychiatr Clin North Am 2000, 23:743–755.

    Article  Google Scholar 

  73. Corrigan FM: Sodium valproate augmentation of fluoxetine or fluvoxamine effects. Biol Psychiatry 1992, 31:1178–1179.

    Article  PubMed  CAS  Google Scholar 

  74. De la FuenteJM, Mendlewicz J: Carbamazepine addition in tricyclic antidepressant-resistant unipolar depression. Biol Psychiatry 1992, 32:369–374.

    Article  PubMed  Google Scholar 

  75. Calabrese JR, Bowden CL, McElroy SL, et al.: Spectrum of activity of lamotrigine in treatment: refractory bipolar disorder. Am J Psychiatry 1999, 156:1019–1023.

    PubMed  CAS  Google Scholar 

  76. Calabrese JR, Bowden CL, Sachs GS, et al.: A double-blind placebo-controlled study of lamotrigine monotherapy in outpatients with bipolar I depression. J Clin Psychiatry 1999, 60:79–88.

    Article  PubMed  CAS  Google Scholar 

  77. Kuch K, Cox BJ, Evans RJ: Posttraumatic stress disorder and motor vehicle accidents: a multidisciplinary overview. Can J Psychiatry 1996, 41:429–434.

    PubMed  CAS  Google Scholar 

  78. Sasson Y, Zohar J, Chopra M, et al.: Epidemiology of obsessivecompulsive disorder: a world view. J Clin Psychiatry 1997, 58(suppl_12):7–10.

    PubMed  Google Scholar 

  79. Davidson JRT, Kudler HS, Smith RD, et al.: Treatment of posttraumatic stress disorder with amitriptyline and placebo. Arch Gen Psychiatry 1990, 47:259–266.

    PubMed  CAS  Google Scholar 

  80. Kosten TR, Frank JB, Dan E, et al.: Pharmacotherapy for posttraumatic stress disorder using phenelzine or imipramine. J Nerv Ment Dis 1991, 179:366–370.

    Article  PubMed  CAS  Google Scholar 

  81. van der KolkBA, Dreyfuss D, Michaels M: Fluoxetine in posttraumatic stress disorder. J Clin Psychiatry 1994, 55:517–522.

    PubMed  Google Scholar 

  82. Connor KM, Sutherland SM, Tupler LA, et al.: Fluoxetine in post-traumatic stress disorder: randomized double-blind study. Br J Psychiatry 1999, 175:17–22.

    Article  PubMed  CAS  Google Scholar 

  83. Brady KT, Pearlstein T, Asnis GM, et al.: Efficacy and safety of sertraline treatment of posttraumatic stress disorder: a randomized controlled trial. JAMA 2000, 283:1837–1844.

    Article  PubMed  CAS  Google Scholar 

  84. Davidson JRT, Rothbaum BO, van der KolkBA, et al.: Multicenter, double-blind comparisons of sertraline and placebo in the treatment of posttraumatic stress disorder. Arch Gen Psychiatry 2001, 58:485–492.

    Article  PubMed  CAS  Google Scholar 

  85. Marshall RD, Schneier FR, Fallon BA, et al.: An open trial of paroxetine in patients with non-combat-related, chronic posttraumatic stress disorder. J Clin Psychopharmacol 1998, 18:10–18.

    Article  PubMed  CAS  Google Scholar 

  86. Seedat S, Stein DJ, Emsley RA: Open trial of citalopram in adults with post-traumatic stress disorder. Int J Neuropsychopharmacol 2000, 3:135–140.

    Article  PubMed  CAS  Google Scholar 

  87. Davidson JRT, Weisler RH, Malik ML, Tupler LA: Fluvoxamine in civilians with posttraumatic stress disorder. J Clin Psychopharmacol 1998, 18:93–95.

    Article  PubMed  CAS  Google Scholar 

  88. Hidalgo RB, Hertzberg MA, Mellman TA, et al.: Nefazodone in post-traumatic stress disorder: results from six open-label trials. Int Clin Psychopharmacol 1999, 14:61–68.

    Article  PubMed  CAS  Google Scholar 

  89. Canive JM, Clark RD, Calaris LA, et al.: Bupropion treatment in veterans with posttraumatic stress disorder: an open study. J Clin Psychopharmacol 1998, 18:379–383.

    Article  PubMed  CAS  Google Scholar 

  90. Connor KM, Davidson JRT, Weisler AH, Ahearn EP: A pilot study of mirtazapine in post-traumatic stress disorder. Int Clin Psychopharmacol 1999, 14:29–31.

    Article  PubMed  CAS  Google Scholar 

  91. Kirkwood CK, Hayes PE: Anxiety disorders. In Pharmacotherapy, edn 3. Edited by DiPiro JT et al. Stamford, CY: Appleton & Lange; 1997:1443–1462.

    Google Scholar 

  92. Rocca P, Fonzo V, Scotta M, et al.: Paroxetine efficacy in the treatment of generalized anxiety disorder. Acta Psychiatr Scand 1997, 95:444–450.

    PubMed  CAS  Google Scholar 

  93. Hedges DW, Reimherr FW, Strong RE, et al.: An open trial of nefazodone in adult patients with generalized anxiety disorder. Psychopharmacol Bull 1996, 32:671–676.

    PubMed  CAS  Google Scholar 

  94. Hoehn-Saric R, McLeod DR, Zimmerli WD: Differential effects of alprazolam and imipramine in generalized anxiety disorder: somatic versus psychic symptoms. J Clin Psychiatry 1988, 49:293–301.

    PubMed  CAS  Google Scholar 

  95. Rickels K, Downing R, Schweizer E, Hassman H: Antidepressants for the treatment of generalized anxiety disorder: a placebo-controlled comparison of imipramine, trazodone, and diazepam. Arch Gen Psychiatry 1993, 50:884–895.

    PubMed  CAS  Google Scholar 

  96. Kahn RJ, McNair DM, Lipman RS, et al.: Imipramine and chlordiazepoxide in depressive and anxiety disorders, II: efficacy in anxious outpatients. Arch Gen Psychiatry 1986, 43:79–85.

    PubMed  CAS  Google Scholar 

  97. Davidson JR, DuPont RL, Hedges D, Haskins JT: Efficacy, safety, and tolerability of venlafaxine extended release and buspirone in outpatients with generalized anxiety disorder. J Clin Psychiatry 1999, 60:528–535.

    Article  PubMed  CAS  Google Scholar 

  98. Rickels K, Pollack MH, Sheehan DV, Haskins JT: Efficacy of extended-release venlafaxine in nondepressed outpatients with generalized anxiety disorder. Am J Psychiatry 2000, 157:968–974.

    Article  PubMed  CAS  Google Scholar 

  99. Gallagher RM, Pasol E: Psychopharmacologic drugs in the chronic pain syndromes. Curr Rev Pain 1997, 1:138–152.

    Google Scholar 

  100. World Health Organization: Cancer pain relief and palliative care. Report of a WHO expert committee [World Health Organization Technical Report Series, 804]. Geneva, Switzerland: World Health Organization; 1990:1–75.

    Google Scholar 

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Verma, S., Gallagher, R.M. The psychopharmacologic treatment of depression and anxiety in the context of chronic pain. Current Science Inc 6, 30–39 (2002). https://doi.org/10.1007/s11916-002-0021-x

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