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Management of Painful Diabetic Neuropathy

  • Therapy In Practice
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Abstract

Type 2 diabetes mellitus is a prevalent disease in the US which affects more than 15 million people. As the disease progresses over time, neuropathic pain can become a common complication; it is present in more than 50% of individuals with diabetes mellitus aged >60 years. The pathogenesis of diabetic neuropathy is theorised to be multifactorial. Numerous medications, some with different mechanisms of action, have been examined regarding their effects on the symptoms associated with diabetic neuropathy such as pain, paraesthesia and numbness. However, the majority of the studies have included small patient populations. Tricyclic antidepressants, amitriptyline and desipramine in particular, have been relatively well studied and shown to be effective. However, anticholinergic adverse effects may limit their usefulness and may preclude use in the elderly. Studies have also shown gabapentin to be effective and well tolerated in the treatment of diabetic neuropathy. Capsaicin cream provides another treatment option with a favourable adverse effect profile. Many other medications have been evaluated in diabetic neuropathy; however, more placebo-controlled studies with adequate patient populations need to be performed to solidify their role in treatment.

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References

  1. Harris MI, Flegal KM, Cowie CC, et al. Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in US adults. The Third National Health and Nutrition Examination Survey, 1988–1994 Diabetes Care 1998; 21: 518–24

    Article  PubMed  CAS  Google Scholar 

  2. Young MJ, Boulton AJM, Macleod AF, et al. A multicentre study of the prevalence of diabetic peripheral neuropathy in the United Kingdom hospital clinic population. Diabetologia 36: 1993; 150–4

    Article  PubMed  CAS  Google Scholar 

  3. Pfeifer MA, Ross DR, Schrage JP, et al. Ahighly successful and novel model for treatment of chronic painful diabetic peripheral neuropathy. Diabetes Care 1993; 16(8): 1103–15

    Article  PubMed  CAS  Google Scholar 

  4. Greene DA, Stevens MJ, Feldman EL. Diabetic neuropathy: scope of the syndrome. Am J Med 1999; 107(2B): 2S–8S

    Article  PubMed  CAS  Google Scholar 

  5. Harati Y. Diabetic peripheral neuropathies. Ann Intern Med 1987; 107: 546–59

    PubMed  CAS  Google Scholar 

  6. Basbaum AI, Fields HL. Endogenous pain control mechanisms: review and hypothesis. Ann Neurol 1978; 4(5): 451–62

    Article  PubMed  CAS  Google Scholar 

  7. Malseed RT, Goldstein FJ. Enhancement of morphine analgesia by tricyclic antidepressants. Neuropharmacology 1979; 18: 827–9

    Article  PubMed  CAS  Google Scholar 

  8. Morley GK, Mooradian AD, Levine AS, et al. Mechanism of pain in diabetic peripheral neuropathy: effect of glucose on pain perception in humans. Am J Med 1984; 77: 79–82

    Article  PubMed  CAS  Google Scholar 

  9. Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329: 977–86

    Article  Google Scholar 

  10. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352: 837–53

    Article  Google Scholar 

  11. Kumar D, Alvaro MS, Julka IS, et al. Diabetic peripheral neuropathy: effectiveness of electrotherapy and amitriptyline for symptomatic relief. Diabetes Care 1998; 21(8): 1322–5

    Article  PubMed  CAS  Google Scholar 

  12. Kumar D, Marshall HJ. Diabetic peripheral neuropathy: amelioration of pain with transcutaneous electrostimulation. Diabetes Care 1997; 20(11): 1702–5

    Article  PubMed  CAS  Google Scholar 

  13. Richelson E. Pharmacology of antidepressants: characteristics of the ideal drug. Mayo Clin Proc 1994; 69: 1069–81

    Article  PubMed  CAS  Google Scholar 

  14. Peters NL. Snipping the thread of life: antimuscarinic side effects of medications in the elderly. Arch Intern Med 1989; 149: 2414–20

    Article  PubMed  CAS  Google Scholar 

  15. Max MB, Culnana M, Schafer SC, et al. Amitriptyline relieves diabetic neuropathy pain in patients with normal or depressed mood. Neurology 1987; 37: 589–96

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  17. 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: 1250–6

    Article  PubMed  CAS  Google Scholar 

  18. Sindrup SH, Gram LF, Skjold T, et al. Clomipramine vs. desipramine vs. placebo in the treatment of diabetic neuropathy symptoms: a double-blind crossover study. Br J Clin Pharmacol 1990; 30: 683–91

    Article  PubMed  CAS  Google Scholar 

  19. Kvinesdal B, Molin J, Froland A, et al. Imipramine treatment of painful diabetic neuropathy. JAMA 1984; 251: 1727–30

    Article  PubMed  CAS  Google Scholar 

  20. Sindrup SH, Ejlertsen B, Froland A, et al. Imipramine treatment in diabetic neuropathy: relief of subjective symptoms without changes in peripheral and autonomic nerve function. Eur J Clin Pharmacol 1989; 37: 151–3

    Article  PubMed  CAS  Google Scholar 

  21. Sindrup SH, Gram LF, Skjold T, et al. Concentration-response relationship in imipramine treatment of diabetic neuropathy symptoms. Clin Pharmacol Ther 1990; 47: 509–15

    Article  PubMed  CAS  Google Scholar 

  22. Gomez-Perez FJ, Rull JA, Dies H, et al. Nortriptyline and fluphenazine in the symptomatic treatment of diabetic neuropathy: a double-blind crossover study. Pain 1985; 23: 395–400

    Article  PubMed  CAS  Google Scholar 

  23. McCleane G. Topical application of doxepin hydrochloride, capsaicin and a combination of both produces analgesia in chronic human neuropathic pain: a randomized, double-blind, placebo-controlled study. Br J Clin Pharmacol 2000; 49: 574–9

    Article  PubMed  CAS  Google Scholar 

  24. Jones ME, Skaufle ML. Systemic adverse effects from topical doxepin cream [letter]. Ann Pharmacother 2001; 35: 505

    Article  PubMed  CAS  Google Scholar 

  25. Beers MH. Explicit criteria for determining potentially inappropriate medication use by the elderly: an update. Arch Intern Med 1997; 157: 1531–6

    Article  PubMed  CAS  Google Scholar 

  26. Richelson E. Antidepressants and brain neurochemistry. Mayo Clin Proc 1990; 65: 1227–36

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  28. Sindrup SH, Jensen TS. Efficacy of pharmacological treatments of neuropathic pain: an update and effect related to mechanism of drug action. Pain 1999; 83: 389–400

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  30. 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; 42: 135–44

    Article  PubMed  CAS  Google Scholar 

  31. Vrethem M, Boivie J, Arnqvist H, et al. A comparison of ami-triptyline and maprotiline in the treatment of painful polyneuropathy in diabetics and nondiabetics. Clin J Pain 1997; 13: 313–23

    Article  PubMed  CAS  Google Scholar 

  32. Lacy CF, Armstrong LL, Goldman MP, et al. Drug information handbook, 8th ed. Hudson (OH): Lexi-Comp, 2000–2001

  33. Khurana RC. Treatment of painful diabetic neuropathy with trazodone [letter]. JAMA 1983; 250: 1392

    Article  PubMed  CAS  Google Scholar 

  34. Wilson RC. The use of low-dose trazodone in the treatment of painful diabetic neuropathy. J Am Podiatr Med Assoc 1999; 89(9): 468–71

    PubMed  CAS  Google Scholar 

  35. Galer BS. Neuropathic pain of peripheral origin. Neurology 1995; 45 (12 Suppl. 9): S17–25

    Article  PubMed  CAS  Google Scholar 

  36. Davis J, Smith R. Painful peripheral diabetic neuropathy treated with venlafaxine HCL extended release capsules. Diabetes Care 1999; 22(11): 1909–10

    Article  PubMed  CAS  Google Scholar 

  37. Backonja M, Beydoun A, Edwards KR, et al. Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus: a randomized controlled trial. JAMA 1998; 280(21): 1831–6

    Article  PubMed  CAS  Google Scholar 

  38. Morello CM, Leckband SG, Stoner CP, et al. Randomized double-blind study comparing the efficacy of gabapentin with amitriptyline on diabetic peripheral neuropathy pain. Arch Intern Med 1999; 159: 1931–7

    Article  PubMed  CAS  Google Scholar 

  39. Rull J, Quibrera R, Fonzalez-Millan H, et al. Symptomatic treatment of peripheral diabetic neuropathy with carbamazepine: a double-blinded crossover study. Diabetologia 1969; 5: 215–20

    Article  PubMed  CAS  Google Scholar 

  40. Gomez-Perez F, Choza R, Rios JM, et al. Nortriptyline-fluphenazine vs. carbamazepine in the symptomatic treatment of diabetic neuropathy. Arch Med Res 1996; 27(4): 525–9

    PubMed  CAS  Google Scholar 

  41. Ellenberg M. Treatment of diabetic neuropathy with diphenylhydantoin. N Y State J Med 1968; 68: 2653–5

    PubMed  CAS  Google Scholar 

  42. Chadda VS, Mathur MS. Double-blind study of the effects of diphenylhydantoin sodium on diabetic neuropathy. J Assoc Physicians India 1977; 26: 403–6

    Google Scholar 

  43. Saudek DC, Werns S, Reidenberg MM. Phenytoin in the treatment of diabetic symmetrical polyneuropathy. Clin Pharmacol Ther 1977; 22: 196–9

    PubMed  CAS  Google Scholar 

  44. McCleane G. 200mg daily of lamotrigine has no analgesic effect in neuropathic pain: a randomized, double-blinded, placebo controlled trial. Pain 1999; 83(1): 105–7

    Article  PubMed  CAS  Google Scholar 

  45. Basha KM, Whitehouse FW. Capsaicin: a therapeutic option for painful diabetic neuropathy. Henry Ford Hosp Med J 1991; 39(2): 138–40

    PubMed  CAS  Google Scholar 

  46. Chad DA, Aronin N, Lundstrom R, et al. Does capsaicin relieve the pain of diabetic neuropathy? Pain 1990; 42: 387–8

    Article  PubMed  CAS  Google Scholar 

  47. Capsaicin Study Group. Treatment of painful diabetic neuropathy with topical capsaicin: a multicenter, double-blind, vehicle-controlled study. Arch Intern Med 1991; 151: 2225–9

    Article  Google Scholar 

  48. Tandan R, Lewis GA, Krusinski PB, et al. Topical capsaicin in painful diabetic neuropathy: controlled study with long-term follow-up. Diabetes Care 1992; 15(1): 8–14

    Article  PubMed  CAS  Google Scholar 

  49. Scheffler NM, Sheitel PL, Lipton MN. Treatment of painful diabetic neuropathy with capsaicin 0.075%. J Am Podiatr Med Assoc 1991; 81(6): 288–93

    PubMed  CAS  Google Scholar 

  50. Capsaicin Study Group. Effect of treatment with capsaicin on daily activities of patients with painful diabetic neuropathy. Diabetes Care 1992; 15(2): 159–65

    Article  Google Scholar 

  51. Tandan R, Lewis GA, Badger GB, et al. Topical capsaicin in painful diabetic neuropathy: effect on sensory function. Diabetes Care 1992; 15(1): 15–8

    Article  PubMed  CAS  Google Scholar 

  52. Kernbaum S, Hauchecorne J. Administration of levodopa for relief of herpes zoster pain. JAMA 1981; 246: 132–34

    Article  PubMed  CAS  Google Scholar 

  53. Jensen TS, Yaksh TL. Effects of an intrathecal dopamine agonist, apomorphine, on thermal and chemical evoked noxious responses in rats. Brain Res 1984; 296: 285–93

    Article  PubMed  CAS  Google Scholar 

  54. Eras M, Sagduyu A, Nilgun A, et al. Use of levodopa to relieve pain from painful symmetrical diabetic polyneuropathy. Pain 1998; 75: 257–9

    Article  Google Scholar 

  55. Byas-Smith MG, Max MB, Muir J, et al. Transdermal clonidine compared to placebo I painful diabetic neuropathy using a two-stage ‘enriched enrolment’ design. Pain 1995; 60: 267–74

    Article  PubMed  CAS  Google Scholar 

  56. Cohen KL, Lucibello FE, Chomiak MA. Lack of effect of clonidine and pentoxifylline in short-term therapy of diabetic peripheral neuropathy. Diabetes Care 1990; 13(10): 1074–6

    Article  PubMed  CAS  Google Scholar 

  57. Zeigler D, Lynch SA, Muir J, et al. Transdermal clonidine versus placebo in painful diabetic neuropathy. Pain 1992; 48: 403–8

    Article  PubMed  CAS  Google Scholar 

  58. Cohen KL, Harris S. Efficacy and safety of nonsteroidal antiinflammatory drugs in the therapy of diabetic neuropathy. Arch Intern Med 147 1987; (8): 1442–4

    Article  PubMed  CAS  Google Scholar 

  59. Harati Y, Gooch C, Swenson M, et al. Double-blinded randomized trail of tramadol for the treatment of the pain of diabetic neuropathy. Neurology 1998; 50: 1842–6

    Article  PubMed  CAS  Google Scholar 

  60. Sindrup S, Andersen G, Madsen C, et al. Tramadol relieves pain and allodynia in polyneuropathy: a randomized, double-blind, controlled trial. Pain 1999; 83: 85–90

    Article  PubMed  CAS  Google Scholar 

  61. Sindrup S, Madsen C, Brosen K, et al. The effect of tramadol in painful polyneuropathy in relation to serum drug and metabolite levels. Clin Pharmacol Ther 1999; 66(6): 636–41

    PubMed  CAS  Google Scholar 

  62. Ortho-McNeil. Ultram package insert. Raritan (NJ): 1999 Dec

    Google Scholar 

  63. Tal M, Bennett G. Dextrorphan relieves neuropathic heat-evoked hyperalgesia in the rat. Neurosci Lett 1993; 151: 107–10

    Article  PubMed  CAS  Google Scholar 

  64. Yamamoto T, Yaksh T. Studies on the spinal interaction of morphine and the NMDA antagonist MK-801 on the hyperesthesia observed in a rat model of sciatic mononeuropathy. Neurosci Lett 1992; 135: 67–70

    Article  PubMed  CAS  Google Scholar 

  65. Kristensen JD, Karlsten R, Gordh T, et al. The NMDA antagonist 3-(2-carboxypoperazin-4yl)propyl-l-phosphonic acid (CCP) has antinociceptive effect after intrathecal injection in the rat. Pain 1994; 56: 59–67

    Article  PubMed  CAS  Google Scholar 

  66. Kristensen JD, Post C, Gordh T, et al. Spinal cord morphology and antinociception after chronic intrathecal administration of excitatory amino acid antagonists in the rat. Pain 1993; 54: 309–16

    Article  PubMed  CAS  Google Scholar 

  67. Nelson K, Park KM, Robinovitz E, et al. High-dose oral dextromethorphan versus placebo in painful diabetic neuropathy and postherpetic neuralgia. Neurology 1997; 48: 1212–8

    Article  PubMed  CAS  Google Scholar 

  68. McQuay HJ, Carroll D, Jadad AR, et al. Dextromethorphan for the treatment of neuropathic pain: a double-blind randomized controlled crossover trial with integral n-of-1 design. Pain 1994; 59: 127–33

    Article  PubMed  CAS  Google Scholar 

  69. Rendell M, Banisedun O. Skin blood flow and current perception in pentoxifylline-treated diabetic neuropathy. Angiology 1992; 43(10): 843–51

    Article  PubMed  CAS  Google Scholar 

  70. Lee Y, Robison M, Wong N, et al. The effect of pentoxifylline on current perception thresholds in patients with diabetic sensory neuropathy. J Diabetes Complications 1997; 11: 274–8

    Article  PubMed  CAS  Google Scholar 

  71. Cohen S, Mathews T. Pentoxifylline in the treatment of distal diabetic neuropathy. Angiology 1991; 42(9): 741–6

    Article  PubMed  CAS  Google Scholar 

  72. Ziegler D, Hanefeld M, Ruhnau KJ, et al. Treatment of symptomatic diabetic peripheral neuropathy with the anti-oxidant α-lipoic acid: a 3-week multicentre randomized controlled trial (ALADIN Study). Diabetologia 1995; 38: 1425–33

    Article  PubMed  CAS  Google Scholar 

  73. Ziegler D, Hanefeld M, Ruhnau KJ, et al. Treatment of symptomatic diabetic polyneuropathy with the antioxidant α-lipoic acid: a 7-month multicenter randomized controlled trial (ALADIN III Study). Diabetes Care 1999; 22(8): 1296–301

    Article  PubMed  CAS  Google Scholar 

  74. Abbas ZG, Swai ABM. Evaluation of the efficacy of thiamine and pyridoxine in the treatment of symptomatic diabetic peripheral neuropathy. East Afr Med J 1997; 74(12): 803–8

    PubMed  CAS  Google Scholar 

  75. Stracke H, Lindemann A, Federlin K. A Benfotiamine-vitamin B combination in treatment of diabetic polyneuropathy. Endocrinol Diabetes 1996; 104: 311–6

    Article  CAS  Google Scholar 

  76. Levin ER, Hanscom TA, Fisher M, et al. The influence of pyridoxine in diabetic peripheral neuropathy. Diabetes Care 1981; 4(6): 606–9

    Article  PubMed  CAS  Google Scholar 

  77. Dejgard A, Petersen P, Kastrup J. Mexiletine for treatment of chronic painful diabetic neuropathy. Lancet 1988; 2(9): 9–11

    Article  Google Scholar 

  78. Koppert W, Ostermeier N, Sittl R, et al. Low-dose lidocaine reduces secondary hyperalgesia by a central mode of action. Pain 2000; 85: 217–24

    Article  PubMed  CAS  Google Scholar 

  79. Kastrup J, Petersen P, Dejgard A, et al. Intravenous lidocaine infusion: a new treatment of chronic painful diabetic neuropathy? Pain 1987; 28: 69–75

    Article  PubMed  CAS  Google Scholar 

  80. Wright JM, Oki JC, Graves III L. Mexiletine in the symptomatic treatment of diabetic peripheral neuropathy. Ann Pharmacother 1997; 31: 29–34

    PubMed  CAS  Google Scholar 

  81. Oskarsson P, Ljunggren JG, Lins PE, et al. et al. Efficacy and safety of mexiletine in the treatment of painful diabetic neuropathy. Diabetes Care 1997; 20(10): 1594–7

    Article  PubMed  CAS  Google Scholar 

  82. Stracke H, Meyer UE, Schumacher HE, et al. Mexiletine in the treatment of diabetic neuropathy. Diabetes Care 1992; 15(11): 1550–5

    Article  PubMed  CAS  Google Scholar 

  83. Giugliano D, Acampora R, Marfella R, et al. Tolrestat in the primary prevention of diabetic neuropathy. Diabetes Care 1995; 18(4): 536–41

    Article  PubMed  CAS  Google Scholar 

  84. Christensen JEJ, Varnek L, Gregersen G. The effect of an aldose reductase inhibitor (Sorbinil®) on diabetic neuropathy and neural function of the retina: a double-blind study. Acta Neurologica Scandinavica 1985; 71: 164–7

    Article  PubMed  CAS  Google Scholar 

  85. Airey M, Bennett C, Nicolucci A, et al. Aldose reductase inhibitors for the prevention and treatment of diabetic peripheral neuropathy. Cochrane Database of Systematic Reviews 2000

    Google Scholar 

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Acknowledgements

We would like to give special thanks to Jacqueline Joss, Pharm. D. for her suggestions during the preparation of this article.

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  1. Department of Pharmaceutical Care, University of Iowa Hospital and Clinics, Iowa City, Iowa, USA

    Patrick G. Jensen & Jennifer R. Larson

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Correspondence to Patrick G. Jensen.

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Jensen, P.G., Larson, J.R. Management of Painful Diabetic Neuropathy. Drugs & Aging 18, 737–749 (2001). https://doi.org/10.2165/00002512-200118100-00003

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