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Low doses of amitriptyline, pregabalin, and gabapentin are preferred for management of neuropathic pain in India: is there a need for revisiting dosing recommendations?

  • Kamble, Sanjay Vasant (Medical Affairs Department, Wockhardt Limited, Wockhardt Towers, Bandra Kurla Complex) ;
  • Motlekar, Salman Abdulrehman (Medical Affairs Department, Wockhardt Limited, Wockhardt Towers, Bandra Kurla Complex) ;
  • D'souza, Lyndon Lincoln (Medical Affairs Department, Wockhardt Limited, Wockhardt Towers, Bandra Kurla Complex) ;
  • Kudrigikar, Vinay Nanda (Medical Affairs Department, Wockhardt Limited, Wockhardt Towers, Bandra Kurla Complex) ;
  • Rao, Sameer Eknath (Medical Affairs Department, Wockhardt Limited, Wockhardt Towers, Bandra Kurla Complex)
  • Received : 2017.01.12
  • Accepted : 2017.05.10
  • Published : 2017.07.01

Abstract

Background: Current therapy for the treatment of neuropathic pain is often unsatisfactory. Considerable variation in treatment pattern still exists in spite of availability of sufficient literature from various guidelines. Recent Indian market data suggested that the utilization (sale) of drugs such as amitriptyline, pregabalin, and gabapentin was more for low-dose unit packs than that of the high-dose unit packs, raising the belief that these drugs are prescribed at a lower dose than is actually recommended in the guidelines. To test this hypothesis, a survey was conducted across speciality throughout the country to observe the prescription pattern of these drugs amongst the health care providers in India. Methods: Three hundred fifty survey forms were distributed of which 281 forms were included for analysis. Results: It was observed that the commonly used initiation and maintenance dose for amitriptyline, pregabalin, and gabapentin was 5-10 mg/day, 50-75 mg/day, and 100-300 mg/day, respectively. The reason to select the lower dosages was to have a balancing effect to achieve good efficacy with minimum side effects. Care-givers reported no side effects/not many side effects as a reason in 22.2%, 16.88%, and 23.86% patients with amitriptyline, pregabalin, and gabapentin, respectively. Sedation and giddiness were commonly reported with all three drugs. Conclusions: Commonly prescribed drugs for management of neuropathic pain, such as amitriptyline, pregabalin, and gabapentin are preferred at lower doses in Indian clinical settings. Acceptable efficacy and low tolerance to the standard dosage is believed to be the reason behind the prescribed dose.

Keywords

References

  1. Nascimento OJ, Pessoa BL, Orsini M, Ribeiro P, Davidovich E, Pupe C, et al. Neuropathic pain treatment: still a challenge. Neurol Int 2016; 8: 6322.
  2. Campbell JN, Meyer RA. Mechanisms of neuropathic pain. Neuron 2006; 52: 77-92. https://doi.org/10.1016/j.neuron.2006.09.021
  3. Dworkin RH, O'Connor AB, Audette J, Baron R, Gourlay GK, Haanpaa ML, et al. Recommendations for the pharmacological management of neuropathic pain: an overview and literature update. Mayo Clin Proc 2010; 85: S3-14.
  4. Moulin D, 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. https://doi.org/10.1155/2014/754693
  5. Attal N, Cruccu G, Baron R, Haanpaa M, Hansson P, Jensen TS, et al. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. Eur J Neurol 2010; 17: 1113-e88. https://doi.org/10.1111/j.1468-1331.2010.02999.x
  6. NICE. Neuropathic pain: the pharmacological management of neuropathic pain in adults in non-specialist settings. Centre for clinical practice at NICE (UK). London, National Institute for Health and Clinical Excellence (UK). 2010, pp 1-138.
  7. Liu Y, Qian C, Yang M. Treatment patterns associated with ACR-recommended medications in the management of Fibromyalgia in the United States. J Manag Care Spec Pharm 2016; 22: 263-71. https://doi.org/10.18553/jmcp.2016.22.3.263
  8. Park HJ, Moon DE. Pharmacologic management of chronic pain. Korean J Pain 2010; 23: 99-108. https://doi.org/10.3344/kjp.2010.23.2.99
  9. Quintiles IMS Sales Data (Total Sales Audit and Secondary Sales Audit): Indian Pharmaceutical Market; Amitripyline, Gabapentin & Pregabalin; Moving Annual Total (MAT) August 2016.
  10. 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. https://doi.org/10.2165/11536200-000000000-00000
  11. Nantz E, Liu-Seifert H, Skljarevski V. Predictors of premature discontinuation of treatment in multiple disease states. Patient Prefer Adherence 2009; 3: 31-43.
  12. Goldstein DJ, Lu Y, Detke MJ, Lee TC, Iyengar S. Duloxetine vs. placebo in patients with painful diabetic neuropathy. Pain 2005; 116: 109-18. https://doi.org/10.1016/j.pain.2005.03.029
  13. Richter RW, Portenoy R, Sharma U, Lamoreaux L, Bockbrader H, Knapp LE. Relief of painful diabetic neuropathy with pregabalin: a randomized, placebo-controlled trial. J Pain 2005; 6: 253-60. https://doi.org/10.1016/j.jpain.2004.12.007
  14. Backonja M, Glanzman RL. Gabapentin dosing for neuropathic pain: evidence from randomized, placebo-controlled clinical trials. Clin Ther 2003; 25: 81-104. https://doi.org/10.1016/S0149-2918(03)90011-7
  15. Dogra S, Beydoun S, Mazzola J, Hopwood M, Wan Y. Oxcarbazepine in painful diabetic neuropathy: a randomized, placebo-controlled study. Eur J Pain 2005; 9: 543-54. https://doi.org/10.1016/j.ejpain.2004.11.006
  16. Vinik AI, Tuchman M, Safirstein B, Corder C, Kirby L, Wilks K, et al. Lamotrigine for treatment of pain associated with diabetic neuropathy: results of two randomized, double-blind, placebo-controlled studies. Pain 2007; 128: 169-79. https://doi.org/10.1016/j.pain.2006.09.040
  17. Patkar AA, Masand PS, Krulewicz S, Mannelli P, Peindl K, Beebe KL, et al. A randomized, controlled, trial of controlled release paroxetine in fibromyalgia. Am J Med 2007; 120: 448-54. https://doi.org/10.1016/j.amjmed.2006.06.006
  18. Arnold LM, Goldenberg DL, Stanford SB, Lalonde JK, Sandhu HS, Keck PE Jr, et al. Gabapentin in the treatment of fibromyalgia: a randomized, double-blind, placebo-controlled, multi-center trial. Arthritis Rheum 2007; 56: 1336-44. https://doi.org/10.1002/art.22457
  19. Crofford LJ, Rowbotham MC, Mease PJ, Russell IJ, Dworkin RH, Corbin AE, et al. Pregabalin for the treatment of fibromyalgia syndrome: results of a randomized, doubleblind, placebo-controlled trial. Arthritis Rheum 2005; 52: 1264-73. https://doi.org/10.1002/art.20983
  20. Arnold LM, Crofford LJ, Martin SA, Young JP, Sharma U. The effect of anxiety and depression on improvements in pain in a randomized, controlled trial of pregabalin for treatment of fibromyalgia. Pain Med 2007; 8: 633-8. https://doi.org/10.1111/j.1526-4637.2007.00332.x
  21. Agius AM, Jones NS, Muscat R. A randomized controlled trial comparing the efficacy of low-dose amitriptyline, amitriptyline with pindolol and surrogate placebo in the treatment of chronic tension-type facial pain. Rhinology 2013; 51: 143-53.
  22. Kautio AL, Haanpaa M, Saarto T, Kalso E. Amitriptyline in the treatment of chemotherapy-induced neuropathic symptoms. J Pain Symptom Manage 2008; 35: 31-9. https://doi.org/10.1016/j.jpainsymman.2007.02.043
  23. Bowsher D. The management of postherpetic neuralgia. Postgrad Med J 1997; 73: 623-9. https://doi.org/10.1136/pgmj.73.864.623
  24. Kulshreshtha P, Gupta R, Yadav RK, Bijlani RL, Deepak KK. Effect of low-dose amitriptyline on autonomic functions and peripheral blood flow in fibromyalgia: a pilot study. Pain Med 2012; 13: 131-6. https://doi.org/10.1111/j.1526-4637.2011.01286.x
  25. Freysoldt A, Fleckenstein J, Lang PM, Irnich D, Grafe P, Carr RW. Low concentrations of amitriptyline inhibit nicotinic receptors in unmyelinated axons of human peripheral nerve. Br J Pharmacol 2009; 158: 797-805. https://doi.org/10.1111/j.1476-5381.2009.00347.x
  26. George RB, McKeen DM, Andreou P, Habib AS. A randomized placebo-controlled trial of two doses of pregabalin for postoperative analgesia in patients undergoing abdominal hysterectomy. Can J Anaesth 2014; 61: 551-7. https://doi.org/10.1007/s12630-014-0147-4
  27. Khurana G, Jindal P, Sharma JP, Bansal KK. Postoperative pain and long-term functional outcome after administration of gabapentin and pregabalin in patients undergoing spinal surgery. Spine (Phila Pa 1976) 2014; 39: E363-8. https://doi.org/10.1097/BRS.0000000000000185
  28. Nishihara M, Arai YC, Yamamoto Y, Nishida K, Arakawa M, Ushida T, et al. Combinations of low-dose antidepressants and low-dose pregabalin as useful adjuvants to opioids for intractable, painful bone metastases. Pain Physician 2013; 16: E547-52.
  29. Zin CS, Nissen LM, O'Callaghan JP, Duffull SB, Smith MT, Moore BJ. A randomized, controlled trial of oxycodone versus placebo in patients with postherpetic neuralgia and painful diabetic neuropathy treated with pregabalin. J Pain 2010; 11: 462-71. https://doi.org/10.1016/j.jpain.2009.09.003
  30. Hounnou P, Nicoucar K. Delayed onset of rotatory selfmotion perception, dysdiadochokinesia and disturbed eye pursuit caused by low-dose pregabalin. BMJ Case Rep [serial on the Internet]. [2014 Apr 11]. Available at http://casereports.bmj.com/content/2014/bcr-2013-201282.long.
  31. Peng PW, Li C, Farcas E, Haley A, Wong W, Bender J, et al. Use of low-dose pregabalin in patients undergoing laparoscopic cholecystectomy. Br J Anaesth 2010; 105: 155-61. https://doi.org/10.1093/bja/aeq116
  32. Randinitis EJ, Posvar EL, Alvey CW, Sedman AJ, Cook JA, Bockbrader HN. Pharmacokinetics of pregabalin in subjects with various degrees of renal function. J Clin Pharmacol 2003; 43: 277-83. https://doi.org/10.1177/0091270003251119
  33. Semel D, Murphy TK, Zlateva G, Cheung R, Emir B. Evaluation of the safety and efficacy of pregabalin in older patients with neuropathic pain: results from a pooled analysis of 11 clinical studies. BMC Fam Pract 2010; 11: 85. https://doi.org/10.1186/1471-2296-11-85
  34. Grice GR, Mertens MK. Gabapentin as a potential option for treatment of sciatica. Pharmacotherapy 2008; 28: 397-402. https://doi.org/10.1592/phco.28.3.397
  35. Arai YC, Matsubara T, Shimo K, Suetomi K, Nishihara M, Ushida T, et al. Low-dose gabapentin as useful adjuvant to opioids for neuropathic cancer pain when combined with low-dose imipramine. J Anesth 2010; 24: 407-10. https://doi.org/10.1007/s00540-010-0913-6

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