A step closer in the management of uncontrolled neuropathic pain: gabapentin-nortriptyline combination

Authors

  • Manish Nilkanth Maladkar Medical and Regulatory Affairs, Scientific Department, Aristo Pharmaceuticals Private Limited, Mumbai, Maharashtra, India
  • Chitra Mohan Tekchandani Medical, Scientific Department, Aristo Pharmaceuticals Private Limited, Mumbai, Maharashtra, India
  • Raveena Kanyalal Bajaj Medical, Scientific Department, Aristo Pharmaceuticals Private Limited, Mumbai, Maharashtra, India

DOI:

https://doi.org/10.18203/issn.2455-4510.IntJResOrthop20204615

Keywords:

Neuropathic pain, Calcium channel alpha-2-delta ligand, Tricyclic antidepressants, Gabapentin, Nortriptyline, Combination therapy

Abstract

Neuropathic pain is extremely distressing as it significantly hampers the performance of daily activities and impedes overall quality of life. A large number of illnesses are linked with neuropathic pain like radiculopathy, sciatica, diabetes, herpes infection, spinal injury, stroke, etc. Treating neuropathic pain is challenging as response to the treatment is at times uncertain and associated with undesirable side effects. Uncontrolled neuropathic pain is observed in large group of patients receiving current treatment regimen. Almost half of the neuropathic pain patients need more than two drugs for pain relief. Various clinical trials have demonstrated better efficacy of combination therapy in reducing pain than monotherapy. Utilizing drug combination with different mechanism of action or acting on two different sites has demonstrated superior analgesic effect in painful neuropathic condition. The first tier agents recommended by various guidelines are calcium channel alpha-2-delta ligands and tricyclic antidepressants that act on different pain pathways. A clinical trial has shown enhanced pain relief with no increase in side effects with the administration of gabapentin and nortriptyline combination in patients suffering from neuropathic pain. Moreover, symptoms associated with neuropathic pain like sleep disturbances, altered mood, decreased walking ability, depression and quality of life were also significantly improved. Hence, combination therapy of gabapentin and nortriptyline offers a pivotal modality in the management of uncontrolled neuropathic pain.

References

England DJ, Arthur AK. Periph Neurop. Lancet. 2004;363 2151-61.

Jensen, Troels S. A new definition of neuropathic pain. Pain. 2011;152(10):2204-5.

Scadding, John, Koltzenburg M. Neuropathic pain. Advan Clin Neuro Rehab. 2003;3:8-14.

The American Academy of Pain Medicine. AAPM facts and figures on pain. AAPM Facts and Figures on Pain. 2013. Accessed on 10 July, 2020.

Gormsen, Lise. Depression, anxiety, health related quality of life and pain in patients with chronic fibromyalgia and neuropathic pain. Eur J Pain. 2010;14(2):127-e1.

Ballantyne, Jane C. Pharmacological management of neuropathic pain. Pain: Clinical Updates. 2010. Accessed on 10 July, 2020.

Attal N. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. Eur J Neurol. 2010;17(9):1113-e88.

Moulin DE. Pharmacological management of chronic neuropathic pain: revised consensus statement from the Canadian Pain Society. Pain Research and Management. 2014;19(6):328-35.

Dworkin, Robert H. Recommendations for the pharmacological management of neuropathic pain: an overview and literature update. Mayo Clinic Proceedings. 2010;85(3):S3-14.

Davies, Pamela S, Bradley S. Galer. Review of lidocaine patch 5% studies in the treatment of postherpetic neuralgia. Drugs. 2004;64(9):937-47.

Meier T. Reduction of chronic pain for non-postherpetic peripheral neuropathies after topical treatment with a lidocaine patch. Schmerz (Berlin, Germany). 2004;18(3):172-8.

Wiffen, Philip J. Antiepileptic drugs for neuropathic pain and fibromyalgia-an overview of Cochrane reviews. Cochrane Database Syst Rev. 2013;11(11):CD010567.

Raison VMCL. Neurobiology of depression, fibromyalgia and neuropathic pain. Frontiers in Bioscience 14. 2009;5291-338.

Taylor, Charles P. Mechanisms of analgesia by gabapentin and pregabalin–Calcium channel α2‐δ [Cavα2‐δ] ligands. Pain. 2009;142(1-2):13-6.

Pop-Busui R, Boulton AJ, Feldman EL. Diabetic Neuropathy: A Position Statement by the American Diabetes Association. Diabetes Care. 2017;40(1):136-54.

Handelsman Y, Bloomgarden ZT, Grunberger G, Umpierrez G, Zimmerman RS, Bailey TS, et al. American Association of Clinical Endocrinologists and American College of Endocrinology— clinical practice guidelines for developing a diabetes mellitus comprehensive care plan—2015. Endocr Pract. 2015;21(1):1-87.

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. Amer Acad Phys Med Rehab Neurol. 2011;76(20):1758-65.

Finnerup, Nanna B, Troels S. Jensen. Clinical use of pregabalin in the management of central neuropathic pain. Neuropsychiatric disease and treatment. 2007;3(6):885-91.

Perret, Danielle, Luo DZ. Targeting voltage-gated calcium channels for neuropathic pain management. Neurotherapeutics. 2009;6(4):679-92.

Lee, Yee-Chi, Chen PP. A review of SSRIs and SNRIs in neuropathic pain. Expert opinion on pharmacotherapy. 2010;11(17):2813-25.

Beydoun A. Symptomatic treatment of neuropathic pain: a focus on the role of anticonvulsants. Medscape CME Circle Lecture. 2001. Accessed on 11 July, 2020.

Raison VMCL. Neurobiology of depression, fibromyalgia and neuropathic pain. Frontiers in Bioscience 14. 2009;5291-338.

de la Calle, José-Luis. Add-on treatment with pregabalin for patients with uncontrolled neuropathic pain who have been referred to pain clinics. Clinical drug investigation. 2014;34(12):833-44.

Harden, Norman, Cohen M. Unmet needs in the management of neuropathic pain. Journal of pain and symptom management. 2003;25(5):S12-7.

José A. Clinical characteristics, patient-reported outcomes, and previous therapeutic management of patients with uncontrolled neuropathic pain referred to pain clinics. Pain research and treatment. 2014;2014:518716.

Turk, Dennis C. Assessment and treatment of psychosocial comorbidities in patients with neuropathic pain. Mayo Clinic Proceedings. 2010;85(3):S42-50.

Dworkin, Robert H. Recommendations for the pharmacological management of neuropathic pain: an overview and literature update. Mayo Clinic Proceedings. 2010;85(3):S3-14.

Ballantyne, Jane C, Carwood CM, Giamberardino MA. Pharmacological management of neuropathic pain. Pain: Clinical Updates. 2010. Accessed on 10 July, 2020.

Attal, Nadine. EFNS guidelines on pharmacological treatment of neuropathic pain. European Journal of Neurology. 2006;13(11):1153-69.

Chaparro, Enrique L. Combination pharmacotherapy for the treatment of neuropathic pain in adults. Cochrane Database Syst Rev 7. 2012.2012(7):CD008943.

Gilron, Ian. Morphine, gabapentin, or their combination for neuropathic pain. New England Journal of Medicine. 2005;352(13):1324-34.

Sinclair, Andrew M, Miller B, Lee LK. Chronic orchialgia: consider gabapentin or nortriptyline before considering surgery. International journal of urology. 2007;14(7):622-5.

Hanna, Magdi, O'Brien C, Wilson MC. Prolonged‐release oxycodone enhances the effects of existing gabapentin therapy in painful diabetic neuropathy patients. European Journal of Pain. 2008;12(6):804-13.

Amr, Yasser Mohamed. Multi-day low dose ketamine infusion as adjuvant to oral gabapentin in spinal cord injury related chronic pain: a prospective, randomized, double blind trial. Pain Physician. 2010;13(3):245-9.

Tesfaye, Solomon. Duloxetine and pregabalin: high-dose monotherapy or their combination? The COMBO-DN study–a multinational, randomized, double-blind, parallel-group study in patients with diabetic peripheral neuropathic pain. PAIN®. 2013;154(12):2616-25.

Maladkar, Manish. Evaluation of efficacy and safety of epalrestat and epalrestat in combination with methylcobalamin in patients with diabetic neuropathy in a randomized, comparative trial. Journal of Diabetes mellitus. 2013;3:22-26.

Freeman, Roy. Randomized study of tramadol/acetaminophen versus placebo in painful diabetic peripheral neuropathy. Current medical research and opinion. 2007;23(1):147-61.

McCleane, Gary. 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. British journal of clinical pharmacology. 2000;49(6):574-9.

Gilron, Ian. Nortriptyline and gabapentin, alone and in combination for neuropathic pain: a double-blind, randomised controlled crossover trial. The Lancet. 2009;374(9697):1252-61.

Longson D. Neuropathic pain–pharmacological management: the pharmacological management of neuropathic pain in adults in non-specialist settings. NICE clinical guideline. 2013;173. Accessed on 10 July, 2020.

Holbech. Combination treatment of neuropathic pain: Danish expert recommendations based on a Delphi process. Journal of Pain Research. 2017:10:1467-75.

Saxena AK, Jain P, Dureja GP, Venkitachalam A, Goswami S, Usmani H, et al. Pharmacological management of neuropathic pain in India: A consensus statement from Indian experts. Indian J Pain. 2018;32:132-44.

Gandey A. Combination Gabapentin and Nortriptyline May Ease Neuropathic Pain. Medscape Medical News. 2009. Accessed on 10 July, 2020.

Soloway B. Gabapentin–Nortriptyline Combination Therapy for Neuropathic Pain. NEJM Journal watch. 2009. Accessed on 11 July, 2020.

Gilron I, Bailey J, Dongsheng T. Combined treatment with gabapentin and nortriptyline improves pain control in peripheral neuropathy more than either agent alone. JCOM 16. 2009;16(12):544-45.

O'Connor, Alec B. Study finds that the combination gabapentin plus nortriptyline reduces neuropathic pain more than either drug alone. Evidence-based medicine. 2010;15(2):45.

Downloads

Published

2020-10-22

Issue

Section

Review Articles