Published: 2020-02-25

Evaluation of clinical outcomes in neuropathic pain with combinations of anti-neuropathic drugs

Shaik A. Pasha, S. Vidyadhara, M. Raghava Kalyan, Lakshmi Banu Sri, N. Keerthi, A. Harshitha, K. Sravani, Ramineni Haribabu


Background: Much of the pharmacological treatment modalities especially individual drugs for treating neuropathic pain have unwanted side effects, multiple day to day dosing, modest efficacy of topical treatments, and their local side effects. Combination drug regimen has the advantage of offering relatively better pain relief at lower drug doses and lesser side effects.

Methods: The study was conducted in the Department of Neurology at NRI General Hospital, Guntur. The patients who met the inclusion and exclusion criteria were enrolled and assigned into 3 groups of the study drug combinations. The baseline characteristics and post interventional scores of Toronto Clinical Scoring System (TCSS), visual analogue scale (VAS), Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Rating Scale (HAM-D) and Medical outcome of sleep scale (MOS) and were analyzed using t test and mean difference.

Results: A statistically significant reduction in neuropathic pain in all the three groups was found. The mean difference between the baseline and post interventional scores of TCSS and VAS of group I, II and III were 2.97, 2.75, and 1.97; 2.32, 1.12, and 0.95 respectively. There was a statistically significant improvement of HAM-A in all the three groups, HAM-D and MOS sleep scale were found significant only in group II.

Conclusions: The study findings revealed that all the three drug combinations were effective in the management of neuropathic pain with pregabalin and oxcarbazepine combination being better with respect to efficacy and tolerability. Regarding the treatment of depression and sleep disturbances associated with NP pregabalin and duloxetine was more effective.


Drug combinations, Neuropathic pain, Toronto clinical scoring systems, Visual analogue scale

Full Text:



Haanpää M, Attal N, Backonja M, Baron R, Bennett M, Bouhassira D, et al. NeuPSIG guidelines on neuropathic pain assessment. PAIN®. 2011;152(1):14-27.

Treede RD, Jensen TS, Campbell JN, Cruccu G, Dostrovsky J, Griffin J, et al. Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurol. 2008;70(18):1630-5.

Hall GC, Carroll D, Parry D, McQuay HJ. Epidemiology and treatment of neuropathic pain: the UK primary care perspective. Pain. 2006;122(1-2):156-62.

Harrison RA, Field TS. Post stroke pain: identification, assessment, and therapy. Cerebrovas Dis. 2015;39(3-4):190-201.

Westaway KP, Alderman CP, Frank OR, Husband AJ, Rowett D, Le Blanc T. Optimising therapy for patients with neuropathic pain. J Pharma Pract Res. 2014;44(1):44-7.

Clark JD. Chronic pain prevalence and analgesic prescribing in a general medical population. J Pain symptom management. 2002;23(2):131-7.

Koleva D, Krulichova I, Bertolini G, Caimi V, Garattini L. Pain in primary care: an Italian survey. Europ J Public Health. 2005;15(5):475-9.

Davies M, Brophy S, Williams R, Taylor A. The prevalence, severity, and impact of painful diabetic peripheral neuropathy in type 2 diabetes. Diabetes Care. 2006;29(7):1518-22.

Bennett MI, Rayment C, Hjermstad M, Aass N, Caraceni A, Kaasa S. Prevalence and aetiology of neuropathic pain in cancer patients: a systematic review. Pain. 2012;153(2):359-65.

Freynhagen R, Baron R, Tölle T, Stemmler E, Gockel U, Stevens M, et al. Screening of neuropathic pain components in patients with chronic back pain associated with nerve root compression: a prospective observational pilot study (MIPORT). Curr Med Res Opinion. 2006;22(3):529-37.

Pollmann W, Feneberg W. Current management of pain associated with multiple sclerosis. CNS Drugs. 2008;22(4):291-324.

Zin CS, Nissen LM, Smith MT, O'Callaghan JP, Moore BJ. An update on the pharmacological management of post-herpetic neuralgia and painful diabetic neuropathy. CNS Drugs. 2008;22(5):417-42.

Bril V, Perkins BA. Validation of the Toronto Clinical Scoring System for diabetic polyneuropathy. Diabetes Care. 2002;25(11):2048-52.

Hawker GA, Mian S, Kendzerska T, French M. Measures of adult pain: Visual analog scale for pain (vas pain), numeric rating scale for pain (nrs pain), mcgill pain questionnaire (mpq), short‐form mcgill pain questionnaire (sf‐mpq), chronic pain grade scale (cpgs), short form‐36 bodily pain scale (sf‐36 bps), and measure of intermittent and constant osteoarthritis pain (icoap). Arthr Care Res. 2011;63(11):240-52.

Hamilton M. The assessment of anxiety states by rating. Brit J Med Psychol. 1959;32:50-5.

Hamilton. M, Hamilton Depression Rating Scale (HAM- D). J Neurol, Neurosurg, Psychiatr. 1960;23:56-62.

Hays RD, Martin SA, Sesti AM, Spritzer KL. Psychometric properties of the medical outcomes study sleep measure. Sleep Med. 2005;6(1):41-4.

Cohen SP, Mao J. Neuropathic pain: mechanisms and their clinical implications. BMJ. 2014;348:7656.

Costigan M, Scholz J, Woolf CJ. Neuropathic pain: a maladaptive response of the nervous system to damage. Annual Rev Neurosci. 2009;32:1-32.

Dworkin RH, O’connor AB, Backonja M, Farrar JT, Finnerup NB, Jensen TS, et al. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain. 2007;132(3):237-51.

Jensen MP, Chodroff MJ, Dworkin RH. The impact of neuropathic pain on health-related quality of life: review and implications. Neurol. 2007;68(15):1178-82.

McCarberg BH, Nicholson BD, Todd KH, Palmer T, Penles L. The impact of pain on quality of life and the unmet needs of pain management: results from pain sufferers and physicians participating in an Internet survey. Am J Therapeut. 2008;15(4):312-20.

Turk DC, Wilson HD, Cahana A. Treatment of chronic non-cancer pain. Lancet. 2011;377(9784):2226-35.

Schaefer C, Sadosky A, Mann R, Daniel S, Parsons B, Tuchman M, et al. Pain severity and the economic burden of neuropathic pain in the United States: BEAT Neuropathic Pain Observational Study. Clinico Economics Outcomes Res: CEOR. 2014;6:483.

McCarberg BH, Billington R. Consequences of neuropathic pain: quality-of-life issues and associated costs. Am J Manag Care. 2006;12(9):263-8.

Hahm T, Ahn H, Ryu S, Gwak M, Choi S, Kim J, et al. Combined carbamazepine and pregabalin therapy in a rat model of neuropathic pain. Brit J Anaesthesia. 2012;109(6):968-74.

Taylor CP, Angelotti T, Fauman E. Pharmacology and mechanism of action of pregabalin: the calcium channel α2–δ (alpha2–delta) subunit as a target for antiepileptic drug discovery. Epilepsy Res. 2007;73(2):137-50.

Tremont-Lukats IW, Megeff C, Backonja MM. Anticonvulsants for neuropathic pain syndromes. Drugs. 2000;60(5):1029-52.

Wiffen PJ, Derry S, Moore RA, Aldington D, Cole P, Rice AS, et al. Antiepileptic drugs for neuropathic pain and fibromyalgia‐an overview of Cochrane reviews. Cochrane Database Systematic Rev. 2013(11).

Tesfaye S, Wilhelm S, Lledo A, Schacht A, Tölle T, Bouhassira D, et al. 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.

Tanenberg RJ, Clemow DB, Giaconia JM, Risser RC. Duloxetine Compared with Pregabalin for Diabetic Peripheral Neuropathic Pain Management in Patients with Suboptimal Pain Response to Gabapentin and Treated with or without Antidepressants: A Post Hoc Analysis. Pain Pract. 2014;14(7):640-8.

Gilron I, Bailey JM, Tu D, Holden RR, Jackson AC, Houlden RL. Nortriptyline and gabapentin, alone and in combination for neuropathic pain: a double-blind, randomised controlled crossover trial. Lancet. 2009;374(9697):1252-61.

Morello CM, Leckband SG, Stoner CP, Moorhouse DF, Sahagian GA. Randomized double-blind study comparing the efficacy of gabapentin with amitriptyline on diabetic peripheral neuropathy pain. Arch Int Med. 1999;159(16):1931-7.

Chaparro LE, Wiffen PJ, Moore RA, Gilron I. Combination pharmacotherapy for the treatment of neuropathic pain in adults. Cochrane Database Systematic Rev. 2012 (7).

Holbech JV, Jung A, Jonsson T, Wanning M, Bredahl C, Bach FW. Combination treatment of neuropathic pain: Danish expert recommendations based on a Delphi process. J pain Res. 2017;10:1467.