Efficacy and safety of pregabalin versus amitriptyline in patients with painful diabetic neuropathy

Sujit R. Daniel, Dinesh K. Badyal, Jubbin J. Jacob, Jasleen Kaur


Background: Painful diabetic neuropathy is a common complication of long standing diabetes mellitus. Amitriptyline is commonly used to treat painful diabetic neuropathy. Pregabalin has been shown to be effective in the treatment of painful diabetic neuropathy with lesser adverse effects. Sustained release (SR) of pregabalin has the advantage of once daily dosing and a better patient compliance. Hence, this study was planned to compare the efficacy and safety of pregabalin-SR with amitriptyline in painful diabetic neuropathy.

Methods: It is a prospective, open labelled, randomized controlled study. A total of 80 patients diagnosed with painful diabetic neuropathy based on Diabetic neuropathy symptom score and Michigan neuropathy screening instrument, were randomized into two groups to receive amitriptyline and pregabalin SR. Amitriptyline was started at 25mg OD and pregabalin SR 75mg OD for 6 weeks with optional dose titration. Patients were assessed for pain relief by using visual analogue scale and an overall improvement in their general condition by patient’s global impression of change scale. Adverse drug reactions were recorded on each follow up.

Results: All patients had significant improvement in pain relief in both the treatment groups. The median VAS (visual analogue scale) score was slightly higher in pregabalin SR group (25 vs 22) however it was not statistically significant. Intergroup comparison did not show any significant differences between the treatment groups. Good and moderate pain relief were noted in 37(92.5%) and 3(7.5%) patients on amitriptyline and 36 (90%) and 4 (10%) patients on pregabalin SR respectively. The common adverse effects reported in amitriptyline group were drowsiness (27.5%) and dry mouth (17.5%) and in pregabalin-SR group were drowsiness (15%) and dizziness (5%). No serious adverse event was reported in either of the groups.

Conclusions: In patients with painful diabetic neuropathy both amitriptyline and pregabalin-SR are equally effective in alleviating pain and improving the patient’s general condition, but pregabalin-SR has the advantage of fewer adverse effects and convenient dosage timing.


Amitriptyline, Painful diabetic neuropathy, Pregabalin

Full Text:



Bansal D, Bhansali A, Hota D, Chakrabarti A, Dutta P. Amitriptyline vs. pregabalin in painful diabetic neuropathy: a randomized double blind clinical trial. Diabet Med. 2009;26:1019-26.

Spruce MC, Potter J, Coppini DV. The pathogenesis and management of painful diabetic neuropathy: a review. Diabet Med. 2003;20:88-98.

Dutta A, Naorem S, Singh TP, Wangjam K. Prevalence of peripheral neuropathy in newly diagnosed type-2 diabetes mellitus. Int J Diab Dev Ctries. 2005;25:30-3.

Boulton AJM, Gries FA, Jervell JA. Guidelines for the diagnosis and outpatient management of diabetic peripheral neuropathy. Diabet Med. 1998;15:508-14.

Brown MJ, Asbury AK. Diabetic neuropathy. Ann Neurol. 1984;15:2-12.

Craner MJ, Klein JP, Renganathan M, Black JA, Waxman SG. Changes of sodium channel expression in experimental painful diabetic neuropathy. Ann Neurol. 2002;52:786-92.

Archer AG, Watkins PJ, Sharma AK, Payan J. The natural history of acute painful neuropathy in diabetes mellitus. J Neurol Neurosurg Psychiat. 1983;46:491-9.

Dejgaard A. Pathophysiology and treatment of diabetic neuropathy. Diabet Med. 1998;15:97-112.

Meijer JW, Smit AJ, Sonderen EV, Groothoff JW, Eisma WH, Links TP. Symptom scoring systems to diagnose distal polyneuropathy in diabetes: the diabetic neuropathy symptom score. Diabet Med. 2002;19:962-5.

Moghtaderi A, Bakhshipour A, Rashidi H. Validation of Michigan neuropathy screening instrument for diabetic peripheral neuropathy. Clin Neurol Neurosurg. 2006;108:477-81.

Richter RW, Portenoy R, Sharma U, Lamoreaux L, Bockbrader H, Knapp LE. Relief of painful DN with pregabilin: A randomized, placebo-controlled trial. J Pain. 2005;6:253-60.

Devi P, Madhu K, Ganapathy B, Sarma GRK, John L, Kulkarni C. Evaluation of efficacy and safety of gabapentin, duloxetine, and pregabalin in patients with painful diabetic peripheral neuropathy. Indian J Pharmacol. 2012;44:51-6.

Rosenstock J, Tuchman M, LaMoreaux L, Sharma U. Pregabalin for the treatment of painful diabetic peripheral neuropathy: a double-blind, placebo-controlled trial. Pain. 2004;110:628-38.

Lesser H, Sharma U, LaMoreaux L, Poole RM. Pregabalin relieves symptoms of painful diabetic neuropathy: a randomized controlled trial. Neurology. 2004;63:2104-10.

Kaur H, Bansal D, Bhansali A, Hota D, Chakrabarti A, Dutta P. A comparative evaluation of amitriptyline and duloxetine in painful diabetic neuropathy: A randomized double blind cross-over clinical trial. Diabetes Care. 2011;34:818-22.

Max MB, Culnane M, Schafer SC, Gracely RH, Walther DJ, Smoller B et al. Amitriptyline relieves diabetic neuropathy pain in patients with normal or depressed mood. Neurology. 1987;37:589-96.

Dallocchio C, Buffa C, Mazzarello P, Chiroli S. Gabapentin vs. amitriptyline in painful diabetic neuropathy: An open-label pilot study. J pain Symptom Manage. 2000;20:280-5.

Lindsay TJ, Rodgers BC, Savath V, Hettinger K. Treating diabetic peripheral neuropathic pain. Am Fam Phys. 2010;82:151-8.

Freeman R, Durso-Decruz E, Emir B. Efficacy, safety, and tolerability of pregabalin treatment for painful diabetic peripheral neuropathy. Diabetes Care. 2008;31:1448-54.

Ghosh AK, Ghosh A, Kundu A, Das AK, Bhattacharya KB. Comparative study of efficacy and safety of pregabalin and gabapentin in neuropathic pain. Asian J Pharm Life Sci. 2012;2:64-71.

Dongre YU, Swami OC. Sustained-release pregabalin with methylcobalamin in neuropathic pain: an Indian real-life experience. Int J Gen Med. 2013;6:413-7.