CLINICAL CHARACTERISTICS, TREATMENT PATTERNS, AND REPORTED TREATMENT RESPONSE AMONG PATIENTS WITH PAINFUL DIABETIC NEUROPATHY RECEIVING AMITRIPTYLINE PREGABALIN DULOXETINE OR MECOBALAMIN; A PROSPECTIVE COHORT STUDY

Abstract

Background: Painful diabetic neuropathy (PDN) is a common and clinically important complication of diabetes that can substantially affect daily functioning and quality of life. Amitriptyline, Pregabalin, duloxetine, and Mecobalamin are used in clinical practice for neuropathic symptoms, but treatment selection and response may vary according to patient characteristics and routine prescribing practices. Real-world data from Pakistan describing treatment patterns and short-term patient-reported response remain limited. This study aimed to describe the clinical characteristics, treatment patterns, and reported treatment response among patients with PDN receiving these medications as initial monotherapy in routine outpatient practice. Methods: This prospective observational cohort study was conducted in the Medical Outpatient Department of Ayub Teaching Hospital, Abbottabad, Khyber Pakhtunkhwa, Pakistan. Adult patients with clinically diagnosed PDN who were newly prescribed amitriptyline, Pregabalin, duloxetine, or Mecobalamin as initial monotherapy by their treating physician were enrolled from 10 March 2025 to 10 August 2025 and followed for four weeks. Treatment allocation was determined by routine clinical practice and was not influenced by the research team. Pain intensity was assessed using the 11-point Numerical Rating Scale (NRS; 0–10) at baseline and at four weeks. The primary outcome was change in NRS pain intensity. A clinically meaningful treatment response was predefined as a ≥30% reduction in NRS pain score from baseline. Adherence, adverse effects, treatment continuation or discontinuation, dose modification, switching, and addition of another neuropathic pain medication were also assessed. Data were analysed using IBM SPSS Statistics version 26. Between-group analyses were considered exploratory, and multivariable logistic regression was performed for achieving a ≥30% reduction in pain after adjustment for clinically relevant baseline variables. Results: A total of 428 patients were enrolled, comprising 171 (40.0%) receiving amitriptyline, 128 (29.9%) Pregabalin, 86 (20.1%) duloxetine, and 43 (10.0%) Mecobalamin. Overall, 411 (96.0%) participants completed the four-week follow-up. The mean age was approximately 55–57 years across treatment cohorts, and most participants had type 2 diabetes. Baseline mean NRS pain scores ranged from 6.5 to 7.0. At four weeks, mean NRS pain scores decreased in all cohorts: from 6.8 to 4.8 with amitriptyline, 7.0 to 4.7 with Pregabalin, 6.9 to 4.5 with duloxetine, and 6.5 to 4.8 with Mecobalamin. The corresponding mean reductions were 2.0, 2.3, 2.4, and 1.7 points, respectively, with a between-group p value of 0.041. Overall, 219 (53.3%) participants achieved a ≥30% reduction in NRS pain intensity, including 82 (49.7%) in the amitriptyline cohort, 69 (56.6%) in the Pregabalin cohort, 52 (62.7%) in the duloxetine cohort, and 16 (39.0%) in the Mecobalamin cohort. Patient-reported improvement was reported by 241 (58.6%) participants. Treatment adherence was reported in 374 (91.0%) participants, while adverse effects occurred in 83 (20.2%) and treatment discontinuation in 37 (9.0%). In exploratory multivariable analysis, duloxetine compared with Mecobalamin was associated with higher odds of achieving a ≥30% reduction in pain (adjusted OR 2.08, 95% CI 1.07–4.05; p=0.031), while the treatment-group findings were interpreted as associations rather than evidence of comparative efficacy. Conclusion: In this prospective observational cohort, pain intensity decreased over four weeks among patients with PDN receiving amitriptyline, Pregabalin, duloxetine, or Mecobalamin as initial monotherapy, with more than half achieving a clinically meaningful ≥30% reduction in pain. Adherence was generally good, while adverse effects and treatment modifications occurred in a minority of patients. The findings provide real-world information on prescribing patterns and short-term treatment response in a tertiary-care setting in Pakistan. However, because treatment was not randomized and the cohorts differed in size and may have been affected by confounding by indication, the observed differences should not be interpreted as evidence of comparative drug efficacy. Longer-term, multicentre prospective studies using standardized dosing and broader patient-reported outcomes are warranted.