A Systematic Review of Treatment of Painful Diabetic Neuropathy by Pain Phenotype versus Treatment Based on Medical Comorbidities

Abstract

BackgroundPainful diabetic neuropathy (PDN) is a serious, polymorphic, and prevalent complication of diabetes mellitus. Most PDN treatment guidelines recommend a selection of drugs based on patient comorbidities. Despite the large numbers of medications available, most randomized clinical trials (RCTs) conducted so far have yielded unsatisfactory outcomes. Therefore, treatment may require a personalized approach based on pain phenotype or comorbidities.MethodsTo evaluate whether or not a patient’s pain phenotype or comorbidities can influence the response to a specific PDN treatment, we conducted a systematic review using two different approaches: pain phenotype and associated comorbidities-based treatment.ResultsOut of 45 identified papers, 7 were thoroughly reviewed. We found four RCTs stratified according to pain phenotype with three main results: (1) paroxysmal pain had a better response to pregabalin; (2) the preservation of thermal sensation or nociception anticipated a positive response to the topical treatment of pain; and, (3) after a failure to duloxetine (60 mg/day), the patients with evoked pain or severe deep pain had a better response to association of duloxetine/pregabalin while those with paresthesia/dysesthesia benefited from duloxetine monotherapy (120 mg/day). By contrast, the other three papers provided weak and even contradictory evidence about PDN treatment based on comorbidities.ConclusionAlthough more studies are needed to provide an adequate recommendation for clinical practice, our systematic review has provided some evidence that PDN phenotyping may optimize clinical outcomes and could, in the future, lead to both less empirical medicine and more personalized pain therapeutics.

Diabetic Peripheral Neuropathy: Epidemiology, Diagnosis, and Pharmacotherapy

“…140 Also, patients who received duloxetine (60 mg/d) as initial therapy had a better response to combined duloxetine and pregabalin for evoked or severe tightness and a greater benefit with high-dose duloxetine (120 mg/d) for paresthesia-dysaesthesia. 140,141 Other Anticonvulsants…”

Distal Symmetric Polyneuropathy Pain in Diabetes Mellitus

“…High blood pressure, dyslipidemia, obesity, and smoking associated with painful diabetic neuropathy cause a higher prevalence of complications in individuals with more than ten years of disease, especially in more than half of people with NP. Current data show that this association occurs when 95.4 % of the studied individuals with pain have high blood pressure, 68.1 % dyslipidemia, 68.2 % obesity, and 54.5 % smoking, physically and emotionally impacting their quality of life (3,38,42).…”

Pregabalin in the Management of Painful Diabetic Neuropathy: A Narrative Review

“…A further exploratory post hoc analysis of COMBO-DN showed that high-dose monotherapy was more favourable in patients with severe pain, whereas combination therapy was more beneficial in patients with moderate and mild pain [ 62 ]. Also, patients who received duloxetine (60 mg/day) as initial therapy had a better response to combined duloxetine and pregabalin for evoked or severe tightness and a greater benefit with high-dose duloxetine (120 mg/day) for paraesthesia-dysaesthesia [ 62 , 63 ]. In another double-blind RCT with a parallel-group design comparing amitriptyline, duloxetine and pregabalin there was no significant difference in analgesic efficacy [ 64 ].…”