Management Of Diabetic Peripheral Neuropathic Pain Research Articles

Comparison of Efficacy of Nortriptyline Versus Transcutaneous Electrical Nerve Stimulation on Painful Peripheral Neuropathy in Patients with Diabetes

Abstract Background and aims: Diabetic peripheral neuropathic pain (DPNP) is one of the most common complications of diabetes and is difficult to treat. Existing treatments are often inadequate at controlling pain and limited by side-effects and drug tolerance. This study assessed the efficacy of nortriptyline versus Transcutaneous Electrical Nerve Stimulation (TENS) in patients with DPNP. Material and method: This is a randomized clinical trial study conducted on 39 patients with DPNP referring to Golestan Hospital in Ahvaz in 2017. Patients were randomly treated with TENS (18 sessions, each session 30 minutes; n=20) or nortriptyline (25 to 75 mg, once daily; n=19) for 6 weeks. Patients were evaluated for side effects and pain relief using visual analog scale (VAS). Results: There was a significant improvement in pain with both treatments compared with baseline (p˂0.001). The patients in nortriptyline group experienced more pain relief (7.21±1.51 to 0.84±1.34) than the TENS group (7.6±1.47 to 2.75 ±2.43) (P=0.001). The 50% pain relief was observed in 14 patients (73%) in nortriptyline group, 6 patients (30%) in TENS group. Moreover, the side effects were seen in 15% of TENS and 55% of patients in nortriptyline groups (P=0.019). Conclusion: Both TENS and nortriptyline were effective and safe in the management of DPNP. But nortriptyline showed a better performance on pain relief.

Diabetic Peripheral Neuropathic Pain From the Perspective of Turkish Patients: A Qualitative Study.

Diabetic peripheral neuropathy (DPN) affects almost 30% to 50% of patients with diabetes, 40% to 60% of whom suffer from diabetic peripheral neuropathic pain (DPNP). Few studies have focused on individual experiences of DPNP in patients with diabetes. The purpose of this qualitative study was to elucidate the effects of DPNP on daily life and individual feelings regarding living with DPNP from the perspective of Turkish patients. A total of 14 patients were interviewed, and interpretative phenomenological analysis was used to identify themes. Findings indicated four main themes, including (a) physical limitations, (b) difficulties with daily routines, (c) social limitations, and (d) psychological impacts such as emotional changes, and being a burden on family. This study revealed that the majority of patients carry significant concerns about becoming a burden on their family and are afraid of becoming dependent on others because of DPNP. For the effective management of DPNP, health professionals need to consider using a holistic approach to address difficulties in daily living such as physical limitations and sexual problems.

Diabetic Peripheral Neuropathic Pain - An Update

Diabetic peripheral neuropathic pain (DPNP) is the clinical presentation of neuropathic pain in Painful Diabetic Peripheral Neuropathy (PDPN) and it is of two types- nerve trunk pain and hyperalgesic pain, involving both small and large nerve fiber dysfunction, secondary to insulin neuritis, glucose influx, and ectopic impulses from dorsal root ganglia, with interaction of spinal/cortical mechanisms. The paper reviews the epidemiology, mechanisms, differential diagnosis and management of DPNP and the existing evidence need to take an evidence-informed shift towards a multidisciplinary biopsychosocial perspective. The treating clinician needs to be aware of the clinical findings, neurodynamic findings, its inter-relationship with other factors such as quality of life, and scores obtained on clinical assessment scales for staging the condition so that an integrated approach involving judicious use of medical, surgical, physiotherapeutic and complementary/alternative medicine methods can be employed for comprehensive management of the condition.

Review of Efficacy and Safety of Duloxetine 40 to 60 mg Once Daily in Patients with Diabetic Peripheral Neuropathic Pain

We summarize efficacy and safety findings from 4 double-blind, placebo-controlled, 12-week studies and 1 open-label, uncontrolled, 34-week maintenance-of-effect (MOE) study that examine duloxetine 40 and 60 mg once daily (QD) in patients with diabetic peripheral neuropathic pain (DPNP). In all placebo-controlled studies, duloxetine showed significantly (P ≤ .01) greater reduction in pain severity (weekly mean of 24-hour average pain severity ratings, primary outcome measure) compared with placebo. In all placebo-controlled studies, duloxetine showed significantly (P ≤ .05) greater improvement on brief pain inventory-Interference ratings. Patient global impression of improvement ratings were superior to placebo (P ≤ .01) for duloxetine patients in all placebo-controlled studies. Response rates (based on 30% pain reduction) ranged from 57% to 68% for duloxetine and from 35% to 47% for placebo and were statistically significantly different (P ≤ .01) between treatment groups in 3 out of 4 studies. The open-label study showed maintenance of analgesic effect of duloxetine in DPNP. In the duloxetine groups, 4.3% to 14.9% of patients discontinued because of adverse events (placebo groups: 2.6% to 7.4%). Most commonly reported treatment-emergent adverse events were nausea, somnolence, and headache. Duloxetine 40 and 60 mg QD was efficacious and well tolerated in the management of DPNP.

A randomized controlled trial of duloxetine in diabetic peripheral neuropathic pain

Serotonin (5-HT) and norepinephrine (NE) are involved in pain modulation via descending inhibitory pathways in the brain and spinal cord. To assess the efficacy of duloxetine, a dual reuptake inhibitor of 5-HT and NE, on the reduction of pain severity, as well as secondary outcome measures in patients with diabetic peripheral neuropathic pain (DPNP). In this double-blind study, patients with DPNP and without comorbid depression were randomly assigned to treatment with duloxetine 60 mg once daily (QD), duloxetine 60 mg twice daily (BID), or placebo for 12 weeks. The primary outcome measure was the weekly mean score of 24-hour average pain severity on the 11-point Likert scale. Secondary measures and health outcome measures were also assessed. Duloxetine 60 mg QD and 60 mg BID demonstrated improvement in the management of DPNP and showed rapid onset of action, with separation from placebo beginning at week 1 on the 24-hour average pain severity score. For all secondary measures for pain (except allodynia), mean changes showed an advantage of duloxetine over placebo, with no significant difference between 60 mg QD and 60 mg BID. Clinical Global Impression of Severity and Patient's Global Impression of Improvement evaluation demonstrated greater improvement on duloxetine- vs placebo-treated patients. Duloxetine showed no notable interference on diabetic controls, and both doses were safely administered. This study confirms previous findings that duloxetine at 60 mg QD and 60 mg BID is effective and safe in the management of diabetic peripheral neuropathic pain.

New perspectives on the management of diabetic peripheral neuropathic pain

Peripheral neuropathy affects about 30% of people with diabetes mellitus. Between 16% and 26% of diabetes patients experience chronic pain. This may be referred to as diabetic neuropathic pain (DNP) or diabetic peripheral neuropathic pain (DPNP). Minimum requirements for diagnosis of DPNP should include assessment of pain and symptoms and neurological examination, with the accent on sensory examination. Given that depression and other co-morbidities are commonly associated with this condition, a broad approach to management is essential. Lifestyle intervention and optimisation of glycaemic control are recommended as initial steps in management. An evidence-based treatment algorithm for DPNP has been proposed, recommending initial use of either a tricyclic antidepressant, selective serotonin noradrenaline re-uptake inhibitor or alpha-2-delta agonist, depending on patient co-morbidities and contra-indications. Addition of an opioid agonist may be required in the event of inadequate pain control. Irrespective of which treatment is offered, only about one third of patients are likely to achieve more than 50% pain relief. Further research to improve the diagnosis and management of DPNP is needed.

Duloxetine in the long-term management of diabetic peripheral neuropathic pain: An open-label, 52-week extension of a randomized controlled clinical trial

Background: Duloxetine hydrochloride, a selective serotonin (5-HT) and norepinephrine (NE) reuptake inhibitor, is relatively balanced in its affinity for both 5-HT and NE reuptake inhibition and is the first US Food and Drug Administration-approved prescription drug for the management of diabetic peripheral neuropathic pain (DPNP). Objectives: The aim of this study was to determine whether management of DPNP with duloxetine interferes with the treatment of diabetes. It also examined the tolerability of long-term exposure to duloxetine with regard to the progression of diabetic complications, and assessed the impact of DPNP management with duloxetine versus routine care. Methods: This was a 52-week, multicenter, re-randomized, open-label extension of a parallel, double-blind, randomized, placebo-controlled, acute (12-week) study. Patients who completed the duloxetine or placebo acute treatment period were randomly reassigned in a 2:1 ratio to treatment with duloxetine 60 mg BID or routine care for an additional 52 weeks. The study included male and female outpatients aged ≥18 years with a diagnosis of DPNP caused by type 1 or type 2 diabetes. Over the course of the 52-week study, visits were scheduled on the following weeks (of the extension phase of the study): 1 (via phone only), 2, 4, 8, 12, 20, 28, 40, and 52. Tolerability was assessed by review and analyses of discontinuation rates, adverse events (AEs), laboratory data, vital signs, electrocardiographic results, concomitant medications, and diabetic complications. Treatment-emergent AEs (TEAEs) were defined as AEs that appeared during therapy (were not present at baseline) or were exacerbated during treatment. Data on AEs and concomitant medications were collected at every visit. Data on blood pressure, heart rate, and significant hypoglycemic events were collected at every visit starting from week 2. Fasting clinical chemistry and electrolyte group laboratory assessments were done at every visit, starting from week 4. Electrocardiographic data was collected at weeks 4 and 52, and glycosylated hemoglobin and lipid profile data were collected at weeks 20 and 52. Hematology and urinalysis laboratory assessments and diabetic complication assessments were done at week 52. All safety data was assessed in cases of early discontinuation. Treatment differences on quality of life (QOL) were compared using the Short Form-36 Health Status Survey (SF-36) and the EQ-5D instrument of the European Health-Related Quality of Life Measures. This was assessed at the last visit or at early discontinuation. Results: The open-label extension-phase study included 337 patients (duloxetine, n = 222; routine care, n = 115). For the duloxetine group, mean age was 60.2 years, 61.3% were male, and 78.4% were white. For the routine-care group, mean age was 58.9 years, 60.0% were male, and 74.8% were white. Mean weight was 95.3 kg for both groups. None of the TEAEs occurred significantly more often in the duloxetine-treated group than in the routine-care-treated group. No TEAEs were reported by >10% of patients in the duloxetine group. The TEAEs reported by >10% of patients in the routine-care group included dizziness (11.3%), somnolence (13.0%), headache (10.4%), and vomiting (10.4%). No significant differences were found between treatment groups in the occurrence of serious AEs or in the number of patients discontinuing because of AEs. Duloxetine was significantly better than routine care on the bodily pain subscale of the SF-36 (mean change: 1.5 vs −4.1; P= 0.021) and on the EQ-5D (mean change: −0.00 vs −0.09; P = 0.001). Conclusions: Over 52 weeks of follow-up, treatment of these diabetic patients with duloxetine for peripheral neuropathic pain was associated with outcomes similar to, or significantly better than, that of routine care on most measures of tolerability, diabetic complications, and QOL.

Evaluation of Duloxetine Effectiveness in the Management of DPNP with Respect to Baseline Characteristics

Abstracts from the ASENT 2006 Annual MeetingMarch 8–11, 2006 Duloxetine in the Management of DiabeticPeripheral Neuropathic Pain: Response Profile Y Pritchett, B McCarberg, J Watkin, A Chappell,M Robinson Eli Lilly and Company and University of California—San Diego Introduction: Analyses examine the response rate at end-point, as well as time course of response, in patients receivingduloxetine for management of diabetic peripheral neuropathicpain (DPNP). Methods: Data were pooled from 3 double-blind, random-ized, placebo-controlled 12-week trials in patients with DPNP 6 months duration, and without depression. Study 1 ( N 457) compared duloxetine 20 mg once daily (QD), 60 mg QD,60 mg twice daily (BID), and placebo; Studies 2 ( N 334) and3( N 348) compared duloxetine 60 mg QD and 60 mg BIDwith placebo. Ethics committees approved the study protocol inaccordance with Declaration of Helsinki principles. Patientsprovided written informed consent prior to study participation.Treatment response was defined a priori as 30% reduction inthe primary efficacy measure, 24-hour average pain severity.Analysis was replicated using alternative criteria (50% reduc-tion or 2-point reduction).

Cost-Effectiveness of Duloxetine Versus Routine Treatment for U.S. Patients With Diabetic Peripheral Neuropathic Pain

The purpose of this study was to compare the cost-effectiveness of duloxetine versus routine treatment in management of diabetic peripheral neuropathic pain (DPNP). Two hundred thirty-three patients with DPNP who completed a 12-week, double-blind, placebo-controlled, randomized, multicenter duloxetine trial were re-randomized into a 52-week, open-label trial of duloxetine 60 mg twice daily versus routine treatment. Routine treatment included pain management therapies. Effectiveness was measured by using the bodily pain domain (BP) of the Medical Outcomes Study Short Form 36 (SF-36). Costs were analyzed from 3 perspectives: third party payer (direct medical costs), employer (direct and indirect medical costs), and societal (patient’s out-of-pocket costs and total medical costs). Costs of study medications were not included because of limited data. Bootstrap method was applied to calculate statistical inference of the incremental cost-effectiveness ratio (ICER). Routine treatment most frequently used included gabapentin (56%), venlafaxine (36%), and amitripytline (15%). From employer and societal perspectives, duloxetine was cost-effective (ICER= –$342 and –$429, respectively, per unit of SF-36 BP; both P ≤ .03) and the dominant therapy compared with routine DPNP treatment (both P < .05). From payer perspective, duloxetine trended toward cost-effectiveness (ICER= –$249 per unit of SF-36 BP; P ≤ .06). These results, however, reflect the controlled environment of a clinical trial. An analysis of real-world data would be beneficial. Perspective Evaluation of the cost and benefit of new pharmacologic treatments is highly desired by decision makers. From both employer perspective and societal perspective (including patient’s out-of-pocket costs), this study demonstrated that duloxetine was more cost-effective than routine treatment in management of DPNP.

A Double-Blind, Randomized Multicenter Trial Comparing Duloxetine with Placebo in the Management of Diabetic Peripheral Neuropathic Pain

Assess efficacy and safety of duloxetine, a selective serotonin and norepinephrine reuptake inhibitor, on the reduction of pain severity, in patients with diabetic peripheral neuropathic pain (DPNP). This was a multicenter, parallel, double-blind, randomized, placebo-controlled trial that enrolled 348 patients with pain due to peripheral neuropathy caused by type 1 or type 2 diabetes mellitus. Patients (N = 116 per group) were randomly assigned to receive duloxetine 60 mg once daily (QD), duloxetine 60 mg twice daily (BID), or placebo, for 12 weeks. The primary outcome measure was the weekly mean score of 24-hour average pain severity evaluated on an 11-point Likert scale. Secondary outcome measures and safety were evaluated. Compared with placebo-treated patients, both duloxetine-treated groups improved significantly more (P < 0.001) on the 24-hour average pain score. Duloxetine demonstrated superiority to placebo in all secondary analyses of the primary efficacy measure. A significant treatment effect for duloxetine was observed in most secondary measures for pain. Discontinuations due to adverse events were more frequent in the duloxetine 60 mg BID- (12.1%) versus the placebo- (2.6%) treated group. Duloxetine showed no adverse effects on diabetic control, and both doses were safely administered and well tolerated. In this clinical trial, duloxetine 60 mg QD and duloxetine 60 mg BID were effective and safe in the management of DPNP.