Duloxetine ((S)-Duloxetine)

Comparison of amitriptyline supplemented with pregabalin, pregabalin supplemented with amitriptyline, and duloxetine supplemented with pregabalin for the treatment of diabetic peripheral neuropathic pain (OPTION-DM): a multicentre, double-blind, randomised crossover trial

Background: Diabetic peripheral neuropathic pain (DPNP) is common and often distressing. Most guidelines recommend amitriptyline, duloxetine, pregabalin, or gabapentin as initial analgesic treatment for DPNP, but there is little comparative evidence on which one is best or whether they should be combined. We aimed to assess the efficacy and tolerability of different combinations of first-line drugs for treatment of DPNP. Methods: OPTION-DM was a multicentre, randomised, double-blind, crossover trial in patients with DPNP with mean daily pain numerical rating scale (NRS) of 4 or higher (scale is 0-10) from 13 UK centres. Participants were randomly assigned (1:1:1:1:1:1), with a predetermined randomisation schedule stratified by site using permuted blocks of size six or 12, to receive one of six ordered sequences of the three treatment pathways: amitriptyline supplemented with pregabalin (A-P), pregabalin supplemented with amitriptyline (P-A), and duloxetine supplemented with pregabalin (D-P), each pathway lasting 16 weeks. Monotherapy was given for 6 weeks and was supplemented with the combination medication if there was suboptimal pain relief (NRS >3), reflecting current clinical practice. Both treatments were titrated towards maximum tolerated dose (75 mg per day for amitriptyline, 120 mg per day for duloxetine, and 600 mg per day for pregabalin). The primary outcome was the difference in 7-day average daily pain during the final week of each pathway. This trial is registered with ISRCTN, ISRCTN17545443. Findings: Between Nov 14, 2017, and July 29, 2019, 252 patients were screened, 140 patients were randomly assigned, and 130 started a treatment pathway (with 84 completing at least two pathways) and were analysed for the primary outcome. The 7-day average NRS scores at week 16 decreased from a mean 6·6 (SD 1·5) at baseline to 3·3 (1·8) at week 16 in all three pathways. The mean difference was -0·1 (98·3% CI -0·5 to 0·3) for D-P versus A-P, -0·1 (-0·5 to 0·3) for P-A versus A-P, and 0·0 (-0·4 to 0·4) for P-A versus D-P, and thus not significant. Mean NRS reduction in patients on combination therapy was greater than in those who remained on monotherapy (1·0 [SD 1·3] vs 0·2 [1·5]). Adverse events were predictable for the monotherapies: we observed a significant increase in dizziness in the P-A pathway, nausea in the D-P pathway, and dry mouth in the A-P pathway. Interpretation: To our knowledge, this was the largest and longest ever, head-to-head, crossover neuropathic pain trial. We showed that all three treatment pathways and monotherapies had similar analgesic efficacy. Combination treatment was well tolerated and led to improved pain relief in patients with suboptimal pain control with a monotherapy. Funding: National Institute for Health Research (NIHR) Health Technology Assessment programme.

Duloxetine and pregabalin in neuropathic pain of lung cancer patients

Introduction: Neuropathic pain occurs in 1% of the population and is difficult to manage. This chronic pain causes psychological distress and impacts patient's quality of life, especially in cancer patients. The aim of this study was to show and compare the efficacy of pregabalin and duloxetine, which are reported in the group of first-line treatment at European Federation of Neurological Societies (EFNS) guidelines on the pharmacological treatment of neuropathic pain (2010 revision) in lung cancer patients by using visual analogue scale (VAS) and Leeds Assessment of Neuropathic Symptoms and Sign (LANSS).
Patients and methods: A prospective, randomized, open label, 3 month of study was conducted. A total of 44 patients that were diagnosed with neuropathic pain (14 women and 30 men) were included in the study. Patient's LANSS and VAS values were recorded before treatment. Then, 22 patients undergo pregabalin and 22 patients undergo duloxetine therapy. But due to side effects (dizziness, constipation), two patients had stopped to use pregabalin. Their LANSS and VAS values were recorded after 1 and 3 months of therapy.
Results: When we compare LANSS and VAS scores before treatment, after 1 and 3 months of treatment with pregabalin and duloxetine, a significant decrease was observed in both groups at the 1 and 3 months (p < .01). Duloxetine is superior to pregabalin in reducing the LANSS scores when we compare two groups.
Conclusions: Both duloxetine and pregabalin are effective in the treatment of neuropathic pain of lung cancer patients. And as far as we know, this is the first study comparing the efficacy of duloxetine and pregabalin in the neuropathic pain of lung cancer patients.

Comparing duloxetine and pregabalin for treatment of pain and depression in women with fibromyalgia: an open-label randomized clinical trial

Background: Duloxetine and pregabalin are among the most widely used medications in the treatment of patients with fibromyalgia syndrome (FM).
Objectives: To add to the very few lines of evidence that exist on the comparative safety and efficacy of these two medications.
Methods: In this open-label randomized clinical trial, outpatient women, who were diagnosed with FM based on American College of Rheumatology 2010 criteria, and had an age range of 18-65 years old were assigned to either duloxetine 30-60 mg or pregabalin 75-150 mg per day for 4 weeks. Patients were excluded in cases of having used duloxetine, pregabalin, gabapentin, or antidepressants within 12 weeks prior to the study, having had a history of comorbid medical conditions that could provoke chronic pain, or having had comorbid neuropsychiatric disorders, except for major depressive/anxiety disorders. Primary outcomes were between-group differences in mean score changes from baseline to end point for Widespread Pain Index (WPI) and Beck Depression Inventory-II. Secondary outcomes were the same statistical estimates, but for Fibromyalgia Impact Questionnaire-Revised and 12-Item Short Form Survey. Descriptive statistics and independent samples t-test were the main methods of analysis. ( www.irct.ir ; IRCT2016030626935N1).
Results: Among all the scales, only WPI scores improved with a statistically significant difference between the two treatment arms, favoring duloxetine (Mean difference in score change - 2.32, 95% CI, -4.46 to - 0.18; p = 0.034; Cohen's d 0.53 95% CI, 0.04 to 1.02). Drop out rate and cumulative incidence of nausea was significantly higher in the duloxetine arm compared to the pregabalin arm.
Conclusion: This study provides further evidence on higher efficacy of duloxetine compared to pregabalin for the treatment of pain in patients with fibromyalgia. Future comprehensive pragmatic clinical trials are warranted.

Pain in Parkinson's disease: new concepts in pathogenesis and treatment

Purpose of review: In this review, we discuss the most recent evidence on mechanisms underlying pathological nociceptive processing in Parkinson's disease patients, as well as novel treatment strategies.
Recent findings: In Parkinson's disease, specific neurodegenerative changes may cause alterations in nociceptive processing at multiple levels. Optimization of dopaminergic therapies should always be the first step in the management of Parkinson's disease pain. Reportedly, rotigotine transdermal patch, a monoamine oxidase type B inhibitor safinamide (as an add-on therapy to levodopa), subcutaneous apomorphine and intrajejunal levodopa infusion therapy may have a beneficial effect on pain sensations in Parkinson's disease patients. Among the nondopaminergic pharmacological therapies, prolonged-release oxycodone/naloxone and duloxetine may be effective in the treatment of chronic pain in Parkinson's disease. Botulinum toxin (BTX) injections should be considered for the treatment of dystonic Parkinson's disease pain. Deep brain stimulation (DBS) may lead to pain relief with a long-lasting effect in Parkinson's disease patients. Physiotherapy and physical activity in general are essential for Parkinson's disease patients suffering from pain.
Summary: Pain in Parkinson's disease is not simply a consequence of motor complainants. The management of Parkinson's disease-related pain implicates maintenance of stable levels of dopaminergic drugs. Nondopaminergic pharmacological therapies (prolonged-release oxycodone/naloxone, duloxetine, BTX) and nonpharmacological interventions (DBS, physiotherapie) may also be beneficial in treatment of Parkinson's disease pain.

Management of diabetic neuropathy

Diabetic neuropathy is a neurodegenerative disorder that may alter both the somatic and autonomic peripheral nervous systems in the context of diabetes mellitus (DM). It is a prevalent and burdensome chronic complication of DM, that requires timely management. Optimized glycemic control (mainly for type 1 DM), multifactorial intervention (mainly for type 2 DM), with lifestyle intervention/physical exercise, and weight loss represent the basis of management for diabetic distal symmetrical polyneuropathy, and should be implemented early in the disease course. Despite better understanding of the pathogenetic mechanisms of diabetic peripheral neuropathy, there is still a stringent need for more pathogenetic-based agents that would significantly modify the natural history of the disease. The paper reviews the available drugs and current recommendations for the management of distal symmetrical polyneuropathy, including pain management, and for diabetic autonomic neuropathy. Evaluation of drug combinations that would perhaps be more efficient in slowing the progression of the disease or even reversing it, and that would provide a better pain management is still needed.