Sodium valproate in the management of painful neuropathy in type 2 diabetes - a randomized placebo controlled study (original) (raw)
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Sodium valproate for painful diabetic neuropathy: a randomized double-blind placebo-controlled study
QJM, 2004
Background: Various drugs are effective in the management of painful diabetic neuropathy, but none is completely satisfactory. We previously found sodium valproate to be effective and safe in a short-term study. Aim: To test the effectiveness and safety of sodium valproate in the management of painful diabetic neuropathy over 3 months. Design: Randomized double-blind placebocontrolled study. Methods: Consecutive attending patients with type 2 diabetes mellitus with painful neuropathy were asked to participate in the trial: 48 agreed. Five were excluded: three with HbA 1c > 11, one with too low a pain level and one who withdrew consent. The remaining 43 were given either drug (group A) or placebo (group B). Each patient was assessed clinically. Quantitative assessment of pain was done by McGill Pain Questionnaire, Visual Analogue Score and Present Pain Intensity, at the beginning of the study, after 1 month and after 3 months. Motor and sensory nerve conduction velocities were measured initially and after 3 months. Liver function tests and other adverse drug-related effects were assessed periodically. Results: Of the 43 patients, four dropped out: one in group A and three in group B. There was significant improvement in pain score in group A, compared to group B, at 3 months (p < 0.001). Changes in electrophysiological data were not significant. The drug was well-tolerated by all patients, except one, who had raised serum AST and ALT levels after 1 month of treatment, and whose treatment was discontinued. Discussion: Sodium valproate is well-tolerated, and provides significant subjective improvement in painful diabetic neuropathy.
Neuroscience, 2002
OBJECTIVE: To study the effectiveness and safety aspects of sodium valproate in the management of painful neuropathy in patients of type 2 diabetes mellitus. MATERIAL AND METHODS: A randomized double-blind placebo controlled trial of sodium valproate was done in type 2 diabetic patients to assess its efficacy and safety in the management of painful neuropathy. We screened 60 patients but eight patients could not complete the study; hence, the present study was done on 52 patients. Each patient was assessed by clinical examination, pain score by short form of the McGill pain questionnaire (SF-MPQ) and electrophysiological examination, which included motor and sensory nerve conduction velocity, amplitude and H-reflex initially and at the end of 1 month of treatment. RESULTS: Significant improvement was noticed in the pain score of patients receiving sodium valproate in comparison to patients receiving placebo at the end of 1 month (P < 0.05). The changes in electrophysiological data were not significant. The drug was well tolerated by all patients except one who developed a raised aspartate transaminase (AST)/ alanine transaminase (ALT) level after 15 days of treatment. CONCLUSION: Sodium valproate is a well-tolerated drug and provides significant subjective improvement in painful diabetic neuropathy. These data provide a basis for future trials of longer duration in a larger group of patients.
Effects of Treatments for Symptoms of Painful Diabetic Neuropathy: Systematic Review
British Medical Journal, 2007
Objective To evaluate the effects of treatments for the symptoms of painful diabetic neuropathy. Design Systematic review. Data sources Articles (English and full text) on double blind randomised trials found by searching with the key words anticonvulsant, antidepressant, non-steroidal antiinflammatory drugs, tramadol, opioid, ion channel blocker, diabetic neuropathy, diabetic peripheral neuropathy, peripheral neuropathy, and neuropathy. The search included Medline, Embase, EMB reviews-AP Journal club, and the Cochrane central register of controlled trials. Study selection Randomised controlled trials comparing topically applied and orally administered drugs with a placebo in adults with painful diabetic neuropathy. Data extraction Data were extracted to examine quality of methods, characteristics of studies and patients, efficacy, and side effects. The primary outcome was dichotomous information for 50% or moderate reduction of pain. Secondary outcomes were 30% reduction of pain and withdrawals related to adverse events. Results Odds ratios were calculated for achievement of 30%, 50%, or moderate pain relief and for withdrawals related to adverse effects. Twenty five reports were included and seven were excluded. The 25 included reports compared anticonvulsants (n=1270), antidepressants (94), opioids (329), ion channel blockers (173), N-methyl-D-aspartate antagonist (14), duloxetine (805), capsaicin (277), and isosorbide dinitrate spray (22) with placebo. The odds ratios in terms of 50% pain relief were 5.33 (95% confidence interval 1.77 to 16.02) for traditional anticonvulsants, 3.25 (2.27 to 4.66) for newer generation anticonvulsants, and 22.24 (5.83 to 84.75) for tricylic antidepressants. The odds ratios in terms of withdrawals related to adverse events were 1.51 (0.33 to 6.96) for traditional anticonvulsants, 2.98 (1.75 to 5.07) for newer generation anticonvulsants, and 2.32 (0.59 to 9.69) for tricylic antidepressants. Insufficient dichotomous data were available to calculate the odds ratios for ion channel blockers. Conclusion Anticonvulsants and antidepressants are still the most commonly used options to manage diabetic neuropathy. Oral tricyclic antidepressants and traditional anticonvulsants are better for short term pain relief than newer generation anticonvulsants. Evidence of the long term effects of oral antidepressants and anticonvulsants is still lacking. Further studies are needed on opioids, N-methyl-D-aspartate antagonists, and ion channel blockers.
Alleviation of pain in painful diabetic neuropathy
Expert Opinion on Drug Metabolism & Toxicology, 2016
Introduction: Painful diabetic neuropathy (PDN) is a disabling pain condition. Its pathomechanism remains unknown, but a sensitization and neuronal hyperexcitabilty have been suggested. Only symptomatic pharmacological pain-alleviation treatment is currently available. Areas covered: The origin of PDN is enigmatic, and the evidence-based therapeutic guidelines therefore consist only of antidepressants and antiepileptics as first-line recommended drugs. This article relates to a MEDLINE/PubMed systematic search (2005-2015). Expert opinion: The results of the meta-analysis from the aspect of the efficacy of amitriptyline, duloxetine, venlafaxine, gabapentin and pregabalin are favorable, but the placebo response rate is relatively high in patients with neuropathic pain. For personalization of the medication of PDN patients, the optimum dosing, the genotyping of the metabolizing enzymes and optimum biomarkers are needed. As concerns the future perspectives, specific sodium channel subtype inhibitors acting on peripheral nociceptive neurons or modified Ttype voltage-gated calcium channel blockers may be promising targets for pharmaceutical innovations. Another attractive strategy for the treatment is based on the effects of monoclonal antibodies against nerve growth factor, sodium channel, specific receptor and cytokines. Botulinum toxin A, capsaicin patch and spinal cord stimulation therapies are the nearest future therapeutic options for the treatment of PDN patients.
Practical Diabetes International, 2004
Painful diabetic neuropathy is a common and troubling complication of diabetes. Many current treatments are based on anecdotal reports or relatively small clinical trials in which the efficacy of the agents is questionable, reflecting the fact that none is specifically licensed for the management of painful diabetic neuropathy. Despite these limitations the authors provide a practical algorithm based on a number needed to treat analysis together with an assessment of drug safety. We advocate an improvement in overall glycaemic control together with a reduction in glucose flux, coupled with a stepwise approach starting with a tricyclic, followed by gabapentin, tramadol and carbamazepine. We do not recommend combination treatment. Copyright ©2004 John Wiley & Sons, Ltd.
Neurology, 2011
Objective: To develop a scientifically sound and clinically relevant evidence-based guideline for the treatment of painful diabetic neuropathy (PDN). Methods: We performed a systematic review of the literature from 1960 to August 2008 and classified the studies according to the American Academy of Neurology classification of evidence scheme for a therapeutic article, and recommendations were linked to the strength of the evidence. The basic question asked was: "What is the efficacy of a given treatment (pharmacological: anticonvulsants, antidepressants, opioids, others; and non-pharmacological: electrical stimulation, magnetic field treatment, low-intensity laser treatment, Reiki massage, others) to reduce pain and improve physical function and quality of life (QOL) in patients with PDN?" Results and Recommendations: Pregabalin is established as effective and should be offered for relief of PDN (Level A). Venlafaxine, duloxetine, amitriptyline, gabapentin, valproate, opioids (morphine sulphate, tramadol, and oxycodone controlled-release), and capsaicin are probably effective and should be considered for treatment of PDN (Level B). Other treatments have less robust evidence or the evidence is negative. Effective treatments for PDN are available, but many have side effects that limit their usefulness, and few studies have sufficient information on treatment effects on function and QOL. PM R 2011;3:345-352 Diabetic sensorimotor polyneuropathy represents a diffuse symmetrical and length-dependent injury to peripheral nerves that has major implications on quality of life (QOL), morbidity, and costs from a public health perspective [1,2]. Painful diabetic neuropathy (PDN) affects 16% of patients with diabetes, and it is frequently unreported (12.5%) and more frequently untreated (39%) . PDN presents an ongoing management problem for patients, caregivers, and physicians. There are many treatment options available, and a rational approach to treating the patient with PDN requires an understanding of the evidence for each intervention. This guideline addresses the efficacy of pharmacological and nonpharmacological treatments to reduce pain and improve physical function and QOL in patients with PDN. The pharmacological agents reviewed include anticonvulsants, antidepressants, opioids, antiarrhythmics, cannabinoids, aldose reductase inhibitors, protein kinase C beta inhibitors, antioxidants (alpha lipoic acid), transketolase activators (thiamines and allithiamines), topical medications (analgesic patches, anesthetic patches, capsaicin cream, clonidine), and others. The nonpharmacological modalities include infrared therapy, shoe magnets, exercise, acupuncture, external stimulation (TENS), spinal cord stimulation, biofeedback and behavioral therapy, surgical decompression, and intrathecal baclofen.
Evaluation in Diagnosis and Management of Diabetic Neuropathy
Journal of Diabetes Mellitus, 2021
The 100-year anniversary of insulin is explored by focusing on diabetic neuropathy. Neuropathy is so common to diabetes, it is well described even in the earliest accounts of diabetes. This article reviews the most common neuropathy syndromes, and the consensus of effective treatment for neuropathic pain. Pharmacological advances in neuropathy are still largely focused on pain control, not neuropathy intervention. The article reviews the established and lesser tested therapies used for pain control. It also reviews the pathophysiology of the disease state, including the many factors and steps that culminate to produce neuropathy and its different iterations. In the future, new ways to treat diabetic neuropathy may be geared toward treating specific pathophysiological step-points on the way to nerve damage. In the future, prevention and a deeper look at the impact of socioeconomic status as a predictor of diabetes will hopefully encompass a bigger part of pre-diabetic care.
Painful diabetic neuropathy: Diagnosis and management
Diabetes & Metabolism, 2011
The prevalence of painful diabetic peripheral neuropathy (PDN) is about 20% in patients with type 2 diabetes and 5% in those with type 1. Patients should be systematically questioned concerning suggestive symptoms, as they are not usually volunteers. As PDN is due to small-fibre injury, the 10 g monofilament pressure test as well as the standard electrophysiological procedures may be normal. Diagnosis is based on clinical findings: type of pain (burning discomfort, electric shock-like sensation, aching coldness in the lower limbs); time of occurrence (mostly at rest and at night); and abnormal sensations (such as tingling or numbness). The DN4 questionnaire is an easy-to-use validated diagnostic tool. Three classes of drugs are of equal value in treating PDN: tricyclic antidepressants; anticonvulsants; and selective serotonin-reuptake inhibitors. These compounds may be prescribed as first-line therapy following pain assessment using a visual analogue scale. If the initial drug at its maximum tolerated dose does not lead to a decrease in pain of at least 30%, another drug class should be prescribed; if the pain is decreased by 30% but remains greater than 3/10, a drug from a different class may be given in association.