Management of diabetic neuropathy by sodium valproate and glyceryl trinitrate spray: A prospective double-blind randomized placebo-controlled study (original) (raw)
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Acta Neurologica Scandinavica, 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.
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.
Diabetes Research and Clinical Practice, 2007
Objectives: Various drugs are effective in the management of painful diabetic neuropathy, but none is completely satisfactory. The objective of this study is to test the effectiveness and safety aspect of glyceryl trinitrate (GTN) in the management of painful diabetic neuropathy as a nitric oxide (NO) donor with local vasodilating properties in spray form. Design: Randomized double blind placebo controlled cross-over study. Methods: Fifty patients with painful diabetic neuropathy (type 2) were screened consecutively, out of which two were excluded (1 with HbA 1 c > 11 and one withdrew his consent). The remaining 48 were given either drug (group A) or placebo (group B) in the first phase. After thorough clinical assessment in the first phase, quantitative assessment of pain was done by McGill Pain Questionnaire, Visual Analogue Score, Present Pain Intensity and 11 point Lickerts Scale, at the beginning and after 4 weeks, followed by 2 weeks wash out period and thereafter receiving 4 weeks of cross-over regimen. Adverse drug effects were assessed periodically. Results: Of the 48 patients, five dropped out, two in group A and three in group B. Both groups A and B experienced significant improvement in pain score in their drug phase of trial, when compared to placebo phase of other group ( p < 0.001). After crossing over the treatment arm, patients of group B observed significant improvement in all pain scores compared to group A ( p < 0.001). The numbers needed to treat (NNT) calculated on VAS as pain parameters came out to be 4. The drug was well tolerated by all the patients except palpitation and headache for some days in five patients. Conclusion: GTN spray, a well tolerated drug, provides significant improvement in painful diabetic neuropathy. These data provide a basis for future trials for longer duration in a larger group of 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.
Treatment of painful diabetic neuropathy
Therapeutic Advances in Chronic Disease, 2014
Painful diabetic neuropathy (PDN) is a debilitating consequence of diabetes that may be present in as many as one in five patients with diabetes. The objective assessment of PDN is difficult, making it challenging to diagnose and assess in both clinical practice and clinical trials. No single treatment exists to prevent or reverse neuropathic changes or to provide total pain relief. Treatment of PDN is based on three major approaches: intensive glycaemic control and risk factor management, treatments based on pathogenetic mechanisms, and symptomatic pain management. Clinical guidelines recommend pain relief in PDN through the use of antidepressants such as amitriptyline and duloxetine, the γ-aminobutyric acid analogues gabapentin and pregabalin, opioids and topical agents such as capsaicin. Of these medications, duloxetine and pregabalin were approved by the US Food and Drug Administration (FDA) in 2004 and tapentadol extended release was approved in 2012 for the treatment of PDN. P...
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.
Role of Different Pain Killers in Control of Diabetic Neuropathy Pain-A Review
BJSTR
Diabetic neuropathy [DN) is a continual complication of diabetes mellitus (DM). It has an approximate pervasiveness ranging from thirty to fifty percent in subjects suffering from this disease, depending on the technique utilized for diagnosis. Additionally, DM has remained the top causative factor of polyneuropathy in the modern world. As much as fifty percent of the polyneuropathies are related to DM. It is more common in chronic DM: it negatively impacts the quality of life (QOL) in those suffering from it. Polyneuropathies cause chronic neuropathic pain, resulting in depression, anxiety, and insomnia among sufferers. Diabetic neuropathy is a painful and disabling condition that has enormous incurring costs in terms of disrupted quality of life and financial implication while treating its complications. Various pain killers have been tried in this regard with varying results. Aim of this review was to delve into various drugs outcomes in this regard.
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.