Delirium After Pregabalin Withdrawal.

Off-Label Use of Gabapentinoids: A New Paradigm

Limited research exists to support the extrapolation of the analgesic efficacy of pregabalin from one neuropathic pain condition to another. This retrospective analysis evaluated similarities in the efficacy of pregabalin for treating neuropathic pain associated with post-herpetic neuralgia (PHN), diabetic peripheral neuropathy (DPN), and spinal cord injury (SCI) in a Japanese population, as a basis for considering the extrapolation of these data to other neuropathic pain conditions. Data were analysed across pregabalin doses within each pain condition, from three comparable 13- to 16-week, randomized, double-blind, placebo-controlled trials (RCTs) and the corresponding 52-week, open-label extension trials of pregabalin in Japanese patients with PHN, DPN or SCI. Efficacy outcomes in the RCTs included endpoint and weekly mean pain and sleep interference scores; endpoint proportions of responders in pain; Patient Global Impression of Change scores; and 36-Item Short Form Health Survey (SF-36) scores or Hospital Anxiety and Depression Scale (HADS) assessments. Study discontinuation rates were compared between treatment groups. The extension trials assessed pain intensity, using the Short-Form McGill Pain Questionnaire. In the RCTs for all pain conditions, significant improvements in comparison with placebo in mean pain and sleep interference scores were evident after 1 week with pregabalin and were sustained throughout the treatment periods (p < 0.05). At the study endpoint, in comparison with placebo, a significantly greater percentage of pregabalin-treated patients experienced a ≥30 % reduction in pain across the RCTs (p < 0.05), and pregabalin significantly improved six of 16 SF-36 subscale scores in the PHN and DPN trials (p < 0.05). In the SCI trial, pregabalin-treated patients had numerically better outcomes of HADS scores. In the extension trials, improvements in pain intensity were maintained over a 52-week period. Similarities in the pregabalin efficacy profiles, including time to onset and magnitude of response, were confirmed regardless of the neuropathic pain condition. These data support the potential for extrapolating analgesic efficacy to other neuropathic pain conditions. CLINICALTRIALS. NCT00394901, NCT00553475, NCT00407745, NCT00424372, NCT00553280, NCT01202227.

Neuropathic pain involving an upper extremity may be due to a variety of peripheral or central neuropathies such as cervical radiculopathy, carpal tunnel syndrome, diabetic polyneuropathy, postherpetic neuralgia, human immunodeficiency virus–related neuropathies, central post-stroke pain, multiple sclerosis, and spinal cord injury. Montgomery et al present an interesting case of a patient with cervical radiculopathy and myelopathy that resolved after a two-level anterior cervical diskectomy and fusion. However, the patient's radicular symptoms recurred 6 months later. A thorough workup and the eventual development of a herpetic rash demonstrated that this new pain was due to herpes zoster (shingles). Although not specifically mentioned, it is also important to note that patients with herpes zoster may present with signs of weakness in addition to radicular pain, as postherpetic neuralgia may develop into zoster-associated limb paresis that lasts several months.1 Although the most common causes of neuropathic pain involving an arm are from cervical radiculopathy (estimated incidence: 83/100,000) and carpal tunnel syndrome (estimated incidence: 105 to 276/1000), the next most common causes are diabetic peripheral neuropathy (estimated incidence: 15/100,000) and postherpetic neuralgia (estimated incidence: 11 to 40/100,000).2 As the authors present here, the presence of two different causes of radiculopathy in such a narrow time period is exceedingly rare. This report emphasizes the need to broaden the differential for recurrent arm pain, especially when patients have risk factors for herpes zoster, such as an advanced age, a weakened immune system, or increased physical stress. In addition to clinical risk factors for herpes zoster, the clinical exam may also help differentiate between cervical radiculopathy from herpes zoster or postherpetic neuralgia. Unfortunately, the specific type of pain was not described in this report. Patients with painful polyneuropathy or postherpetic neuralgia typically suffer from a burning pain and mechanical allodynia, whereas painful radiculopathy is usually described as lancinating or “electric-like” in nature. One theory is that the two types of pain are from different pain generators: radiculopathy is often due to a lesion proximal to the dorsal root ganglion, and postherpetic neuralgia affects the ganglion.3 Recurrent radiculopathy after cervical decompression is not uncommon, and Montgomery et al highlight the fact that a herpes zoster infection as well as other causes of cervical neuropathic pain should remain on the differential diagnosis. Appropriate additional imaging and studies should be performed to rule out cervical spinal stenosis, carpal tunnel syndrome, and polyneuropathies. In addition, a detailed and accurate physical examination may assist in determining the etiology.

Key words : diabetic peripheral neuropathy, neuropathic pain, postherpetic neuralgia, pregabalin, randomized clinical trials, spinal cord injury. Introduction and Overview Neuropathic pain is caused by lesions or diseases affecting somatosensory pathways within the peripheral or central nervous system (IASP Special Interest Group on Neuropathic Pain, 2006; Merskey & Bogduk, 1994). Chronic neuropathic pain is common in clinical practice, and patients with conditions such as diabetic peripheral neuropathy (DPN), HIV sensory neuropathy, and spinal cord injury suffer from neuropathic pain that impairs their health-related quality of life, causing physical disability and emotional distress (Jensen et al ., 2007). The distinction between neuropathic pain and non-neuropathic inflammatory or musculoskeletal pain is important because it reflects at least partially distinct pathophysiologic mechanisms and somewhat different patterns of treatment efficacy. Neuropathic pain can be diagnosed based on a medical history of a nervous system lesion or disease consistent with the patient's report of pain and neurological examination findings of negative and positive sensory phenomena in the same area innervated by damaged nervous system pathways (Dworkin et al ., 2003a). Chronic neuropathic pain is more common than generally appreciated, with as many as three million patients with painful DPN (Schmader, 2002) and one million patients with postherpetic neuralgia (PHN) (Bowsher, 1999) in the United States. Until relatively recently, there were few treatments available with established efficacy for patients with chronic neuropathic pain. On the basis of results from randomized placebo-controlled trials published within the past several years (Dworkin et al ., in press; Finnerup et al ., 2005), an evidence-based treatment approach for patients with chronic neuropathic pain is now possible.

Painful peripheral neuropathy is a common complication of diabetes that is often difficult to treat. Typically, treatment involves varying combinations of opiates, tricyclic antidepressants and anticonvulsants. Factors including side effects, drug interactions and patient adherence often limit control of symptoms. Topical lidocaine therapy has been used for the treatment of postherpetic neuralgia for some time. No large scale trials have been carried out reviewing the use of topical lidocaine therapy in diabetic peripheral neuropathy, but there is evidence to suggest that topical lidocaine therapy may be a treatment option for painful diabetic peripheral neuropathy. Figure 1 outlines the pharmacological action of the topical anaesthetic lidocaine. It acts directly on nerve cells to block conduction of impulses down axons, therefore blocking transmission of nociceptive signals. Structurally, lidocaine contains a hydrophilic amide and a hydrophobic aromatic portion allowing it to diffuse to the nerves and through perineural tissue. Mechanism of action of lidocaine At a molecular level, lidocaine binds to voltage-gated sodium channels. This binding occurs at the intracellular surface. By binding to the channel, sodium influx is blocked and the depolarisation required for action potentials to be generated is inhibited. As a result, impulse conduction is blocked. Local anaesthetics such as lidocaine are weak bases, requiring a local pH of between 8 and 10 for efficacy. Clinically, a common comorbidity in diabetic peripheral neuropathy is ulceration/local tissue infection. This results in a localised metabolic acidosis, dropping the pH and reducing the ability of the lidocaine to permeate through cell membranes, thus reducing its clinical effect. Topical use of the drug has relatively few systemic side effects. The drug is either resorbed through the capillaries into the vasculature and hepatically cleared, or metabolised locally. Following this, nerve function returns to its previous state. A number of randomised controlled trials have now demonstrated the tolerability and effectiveness of 5% lidocaine patches for the treatment of postherpetic neuralgia (PHN). In a double-blind, randomised, placebo cross-over trial comparing lidocaine patch to a placebo vehicle patch in the treatment of PHN, 32 patients suffering from PHN were randomised into two groups, one receiving lidocaine patch and the other placebo.1 The trial consisted of two phases (placebo phase/lidocaine phase), each for a maximum of 14 days. Patients in both groups underwent daily assessment of their pain control via interview using a six-point Pain Relief Scale (5 = complete relief of pain, 4 = a lot of relief, 3 = moderate relief, 2 = slight relief, 1 = no change, 0 = worse pain). During the trial, a total of three patches were applied to the area of pain. A pain score deterioration of two or more points over two or more days led to exit from a trial phase. The mean outcome measure was average time to exit each phase. For the lidocaine patch this was 14 days, and 3.8 days for the vehicle patch. Twenty-nine of the trial patients (90%) reported a pain score of four to five for at least five days. In a similar randomised, double-blind, placebo-controlled study, 58 patients were recruited and treated in two trial phases with lidocaine or placebo.2 Participants had a variety of underlying pathologies causing neuropathy, including PHN, meralgia paraesthetica and post-surgical neuralgia. Evaluation of the patch efficacy involved an assessment of pain score and quality of sleep. The results of this study confirmed a reduction in pain and improvement in sleep quality during the lidocaine treatment phase. Data produced suggested that the number needed to treat (NNT) for one patient to have a 50% reduction in pain was 4.4, and for a pain reduction of 30% the NNT was 3.6. There are few trials exclusively reviewing the efficacy of 5% lidocaine patches in the treatment of painful diabetic peripheral neuro pathy. There are no randomised controlled trials that we could find in the literature. In an open-label study, with flexible dosing using 5% lidocaine patch therapy in painful diabetic peripheral neuropathy, 53 patients were studied for a three-week duration.3 Inclusion criteria included a greater than three-month duration of neuropathy pain, Brief Pain Inventory (BPI) rating of >4, and stable analgesic regimen for at least one week. Patients with open wounds or previous lidocaine treatment were excluded. The primary outcome variable was the change in mean daily pain diary ratings from baseline to week three. Secondary outcome measures of change from baseline to week three and baseline to week eight included the additional pain measures (Short Form McGill Pain Questionnaire [SFMPQ], pain quality and intensity scales and BPI pain relief), the health-related quality-of-life (QOL) measures (sleep quality, pain interference, depression and mood), and assessments of safety and tolerability. Patients applied four patches daily, for 18 hours. Patients recorded daily pain scores. During the three-week study period, patients were not allowed to titrate their other analgesics, which included opiates and tricyclics. The results showed that 70% (37) of patients had a reduction in pain of at least 30% from baseline to week three. No dose titration of patches was needed to achieve these results. The pain reduction was also accompanied by improvement in sleep quality and BPI score. Twenty-eight of the patients underwent an additional five-week study period during which they were allowed to alter the dosages of their usual pain medications as required. None of these patients had to increase their analgesics and several reduced their dosages. Three patients were able to discontinue other treatments, including amitriptyline and gabapentin. From the trials described here, including those in PHN, no severe adverse effects of 5% lidocaine patches were noted. In all of the trials there were reports of local skin reactions with the patch. Reactions included burning, itch and local rash. The incidence of these was variable but, in one placebo-controlled trial, the vehicle placebo patch had a similar incidence of local reactions.1 No systemic side effects were noted in any of the trials. In the open-label diabetes study,3 peak lignocaine concentrations 12 hours post application of patch were well below 1.5μg/ml (the level associated with a potential antiarrythmic effect). A further safety study4 confirmed safe blood levels of lidocaine with a dose of four patches/18 hours per day (the dose licensed for PHN by the US Food and Drug Administration). There is established evidence that topical lidocaine therapy is effective in the treatment of peripheral neuropathic pain syndromes, particularly PHN. This therapy has been shown to improve pain control and quality of life. It is a well tolerated therapy with no systemic side effects reported. All side effects reported were localised to site of application. Some evidence is available that shows positive outcomes on pain control in patients with painful diabetic peripheral neuropathy, but a large scale, randomised clinical trial is required to confirm the benefits. There are no conflicts of interest. Topical lidocaine acts in peripheral neuropathic pain to block nerve conduction and suppresses spontaneous ectopic discharge from damaged peripheral nerves Topical therapy can produce significant reductions in patient perceived pain scores, without the need for dose titration or the development of systemic side effects There is a need for a randomised controlled trial to confirm effectiveness of use in painful diabetic peripheral neuropathy

BackgroundThe anticonvulsants pregabalin and gabapentin are both indicated for the treatment of peripheral neuropathic pain. The decision on which treatment provides the best alternative, should take into account all aspects of costs and outcomes associated with the two therapeutic options. The objective of this study was to examine the cost – effectiveness of the two agents in the management of patients with painful diabetic neuropathy or post – herpetic neuralgia, under the third party payer perspective in Greece.MethodsThe analysis was based on a dynamic simulation model which estimated and compared the costs and outcomes of pregabalin and gabapentin in a hypothetical cohort of 1,000 patients suffering from painful Diabetic Peripheral Neuropathy (DPN) or Post-Herpetic Neuralgia (PHN). In the model, each patient was randomly allocated an average pretreatment pain score, measured using an eleven-point visual analogue scale (0 – 10) and was “run through” the model, simulating their daily pain intensity and allowing for stochastic calculation of outcomes, taking into account medical interventions and the effectiveness of each treatment.ResultsPregabalin demonstrated a reduction in days with moderate to severe pain when compared to gabapentin. During the 12 weeks the pregabalin arm demonstrated a 0.1178 (SE 0.0002) QALY gain, which proved to be 0.0063 (SE 0.0003) higher than that in the gabapentin arm. The mean medication cost per patient was higher for the pregabalin arm when compared to the gabapentin arm (i.e. €134.40) over the 12 week treatment period. However, this higher cost was partially offset by the reduced direct medical costs (i.e. the cost of specialist visits, the cost of diagnostic tests and the other applied interventions). Comparing costs with respective outcomes, the ICERs for pregabalin versus gabapentin were €13 (95%CI: 8 – 18) per additional day with no or mild pain and €19,320 (95%CI: 11,743 – 26,755) per QALY gained.ConclusionsNeuropathic pain carries a great disease burden for patients and society and, is also, associated with a significant economic burden. The treatment of pain associated with DPN and PHN with pregabalin is a cost-effective intervention for the social security in Greece compared to gabapentin. Thus, these findings need to be taken into consideration in the decision – making process when considering which therapy to use for the treatment of neuropathic pain.

There are few repeated dose-controlled trials of N-methyl-d-aspartate glutamate receptor antagonists in patients with neuropathic pain. The authors sought to evaluate two low-affinity N-methyl-d-aspartate antagonists using a novel two-stage design. The authors studied patients with painful diabetic neuropathy (DN) and postherpetic neuralgia (PHN) in two crossover trials: (1) efficacy trial (dextromethorphan vs. memantine vs. active placebo [lorazepam]) and (2) dose-response trial of the preferred active drug in responders from the first study (0% vs. 25% vs. 50% vs. 100% of each patient's maximally tolerated dose). Pain intensity was measured on a 20-point scale. Nineteen of 23 DN patients and 17 of 21 PHN patients completed the efficacy trial. Median doses for DN and PHN were 400 and 400 mg/day dextromethorphan, 55 and 35 mg/day memantine, and 1.8 and 1.2 mg/day lorazepam. In the efficacy trial, among patients with DN, dextromethorphan reduced pain intensity by a mean of 33% from baseline, memantine reduced pain intensity by a mean of 17%, and lorazepam reduced pain intensity by a mean of 16%; the proportions of subjects achieving greater than moderate pain relief were 68% with dextromethorphan, 47% with memantine, and 37% with lorazepam. Mean reductions in pain intensity in patients with PHN were 6% with dextromethorphan, 2% with memantine, and 0% with lorazepam. No comparison with placebo reached statistical significance in the efficacy trial. In the 10 DN subjects who responded to dextromethorphan, there was a significant dose-response effect on pain intensity (P = 0.035), with the highest dose significantly better than that of lorazepam (P = 0.03). Dextromethorphan is effective in a dose-related fashion in selected patients with DN. This was not true of PHN, suggesting a difference in pain mechanisms. Selective approaches to pain-relevant N-methyl-d-aspartate receptors are warranted.

Long term results of Dorsal Root Entry Zone (DREZ) lesions for the treatment of intractable pain: A systematic review of the literature on 1242 cases

Background: Neuropathic pain (NeP) is caused by a disease like lesion; it is the disease of the somatosensory nervous system. NeP also caused some severe health disorders such as diabetic peripheral neuropathy (DPN), postherpetic neuralgia (PHN), and spinal cord injury (SCI). Along with the severe health issues, NeP adversely affects the quality of life (QOL) as well as an economic burden on the infected persons and their family plus society.Aim: The aim of the study is to define the efficiency of pregabalin for the treatment of moderate or severe baseline neuropathic pain at a tertiary care centre in Ganjam, Odisha.Materials and Methods: It was a randomized study conducted between August 2019 and January 2020 at the MKCG Medical College Berhampur, Ganjam, Odisha on 700 patients. Simple randomization technique was employed to give patients either pregabalin or placebo. All the patients aged &gt;18 years were selected for the study. The pain was assessed for all the patients using the 11-point numeric rating scale, where 0 = no pain and 10 = worst possible pain. All the patients having pain score &gt;4 were involved in the study. Patients who were below 18 years of age were omitted from the study. Further, the patients whose painscore was below four were also omitted from the study.Results: It was observed that there were 455 patients in the Pregabalin group, and in the placebo group, there were 245 patients. The patients were also bifurcated as per the severity of their discomfort, in which 513 patients were comprised in the moderate section, whereas 187 patients were encompassed in the severe section. 63-71 years was the median age. In the moderate and severe pain group, standard mean pain scores were equivalent among the pregabalin and placebo treatment groups. There was a statistically significant difference among both the groups with respect to the change in pain score. This implies that pregabalinreduced pain more significantly as compared to the placebo group. The above table also depicted the improvement in mean sleep scores as well. There was a statistically significant difference among both the groups with respect to the sleep scores. The sleep score in the pregabalin group improved from the baseline to endpoint more significantly as compared to the placebo group. In the moderate to severe pregabalin group, 90% of the patients experienced at least one treatment-emergent as compared to 70% in the placebo group. The most common side effects of the AE were weight gain, dizziness, and peripheral edema. The highest discontinuation from the study was observed in the pregabalin group.Conclusion: It was found that the pregabalin was effective in terms of reducing pain and had greater tolerability with the patients. It was also identified that the patients in the severe pain segment shifted to mild segment with the use of pregabalin dosage.

Integrating information on physical function and pain intensity into a composite measure may provide a useful method for assessing treatment efficacy in clinical trials of chronic pain. Accordingly, we evaluated composite outcomes in trials of duloxetine, gabapentin, and pregabalin. Data on 2287 patients in 9 trials for painful diabetic peripheral neuropathy (DPN) and 1513 patients in 6 trials for postherpetic neuralgia (PHN) were analyzed. All trials assessed pain intensity on a 0 to 10 numeric rating scale and physical function with the 10-item subscale of the Short Form-36, ranging 0 to 100 with higher scores indicating better function. Correlation between change in pain intensity from baseline to posttreatment and change in physical function was small in DPN (ρ = -0.22; P < 0.001) and nonsignificant in PHN (ρ = -0.05; P = 0.08). Assay sensitivities of 10 composite outcomes were examined in a random subsample of patients enrolled in pregabalin trials for DPN and PHN. Of these, a responder outcome of ≥50% improvement in pain intensity, or a ≥20% improvement in pain intensity and ≥30% improvement in physical function was not only significantly associated with pregabalin vs placebo in the development cohorts for both pain conditions but also in the validation cohorts. Furthermore, this composite outcome was cross-validated in trials of gabapentin for PHN and duloxetine for DPN, and had slightly lower number needed to treat than a standard responder outcome of ≥50% reduction in pain intensity. In summary, this study identified a composite outcome of pain intensity and physical function that may improve the assay sensitivity of future neuropathic pain trials.

Efficacy of Pregabalin for Peripheral Neuropathic Pain: Results of an 8-Week, Flexible-Dose, Double-Blind, Placebo-Controlled Study Conducted in China

Valproic acid and its sodium salt (sodium valproate) are antiepileptic drugs that are sometimes used to treat chronic neuropathic pain and fibromyalgia, although they are not licensed for this use. To evaluate the analgesic efficacy and adverse effects of valproic acid and sodium valproate in the management of chronic neuropathic pain and fibromyalgia. We identified randomised controlled trials (RCTs) of valproic acid and sodium valproate in acute, and chronic pain by searching MEDLINE, EMBASE and Cochrane CENTRAL to June 2011, together with reference lists of retrieved papers and reviews. RCTs that were double blind and of eight-weeks duration or longer, reporting on analgesic effects and adverse events with valproic acid and sodium valproate in the treatment of chronic neuropathic pain and fibromyalgia. Two review authors independently extracted results and scored for quality. We extracted efficacy and adverse event data, and examined issues of study quality. We included three studies, two in diabetic neuropathy (42 participants treated with valproate, 42 with placebo), and one in post-herpetic neuralgia (23 treated with divalproex sodium, 22 with placebo). Study duration was eight or 12 weeks. No studies were found in fibromyalgia.Only one study reported one of our primary outcomes (≥ 50% pain relief), while all three reported group means for pain reduction from baseline to endpoint. In all three studies; efficacy results were given only for participants who completed the study. One study in diabetic neuropathy and the study in post-herpetic neuralgia reported significant differences between active and placebo groups, but there were insufficient data for reliable pooled analysis.More adverse events were reported with active treatment than placebo, and included nausea, drowsiness and abnormal liver function tests. One participant taking sodium valproate withdrew due to serious derangement of liver enzymes. These three studies no more than hint that sodium valproate may reduce pain in diabetic neuropathy, and divalproex sodium in post-herpetic neuralgia, but the use of 'completer' analysis may overestimate efficacy, and there were too few data for pooled analysis of efficacy or harm, or to have confidence in the results of the individual studies. There is insufficient evidence to support the use of valproic acid or sodium valproate as a first-line treatment for neuropathic pain. There is more robust evidence of greater efficacy for a small number of other drugs.

Topical analgesics: Lidocaine patch 5% effectively treats neuropathic pain qualities in three chronic pain states: results of a 2-week, prospective, open-label trial

The results of 3 proof-of-concept studies to evaluate carisbamate's efficacy and safety in treating neuropathic pain are presented. In studies 1 (postherpetic neuralgia, n=91) and 2 (diabetic neuropathy, n=137), patients received carisbamate 400mg/day or placebo for 4weeks and then crossed over to the other treatment for 4weeks. In study 3 (diabetic neuropathy, higher carisbamate doses), patients (n=386) were randomized (1:1:1:1) to receive either carisbamate 800mg/day, 1200mg/day, pregabalin 300mg/day or placebo for 15weeks. Primary efficacy end point was the mean of the last 7 average daily pain scores obtained on days the study drug was taken, for all 3 studies. Least square mean (95% CI) differences between carisbamate and placebo groups on the primary end point were as follows: study 1: -0.512 (-1.32, 0.29) carisbamate 400mg/day; study 2: -0.307 (-0.94, 0.33) carisbamate 400mg/day; and study 3: -0.51 (-1.10, 0.08), carisbamate 800mg/day; -0.55 (-1.13, 0.04), carisbamate 1200mg/day; and -0.43 (-1.01, 0.15), pregabalin 300mg/day. Neither carisbamate (all 3 studies) nor pregabalin (study 3) significantly differed from placebo, although multiple secondary end points showed significant improvement in efficacy with carisbamate in studies 1 and 2. Dizziness was the only treatment-emergent adverse event occurring at ≥10% difference in carisbamate groups versus placebo (study 1: 12% vs. 1%; study 3: 14% vs. 4%; study 2: 1% vs. 2%). Carisbamate, although well tolerated, did not demonstrate efficacy in neuropathic pain across these studies, nor did the active comparator pregabalin (study 3).

Diabetic neuropathy and reduced sleep quality are both frequent complications of diabetes mellitus, yet their interaction and mutual influence remain poorly understood. This review aimed to synthesize current evidence on the association between diabetic neuropathy and sleep quality. A systematic literature search was conducted in PubMed, Embase, and the Cochrane Library. Of 1356 identified records, 32 studies met the inclusion criteria. Three randomized clinical trials were included in a post-hoc exploratory meta-analysis to evaluate the effect of gabapentinoids on Sleep Interference Scores in people with painful diabetic peripheral neuropathy. Our evidence synthesis showed that sleep disturbances were more prevalent in people with diabetic peripheral neuropathy compared to people without, especially in those experiencing neuropathic pain. Obstructive sleep apnea was common in individuals with autonomic neuropathy. Furthermore, poor sleep quality in diabetes mellitus may itself increase the risk of developing diabetic neuropathy. The pooled overall mean difference in Sleep Interference Scores was -1.07 (95% CI: -1.86 to -0.28), although heterogeneity was high (I2=83%). These findings indicate that poor sleep quality is highly prevalent in people with diabetic neuropathy, especially in those with neuropathic pain. Gabapentinoids appear to reduce Sleep Interference Scores in people with painful diabetic peripheral neuropathy.