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Tremor and Other Hyperkinetic Movements... 2023The objective of this review is to provide updated information on the epidemiology, correlating factors and treatment of chronic kidney disease associated restless legs... (Review)
Review
OBJECTIVES
The objective of this review is to provide updated information on the epidemiology, correlating factors and treatment of chronic kidney disease associated restless legs syndrome (CKD-A-RLS) in both adult and pediatric population.
MATERIALS AND METHODS
We have reviewed the Medline search and Google Scholar search up to May 2022, using key words restless legs syndrome, chronic kidney disease and hemodialysis and kidney transplant. The reviewed articles were studied for epidemiology, correlating factors, as well as pharmacologic and non-pharmacologic treatment options.
RESULTS
Our search revealed 175 articles, 111 were clinical trials or cross- sectional studies and 64 were review articles. All 111 articles were retrieved and studied in detail. Of these, 105 focused on adults and 6 on children. A majority of studies on dialysis patients reported a prevalence between 15-30%, which is notably higher than prevalence of RLS in general population (5-10%). The correlation between presence of CKD-A-RLS with age, gender, abnormalities of hemogram, iron, ferritin, serum lipids, electrolytes and parathyroid hormones were also reviewed. The results were inconsistent and controversial. Limited studies have reported on the treatment of CKD-A-RLS. Non-pharmacological treatment focused on the effect(s) of exercise, acupuncture, massage with different oils and infra-red light whereas, pharmacologic treatment options include the effects of dopaminergic drugs, Alpha2-Delta ligands (gabapentin and pregabalin), vitamins E and C, and intravenous iron infusion.
CONCLUSION
This updated review showed that RLS is two to three times more common in patients with CKD compared to the general population. More patients with CKD-A-RLS demonstrated increased mortality, increased incidence of cardiovascular accident, depression, insomnia and impaired quality of life than those with CKD without RLS. Dopaminergic drugs such as levodopa, ropinirole, pramipexole and rotigotine as well as calcium channel blockers (gabapentin and pregabalin) are helpful for treatment of RLS. High quality studies with these agents are currently underway and hopefully confirm the efficacy and practicality of using these drugs in CKD-A-RLS. Some studies have shown that aerobic exercise and massage with lavender oil can improve symptoms of CKD-A- RLS suggesting that these measures can be useful as adjunct therapy.
Topics: Humans; Child; Gabapentin; Restless Legs Syndrome; Pregabalin; Quality of Life; Dopamine Agents; Renal Insufficiency, Chronic; Iron
PubMed: 37008995
DOI: 10.5334/tohm.752 -
Clinical Journal of the American... Jun 2019Pain is common and poorly managed in patients with advanced CKD, likely due to both under and over prescription of appropriate analgesics. Poorly managed pain...
Pain is common and poorly managed in patients with advanced CKD, likely due to both under and over prescription of appropriate analgesics. Poorly managed pain contributes to patients' poor quality of life and excessive health care use. There is tremendous variability within and between countries in prescribing patterns of analgesics, suggesting that factors other than patient characteristics account for these differences. This article discusses the pharmacologic management of acute and chronic pain in patients with advanced CKD, and the role analgesics, including opioids, play in the overall approach to pain management.
Topics: Acetaminophen; Acute Pain; Analgesics, Non-Narcotic; Analgesics, Opioid; Carbamazepine; Chronic Pain; Gabapentin; Humans; Ketamine; Kidney Failure, Chronic; Neuralgia; Nociceptive Pain; Pain Management; Renal Dialysis
PubMed: 30833302
DOI: 10.2215/CJN.05180418 -
The Journal of Headache and Pain May 2023While there are several trials that support the efficacy of various drugs for migraine prophylaxis against placebo, there is limited evidence addressing the comparative... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
While there are several trials that support the efficacy of various drugs for migraine prophylaxis against placebo, there is limited evidence addressing the comparative safety and efficacy of these drugs. We conducted a systematic review and network meta-analysis to facilitate comparison between drugs for migraine prophylaxis.
METHODS
We searched MEDLINE, EMBASE, CENTRAL, and clinicaltrials.gov from inception to August 13, 2022, for randomized trials of pharmacological treatments for migraine prophylaxis in adults. Reviewers worked independently and in duplicate to screen references, extract data, and assess risk of bias. We performed a frequentist random-effects network meta-analysis and rated the certainty (quality) of evidence as either high, moderate, low, or very low using the GRADE approach.
RESULTS
We identified 74 eligible trials, reporting on 32,990 patients. We found high certainty evidence that monoclonal antibodies acting on the calcitonin gene related peptide or its receptor (CGRP(r)mAbs), gepants, and topiramate increase the proportion of patients who experience a 50% or more reduction in monthly migraine days, compared to placebo. We found moderate certainty evidence that beta-blockers, valproate, and amitriptyline increase the proportion of patients who experience a 50% or more reduction in monthly migraine days, and low certainty evidence that gabapentin may not be different from placebo. We found high certainty evidence that, compared to placebo, valproate and amitriptyline lead to substantial adverse events leading to discontinuation, moderate certainty evidence that topiramate, beta-blockers, and gabapentin increase adverse events leading to discontinuation, and moderate to high certainty evidence that (CGRP(r)mAbs) and gepants do not increase adverse events.
CONCLUSIONS
(CGRP(r)mAbs) have the best safety and efficacy profile of all drugs for migraine prophylaxis, followed closely by gepants.
Topics: Adult; Humans; Topiramate; Valproic Acid; Gabapentin; Calcitonin Gene-Related Peptide; Network Meta-Analysis; Amitriptyline; Antibodies, Monoclonal; Migraine Disorders
PubMed: 37208596
DOI: 10.1186/s10194-023-01594-1 -
International Journal of Molecular... May 2020Post-burn pruritus is the pruritus that occurs after burn during the rehabilitation and healing process of burn wounds. The post-burn pruritus is a common and serious... (Review)
Review
Post-burn pruritus is the pruritus that occurs after burn during the rehabilitation and healing process of burn wounds. The post-burn pruritus is a common and serious complication of burn injury, which severely lowers the quality of life of the patient. Many potential treatments are available for pruritus but there is no consensus of the best single treatment yet. The precise mechanism of post-burn pruritus has not been elucidated, but it appears to have pruritogenic and neuropathic aspects. Clinically, post-burn pruritus tends to be intractable to conventional treatment but rather responds to neuroleptic agents, such as gabapentin and pregabalin. During wound healing, various neuropeptides secreted from the nerves of the skin control epidermal and vascular proliferation and connective tissue cells. When keratinocytes are activated by an itch-inducing substance, they secrete a variety of inflammatory substances that increase the susceptibility of the itch receptor. There are two mechanisms underlying post-burn neuropathic pruritus. The first one is peripheral sensitization. The second one is the intact nociceptor hypothesis. An effective treatment for post-burn pruritus will also be effective in other neuropathic and intractable itching. In this review, we summarized the interaction and mechanism of keratinocytes, immune cells, and nerve fibers related to post-burn pruritus.
Topics: Animals; Antipsychotic Agents; Burns; Gabapentin; Histamine Antagonists; Humans; Inflammation; Keratinocytes; Narcotic Antagonists; Neuropeptides; Ondansetron; Pregabalin; Pruritus; Receptors, Opioid; Wound Healing
PubMed: 32485929
DOI: 10.3390/ijms21113880 -
JAMA Neurology Jan 2019Optimal pharmacologic treatment for chronic sciatica (CS) is currently unclear. While gabapentin (GBP) and pregabalin (PGB) are both used to treat CS, equipoise exists.... (Comparative Study)
Comparative Study Randomized Controlled Trial
IMPORTANCE
Optimal pharmacologic treatment for chronic sciatica (CS) is currently unclear. While gabapentin (GBP) and pregabalin (PGB) are both used to treat CS, equipoise exists. Nevertheless, pharmaceutical regulation authorities typically subsidize one drug over the other. This hinders interchange wherever the favored drug is either ineffective or ill-tolerated.
OBJECTIVE
To assess GBP vs PGB head to head for the treatment of CS.
DESIGN, SETTING, AND PARTICIPANTS
A preplanned interim analysis of a randomized, double-blind, double-dummy crossover trial of PGB vs GBP for management of CS at half the estimated final sample size was performed in a single-center, tertiary referral public hospital. A total of 20 patients underwent randomization from March 2016 to March 2018, and 2 were excluded with 1 lost to follow-up and the other requiring urgent surgery unrelated to the study. Patients attending a specialist neurosurgery clinic with unilateral CS were considered for trial recruitment. Chronic sciatica was defined as pain lasting for at least 3 months radiating into 1 leg only to, at, or below the knee level. Imaging (magnetic resonance imaging with or without computed tomography) corroborating a root-level lesion concordant with symptoms and/or signs was determined by the trial clinician. Inclusion criteria included patients who had not used GBP and PGB and were 18 years or older. Analyses were intention to treat and began February 2018.
INTERVENTIONS
Randomly assigned participants received GBP (400 mg to 800 mg 3 times a day) then PGB (150 mg to 300 mg twice daily) or vice versa, each taken for 8 weeks. Crossover followed a 1-week washout.
MAIN OUTCOMES AND MEASURES
The primary outcome was pain intensity (10-point visual analog scale) at baseline and 8 weeks. Secondary outcomes included disability (using the Oswestry Disability Index) and severity/frequency of adverse events.
RESULTS
The total trial population (N = 18) consisted mostly of men (11 [61%]) with a mean (SD) age of 57 (16.5) years. A third of the cohort were smokers (5 [28%]), and more than half consumed alcohol (12 [67%]). Gabapentin was superior to PGB, with fewer and less severe adverse events. Both GBP (mean [SD], 7.54 [1.39] to 5.82 [1.72]; P < .001) and PGB (mean [SD], 7.33 [1.30] to 6.38 [1.88]; P = .002) displayed significant visual analog pain intensity scale reduction and Oswestry Disability Index reduction (mean [SD], 59.22 [16.88] to 48.54 [15.52]; P < .001 for both). Head to head, GBP showed superior visual analog pain intensity scale reduction (mean [SD], GBP: 1.72 [1.17] vs PGB: 0.94 [1.09]; P = .035) irrespective of sequence order; however, Oswestry Disability Index reduction was unchanged. Adverse events for PGB were more frequent (PGB, 31 [81%] vs GBP, 7 [19%]; P = .002) especially when PGB was taken first.
CONCLUSIONS AND RELEVANCE
Pregabalin and GBP were both significantly efficacious. However, GBP was superior with fewer and less severe adverse events. Gabapentin should be commenced before PGB to permit optimal crossover of medicines.
TRIAL REGISTRATION
anzctr.org.au Identifier: ACTRN12613000559718.
Topics: Adult; Aged; Analgesics; Chronic Pain; Cross-Over Studies; Double-Blind Method; Female; Gabapentin; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Pregabalin; Sciatica
PubMed: 30326006
DOI: 10.1001/jamaneurol.2018.3077 -
International Journal of Clinical... Jun 2023There are increasing concerns regarding the abusive potential of gabapentinoids putting at risk patients with neuropathic pain requiring long-term pain management. The... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There are increasing concerns regarding the abusive potential of gabapentinoids putting at risk patients with neuropathic pain requiring long-term pain management. The evidence to support this is rather inconcusive.
AIM
This systematic review aimed to evaluate the safety and efficacy of gabapentinoids in the management of neuropathic pain with a focus on randomised controlled trials (RCTs) and categorising the side effects according to the body systems they were affecting.
METHOD
Searches were conducted in MEDLINE (PubMed), EMBASE, Web of Science, PsycoINFO, and CINAHL (EBSCO), and included RCTs to identify and critically appraise studies investigating safety and therapeutic effects of gabapentionoids in adults with neuropathic pain. Data extraction was conducted using an established Cochrane form and the risk-of-bias tool was used in the assessment of quality.
RESULTS
50 studies (12,398 participants) were included. The majority of adverse events pertained to the nervous system (7 effects) or psychiatric (3 effects) disorders. There were more adverse effects reported with pregabalin (36 effects) than with gabapentin (22 effects). Six pregabalin studies reported euphoria as a side effect, while no studies reported euphoria with gabapentin. This was the only side effect that may correlate with addictive potential. Gabapentioids were reported to significantly reduce pain compared to placebo.
CONCLUSION
Despite RCTs documenting the adverse events of gabapentionoids on the nervous system, there was no evidence of gabapentinoid use leading to addiction, suggesting an urgent need to design studies investigating their abusive potential.
Topics: Adult; Humans; Gabapentin; Pregabalin; Analgesics; gamma-Aminobutyric Acid; Amines; Cyclohexanecarboxylic Acids; Neuralgia; Randomized Controlled Trials as Topic
PubMed: 36848024
DOI: 10.1007/s11096-022-01528-y -
Nature Jul 2023Voltage-gated ion channels (VGICs) comprise multiple structural units, the assembly of which is required for function. Structural understanding of how VGIC subunits...
Voltage-gated ion channels (VGICs) comprise multiple structural units, the assembly of which is required for function. Structural understanding of how VGIC subunits assemble and whether chaperone proteins are required is lacking. High-voltage-activated calcium channels (Cas) are paradigmatic multisubunit VGICs whose function and trafficking are powerfully shaped by interactions between pore-forming Ca1 or Ca2 Caα (ref. ), and the auxiliary Caβ and Caαδ subunits. Here we present cryo-electron microscopy structures of human brain and cardiac Ca1.2 bound with Caβ to a chaperone-the endoplasmic reticulum membrane protein complex (EMC)-and of the assembled Ca1.2-Caβ-Caαδ-1 channel. These structures provide a view of an EMC-client complex and define EMC sites-the transmembrane (TM) and cytoplasmic (Cyto) docks; interaction between these sites and the client channel causes partial extraction of a pore subunit and splays open the Caαδ-interaction site. The structures identify the Caαδ-binding site for gabapentinoid anti-pain and anti-anxiety drugs, show that EMC and Caαδ interactions with the channel are mutually exclusive, and indicate that EMC-to-Caαδ hand-off involves a divalent ion-dependent step and Ca1.2 element ordering. Disruption of the EMC-Ca complex compromises Ca function, suggesting that the EMC functions as a channel holdase that facilitates channel assembly. Together, the structures reveal a Ca assembly intermediate and EMC client-binding sites that could have wide-ranging implications for the biogenesis of VGICs and other membrane proteins.
Topics: Humans; Binding Sites; Brain; Calcium Channels, L-Type; Cryoelectron Microscopy; Endoplasmic Reticulum; Gabapentin; Membrane Proteins; Myocardium
PubMed: 37196677
DOI: 10.1038/s41586-023-06175-5 -
Indian Journal of Dermatology,... 2018
Review
Topics: Anticonvulsants; Dermatology; Gabapentin; Humans; Pain; Pregabalin; Pruritus
PubMed: 29855453
DOI: 10.4103/ijdvl.IJDVL_480_17 -
Anesthesiology Aug 2020Widely used for acute pain management, the clinical benefit from perioperative use of gabapentinoids is uncertain. The aim of this systematic review was to assess the...
BACKGROUND
Widely used for acute pain management, the clinical benefit from perioperative use of gabapentinoids is uncertain. The aim of this systematic review was to assess the analgesic effect and adverse events with the perioperative use of gabapentinoids in adult patients.
METHODS
Randomized controlled trials studying the use of gabapentinoids in adult patients undergoing surgery were included. The primary outcome was the intensity of postoperative acute pain. Secondary outcomes included the intensity of postoperative subacute pain, incidence of postoperative chronic pain, cumulative opioid use, persistent opioid use, lengths of stay, and adverse events. The clinical significance of the summary estimates was assessed based on established thresholds for minimally important differences.
RESULTS
In total, 281 trials (N = 24,682 participants) were included in this meta-analysis. Compared with controls, gabapentinoids were associated with a lower postoperative pain intensity (100-point scale) at 6 h (mean difference, -10; 95% CI, -12 to -9), 12 h (mean difference, -9; 95% CI, -10 to -7), 24 h (mean difference, -7; 95% CI, -8 to -6), and 48 h (mean difference, -3; 95% CI, -5 to -1). This effect was not clinically significant ranging below the minimally important difference (10 points out of 100) for each time point. These results were consistent regardless of the type of drug (gabapentin or pregabalin). No effect was observed on pain intensity at 72 h, subacute and chronic pain. The use of gabapentinoids was associated with a lower risk of postoperative nausea and vomiting but with more dizziness and visual disturbance.
CONCLUSIONS
No clinically significant analgesic effect for the perioperative use of gabapentinoids was observed. There was also no effect on the prevention of postoperative chronic pain and a greater risk of adverse events. These results do not support the routine use of pregabalin or gabapentin for the management of postoperative pain in adult patients.
Topics: Acute Pain; Adult; Analgesics; Gabapentin; Humans; Pain, Postoperative; Pregabalin
PubMed: 32667154
DOI: 10.1097/ALN.0000000000003428 -
Anaesthesia Jan 2016Chronic postoperative pain is common. Nerve injury and inflammation promote chronic pain, the risk of which is influenced by patient factors, including psychological... (Review)
Review
Chronic postoperative pain is common. Nerve injury and inflammation promote chronic pain, the risk of which is influenced by patient factors, including psychological characteristics. Interventional trials to prevent chronic postoperative pain have been underpowered with inadequate patient follow-up. Ketamine may reduce chronic postoperative pain, although the optimum treatment duration and dose for different operations have yet to be identified. The evidence for gabapentin and pregabalin is encouraging but weak; further work is needed before these drugs can be recommended for the prevention of chronic pain. Regional techniques reduce the rates of chronic pain after thoracotomy and breast cancer surgery. Nerve-sparing surgical techniques may be of benefit, although nerve injury is not necessary or sufficient for chronic pain to develop.
Topics: Amines; Analgesics; Chronic Pain; Cyclohexanecarboxylic Acids; Gabapentin; Humans; Ketamine; Pain, Postoperative; Pregabalin; Thoracotomy; gamma-Aminobutyric Acid
PubMed: 26620149
DOI: 10.1111/anae.13306