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BMJ Supportive & Palliative Care Jun 2024Chemotherapy-induced peripheral neuropathy (CIPN) affects patients' quality of life and treatment effectiveness. Gabapentinoids, like gabapentin and pregabalin, are...
INTRODUCTION
Chemotherapy-induced peripheral neuropathy (CIPN) affects patients' quality of life and treatment effectiveness. Gabapentinoids, like gabapentin and pregabalin, are often used for CIPN treatment, but their efficacy and safety remain uncertain. This study reviews and analyses randomised controlled trial data on this topic.
MATERIALS/METHODS
We searched PubMed, Embase and Cochrane CENTRAL until 29 August 2022 for studies on gabapentinoid use in CIPN. Meta-analysis was performed using RevMan V.5.4 and the Metafor package in R. Outcomes included pain scores, quality of life and adverse drug events.
RESULTS
For the prevention setting, our meta-analysis shows that pregabalin did not significantly improve average pain (standardised mean difference (SMD) -0.14, 95% CI -0.51 to 0.23; I=26% (95% CI 0% to >98%)) or quality of life (mean difference (MD) 2.5, 95% CI -4.67 to 9.67; p=0.49) in preventing CIPN compared with placebo. However, it showed a potential trend towards reducing the worst pain (SMD -0.28, 95% CI -0.57 to 0.01; I=0% (95% CI 0% to 98%; p=0.06)). For the treatment setting, some studies have shown a potential therapeutic effect of gabapentinoids. However, the results are not consistent between studies. Given the studies' heterogeneity, a meta-analysis in treatment setting was not performed.
CONCLUSION
There is limited evidence to support the use of gabapentinoids in CIPN. In prevention setting, gabapentinoids do not significantly prevent CIPN. In treatment setting, studies have been inconsistent in their conclusions, lacking definitive benefits over placebo. More comprehensive and higher quality research is needed in the future.
PROSPERO REGISTRATION NUMBER
CRD42022361193.
PubMed: 38936970
DOI: 10.1136/spcare-2023-004362 -
Pain Reports Apr 2024Neuropathic pain is a challenging chronic pain condition. Limited knowledge exists regarding the relative effectiveness of pharmacological treatments, and differences in... (Review)
Review
Neuropathic pain is a challenging chronic pain condition. Limited knowledge exists regarding the relative effectiveness of pharmacological treatments, and differences in trial design and impact of the placebo response preclude indirect comparisons of efficacy between drug classes. The purpose of this systematic review and meta-analysis of head-to-head trials was to compare the efficacy and tolerability of drugs recommended for neuropathic pain. We conducted a systematic review and meta-analysis of direct-comparison double-blind randomized trials. Primary outcomes were mean change in pain intensity and number of responders with a 50% reduction in pain intensity. Secondary outcomes encompassed quality of life, sleep, emotional functioning, and number of dropouts because of adverse events. We included 30 trials (4087 patients), comprising 16 crossover and 14 parallel-group design studies. All studies were conducted in adults, and the majority were investigator-initiated trials. We found moderate-quality evidence for equivalence (no clinically relevant difference) between tricyclic antidepressants (TCA) and gabapentin/pregabalin with a combined mean difference in pain score of 0.10 (95% CI -0.13 to 0.32). We could not document differences between TCA and serotonin-noradrenaline reuptake inhibitors (SNRI), between SNRI and gabapentin/pregabalin, or between opioids and TCA (low quality of evidence). We found more dropouts because of adverse events with SNRI and opioids compared with TCA (low quality of evidence). We did not identify any studies that included topical treatments. This systematic review of direct-comparison studies found evidence for equivalence between TCA and gabapentin/pregabalin and fewer dropouts with TCA than SNRI and opioids.
PubMed: 38932764
DOI: 10.1097/PR9.0000000000001138 -
European Review For Medical and... May 2024Painful peripheral diabetic neuropathy (PRDN) is a common disabling condition. Pregabalin and amitriptyline are commonly prescribed as the first-line for PPDN despite... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Painful peripheral diabetic neuropathy (PRDN) is a common disabling condition. Pregabalin and amitriptyline are commonly prescribed as the first-line for PPDN despite the contradicting recommendations. There is a need to inform the scientific community regarding first-line pain control among patients with PPDN. This meta-analysis assessed pregabalin and amitriptyline effects on PPDN.
PATIENTS AND METHODS
We searched PubMed, MEDLINE, Cochrane Library, EBSCO, and Google Scholar; the terms used were amitriptyline, pregabalin, painful diabetic neuropathy, antidepressant, gabapentinoids, quality of life, and adverse events. Boolean operators like AND, and OR were used. Six hundred and thirty-one studies were retrieved, and 37 full texts were screened. However, only six randomized controlled trials fulfilled the inclusion and exclusion criteria.
RESULTS
No significant statistical differences between amitriptyline and pregabalin regarding pain score and significant pain reduction (odd ratio, -0.82, 95% CI, -2.21-0.58, and odd ratio, 1.16, 95% CI, 0.76-1.76 respectively). Quality of life, total adverse events, and drug discontinuation were not different between the two drugs (odd ratio, 0.89, 95% CI, -2.11-3.89, odd ratio, 0.98, 95% CI, 0.52-1.85, and odd ratio, 0.51, 95% CI, 0.08-3.15, respectively).
CONCLUSIONS
No significant statistical differences between amitriptyline and pregabalin regarding their effects on pain and quality of life. The drugs showed similar total adverse events and drug withdrawal. Further larger real-world studies are needed.
Topics: Pregabalin; Amitriptyline; Humans; Diabetic Neuropathies; Analgesics; Quality of Life
PubMed: 38856135
DOI: 10.26355/eurrev_202405_36296 -
The Cochrane Database of Systematic... Jun 2024Postburn pruritus (itch) is a common and distressing symptom experienced on healing or healed burn or donor site wounds. Topical, systemic, and physical treatments are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Postburn pruritus (itch) is a common and distressing symptom experienced on healing or healed burn or donor site wounds. Topical, systemic, and physical treatments are available to control postburn pruritus; however, it remains unclear how effective these are.
OBJECTIVES
To assess the effects of interventions for treating postburn pruritus in any care setting.
SEARCH METHODS
In September 2022, we searched the Cochrane Wounds Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE (including In-Process & Other Non-Indexed Citations), Ovid Embase, and EBSCO CINAHL Plus. We also searched clinical trials registries and scanned references of relevant publications to identify eligible trials. There were no restrictions with respect to language, publication date, or study setting.
SELECTION CRITERIA
Randomised controlled trials (RCTs) that enrolled people with postburn pruritus to compare an intervention for postburn pruritus with any other intervention, placebo or sham intervention, or no intervention.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures expected by Cochrane. We used GRADE to assess the certainty of the evidence.
MAIN RESULTS
We included 25 RCTs assessing 21 interventions with 1166 randomised participants. These 21 interventions can be grouped into six categories: neuromodulatory agents (such as doxepin, gabapentin, pregabalin, ondansetron), topical therapies (such as CQ-01 hydrogel, silicone gel, enalapril ointment, Provase moisturiser, beeswax and herbal oil cream), physical modalities (such as massage therapy, therapeutic touch, extracorporeal shock wave therapy, enhanced education about silicone gel sheeting), laser scar revision (pulsed dye laser, pulsed high-intensity laser, fractional CO2 laser), electrical stimulation (transcutaneous electrical nerve stimulation, transcranial direct current stimulation), and other therapies (cetirizine/cimetidine combination, lemon balm tea). Most RCTs were conducted at academic hospitals and were at a high risk of performance, attrition, and detection bias. While 24 out of 25 included studies reported change in burn-related pruritus, secondary outcomes such as cost-effectiveness, pain, patient perception, wound healing, and participant health-related quality of life were not reported or were reported incompletely. Neuromodulatory agents versus antihistamines or placebo There is low-certainty evidence that doxepin cream may reduce burn-related pruritus compared with oral antihistamine (mean difference (MD) -2.60 on a 0 to 10 visual analogue scale (VAS), 95% confidence interval (CI) -3.79 to -1.42; 2 studies, 49 participants). A change of 2 points represents a minimal clinically important difference (MCID). Due to very low-certainty evidence, it is uncertain whether doxepin cream impacts the incidence of somnolence as an adverse event compared to oral antihistamine (risk ratio (RR) 0.64, 95% CI 0.32 to 1.25; 1 study, 24 participants). No data were reported on pain in the included study. There is low-certainty evidence that gabapentin may reduce burn-related pruritus compared with cetirizine (MD -2.40 VAS, 95% CI -4.14 to -0.66; 1 study, 40 participants). A change of 2 points represents a MCID. There is low-certainty evidence that gabapentin reduces the incidence of somnolence compared to cetirizine (RR 0.02, 95% CI 0.00 to 0.38; 1 study, 40 participants). No data were reported on pain in the included study. There is low-certainty evidence that pregabalin may result in a reduction in burn-related pruritus intensity compared with cetirizine with pheniramine maleate (MD -0.80 VAS, 95% CI -1.24 to -0.36; 1 study, 40 participants). A change of 2 points represents a MCID. There is low-certainty evidence that pregabalin reduces the incidence of somnolence compared to cetirizine (RR 0.04, 95% CI 0.00 to 0.69; 1 study, 40 participants). No data were reported on pain in the included study. There is moderate-certainty evidence that ondansetron probably results in a reduction in burn-related pruritus intensity compared with diphenhydramine (MD -0.76 on a 0 to 10 numeric analogue scale (NAS), 95% CI -1.50 to -0.02; 1 study, 38 participants). A change of 2 points represents a MCID. No data were reported on pain and adverse events in the included study. Topical therapies versus relevant comparators There is moderate-certainty evidence that enalapril ointment probably decreases mean burn-related pruritus compared with placebo control (MD -0.70 on a 0 to 4 scoring table for itching, 95% CI -1.04 to -0.36; 1 study, 60 participants). No data were reported on pain and adverse events in the included study. Physical modalities versus relevant comparators Compared with standard care, there is low-certainty evidence that massage may reduce burn-related pruritus (standardised mean difference (SMD) -0.86, 95% CI -1.45 to -0.27; 2 studies, 166 participants) and pain (SMD -1.32, 95% CI -1.66 to -0.98). These SMDs equate to a 4.60-point reduction in pruritus and a 3.74-point reduction in pain on a 10-point VAS. A change of 2 VAS points in itch represents a MCID. No data were reported on adverse events in the included studies. There is low-certainty evidence that extracorporeal shock wave therapy (ESWT) may reduce burn-related pruritus compared with sham stimulation (SMD -1.20, 95% CI -1.65 to -0.75; 2 studies, 91 participants). This equates to a 5.93-point reduction in pruritus on a 22-point 12-item Pruritus Severity Scale. There is low-certainty evidence that ESWT may reduce pain compared with sham stimulation (MD 2.96 on a 0 to 25 pressure pain threshold (PPT), 95% CI 1.76 to 4.16; 1 study, 45 participants). No data were reported on adverse events in the included studies. Laser scar revision versus untreated or placebo controls There is moderate-certainty evidence that pulsed high-intensity laser probably results in a reduction in burn-related pruritus intensity compared with placebo laser (MD -0.51 on a 0 to 1 Itch Severity Scale (ISS), 95% CI -0.64 to -0.38; 1 study, 49 participants). There is moderate-certainty evidence that pulsed high-intensity laser probably reduces pain compared with placebo laser (MD -3.23 VAS, 95% CI -5.41 to -1.05; 1 study, 49 participants). No data were reported on adverse events in the included studies.
AUTHORS' CONCLUSIONS
There is moderate to low-certainty evidence on the effects of 21 interventions. Most studies were small and at a high risk of bias related to blinding and incomplete outcome data. Where there is moderate-certainty evidence, practitioners should consider the applicability of the evidence for their patients.
Topics: Humans; Pruritus; Burns; Randomized Controlled Trials as Topic; Bias; Antipruritics
PubMed: 38837237
DOI: 10.1002/14651858.CD013468.pub2 -
International Clinical... May 2024This systematic literature review aimed to assess the efficacy and tolerability of agomelatine versus approved medications for the treatment of generalized anxiety...
This systematic literature review aimed to assess the efficacy and tolerability of agomelatine versus approved medications for the treatment of generalized anxiety disorder (GAD) in adult patients. We selected randomized controlled trials on various medications used to treat GAD in adult patients. An existing systematic literature review (Kong et al., 2020) was used to identify relevant studies published before 2020. Outcomes of remission and discontinuation due to adverse events (AEs) were analyzed, following a random-effects network meta-analysis approach. Of 25 identified studies, 20 and 22 studies were included in the network meta-analysis for studying the remission and discontinuation (due to AEs) outcomes, respectively. A statistically significant difference in the remission rate was observed between agomelatine and pregabalin [odds ratio (OR), 2.22; 95% confidence interval (CI), 1.19-4.21]. For the other comparators, the results were nonsignificant; however, all the point estimates were in favor of agomelatine. Similarly, for discontinuation because of AEs, the point estimates leaned consistently toward agomelatine suggesting its higher tolerability. The probabilities of agomelatine having the highest remission rate and lowest discontinuation (due to AEs) rate were 67% and 68%, respectively. Based on its demonstrated effectiveness and tolerability, agomelatine can be considered as a drug of choice for the treatment of GAD.
PubMed: 38804215
DOI: 10.1097/YIC.0000000000000551 -
Brain & Spine 2024The effectiveness of post-surgical rehabilitation following lumbar disc herniation (LDH) surgery is unclear. (Review)
Review
INTRODUCTION
The effectiveness of post-surgical rehabilitation following lumbar disc herniation (LDH) surgery is unclear.
RESEARCH QUESTION
To investigate the effectiveness and safety of rehabilitation interventions initiated within three months post-surgery for adults treated surgically for LDH.
MATERIAL AND METHODS
This systematic review searched seven databases from inception to November 2023. Independent reviewers screened studies, assessed and extracted data, and rated the certainty of the evidence using the GRADE approach.
RESULTS
This systematic review retrieved 20,531 citations and included 25 randomized controlled trials. The high certainty evidence suggests that adding Pilates exercise to routine care and cognitive behavioral therapy may improve function immediately post-intervention (1 RCT), and that adding whole-body magnetic therapy to exercise, pharmacological and aquatic therapy may reduce low back pain intensity (1 RCT) immediately post-intervention. Compared to placebo, pregabalin did not reduce low back pain or leg pain intensity (1 RCT) (moderate to high certainty evidence). We found no differences between: 1) behavioral graded activity vs. physiotherapy (1 RCT); 2) exercise and education vs. neck massage or watchful waiting (1 RCT); 3) exercise, education, and in-hospital usual care vs. in-hospital usual care (1 RCT); 4) functional or staged exercise vs. usual post-surgical care including exercise (2 RCTs); and 5) supervised exercise with education vs. education (1 RCT). No studies assessed adverse events.
DISCUSSION AND CONCLUSION
Evidence on effective and safe post-surgical rehabilitation interventions is sparse. This review identified two interventions with potential short-term benefits (Pilates exercises, whole-body magnetic therapy) but safety is unclear, and one with an iatrogenic effect (pregabalin).
PubMed: 38690091
DOI: 10.1016/j.bas.2024.102806 -
The Clinical Journal of Pain Jul 2024This study aimed to systematically evaluate the clinical efficacy of gabapentin and pregabalin in the treatment of acute herpes zoster (HZ) neuralgia, including pain... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study aimed to systematically evaluate the clinical efficacy of gabapentin and pregabalin in the treatment of acute herpes zoster (HZ) neuralgia, including pain control and the occurrence of adverse effects.
METHODS
A systematic computerized search was conducted in October 2023 in PubMed, Embase, Web of Science, Cochrane Library, VIP, CNKI, and Wanfang databases. Data from randomized controlled trials (RCTs) comparing gabapentin analogs for the treatment of acute HZ neuralgia were searched. Endpoints were visual analog scores (Visual Analog Scale) and adverse effects at 1, 2, and 4 weeks. Data from studies that met the inclusion criteria were extracted for meta-analysis and sensitivity analysis using Revman 5.4 and Stata16.
RESULTS
The study included 292 patients from 6 RCTs. Of these, 118 were in the gabapentin-treated group, 37 were in the pregabalin-treated group, and 137 were in the placebo-controlled group. The gabapentin group showed superior pain reduction compared with the placebo group ( P < 0.05), but adverse events were more frequent.
CONCLUSION
Gabapentin can effectively reduce acute HZ neuralgia in patients. Pregabalin requires additional RCTs to supplement the analysis.
Topics: Humans; Gabapentin; Randomized Controlled Trials as Topic; Herpes Zoster; Analgesics; Pregabalin; Neuralgia, Postherpetic; Neuralgia
PubMed: 38651606
DOI: 10.1097/AJP.0000000000001218 -
Frontiers in Medicine 2024This network meta-analysis was to analyze and rank the efficacy and safety of different systemic drugs in the treatment of uremic pruritus (UP) among hemodialysis...
Efficacy and safety of different systemic drugs in the treatment of uremic pruritus among hemodialysis patients: a network meta-analysis based on randomized clinical trials.
AIM
This network meta-analysis was to analyze and rank the efficacy and safety of different systemic drugs in the treatment of uremic pruritus (UP) among hemodialysis patients.
METHOD
PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception to 10 July 2023 for randomized controlled trials (RCTs) investigating different drugs in the treatment of UP among hemodialysis patients. Drugs including cromolyn sodium, dexchlorpheniramine, difelikefalin, gabapentin, hydroxyzine, ketotifen, melatonin, montelukast, nalbuphine, nalfurafine, nemolizumab, nicotinamide, pregabalin, sertraline, thalidomide, and placebo were assessed. Outcome measures, including pruritus relief, response, and adverse events, were analyzed. Network plots, forest plots, league tables, and the surface under the cumulative ranking (SUCRA) probabilities were depicted for each outcome.
RESULTS
The network meta-analysis retrieved 22 RCTs. Gabapentin (69.74%) had the highest likelihood to be the most effective drug for pruritus relief in UP patients receiving hemodialysis, followed by cromolyn sodium and hydroxyzine. Thalidomide (60.69%) and gabapentin (58.99%) were associated with significantly more drug responses for treating UP among patients receiving hemodialysis. Patients who were treated with gabapentin (40.01%) were likely to have risks of adverse events and dizziness. Lower risks of adverse events, nausea, and diarrhea were found in patients who received cromolyn sodium and lower risks of somnolence.
CONCLUSION
This study suggests considering gabapentin treatment when facing a patient suffering from UP. This study provides a reference for the selection of drug therapy for UP patients receiving hemodialysis.
PubMed: 38646551
DOI: 10.3389/fmed.2024.1334944 -
Neurology Apr 2024To undertake a systematic review of the available literature to examine the relationship between prenatal antiseizure medication (ASM) exposure and adverse postnatal...
BACKGROUND AND OBJECTIVES
To undertake a systematic review of the available literature to examine the relationship between prenatal antiseizure medication (ASM) exposure and adverse postnatal neurodevelopmental outcomes, focusing on social, emotional, behavioral, and adaptive domains of human function, and the frequency of neurodevelopmental and psychiatric disorders in ASM-exposed offspring.
METHODS
Electronic searches of MEDLINE, PsychINFO, and EMBASE were conducted and limited to studies published between 1990 and 2023 in English. Studies were eligible if they prospectively or retrospectively reported neurodevelopmental outcomes of ASM-exposed offspring. The Newcastle-Ottawa scale was used to conduct methodologic quality assessments of included studies, and a narrative synthesis integrated the review findings.
RESULTS
Forty-three studies were included. Valproate has been consistently associated with a 2- to 4-fold increased risk of autism spectrum disorder (ASD), 2- to 5-fold increased risk of intellectual disability (ID), and poor adaptive functioning. Growing evidence indicates that topiramate is associated with a 2-fold increased risk of ASD and 3- to 4-fold increased risk of ID. The risks of adverse neurodevelopmental outcomes for valproate and topiramate seem to be dose dependent. Phenobarbital has been suggested to be associated with deleterious neurodevelopmental effects, but data are limited. Levetiracetam has recently been linked with an increased risk of attention deficit hyperactivity disorder and anxiety disorders in a single study. Carbamazepine has been associated with variable neurodevelopmental outcomes. Lamotrigine seems to be "safe" in terms of postnatal neurodevelopment. Data for oxcarbazepine, phenytoin, and clonazepam are limited but seem to have little-to-no risk of adverse outcomes. Evidence for the remaining ASMs, including gabapentin, pregabalin, lacosamide, zonisamide, clobazam, perampanel, ethosuximide, or brivaracetam, is lacking. Several methodologic limitations impeded data synthesis, including heterogeneity in outcome measures and small samples of monotherapy exposures.
DISCUSSION
The findings of this review support the conclusion that valproate and topiramate use during pregnancy is associated with a significantly increased risk of neurodevelopmental effects on the fetus. Apart from lamotrigine, which seems to be free of adverse neurodevelopmental effects, data for the other ASMs are mixed or inadequate to draw definite conclusions. Further research into the neurodevelopmental effects of prenatal exposure to ASMs, including most newer agents, is much needed.
Topics: Pregnancy; Female; Humans; Valproic Acid; Lamotrigine; Topiramate; Autism Spectrum Disorder; Retrospective Studies; Anticonvulsants
PubMed: 38531021
DOI: 10.1212/WNL.0000000000209175 -
Orthopedic Reviews 2024The opioid crisis has become a present concern in the medical field. In an effort to address these complications, antineuropathic pain medications have been considered...
BACKGROUND
The opioid crisis has become a present concern in the medical field. In an effort to address these complications, antineuropathic pain medications have been considered as alternatives to prescribed opioids.
OBJECTIVE
This review focuses on the analgesic effects of neuromodulators, such as gabapentin, duloxetine, and pregabalin, that provide room for less dependence on narcotic analgesics following orthopedic surgery.
METHODS
During the database searches, 1,033 records were identified as a preliminary result. After duplicates were removed, an initial screen of each article was completed which identified records to be removed due to absence of a full-text article. Articles were excluded if they were not either prospective or retrospective, showcased an irrelevant medication (such as tricyclic antidepressants) which are not pertinent to this review, or deemed to be unrelated to the topic.
RESULTS
Ultimately, 19 articles were selected. Three different drugs, gabapentin, pregabalin, and duloxetine, were analyzed to compile data on the effectiveness of preventing opioid overuse and addiction following hand surgery. This review identifies potential evidence that peri-operative gabapentin, pregabalin, and duloxetine administration decreases post-operative pain and lowers opioid dependency.
CONCLUSION
Gabapentin, pregabalin, and duloxetine have potential to further decrease post-operative pain and lower opioid dependency. This review creates an opening for further research in hand surgery to assess an updated protocol for pain management to reduce opioid dependency.
PubMed: 38505138
DOI: 10.52965/001c.93012