-
The Journal of Headache and Pain Dec 2023Migraine is the world's second most common disabling disorder, affecting 15% of UK adults and costing the UK over £1.5 billion per year. Several costly new drugs have... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Migraine is the world's second most common disabling disorder, affecting 15% of UK adults and costing the UK over £1.5 billion per year. Several costly new drugs have been approved by National Institute for Health and Care Excellence.
AIM
To assess the cost-effectiveness of drugs used to treat adults with chronic migraine.
METHODS
We did a systematic review of placebo-controlled trials of preventive drugs for chronic migraine. We then assessed the cost-effectiveness of the currently prescribable drugs included in the review: Onabotulinum toxin A (BTA), Eptinezumab (100mg or 300mg), Fremanezumab (monthly or quarterly dose), Galcanezumab or Topiramate, each compared to placebo, and we evaluated them jointly. We developed a Markov (state-transition) model with a three-month cycle length to estimate the costs and quality-adjusted life years (QALYs) for the different medications from a UK NHS and Personal Social Services perspective. We used a two-year time horizon with a starting age of 30 years for the patient cohort. We estimated transition probabilities based on monthly headache days using a network meta-analysis (NMA) developed by us, and from published literature. We obtained costs from published sources and applied discount rates of 3.5% to both costs and outcomes.
RESULTS
Deterministic results suggest Topiramate was the least costly option and generated slightly more QALYs than the placebo, whereas Eptinezumab 300mg was the more costly option and generated the most QALYs. After excluding dominated options, the incremental cost-effectiveness ratio (ICER) between BTA and Topiramate was £68,000 per QALY gained and the ICER between Eptinezumab 300mg and BTA was not within plausible cost-effectiveness thresholds. The cost-effectiveness acceptability frontier showed that Topiramate is the most cost-effective medication for any amount the decision maker is willing-to-pay per QALY.
CONCLUSIONS
Among the various prophylactic medications for managing chronic migraine, only Topiramate was within typical cost-effectiveness threshold ranges. Further research is needed, ideally an economic evaluation alongside a randomised trial, to compare these newer, expensive CGRP MAbs with the cheaper oral medications.
Topics: Adult; Humans; Topiramate; Migraine Disorders; Headache; Cost-Benefit Analysis; Decision Making; Quality-Adjusted Life Years
PubMed: 38053051
DOI: 10.1186/s10194-023-01686-y -
JAMA Network Open Aug 2023Patients undergoing spine surgery often experience severe pain. The optimal dosage of pregabalin and gabapentin for pain control and safety in these patients has not... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Patients undergoing spine surgery often experience severe pain. The optimal dosage of pregabalin and gabapentin for pain control and safety in these patients has not been well established.
OBJECTIVE
To evaluate the associations of pain, opioid consumption, and adverse events with different dosages of pregabalin and gabapentin in patients undergoing spine surgery.
DATA SOURCES
PubMed/MEDLINE, Embase, Web of Science, Cochrane library, and Scopus databases were searched for articles until August 7, 2021.
STUDY SELECTION
Randomized clinical trials conducted among patients who received pregabalin or gabapentin while undergoing spine surgery were included.
DATA EXTRACTION AND SYNTHESIS
Two investigators independently performed data extraction following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) reporting guideline. The network meta-analysis was conducted from August 2022 to February 2023 using a random-effects model.
MAIN OUTCOMES AND MEASURES
The primary outcome was pain intensity measured using the Visual Analog Scale (VAS), and secondary outcomes included opioid consumption and adverse events.
RESULTS
Twenty-seven randomized clinical trials with 1861 patients (median age, 45.99 years [range, 20.00-70.00 years]; 759 women [40.8%]) were included in the systematic review and network meta-analysis. Compared with placebo, the VAS pain score was lowest with gabapentin 900 mg per day, followed by gabapentin 1200 mg per day, gabapentin 600 mg per day, gabapentin 300 mg per day, pregabalin 300 mg per day, pregabalin 150 mg per day, and pregabalin 75 mg per day. Additionally, gabapentin 900 mg per day was found to be associated with the lowest opioid consumption among all dosages of gabapentin and pregabalin, with a mean difference of -22.07% (95% CI, -33.22% to -10.92%) for the surface under the cumulative ranking curve compared with placebo. There was no statistically significant difference in adverse events (nausea, vomiting, and dizziness) among all treatments. No substantial inconsistency between direct and indirect evidence was detected for all outcomes.
CONCLUSIONS AND RELEVANCE
These findings suggest that gabapentin 900 mg per day before spine surgery is associated with the lowest VAS pain score among all dosages. In addition, no differences in adverse events were noted among all treatments.
Topics: Humans; Female; Middle Aged; Gabapentin; Pregabalin; Analgesics; Analgesics, Opioid; Network Meta-Analysis; Pain, Postoperative
PubMed: 37556139
DOI: 10.1001/jamanetworkopen.2023.28121 -
Epilepsia Open Apr 2024Antiseizure medications (ASMs) constitute the principal of treatment for patients with epilepsy, where long-term treatment is usually necessary. The purpose of this... (Review)
Review
Antiseizure medications (ASMs) constitute the principal of treatment for patients with epilepsy, where long-term treatment is usually necessary. The purpose of this systematic review is to provide practical and useful information regarding various aspects of the interactions between ASMs and foods and drinks. MEDLINE and ScienceDirect, from the inception to July 15, 2023, were searched for related publications. In both electronic databases, the following search strategy was applied, and the following keywords were used (in title/abstract): "food OR drink" AND "antiepileptic OR antiseizure." The primary search yielded 738 studies. After implementing our inclusion and exclusion criteria, we could identify 19 studies on the issue of interest for our endeavor. Four studies were identified in the recheck process and not by the primary search. All studies provided low level of evidence. Interactions between foods and ASMs are a common phenomenon. Many factors may play a role for such an interaction to come to play; these include drug properties, administration route, and administration schedule, among others. Drugs-foods (-drinks) interactions may change the drug exposure or plasma levels of drugs (e.g., grapefruit juice increases carbamazepine concentrations and the bioavailability of cannabidiol is increased 4-5 folds with concomitant intake of fat-rich food); this may require dosage adjustments. Interactions between ASMs and foods and drinks may be important. This should be taken seriously into consideration when consulting patients and their caregivers about ASMs. Future well-designed investigations should explore the specific interactions between foods (and drinks) and ASMs to clarify whether they are clinically important. PLAIN LANGUAGE SUMMARY: Interactions between antiseizure medications and foods and drinks may be important. This should be taken into consideration in patients with epilepsy.
Topics: Humans; Anticonvulsants; Biological Availability; Benzodiazepines; Food; Epilepsy
PubMed: 38345419
DOI: 10.1002/epi4.12918 -
The Journal of Headache and Pain Oct 2023Topiramate is a repurposed first-line treatment for migraine prophylaxis. The aim of this systematic review and meta-analysis is to critically re-appraise the existing... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Topiramate is a repurposed first-line treatment for migraine prophylaxis. The aim of this systematic review and meta-analysis is to critically re-appraise the existing evidence supporting the efficacy and tolerability of topiramate.
METHODS
A systematic search in MEDLINE, EMBASE, Cochrane CENTRAL, and ClinicalTrials.gov was performed for trials of pharmacological treatment in migraine prophylaxis as of August 13, 2022, following the Preferred Reporting Items for Systematic Reviews (PRISMA). Randomized controlled trials in adult patients that used topiramate for the prophylactic treatment of migraine, with placebo as active comparator, were included. Two reviewers independently screened the retrieved studies and extracted all data. Outcomes of interest were the 50% responder rates, the reduction in monthly migraine days, and adverse events leading to treatment discontinuation. Results were pooled and meta-analyzed, with sensitivity analysis based on the risk of bias of the studies, the monthly migraine days at baseline, and the previous use of other prophylactic treatments. Certainty evidence was judged according to the GRADE framework.
RESULTS
Eight out of 10,826 studies fulfilled the inclusion/exclusion criteria, accounting for 2,610 randomized patients. Six studies included patients with episodic migraine and two with chronic migraine. Topiramate dose ranged from 50 to 200 mg/day, and all studies included a placebo arm. There was a high certainty that topiramate: 1) increased the proportion of patients who achieved a 50% responder rate in monthly migraine days, compared to placebo [relative risk: 1.61 (95% confidence interval (CI): 1.29-2.01); absolute risk difference: 168 more per 1,000 (95% CI: 80 to 278 more)]; 2) was associated with 0.99 (95% CI: 1.41-0.58) fewer migraine days than placebo; 3) and had a higher proportion of patients with adverse events leading to treatment discontinuation [absolute risk difference 80 patients more per 1,000 (95% CI: 20 to 140 more patients)].
CONCLUSIONS
There is high-quality evidence of the efficacy of topiramate in the prophylaxis of migraine, albeit its use poses a risk of adverse events that may lead to treatment discontinuation, with a negative effect on patient satisfaction and adherence to care.
Topics: Adult; Humans; Topiramate; Migraine Disorders; Headache; Patient Satisfaction; Transcription Factors
PubMed: 37814223
DOI: 10.1186/s10194-023-01671-5 -
CNS Drugs Sep 2023Although one of the major presentations of vestibular migraine is dizziness with/without unsteady gait, it is still classified as one of the migraine categories.... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Although one of the major presentations of vestibular migraine is dizziness with/without unsteady gait, it is still classified as one of the migraine categories. However, in contrast to ordinary migraine, vestibular migraine patients have distinct characteristics, and the detailed treatment strategy for vestibular migraine is different and more challenging than ordinary migraine treatment. Currently, there is no conclusive evidence regarding its management, including vestibular migraine prophylaxis.
AIM
The objective of this current network meta-analysis (NMA) was to compare the efficacy and acceptability of individual treatment strategies in patients with vestibular migraine.
METHODS
The PubMed, Embase, ScienceDirect, ProQuest, Web of Science, ClinicalKey, Cochrane Central, and ClinicalTrials.gov databases were systematically searched for randomized controlled trials (RCTs), with a final literature search date of 30 December 2022. Patients diagnosed with vestibular migraine were included. The PICO of the current study included (1) patients with vestibular migraine; (2) intervention: any active pharmacologic or non-pharmacologic intervention; (3) comparator: placebo-control, active control, or waiting list; and (4) outcome: changes in migraine frequency or severity. This NMA of RCTs of vestibular migraine treatment was conducted using a frequentist model. We arranged inconsistency and similarity tests to re-examine the assumption of NMA, and also conducted a subgroup analysis focusing on RCTs of pharmacological treatment for vestibular migraine management. The primary outcome was changes in the frequency of vestibular migraines, while the secondary outcomes were changes in vestibular migraine severity and acceptability. Acceptability was set as the dropout rate, which was defined as the participant leaving the study before the end of the trial for any reason. Two authors independently evaluated the risk of bias for each domain using the Cochrane risk-of-bias tool.
RESULTS
Seven randomized controlled trials (N = 828, mean age 37.6 years, 78.4% female) and seven active regimens were included. We determined that only valproic acid (standardized mean difference [SMD] -1.61, 95% confidence interval [CI] -2.69, -0.54), propranolol (SMD -1.36, 95% CI -2.55, -0.17), and venlafaxine (SMD -1.25, 95% CI -2.32, -0.18) were significantly associated with better improvement in vestibular migraine frequency than the placebo/control groups. Furthermore, among all the investigated pharmacologic/non-pharmacologic treatments, valproic acid yielded the greatest decrease in vestibular migraine frequency among all the interventions. In addition, most pharmacologic/non-pharmacologic treatments were associated with similar acceptability (i.e. dropout rate) as those of the placebo/control groups.
CONCLUSIONS
The current study provides evidence that only valproic acid, propranolol, and venlafaxine might be associated with beneficial efficacy in vestibular migraine treatment.
TRIAL REGISTRATION
CRD42023388343.
Topics: Adult; Female; Humans; Male; Migraine Disorders; Network Meta-Analysis; Propranolol; Valproic Acid; Venlafaxine Hydrochloride
PubMed: 37676473
DOI: 10.1007/s40263-023-01037-0 -
The Journal of Headache and Pain Sep 2023Novel disease-specific and mechanism-based treatments sharing good evidence of efficacy for migraine have been recently marketed. However, reimbursement by insurers... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Novel disease-specific and mechanism-based treatments sharing good evidence of efficacy for migraine have been recently marketed. However, reimbursement by insurers depends on treatment failure with classic anti-migraine drugs. In this systematic review and meta-analysis, we aimed to identify and rate the evidence for efficacy of flunarizine, a repurposed, first- or second-line treatment for migraine prophylaxis.
METHODS
A systematic search in MEDLINE, Cochrane CENTRAL, and ClinicalTrials.gov was performed for trials of pharmacological treatment in migraine prophylaxis, following the Preferred Reporting Items for Systematic Reviews (PRISMA). Eligible trials for meta-analysis were randomized, placebo-controlled studies comparing flunarizine with placebo. Outcomes of interest according to the Outcome Set for preventive intervention trials in chronic and episodic migraine (COSMIG) were the proportion of patients reaching a 50% or more reduction in monthly migraine days, the change in monthly migraine days (MMDs), and Adverse Events (AEs) leading to discontinuation.
RESULTS
Five trials were eligible for narrative description and three for data synthesis and analysis. No studies reported the predefined outcomes, but one study assessed the 50% reduction in monthly migraine attacks with flunarizine as compared to placebo showing a benefit from flunarizine with a low or probably low risk of bias. We found that flunarizine may increase the proportion of patients who discontinue due to adverse events compared to placebo (risk difference: 0.02; 95% CI -0.03 to 0.06).
CONCLUSIONS
Published flunarizine trials predate the recommended endpoints for evaluating migraine prophylaxis drugs, hence the lack of an adequate assessment for these endpoints. Further, modern-day, large-scale studies would be valuable in re-evaluating the efficacy of flunarizine for the treatment of migraines, offering additional insights into its potential benefits.
Topics: Humans; Flunarizine; Headache; Migraine Disorders; Migraine with Aura; Research Design; Transcription Factors
PubMed: 37723437
DOI: 10.1186/s10194-023-01657-3 -
International Journal of Molecular... Aug 2023The pharmacological treatment of postherpetic neuralgia (PHN) is unsatisfactory, and there is a clinical need for new approaches. Several drugs under advanced clinical...
The pharmacological treatment of postherpetic neuralgia (PHN) is unsatisfactory, and there is a clinical need for new approaches. Several drugs under advanced clinical development are addressed in this review. A systematic literature search was conducted in three electronic databases (Medline, Web of Science, Scopus) and in the ClinicalTrials.gov register from 1 January 2016 to 1 June 2023 to identify Phase II, III and IV clinical trials evaluating drugs for the treatment of PHN. A total of 18 clinical trials were selected evaluating 15 molecules with pharmacological actions on nine different molecular targets: Angiotensin Type 2 Receptor (AT2R) antagonism (olodanrigan), Voltage-Gated Calcium Channel (VGCC) α2δ subunit inhibition (crisugabalin, mirogabalin and pregabalin), Voltage-Gated Sodium Channel (VGSC) blockade (funapide and lidocaine), Cyclooxygenase-1 (COX-1) inhibition (TRK-700), Adaptor-Associated Kinase 1 (AAK1) inhibition (LX9211), Lanthionine Synthetase C-Like Protein (LANCL) activation (LAT8881), N-Methyl-D-Aspartate (NMDA) receptor antagonism (esketamine), mu opioid receptor agonism (tramadol, oxycodone and hydromorphone) and Nerve Growth Factor (NGF) inhibition (fulranumab). In brief, there are several drugs in advanced clinical development for treating PHN with some of them reporting promising results. AT2R antagonism, AAK1 inhibition, LANCL activation and NGF inhibition are considered first-in-class analgesics. Hopefully, these trials will result in a better clinical management of PHN.
Topics: Humans; Drugs, Investigational; Nerve Growth Factor; Neuralgia, Postherpetic; Pregabalin; Randomized Controlled Trials as Topic
PubMed: 37629168
DOI: 10.3390/ijms241612987 -
Cureus Mar 2024Mental health problems among children and adolescents are a significant global public health concern, with a prevalence of approximately 10-20%. Psychotropic... (Review)
Review
Mental health problems among children and adolescents are a significant global public health concern, with a prevalence of approximately 10-20%. Psychotropic medications, including stimulants, antipsychotics, antidepressants, and mood stabilizers, have been proven effective in treating various psychiatric disorders among children and adolescents. Despite the common use of these medications, they have various side effects and complications. This systematic review aimed to assess the trends and prevalence of psychotropic medication use among children and adolescents from 2013 to 2023. A comprehensive literature search was conducted in PubMed, Web of Science, Ovid, Scopus, and Cochrane databases using relevant keywords. Two independent researchers screened the studies for inclusion and exclusion criteria. Data were extracted using a Microsoft Excel spreadsheet (Microsoft Corporation, Redmond, WA), including information on study characteristics, participant demographics, psychiatric disorders, and psychotropic medications. The risk of bias assessment was performed using the ROBINS-I (Risk of Bias in Non-randomized Studies of Interventions) tool for non-randomized studies of interventions (NRSI) and Risk of Bias 2 (ROB2) for the randomized clinical trial. Data synthesis was conducted through a qualitative interpretation of the findings. A total of 52 papers were identified through the search, with 37 remaining after duplicate removal. After applying the inclusion and exclusion criteria, nine articles were considered suitable for the systematic review. A total of 9,034,109 patients suffered from several psychiatric diseases, such as autism, major depressive disorder, Down syndrome, attention-deficit/hyperactivity disorder, adjustment disorder, anxiety, bipolar disorder, conduct disorder, depression, personality disorder, psychotic disorder, tic disorder, pervasive developmental disorder, and disruptive behavior disorder. Stimulants showed a consistent prevalence rate over the years. Antidepressants, including selective serotonin reuptake inhibitors, have demonstrated variations over the years, with a substantial increase in 2015, followed by a decrease in subsequent years. In addition, antipsychotics, including atypical antipsychotics, have varied over the years; however, their use increased in 2023. Anticonvulsants and anxiolytics were also utilized, albeit at lower prevalence rates. This systematic review provides an overview of the trends and prevalence of psychotropic medication use among children and adolescents from 2013 to 2023. The prevalence of antipsychotic prescribing has shown fluctuations among different countries over the years, with a decline in recent years but a slight increase in 2023. Further research is warranted to explore the factors influencing these trends and to assess the long-term effectiveness and safety of psychotropic medications in children and adolescents.
PubMed: 38571846
DOI: 10.7759/cureus.55452 -
International Journal of Molecular... Feb 2024Cannabidiol (CBD), a non-psychoactive phytocannabinoid abundant in , has gained considerable attention for its anti-inflammatory, antioxidant, analgesic, and... (Review)
Review
Cannabidiol (CBD), a non-psychoactive phytocannabinoid abundant in , has gained considerable attention for its anti-inflammatory, antioxidant, analgesic, and neuroprotective properties. It exhibits the potential to prevent or slow the progression of various diseases, ranging from malignant tumors and viral infections to neurodegenerative disorders and ischemic diseases. Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease, and viral hepatitis stand as prominent causes of morbidity and mortality in chronic liver diseases globally. The literature has substantiated CBD's potential therapeutic effects across diverse liver diseases in in vivo and in vitro models. However, the precise mechanism of action remains elusive, and an absence of evidence hinders its translation into clinical practice. This comprehensive review emphasizes the wealth of data linking CBD to liver diseases. Importantly, we delve into a detailed discussion of the receptors through which CBD might exert its effects, including cannabinoid receptors, CB1 and CB2, peroxisome proliferator-activated receptors (PPARs), G protein-coupled receptor 55 (GPR55), transient receptor potential channels (TRPs), and their intricate connections with liver diseases. In conclusion, we address new questions that warrant further investigation in this evolving field.
Topics: Humans; Cannabidiol; Receptors, Cannabinoid; Cannabis; Digestive System Diseases; Liver Diseases, Alcoholic; Receptor, Cannabinoid, CB1
PubMed: 38397045
DOI: 10.3390/ijms25042370 -
Epilepsia Open Apr 2024Stiripentol, fenfluramine, and cannabidiol are licensed add-on therapies to treat seizures in Dravet Syndrome (DS). There are no direct or indirect comparisons assessing... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Stiripentol, fenfluramine, and cannabidiol are licensed add-on therapies to treat seizures in Dravet Syndrome (DS). There are no direct or indirect comparisons assessing their full licensed dose regimens, across different jurisdictions, as first-line add-on therapies in DS.
METHODS
We conducted a systematic review and frequentist network meta-analysis (NMA) of randomized controlled trial (RCT) data for licensed add-on DS therapies. We compared the proportions of patients experiencing: reductions from baseline in monthly convulsive seizure frequency (MCSF) of ≥50% (clinically meaningful), ≥75% (profound), and 100% (seizure-free); serious adverse events (SAEs); discontinuations due to AEs.
RESULTS
We identified relevant data from two placebo-controlled RCTs for each drug. Stiripentol 50 mg/kg/day and fenfluramine 0.7 mg/kg/day had similar efficacy in achieving ≥50% (clinically meaningful) and ≥75% (profound) reductions from baseline in MCSF (absolute risk difference [RD] for stiripentol versus fenfluramine 1% [95% confidence interval: -20% to 22%; p = 0.93] and 6% [-15% to 27%; p = 0.59], respectively), and both were statistically superior (p < 0.05) to licensed dose regimens of cannabidiol (10 or 20 mg/kg/day, with/irrespective of clobazam) for these outcomes. Stiripentol was statistically superior in achieving seizure-free intervals compared to fenfluramine (RD = 26% [CI: 8% to 44%; p < 0.01]) and licensed dose regimens of cannabidiol. There were no significant differences in the proportions of patients experiencing SAEs. The risk of discontinuations due to AEs was lower for stiripentol, although the stiripentol trials were shorter.
SIGNIFICANCE
This NMA of RCT data indicates stiripentol, as a first-line add-on therapy in DS, is at least as effective as fenfluramine and both are more effective than cannabidiol in reducing convulsive seizures. No significant difference in the incidence of SAEs between the three add-on agents was observed, but stiripentol may have a lower risk of discontinuations due to AEs. These results may inform clinical decision-making and the continued development of guidelines for the treatment of people with DS.
PLAIN LANGUAGE SUMMARY
This study compared three drugs (stiripentol, fenfluramine, and cannabidiol) used alongside other medications for managing seizures in a severe type of epilepsy called DS. The study found that stiripentol and fenfluramine were similarly effective in reducing seizures and both were more effective than cannabidiol. Stiripentol was the best drug for stopping seizures completely based on the available clinical trial data. All three drugs had similar rates of serious side effects, but stiripentol had a lower chance of being stopped due to side effects. This information can help guide treatment choices for people with DS.
Topics: Humans; Cannabidiol; Anticonvulsants; Fenfluramine; Network Meta-Analysis; Seizures; Epilepsies, Myoclonic; Randomized Controlled Trials as Topic; Dioxolanes
PubMed: 38427284
DOI: 10.1002/epi4.12923