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Journal of Managed Care & Specialty... Dec 2023People with multiple sclerosis (MS) are often prescribed medications associated with adverse effects on bone health. However, it is unclear whether these medications... (Meta-Analysis)
Meta-Analysis
BACKGROUND
People with multiple sclerosis (MS) are often prescribed medications associated with adverse effects on bone health. However, it is unclear whether these medications incur decreases in areal bone mineral density (aBMD) and higher fracture risk in this population.
OBJECTIVE
To investigate the effects of commonly used medications on aBMD and fracture risk among people with MS.
METHODS
MEDLINE, Embase, Scopus, CINAHL, and Web of Science were searched from their inception until February 5, 2023. We included randomized controlled trials as well as cross-sectional, retrospective, and prospective studies investigating whether glucocorticoids, immunomodulators, antidepressants, anticonvulsants, anxiolytics, opioids, or antipsychotics influenced aBMD or fracture risk in people with MS. Data were pooled using random effects meta-analyses to determine hazard ratios (HRs) and 95% CIs.
RESULTS
We included 22 studies (n = 18,193). Six studies were included in the meta-analyses of glucocorticoid use and aBMD, whereas 2 studies were included in the medication use and fracture risk meta-analyses. No studies assessed the effect of antidepressants, anxiolytics, anticonvulsants, opioids, and antipsychotics on aBMD, and no studies assessed the effect of immunomodulators on fracture risk. Glucocorticoid use was significantly negatively associated with femoral neck aBMD (correlation = -0.21 [95% CI = -0.29 to -0.13]), but not with lumbar spine aBMD (correlation = -0.21 [95% CI = -0.50 to 0.12]). There were no differences in fracture risk between users of glucocorticoids (HR = 1.71 [95% CI = 0.04 to 76.47]), antidepressants (HR = 1.84 [95% CI = 0.09 to 38.49]), or anxiolytics (HR = 2.01 [95% CI = 0.06 to 64.22]), compared with nonusers.
CONCLUSIONS
The available evidence is insufficient to support a relationship between greater fracture risk for people with MS taking glucocorticoid, antidepressant, or anxiolytic medication, compared with nonusers, and it is unclear whether these medications are associated with bone loss in people with MS, beyond that in the general population. Additional high-quality studies with homogenous methodology exploring how medications influence aBMD and fracture risk in people with MS are required.
Topics: Humans; Bone Density; Prospective Studies; Anticonvulsants; Anti-Anxiety Agents; Retrospective Studies; Cross-Sectional Studies; Glucocorticoids; Multiple Sclerosis; Fractures, Bone; Antidepressive Agents; Immunologic Factors
PubMed: 38058136
DOI: 10.18553/jmcp.2023.29.12.1331 -
Archives of Gynecology and Obstetrics Mar 2024Magnesium sulfate (MgSO) has been widely used in obstetrics as a mean to help decrease maternal and neonatal morbidity in various antenatal pathology. As a factor, it... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Magnesium sulfate (MgSO) has been widely used in obstetrics as a mean to help decrease maternal and neonatal morbidity in various antenatal pathology. As a factor, it seems to regulate immunity and can, thus, predispose to infectious morbidity. To date, it remains unknown if its administration can increase the risk of chorioamnionitis. In the present meta-analysis, we sought to accumulate the available evidence.
METHODS
We systematically searched Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL, and Google Scholar databases in our primary search along with the reference lists of electronically retrieved full-text papers.
RESULTS
Eight studies were included that investigated the incidence of chorioamnionitis among parturient that received MgSO and control patients. Magnesium sulfate was administered in 3229 women and 3330 women served as controls as they did not receive MgSO. The meta-analysis of data revealed that there was no association between the administration of magnesium sulfate and the incidence of chorioamnionitis (OR 0.98, 95% CI 0.73, 1.32). Rucker's analysis revealed that small studies did not significantly influence the statistical significance of this finding (OR 1.12, 95% CI 0.82, 1.53). Trial sequential analysis revealed that the required number to safely interpret the primary outcome was not reached. Two studies evaluated the impact of MgSO in neonates delivered in the setting of chorioamnionitis. Neither of these indicated the presence of a beneficial effect in neonatal morbidity, including the risk of cerebral palsy, intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, sepsis, stillbirth, or neonatal death.
CONCLUSION
Current evidence indicates that magnesium sulfate is not associated with an increased risk of maternal chorioamnionitis. However, it should be noted that its effect on neonatal outcomes of offspring born in the setting of chorioamnionitis might be subtle if any, although the available evidence is very limited.
Topics: Infant, Newborn; Pregnancy; Humans; Female; Chorioamnionitis; Magnesium Sulfate; Stillbirth; Fetal Diseases; Perinatal Death
PubMed: 37768342
DOI: 10.1007/s00404-023-07221-3 -
PloS One 2024Juvenile Myoclonic Epilepsy (JME) is a prevalent form of epileptic disorder, specifically categorized within the realm of Genetic Generalized Epilepsy (GGE). Its... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Juvenile Myoclonic Epilepsy (JME) is a prevalent form of epileptic disorder, specifically categorized within the realm of Genetic Generalized Epilepsy (GGE). Its hallmark features encompass unprovoked bilateral myoclonus and tonic-clonic seizures that manifest during adolescence. While most JME patients respond favorably to anti-seizure medication (ASM), a subset experiences refractory JME, a condition where seizures persist despite rigorous ASM treatment, often termed "Drug-Resistant Epilepsy" (DRE). This systematic review and meta-analysis aims to determine the prevalence of refractory JME, and further to identify socio-demographic, electrophysiological and clinical risk factors associated with its occurrence. Pinpointing these factors is crucial as it offers the potential to predict ASM responsiveness, enabling early interventions and tailored care strategies for patients.
MATERIAL AND METHODS
The systematic review and meta-analysis followed the Cochrane Handbook and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The study evaluated outcomes post ASM treatment in JME cohorts by searching papers published up to September 2023 in PubMed/MEDLINE, Scopus, and Google Scholar databases. Predefined inclusion criteria were met by 25 eligible studies, forming the basis for analysis.
RESULTS
A total of 22 potential risk factors for refractory JME were documented. Notably, robust risk factors for treatment resistance included Psychiatric Disorder (Odds Ratio (OR), 3.42 [2.54, 4.61] (95% Confidence Inverval (Cl)), Febrile Seizures (OR, 1.83 [1.14, 2.96] (95% Cl)), Alcohol Consumption (OR, 16.86 [1.94, 146.88] (95%Cl)), Aura (OR, 2.15 [1.04, 4.47] (95%Cl)), childhood absence epilepsy (CAE) evolving into JME (OR, 4.54 [1.61, 12.78] (95%CI)), occurrence of three seizure types (OR, 2.96 [1.96, 4.46] (95%CI)), and Focal EEG abnormalities (OR, 1.85 [1.13, 3.01] (95%Cl)). In addition, there were some non-significant risk factors for DRE because of noticeable heterogeneity.
CONCLUSION
In aggregate, over 36% of JME patients demonstrated drug resistance, with seven significant risk factors closely linked to this refractoriness. The interplay between these factors and whether they denote treatment non-response or heightened disease burden remains an open question and more studies would be required to fully examine their influence.
Topics: Adolescent; Humans; Child; Myoclonic Epilepsy, Juvenile; Epilepsy, Absence; Seizures; Drug Resistant Epilepsy; Risk Factors; Electroencephalography; Anticonvulsants
PubMed: 38593118
DOI: 10.1371/journal.pone.0300930 -
The Journal of Headache and Pain Dec 2023Chronic migraine can be a profoundly disabling disorder that may be treated with preventive medications. However, uncertainty remains as to which preventive medication... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chronic migraine can be a profoundly disabling disorder that may be treated with preventive medications. However, uncertainty remains as to which preventive medication is the most effective. We present a network meta-analysis to determine the effectiveness and rank of preventive drugs for chronic migraine in adults.
METHODS
We identified, reviewed, and extracted data from randomised controlled trials (RCTs) of preventive drugs for chronic migraine with at least 200 participants. Data were analysed using network meta-analysis.
FINDINGS
We included 12 RCTs of six medications (Eptinezumab, Erenumab, Fremanezumab, Galcanezumab, Onabotulinumtoxin A, and Topiramate) compared to placebo or each other. All drugs effectively reduced monthly headache and migraine days compared with placebo. The most effective drug for monthly headache days was Eptinezumab 300mg, with a mean difference of -2.46 days, 95% Credible Interval (CrI): -3.23 to -1.69. On the Surface Under the Cumulative Ranking Area (SUCRA) analysis, the probability that Eptinezumab 300mg was ranked highest was 0.82. For monthly migraine days, the most effective medication was Fremanezumab-monthly, with a mean difference: -2.77 days, 95% CrI: -3.36 to -2.17, and 0.98 probability of being ranked the highest. All included drugs, except Topiramate, improved headache-related quality of life. No eligible studies were identified for the other common preventive oral medications such as Amitriptyline, Candesartan, and Propranolol. The main reasons were that the studies did not define chronic migraine, were undertaken before the definition of chronic migraine, or were too small.
INTERPRETATION
All six medications were more effective than the placebo on monthly headache and migraine days. The absolute differences in the number of headache/migraine days are, at best, modest. No evidence was found to determine the relative effectiveness of the six included drugs with other oral preventive medications.
REGISTRATION
PROSPERO (number CRD42021265990).
Topics: Adult; Humans; Topiramate; Network Meta-Analysis; Migraine Disorders; Treatment Outcome; Headache; Double-Blind Method
PubMed: 38057728
DOI: 10.1186/s10194-023-01696-w -
Neuropsychopharmacology Reports Sep 2023Previous behavioral pharmacology studies involving rodents suggested riluzole had potential to be an ideal psychotropic drug for psychiatric disorders with anxiety or... (Review)
Review
AIM
Previous behavioral pharmacology studies involving rodents suggested riluzole had potential to be an ideal psychotropic drug for psychiatric disorders with anxiety or fear as primary symptoms. Several clinical studies have recently been conducted. The purpose of this study was to gather information about the efficacy and tolerability of riluzole for patients with those symptoms.
METHODS
We searched PubMed, PsycINFO, CINAHL, EMBASE, and the Cochrane database from inception until April 2021, and performed manual searches for additional relevant articles. This review included: (1) studies involving participants that were patients with generalized anxiety disorder (GAD), social anxiety disorder, panic disorder, obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), acute stress disorder, or phobias; and (2) randomized controlled trials (RCTs) or intervention studies (e.g., single arm trials) examining the effects and safety of riluzole.
RESULTS
Of the 795 identified articles, four RCTs, one RCT subgroup-analysis, and three open-label trials without control groups met the inclusion criteria. Most trials evaluated the efficacy of riluzole as an augmentation therapy with selective serotonin reuptake inhibitors and other antidepressants for PTSD, OCD, or GAD. However, there was insufficient evidence to confirm the effects of riluzole for patients with these psychiatric disorders. Most trials demonstrated adequate study quality.
CONCLUSIONS
This review found insufficient evidence to confirm the effects of riluzole for psychiatric disorders with anxiety or fear as primary symptoms. It would be worthwhile to conduct studies that incorporate novel perspectives, such as examining the efficacy of riluzole as a concomitant medication for psychotherapy.
Topics: Humans; Riluzole; Anxiety Disorders; Anxiety; Obsessive-Compulsive Disorder; Fear
PubMed: 37463744
DOI: 10.1002/npr2.12364 -
Epilepsy & Behavior : E&B Aug 2023Epilepsy is one of the most common neurological conditions worldwide. The main goal of its treatment is to achieve seizure freedom without intolerable adverse effects....
Value contribution of cenobamate for the treatment of Focal-Onset Seizures (FOS) in patients with drug-resistant epilepsy (DRE) in Spain through reflective Multi-Criteria Decision Analysis (MCDA).
INTRODUCTION
Epilepsy is one of the most common neurological conditions worldwide. The main goal of its treatment is to achieve seizure freedom without intolerable adverse effects. However, despite the availability of many anti-seizure medications, including the latest options, called third-generation anti-seizure medications (ASMs), approximately 40% of people with epilepsy present drug-resistant epilepsy (DRE). Cenobamate is the first ASM approved in Spain for the adjunctive treatment of Focal-Onset Seizures (FOS) in adult patients with DRE. In a chronic disease with a portfolio of available ASMs, the decision to introduce a new therapeutic alternative must follow a holistic evaluation of value provided. Reflective Multi-Criteria Decision Analysis (MCDA) methodology allows to determine the value contribution of a treatment in a given indication considering all relevant criteria for healthcare decision-making in a transparent and systematic manner from the perspective of relevant stakeholders.
PURPOSE
The aim of this study was to determine the relative value contribution of cenobamate in the treatment of FOS in patients with DRE compared with third-generation ASMs using reflective MCDA-based methodology.
METHODS
A systematic literature review (combining biomedical databases and grey literature sources) was performed to populate the Evidence and Value: Impact on DEcisionMaking (EVIDEM) MCDA framework adapted to determine what represents value in the management of FOS in patients with DRE in Spain. The study was conducted in two phases. The first took place in 2021 with a multi-stakeholder group of eight participants. The second phase was conducted in 2022 with a multi-stakeholder group of 32 participants. Participants were trained in MCDA methodology and scored four evidence matrices (cenobamate vs. brivaracetam, vs. perampanel, vs. lacosamide and vs. eslicarbazepine acetate). Results were analyzed and discussed in a group meeting through reflective MCDA discussion methodology.
RESULTS
DRE is considered a very severe condition associated with many important unmet needs, mainly with regard to the lack of more effective treatments to achieve the ultimate goal of treatment. Compared to third-generation ASMs, cenobamate is perceived to have a better efficacy profile based on improvements in responder rate and seizure freedom. Regarding safety, it is considered to have a similar profile to alternatives and a positive quality-of-life profile. Cenobamate results in lower direct medical costs (excluding pharmacological) and indirect costs. Overall, cenobamate is regarded as providing a high therapeutic impact and supported by high-quality evidence.
CONCLUSIONS
Based on reflective MCDA methodology and stakeholders' experience in clinical management of epilepsy in Spain, cenobamate is perceived as a value-added option for the treatment of patients with DRE when compared with third-generation ASMs.
Topics: Adult; Humans; Spain; Drug Resistant Epilepsy; Epilepsy; Treatment Outcome; Decision Support Techniques; Anticonvulsants
PubMed: 37480633
DOI: 10.1016/j.yebeh.2023.109350 -
Journal of Neurology Oct 2023The epileptogenic properties of white matter lesions (WML) in cerebral small vessel disease (CSVD) are not yet understood. The aim of our systematic review and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The epileptogenic properties of white matter lesions (WML) in cerebral small vessel disease (CSVD) are not yet understood. The aim of our systematic review and meta-analysis was to estimate the association between the extent of WML in CSVD and epilepsy, analyze whether these WML are associated with an increased risk of seizure recurrence, and evaluate if treatment with anti-seizure medication (ASM) is justified in first-seizure patients with WML and no cortical lesions.
METHODS
Following a pre-registered study protocol (PROSPERO-ID CRD42023390665), we systematically searched Pubmed and Embase for relevant literature comparing WML load between patients with epilepsy and controls as well as studies on seizure recurrence risk and ASM therapy in the presence vs. absence of WML. We calculated pooled estimates using a random effects model.
RESULTS
Eleven studies comprising 2983 patients were included in our study. Presence of WML (OR 2.14, 95% CI 1.38-3.33) and presence of relevant WML as assessed by visual rating scales (OR 3.96, 95% CI 2.55-6.16) but not WML volume (OR 1.30, 95% CI 0.91-1.85) were significantly associated with seizures. These results stayed robust in sensitivity analyses restricted to studies on patients with late-onset seizures/epilepsy. Only two studies assessed the association between WML and risk of seizure recurrence with conflicting results. Currently, there are no studies on the efficacy of ASM therapy in the presence of WML in CSVD.
CONCLUSIONS
This meta-analysis suggests an association between presence of WML in CSVD and seizures. More research is needed addressing the association between WML and risk of seizure recurrence and ASM therapy focusing on a population of patients with a first unprovoked seizure.
Topics: Humans; Anticonvulsants; White Matter; Epilepsy; Cerebral Small Vessel Diseases
PubMed: 37341807
DOI: 10.1007/s00415-023-11828-6 -
Progress in Neuro-psychopharmacology &... Jul 2024Increasing evidence suggests that the physiological changes of pregnancy may impact pharmacokinetics of antiseizure medications (ASM), and this may affect treatment... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Increasing evidence suggests that the physiological changes of pregnancy may impact pharmacokinetics of antiseizure medications (ASM), and this may affect treatment outcomes. The aim of this study was to quantify the pregnancy impact on the ASM pharmacokinetics.
METHODS
A systematic literature search was conducted in PubMed/EMBASE in November 2022 and updated in August 2023 for studies comparing levels of ASM in the same individuals during pregnancy and in the preconception/postpartum period. Alteration ratios between the 3rd trimester and baseline were estimated. We also performed a random-effects meta-analysis calculating between-timepoint differences in mean differences (MDs) and 95% confidence intervals (95%CIs) for dose-adjusted plasma concentrations (C/D ratios). Study quality was assessed using the ClinPK guidelines.
RESULTS
A total of 65 studies investigating 15 ASMs in 674 pregnancies were included. The largest differences were reported for lamotrigine, oxcarbazepine and levetiracetam (alteration ratio 0.42, range 0.07-2.45, 0.42, range 0.08-0.82 and 0.52, range 0.04-2.77 respectively): accordingly, C/D levels were lower in the 3rd trimester for lamotrigine, levetiracetam and the main oxcarbazepine metabolite monohydroxycarbazepine (MD = -12.33 × 10, 95%CI = -16.08 to -8.58 × 10 (μg/mL)/(mg/day), p < 0.001, MD = -7.16 (μg/mL)/(mg/day), 95%CI = -9.96 to -4.36, p < 0.001, and MD = -4.87 (μg/mL)/(mg/day), 95%CI = -9.39 to -0.35, p = 0.035, respectively), but not for oxcarbazepine (MD = 1.16 × 10 (μg/mL)/(mg/day), 95%CI = -2.55 to 0.24 × 10, p = 0.10). The quality of studies was acceptable with an average rating score of 11.5.
CONCLUSIONS
Data for lamotrigine, oxcarbazepine (and monohydroxycarbazepine) and levetiracetam demonstrate major changes in pharmacokinetics during pregnancy, suggesting the importance of therapeutic drug monitoring to assist clinicians in optimizing treatment outcomes.
Topics: Humans; Pregnancy; Anticonvulsants; Female; Pregnancy Complications; Levetiracetam; Lamotrigine; Epilepsy; Oxcarbazepine
PubMed: 38762161
DOI: 10.1016/j.pnpbp.2024.111030 -
Psychiatry Research Jun 2024Cannabidiol (CBD), as one of the phytocannabinoids, has a wide range of therapeutic properties for various neuropsychiatric disorders due to central nervous system... (Review)
Review
Cannabidiol (CBD), as one of the phytocannabinoids, has a wide range of therapeutic properties for various neuropsychiatric disorders due to central nervous system effects. These therapeutic properties demonstrated by preclinical and clinical studies encompass more than just anticonvulsant, anti-arthritic, analgesic, anti-inflammatory, antioxidant, antitumor, antiemetic, antipsychotic and neuroprotective effects. It has been hypothesized that CBD holds potential in the treatment of various neuropsychiatric and anxiety disorders. Thus, PRISMA was used as a guide for our systematic review. Eight of the 1550 articles screened in June 2023 were eligible for meta-analysis. Based on the 316 participants included in these eight articles, this meta-analysis revealed a substantial significant impact of CBD on anxiety with a considerable effect size (Hedges' g = -0.92, 95% CI -1.80 to -0.04). In addition, this meta-analysis focuses on the efficacy of CBD in treating anxiety disorders such as generalized anxiety disorder (GAD), social anxiety disorder (SAD), and post-traumatic stress disorder (PTSD). However, caution should be exercised in interpreting our findings due to the limited size of the clinical sample, and additional trials ought to be carried out if deemed necessary.
PubMed: 38924898
DOI: 10.1016/j.psychres.2024.116049 -
Frontiers in Medicine 2023Stevens-Johnson syndrome (SJS) is considered a hypersensitivity syndrome affecting the skin and mucous membranes. It has been reported that an anticonvulsant drug,...
BACKGROUND
Stevens-Johnson syndrome (SJS) is considered a hypersensitivity syndrome affecting the skin and mucous membranes. It has been reported that an anticonvulsant drug, oxcarbazepine, may cause Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN). However, the clinical features of oxcarbazepine-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) remain ambiguous. This article aims to explore the clinical features of SJS/TEN.
METHODS
Systematic searches of several Chinese and English databases were conducted for case reports published on PubMed, EMBASE, Web of Science, MEDLINE, CNKI from January 1, 2007 to March 1, 2023.
RESULTS
A total of seventeen patients (10 males and 7 females) were included in this study, including nine adult patients and eight pediatric patients. The results showed that males seem to have a higher prevalence of SJS/TEN than females, and SJS/TEN usually occurs within 2 weeks after administration of oxcarbazepine (OXC). The main clinical manifestations among the included patients were rashes or maculopapules (17 cases, 100%), fever (11 cases, 64.7%), mucosal lesions (15 cases, 88.2%), conjunctivitis with/without ocular discharge (12 cases, 70.6%), and blisters (12 cases, 70.6%). After stopping OXC or switching to other drugs that treat primary disease as well as treatment with IVIG, glucocorticoid, anti-allergy, and fluid replacement, eight of the included patients recovered completely, and another eight of the included patients reported symptomatic improvement, while the prognosis of one of the included patients was not reported.
CONCLUSION
Diverse clinical signs and symptoms of SJS/TEN might result in misinterpretation and delayed diagnosis. It should be identified and treated immediately to avoid significant consequences and potentially jeopardize patients' lives.
PubMed: 37881633
DOI: 10.3389/fmed.2023.1232969