Dataset Information

Efficacy, Safety, and Acceptability of Pharmacologic Treatments for Pediatric Migraine Prophylaxis: A Systematic Review and Network Meta-analysis.

ABSTRACT:

Importance

Migraine is one of the most common neurologic disorders in children and adolescents. However, a quantitative comparison of multiple preventive pharmacologic treatments in the pediatric population is lacking.

Objective

To examine whether prophylactic pharmacologic treatments are more effective than placebo and whether there are differences between drugs regarding efficacy, safety, and acceptability.

Data sources

Systematic review and network meta-analysis of studies in MEDLINE, Cochrane, Embase, and PsycINFO published through July 2, 2018.

Study selection

Randomized clinical trials of prophylactic pharmacologic treatments in children and adolescents diagnosed as having episodic migraine were included. Abstract, title, and full-text screening were conducted independently by 4 reviewers.

Data extraction and synthesis

Data extraction was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis network meta-analysis guidelines. Quality was assessed with the Cochrane Risk of Bias tool. Effect sizes, calculated as standardized mean differences for primary outcomes and risk ratios for discontinuation rates, were assessed in a random-effects model.

Main outcomes and measures

Primary outcomes were efficacy (ie, migraine frequency, number of migraine days, number of headache days, headache frequency, or headache index), safety (ie, treatment discontinuation owing to adverse events), and acceptability (ie, treatment discontinuation for any reason).

Results

Twenty-three studies (2217 patients) were eligible for inclusion. Prophylactic pharmacologic treatments included antiepileptics, antidepressants, calcium channel blockers, antihypertensive agents, and food supplements. In the short term (<5 months), propranolol (standard mean difference, 0.60; 95% CI, 0.03-1.17) and topiramate (standard mean difference, 0.59; 95% CI, 0.03-1.15) were significantly more effective than placebo. However, the 95% prediction intervals for these medications contained the null effect. No significant long-term effects for migraine prophylaxis relative to placebo were found for any intervention.

Conclusions and relevance

Prophylactic pharmacologic treatments have little evidence supporting efficacy in pediatric migraine. Future research could (1) identify factors associated with individual responses to pharmacologic prophylaxis, (2) analyze fluctuations of migraine attack frequency over time and determine the most clinically relevant length of probable prophylactic treatment, and (3) identify nonpharmacologic targets for migraine prophylaxis.

SUBMITTER: Locher C

PROVIDER: S-EPMC7042942 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Efficacy, Safety, and Acceptability of Pharmacologic Treatments for Pediatric Migraine Prophylaxis: A Systematic Review and Network Meta-analysis.

Locher Cosima C Kossowsky Joe J Koechlin Helen H Lam Thanh Lan TL Barthel Johannes J Berde Charles B CB Gaab Jens J Schwarzer Guido G Linde Klaus K Meissner Karin K

JAMA pediatrics 20200401 4

<h4>Importance</h4>Migraine is one of the most common neurologic disorders in children and adolescents. However, a quantitative comparison of multiple preventive pharmacologic treatments in the pediatric population is lacking.<h4>Objective</h4>To examine whether prophylactic pharmacologic treatments are more effective than placebo and whether there are differences between drugs regarding efficacy, safety, and acceptability.<h4>Data sources</h4>Systematic review and network meta-analysis of studi ...[more]

PMID: 32040139

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Project description:ObjectivesSystematic review of preventive pharmacologic treatments for community-dwelling adults with episodic migraine.Data sourcesElectronic databases through May 20, 2012.Eligibility criteriaEnglish-language randomized controlled trials (RCTs) of preventive drugs compared to placebo or active treatments examining rates of ?50 % reduction in monthly migraine frequency or improvement in quality of life.Study appraisal and synthesis methodsWe assessed risk of bias and strength of evidence and conducted random effects meta-analyses of absolute risk differences and Bayesian network meta-analysis.ResultsOf 5,244 retrieved references, 215 publications of RCTs provided mostly low-strength evidence because of the risk of bias and imprecision. RCTs examined 59 drugs from 14 drug classes. All approved drugs, including topiramate (9 RCTs), divalproex (3 RCTs), timolol (3 RCTs), and propranolol (4 RCTs); off-label beta blockers metoprolol (4 RCTs), atenolol (1 RCT), nadolol (1 RCT), and acebutolol (1 RCT); angiotensin-converting enzyme inhibitors captopril (1 RCT) and lisinopril (1 RCT); and angiotensin II receptor blocker candesartan (1 RCT), outperformed placebo in reducing monthly migraine frequency by ?50 % in 200-400 patients per 1,000 treated. Adverse effects leading to treatment discontinuation (68 RCTs) were greater with topiramate, off-label antiepileptics, and antidepressants than with placebo. Limited direct evidence as well as frequentist and exploratory network Bayesian meta-analysis showed no statistically significant differences in benefits between approved drugs. Off-label angiotensin-inhibiting drugs and beta-blockers were most effective and tolerable for episodic migraine prevention.LimitationsWe did not quantify reporting bias or contact principal investigators regarding unpublished trials.ConclusionsApproved drugs prevented episodic migraine frequency by ?50 % with no statistically significant difference between them. Exploratory network meta-analysis suggested that off-label angiotensin-inhibiting drugs and beta-blockers had favorable benefit-to-harm ratios. Evidence is lacking for long-term effects of drug treatments (i.e., trials of more than 3 months duration), especially for quality of life.

Project description:BackgroundIn the absence of head-to-head trials, comprehensive evidence comparing onset of efficacy of novel agents for acute treatment of migraine is lacking. This study aimed to explore the relative efficacy of lasmiditan (serotonin [5-hydroxytryptamine] 1F receptor agonist) versus rimegepant and ubrogepant (calcitonin gene-related peptide antagonists) for the acute oral treatment of migraine through network meta-analysis (NMA).MethodsData included in the NMA were identified through a systematic literature search (conducted April 2018, updated May/December 2020) of phase II-IV, randomised controlled trials (RCTs) in adults with chronic/episodic migraine with/without aura. Treatments included: lasmiditan 50, 100, 200 mg; rimegepant 75 mg; ubrogepant 25, 50, 100 mg. Pairwise treatment comparisons from Bayesian fixed-effect/random-effects NMA, adjusted by baseline risk where appropriate, were conducted. Comparisons were reported as odds ratios with 95% credible intervals. Early-onset efficacy endpoints included: pain freedom at 2 hours and pain relief at 1 and 2 hours. Adverse drug reaction (ADR) profiles were summarised. Heterogeneity and inconsistency in the network were explored; sensitivity analyses investigated robustness of findings.ResultsAcross 12 RCTs included in the base case, females represented >80% of included patients (mean age 37.9-45.7 years). Odds of achieving both pain freedom and pain relief at 2 hours were higher with lasmiditan 100 and 200 mg versus rimegepant 75 mg and ubrogepant 25 and 50 mg. Results for pain relief at 1 hour were consistent with those at 2 hours, but fewer comparisons were available. There were no statistically significant differences between lasmiditan 50 mg and ubrogepant or rimegepant for any outcome. Sensitivity analyses were in the same direction as base case analyses. Most commonly reported ADRs (incidence ≥2%) were: dizziness, fatigue, paraesthesia, sedation, nausea/vomiting and muscle weakness with lasmiditan; nausea with rimegepant; and nausea, somnolence and dry mouth with ubrogepant.ConclusionsThe efficacy findings of this indirect comparison indicate that lasmiditan 100 mg or 200 mg might be an appropriate acute treatment option for patients with migraine seeking a fast onset of action. Differently from rimegepant and ubrogepant, lasmiditan use is associated with mainly neurological events, which are mostly mild or moderate in severity and self-limiting. 350/350 words.

Project description:BackgroundCumulative exposure to one or more anticholinergic medications ("anticholinergic burden") is associated with an increased risk of adverse outcomes, particularly among older individuals. Mirabegron, an oral selective β3-adrenergic receptor agonist, has demonstrated efficacy in managing the symptoms of overactive bladder without contributing to anticholinergic burden. However, it is not known whether the favorable safety profile of mirabegron relative to antimuscarinics varies with increasing age among a patient population who may have a high anticholinergic burden.ObjectiveThe primary objective of this study was to indirectly compare the safety and efficacy profile of mirabegron relative to antimuscarinics in older adults with overactive bladder.MethodsA systematic literature review was conducted to identify randomized controlled trials that reported safety and efficacy endpoints among patients aged ≥ 65 years. Identified randomized controlled trials were subsequently synthesized via a network meta-analysis. Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines in designing, performing, and reporting the literature review were followed. In line with current best practices, the network meta-analysis was conducted using a Bayesian approach and according to the overall general guidance for evidence synthesis developed by the National Institute for Health and Care Excellence decision support unit. Estimates of relative safety were assessed via the odds ratio and estimates of relative efficacy were assessed via means and credible intervals.ResultsA total of 3078 abstracts, 300 of which underwent full-text screening, were identified using the search criteria. Twenty articles reporting on 21 randomized controlled trials were eligible for data extraction and synthesis. Following review, five safety and five efficacy endpoints were considered for inclusion in the network meta-analysis. Regarding findings typical of anticholinergic exposure in older adults, mirabegron was not associated with an increased odds of dry mouth (odds ratio 95% credible interval 0.76 [0.26-2.37]) or constipation (1.08 [0.39-3.02]) relative to placebo, whereas antimuscarinics were strongly associated with these events (odds ratio range 3.78-7.85 and 2.12-4.66, respectively). In this older population, mirabegron was associated with a similar odds of experiencing adverse event-related treatment discontinuations relative to placebo (0.99 [0.57-1.70]), while the odds of experiencing an adverse event-related treatment discontinuation for antimuscarinics had a range of 1.14-3.03 (in most cases, the association was mild). No increased odds of experiencing overall treatment-emergent adverse events was observed for mirabegron or antimuscarinics (odds ratio range 1.25-1.55), apart from fesoterodine (2.23 [1.37-3.37]). Finally, a similar treatment effect was observed across all efficacy endpoints between mirabegron and antimuscarinics in this older population.ConclusionsThis study indicates that the safety and efficacy profile of mirabegron remains favorable compared with antimuscarinics among older adults. This includes safety outcomes typically associated with anticholinergic burden, which were less frequently observed in patients treated with mirabegron.

Project description:ObjectiveTo determine, in critically ill patients, the relative impact of proton pump inhibitors (PPIs), histamine-2 receptor antagonists (H2RAs), sucralfate, or no gastrointestinal bleeding prophylaxis (or stress ulcer prophylaxis) on outcomes important to patients.DesignSystematic review and network meta-analysis.Data sourcesMedline, PubMed, Embase, Cochrane Central Register of Controlled Trials, trial registers, and grey literature up to March 2019.Eligibility criteria for selecting studies and methodsWe included randomised controlled trials that compared gastrointestinal bleeding prophylaxis with PPIs, H2RAs, or sucralfate versus one another or placebo or no prophylaxis in adult critically ill patients. Two reviewers independently screened studies for eligibility, extracted data, and assessed risk of bias. A parallel guideline committee (BMJ Rapid Recommendation) provided critical oversight of the systematic review, including identifying outcomes important to patients. We performed random-effects pairwise and network meta-analyses and used GRADE to assess certainty of evidence for each outcome. When results differed between low risk and high risk of bias studies, we used the former as best estimates.ResultsSeventy two trials including 12?660 patients proved eligible. For patients at highest risk (>8%) or high risk (4-8%) of bleeding, both PPIs and H2RAs probably reduce clinically important gastrointestinal bleeding compared with placebo or no prophylaxis (odds ratio for PPIs 0.61 (95% confidence interval 0.42 to 0.89), 3.3% fewer for highest risk and 2.3% fewer for high risk patients, moderate certainty; odds ratio for H2RAs 0.46 (0.27 to 0.79), 4.6% fewer for highest risk and 3.1% fewer for high risk patients, moderate certainty). Both may increase the risk of pneumonia compared with no prophylaxis (odds ratio for PPIs 1.39 (0.98 to 2.10), 5.0% more, low certainty; odds ratio for H2RAs 1.26 (0.89 to 1.85), 3.4% more, low certainty). It is likely that neither affect mortality (PPIs 1.06 (0.90 to 1.28), 1.3% more, moderate certainty; H2RAs 0.96 (0.79 to 1.19), 0.9% fewer, moderate certainty). Otherwise, results provided no support for any affect on mortality, Clostridium difficile infection, length of intensive care stay, length of hospital stay, or duration of mechanical ventilation (varying certainty of evidence).ConclusionsFor higher risk critically ill patients, PPIs and H2RAs likely result in important reductions in gastrointestinal bleeding compared with no prophylaxis; for patients at low risk, the reduction in bleeding may be unimportant. Both PPIs and H2RAs may result in important increases in pneumonia. Variable quality evidence suggested no important effects of interventions on mortality or other in-hospital morbidity outcomes.Systematic review registrationPROSPERO CRD42019126656.

Project description:ImportancePosttraumatic stress disorder (PTSD) is a prevalent mental disorder, with a high risk of chronicity, comorbidity, and functional impairment; PTSD is complicated to treat, and the debate on the best treatment approach is ongoing.ObjectiveTo examine comparative outcomes and acceptability of psychotherapeutic and pharmacological treatments and their combinations in adults with PTSD.Data sourcesEmbase, MEDLINE, PsycINFO, Cochrane Controlled Trials Register, and PSYNDEX were searched for studies published from January 1, 1980, to February 28, 2018. Reference lists of included studies and of previously published guidelines and systematic reviews were also searched.Study selectionOf 11 417 records identified, 12 published randomized clinical trials (RCTs) comprising 922 participants, contributing 23 direct comparisons between psychotherapeutic and pharmacological treatments or their combinations were included.Data extraction and synthesisStandardized mean differences (SMDs) and odds ratios were aggregated using random-effects network and pairwise meta-analyses. Risk of bias and indirectness was rated for each study, and network confidence was rated using the Confidence in Network Meta-Analysis framework.Main outcomes and measuresThe primary outcome was the comparative benefit between 2 treatment approaches to PTSD symptom improvement, and secondary outcome was the comparative acceptability of the treatment approaches, as indicated by patient dropout rates before treatment termination.ResultsNo treatment approach was found to be superior at the end of treatment (for all, 95% CI included 0). At the last follow-up, psychotherapeutic treatments showed greater benefit than pharmacological treatments in both network (SMD, -0.83; 95% CI, -1.59 to -0.07) and pairwise (SMD, -0.63; 95% CI, -1.18 to -0.09, 3 RCTs) meta-analyses. No difference was found between combined treatments and psychotherapeutic treatments at long-term follow-up, and combined treatments were associated with better outcomes than pharmacological treatments in the network meta-analysis (SMD, -0.96; 95% CI, -1.87 to -0.04), but not in the pairwise meta-analysis, which included 2 RCTs (SMD, -1.02; 95% CI, -2.77 to 0.72). No evidence was found for differential acceptability of the 3 treatment approaches.Conclusions and relevanceThese results suggest superiority of psychotherapeutic treatments over pharmacological treatments; network, but not pairwise, meta-analyses suggest superiority of combined treatments over pharmacological treatments in improving PTSD symptom severity in the long term. The scarcity of reported long-term findings hampers definite conclusions and demonstrates the need for robust evidence from large-scaled comparative trials providing long-term follow-up data.

Project description:BackgroundMigraine is a chronic paroxysmal incapacitating neurological disorder, which endangers the health of human worldwide ranking as the third most prevalent medical condition. There are no comprehensive estimates of treatments for migraine. We will conduct this systematic review and Bayesian network meta-analysis (NMA) to synthesis quantitative and comparative evidence on the efficacy and tolerability of all the known pharmacological and non-pharmacological interventions for migraine.MethodWe will perform the systematic electronic search of the literature utilizing MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing & Allied Health (CINAHL), and PsycINFO. We will only include randomized controlled trials (RCTs) of high quality which appraise the efficacy or safety of any potential pharmacological or non-pharmacological interventions in the treatment of patients with migraine. The traditional pairwise meta-analyses will be performed to anticipate the heterogeneities and publication bias and the NMA will be conducted within a Bayesian hierarchical model framework to obtain estimates for all valuable treatments for migraine. The entire heterogeneity will be quantified by Q statistic and I2 index. Other analyses included sensitivity analyses, meta-regression, and subgroup analyses will also be conducted. The whole process will be conducted using in R-3.6.0 software.ResultsThis study will obtain the efficacy and tolerability of all potential treatments for migraine, aiming at providing consolidated evidence to help make the best choice of interventions. The results will be published in a peer-reviewed journal.DiscussionThis Bayesian network meta-analysis may be the first attempt to quantitatively synthesize the efficacy and tolerability of all potential treatments for migraine. And this method can ensure us to fully utilize both the direct and indirect evidence as well as gain the comparative estimates displayed in the derived hierarchies. Besides, we have registered this protocol on the international prospective register of systematic review (PROSPERO) (CRD42020157278).

Dataset Information

Efficacy, Safety, and Acceptability of Pharmacologic Treatments for Pediatric Migraine Prophylaxis: A Systematic Review and Network Meta-analysis.

Importance

Objective

Data sources

Study selection

Data extraction and synthesis

Main outcomes and measures

Results

Conclusions and relevance

Publications

Efficacy, Safety, and Acceptability of Pharmacologic Treatments for Pediatric Migraine Prophylaxis: A Systematic Review and Network Meta-analysis.

Similar Datasets

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