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Academic Emergency Medicine : Official... Sep 2022This review was designated to evaluate the efficacy of parenteral ketorolac in treating acute migraine headache. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This review was designated to evaluate the efficacy of parenteral ketorolac in treating acute migraine headache.
METHODS
We searched databases Cochrane Central Register of Controlled Trials (CENTRAL), Medline, and Google Scholar up to January 2021 and identified randomized controlled trials comparing ketorolac to any other medications in treating patients presenting with migraine headache.
RESULTS
Thirteen trials were included in our review, comprising 944 participants. We derived seven comparisons: ketorolac versus phenothiazines, metoclopramide, sumatriptan, dexamethasone, sodium valproate, caffeine, and diclofenac. There were no significant differences in the reduction of pain intensity at 1 h under the comparisons between ketorolac and phenothiazines (standard mean difference [SMD] = 0.09, p = 0.74) or metoclopramide (SMD = 0.02, p = 0.95). We also found no difference in the outcome recurrence of headache (ketorolac vs. phenothiazines (risk ratio [RR] =0.98, p = 0.97)], ability to return to work or usual activity (ketorolac vs. metoclopramide [RR = 0.64, p = 0.13]), need for rescue medication (ketorolac vs. phenothiazines [RR = 1.72, p = 0.27], ketorolac vs. metoclopramide [RR 2.20, p = 0.18]), and frequency of adverse effects (ketorolac vs. metoclopramide [RR = 1.07, p = 0.82]). Limited trials suggested that ketorolac offered better pain relief at 1 h compared to sumatriptan and dexamethasone; had lesser frequency of adverse effects than phenothiazines; and was superior to sodium valproate in terms of reduction of pain intensity at 1 h, need for rescue medication, and sustained headache freedom within 24 h.
CONCLUSIONS
Ketorolac may have similar efficacy to phenothiazines and metoclopramide in treating acute migraine headache. Ketorolac may also offer better pain control than sumatriptan, dexamethasone, and sodium valproate. However, given the lack of evidence due to inadequate number of trials available, future studies are warranted.
Topics: Caffeine; Dexamethasone; Diclofenac; Humans; Ketorolac; Metoclopramide; Migraine Disorders; Pain; Phenothiazines; Sumatriptan; Valproic Acid
PubMed: 35138658
DOI: 10.1111/acem.14457 -
European Review For Medical and... Nov 2021This systematic review with network meta-analysis was performed to compare the effectiveness of oral anti-inflammatory drugs used in Brazil for osteoarthritis. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This systematic review with network meta-analysis was performed to compare the effectiveness of oral anti-inflammatory drugs used in Brazil for osteoarthritis.
PATIENTS AND METHODS
Randomized clinical trials evaluating ultramicronised diclofenac, diclofenac, celecoxib, etodolac and placebo in patients with osteoarthritis were identified. A search was conducted in May 2021 through PubMed, Scopus and Web of Science databases. A network meta-analysis was developed for efficacy outcome related to analgesia measured by the pain subscale of the Western Ontario and McMaster Universities tool. In addition, surface under the cumulative ranking was performed to rank the drugs in relation to this outcome.
RESULTS
Twelve randomized clinical trials were included. Overall, ultramicronised diclofenac 105 mg/day (UD105) was better than all the others, including ultramicronised diclofenac 70 mg/day (UD70). In addition, surface under the cumulative ranking resulted in the following order: 1) ultramicronised diclofenac 105 mg/day (100%), 2) ultramicronised diclofenac 70 mg/day (80%), 3) celecoxib 200 mg/day (49%), 4) diclofenac 100 mg/day (48%), 5) placebo (19%) and 6) diclofenac 150 mg/day (6%).
CONCLUSIONS
Ultramicronised diclofenac demonstrated superior efficacy compared to other conventional anti-inflammatory drugs and placebo in relieving osteoarthritis pain.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Celecoxib; Diclofenac; Humans; Network Meta-Analysis; Osteoarthritis; Pain; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 34859865
DOI: 10.26355/eurrev_202111_27252 -
Alcohol-medication interactions: A systematic review and meta-analysis of placebo-controlled trials.Neuroscience and Biobehavioral Reviews Jan 2022Alcohol and other xenobiotics may limit the therapeutic effects of medications. We aimed at investigating alcohol-medication interactions (AMI) after the exclusion of... (Meta-Analysis)
Meta-Analysis Review
Alcohol and other xenobiotics may limit the therapeutic effects of medications. We aimed at investigating alcohol-medication interactions (AMI) after the exclusion of confounding effects related to other xenobiotics. We performed a systematic review and meta-analysis of controlled studies comparing the effects induced by alcohol versus placebo on pharmacodynamic and/or pharmacokinetic parameters of approved medications. Certainty in the evidence of AMI was assessed when at least 3 independent studies and at least 200 participants were available. We included 107 articles (3097 participants): for diazepam, cannabis, opioids, and methylphenidate, we found significant AMI and enough data to assign the certainty of evidence. Alcohol consumption significantly increases the peak plasma concentration of diazepam (low certainty; almost 290 participants), cannabis (high certainty; almost 650 participants), opioids (low certainty; 560 participants), and methylphenidate (moderate certainty; 290 participants). For most medications, we found some AMI but not enough data to assign them the certainty grades; for some medications, we found no differences between alcohol and placebo in any outcomes evaluated. Our results add further evidence for interactions between alcohol and certain medications after the exclusion of confounding effects related to other xenobiotics. Physicians should advise patients who use these specific medications to avoid alcohol consumption. Further studies with appropriate control groups, enough female participants to investigate sex differences, and elderly population are needed to expand our knowledge in this field. Short phrases suitable for indexing terms.
Topics: Aged; Female; Humans; Methylphenidate; Randomized Controlled Trials as Topic
PubMed: 34826511
DOI: 10.1016/j.neubiorev.2021.11.019 -
Medicine Nov 2021Attention-deficit hyperactivity disorder (ADHD) is the most common childhood-onset neurodevelopmental disorder, and methylphenidate (MPH) is considered one of the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Attention-deficit hyperactivity disorder (ADHD) is the most common childhood-onset neurodevelopmental disorder, and methylphenidate (MPH) is considered one of the first-line medicine for ADHD. Unfortunately, this medication is only effective for some children with ADHD. This meta-analysis was conducted to evaluate whether noradrenergic gene polymorphisms impact the efficacy of MPH in children with ADHD.
METHODS
Candidate gene studies published in English until March 1, 2020, were identified through literature searches on PubMed, Web of Science, and Embase. Data were pooled from individual clinical trials considering MPH pharmacogenomics. According to the heterogeneity, the odds ratio and mean differences were calculated by applying fixed-effects or random-effects models.
RESULTS
This meta-analysis includes 15 studies and 1382 patients. Four polymorphisms of the NET gene (rs5569, rs28386840, rs2242446, rs3785143) and 2 polymorphisms of the α2A-adrenergic receptor gene (ADRA2A) gene (MspI and DraI) were selected for the analysis. In the pooled data from all studies, T allele carriers of the rs28386840 polymorphism were significantly more likely to respond to MPH (P < .001, ORTcarriers = 2.051, 95% confidence interval [CI]:1.316, 3.197) and showed a relationship with significantly greater hyperactive-impulsive symptoms improvement (P < .001, mean difference:1.70, 95% CI:0.24, 3.16). None of the ADRA2A polymorphisms correlated significantly with MPH response as a whole. However, G allele carriers of the MspI polymorphism showed a relationship with significantly inattention symptoms improvement (P < .001, mean difference:0.31, 95% CI: 0.15, 0.47).
CONCLUSION
Our meta-analysis results indicate that the noradrenergic gene polymorphisms may impact MPH response. The NET rs28386840 is linked to improved MPH response in ADHD children. And the ADRA2A MspI is associated with inattention symptom improvements. Further investigations with larger samples will be needed to confirm these results.Registration: PROSPERO (no. CRD42021265830).
Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Humans; Methylphenidate; Norepinephrine; Norepinephrine Plasma Membrane Transport Proteins; Pharmacogenetics; Polymorphism, Genetic; Receptors, Adrenergic, alpha-2; Treatment Outcome
PubMed: 34797323
DOI: 10.1097/MD.0000000000027858 -
Journal of Clinical Epidemiology Mar 2022To assess whether drug regulatory agencies decided on applications for extended-release methylphenidate for use in adult ADHD based on select samples of trials.
OBJECTIVES
To assess whether drug regulatory agencies decided on applications for extended-release methylphenidate for use in adult ADHD based on select samples of trials.
STUDY DESIGN AND SETTING
Case series of publicly available regulatory documents. We matched an index of extended-release methylphenidate trials for adult ADHD with trials appearing in regulatory documents of extended-release methylphenidate applications. Trials and regulatory documents were identified as part of this systematic review (https://doi.org/10.1002/14651858.CD012857). We sought to identify missing trials in the regulatory documents and to clarify regulatory submission requirements.
RESULTS
We indexed 18 trials and matched those with 13 drug applications (11 approved, 2 rejected) published by 7 agencies. There were trials missing in 7 (54%) of 13 applications, median 4 trials (range 1-6). The median proportion of missing trial participants was 45% (range 23% - 72%). Regulators seemingly require that all trials must be included in new drug applications, but wording is ambiguous.
CONCLUSION
In this sample of extended-release methylphenidate drug applications for adult ADHD, 7 of 13 regulatory decisions were missing entire trials according to public documents, even though regulatory requirements seem to stipulate that all available trials should be included in drug applications.
Topics: Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Delayed-Action Preparations; Humans; Methylphenidate; Treatment Outcome
PubMed: 34752938
DOI: 10.1016/j.jclinepi.2021.10.027 -
Psychological Medicine Jan 2022There is mixed evidence on the association between headache and attention-deficit/hyperactivity disorder (ADHD), as well as headache and ADHD medications. This... (Meta-Analysis)
Meta-Analysis Review
There is mixed evidence on the association between headache and attention-deficit/hyperactivity disorder (ADHD), as well as headache and ADHD medications. This systematic review and meta-analysis investigated the co-occurrence of headache in children with ADHD, and the effects of ADHD medications on headache. Embase, Medline and PsycInfo were searched for population-based and clinical studies comparing the prevalence of headache in ADHD and controls through January 26, 2021. In addition, we updated the search of a previous systematic review and network meta-analysis of double-blind randomized controlled trials (RCTs) on ADHD medications on June 16, 2020. Trials of amphetamines, atomoxetine, bupropion, clonidine, guanfacine, methylphenidate, and modafinil with a placebo arm and reporting data on headache as an adverse event, were included. Thirteen epidemiological studies and 58 clinical trials were eligible for inclusion. In epidemiological studies, a significant association between headache and ADHD was found [odds ratio (OR) = 2.01, 95% confidence interval (CI) = 1.63-2.46], which remained significant when limited to studies reporting ORs adjusted for possible confounders. The pooled prevalence of headaches in children with ADHD was 26.6%. In RCTs, three ADHD medications were associated with increased headache during treatment periods, compared to placebo: atomoxetine (OR = 1.29, 95% CI = 1.06-1.56), guanfacine (OR = 1.43, 95% CI = 1.12-1.82), and methylphenidate (OR = 1.33, 95% CI = 1.09-1.63). The summarized evidence suggests that headache is common in children with ADHD, both as part of the clinical presentation as such and as a side effect of some standard medications. Monitoring and clinical management strategies of headache in ADHD, in general, and during pharmacological treatment are recommended.
Topics: Child; Humans; Attention Deficit Disorder with Hyperactivity; Atomoxetine Hydrochloride; Guanfacine; Central Nervous System Stimulants; Methylphenidate; Drug-Related Side Effects and Adverse Reactions; Comorbidity; Headache; Randomized Controlled Trials as Topic
PubMed: 34635194
DOI: 10.1017/S0033291721004141 -
BMJ Supportive & Palliative Care Sep 2023Cancer-related fatigue (CRF) is a very common symptom in patients with cancer, and one of the five areas of highest priority in cancer research. There is currently no... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Cancer-related fatigue (CRF) is a very common symptom in patients with cancer, and one of the five areas of highest priority in cancer research. There is currently no consensus on pharmacologic interventions for treating CRF. The aim of this systematic review is to provide more clarity on which pharmacologic interventions may be most promising, for future clinical trials. The network meta-analysis provides the ability to compare multiple agents when no direct head-to-head trials of all agents have been performed.
METHODS
Medline (PubMed), EMBASE and Cochrane Central Register of Controlled Trials were searched up until 5 March 2021. Studies were included if they reported on a pharmacologic intervention for CRF. Standardised mean differences and corresponding 95% CIs were computed using a random-effects maximum-likelihood model.
RESULTS
This review reports on 18 studies and 2604 patients, the most comprehensive review of pharmacologic interventions for CRF at the time of this publication. Methylphenidate, modafinil and paroxetine were superior to placebo. Methylphenidate and modafinil were equivalent to one another. Paroxetine was superior to modafinil.
CONCLUSION
Paroxetine should be further studied in future trials. As well, more safety data are needed on pharmacologic interventions.
Topics: Humans; Modafinil; Central Nervous System Stimulants; Paroxetine; Network Meta-Analysis; Methylphenidate; Fatigue; Neoplasms
PubMed: 34593386
DOI: 10.1136/bmjspcare-2021-003244 -
The Journal of Head Trauma...To provide a systematic review of published interventions for posttraumatic brain injury fatigue (PTBIF).
OBJECTIVE
To provide a systematic review of published interventions for posttraumatic brain injury fatigue (PTBIF).
METHODS
PubMed and OneSearch were systematically searched for PTBIF interventions published between January 1, 1989, and March 31, 2019. Search results were evaluated for inclusion based on an abstract and full-text review. Inclusion criteria were (1) an investigation of an intervention, (2) participant sample including individuals with traumatic brain injury (TBI), (3) report of fatigue outcome data among individuals with TBI, and (4) articles available in English, Spanish, French, German, Afrikaans, or Dutch. A risk of bias assessment was conducted on all included publications.
RESULTS
The search resulted in 2343 publications, with 37 meeting inclusion criteria for this review. Categories of PTBIF interventions were pharmacological ( n = 13), psychological ( n = 9), exercise-based ( n = 4), complementary alternative medicine ( n = 5), electrotherapeutic ( n = 3), and multimodal ( n = 3). Only methylphenidate, modafinil, and cognitive behavioral therapy interventions included multiple cohorts. Pharmacological and psychological interventions represented the groups with the lowest risk of bias.
CONCLUSIONS
This review includes 37 studies, with 21 studies published after 2014. Methylphenidate and melatonin were the only pharmacological agents found to reduce fatigue in randomized controlled trials. Creatine given to children prospectively at onset of injury reduced fatigue at follow-up. Walking and water aerobics were effective exercise interventions in isolated randomized controlled studies. One multimodal study of children after concussion was more effective at reducing fatigue and postconcussion symptoms than community standard of care. Other interventions had equivocal results. Overall, more work remains to understand and develop treatments for PTBIF.
Topics: Brain Concussion; Brain Injuries, Traumatic; Creatine; Fatigue; Humans; Melatonin; Methylphenidate
PubMed: 34354018
DOI: 10.1097/HTR.0000000000000710 -
Journal of Clinical Pharmacy and... Jan 2022Attention-deficit hyperactivity disorder (ADHD) symptoms usually impairs academic achievement and can trigger the onset of medication. Methylphenidate is a drug widely...
WHAT IS KNOWN AND OBJECTIVE
Attention-deficit hyperactivity disorder (ADHD) symptoms usually impairs academic achievement and can trigger the onset of medication. Methylphenidate is a drug widely prescribed to treat ADHD. However, systematic reviews of randomized clinical trials suggest that it does not lead to great improvements in academic performance. Thus, we aimed to evaluate the evidence on the "real-world" effectiveness of methylphenidate in improving the academic achievement of ADHD students.
METHODS
We conducted a systematic review of observational studies retrieved from five electronic databases, besides a manual search and search in grey literature. Studies evaluating treatment with methylphenidate compared to no treatment or other pharmacological/non-pharmacological alternatives used in ADHD were included. The risk of bias of the selected studies was assessed using adapted versions of the Newcastle-Ottawa Scale.
RESULTS AND DISCUSSION
Nine studies (from ten reports) were included in the review: four cohorts, two before-and-after designs and three cross-sectional studies. They involved 12,269 children and adolescents aged 6-18 years. The doses of methylphenidate ranged from 10 to 72 mg/day, and the duration of the treatment from 2.6 months to 4.25 years. Five of these studies concluded that methylphenidate improves academic performance. However, three of the four lowest-bias risk studies concluded that the drug is ineffective. Five studies assessed the long-term use of methylphenidate, and four of them concluded that it does not result in better outcomes in the school setting. Most included studies had considerable limitations and significant heterogeneity regarding methodological design and academic performance measurement criteria.
WHAT IS NEW AND CONCLUSION
Although some studies indicate that the short-term use of methylphenidate may improve outcomes in the school environment, the available evidence does not support the establishment of adequate conclusions about the real benefits of methylphenidate in the academic improvement of ADHD students.
Topics: Academic Success; Adolescent; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Cross-Sectional Studies; Humans; Methylphenidate; Observational Studies as Topic; Students
PubMed: 34254328
DOI: 10.1111/jcpt.13486 -
Journal of Affective Disorders Sep 2021Globally, depression impacts nearly 300 million people, and roughly half do not achieve remission with standard first-line therapies. For such individuals, augmentation... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Globally, depression impacts nearly 300 million people, and roughly half do not achieve remission with standard first-line therapies. For such individuals, augmentation strategies are often helpful at reducing the severity of depression. While there are many potential adjunctive medication choices, psychostimulants are among the more controversial options.
OBJECTIVES
The present review sought to clarify the comparative efficacy and safety of different stimulant-like medications to treat depression.
METHODS
We conducted a systematic review and network meta-analysis of randomized, controlled trials (RCTs) using psychostimulant medications to treat adults with depression. Outcomes were pooled using rate ratios (RRs) for dichotomous outcomes (e.g., response, adverse events) and standardized mean differences (SMDs) for continuous outcomes (e.g., change in depression scores).
RESULTS
We identified 37 eligible studies (ranging from 1958 to 2016). We assessed nine psychostimulants: methylphenidate (n=14), dextroamphetamine (n=9), modafinil (n=6), lisdexamphetamine (n=3), methylamphetamine (n=3), pemoline (n=2), atomoxetine (n=1), desipramine (n=1), and imipramine (n=1). Overall, psychostimulants demonstrated efficacy for depression, reduced fatigue and sleepiness, and appeared well-tolerated. However, there was inconsistent evidence across particular psychostimulants. For example, the only psychostimulant which demonstrated efficacy for depression-in terms of both symptom severity and response rates-was methylphenidate.
CONCLUSIONS
While our review suggests that some psychostimulants-particularly methylphenidate-appear well-tolerated and demonstrate some efficacy for depression, as well as fatigue and sleepiness, the strength of evidence in our estimates was low to very low for most agents given the small sample sizes, few RCTs, and imprecision in most estimates. A lack of consistent evidence precludes a definitive hierarchy of treatments and points to a need for additional, high-quality RCTs.
Topics: Adult; Central Nervous System Stimulants; Depression; Fatigue; Humans; Methylphenidate; Network Meta-Analysis
PubMed: 34144366
DOI: 10.1016/j.jad.2021.05.119