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Journal of Clinical Sleep Medicine :... Sep 2021This systematic review provides supporting evidence for the accompanying clinical practice guideline on the treatment of central disorders of hypersomnolence in adults... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
This systematic review provides supporting evidence for the accompanying clinical practice guideline on the treatment of central disorders of hypersomnolence in adults and children. The review focuses on prescription medications with U.S. Food & Drug Administration approval and nonpharmacologic interventions studied for the treatment of symptoms caused by central disorders of hypersomnolence.
METHODS
The American Academy of Sleep Medicine commissioned a task force of experts in sleep medicine to perform a systematic review. Randomized controlled trials and observational studies addressing pharmacological and nonpharmacological interventions for central disorders of hypersomnolence were identified. Statistical analyses were performed to determine the clinical significance of all outcomes. Finally, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process was used to assess the evidence for the purpose of making specific treatment recommendations.
RESULTS
The literature search identified 678 studies; 144 met the inclusion criteria and 108 provided data suitable for statistical analyses. Evidence for the following interventions is presented: armodafinil, clarithromycin, clomipramine, dextroamphetamine, flumazenil, intravenous immune globulin (IVIG), light therapy, lithium, l-carnitine, liraglutide, methylphenidate, methylprednisolone, modafinil, naps, pitolisant, selegiline, sodium oxybate, solriamfetol, and triazolam. The task force provided a detailed summary of the evidence along with the quality of evidence, the balance of benefits and harms, patient values and preferences, and resource use considerations.
CITATION
Maski K, Trotti LM, Kotagal S, et al. Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment. 2021;17(9):1895-1945.
Topics: Adult; Child; Disorders of Excessive Somnolence; GRADE Approach; Humans; Modafinil; Sleep; Sodium Oxybate; United States
PubMed: 34743790
DOI: 10.5664/jcsm.9326 -
The Cochrane Database of Systematic... Apr 2023Attention deficit hyperactivity disorder (ADHD) is a major problem in children and adolescents, characterised by age-inappropriate levels of inattention, hyperactivity,... (Review)
Review
BACKGROUND
Attention deficit hyperactivity disorder (ADHD) is a major problem in children and adolescents, characterised by age-inappropriate levels of inattention, hyperactivity, and impulsivity, and is associated with long-term social, academic, and mental health problems. The stimulant medications methylphenidate and amphetamine are the most frequently used treatments for ADHD, but these are not always effective and can be associated with side effects. Clinical and biochemical evidence suggests that deficiencies of polyunsaturated fatty acids (PUFA) could be related to ADHD. Research has shown that children and adolescents with ADHD have significantly lower plasma and blood concentrations of PUFA and, in particular, lower levels of omega-3 PUFA. These findings suggest that PUFA supplementation may reduce the attention and behaviour problems associated with ADHD. This review is an update of a previously published Cochrane Review. Overall, there was little evidence that PUFA supplementation improved symptoms of ADHD in children and adolescents.
OBJECTIVES
To compare the efficacy of PUFA to other forms of treatment or placebo in treating the symptoms of ADHD in children and adolescents.
SEARCH METHODS
We searched 13 databases and two trials registers up to October 2021. We also checked the reference lists of relevant studies and reviews for additional references.
SELECTION CRITERIA
We included randomised and quasi-randomised controlled trials that compared PUFA with placebo or PUFA plus alternative therapy (medication, behavioural therapy, or psychotherapy) with the same alternative therapy alone in children and adolescents (aged 18 years and under) diagnosed with ADHD.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcome was severity or improvement of ADHD symptoms. Our secondary outcomes were severity or incidence of behavioural problems; quality of life; severity or incidence of depressive symptoms; severity or incidence of anxiety symptoms; side effects; loss to follow-up; and cost. We used GRADE to assess the certainty of evidence for each outcome.
MAIN RESULTS
We included 37 trials with more than 2374 participants, of which 24 trials were new to this update. Five trials (seven reports) used a cross-over design, while the remaining 32 trials (52 reports) used a parallel design. Seven trials were conducted in Iran, four each in the USA and Israel, and two each in Australia, Canada, New Zealand, Sweden, and the UK. Single studies were conducted in Brazil, France, Germany, India, Italy, Japan, Mexico, the Netherlands, Singapore, Spain, Sri Lanka, and Taiwan. Of the 36 trials that compared a PUFA to placebo, 19 used an omega-3 PUFA, six used a combined omega-3/omega-6 supplement, and two used an omega-6 PUFA. The nine remaining trials were included in the comparison of PUFA to placebo, but also had the same co-intervention in the PUFA and placebo groups. Of these, four trials compared a combination of omega-3 PUFA plus methylphenidate to methylphenidate. One trial each compared omega-3 PUFA plus atomoxetine to atomoxetine; omega-3 PUFA plus physical training to physical training; and an omega-3 or omega-6 supplement plus methylphenidate to methylphenidate; and two trials compared omega-3 PUFA plus dietary supplement to dietary supplement. Supplements were given for a period of between two weeks and six months. Although we found low-certainty evidence that PUFA compared to placebo may improve ADHD symptoms in the medium term (risk ratio (RR) 1.95, 95% confidence interval (CI) 1.47 to 2.60; 3 studies, 191 participants), there was high-certainty evidence that PUFA had no effect on parent-rated total ADHD symptoms compared to placebo in the medium term (standardised mean difference (SMD) -0.08, 95% CI -0.24 to 0.07; 16 studies, 1166 participants). There was also high-certainty evidence that parent-rated inattention (medium-term: SMD -0.01, 95% CI -0.20 to 0.17; 12 studies, 960 participants) and hyperactivity/impulsivity (medium-term: SMD 0.09, 95% CI -0.04 to 0.23; 10 studies, 869 participants) scores were no different compared to placebo. There was moderate-certainty evidence that overall side effects likely did not differ between PUFA and placebo groups (RR 1.02, 95% CI 0.69 to 1.52; 8 studies, 591 participants). There was also moderate-certainty evidence that medium-term loss to follow-up was likely similar between groups (RR 1.03, 95% CI 0.77 to 1.37; 13 studies, 1121 participants).
AUTHORS' CONCLUSIONS
Although we found low-certainty evidence that children and adolescents receiving PUFA may be more likely to improve compared to those receiving placebo, there was high-certainty evidence that PUFA had no effect on total parent-rated ADHD symptoms. There was also high-certainty evidence that inattention and hyperactivity/impulsivity did not differ between PUFA and placebo groups. We found moderate-certainty evidence that overall side effects likely did not differ between PUFA and placebo groups. There was also moderate-certainty evidence that follow-up was similar between groups. It is important that future research addresses the current weaknesses in this area, which include small sample sizes, variability of selection criteria, variability of the type and dosage of supplementation, and short follow-up times.
Topics: Child; Humans; Adolescent; Attention Deficit Disorder with Hyperactivity; Atomoxetine Hydrochloride; Quality of Life; Fatty Acids, Unsaturated; Methylphenidate; Fatty Acids, Omega-3; Amphetamine
PubMed: 37058600
DOI: 10.1002/14651858.CD007986.pub3 -
JAMA Psychiatry Feb 2024Stimulants (methylphenidate and amphetamines) are often prescribed at unlicensed doses for adults with attention-deficit/hyperactivity disorder (ADHD). Whether dose... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Stimulants (methylphenidate and amphetamines) are often prescribed at unlicensed doses for adults with attention-deficit/hyperactivity disorder (ADHD). Whether dose escalation beyond US Food and Drug Administration recommendations is associated with positive risk benefits is unclear.
OBJECTIVE
To investigate the impact, based on averages, of stimulant doses on treatment outcomes in adults with ADHD and to determine, based on averages, whether unlicensed doses are associated with positive risk benefits compared with licensed doses.
DATA SOURCES
Twelve databases, including published (PubMed, Cochrane Library, Embase, Web of Sciences) and unpublished (ClinicalTrials.gov) literature, up to February 22, 2023, without language restrictions.
STUDY SELECTION
Two researchers independently screened records to identify double-blinded randomized clinical trials of stimulants against placebo in adults (18 years and older) with ADHD.
DATA EXTRACTION AND SYNTHESIS
Aggregate data were extracted and synthesized in random-effects dose-response meta-analyses and network meta-analyses.
MAIN OUTCOME MEASURES
Change in ADHD symptoms and discontinuations due to adverse events.
RESULTS
A total of 47 randomized clinical trials (7714 participants; mean age, 35 (SD, 11) years; 4204 male [56%]) were included. For methylphenidate, dose-response curves indicated additional reductions of symptoms with increments in doses, but the gains were progressively smaller and accompanied by continued additional risk of adverse events dropouts. Network meta-analyses showed that unlicensed doses were associated with greater reductions of symptoms compared with licensed doses (standardized mean difference [SMD], -0.23; 95% CI, -0.44 to -0.02; very low certainty of evidence), but the additional gain was small and accompanied by increased risk of adverse event dropouts (odds ratio, 2.02; 95% CI, 1.19-3.43; moderate certainty of evidence). For amphetamines, the dose-response curve approached a plateau and increments in doses did not indicate additional reductions of symptoms, but there were continued increments in the risk of adverse event dropouts. Network meta-analysis did not identify differences between unlicensed and licensed doses for reductions of symptoms (SMD, -0.08; 95% CI, -0.24 to 0.08; very low certainty of evidence).
CONCLUSIONS AND RELEVANCE
Based on group averages, unlicensed doses of stimulants may not have positive risk benefits compared with licensed doses for adults with ADHD. In general, practitioners should consider unlicensed doses cautiously. Practitioners may trial unlicensed doses if needed and tolerated but should be aware that there may not be large gains in the response to the medication with those further increments in dose. However, the findings are averages and will not generalize to every patient.
Topics: Adult; Male; Humans; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Methylphenidate; Amphetamines; Treatment Outcome
PubMed: 37878348
DOI: 10.1001/jamapsychiatry.2023.3985 -
Brain Sciences Jul 2023Apathy, a frequent neuropsychiatric symptom in aging neurocognitive disorders, has been associated with cognitive decline and functional disability. Therefore, timely... (Review)
Review
OBJECTIVE
Apathy, a frequent neuropsychiatric symptom in aging neurocognitive disorders, has been associated with cognitive decline and functional disability. Therefore, timely provision of pharmacological interventions for apathy is greatly needed.
DESIGN
A systematical literature review of existing studies was conducted up to 30 May 2023 in several databases (PubMed, PsychInfo, Cochrane, Google Scholar, etc.) that included randomized controlled trials (RCTs) and meta-analyses assessing pharmacological treatments for apathy in aging neurocognitive disorders. The quality of the studies was appraised.
RESULTS
In patients with Alzheimer's Disease (AD), donepezil, galantamine, rivastigmine, methylphenidate, and gingko biloba were proven efficacious for apathy, while rivastigmine, cognitive enhancer IRL752 and piribedil were found to be beneficial in patients with Parkinson's Disease (PD) and agomelatine in patients with Frontotemporal Dementia (FD). The extensive proportion of RCTs in which apathy was used as a secondary outcome measure, along with the considerable methodological heterogeneity, did not allow the evaluation of group effects.
CONCLUSIONS
Pharmacological interventions for apathy in aging neurocognitive disorders are complex and under-investigated. The continuation of systematic research efforts and the provision of individualized treatment for patients suffering from these disorders is vital.
PubMed: 37508993
DOI: 10.3390/brainsci13071061 -
Expert Opinion on Pharmacotherapy 2023The data suggests that in children and adolescents, bipolar disorder (BD) and attention deficit hyperactivity disorder (ADHD) may be strongly correlated. Even though... (Review)
Review
INTRODUCTION
The data suggests that in children and adolescents, bipolar disorder (BD) and attention deficit hyperactivity disorder (ADHD) may be strongly correlated. Even though drugs for ADHD and BD are largely accepted, there is relatively little research on the management of comorbidity in children and adolescents, particularly in terms of safety. We provide a synthesis of these findings because one hasn't been made yet.
AREAS COVERED
As a primary outcome, we wanted to determine whether stimulant or non-stimulant treatment of children and adolescents with ADHD and comorbid BD was effective. As a secondary outcome, we wanted to determine tolerability, especially the risk of mood switch.
EXPERT OPINION
The findings of this systematic review suggest that methylphenidate, when used with a mood stabilizer, may be safe and not significantly increase the risk of a manic switch or psychotic symptoms when used to treat ADHD that co-occurs with a BD. In situations where stimulants are ineffective or have low tolerance, atomoxetine also seems to be a good alternative, and also in cases of co-morbid anxiety, oppositional defiant disorder, conduct disorders, ICT disorders, and substance use disorders. Additional research with a higher level of evidence is necessary to corroborate these preliminary findings.
Topics: Child; Humans; Adolescent; Attention Deficit Disorder with Hyperactivity; Bipolar Disorder; Atomoxetine Hydrochloride; Methylphenidate; Central Nervous System Stimulants
PubMed: 37300473
DOI: 10.1080/14656566.2023.2224920 -
Cancer Medicine May 2023Neurocognitive impairments are common in patients with current or previously treated brain tumours, and such impairments can negatively affect patient outcomes including... (Review)
Review
BACKGROUND
Neurocognitive impairments are common in patients with current or previously treated brain tumours, and such impairments can negatively affect patient outcomes including quality of life and survival. This systematic review aimed to identify and describe interventions used to ameliorate (improve) or prevent cognitive impairments in adults with brain tumours.
METHODS
We performed a literature search of the Ovid MEDLINE, PsychINFO and PsycTESTS databases from commencement until September 2021.
RESULTS
In total, 9998 articles were identified by the search strategy; an additional 14 articles were identified through other sources. Of these, 35 randomised and nonrandomised studies were deemed to meet the inclusion/exclusion criteria of our review and were subsequently included for evaluation. A range of interventions were associated with positive effects on cognition, including pharmacological agents such as memantine, donepezil, methylphenidate, modafinil, ginkgo biloba and shenqi fuzheng, and nonpharmacological interventions such as general and cognitive rehabilitation, working memory training, Goal Management Training, aerobic exercise, virtual reality training combined with computer-assisted cognitive rehabilitation, hyperbaric oxygen therapy and semantic strategy training. However, most identified studies had a number of methodological limitations and were judged to be at moderate-to-high risk of bias. In addition, it remains unclear whether and to what extent the identified interventions lead to durable cognitive benefits after cessation of the intervention.
CONCLUSION
The 35 studies identified in this systematic review have indicated potential cognitive benefits for a number of pharmacological and nonpharmacological interventions in patients with brain tumours. Study limitations were identified and further studies should focus on improved study reporting, methods to reduce bias and minimise participant drop-out and withdrawal where possible, and consider standardisation of methods and interventions across studies. Greater collaboration between centres could result in larger studies with standardised methods and outcome measures, and should be a focus of future research in the field.
Topics: Adult; Humans; Quality of Life; Cognitive Dysfunction; Cognition; Cognition Disorders; Brain Neoplasms
PubMed: 36880363
DOI: 10.1002/cam4.5760 -
Cureus May 2023The literature on pharmacologic treatments for postural orthostatic tachycardia syndrome (POTS) is inconsistent and unstandardized. Therefore, we aimed to evaluate... (Review)
Review
The literature on pharmacologic treatments for postural orthostatic tachycardia syndrome (POTS) is inconsistent and unstandardized. Therefore, we aimed to evaluate choices in pharmacologic treatment options for POTS and the challenges encountered in the studies. We searched numerous databases like PubMed, Scopus, Embase, Web of Science, and Google Scholar for literature published before April 8, 2023. The search was done to retrieve potential peer-reviewed articles that explored drug therapy in POTS. Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were used to conduct the systematic review. Of the 421 potential articles assessed, 17 met the inclusion criteria. Results demonstrated that pharmacologic treatment options for POTS were effective in reducing symptoms of POTS, but most of the studies were underpowered. Several were terminated due to various reasons. Midodrine ivabradine, bisoprolol, fludrocortisone, droxidopa, desmopressin, propranolol, modafinil, methylphenidate, and melatonin have been studied with positive impact but sample sizes that were low in the range of 10-50 subjects. Therefore, we concluded the treatment options effectively improve symptoms of POTS and increase orthostatic tolerance, but more evidence is needed as most studies had a low sample size and thus are underpowered.
PubMed: 37313107
DOI: 10.7759/cureus.38887 -
European Neuropsychopharmacology : the... Jul 2023Selegiline is an irreversible, selective type-B monoamine oxidase inhibitor (MAOI) approved for Parkison's disease-oral and major depressive disorder-transdermal... (Meta-Analysis)
Meta-Analysis
Selegiline is an irreversible, selective type-B monoamine oxidase inhibitor (MAOI) approved for Parkison's disease-oral and major depressive disorder-transdermal formulation) resulting in non-selective MAOI activity at oral doses≥20 mg/day. The present systematic review and meta-analysis appraises the evidence of different formulations/dosages of selegiline across different psychiatric conditions. We inquired PubMed/MEDLINE/Cochrane-Central/WHO-ICTRP/Clarivate-WebOfScience and the Chinese-Electronic-Journal Database from inception to 10/26/2022 for selegiline trials involving psychiatric patients. Random-effects meta-analyses assessed heterogeneity, publication/risk biases, and confidence in the evidence, followed by sensitivity, subgroup, and meta-regression analyses. Co-primary outcomes were: changes in symptom score (standardized mean difference=SMD) and author-defined response (risk ratios=RRs). RRs of adverse events and all-cause discontinuation were secondary and acceptability outcomes, respectively. Systematic-review included 42 studies; meta-analysis, 23. Selegiline outperformed placebo in depressive symptom reduction (SMD=-0.96, 95%C.I.=-1.78, -0.14, k = 10, n = 1,308), depression (RR=1.61, 95%C.I.=1.20, 2.15, k = 9, n = 1,238) and atypical-depression response (RR=2.23, 95%C.I.=1.35, 3.68, k = 3, n = 136). Selegiline failed to outperform the placebo in negative (k = 4) or positive symptoms of schizophrenia (k = 4), attention-deficit-hyperactivity disorder (ADHD) symptoms reduction (k = 2), and smoking abstinence rate (k = 4). Selegiline did not differ from methylphenidate and ADHD scores (k = 2). No significant difference emerged in acceptability, incident diarrhea, headache, dizziness, and nausea RRs, in contrast to xerostomia (RR=1.58, 95%C.I. =1.03, 2.43, k = 6, n = 1,134), insomnia (RR=1.61, 95%C.I.=1.19, 2.17, k = 10, n = 1,768), and application-site reaction for transdermal formulation (RR=1.81, 95%C.I.=1.40, 2.33, k = 6, n = 1,662). Confidence in findings was low/very-low for most outcomes; moderate for depressive symptoms reduction (transdermal). Selegiline proved effective, safe, and well-tolerated for depressive disorders, yet further evidence is warranted about specific psychiatric disorders.
Topics: Humans; Selegiline; Depressive Disorder, Major; Monoamine Oxidase Inhibitors; Attention Deficit Disorder with Hyperactivity; Methylphenidate
PubMed: 37087864
DOI: 10.1016/j.euroneuro.2023.03.012 -
Journal of Attention Disorders Oct 2023To report the characteristics associated with response to methylphenidate (MPH) in children and adolescents with ADHD. (Review)
Review
OBJECTIVE
To report the characteristics associated with response to methylphenidate (MPH) in children and adolescents with ADHD.
METHODS
Studies reporting potentials predictors of response to MPH were searched in Medline and Embase from January 1998 to March 2022. Narrative synthesis was performed.
RESULTS
Fifty-seven reports of 46 studies totaling 6,656 ADHD patients were included. No association appears between response to MPH and age, gender, MPH dosage, ADHD subtype, comorbidities nor socioeconomic status when considering a specific patient. No conclusion could be drawn about body weight, ADHD severity, intelligence quotient, and parental symptoms of depression or ADHD.
CONCLUSIONS
None of these potential predictors have proven their usefulness to predict response to MPH on an individual basis in clinical practice. In research, potential predictors should be measured, their association with response to MPH assessed, in order to control for confounding variables when modeling response to MPH.
Topics: Humans; Child; Adolescent; Methylphenidate; Central Nervous System Stimulants; Attention Deficit Disorder with Hyperactivity; Intelligence Tests; Parents; Treatment Outcome
PubMed: 37243373
DOI: 10.1177/10870547231177234 -
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