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The Lancet. Psychiatry Sep 2018The benefits and safety of medications for attention-deficit hyperactivity disorder (ADHD) remain controversial, and guidelines are inconsistent on which medications are... (Comparative Study)
Comparative Study Meta-Analysis
Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis.
BACKGROUND
The benefits and safety of medications for attention-deficit hyperactivity disorder (ADHD) remain controversial, and guidelines are inconsistent on which medications are preferred across different age groups. We aimed to estimate the comparative efficacy and tolerability of oral medications for ADHD in children, adolescents, and adults.
METHODS
We did a literature search for published and unpublished double-blind randomised controlled trials comparing amphetamines (including lisdexamfetamine), atomoxetine, bupropion, clonidine, guanfacine, methylphenidate, and modafinil with each other or placebo. We systematically contacted study authors and drug manufacturers for additional information. Primary outcomes were efficacy (change in severity of ADHD core symptoms based on teachers' and clinicians' ratings) and tolerability (proportion of patients who dropped out of studies because of side-effects) at timepoints closest to 12 weeks, 26 weeks, and 52 weeks. We estimated summary odds ratios (ORs) and standardised mean differences (SMDs) using pairwise and network meta-analysis with random effects. We assessed the risk of bias of individual studies with the Cochrane risk of bias tool and confidence of estimates with the Grading of Recommendations Assessment, Development, and Evaluation approach for network meta-analyses. This study is registered with PROSPERO, number CRD42014008976.
FINDINGS
133 double-blind randomised controlled trials (81 in children and adolescents, 51 in adults, and one in both) were included. The analysis of efficacy closest to 12 weeks was based on 10 068 children and adolescents and 8131 adults; the analysis of tolerability was based on 11 018 children and adolescents and 5362 adults. The confidence of estimates varied from high or moderate (for some comparisons) to low or very low (for most indirect comparisons). For ADHD core symptoms rated by clinicians in children and adolescents closest to 12 weeks, all included drugs were superior to placebo (eg, SMD -1·02, 95% CI -1·19 to -0·85 for amphetamines, -0·78, -0·93 to -0·62 for methylphenidate, -0·56, -0·66 to -0·45 for atomoxetine). By contrast, for available comparisons based on teachers' ratings, only methylphenidate (SMD -0·82, 95% CI -1·16 to -0·48) and modafinil (-0·76, -1·15 to -0·37) were more efficacious than placebo. In adults (clinicians' ratings), amphetamines (SMD -0·79, 95% CI -0·99 to -0·58), methylphenidate (-0·49, -0·64 to -0·35), bupropion (-0·46, -0·85 to -0·07), and atomoxetine (-0·45, -0·58 to -0·32), but not modafinil (0·16, -0·28 to 0·59), were better than placebo. With respect to tolerability, amphetamines were inferior to placebo in both children and adolescents (odds ratio [OR] 2·30, 95% CI 1·36-3·89) and adults (3·26, 1·54-6·92); guanfacine was inferior to placebo in children and adolescents only (2·64, 1·20-5·81); and atomoxetine (2·33, 1·28-4·25), methylphenidate (2·39, 1·40-4·08), and modafinil (4·01, 1·42-11·33) were less well tolerated than placebo in adults only. In head-to-head comparisons, only differences in efficacy (clinicians' ratings) were found, favouring amphetamines over modafinil, atomoxetine, and methylphenidate in both children and adolescents (SMDs -0·46 to -0·24) and adults (-0·94 to -0·29). We did not find sufficient data for the 26-week and 52-week timepoints.
INTERPRETATION
Our findings represent the most comprehensive available evidence base to inform patients, families, clinicians, guideline developers, and policymakers on the choice of ADHD medications across age groups. Taking into account both efficacy and safety, evidence from this meta-analysis supports methylphenidate in children and adolescents, and amphetamines in adults, as preferred first-choice medications for the short-term treatment of ADHD. New research should be funded urgently to assess long-term effects of these drugs.
FUNDING
Stichting Eunethydis (European Network for Hyperkinetic Disorders), and the UK National Institute for Health Research Oxford Health Biomedical Research Centre.
Topics: Adolescent; Adrenergic alpha-2 Receptor Agonists; Adult; Attention Deficit Disorder with Hyperactivity; Bupropion; Central Nervous System Stimulants; Child; Clonidine; Dose-Response Relationship, Drug; Humans; Methylphenidate; Network Meta-Analysis; Randomized Controlled Trials as Topic
PubMed: 30097390
DOI: 10.1016/S2215-0366(18)30269-4 -
Journal of Affective Disorders Apr 2022To compare the efficacy and discontinuation of augmentation agents in adult patients with treatment-resistant depression (TRD). We conducted a systematic review and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To compare the efficacy and discontinuation of augmentation agents in adult patients with treatment-resistant depression (TRD). We conducted a systematic review and network meta-analyses (NMA) to combine direct and indirect comparisons of augmentation agents.
METHODS
We included randomized controlled trials comparing one active drug with another or with placebo following a treatment course up to 24 weeks. Nineteen agents were included: stimulants, atypical antipsychotics, thyroid hormones, antidepressants, and mood stabilizers. Data for response/remission and all-cause discontinuation rates were analyzed. We estimated effect-size by relative risk using pairwise and NMA with random-effects model.
RESULTS
A total of 65 studies (N = 12,415) with 19 augmentation agents were included in the NMA. Our findings from the NMA for response rates, compared to placebo, were significant for: liothyronine, nortriptyline, aripiprazole, brexpiprazole, quetiapine, lithium, modafinil, olanzapine (fluoxetine), cariprazine, and lisdexamfetamine. For remission rates, compared to placebo, were significant for: thyroid hormone(T4), aripiprazole, brexpiprazole, risperidone, quetiapine, and olanzapine (fluoxetine). Compared to placebo, ziprasidone, mirtazapine, and cariprazine had statistically significant higher discontinuation rates. Overall, 24% studies were rated as having low risk of bias (RoB), 63% had moderate RoB and 13% had high RoB.
LIMITATIONS
Heterogeneity in TRD definitions, variable trial duration and methodological clinical design of older studies and small number of trials per comparisons.
CONCLUSIONS
This NMA suggests a superiority of the regulatory approved adjunctive atypical antipsychotics, thyroid hormones, dopamine compounds (modafinil and lisdexamfetamine) and lithium. Acceptability was lower with ziprasidone, mirtazapine, and cariprazine. Further research and head-to-head studies should be considered to strengthen the best available options for TRD.
Topics: Adult; Antidepressive Agents; Antipsychotic Agents; Depression; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Humans; Network Meta-Analysis
PubMed: 34986373
DOI: 10.1016/j.jad.2021.12.134 -
Brain Sciences Mar 2021Cognitive enhancers (CEs), also known as "smart drugs", "study aids" or "nootropics" are a cause of concern. Recent research studies investigated the use of CEs being... (Review)
Review
INTRODUCTION
Cognitive enhancers (CEs), also known as "smart drugs", "study aids" or "nootropics" are a cause of concern. Recent research studies investigated the use of CEs being taken as study aids by university students. This manuscript provides an overview of popular CEs, focusing on a range of drugs/substances (e.g., prescription CEs including amphetamine salt mixtures, methylphenidate, modafinil and piracetam; and non-prescription CEs including caffeine, cobalamin (vitamin B12), guarana, pyridoxine (vitamin B6) and vinpocetine) that have emerged as being misused. The diverted non-prescription use of these molecules and the related potential for dependence and/or addiction is being reported. It has been demonstrated that healthy students (i.e., those without any diagnosed mental disorders) are increasingly using drugs such as methylphenidate, a mixture of dextroamphetamine/amphetamine, and modafinil, for the purpose of increasing their alertness, concentration or memory.
AIM
To investigate the level of knowledge, perception and impact of the use of a range of CEs within Higher Education Institutions.
METHODOLOGY
A systematic review was conducted in adherence with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Whilst 1400 studies were identified within this study through a variety of electronic databases (e.g., 520 through PubMed, 490 through Science Direct and 390 through Scopus), 48 papers were deemed relevant and were included in this review.
RESULTS
The most popular molecules identified here included the stimulant CEs, e.g., methylphenidate, modafinil, amphetamine salt mixtures and caffeine-related compounds; stimulant CEs' intake was more prevalent among males than females; drugs were largely obtained from friends and family, as well as via the Internet. It is therefore suggested that CEs are increasingly being used among healthy individuals, mainly students without any diagnosed cognitive disorders, to increase their alertness, concentration, or memory, in the belief that these CEs will improve their performance during examinations or when studying. The impact of stimulant CEs may include tolerance, dependence and/or somatic (e.g., cardiovascular; neurological) complications.
DISCUSSION
The availability of CEs for non-medical indications in different countries is influenced by a range of factors including legal, social and ethical factors. Considering the risk factors and motivations that encourage university students to use CE drugs, it is essential to raise awareness about CE-related harms, counteract myths regarding "safe" CE use and address cognitive enhancement in an early stage during education as a preventative public health measure.
PubMed: 33802176
DOI: 10.3390/brainsci11030355 -
The American Journal of Psychiatry Aug 2015The authors examined research on effects, costs, and patient and caregiver views of pharmacological management strategies for Lewy body dementia. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The authors examined research on effects, costs, and patient and caregiver views of pharmacological management strategies for Lewy body dementia.
METHOD
Studies were identified through bibliographic databases, trials registers, gray literature, reference lists, and experts. The authors used the search terms "Lewy or parkinson" and "dementia" through March 2015 and used the following inclusion criteria: participants with diagnoses of Lewy body dementia, dementia with Lewy bodies, or Parkinson's disease dementia (or participants' caregivers); investigation of pharmacological management strategies; outcome measures and test scores reported. Data extraction and quality assessment were conducted by at least two authors. Meta-analyses were conducted, and when studies could not be combined, summaries were provided.
RESULTS
Forty-four studies examining 22 strategies were included in the review. Meta-analysis indicated beneficial effects of donepezil and rivastigmine for cognitive and psychiatric symptoms. Rivastigmine, but not donepezil, was associated with greater risk of adverse events. Meta-analysis of memantine suggested that it is well tolerated but with few benefits. Descriptive summaries provide some evidence of benefits for galantamine, modafinil, levodopa, rotigotine, clozapine, duloxetine, clonazepam, ramelteon, gabapentin, zonisamide, and yokukansan. Piracetam, amantadine, selegiline, olanzapine, quetiapine, risperidone, and citalopram do not appear to be effective.
CONCLUSIONS
High-level evidence related to pharmacological strategies for managing Lewy body dementia is rare. Strategies for important areas of need in Lewy body dementia, such as autonomic symptoms and caregiver burden, have not been investigated, nor have the views of patients and caregivers about pharmacological strategies.
Topics: Antidepressive Agents; Antipsychotic Agents; Attitude to Health; Caregivers; Excitatory Amino Acid Antagonists; Humans; Lewy Body Disease; Neuroprotective Agents; Nootropic Agents; Treatment Outcome
PubMed: 26085043
DOI: 10.1176/appi.ajp.2015.14121582 -
PloS One 2020Attention deficit hyperactivity disorder (ADHD) affects approximately 3% of adults globally. Many pharmacologic treatments options exist, yet the comparative benefits... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Attention deficit hyperactivity disorder (ADHD) affects approximately 3% of adults globally. Many pharmacologic treatments options exist, yet the comparative benefits and harms of individual treatments are largely unknown. We performed a systematic review and network meta-analysis to assess the relative effects of individual pharmacologic treatments for adults with ADHD.
METHODS
We searched English-language published and grey literature sources for randomized clinical trials (RCTs) involving pharmacologic treatment of ADHD in adults (December 2018). The primary outcome was clinical response; secondary outcomes were quality of life, executive function, driving behaviour, withdrawals due to adverse events, treatment discontinuation, serious adverse events, hospitalization, cardiovascular adverse events, and emergency department visits. Data were pooled via pair-wise meta-analyses and Bayesian network meta-analyses. Risk of bias was assessed by use of Cochrane's Risk of Bias tool, and the certainty of the evidence was assessed by use of the GRADE framework.
RESULTS
Eighty-one unique trials that reported at least one outcome of interest were included, most of which were at high or unclear risk of at least one important source of bias. Notably, only 5 RCTs were deemed at overall low risk of bias. Included pharmacotherapies were methylphenidate, atomoxetine, dexamfetamine, lisdexamfetamine, guanfacine, bupropion, mixed amphetamine salts, and modafinil. As a class, ADHD pharmacotherapy improved patient- and clinician-reported clinical response compared with placebo (range: 4 to 15 RCTs per outcome); however, these findings were not conserved when the analyses were restricted to studies at low risk of bias, and the certainty of the finding is very low. There were few differences among individual medications, although atomoxetine was associated with improved patient-reported clinical response and quality of life compared with placebo. There was no significant difference in the risk of serious adverse events or treatment discontinuation between ADHD pharmacotherapies and placebo; however, the proportion of participants who withdrew due to adverse events was significantly higher among participants who received any ADHD pharmacotherapy. Few RCTs reported on the occurrence of adverse events over a long treatment duration.
CONCLUSIONS
Overall, despite a class effect of improving clinical response relative to placebo, there were few differences among the individual ADHD pharmacotherapies, and most studies were at risk of at least one important source of bias. Furthermore, the certainty of the evidence was very low to low for all outcomes, and there was limited reporting of long-term adverse events. As such, the choice between ADHD pharmacotherapies may depend on individual patient considerations, and future studies should assess the long-term effects of individual pharmacotherapies on patient-important outcomes, including quality of life, in robust blinded RCTs.
REGISTRATION
PROSPERO no. CRD 42015026049.
Topics: Adult; Amphetamine; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Bayes Theorem; Bupropion; Central Nervous System Stimulants; Dextroamphetamine; Drug-Related Side Effects and Adverse Reactions; Female; Guanfacine; Humans; Lisdexamfetamine Dimesylate; Male; Methylphenidate; Modafinil; Network Meta-Analysis; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 33085721
DOI: 10.1371/journal.pone.0240584 -
Neuroscience and Biobehavioral Reviews May 2021Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders worldwide, and in the majority of patients persists into... (Review)
Review
Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders worldwide, and in the majority of patients persists into adulthood. However, it remains unclear how maternal ADHD could affect pregnancy and birth as well as early mother-(father)-child interaction. There are several studies investigating the effect of depressed or anxious parents on parent-child-interactions in early infancy, but data about the influence of parental ADHD is lacking although it is a common mental disorder in parents. Additionally, the prescription of stimulant and other ADHD medication for adult ADHD patients is rising due to improved diagnostic procedures and a greater awareness of this disorder in adulthood among psychiatrists and psychologists. However, this leads to increased numbers of treated ADHD women that wish to have children or experience unplanned pregnancies while taking stimulant medication. In our systematic review we aimed at analysing the current evidence for the association of maternal ADHD with pregnancy and birth outcomes, pregnancy risks and health behaviour in pregnancy, as well as the association of parental ADHD with early parent-child interaction and early child development in the first 3 years. Furthermore, we reviewed recent evidence on the risks of stimulant and non-stimulant treatment for ADHD in pregnancy and lactation.
Topics: Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Female; Humans; Methylphenidate; Parent-Child Relations; Parents; Postpartum Period; Pregnancy
PubMed: 33516734
DOI: 10.1016/j.neubiorev.2021.01.002 -
Expert Review of Neurotherapeutics 2016Adult Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent psychiatric condition associated with high disability and frequent comorbidity. Current standard... (Review)
Review
Adult Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent psychiatric condition associated with high disability and frequent comorbidity. Current standard pharmacotherapy (methylphenidate and atomoxetine) improves ADHD symptoms in the short-term, but poor data were published about long-term treatment. In addition a number of patients present partial or no response to methylphenidate and atomoxetine. Research into the main database sources has been conducted to obtain an overview of alternative pharmacological approaches in adult ADHD patients. Among alternative compounds, amphetamines (mixed amphetamine salts and lisdexamfetamine) have the most robust evidence of efficacy, but they may be associated with serious side effects (e.g. psychotic symptoms or hypertension). Antidepressants, particularly those acting as noradrenaline or dopamine enhancers, have evidence of efficacy, but they should be avoided in patients with comorbid bipolar disorder. Finally metadoxine and lithium may be particularly suitable in case of comorbid alcohol misuse or bipolar disorder.
Topics: Adrenergic alpha-Agonists; Adult; Amphetamines; Antidepressive Agents; Attention Deficit Disorder with Hyperactivity; Benzhydryl Compounds; Bridged Bicyclo Compounds, Heterocyclic; Bupropion; Central Nervous System Stimulants; Desipramine; Dopamine Agents; Droxidopa; Drug Combinations; Duloxetine Hydrochloride; Guanfacine; Histamine Agents; Humans; Lisdexamfetamine Dimesylate; Lithium Compounds; Lobeline; Mecamylamine; Memantine; Modafinil; Morpholines; Nicotinic Agonists; Nicotinic Antagonists; Nomifensine; Paroxetine; Pyridines; Pyridoxine; Pyrrolidonecarboxylic Acid; Quinazolinones; Reboxetine; Venlafaxine Hydrochloride; Wakefulness-Promoting Agents
PubMed: 26693882
DOI: 10.1586/14737175.2016.1135735 -
Journal of Child Psychology and... Jun 2021Clinically significant attention-deficit/hyperactivity disorder (ADHD) symptoms are common and impairing in children and youth with autism spectrum disorder(ASD). The... (Meta-Analysis)
Meta-Analysis
Practitioner Review: Pharmacological treatment of attention-deficit/hyperactivity disorder symptoms in children and youth with autism spectrum disorder: a systematic review and meta-analysis.
BACKGROUND
Clinically significant attention-deficit/hyperactivity disorder (ADHD) symptoms are common and impairing in children and youth with autism spectrum disorder(ASD). The aim of this systematic review and meta-analysis was to (a) evaluate the efficacy and safety of pharmacotherapy for the treatment of ADHD symptoms in ASD and (b) distil findings for clinical translation.
METHODS
We searched electronic databases and clinical trial registries (1992 onwards). We selected randomized controlled trials conducted in participants <25 years of age, diagnosed with ASD that evaluated ADHD outcomes (hyperactivity/impulsivity and inattention) following treatment with stimulants (methylphenidate or amphetamines), atomoxetine, alpha-2 adrenergic receptor agonists, antipsychotics, tricyclic antidepressants, bupropion, modafinil, venlafaxine, or a combination, in comparison with placebo, any of the listed medications, or behavioral therapies. Data were pooled using a random-effects model.
RESULTS
Twenty-five studies (4 methylphenidate, 4 atomoxetine, 1 guanfacine, 14 antipsychotic, 1 venlafaxine, and 1 tianeptine) were included. Methylphenidate reduced hyperactivity (parent-rated: standardized mean difference [SMD] = -.63, 95%CI = -.95,-.30; teacher-rated: SMD = -.81, 95%CI = -1.43,-.19) and inattention (parent-rated: SMD = -.36, 95%CI = -.64,-.07; teacher-rated: SMD = -.30, 95%CI = -.49,-.11). Atomoxetine reduced inattention (parent-rated: SMD = -.54, 95%CI = -.98,-.09; teacher/investigator-rated: SMD = -0.38, 95%CI = -0.75, -0.01) and parent-rated hyperactivity (parent-rated: SMD = -.49, 95%CI = -.76,-.23; teacher-rated: SMD = -.43, 95%CI = -.92, .06). Indirect evidence for significant reductions in hyperactivity with second-generation antipsychotics was also found. Quality of evidence for all interventions was low/very low. Methylphenidate was associated with a nonsignificant elevated risk of dropout due to adverse events.
CONCLUSIONS
Direct pooled evidence supports the efficacy and tolerability of methylphenidate or atomoxetine for treatment of ADHD symptoms in children and youth with ASD. The current review highlights the efficacy of standard ADHD pharmacotherapy for treatment of ADHD symptoms in children and youth with ASD. Consideration of the benefits weighed against the limitations of safety/efficacy data and lack of data evaluating long-term continuation is undertaken to help guide clinical decision-making regarding treatment of co-occurring ADHD symptoms in children and youth with ASD.
Topics: Adolescent; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Central Nervous System Stimulants; Child; Guanfacine; Humans; Methylphenidate
PubMed: 32845025
DOI: 10.1111/jcpp.13305 -
Annals of Internal Medicine May 2023Excessive daytime sleepiness (EDS) is common among patients with obstructive sleep apnea (OSA). The comparative effectiveness of pharmacologic agents is unknown. (Meta-Analysis)
Meta-Analysis
Comparative Efficacy and Safety of Wakefulness-Promoting Agents for Excessive Daytime Sleepiness in Patients With Obstructive Sleep Apnea : A Systematic Review and Network Meta-analysis.
BACKGROUND
Excessive daytime sleepiness (EDS) is common among patients with obstructive sleep apnea (OSA). The comparative effectiveness of pharmacologic agents is unknown.
PURPOSE
To compare the effectiveness of drugs for EDS in OSA using network meta-analysis.
DATA SOURCES
MEDLINE, CENTRAL, EMBASE, and ClinicalTrials.gov to 7 November 2022.
STUDY SELECTION
Reviewers identified randomized trials that enrolled patients with EDS-associated OSA on or eligible for conventional therapy assigned to any pharmacologic intervention.
DATA EXTRACTION
Paired reviewers independently extracted data addressing effects of drugs on the Epworth Sleepiness Scale (ESS), Maintenance of Wakefulness Test (MWT), and adverse events at the longest reported follow-up. The certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.
DATA SYNTHESIS
Fourteen trials (3085 patients) were eligible. At 4 weeks, compared with placebo, solriamfetol improves ESS scores (mean difference [MD], -3.85 [95% CI, -5.24 to -2.50]; high certainty), and armodafinil-modafinil (MD, -2.25 [CI, -2.85 to -1.64]; moderate certainty) and pitolisant-H3-autoreceptor blockers (MD, -2.78 [CI, -4.03 to -1.51]; moderate certainty) probably improve ESS scores. At 4 weeks, compared with placebo, solriamfetol (standardized mean difference [SMD], 0.9 [CI, 0.64 to 1.17]) and armodafinil-modafinil (SMD, 0.41 [CI, 0.27 to 0.55]) improve MWT (both high certainty), whereas pitolisant-H3-autoreceptor blockers probably do not (moderate certainty). At 4 weeks, armodafinil-modafinil probably increases the risk for discontinuation due to adverse events (relative risk [RR], 2.01 [CI, 1.14 to 3.51]; moderate certainty); solriamfetol may increase the risk for discontinuation due to adverse events (RR, 2.07 [CI, 0.67 to 6.25]; low certainty). Low certainty evidence suggests these interventions may not increase the risk for serious adverse events.
LIMITATIONS
There is limited evidence on long term or effectiveness among patients nonadherent or with mixed adherence to conventional OSA therapies.
CONCLUSION
Solriamfetol, armodafinil-modafinil, and pitolisant reduce daytime sleepiness for patients with OSA already on conventional therapy, with solriamfetol likely superior. Adverse events probably increase the risk for discontinuation of armodafinil-modafinil and may increase the risk for discontinuation with solriamfetol.
PRIMARY FUNDING SOURCE
None.
Topics: Humans; Autoreceptors; Disorders of Excessive Somnolence; Modafinil; Network Meta-Analysis; Sleep Apnea, Obstructive; Wakefulness-Promoting Agents
PubMed: 37155992
DOI: 10.7326/M22-3473 -
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