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Sleep Medicine Sep 2023Narcolepsy type 1 is a primary sleep disorder caused by deficient hypocretin transmission leading to excessive daytime sleepiness and cataplexy. Opioids have been...
OBJECTIVE
Narcolepsy type 1 is a primary sleep disorder caused by deficient hypocretin transmission leading to excessive daytime sleepiness and cataplexy. Opioids have been suggested to increase the number of hypocretin-producing neurons. We aimed to assess opioid use and its self-reported effect on narcolepsy type 1 symptom severity through a literature review and questionnaire study.
METHODS
We systematically reviewed literature on opioid use in narcolepsy. We also recruited 100 people with narcolepsy type 1 who completed an online questionnaire on opioid use in the previous three years. The main questionnaire topics were the indication for use, and the possible effects on narcolepsy symptom severity. Structured follow-up interviews were conducted when opioid use was reported.
RESULTS
The systematic literature review mainly showed improvements in narcolepsy symptom severity. Recent opioid use was reported by 16/100 questionnaire respondents, who had used 20 opioids (codeine: 7/20, tramadol: 6/20, oxycodone: 6/20, fentanyl: 1/20). Narcolepsy symptom changes were reported in 11/20. Positive effects on disturbed nocturnal sleep (9/20), excessive daytime sleepiness (4/20), hypnagogic hallucinations (3/17), cataplexy (2/18), and sleep paralysis (1/13) were most pronounced for oxycodone (4/6) and codeine (4/7).
CONCLUSIONS
Opioids were relatively frequently used compared to a similarly young general Dutch sample. Oxycodone and, to a lesser extent, codeine were associated with self-reported narcolepsy symptom severity improvements. Positive changes in disturbed nocturnal sleep and daytime sleepiness were most frequently reported, while cataplexy effects were less pronounced. Randomised controlled trials are now needed to verify the potential of opioids as therapeutic agents for narcolepsy.
Topics: Humans; Cataplexy; Analgesics, Opioid; Orexins; Oxycodone; Narcolepsy; Disorders of Excessive Somnolence; Surveys and Questionnaires
PubMed: 37437491
DOI: 10.1016/j.sleep.2023.06.008 -
PloS One 2022For the past few years, only a few monovalent EV71 vaccines have been developed, while other enterovirus vaccines are in short supply. We conducted a quantitative... (Meta-Analysis)
Meta-Analysis
BACKGROUND
For the past few years, only a few monovalent EV71 vaccines have been developed, while other enterovirus vaccines are in short supply. We conducted a quantitative meta-analysis to explore the epidemiological characteristics, routine laboratory diagnosis, clinical signs and risk factors for hand, foot and mouth disease (HFMD).
METHODS
PubMed, Embase and the Web of Science were searched for eligible reports published before April 16, 2021, with no publication time or language restrictions. The primary outcome was the odds ratio of the epidemiological characteristics, routine laboratory diagnosis, and clinical signs associated with HFMD severity and death.
RESULTS
After screening 10522 records, we included 32 articles comprising 781903 cases of hand, foot and mouth disease. Patients with severe illness developed some clinical signs (hypersomnia (OR = 21.97, 95% CI: 4.13 to 116.74), convulsion (OR = 16.18, 95% CI: 5.30 to 49.39), limb shaking (OR = 47.96, 95% CI: 15.17 to 151.67), and breathlessness (OR = 7.48, 95% CI: 1.90 to 29.40)) and had some changes in laboratory parameters (interleukin-6 levels standardized mean difference (SMD) = 1.57, 95%CI: 0.55 to 2.60), an increased neutrophils ratio (SMD = 0.55, 95%CI: 0.17 to 0.93), cluster of differentiation 4 (CD4+) (SMD = -1.38, 95%CI: -2.33 to -0.43) and a reduced lymphocytes ratio (SMD = -0.48, 95%CI: -0.93 to -0.33)) compared with patients with mild illness. The risk factors for death included cyanosis (OR = 5.82, 95% CI: 2.29 to 14.81), a fast heart rate (OR = 3.22, 95% CI: 1.65 to 6.30), vomiting (OR = 2.70, 95% CI: 1.33 to 5.49) and an increased WBC count (SMD = 0.60, 95% CI: 0.27 to 0.93).
CONCLUSIONS
China has the highest incidence of HFMD. Our meta-analyses revealed important risk factors that are associated with the severity and mortality of HFMD.
Topics: Blood Coagulation Tests; Enterovirus A, Human; Hand, Foot and Mouth Disease; Humans; Mouth Diseases; Risk Factors
PubMed: 35482791
DOI: 10.1371/journal.pone.0267716 -
The Cochrane Database of Systematic... Oct 2018Gamma aminobutyric acid (GABA) receptor agonists have been shown to have a neuroprotectant effect in reducing infarct size and improving functional outcome in animal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Gamma aminobutyric acid (GABA) receptor agonists have been shown to have a neuroprotectant effect in reducing infarct size and improving functional outcome in animal models of cerebrovascular disease. However, the sedative effects of GABA receptor agonists have limited their wider application in people with acute stroke, due to the potential risk of stupor. This is an update of a Cochrane Review first published in 2013, and previously updated in 2014 and 2016.
OBJECTIVES
To determine the efficacy and safety of GABA receptor agonists in the treatment of acute stroke.
SEARCH METHODS
We searched the Cochrane Stroke Group Trials Register (accessed May 2018), the Cochrane Central Register of Controlled Trials (CENTRAL) 2018, Issue 4 (accessed May 2018), MEDLINE (from 1949 to May 2018), Embase (from 1980 to May 2018), CINAHL (from 1982 to May 2018), AMED (from 1985 to May 2018), and 11 Chinese databases (accessed May 2018). In an effort to identify further published, unpublished, and ongoing trials we searched ongoing trial registers, reference lists, and relevant conference proceedings, and contacted authors and pharmaceutical companies.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) investigating GABA receptor agonists versus placebo for people with acute stroke (within 12 hours after stroke onset), with the primary outcomes of efficacy and safety.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted eligible data, cross-checked the data for accuracy, and assessed the risk of bias. We used the GRADE approach to assess the quality of the evidence.
MAIN RESULTS
We included five trials with 3838 participants (acute ischemic or hemorrhagic stroke patients, 3758 analyzed). Most of the participants recruited had acute ischaemic stroke, with limited data available from participants with other stroke subtypes, including total anterior circulation syndrome (TACS). The methodological quality of the included trials was generally good, with an unclear risk for selection bias only. For death and dependency at three months, pooled results did not find a significant difference for chlormethiazole versus placebo (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.96 to 1.11; four trials; 2909 participants; moderate-quality evidence) and for diazepam versus placebo (RR 0.94, 95% CI 0.82 to 1.07; one trial; 849 participants; moderate-quality evidence). The most frequent adverse events related to chlormethiazole were somnolence (RR 4.56, 95% CI 3.50 to 5.95; two trials; 2527 participants; moderate-quality evidence) and rhinitis (RR 4.75, 95% CI 2.67 to 8.46; two trials; 2527 participants; moderate-quality evidence).
AUTHORS' CONCLUSIONS
This review provides moderate-quality evidence that fails to support the use of GABA receptor agonists (chlormethiazole or diazepam) for the treatment of people with acute stroke. More well-designed RCTs with large samples of participants with total anterior circulation syndrome are required to determine if there are benefits for this subgroup. Somnolence and rhinitis are frequent adverse events related to chlormethiazole.
Topics: Acute Disease; Chlormethiazole; Diazepam; Disorders of Excessive Somnolence; GABA Agonists; Humans; Neuroprotective Agents; Randomized Controlled Trials as Topic; Rhinitis; Stroke; gamma-Aminobutyric Acid
PubMed: 30376593
DOI: 10.1002/14651858.CD009622.pub5 -
BMJ Open Jul 2019To summarise the definitions and combinations of codes used to identify outcomes of anxiety, depression, fatigue, cognitive dysfunction (including mild cognitive...
OBJECTIVES
To summarise the definitions and combinations of codes used to identify outcomes of anxiety, depression, fatigue, cognitive dysfunction (including mild cognitive dysfunction and dementia), sexual dysfunction, pain, sleep disorders, and fatal and non-fatal self-harm in studies using electronic health records from primary care databases in the UK.
DESIGN
Systematic review.
DATA SOURCES
Medline, Embase and lists of publications of the main primary care databases in the UK.
ELIGIBILITY CRITERIA
Included data from a UK primary care database and studied outcome(s) of interest.
DATA EXTRACTION AND SYNTHESIS
We abstracted information on the outcomes definition and codelists. When necessary, authors were contacted to request codelists.
RESULTS
120 studies were eligible. Codelists were available for 17/42 studies of depression; 21/41 studies of fatal and non-fatal self-harm; 17/27 studies of dementia/cognitive dysfunction; 5/12 studies of anxiety; 4/8 studies of pain; 3/6 studies of fatigue and sexual dysfunction; 1/2 studies of sleep disorders. Depression was most often defined using codes for diagnoses (37/42 studies) and/or antidepressants prescriptions (21/42 studies); six studies reported including symptoms in their definition. Anxiety was defined with codes for diagnoses (12/12 studies); four studies also reported including symptoms. Fatal self-harm was ascertained in primary care data linked to the Office for National Statistics mortality database in nine studies. Most studies of cognitive dysfunction included Alzheimer's disease, and vascular and frontotemporal dementia. Fatigue definitions varied little, including chronic fatigue syndrome, neurasthenia and postviral fatigue syndrome. All studies of sexual dysfunction focused on male conditions, principally erectile dysfunction. Sleep disorders included insomnia and hypersomnia. There was substantial variability in the codelists; validation was carried out i21/120 studies.
CONCLUSIONS
There is a need for standardised definitions and validated list of codes to assess mental health and quality of life outcomes in primary care databases in the UK.
Topics: Databases, Factual; Humans; Mental Disorders; Mental Health; Outcome Assessment, Health Care; Primary Health Care; Quality of Life; United Kingdom
PubMed: 31270119
DOI: 10.1136/bmjopen-2019-029227 -
The Cochrane Database of Systematic... Sep 2018Olanzapine as an antiemetic represents a new use of an antipsychotic drug. People with cancer may experience nausea and vomiting whilst receiving chemotherapy or... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Olanzapine as an antiemetic represents a new use of an antipsychotic drug. People with cancer may experience nausea and vomiting whilst receiving chemotherapy or radiotherapy, or whilst in the palliative phase of illness.
OBJECTIVES
To assess the efficacy and safety of olanzapine when used as an antiemetic in the prevention and treatment of nausea and vomiting related to cancer in adults.
SEARCH METHODS
We searched CENTRAL, MEDLINE and Embase for published data on 20th September 2017, as well as ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform for unpublished trials. We checked reference lists, and contacted experts in the field and study authors.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of olanzapine versus any comparator with or without adjunct therapies for the prevention or treatment, or both, of nausea or vomiting in people with cancer aged 18 years or older, in any setting, of any duration, with at least 10 participants per treatment arm.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology. We used GRADE to assess quality of evidence for each main outcome. We extracted data for absence of nausea or vomiting and frequency of serious adverse events as primary outcomes. We extracted data for patient perception of treatment, other adverse events, somnolence and fatigue, attrition, nausea or vomiting severity, breakthrough nausea and vomiting, rescue antiemetic use, and nausea and vomiting as secondary outcomes at specified time points.
MAIN RESULTS
We included 14 RCTs (1917 participants) from high-, middle- and low-income countries, representing over 24 different cancers. Thirteen studies were in chemotherapy-induced nausea and vomiting. Oral olanzapine was administered during highly emetogenic (HEC) or moderately emetogenic (MEC) chemotherapy (12 studies); chemoradiotherapy (one study); or palliation (one study). Eight studies await classification and 13 are ongoing.The main comparison was olanzapine versus placebo/no treatment. Other comparisons were olanzapine versus NK1 antagonist, prokinetic, 5-HT3 antagonist or dexamethasone.We assessed all but one study as having one or more domains that were at high risk of bias. Eight RCTs with fewer than 50 participants per treatment arm, and 10 RCTs with issues related to blinding, were at high risk of bias. We downgraded GRADE assessments due to imprecision, inconsistency and study limitations.Olanzapine versus placebo/no treatmentPrimary outcomesOlanzapine probably doubles the likelihood of no nausea or vomiting during chemotherapy from 25% to 50% (risk ratio (RR) 1.98, 95% confidence interval (CI) 1.59 to 2.47; 561 participants; 3 studies; solid tumours; HEC or MEC therapy; moderate-quality evidence) when added to standard therapy. Number needed to treat for additional beneficial outcome (NNTB) was 5 (95% CI 3.3 - 6.6).It is uncertain if olanzapine increases the risk of serious adverse events (absolute risk difference 0.7% more, 95% CI 0.2 to 5.2) (RR 2.46, 95% CI 0.48 to 12.55; 7 studies, 889 participants, low-quality evidence).Secondary outcomesFour studies reported patient perception of treatment. One study (48 participants) reported no difference in patient preference. Four reported quality of life but data were insufficient for meta-analysis.Olanzapine may increase other adverse events (RR 1.71, 95% CI 0.99 to 2.96; 332 participants; 4 studies; low-quality evidence) and probably increases somnolence and fatigue compared to no treatment or placebo (RR 2.33, 95% CI 1.30 to 4.18; anticipated absolute risk 8.2% more, 95% CI 1.9 to 18.8; 464 participants; 5 studies; moderate-quality evidence). Olanzapine probably does not affect all-cause attrition (RR 0.99, 95% CI 0.57 to 1.73; 943 participants; 8 studies; I² = 0%). We are uncertain if olanzapine increases attrition due to adverse events (RR 3.00, 95% CI 0.13 to 70.16; 422 participants; 6 studies). No participants withdrew due to lack of efficacy.We are uncertain if olanzapine reduces breakthrough nausea and vomiting (RR 0.38, 95% CI 0.10 to 1.47; 501 participants; 2 studies; I² = 54%) compared to placebo or no treatment. No studies reported 50% reduction in severity of nausea or vomiting, use of rescue antiemetics, or attrition.We are uncertain of olanzapine's efficacy in reducing acute nausea or vomiting. Olanzapine probably reduces delayed nausea (RR 1.71, 95% CI 1.40 to 2.09; 585 participants; 3 studies) and vomiting (RR 1.28, 95% CI 1.14 to 1.42; 702 participants; 5 studies).Subgroup analysis: 5 mg versus 10 mgPlanned subgroup analyses found that it is unclear if 5 mg is as effective an antiemetic as 10 mg. There is insufficient evidence to exclude the possibility that 5 mg may confer a lower risk of somnolence and fatigue than 10 mg.Other comparisonsOne study (20 participants) compared olanzapine versus NK1 antagonists. We observed no difference in any reported outcomes.One study (112 participants) compared olanzapine versus a prokinetic (metoclopramide), reporting that olanzapine may increase freedom from overall nausea (RR 2.95, 95% CI 1.73 to 5.02) and overall vomiting (RR 3.03, 95% CI 1.78 to 5.14).One study (62 participants) examined olanzapine versus 5-HT3 antagonists, reporting olanzapine may increase the likelihood of 50% or greater reduction in nausea or vomiting at 48 hours (RR 1.82, 95% CI 1.11 to 2.97) and 24 hours (RR 1.36, 95% CI 0.80 to 2.34).One study (229 participants) compared olanzapine versus dexamethasone, reporting that olanzapine may reduce overall nausea (RR 1.73, 95% CI 1.37 to 2.18), overall vomiting (RR 1.27, 95% CI 1.10 to 1.48), delayed nausea (RR 1.66, 95% CI 1.33 to 2.08) and delayed vomiting (RR 1.25, 95% CI 1.07 to 1.45).
AUTHORS' CONCLUSIONS
There is moderate-quality evidence that oral olanzapine probably increases the likelihood of not being nauseous or vomiting during chemotherapy from 25% to 50% in adults with solid tumours, in addition to standard therapy, compared to placebo or no treatment. There is uncertainty whether it increases serious adverse events. It may increase the likelihood of other adverse events, probably increasing somnolence and fatigue. There is uncertainty about relative benefits and harms of 5 mg versus 10 mg.We identified only RCTs describing oral administration. The findings of this review cannot be extrapolated to provide evidence about the efficacy and safety of any injectable form (intravenous, intramuscular or subcutaneous) of olanzapine.
Topics: Adult; Antiemetics; Antineoplastic Agents; Benzodiazepines; Chemoradiotherapy; Dexamethasone; Disorders of Excessive Somnolence; Fatigue; Humans; Metoclopramide; Nausea; Neoplasms; Olanzapine; Quality of Life; Randomized Controlled Trials as Topic; Vomiting
PubMed: 30246876
DOI: 10.1002/14651858.CD012555.pub2 -
Sleep Medicine Reviews Apr 2018Road traffic injuries are projected to be the leading cause of death for those aged between 15 and 29 years by the year 2030, and sleepiness is estimated to be the... (Review)
Review
Road traffic injuries are projected to be the leading cause of death for those aged between 15 and 29 years by the year 2030, and sleepiness is estimated to be the underlying cause in up to 15-20% of all motor vehicle accidents. Sleepiness at the wheel is most often caused by socially induced sleep deprivation or poor sleep hygiene in otherwise healthy individuals, medical disorders, or the intake of drugs. Validated methods for objectifying sleepiness are urgently sought, particularly in the context of driving. Based on the assumption that the identification and treatment of sleepiness, and its causes, may prevent motor vehicle accidents, driving simulators are a seemingly promising diagnostic tool. Despite the rising use of these in research, the reliability of their conclusions in healthy sleepy individuals and patients is still unclear. This systematic review aims to evaluate the practical value of driving simulators in a clinical environment when judging fitness to drive in sleepy individuals. From the 1674 records screened, 12 studies in sleepy individuals containing both simulated and real driving data were included. In general, simulated driving did not reliably predict real-life motor vehicle accidents, and especially not on an individual level, despite the moderate relationship between simulated and real-road test driving performance. The severity of sleepiness is most likely not the critical factor leading to motor vehicle accidents, but rather the perception of sleepiness. The self-perception of sleepiness related impairment, and risky behaviour while at the wheel should also be considered as key influencing factors.
Topics: Accidents, Traffic; Automobile Driver Examination; Automobile Driving; Disorders of Excessive Somnolence; Humans; Risk-Taking; Sleep Deprivation
PubMed: 28647501
DOI: 10.1016/j.smrv.2017.04.004 -
European Psychiatry : the Journal of... Feb 2020Distinguishing prodromes of bipolar disorder (BD) specific to children/adolescents, adults, and elderly patients is essential. The primary objective of this systematic...
BACKGROUND
Distinguishing prodromes of bipolar disorder (BD) specific to children/adolescents, adults, and elderly patients is essential. The primary objective of this systematic review was to determine initial and relapse prodromes identifying adult patients with BD.
METHODS
PubMed, PsycINFO, and Web of Science databases were searched using a predetermined strategy. A controlled process of study selection and data extraction was performed.
RESULTS
The 22 articles selected included 1,809 adult patients with BD. Initial prodromes cited most frequently in these studies showed low specificity. Among relapse prodromes cited most frequently, more talkative than usual, increased energy/more goal-directed behavior, thoughts start to race, increased self-esteem, strong interest in sex, increase in activity, and spending too much were identified exclusively before a manic/hypomanic episode, while loss of interest and hypersomnia were detected only before a depressive episode. Initial prodromal phases lasted longer than prodromal relapse phases. In the selected studies, the most used prodrome identification procedure was the clinical interview.
CONCLUSIONS
For adult patients with BD, initial and relapse prodromes of manic, hypomanic, and depressive episodes were identified. It is proposed that the most frequent prodromes found in this review be incorporated into a smartphone app that monitors the functioning of people at risk of BD and patients who have already been diagnosed. Data from this app would constitute a relevant source of big data.
Topics: Adult; Bipolar Disorder; Humans; Prodromal Symptoms; Recurrence
PubMed: 32093795
DOI: 10.1192/j.eurpsy.2019.18 -
Sleep Oct 2022To systematically determine subjective and objective outcome measures used to measure the efficacy of narcolepsy interventions in randomized controlled trials (RCTs) in...
STUDY OBJECTIVES
To systematically determine subjective and objective outcome measures used to measure the efficacy of narcolepsy interventions in randomized controlled trials (RCTs) in adults and children and assess psychometric properties of patient-reported outcome measures (PROMs) used.
METHODS
We searched bibliographical databases and clinical trial registries for narcolepsy RCTs and extracted objective and subjective outcome measures. If PROMs were used, we searched for psychometric studies conducted in a narcolepsy population using bibliographical databases and appraised using Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) guidelines.
RESULTS
In total, 80 different outcome measures were used across 100 RCTs. Epworth Sleepiness Scale (ESS) (n = 49) and Maintenance of Wakefulness Test (n = 47) were the most frequently used outcome measures. We found 19 validation studies of 10 PROMs in narcolepsy populations. There was limited evidence for validity or responsiveness of the ESS; yet sufficient reliability (pooled ICC: 0.81-0.87). Narcolepsy Severity Scale (NSS) had sufficient reliability (pooled ICC: 0.71-0.92) and both adult and pediatric versions had sufficient discriminant validity (treated/untreated). Content validity was only evaluated in pediatric populations for ESS-CHAD and NSS-P and rated inconclusive. Quality of evidence of the psychometric studies for all scales ranged from very low to low.
CONCLUSIONS
Although recognized by regulatory bodies and widely used as primary outcome measures in trials, there is surprisingly little evidence for the validity, reliability, and responsiveness of PROMs frequently used to assess treatment efficacy in narcolepsy. The field needs to establish patient-centered minimal clinically important differences for the PROMs used in these trials.
Topics: Adult; Child; Humans; Narcolepsy; Patient Reported Outcome Measures; Psychometrics; Quality of Life; Randomized Controlled Trials as Topic; Reproducibility of Results; Wakefulness
PubMed: 35797589
DOI: 10.1093/sleep/zsac156 -
Sleep Medicine Nov 2020Excessive daytime sleepiness (EDS) is the inability to maintain wakefulness and alertness during the major waking episodes of the day, with sleep occurring... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Excessive daytime sleepiness (EDS) is the inability to maintain wakefulness and alertness during the major waking episodes of the day, with sleep occurring unintentionally or at inappropriate times. Solriamfetol is a selective norepinephrine-dopamine reuptake inhibitor approved for EDS. This review was done to assess the efficacy and safety of solriamfetol in patients with EDS in narcolepsy or OSA.
METHODS
A systematic search of the electronic database was conducted for relevant studies. Any randomized controlled trial with outcome measures on the efficacy or safety of solriamfetol in EDS were eligible for inclusion. The primary outcomes were mean difference in the maintenance of wakefulness test (MWT), Epworth sleepiness scale (ESS) score, and risk ratio of adverse events. The random-effects model was used to calculate pooled effect estimates.
RESULTS
We identified 336 records from the database search. We analyzed eight articles reported from six clinical trials. We pooled outcome measures from five trials. The overall mean difference for MWT was 9.93 min (95% CI: 8.25-11.61), and the mean difference of ESS score was -4.44 (95% CI: -5.50 to -3.38), both in favor of solriamfetol over placebo. The overall risk ratio of adverse events with solriamfetol was 1.47 (95% CI: 1.28-1.69). The most common adverse events reported were headache, nausea, decreased appetite, anxiety, nasopharyngitis, and insomnia.
CONCLUSIONS
Solriamfetol is efficacious and has a favorable safety profile in the treatment of EDS in patients with narcolepsy and OSA. Solriamfetol is well tolerated and may be recommended for the treatment of EDS in these patients.
Topics: Carbamates; Disorders of Excessive Somnolence; Humans; Narcolepsy; Phenylalanine; Sleep Apnea, Obstructive
PubMed: 33032062
DOI: 10.1016/j.sleep.2020.09.019 -
Pharmacological Research May 2021Excessive daytime sleepiness is considered as the prominent symptom in narcolepsy and Obstructive Sleep Apnea (OSA). Pitolisant is a novel selective histamine H3... (Meta-Analysis)
Meta-Analysis
Excessive daytime sleepiness is considered as the prominent symptom in narcolepsy and Obstructive Sleep Apnea (OSA). Pitolisant is a novel selective histamine H3 receptor antagonist approved for improving excessive daytime sleepiness. The meta-analysis is conducted to assess the efficacy and safety of pitolisant versus placebo for excessive daytime sleepiness in narcolepsy and OSA. PubMed, Embase and Cochrane Library databases were searched from earliest date to November 2020 for randomized controlled trials (RCTs). The primary outcomes were mean changes in Epworth Sleepiness Scale (ESS), mean sleep latency, European quality-of-life questionnaire (EQ-5D), and risk ratio of treatment-emergent adverse events (TEAEs). We pooled 678 patients from four RCTs and found pitolisant significantly decreased ESS by mean difference (MD) of - 2.86 points (95% CI: -3.75 to -1.96), increased mean sleep latency by MD of 3.14 min (95% CI: 2.18-4.11), and increased EQ-5D by MD of 3.32 points (95% CI: 0.26-6.39) compared with placebo. The risk ratio of TEAE was 1.37 (95% CI: 1.08-1.74). Insomnia was the only TEAE significantly associated with pitolisant treatment. In conclusion, pitolisant showed great efficacy and controllable security versus placebo for excessive daytime sleepiness in narcolepsy and OSA. Compared with narcolepsy, patients with OSA were deemed to benefit more from pitolisant especially in terms of improving mobility and quality of life of patients without continuous positive airway pressure therapy.
Topics: Disorders of Excessive Somnolence; Histamine Antagonists; Humans; Narcolepsy; Piperidines; Placebo Effect; Quality of Life; Randomized Controlled Trials as Topic; Sleep Apnea, Obstructive
PubMed: 33667687
DOI: 10.1016/j.phrs.2021.105522