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Pesquisa : C10.886.425.800.200.750.500 [Categoria DeCS]
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[PMID]:28449891
[Au] Autor:Kollb-Sielecka M; Demolis P; Emmerich J; Markey G; Salmonson T; Haas M
[Ad] Endereço:European Medicines Agency (EMA), London, United Kingdom. Electronic address: marta.kollb-sielecka@ema.europa.
[Ti] Título:The European Medicines Agency review of pitolisant for treatment of narcolepsy: summary of the scientific assessment by the Committee for Medicinal Products for Human Use.
[So] Source:Sleep Med;33:125-129, 2017 May.
[Is] ISSN:1878-5506
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:On 31 March 2016, the European Commission issued a decision for a marketing authorisation valid throughout the European Union (EU) for pitolisant (Wakix) for the treatment of narcolepsy with or without cataplexy in adults. Pitolisant is an antagonist/inverse agonist of the human histamine H3 receptor. The dose should be selected using an up-titration scheme depending on individual patient response and tolerance and should not exceed 36 mg/day. The main evidence of efficacy of pitolisant was based on two Phase III clinical trials. The improvement on excessive daytime sleepiness was shown against placebo in the Harmony I study (-3.33 points; 95% confidence interval (CI) [-5.83; -0.83]; p = 0.024) and in Harmony CTP (-3.41 points; 95% CI [-4.95; -1.87]; p < 0.0001). The daily cataplexy rate in Harmony I improved against placebo with a rate ratio (rR) of 0.38 whilst in the Harmony CTP the ratio of improvement on weekly cataplexy rate against placebo was 0.512. The most commonly reported adverse reactions were headache, insomnia and nausea. This article summarizes the scientific review leading to approval of pitolisant in the EU. The assessment report and product information are available on the European Medicines Agency website (http://www.ema.europa.eu).
[Mh] Termos MeSH primário: Narcolepsia/tratamento farmacológico
Piperidinas/uso terapêutico
Receptores Histamínicos H3/efeitos dos fármacos
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Animais
Atenção/efeitos dos fármacos
Cataplexia/tratamento farmacológico
Ensaios Clínicos Fase III como Assunto
Cognição/efeitos dos fármacos
Agonismo Inverso de Drogas
Seres Humanos
Meia-Idade
Piperidinas/administração & dosagem
Piperidinas/efeitos adversos
Piperidinas/metabolismo
Receptores Histamínicos H3/fisiologia
Resultado do Tratamento
Promotores da Vigília/farmacologia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Piperidines); 0 (Receptors, Histamine H3); 0 (Wakefulness-Promoting Agents); 4BC83L4PIY (1-(3-(3-(4-chlorophenyl)propoxy)propyl)piperidine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE


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[PMID]:28472332
[Au] Autor:Antelmi E; Pizza F; Vandi S; Neccia G; Ferri R; Bruni O; Filardi M; Cantalupo G; Liguori R; Plazzi G
[Ad] Endereço:Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum, University of Bologna, Bologna, Italy.
[Ti] Título:The spectrum of REM sleep-related episodes in children with type 1 narcolepsy.
[So] Source:Brain;140(6):1669-1679, 2017 Jun 01.
[Is] ISSN:1460-2156
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Type 1 narcolepsy is a central hypersomnia due to the loss of hypocretin-producing neurons and characterized by cataplexy, excessive daytime sleepiness, sleep paralysis, hypnagogic hallucinations and disturbed nocturnal sleep. In children, close to the disease onset, type 1 narcolepsy has peculiar clinical features with severe cataplexy and a complex admixture of movement disorders occurring while awake. Motor dyscontrol during sleep has never been systematically investigated. Suspecting that abnormal motor control might affect also sleep, we systematically analysed motor events recorded by means of video polysomnography in 40 children with type 1 narcolepsy (20 females; mean age 11.8 ± 2.6 years) and compared these data with those recorded in 22 age- and sex-matched healthy controls. Motor events were classified as elementary movements, if brief and non-purposeful and complex behaviours, if simulating purposeful behaviours. Complex behaviours occurring during REM sleep were further classified as 'classically-defined' and 'pantomime-like' REM sleep behaviour disorder episodes, based on their duration and on their pattern (i.e. brief and vivid-energetic in the first case, longer and with subcontinuous gesturing mimicking daily life activity in the second case). Elementary movements emerging either from non-REM or REM sleep were present in both groups, even if those emerging from REM sleep were more numerous in the group of patients. Conversely, complex behaviours could be detected only in children with type 1 narcolepsy and were observed in 13 patients, with six having 'classically-defined' REM sleep behaviour disorder episodes and seven having 'pantomime-like' REM sleep behaviour disorder episodes. Complex behaviours during REM sleep tended to recur in a stereotyped fashion for several times during the night, up to be almost continuous. Patients displaying a more severe motor dyscontrol during REM sleep had also more severe motor disorder during daytime (i.e. status cataplecticus) and more complaints of disrupted nocturnal sleep and of excessive daytime sleepiness. The neurophysiological hallmark of this severe motor dyscontrol during REM sleep was a decreased atonia index. The present study reports for the first time the occurrence of a severe and peculiar motor disorder during REM sleep in paediatric type 1 narcolepsy and confirms the presence of a severe motor dyscontrol in these patients, emerging not only from wakefulness (i.e. status cataplecticus), but also from sleep (i.e. complex behaviours during REM sleep). This is probably related to the acute imbalance of the hypocretinergic system, which physiologically acts by promoting movements during wakefulness and suppressing them during sleep.
[Mh] Termos MeSH primário: Cataplexia/fisiopatologia
Narcolepsia/fisiopatologia
Transtorno do Comportamento do Sono REM/fisiopatologia
[Mh] Termos MeSH secundário: Adolescente
Fenômenos Biomecânicos
Cataplexia/etiologia
Criança
Feminino
Seres Humanos
Masculino
Narcolepsia/complicações
Polissonografia
Transtorno do Comportamento do Sono REM/etiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170719
[Lr] Data última revisão:
170719
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1093/brain/awx096


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[PMID]:28443381
[Au] Autor:Kallweit U; Bassetti CL
[Ad] Endereço:a Department of Neurology , Bern University Hospital and University of Bern , Bern , Switzerland.
[Ti] Título:Pharmacological management of narcolepsy with and without cataplexy.
[So] Source:Expert Opin Pharmacother;18(8):809-817, 2017 Jun.
[Is] ISSN:1744-7666
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Narcolepsy is an orphan neurological disease and presents with sleep-wake, motoric, neuropsychiatric and metabolic symptoms. Narcolepsy with cataplexy is most commonly caused by an immune-mediated process including genetic and environmental factors, resulting in the selective loss of hypocretin-producing neurons. Narcolepsy has a major impact on workableness and quality of life. Areas covered: This review provides an overview of the temporal available treatment options for narcolepsy (type 1 and 2) in adults, including authorization status by regulatory agencies. First- and second-line options are discussed as well as combination therapies. In addition, treatment options for frequent coexisting co-morbidities and different phenotypes of narcolepsy are presented. Finally, this review considers potential future management strategies. Non-pharmacological approaches are important in the management of narcolepsy but will not be covered in this review. Expert opinion: Concise evaluation of symptoms and type of narcolepsy, coexisting co-morbidities and patients´ distinct needs is mandatory in order to identify a suitable, individual pharmacological treatment. First-line options include Modafinil/Armodafinil (for excessive daytime sleepiness, EDS), Sodium Oxybate (for EDS and/with cataplexy), Pitolisant (for EDS and cataplexy) and Venlafaxine (for cataplexy (off-label) and co-morbid depression). New symptomatic and causal treatment most probably will be completed by hypocretin-replacement and immune-modifying strategies.
[Mh] Termos MeSH primário: Narcolepsia/tratamento farmacológico
Sono/efeitos dos fármacos
Promotores da Vigília/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Compostos Benzidrílicos/administração & dosagem
Compostos Benzidrílicos/uso terapêutico
Cataplexia/complicações
Cataplexia/diagnóstico
Cataplexia/tratamento farmacológico
Quimioterapia Combinada
Seres Humanos
Narcolepsia/complicações
Narcolepsia/diagnóstico
Neuropeptídeos/metabolismo
Uso Off-Label
Orexinas/metabolismo
Piperidinas/administração & dosagem
Piperidinas/uso terapêutico
Qualidade de Vida
Oxibato de Sódio/administração & dosagem
Oxibato de Sódio/uso terapêutico
Cloridrato de Venlafaxina/administração & dosagem
Cloridrato de Venlafaxina/uso terapêutico
Promotores da Vigília/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Benzhydryl Compounds); 0 (Neuropeptides); 0 (Orexins); 0 (Piperidines); 0 (Wakefulness-Promoting Agents); 4BC83L4PIY (1-(3-(3-(4-chlorophenyl)propoxy)propyl)piperidine); 7D7RX5A8MO (Venlafaxine Hydrochloride); 7G33012534 (Sodium Oxybate); R3UK8X3U3D (modafinil); V63XWA605I (armodafinil)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170427
[St] Status:MEDLINE
[do] DOI:10.1080/14656566.2017.1323877


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[PMID]:28364512
[Au] Autor:Zhang X; Kantelhardt JW; Dong XS; Krefting D; Li J; Yan H; Pillmann F; Fietze I; Penzel T; Zhao L; Han F
[Ad] Endereço:Department of Respiratory Medicine, Peking University International Hospital, Beijing, China.
[Ti] Título:Nocturnal Dynamics of Sleep-Wake Transitions in Patients With Narcolepsy.
[So] Source:Sleep;40(2), 2017 Feb 01.
[Is] ISSN:1550-9109
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Introduction: We investigate how characteristics of sleep-wake dynamics in humans are modified by narcolepsy, a clinical condition that is supposed to destabilize sleep-wake regulation. Subjects with and without cataplexy are considered separately. Differences in sleep scoring habits as a possible confounder have been examined. Aims and Methods: Four groups of subjects are considered: narcolepsy patients from China with (n = 88) and without (n = 15) cataplexy, healthy controls from China (n = 110) and from Europe (n = 187, 2 nights each). After sleep-stage scoring and calculation of sleep characteristic parameters, the distributions of wake-episode durations and sleep-episode durations are determined for each group and fitted by power laws (exponent α) and by exponentials (decay time τ). Results: We find that wake duration distributions are consistent with power laws for healthy subjects (China: α = 0.88, Europe: α = 1.02). Wake durations in all groups of narcolepsy patients, however, follow the exponential law (τ = 6.2-8.1 min). All sleep duration distributions are best fitted by exponentials on long time scales (τ = 34-82 min). Conclusions: We conclude that narcolepsy mainly alters the control of wake-episode durations but not sleep-episode durations, irrespective of cataplexy. Observed distributions of shortest wake and sleep durations suggest that differences in scoring habits regarding the scoring of short-term sleep stages may notably influence the fitting parameters but do not affect the main conclusion.
[Mh] Termos MeSH primário: Narcolepsia/diagnóstico
Narcolepsia/fisiopatologia
Fases do Sono/fisiologia
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Idoso de 80 Anos ou mais
Cataplexia/diagnóstico
Cataplexia/epidemiologia
Cataplexia/fisiopatologia
Criança
Pré-Escolar
China/epidemiologia
Europa (Continente)/epidemiologia
Feminino
Seres Humanos
Masculino
Meia-Idade
Narcolepsia/epidemiologia
Sono/fisiologia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171004
[Lr] Data última revisão:
171004
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170402
[St] Status:MEDLINE
[do] DOI:10.1093/sleep/zsw050


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[PMID]:28364477
[Au] Autor:Lopez R; Barateau L; Evangelista E; Chenini S; Robert P; Jaussent I; Dauvilliers Y
[Ad] Endereço:Unité des Troubles du Sommeil Service de Neurologie, Centre National de Référence Narcolepsie Hypersomnies, Hôpital Gui-de-Chauliac, Montpellier F-34000, France.
[Ti] Título:Temporal Changes in the Cerebrospinal Fluid Level of Hypocretin-1 and Histamine in Narcolepsy.
[So] Source:Sleep;40(1), 2017 Jan 01.
[Is] ISSN:1550-9109
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Study Objectives: To follow the temporal changes of cerebrospinal fluid (CSF) biomarker levels in narcoleptic patients with unexpected hypocretin level at referral. Methods: From 2007 to 2015, 170 human leukocyte antigen (HLA) DQB1*06:02-positive patients with primary narcolepsy and definite (n = 155, 95 males, 60 females, 36 children) or atypical cataplexy (n = 15, 4 males, 3 children) were referred to our center. Cerebrospinal hypocretin deficiency was found in 95.5% and 20% of patients with definitive and atypical cataplexy, respectively. CSF hypocretin-1 (n = 6) and histamine/tele-methylhistamine (n = 5) levels were assessed twice (median interval: 14.4 months) in four patients with definite and in two with atypical cataplexy and hypocretin level greater than 100 pg/mL at baseline. Results: CSF hypocretin levels decreased from normal/intermediate to undetectable levels in three of the four patients with definite cataplexy and remained stable in the other (>250 pg/mL). Hypocretin level decreased from 106 to 27 pg/mL in one patient with atypical cataplexy, and remained stable in the other (101 and 106 pg/mL). CSF histamine and tele-methylhistamine levels remained stable, but for one patient showing increased frequency of cataplexy and a strong decrease (-72.5%) of tele-methylhistamine levels several years after disease onset. No significant association was found between relative or absolute change in hypocretin level and demographic/clinical features. Conclusions: These findings show that in few patients with narcolepsy with cataplexy, symptoms and CSF marker levels can change over time. In these rare patients with cataplexy without baseline hypocretin deficiency, CSF markers should be monitored over time with potential for immune therapies in early stages to try limiting hypocretin neuron loss.
[Mh] Termos MeSH primário: Histamina/líquido cefalorraquidiano
Narcolepsia/líquido cefalorraquidiano
Orexinas/líquido cefalorraquidiano
[Mh] Termos MeSH secundário: Adolescente
Adulto
Biomarcadores/líquido cefalorraquidiano
Cataplexia/líquido cefalorraquidiano
Criança
Feminino
Cadeias beta de HLA-DQ/imunologia
Teste de Histocompatibilidade
Seres Humanos
Masculino
Metilistaminas/líquido cefalorraquidiano
Meia-Idade
Orexinas/deficiência
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (HLA-DQ beta-Chains); 0 (HLA-DQB1 antigen); 0 (Methylhistamines); 0 (Orexins); 820484N8I3 (Histamine); KCB81T4EOF (tele-methylhistamine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170402
[St] Status:MEDLINE
[do] DOI:10.1093/sleep/zsw010


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[PMID]:28235898
[Au] Autor:Mahoney CE; Agostinelli LJ; Brooks JN; Lowell BB; Scammell TE
[Ad] Endereço:Department of Neurology and.
[Ti] Título:GABAergic Neurons of the Central Amygdala Promote Cataplexy.
[So] Source:J Neurosci;37(15):3995-4006, 2017 Apr 12.
[Is] ISSN:1529-2401
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Narcolepsy is characterized by chronic sleepiness and cataplexy-sudden muscle paralysis triggered by strong, positive emotions. This condition is caused by a lack of orexin (hypocretin) signaling, but little is known about the neural mechanisms that mediate cataplexy. The amygdala regulates responses to rewarding stimuli and contains neurons active during cataplexy. In addition, lesions of the amygdala reduce cataplexy. Because GABAergic neurons of the central nucleus of the amygdala (CeA) target brainstem regions known to regulate muscle tone, we hypothesized that these cells promote emotion-triggered cataplexy. We injected adeno-associated viral vectors coding for Cre-dependent DREADDs or a control vector into the CeA of orexin knock-out mice crossed with vGAT-Cre mice, resulting in selective expression of the excitatory hM3 receptor or the inhibitory hM4 receptor in GABAergic neurons of the CeA. We measured sleep/wake behavior and cataplexy after injection of saline or the hM3/hM4 ligand clozapine oxide (CNO) under baseline conditions and under conditions that should elicit positive emotions. In mice expressing hM3, CNO approximately doubled the amount of cataplexy in the first 3 h after dosing under baseline conditions. Rewarding stimuli (chocolate or running wheels) also increased cataplexy, but CNO produced no further increase. In mice expressing hM4, CNO reduced cataplexy in the presence of chocolate or running wheels. These results demonstrate that GABAergic neurons of the CeA are sufficient and necessary for the production of cataplexy in mice, and they likely are a key part of the mechanism through which positive emotions trigger cataplexy. Cataplexy is one of the major symptoms of narcolepsy, but little is known about how strong, positive emotions trigger these episodes of muscle paralysis. Prior research shows that amygdala neurons are active during cataplexy and cataplexy is reduced by lesions of the amygdala. We found that cataplexy is substantially increased by selective activation of GABAergic neurons in the central nucleus of the amygdala (CeA). We also demonstrate that inhibition of these neurons reduces reward-promoted cataplexy. These results build upon prior work to establish the CeA as a crucial element in the neural mechanisms of cataplexy. These results demonstrate the importance of the CeA in regulating responses to rewarding stimuli, shedding light on the broader neurobiology of emotions and motor control.
[Mh] Termos MeSH primário: Cataplexia/genética
Cataplexia/metabolismo
Núcleo Central da Amígdala/metabolismo
Neurônios GABAérgicos/metabolismo
[Mh] Termos MeSH secundário: Animais
Locomoção/fisiologia
Masculino
Camundongos
Camundongos Knockout
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1704
[Cu] Atualização por classe:171013
[Lr] Data última revisão:
171013
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170226
[St] Status:MEDLINE
[do] DOI:10.1523/JNEUROSCI.4065-15.2017


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[PMID]:28209737
[Au] Autor:Snow MB; Fraigne JJ; Thibault-Messier G; Chuen VL; Thomasian A; Horner RL; Peever J
[Ad] Endereço:Centre for Biological Timing and Cognition.
[Ti] Título:GABA Cells in the Central Nucleus of the Amygdala Promote Cataplexy.
[So] Source:J Neurosci;37(15):4007-4022, 2017 Apr 12.
[Is] ISSN:1529-2401
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cataplexy is a hallmark of narcolepsy characterized by the sudden uncontrollable onset of muscle weakness or paralysis during wakefulness. It can occur spontaneously, but is typically triggered by positive emotions such as laughter. Although cataplexy was identified >130 years ago, its neural mechanism remains unclear. Here, we show that a newly identified GABA circuit within the central nucleus of the amygdala (CeA) promotes cataplexy. We used behavioral, electrophysiological, immunohistochemical, and chemogenetic strategies to target and manipulate CeA activity selectively in narcoleptic ( ) mice to determine its functional role in controlling cataplexy. First, we show that chemogenetic activation of the entire CeA produces a marked increase in cataplexy attacks. Then, we show that GABA cells within the CeA are responsible for mediating this effect. To manipulate GABA cells specifically, we developed a new mouse line that enables genetic targeting of GABA cells in mice. We found that chemogenetic activation of GABA CeA cells triggered a 253% increase in the number of cataplexy attacks without affecting their duration, suggesting that GABA cells play a functional role in initiating but not maintaining cataplexy. We show that GABA cell activation only promotes cataplexy attacks associated with emotionally rewarding stimuli, not those occurring spontaneously. However, we found that chemogenetic inhibition of GABA CeA cells does not prevent cataplexy, suggesting these cells are not required for initiating cataplexy attacks. Our results indicate that the CeA promotes cataplexy onset and that emotionally rewarding stimuli may trigger cataplexy by activating GABA cells in the CeA. Although cataplexy has been closely linked to positive emotions for >130 years, the neural circuitry that underlies this relationship is poorly understood. Recent work suggests that the amygdala, a brain area important for processing emotion, may be part of this circuit. This study provides the first functional evidence to implicate GABA cells in the amygdala as regulators of cataplexy triggered by positive emotions and identifies the amygdala as the brain region important more for gating the entrance into rather than the exit from cataplexy. We also generated a new mouse model for studying GABA neurons in narcoleptic mice, which could serve as a useful tool for studying the neurobiological underpinnings of narcolepsy.
[Mh] Termos MeSH primário: Cataplexia/metabolismo
Núcleo Central da Amígdala/metabolismo
Neurônios GABAérgicos/metabolismo
[Mh] Termos MeSH secundário: Animais
Cataplexia/fisiopatologia
Núcleo Central da Amígdala/fisiopatologia
Eletroencefalografia/métodos
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Orexinas/deficiência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Orexins)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170419
[Lr] Data última revisão:
170419
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170218
[St] Status:MEDLINE
[do] DOI:10.1523/JNEUROSCI.4070-15.2017


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[PMID]:28129985
[Au] Autor:Szakacs Z; Dauvilliers Y; Mikhaylov V; Poverennova I; Krylov S; Jankovic S; Sonka K; Lehert P; Lecomte I; Lecomte JM; Schwartz JC; HARMONY-CTP study group
[Ad] Endereço:State Health Center, Budapest, Hungary.
[Ti] Título:Safety and efficacy of pitolisant on cataplexy in patients with narcolepsy: a randomised, double-blind, placebo-controlled trial.
[So] Source:Lancet Neurol;16(3):200-207, 2017 03.
[Is] ISSN:1474-4465
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Histaminergic neurons are crucial to maintain wakefulness, but their role in cataplexy is unknown. We assessed the safety and efficacy of pitolisant, a histamine H3 receptor inverse agonist, for treatment of cataplexy in patients with narcolepsy. METHODS: For this randomised, double-blind, placebo-controlled trial we recruited patients with narcolepsy from 16 sleep centres in nine countries (Bulgaria, Czech Republic, Hungary, Macedonia, Poland, Russia, Serbia, Turkey, and Ukraine). Patients were eligible if they were aged 18 years or older, diagnosed with narcolepsy with cataplexy according to version two of the International Classification of Sleep Disorders criteria, experienced at least three cataplexies per week, and had excessive daytime sleepiness (defined as an Epworth Sleepiness Scale score ≥12). We used a computer-generated sequence via an interactive web response system to randomly assign patients to receive either pitolisant or placebo once per day (1:1 ratio). Randomisation was done in blocks of four. Participants and investigators were masked to treatment allocation. Treatment lasted for 7 weeks: 3 weeks of flexible dosing decided by investigators according to efficacy and tolerance (5 mg, 10 mg, or 20 mg oral pitolisant), followed by 4 weeks of stable dosing (5 mg, 10 mg, 20 mg, or 40 mg). The primary endpoint was the change in the average number of cataplexy attacks per week as recorded in patient diaries (weekly cataplexy rate [WCR]) between the 2 weeks of baseline and the 4 weeks of stable dosing period. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01800045. FINDINGS: The trial was done between April 19, 2013, and Jan 28, 2015. We screened 117 patients, 106 of whom were randomly assigned to treatment (54 to pitolisant and 52 to placebo) and, after dropout, 54 patients from the pitolisant group and 51 from the placebo group were included in the intention-to-treat analysis. The WCR during the stable dosing period compared with baseline was decreased by 75% (WCR =2·27; WCR =9·15; WCR =0·25) in patients who received pitolisant and 38% (WCR =4·52; WCR =7·31; WCR =0·62) in patients who received placebo (rate ratio 0·512; 95% CI 0·43-0·60, p<0·0001). Treatment-related adverse events were significantly more common in the pitolisant group than in the placebo group (15 [28%] of 54 vs 6 [12%] of 51; p=0·048). There were no serious adverse events, but one case of severe nausea in the pitolisant group. The most frequent adverse events in the pitolisant group (headache, irritability, anxiety, and nausea) were mild or moderate except one case of severe nausea. No withdrawal syndrome was detected following pitolisant treatment; one case was detected in the placebo group. INTERPRETATION: Pitolisant was well tolerated and efficacious in reducing cataplexy. If confirmed in long-term studies, pitolisant might constitute a useful first-line therapy for cataplexy in patients with narcolepsy, for whom there are currently few therapeutic options. FUNDING: Bioprojet, France.
[Mh] Termos MeSH primário: Cataplexia/tratamento farmacológico
Cataplexia/etiologia
Antagonistas dos Receptores Histamínicos H3/uso terapêutico
Narcolepsia/complicações
Piperidinas/uso terapêutico
Resultado do Tratamento
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Bases de Dados Bibliográficas/estatística & dados numéricos
Método Duplo-Cego
Feminino
Seguimentos
Seres Humanos
Masculino
Meia-Idade
Estudos Retrospectivos
Índice de Gravidade de Doença
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Histamine H3 Antagonists); 0 (Piperidines); 4BC83L4PIY (1-(3-(3-(4-chlorophenyl)propoxy)propyl)piperidine)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170727
[Lr] Data última revisão:
170727
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170129
[St] Status:MEDLINE


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[PMID]:27838095
[Au] Autor:Monaca C; Franco P; Philip P; Dauvilliers Y
[Ad] Endereço:Unité des troubles du sommeil, neurophysiologie clinique, CHRU de Lille, 2, avenue Oscar-Lambret, 59000 Lille, France; Inserm U1171, 59000 Lille, France.
[Ti] Título:French consensus. Type 1 and type 2 Narcolepsy: Investigations and follow-up..
[So] Source:Rev Neurol (Paris);173(1-2):25-31, 2017 Jan - Feb.
[Is] ISSN:0035-3787
[Cp] País de publicação:France
[La] Idioma:fre
[Ab] Resumo:In the new international classification of sleep disorders (ICSD-3), narcolepsy is differentiated into two distinct pathologies: type 1 narcolepsy (NT1) and type 2 narcolepsy (NT2). NT1 is characterised by periods of an irrepressible need to sleep, cataplexy (a sudden loss of muscle tone triggered by emotion) and in some cases the presence of symptoms such as hypnagogic hallucinations, sleep paralysis and disturbed night-time sleep. Its physiopathology is based on the loss of hypocretin neurons in the hypothalamus, seemingly connected to an auto-immune process. By definition, cataplexy is absent and the hypocretin levels in the CSF are normal in NT2. Confirming the diagnosis requires polysomnography and multiple sleep latency tests. The choice of further investigations is based on the presence or absence of typical cataplexy. Further investigations include HLA typing, lumbar puncture to measure the hypocretin level in the CSF, or even brain imagery in the case of narcolepsy suspected to be secondary to an underlying pathology. In this consensus we propose recommendations for the work-up to be carried out during diagnosis and follow-up for patients suffering from narcolepsy.
[Mh] Termos MeSH primário: Narcolepsia/classificação
Narcolepsia/diagnóstico
[Mh] Termos MeSH secundário: Assistência ao Convalescente/métodos
Cataplexia/diagnóstico
Cataplexia/epidemiologia
Cataplexia/fisiopatologia
Técnicas de Diagnóstico Neurológico
França/epidemiologia
Seres Humanos
Narcolepsia/epidemiologia
Narcolepsia/terapia
Polissonografia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161114
[St] Status:MEDLINE


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[PMID]:27835717
[Au] Autor:Ruoff CM; Reaven NL; Funk SE; McGaughey KJ; Ohayon MM; Guilleminault C; Black J
[Ad] Endereço:Stanford Center for Sleep Sciences and Medicine, Palo Alto, California, USA.
[Ti] Título:High Rates of Psychiatric Comorbidity in Narcolepsy: Findings From the Burden of Narcolepsy Disease (BOND) Study of 9,312 Patients in the United States.
[So] Source:J Clin Psychiatry;78(2):171-176, 2017 Feb.
[Is] ISSN:1555-2101
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To evaluate psychiatric comorbidity patterns in patients with a narcolepsy diagnosis in the United States. METHODS: Truven Health Analytics MarketScan Research Databases were accessed to identify individuals ≥ 18 years of age with ≥ 1 ICD-9 diagnosis code(s) for narcolepsy continuously insured between 2006 and 2010 and non-narcolepsy controls matched 5:1 (age, gender, region, payer). Extensive subanalyses were conducted to confirm the validity of narcolepsy definitions. Narcolepsy subjects and controls were compared for frequency of psychiatric comorbid conditions (based on ICD-9 codes/Clinical Classification Software [CCS] level 2 categories) and psychiatric medication use. RESULTS: The final population included 9,312 narcolepsy subjects and 46,559 controls (each group, mean age = 46.1 years; 59% female). All categories of mental illness were significantly more prevalent in patients with narcolepsy versus controls, with the highest excess prevalence noted for CCS 5.8 Mood disorders (37.9% vs 13.8%; odds ratio [OR] = 4.0; 95% CI, 3.8-4.2), CCS 5.8.2 Depressive disorders (35.8% vs 13.0%; OR = 3.9; 95% CI, 3.7-4.1), and CCS 5.2 Anxiety disorders (25.1% vs 11.9%; OR = 2.5; 95% CI, 2.4-2.7). Excess prevalence of anxiety and mood disorders (narcolepsy vs controls) was higher in younger age groups versus older age groups. Psychiatric medication usage was higher in the narcolepsy group versus controls in the following categories: selective serotonin reuptake inhibitors (36% vs 17%), anxiolytic benzodiazepines (34% vs 19%), hypnotics (29% vs 13%), serotonin-norepinephrine reuptake inhibitors (21% vs 6%), and tricyclic antidepressants (13% vs 4%) (all P values < .0001). CONCLUSIONS: Narcolepsy is associated with significant comorbid psychiatric illness burden and higher psychiatric medication usage compared with the non-narcolepsy population.
[Mh] Termos MeSH primário: Efeitos Psicossociais da Doença
Transtornos Mentais/epidemiologia
Narcolepsia/epidemiologia
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Cataplexia/diagnóstico
Cataplexia/epidemiologia
Cataplexia/psicologia
Estudos de Coortes
Comorbidade
Estudos Transversais
Feminino
Inquéritos Epidemiológicos
Seres Humanos
Masculino
Transtornos Mentais/diagnóstico
Transtornos Mentais/psicologia
Meia-Idade
Narcolepsia/diagnóstico
Narcolepsia/psicologia
Estados Unidos
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170608
[Lr] Data última revisão:
170608
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161112
[St] Status:MEDLINE
[do] DOI:10.4088/JCP.15m10262



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