Narcolepsia: uma interface entre neurologia, imunologia, sono e genética

Coelho, Fernando Morgadinho Santos

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Arquivos de Neuro-Psiquiatria

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Sumário

View and Review • Arq. Neuro-Psiquiatr. 82 (6) • 2024 • https://doi.org/10.1055/s-0044-1779299 copiar

Narcolepsia: uma interface entre neurologia, imunologia, sono e genética

Autoria SCIMAGO INSTITUTIONS RANKINGS

Resumo

A narcolepsia é um distúrbio primário do sistema nervoso central resultante das interações genéticas, ambientais e imunológicas definidas como sonolência diurna excessiva mais cataplexia, alucinações, paralisia do sono e fragmentação do sono. A fisiopatologia não é completamente conhecida, mas a interação entre predisposição genética, exposição ambiental e componente imunológico com consequente deficiência de hipocretina-1 é o modelo para explicar a narcolepsia tipo I. O mecanismo da narcolepsia tipo II é menos compreendido. Há um atraso de mais de dez anos para o diagnóstico da narcolepsia em todo o mundo. Pacientes com narcolepsia apresentam muitas comorbidades com impacto negativo na qualidade de vida. O tratamento da narcolepsia deve conter uma abordagem educativa para a família, colegas de trabalho e pacientes. Cochilos programados e higiene do sono são importantes para minimizar a dose dos medicamentos. Muito progresso foi observado no tratamento farmacológico da narcolepsia com novos estimulantes, diferentes apresentações de oxibato e estudos recentes com agonistas de orexina. A narcolepsia é uma doença rara que precisa ser mais compreendida e destacada para evitar atrasos no diagnóstico e incapacidades graves nos pacientes.

Palavras-chave
Narcolepsia; Diagnóstico; Comorbidade; Terapêutica

	0	1	2	3
1. Chance of dozing off while sitting and reading?	Never	Slight	Moderate	High
2. Chance of dozing off while watching TV?	Never	Slight	Moderate	High
3. Chance of dozing off while Sitting, inactive in a public place?	Never	Slight	Moderate	High
4. Chance of dozing off as a passenger in a car for an hour without a break?	Never	Slight	Moderate	High
5. Chance of dozing off while lying down to rest in the afternoon when circumstances permit?	Never	Slight	Moderate	High
6. Chance of dozing off while sitting and talking to someone?	Never	Slight	Moderate	High
7. Chance of dozing off while sitting quietly after lunch without alcohol?	Never	Slight	Moderate	High
8. Chance of dozing off while in a car, while stopped for a few minutes in traffic?	Never	Slight	Moderate	High
Scores can be interpreted as follows: 0–5 lower normal daytime sleepiness. 6–10 normal daytime sleepiness. 11–12 mild excessive daytime symptoms. 13–15 moderate excessive daytime symptoms. 16–24 severe excessive daytime symptoms.

Drug	Recommendation	Strengths of recommendation	Quality of evidence	Dosage	Side effects/notes
Modafinil	Excessive daytime sleepiness	Strong	Moderate	100–400mg	Headache, nausea, dry mouth, nervousness, dyspepsia, pain, vomiting, increased blood pressure, psychosis, and mania. # Risk of cardiovascular disorders.⁵⁶56 Bassetti CLA, Kallweit U, Vignatelli L, et al. European guideline and expert statements on the management of narcolepsy in adults and children. J Sleep Res 2021;30(06):e13387. Doi: 10.1111/jsr.13387 https://doi.org/10.1111/jsr.13387...
Armodafinil	Excessive daytime sleepiness	Strong	Moderate	150–250mg	Headache, nausea, dry mouth, nervousness, dyspepsia, pain, vomiting, increased blood pressure, psychosis, and mania. # Risk of cardiovascular disorders.⁵⁶56 Bassetti CLA, Kallweit U, Vignatelli L, et al. European guideline and expert statements on the management of narcolepsy in adults and children. J Sleep Res 2021;30(06):e13387. Doi: 10.1111/jsr.13387 https://doi.org/10.1111/jsr.13387... 57 Aguilar AC, Frange C, Pimentel Filho LH, Reis MJ, Tufik S, Coelho FMS. Lisdexamfetamine to improve excessive daytime sleepiness and weight management in narcolepsy: a case series. Br J Psychiatry 2020;42(03):314–316. Doi: 10.1590/1516-4446-2019-0544 https://doi.org/10.1590/1516-4446-2019-0... -⁵⁸58 Lin JS, Gervasoni D, Hou Y, et al. Effects of amphetamine and modafinil on the sleep/wake cycle during experimental hypersomnia induced by sleep deprivation in the cat. J Sleep Res 2000;9 (01):89–96. https://www.ncbi.nlm.nih.gov/pubmed/10733694 https://www.ncbi.nlm.nih.gov/pubmed/1073...
Methylphenidate	Excessive daytime sleepiness	Weak	Low	5–60mg	Headache, nausea, dry mouth, nervousness, dyspepsia, pain, vomiting, increased blood pressure, psychosis, and mania. # Risk of cardiovascular disorders.⁵⁶56 Bassetti CLA, Kallweit U, Vignatelli L, et al. European guideline and expert statements on the management of narcolepsy in adults and children. J Sleep Res 2021;30(06):e13387. Doi: 10.1111/jsr.13387 https://doi.org/10.1111/jsr.13387...
Amphetamines	Excessive daytime sleepiness	Weak	Low	Lisdexanfetamina 10–70mg	Headache, nausea, dry mouth, nervousness, dyspepsia, pain, vomiting, increased blood pressure, psychosis, and mania. # Risk of cardiovascular disorders.⁵⁶56 Bassetti CLA, Kallweit U, Vignatelli L, et al. European guideline and expert statements on the management of narcolepsy in adults and children. J Sleep Res 2021;30(06):e13387. Doi: 10.1111/jsr.13387 https://doi.org/10.1111/jsr.13387... ,⁶²62 Dauvilliers Y, Mignot E, Del Río Villegas R, et al. Oral Orexin Receptor 2 Agonist in Narcolepsy Type 1. N Engl J Med 2023;389 (04):309–321. Doi: 10.1056/NEJMoa2301940 https://doi.org/10.1056/NEJMoa2301940...
Solriamfetol	Excessive daytime sleepiness	Strong	Moderate	37.5mg-150mg	Insomnia, headache, nausea, decreased appetite, anxiety.⁵⁶56 Bassetti CLA, Kallweit U, Vignatelli L, et al. European guideline and expert statements on the management of narcolepsy in adults and children. J Sleep Res 2021;30(06):e13387. Doi: 10.1111/jsr.13387 https://doi.org/10.1111/jsr.13387... Solriamfetol is not available in Brazil.
L-Carnitine	Excessive daytime sleepiness	Weak	Low	510mg	It is safe during pregnancy.⁶⁵65 Calvo-Ferrandiz E, Peraita-Adrados R. Narcolepsy with cataplexy and pregnancy: a case-control study. J Sleep Res 2018;27(02): 268–272. Doi: 10.1111/jsr.12567 https://doi.org/10.1111/jsr.12567... ,⁶⁶66 Barros F, Aguilar ACR, Tufik S, Coelho FM. Oral L–Carnitine used to treat narcoleptic type 1 patient during pregnancy - A case report. Sleep Sci 2018;11(04):215–216. Doi: 10.5935/1984-0063.20180035 https://doi.org/10.5935/1984-0063.201800... ,⁶⁹69 Dauvilliers Y, Carlander B, Rivier F, Touchon J, Tafti M. Successful management of cataplexy with intravenous immunoglobulins at narcolepsy onset. Ann Neurol 2004;56(06):905–908. Doi: 10.1002/ana.20339 https://doi.org/10.1002/ana.20339...
Selegiline	Excessive daytime sleepiness	Strong	Low	5–10mg	Dry mouth, headache, insomnia, sweating.⁵⁶56 Bassetti CLA, Kallweit U, Vignatelli L, et al. European guideline and expert statements on the management of narcolepsy in adults and children. J Sleep Res 2021;30(06):e13387. Doi: 10.1111/jsr.13387 https://doi.org/10.1111/jsr.13387...
Caffeine	Excessive daytime sleepiness	Weak	Low	200mg	Complementary therapy.⁷⁰70 Aldosari MS, Olaish AH, Nashwan SZ, Abulmeaty MMA, BaHammam AS. The effects of caffeine on drowsiness in patients with narcolepsy: a double-blind randomized controlled pilot study. Sleep Breath 2020;24(04):1675–1684. Doi: 10.1007/s11325-020-02065-6. https://doi.org/10.1007/s11325-020-02065...
Hypocretin receptor agonists	Excessive daytime sleepiness and cataplexy	No evidence	No evidence	–	A recent study was published with promissory results and liver toxicity.⁶¹61 Dauvilliers Y, Shapiro C, Mayer G, et al. Solriamfetol for the Treatment of Excessive Daytime Sleepiness in Participants with Narcolepsy with and without Cataplexy: Subgroup Analysis of Efficacy and Safety Data by Cataplexy Status in a Randomized Controlled Trial. CNS Drugs 2020;34(07):773–784. Doi: 10.1007/ s40263-020-00744-2 https://doi.org/10.1007/s40263-020-00744...
Pitolisant	Excessive daytime sleepiness and cataplexy	Strong	Moderate	8.9–35.6mg	Headache, insomnia, and abdominal discomfort.⁵⁶56 Bassetti CLA, Kallweit U, Vignatelli L, et al. European guideline and expert statements on the management of narcolepsy in adults and children. J Sleep Res 2021;30(06):e13387. Doi: 10.1111/jsr.13387 https://doi.org/10.1111/jsr.13387... Pitolisant is not available in Brazil.
Sodium Oxybate	Excessive daytime sleepiness and Cataplexy	Strong	Moderate	1.5–9 g	Nocturnal confusion, enuresis, dizziness, nausea, weight loss, psychosis, depression, and worsening of OSA.⁵⁶56 Bassetti CLA, Kallweit U, Vignatelli L, et al. European guideline and expert statements on the management of narcolepsy in adults and children. J Sleep Res 2021;30(06):e13387. Doi: 10.1111/jsr.13387 https://doi.org/10.1111/jsr.13387... Oxybate is not available in Brazil.
Tricyclic antidepressants	Cataplexy	Strong	Low	Clomipramine 10–150mg	Weight gain, sexual dysfunction, constipation, and dry mouth.⁵⁶56 Bassetti CLA, Kallweit U, Vignatelli L, et al. European guideline and expert statements on the management of narcolepsy in adults and children. J Sleep Res 2021;30(06):e13387. Doi: 10.1111/jsr.13387 https://doi.org/10.1111/jsr.13387...
Other antidepressants	Cataplexy	Strong	Low	Venlafaxine 37.5–225mg	Nausea, dizziness, decreased appetite, irritability, insomnia, weight gain, sexual dysfunction, hyperhidrosis, diarrhea, constipation.⁵⁶56 Bassetti CLA, Kallweit U, Vignatelli L, et al. European guideline and expert statements on the management of narcolepsy in adults and children. J Sleep Res 2021;30(06):e13387. Doi: 10.1111/jsr.13387 https://doi.org/10.1111/jsr.13387...
Baclofen	Cataplexy	Weak	Low	10–40mg	Sleepiness, nausea, vomiting, diarrhea, headaches, dry mouth, blurred vision or difficulty focusing, excessive sweating, and rash.⁶⁴64 Huang YS, Guilleminault C. Narcolepsy: action of two gammaaminobutyric acid type B agonists, baclofen and sodium oxybate. Pediatr Neurol 2009;41(01):9–16. Doi: 10.1016/j.pediatrneurol.2009.02.008 https://doi.org/10.1016/j.pediatrneurol....

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[1] Address for correspondence Fernando Morgadinho Santos Coelho (email: fernandomorgadinho@hotmail.com)