European Guidelines for Managing Narcolepsy

European Guidelines for the Management of Narcolepsy in Adults and Children

Narcolepsy is a rare hypothalamic disorder that affects 25-50 persons out of 100,000.
It can significantly affect quality of life, with symptoms including excessive daytime sleepiness, fragmented and disturbed nighttime sleep, cataplexy, and hallucinatory experiences around sleep-wake transitions.
Narcolepsy is usually a sporadic acquired immune-mediated condition that develops in people who are genetically predisposed.
The European Academy of Neurology, European Sleep Research Society, and European Narcolepsy Network created a task force of 18 narcolepsy specialists and 4 patient representatives to provide evidence-based guidelines for the management of narcolepsy in adults and children.
A total of 10,247 references were evaluated, 308 studies were assessed and 155 finally included in developing the guidelines.
The main recommendations include scheduled naps, modafinil, pitolisant, sodium oxybate, and solriamfetol for excessive daytime sleepiness in adults, and scheduled naps, sodium oxybate, modafinil, methylphenidate, pitolisant, and amphetamine derivatives for excessive daytime sleepiness in children.
For cataplexy in adults, sodium oxybate, venlafaxine, clomipramine, and pitolisant are recommended, and for cataplexy in children, sodium oxybate and antidepressants are recommended.
Treatment choices should be tailored to each patient's symptoms, comorbidities, tolerance, and risk of potential drug interactions.
The guidelines also evaluate pharmacological treatments that are potentially disease-modifying as well as therapies for a variety of comorbid conditions such as obesity, sleep-disordered breathing, rapid eye movement sleep behavior disorder, restless legs syndrome, and periodic limb movements.
Non-pharmacological treatments such as cognitive-behavioral therapy, sleep hygiene, and regular exercise can also improve symptoms of narcolepsy.
The guidelines also include expert statements and patient perspectives on the management of narcolepsy.
The aim of the guidelines is to provide up-to-date, evidence-based recommendations for the management of narcolepsy in both adults and children.Clinical Guidelines for the Management of Narcolepsy
The guidelines were developed by a task force established by three societies in 2017 and finalized in September 2020.
The task force used the GRADE approach and identified key questions and outcomes essential for clinical management.
The literature search was conducted between July and October 2018 and updated in July and October 2020.
Non-pharmacological management should always be considered first, and individual factors should be taken into account.
There is limited scientific evidence for the efficacy of non-pharmacological treatments other than scheduled napping.
Disease-modifying treatments for narcolepsy are not currently recommended.
Wake-promoting agents and sodium oxybate are effective in improving excessive daytime sleepiness (EDS).
Different compositions or formulations of sodium oxybate may have an additional impact on improving disturbed nocturnal sleep (DNS).
Stimulants may increase heart rate and blood pressure and require careful monitoring.
Sleep paralysis and hypnagogic/hypnopompic hallucinations are reported by approximately 50% of patients with narcolepsy, but there is no evidence for the efficacy of treatments.
There is a need for specific trials on the impact of compounds, including antidepressants and sodium oxybate, on sleep paralysis and hypnagogic/hypnopompic hallucinations.
Improving daily performance, quality of life measures, and the ability to work are key aims of narcolepsy management.Pharmacological Treatment and Management of Narcolepsy: Recommendations and Future Directions
Psychiatric disturbances, including depression and anxiety, are common in narcolepsy patients.
Treatment for psychiatric disorders in narcolepsy should follow general principles for the general population.
Shared compounds for symptoms of narcolepsy and comorbid mood disorders should be considered where appropriate.
There is no established recommendation for the use of narcoleptic drugs during puberty.
Treatment strategies for narcolepsy in children and adolescents should take into account developmental aspects.
Non-pharmacological approaches, such as cognitive behavioral therapy, should be considered for psychiatric comorbidities in narcolepsy.
The lack of specific studies makes it difficult to support any particular treatments for depression in narcolepsy.
Almost no head-to-head trials have been performed between drugs for the treatment of narcolepsy.
Sodium oxybate is the only EU-approved medication for the treatment of narcolepsy.
Trials on the safety and efficacy of pitolisant in children are yet to be published.
The clinical efficacy of sodium oxybate for the treatment of EDS and cataplexy in children was first reported in 2018.
The clinical evidence for efficacy of pharmacological treatment of any symptom of narcolepsy in children is limited.Guidelines for the Management of Narcolepsy: Key Recommendations and Patient Perspectives
Narcolepsy is a sleep disorder that affects multiple aspects of daily life, including excessive daytime sleepiness (EDS), cataplexy, and disturbed nocturnal sleep (DNS).
Pharmacological treatment is the primary approach to managing narcolepsy, with various drugs available, including modafinil, methylphenidate, sodium oxybate, amphetamine derivatives, and pitolisant.
Treatment may be complicated by factors such as age, pregnancy, breastfeeding, and comorbidities, and discontinuation of drug therapy before pregnancy is strongly advised.
Low doses of antidepressants seem relatively safe for narcolepsy treatment, but recent studies have raised doubts about the safety of modafinil and its potential to cause congenital defects.
L-carnitine may have a positive effect on reducing daytime nap time in some patients.
Perioperative risk in narcolepsy is generally not an independent risk factor for surgery, but existing comorbidities and medication use may affect risk.
Patients' views and needs should be considered in developing clinical practice and patient-oriented guidelines, including addressing non-pharmacological treatments and specialized ancillary health workers.
Non-pharmacological treatments such as regular naps, exercise, good sleeping habits, and regular schedules may help manage symptoms of narcolepsy.
Complete symptom control in narcolepsy is relatively rare, and less than 50% of treated patients are normalized on subjective measures of EDS.
There is an unmet need for specialized ancillary health workers, including nurses and psychologists, working in sleep centers specializing in narcolepsy.
Clinical observational studies with long-term follow-up and precise individual treatment plans are necessary to improve the development of disease-modifying drugs and evaluate symptomatic medications.
The guidelines will be updated in 5 years or earlier if major changes in evidence or new interventions become available.