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Management and prognosis of narcolepsy in children

Management and prognosis of narcolepsy in children
Authors:
Kiran Maski, MD
Suresh Kotagal, MD
Section Editors:
Thomas E Scammell, MD
Ronald D Chervin, MD, MS
Deputy Editor:
April F Eichler, MD, MPH
Literature review current through: Feb 2022. | This topic last updated: Nov 02, 2021.

INTRODUCTION — Narcolepsy is a rare, chronic neurologic disorder characterized by excessive daytime sleepiness. Many patients also have cataplexy, hypnagogic hallucinations, sleep paralysis, and disrupted nighttime sleep. Symptom onset in pediatric cases is typically between ages 10 and 15 years, but diagnostic delays and misdiagnosis are common.

The management and prognosis of narcolepsy in children are reviewed here. The clinical features and diagnosis of narcolepsy and the approach to evaluating sleep disorders in children are presented separately. (See "Clinical features and diagnosis of narcolepsy in children" and "Assessment of sleep disorders in children".)

Diagnosis and management of narcolepsy in adults are also reviewed separately. (See "Clinical features and diagnosis of narcolepsy in adults" and "Treatment of narcolepsy in adults".)

BEHAVIORAL AND LIFESTYLE MODIFICATION — All children and families should receive education about behavioral strategies and lifestyle adjustments to reduce the impact of the disease [1].

Sleep habits and daytime naps — Patients should maintain regular sleep-wake schedules and receive adequate time for sleep at night (at least 10 hours for school-age children and at least 8 hours for adolescents). Although this is good advice for any child, it is especially important for a child with narcolepsy.

Scheduled naps during the daytime can partially mitigate drowsiness. Depending on the age of the child, naps may be planned at school or upon return home from school for 15 to 30 minutes, and most patients feel substantially more alert afterwards.

Diet and exercise — To promote daytime alertness and aid sleep hygiene, we advise patients avoid heavy carbohydrate-rich meals, excessive sugar intake, and eating heavy meals before bedtime. In our experience, caffeine use does not produce a sustained alerting effect in people with narcolepsy, and side effects of anxious feeling or tachycardia outweigh benefits. The effects of specific diets on daytime sleepiness and alertness have yet to be studied in narcolepsy.

Regular exercise during the daytime can enhance alertness.

Psychiatric care — Caregivers and clinicians should maintain heightened awareness for psychiatric comorbidity in children with narcolepsy. Depression, anxiety, obsessive compulsive disorder, and social phobia have been reported in up to 35 percent of patients [2]. (See "Clinical features and diagnosis of narcolepsy in children", section on 'Neuropsychiatric symptoms'.)

We also encourage psychological counseling from the time of diagnosis, including family counseling if needed to cope with this chronic disease. Cognitive behavior therapy for narcolepsy management is a useful complement to pharmacotherapy [3] and, in our experience, promotes treatment adherence and agency among patients.

School and career planning — Children may need special accommodations at school to promote an optimal learning environment. Clinicians and caregivers may find it helpful to work closely with a school guidance counselor or other school official to ensure the opportunity for one to two brief daytime naps. Schools can sometimes make other accommodations to improve a child's alertness, such as sitting at the front of the class, movement/stretch breaks, being allowed to chew gum or drink cold water in class, and/or taking "stop the clock" breaks during longer timed tests.

Young people with narcolepsy may also benefit from advice regarding the choice of a career. In general, individuals with narcolepsy may be more at ease in jobs that allow for standing and moving about rather than desk jobs. Workplace accommodations may be needed to allow more frequent breaks, opportunities for brief naps, and flexible schedules. Late-night shifts or frequent changes to work hours can be very difficult for people with narcolepsy [1].

Support groups such as the Narcolepsy Network, Project Sleep, Hypersomnia Foundation, and Wake-Up Narcolepsy can be very helpful to patients and caregivers.

Safety and driving — Safety considerations are important to review. Patients should consider avoiding heights if they have severe and uncontrolled cataplexy that puts them at risk for falls and potentially dangerous machinery if daytime sleepiness and/or cataplexy are not well controlled. Swimming with supervision is recommended if swimming triggers cataplexy.

People with narcolepsy have an increased risk of car accidents due to sleepiness. We caution adolescents against driving for more than 25 to 30 minutes at a time, and highway driving should be avoided when possible. These recommendations may be modified depending on severity of symptoms, treatment adherence, and driving capabilities. Similarly, patients should avoid potentially dangerous machinery if daytime sleepiness and/or cataplexy are not well controlled. Further considerations on driving safety are reviewed separately. (See "Treatment of narcolepsy in adults", section on 'Driving safety'.)

Alcohol, marijuana, and other sedating substances should be strictly avoided due to potential adverse interactions with medications and their potential to worsen sleep quality.

PHARMACOTHERAPY — Narcolepsy is a lifelong disorder. There are no curative therapies currently available, and management is symptomatic. In addition to nonpharmacologic strategies, pharmacotherapy is required in nearly all children to target sleepiness, cataplexy, and other bothersome symptoms.

Overview of approach — At the time of diagnosis, nearly all children with narcolepsy are significantly impaired by sleepiness, consequent behavioral or cognitive difficulties, and/or cataplexy. Nonpharmacologic strategies are only partially effective, and drug therapy is required in nearly all children.

Medications used to treat narcolepsy in children are listed in the tables (table 1 and table 2). To date, the only US Food and Drug Administration (FDA)-approved therapies in pediatric narcolepsy are:

Traditional stimulants for treatment of daytime sleepiness associated with narcolepsy

Sodium oxybate for treatment of excessive sleepiness and cataplexy (ages 7 to 17 years)

Oxybate salts (a low-sodium version of sodium oxybate) for treatment of excessive sleepiness and cataplexy (ages 7 to 17 years)

The 2021 American Academy of Sleep Medicine (AASM) clinical practice guidelines for treatment of central disorders of hypersomnolence include treatment recommendations for pediatric narcolepsy [4,5]. However, these recommendations were limited by a paucity of clinical trials specifically reporting risks and benefits in children and adolescents with narcolepsy. Thus, the treatment strategies provided below are mostly based on clinical experience, case reports and case series in children, and indirect evidence of benefit and safety in adults with narcolepsy.

Target predominant symptoms first — The choice of first-line pharmacotherapy should be individualized according to symptoms that are most bothersome to the patient (eg, sleepiness, cataplexy), side effect profiles and risks, and patient and clinician preferences.

For patients with predominant sleepiness, we start with a central nervous system stimulant such as methylphenidate. When cataplexy is also functionally limiting, produces risk of injury or falls, and/or is socially bothersome to the patients, we add an anti-cataplexy, antidepressant medication, or we start with sodium oxybate, which has the advantage that it can target both sleepiness and cataplexy.

Titrate and monitor — Medications are titrated with the goal of maximally controlling symptoms while minimizing side effects and toxicity. All children on drug therapy require careful and periodic monitoring to determine efficacy and adverse effects [6].

Monotherapy versus polytherapy — Once the most significant symptoms have been controlled, other symptoms can then be treated with additional medication, if necessary. Monotherapy is preferred but not always possible.

Daytime sleepiness — Treatment options for daytime sleepiness in children with narcolepsy include central nervous system stimulants (methylphenidate or amphetamines), wake-promoting agents such as modafinil or armodafinil, and oxybates (sodium oxybate and oxybate salts) (table 1) [7-9]. There have been no head-to-head studies comparing various medications in narcolepsy, and various classes of medications have similar effects on alertness and daytime function in children with narcolepsy.

First-line therapy — We suggest starting with a central nervous system stimulant (methylphenidate or amphetamine) to target sleepiness. We use modafinil or armodafinil as second-line therapies if there is an inadequate response to stimulants, side effects to stimulants, or contraindication to stimulant use. If both cataplexy and daytime sleepiness are problematic, sodium oxybate or mixed oxybate salts can be initiated rather than a stimulant. (See 'Cataplexy' below.)

Our preference for starting with a stimulant rather than a wake-promoting agent such as modafinil in children with predominant sleepiness is based primarily on the extensive experience with the safety and tolerability of stimulants in children with attention deficit hyperactivity disorder (ADHD), and the more limited experience with modafinil or armodafinil in children. Cost of medications and insurance coverage may also influence the choice of first-line therapy.

Dosing and titration – The choice among various stimulants depends largely on individual preferences of the clinician and family, as well as considerations of duration of action and whether or not the child can swallow pills.

We almost always use sustained-release formulations of stimulants to begin with, since optimizing daytime alertness for attendance at school is important. However, "booster" doses of immediate-release stimulants may be required in the afternoon or after school for homework management.

Recommended starting and maximum doses of stimulants for children with narcolepsy are the same as for more common indications (table 1). Stimulant medications are typically started at the lowest dose that may produce an effect and increased gradually (every three to seven days) until target symptoms improve. The same principles apply to the titration of dextroamphetamine.

Side effects – Relatively common side effects of all stimulants include anorexia, weight loss due to appetite suppression, sleep disturbance, jitteriness, tachycardia, emotional lability, and the development of tics. Stimulants can worsen underlying mood disorders, and thus discussion of use and close monitoring with the patient's psychiatrist are strongly recommended.

Blood pressure should be monitored with stimulants to check for elevated blood pressure. Stimulants should generally not be prescribed in patients with personal history or family history of serious heart problems such as cardiac arrhythmias; when therapy is deemed necessary, it should be managed in consultation with a cardiologist. (See "Pharmacology of drugs used to treat attention deficit hyperactivity disorder in children and adolescents", section on 'Stimulants' and "Cardiac evaluation of patients receiving pharmacotherapy for attention deficit hyperactivity disorder".)

Second-line therapy — If sleepiness remains problematic despite the use of stimulant medications, modafinil or armodafinil may be substituted or added to the stimulant regimen [10].

Because of risk of serious cutaneous hypersensitivity (Stevens-Johnson Syndrome) and psychiatric adverse reactions, the use of modafinil is not approved by the FDA in the pediatric population (<18 years old). However, based on two observational studies showing clinically significant improvements in disease severity and excessive daytime sleepiness and only minor side effects [8,11], the AASM clinical practice guidelines suggest modafinil is an option for use in the pediatric narcolepsy population [4].

Dosing Modafinil and armodafinil are typically started as a single 50 mg dose in the morning so that any potential side effects can be closely monitored before further titration (table 1).

Modafinil has a shorter half-life (approximately seven hours) in children compared with adults, and thus most children with narcolepsy will typically require a second dose midday. The usual effective dose of modafinil ranges from 50 to 100 mg twice daily for children and 100 to 200 mg twice daily for adolescents.

Armodafinil has higher potency and sustains higher plasma concentrations throughout the day [12]. It is therefore typically dosed once in the morning, with a usual effective dose range of 50 to 250 mg depending on age and weight.

Side effects – Reported side effects of modafinil and armodafinil include headache, nervousness and irritability, dry mouth, nausea, and loss of appetite. Given the potential for Stevens-Johnson syndrome, modafinil/armodafinil should be stopped if any unexplained rash is observed with treatment.

Importantly, modafinil and armodafinil can impair the effectiveness of steroidal contraceptives due to induction of CYP3A4/5. Exposure to either drug during pregnancy has been associated with an increased risk of major congenital anomalies [13]. Guidance on alternative or concomitant methods of contraception is recommended for adolescent females to prevent pregnancy. (See "Treatment of narcolepsy in adults", section on 'Pregnancy and lactation'.)

Other options — Atomoxetine, a selective norepinephrine reuptake inhibitor, may also be used alone or in combination with other agents [8,14]. Potential side effects include headache, elevation of blood pressure, tachycardia, and weight loss. (See "Pharmacology of drugs used to treat attention deficit hyperactivity disorder in children and adolescents", section on 'Atomoxetine'.)

Cataplexy — Treatment options for cataplexy in children with narcolepsy type 1 include oxybates (sodium oxybate or a newer mixed oxybate salts formulation) and certain antidepressant medications, which have an anticataplectic effect through suppression of rapid eye movement (REM) sleep neural pathways (table 2). When mild, cataplexy may not require pharmacologic treatment.

Sodium oxybate — When cataplexy is the most bothersome symptom, or when both cataplexy and sleepiness are problematic, we suggest initial therapy with sodium oxybate (or oxybate salts, as discussed below (see 'Mixed oxybate salts' below)). We also consider sodium oxybate as an initial agent when cataplexy and sleepiness are equally problematic, although experts vary. Some prefer a stimulant and an antidepressant in this setting.

The rationale for sodium oxybate as the initial agent is that it targets both cataplexy and daytime sleepiness, thus reducing risk for polypharmacy, and it may be the most potent anticataplectic therapy available. However, less potent anticataplectic therapies may be better tolerated, and some experts prefer to start with one of the antidepressant medications discussed below, particularly if cataplexy is relatively mild or accompanied by comorbid depression.

The AASM clinical practice guidelines suggest sodium oxybate as an option for treatment of pediatric narcolepsy based on one randomized controlled study and a few observational studies showing clinically significant improvements in cataplexy, disease severity, and excessive daytime sleepiness [4,15-18].

If sleepiness remains problematic on sodium oxybate despite adequate control of cataplexy, a stimulant or a wake-promoting agent can be added in the daytime. (See 'Daytime sleepiness' above.)

Mechanism Sodium oxybate is the sodium salt of gamma hydroxybutyrate (GHB). It is a metabolite of gamma-aminobutyric acid (GABA) and may act as a GABA-B and GHB receptor agonist. It stabilizes nocturnal sleep architecture, which is often disrupted in patients with narcolepsy.

DosingSodium oxybate must be given in two divided doses at night. The first dose is administered at bedtime, and the second dose is given 2.5 to 4 hours after initial sleep onset. Twice nightly dosing is necessary due to the drug's short half-life (0.5 to 2 hours) and rapid absorption. We typically start with 2 g per night in divided doses and titrate gradually (eg, increments of 1 g per night [0.5 g/dose] no faster than once per week) according to effect and tolerability. In one pediatric series, the mean daily dose of sodium oxybate was 5 g [19].

Per manufacturer labeling, the maximum recommended daily dose in children (≥7 years of age) is 6 g per night in divided doses for children weighing 20 to <30 kg, 7.5 g per night in divided doses for those weighing 30 to <45 kg, and 9 g per night in divided doses for those weighing ≥45 kg [20].

A mixed-salt oral solution (oxybate salts), comprised of calcium, magnesium, potassium, and sodium oxybate, is discussed below. (See 'Mixed oxybate salts' below.)

Side effects and precautions – Common side effects of sodium oxybate include weight loss, nausea, worsening of sleep apnea, nocturnal enuresis, worsening of pre-existing depression, sleepwalking, and tremor. More serious side effects need to be warned about and monitored per the required Risk Evaluation and Mitigation Strategies (REMS) program.

Caution is advised in patients with pre-existing anxiety or depression due to the potential for depression to worsen on sodium oxybate. In the clinical trial in children, baseline depression and anxiety scales were in the normal range in the two subjects who developed suicidality or psychosis [16]; hence, ongoing screening for any changes in mood or suicidality is recommended.

Cases of central sleep apnea have been reported with sodium oxybate, and monitoring for symptoms of pauses in breathing, gasping at night, and/or new snoring should be performed at clinical visits.

Due to the potential for drug diversion, sodium oxybate (otherwise known as the "date rape drug" before the medical indication for cataplexy was first confirmed) is prescribed only by sleep specialists and made available to patients via a centralized pharmacy. In the United States, prescribers must register with the REMS program. As oxybates are often intensely sedating, it can be hard to wake to a phone or smoke alarm, so precaution is advised when patients live with college roommates or in other potentially vulnerable or dangerous situations. Oxybates should never be used with alcohol and other sedating substances. We recommend patients living in dorms keep oxybates, stimulants, and other potentially abused medications in locked storage.

Efficacy – Randomized trials in adults with narcolepsy type 1 have shown that sodium oxybate reduces the number of cataplexy attacks, improves daytime wakefulness, and reduces sleep attacks compared with placebo [21]. (See "Treatment of narcolepsy in adults", section on 'Oxybates'.)

Safety and efficacy data in children include several retrospective case series and a multicenter prospective trial with a two-week randomized discontinuation phase [8,9,15,16,19,22,23]. The trial enrolled 106 children and adolescents (mean age 12 years) with narcolepsy type 1 who were either already taking sodium oxybate (30 percent) or who were newly titrated to a stable dose over a 3- to 10-week period [16]. In the blinded, randomized withdrawal portion of the study (63 patients), those assigned to discontinue sodium oxybate (the placebo group) had increased cataplexy (median increase of 12.7 attacks per week) compared with those assigned to continue sodium oxybate (median increase of 0.3 attacks per week; p <0.0001). Other efficacy outcomes also favored sodium oxybate, including cataplexy severity, daytime sleepiness, and overall narcolepsy severity scores. The most common adverse events attributed to sodium oxybate among 104 treated patients were enuresis (18 percent), nausea and vomiting (17 and 16 percent, respectively), headache (16 percent), and weight loss (12 percent). There were two serious adverse events (acute psychosis and suicidal ideation), both of which improved with discontinuation of drug.

Preliminary data also suggest that sodium oxybate can improve REM sleep behavior disorder in children with narcolepsy type 1 [24].

Mixed oxybate salts — A lower sodium version of GHB (calcium, magnesium, potassium, and sodium oxybates; oxybate salts) received FDA approval in 2020 for treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy as young as seven years old. Insurance coverage is variable, and there are no published guidelines that include oxybate salts.

Until further data are available, we prioritize use of mixed oxybate salts instead of sodium oxybate if there is concern about the high sodium content of sodium oxybate (eg, a child with elevated blood pressure). Sodium oxybate contains a sodium content of 1640 mg per day at the maximum recommended dose (4.5 grams twice nightly for patients >45 kg); oxybate salts contain 131 mg of sodium at this dose. As such, children with narcolepsy with hypertension might benefit from this treatment to reduce risk of long-term cardiovascular comorbidities. Prospective studies are not yet available, however.

The active moiety of oxybate salts is the same as that of sodium oxybate (ie, GHB), and dosing is the same. The manufacturer recommends a one-to-one conversion from sodium oxybate to oxybate salts, with no overlap period. As with sodium oxybate, prescribers in the United States must register with the REMS program. (See 'Sodium oxybate' above.)

Antidepressants — If sodium oxybate is ineffective or poorly tolerated, we typically try a tricyclic antidepressant such as clomipramine or protriptyline (table 2). These drugs suppress cataplexy by blocking the reuptake of 5-hydroxytriptamine and/or through a central anticholinergic effect. Side effects include weight gain, dry mouth, orthostatic hypotension, tremor, and constipation. They may need to be administered in two divided doses.

A selective serotonin reuptake inhibitor or serotonin-norepinephrine reuptake inhibitor may be beneficial when mood and behavioral problems coexist, because these agents treat both mood disorders and cataplexy. In case series, fluoxetine, citalopram, sertraline, and venlafaxine all have some evidence of benefit in patients with narcolepsy [8,9,25,26]. Careful monitoring of mood is required, given the potential for increased suicidal ideation in some children.

Of note, in the authors' experience, higher doses of fluoxetine (eg, 40 to 60 mg) and venlafaxine (eg, 150 to 225 mg) than those used for mood disorders may be needed in some patients for maximal anti-cataplexy effects. Use of these higher doses depends on clinical judgment and the ability to maintain adequate safety monitoring.

Emerging therapies — Emerging treatments for children with narcolepsy include two newer medications approved for narcolepsy treatment in adults (pitolisant and solriamfetol) and several medications still in development [27].

Histamine H3 inverse agonistsPitolisant, an inverse agonist of the histamine H3 receptor, decreases cataplexy attacks and enhances wakefulness in adults with narcolepsy type 1 [28]. Pitolisant has not yet been studied in children. (See "Treatment of narcolepsy in adults", section on 'Pitolisant'.)

Alternative stimulantsSolriamfetol, a selective dopamine and norepinephrine reuptake inhibitor, has received regulatory approval in the United States for treatment of excessive daytime sleepiness in adults with narcolepsy [29,30] but has not yet been studied in children. (See "Treatment of narcolepsy in adults", section on 'Approach to pharmacotherapy'.)

Orexin analogs – A phase I study of an orexin/hypocretin 2 receptor-selective agonist TAK-925 (administered intravenously) showed high efficacy and good tolerability in adult healthy controls (n = 36) and adults with narcolepsy type 1 (n = 14) [31]. Side effects included elevations in blood pressure and heart rate. Significant improvements in excessive daytime sleepiness based on the maintenance of wakefulness test and Karolinska Sleepiness Scale were reported in patients with narcolepsy. Another hypocretin/orexin 2 receptor-selective agonist, TAK-994 (administered orally), is currently being evaluated in a phase II study in adults with narcolepsy type 1.

PROGNOSIS — There are limited longitudinal studies of pediatric narcolepsy, but it is a lifelong disorder. Generally, disease severity is often maximal in the first two years. Symptoms can improve from symptom onset and then generally stabilize thereafter. There are no longitudinal studies following pediatric narcolepsy patients across adulthood, but symptom management typically improves with time in our experience.

One study conducted over three years showed that children with narcolepsy slept more at disease onset, but the amount of sleep then normalized across the two-year study period [32]. In this study, pediatric patients with a more static form of cataplexy presenting as persistent facial weakness (cataplectic facies) at younger age evolved to having the classic cataplexy triggered by strong emotions by the end of the study.

In our experience, symptom severity can fluctuate based on life experiences (eg, pregnancy, changes in school/college schedules), stress, changes in sleep schedule/habits, social triggers that induce cataplexy, and sometimes puberty.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Parasomnias, hypersomnias, and circadian rhythm disorders".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topic (see "Patient education: Narcolepsy (The Basics)")

SUMMARY AND RECOMMENDATIONS

Narcolepsy in children results in often severe daytime sleepiness with broad impacts on physical, psychological, social, and emotional health. Management involves both behavioral and lifestyle modifications as well as symptomatic pharmacotherapy to target excessive daytime sleepiness and cataplexy. (See 'Introduction' above.)

Behavioral strategies and lifestyle adjustments to reduce the impact of the disease include:

Sleep-wake scheduling – Patients should maintain regular sleep-wake schedules and receive adequate time for sleep at night (at least 10 hours for school-age children and at least 8 hours for adolescents). Scheduled naps during the daytime can partially mitigate drowsiness. (See 'Sleep habits and daytime naps' above.)

Diet and exercise – We advise patients to engage in regular exercise and avoid heavy carbohydrate-rich meals, excessive sugar intake, and eating heavy meals before bedtime. (See 'Diet and exercise' above.)

Psychiatric care – We encourage psychological counseling from the time of diagnosis, including family counseling if needed to cope with new chronic disease. Anxiety, obsessive compulsive disorder, social phobia, and/or depression are common comorbidities that require appropriate psychiatric referral and care. (See 'Psychiatric care' above.)

School support – Children should receive necessary accommodations at school to promote an optimal learning environment. Interventions may include scheduled time for one or two brief daytime naps and breaks during long classes and tests to improve alertness. (See 'School and career planning' above.)

Safety and driving – People with narcolepsy have an increased risk of car accidents due to sleepiness. We caution adolescents against driving for more than 25 to 30 minutes at a time, and highway driving should be avoided when possible. (See 'Safety and driving' above.)

Pharmacotherapy is required in nearly all children to target disabling sleepiness, cataplexy, and other bothersome symptoms. Selection of initial pharmacotherapy should be individualized based on the symptom that is most bothersome to the patient (table 1 and table 2). (See 'Overview of approach' above.)

Excessive daytime sleepiness – For children whose predominant symptom is excessive daytime sleepiness, we suggest initial therapy with a stimulant medication such as methylphenidate (Grade 2C). Wake-promoting agents such as modafinil and armodafinil are a reasonable alternative to stimulants, although experience with these drugs in children is more limited, and rare severe adverse reactions, including Stevens-Johnson syndrome and severe psychiatric events, have been reported. (See 'First-line therapy' above and 'Second-line therapy' above.)

Predominant cataplexy – For children with narcolepsy type 1 whose predominant symptom is cataplexy or patients with problematic cataplexy and sleepiness, we suggest initial therapy with sodium oxybate (Grade 2C). Tricyclic antidepressants, serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors are alternative first-line therapies for cataplexy, particularly in children with comorbid depression. (See 'Sodium oxybate' above and 'Antidepressants' above.)

Prognosis – Narcolepsy is considered a lifelong disorder. Disease severity is typically maximal at symptom onset. Symptoms generally stabilize thereafter. (See 'Prognosis' above.)

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  27. Thorpy MJ. Recently Approved and Upcoming Treatments for Narcolepsy. CNS Drugs 2020; 34:9.
  28. Szakacs Z, Dauvilliers Y, Mikhaylov V, et al. Safety and efficacy of pitolisant on cataplexy in patients with narcolepsy: a randomised, double-blind, placebo-controlled trial. Lancet Neurol 2017; 16:200.
  29. Baladi MG, Forster MJ, Gatch MB, et al. Characterization of the Neurochemical and Behavioral Effects of Solriamfetol (JZP-110), a Selective Dopamine and Norepinephrine Reuptake Inhibitor. J Pharmacol Exp Ther 2018; 366:367.
  30. Thorpy MJ, Shapiro C, Mayer G, et al. A randomized study of solriamfetol for excessive sleepiness in narcolepsy. Ann Neurol 2019; 85:359.
  31. Evans R, Tanaka S, Tanaka S, et al. A phase 1 single ascending dose study of a novel orexin 2 receptor agonist, TAK-925, in healthy volunteers (HV) and subjects with narcolepsy type 1 (NT1) to assess safety, tolerability, pharmacokinetics, and pharmacodynamic outcomes [oral presentation]. World Sleep Congress; 20–25 Sep 2019; Vancouver.
  32. Pizza F, Franceschini C, Peltola H, et al. Clinical and polysomnographic course of childhood narcolepsy with cataplexy. Brain 2013; 136:3787.
Topic 131001 Version 4.0

References

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2 : Anxiety and mood disorders in narcolepsy: a case-control study.

3 : Cognitive behavioral treatment for narcolepsy: can it complement pharmacotherapy?

4 : Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine clinical practice guideline

5 : Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment.

6 : Practice parameters for the treatment of narcolepsy and other hypersomnias of central origin.

7 : Narcolepsy in children: a diagnostic and management approach.

8 : Clinical and therapeutic aspects of childhood narcolepsy-cataplexy: a retrospective study of 51 children.

9 : Pharmacological management of narcolepsy and cataplexy in pediatric patients.

10 : Clinical experience suggests that modafinil is an effective and safe treatment for paediatric narcolepsy.

11 : Efficacy of modafinil in 10 Taiwanese patients with narcolepsy: findings using the Multiple Sleep Latency Test and Epworth Sleepiness Scale.

12 : Armodafinil and modafinil have substantially different pharmacokinetic profiles despite having the same terminal half-lives: analysis of data from three randomized, single-dose, pharmacokinetic studies.

13 : Armodafinil and modafinil have substantially different pharmacokinetic profiles despite having the same terminal half-lives: analysis of data from three randomized, single-dose, pharmacokinetic studies.

14 : EFNS guidelines on management of narcolepsy.

15 : In-field assessment of sodium oxybate effect in pediatric type 1 narcolepsy: an actigraphic study.

16 : Treatment of paediatric narcolepsy with sodium oxybate: a double-blind, placebo-controlled, randomised-withdrawal multicentre study and open-label investigation.

17 : Narcolepsy: action of two gamma-aminobutyric acid type B agonists, baclofen and sodium oxybate.

18 : Sodium oxybate in the treatment of childhood narcolepsy-cataplexy: a retrospective study.

19 : Tolerance and efficacy of sodium oxybate in childhood narcolepsy with cataplexy: a retrospective study.

20 : Tolerance and efficacy of sodium oxybate in childhood narcolepsy with cataplexy: a retrospective study.

21 : Sodium oxybate for narcolepsy with cataplexy: systematic review and meta-analysis.

22 : Off-label treatment of severe childhood narcolepsy-cataplexy with sodium oxybate.

23 : Narcolepsy in children: a single-center clinical experience.

24 : REM Sleep Behavior Disorder in Children With Type 1 Narcolepsy Treated With Sodium Oxybate.

25 : Treatment with venlafaxine in six cases of children with narcolepsy and with cataplexy and hypnagogic hallucinations.

26 : Treatment of cataplexy in a three-year-old using venlafaxine.

27 : Recently Approved and Upcoming Treatments for Narcolepsy.

28 : Safety and efficacy of pitolisant on cataplexy in patients with narcolepsy: a randomised, double-blind, placebo-controlled trial.

29 : Characterization of the Neurochemical and Behavioral Effects of Solriamfetol (JZP-110), a Selective Dopamine and Norepinephrine Reuptake Inhibitor.

30 : A randomized study of solriamfetol for excessive sleepiness in narcolepsy.

31 : A randomized study of solriamfetol for excessive sleepiness in narcolepsy.

32 : Clinical and polysomnographic course of childhood narcolepsy with cataplexy.