eMedicine Specialties > Neurology > Sleep-Related Diseases
Narcolepsy: Treatment & Medication
Updated: Sep 12, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
- Nonpharmacologic treatment
- Sleep hygiene is important. Most patients improve if they maintain a regular sleep schedule, usually 7.5-8 hours of sleep per night.
- Scheduled naps during the day also may help.
- Provide emotional support and career/vocational counseling to the patient and parent.
- Assist with documentation for special academic needs, insurance, disability forms, and attaining a driver's license.
- Question patients about high-risk behaviors such as alcohol and drug use, which may exacerbate symptoms.
- Inquiries into depression, family conflict, and other psychosocial problems are also important.
- Encourage children to participate in after-school activities and sports. A well-designed exercise program can be beneficial and stimulating. School personnel should have the child with narcolepsy refrain from activities if he or she appear drowsy.
- Avoidance of foods high in refined sugars may improve daytime sleepiness.
- Pharmacologic treatment
- CNS stimulants such as methylphenidate, dextroamphetamine sulfate, methamphetamine, and amphetamine are used for treatment of narcolepsy.
- Older stimulants are thought to act primarily through brainstem dopamine, nigrostriatal, and mesocorticolimbic pathways. These medications help reduce daytime sleepiness, improving the symptom in 65-85% of patients.
- Methylphenidate, the most frequently used stimulant, improves sleep tendency in a dose-related fashion.
- Undesirable side effects include headache, irritability, nervousness, and gastrointestinal complaints.
- Nocturnal sleep may be impaired, thus decreasing total sleep time.
- Modafinil was discovered recently as a novel wake-promoting agent.
- The mechanism of action is not understood, but it does not appear to alter levels of dopamine or norepinephrine.
- Modafinil's safety and efficacy have been evaluated in a multicenter, double-blind, placebo-controlled trial. The treatment group experienced both subjective and objective improvement in sleepiness.
- Unlike traditional medications, modafinil does not appear to affect total sleep time or suppress REM sleep.
- The most common adverse effect is headache. Its safety in children has not been established.
- Sodium oxybate is the only FDA-approved treatment for cataplexy. It is also used to treat EDS. Sodium oxybate is a CNS depressant and should not be used with alcohol or other CNS depressants.
- Tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRI) have also been used to treat cataplexy.
- Currently, no FDA-approved pharmacotherapy is available for children with narcolepsy. However, the medications used to treat narcolepsy in adults have been used off-label in the pediatric population with positive results.
- CNS stimulants such as methylphenidate, dextroamphetamine sulfate, methamphetamine, and amphetamine are used for treatment of narcolepsy.
Consultations
A child in whom narcolepsy is suspected must be evaluated by a pediatric neurologist. Further evaluation at a sleep disorders clinic is also imperative.
Diet
Patients with narcolepsy should avoid heavy meals and alcohol.
Activity
- Recommendations
- Scheduled short naps
- Exercise program
- Restrict driving when sleepy (Patients with narcolepsy should avoid driving or operating heavy machinery when sleepy.)
Medication
The main focus is symptomatic treatment of excessive somnolence and cataplexy with CNS stimulants and antidepressants. Stimulants improve wakefulness, while antidepressants such as clomipramine and fluoxetine reduce cataplectic attacks.
CNS stimulants
These stimulants increase wakefulness, vigilance, and performance. They are thought to alter midbrain dopaminergic activity, but the precise mechanism of action is unknown. Interpatient variability in dose required to alleviate EDS is considerable and unpredictable. Some patients are relieved of daytime sleepiness completely with 5 mg of methylphenidate daily; others require higher doses. Initiate treatment at low doses and individualize the therapy.
Pemoline (Cylert)
Initial drug of choice in children younger than 7 y with narcolepsy; has relatively little effect on blood pressure. The United States FDA concluded that the overall risk of liver toxicity from pemoline outweighs the benefits. In May 2005, Abbott chose to stop sales and marketing of their brand of pemoline (Cylert) in the United States. In October 2005, all companies that produced generic versions of pemoline also agreed to stop sales and marketing of pemoline.
Adult
60-200 mg PO qd
Pediatric
<7 years: Not established
>7 years: 18.75 mg PO bid titrated to symptoms; average daily dose, 187 mg/d
May cause decreased seizure threshold in patients receiving antiepileptic drugs
Documented hypersensitivity; impaired hepatic function
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
May exacerbate symptoms in psychotic children, tics, or Tourette syndrome; liver enzyme levels may increase—check liver function prior to starting therapy and periodically thereafter
Methylphenidate (Ritalin)
Piperidine derivative most commonly prescribed; efficacy has been demonstrated in randomized, double-blind, dose-response, and placebo-controlled trials.
Adult
30-60 mg PO qd
Pediatric
Average pediatric dose similar to that of adults, approximately 50 mg PO qd
May inhibit metabolism of coumarin anticoagulants, anticonvulsants, phenylbutazone, and tricyclic drugs (eg, imipramine, clomipramine, desipramine)
Documented hypersensitivity; marked anxiety, tension, and agitation (may aggravate these symptoms); glaucoma; motor tics; family history or diagnosis of Tourette syndrome
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution with hypertensive patients; check periodic CBC, differential, and platelet counts during prolonged therapy; high abuse potential (schedule II)
Modafinil (Provigil)
Pharmacologically distinct from other stimulants, does not appear to act via dopaminergic system.
Adult
200-400 mg PO qd in single morning dose or divided doses
Pediatric
<16 years: Not established
>16 years: Administer as in adults
May decrease levels of cyclosporine or steroidal contraceptives and, to lesser degree, theophylline; may increase concentrations of diazepam, propranolol, and phenytoin
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Monitor patients closely for signs of misuse or abuse, especially those with history of abuse of drugs or stimulants such as methylphenidate, amphetamine, and cocaine
Armodafinil (Nuvigil)
R-enantiomer of modafinil (mixture of R- and S-enantiomers). Elicits wake-promoting actions similar to sympathomimetic agents, although pharmacologic profile is not identical to sympathomimetic amines. In vitro, binds dopamine transporter and inhibits dopamine reuptake. Not a direct- or indirect-acting dopamine receptor agonist. Indicated to improve wakefulness in individuals with excessive sleepiness associated with narcolepsy, obstructive sleep apnea-hypopnea syndrome (OSAHS), or shift-work sleep disorder.
Adult
150-250 mg PO qam
Pediatric
<17 years: Not established
>17 years: Administer as in adults
Weakly induces CYP1A2 and CYP3A; may decrease levels of drugs metabolized by CYP1A2 (eg, theophylline) and CYP3A (eg, cyclosporine, midazolam, triazolam, steroidal contraceptives); may inhibit CYP2C19 activity, thereby increasing serum levels of CYP2C19 substrates (eg, omeprazole, phenytoin, propranolol)
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in hepatic impairment and decrease dose with severe hepatic impairment; serious rash, including Stevens-Johnson syndrome, has been reported; other serious hypersensitivity reactions include angioedema, anaphylactoid reactions, and multiorgan hypersensitivity reactions; psychiatric adverse events (eg, mania, delusions, hallucinations, suicidal ideation) have been reported with modafinil; may increase blood pressure; monitor patients closely for signs of misuse or abuse, especially those with a history of drug or stimulant abuse (eg, methylphenidate, amphetamine, or cocaine)
Anticataplectic agents
Clomipramine, fluoxetine, and sodium oxybate treat cataplexy in patients with narcolepsy.
Clomipramine (Anafranil)
Dibenzazepine compound belonging to family of tricyclic antidepressants, reduces frequency of cataplexy and other auxiliary symptoms in narcolepsy.
Adult
75-125 mg/d PO
Pediatric
1 mg/kg/d PO
Haldol and possibly methylphenidate increase levels; increases level of phenobarbital; metabolized through P450 2D6 enzyme system
History of hypersensitivity to clomipramine HCl or other tricyclic antidepressants; recent myocardial infarction; MAOI within last 14 d
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May cause seizures, orthostatic hypotension, occasional elevation of liver enzymes, possible cardiac toxicity, rare cases of bone marrow suppression, hyperthermia
Fluoxetine (Prozac)
SSRI that treats cataplexy. Fewer side effects than tricyclic antidepressants. Its toxicity profile is also lower.
Adult
20-40 mg/d PO
Pediatric
Average daily dose: 30 mg/d PO
Interacts with flecainide, vinblastine, tricyclics, and drugs metabolized by P450 2D6; may cause occasional elevation of phenytoin and carbamazepine levels; may cause shift in protein binding of warfarin and digoxin
Documented hypersensitivity; hypersensitivity to SSRIs; MAOI within last 14 d
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Use with caution in patients with hepatic impairment or history of seizures; discontinue MAOIs at least 14 d before initiating fluoxetine
Sodium oxybate (Xyrem)
Also known as gamma hydroxybutyrate (GHB). It is a central nervous system depressant used to treat patients with EDS and cataplexy. The precise mechanism by which sodium oxybate produces an effect on cataplexy is unknown.
Because of sodium oxybate's history of abuse as a recreational drug, the FDA approved it as a Schedule III Controlled Substance. A limited distribution program that includes physician education, patient education, a patient and physician registry, and detailed patient surveillance has been established. Under the program, prescribers and patients will be able to obtain the product only through the Xyrem Success Program, using a single centralized pharmacy 1-866-997-3688. Available as an oral solution 500 mg/mL.
Adult
Initial dose: 2.25 g PO hs (while in bed), then repeat dose 2.5-4 h following first dose (total initial dose 4.5 g)
May increase dose by 1.5 g/d (ie, 0.75 g/dose) q2wk; not to exceed 9 g/d
Take on empty stomach at least 2 h after eating
Pediatric
Not established
Coadministration with other CNS depressants or sedative hypnotics may increase toxicity; food significantly reduces bioavailability
Succinic semialdehyde dehydrogenase deficiency; coadministration with other CNS depressants or sedative hypnotic agents
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
May cause confusion, depression, nausea, vomiting, dizziness, loss of consciousness, headache, incontinence, sleep dyspnea, or sleepwalking; abuse may lead to dependence and severe withdrawal symptoms; decrease initial dose by 50% with hepatic impairment; administer only at bedtime and while in bed; for at least 6 h after ingesting, do not engage in hazardous occupations or activities requiring complete mental alertness or motor coordination
More on Narcolepsy |
| Overview: Narcolepsy |
| Differential Diagnoses & Workup: Narcolepsy |
 Treatment & Medication: Narcolepsy |
| Follow-up: Narcolepsy |
| References |
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Further Reading
Keywords
narcolepsy, excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, sleep paralysis, hypersomnolence, sleep disorder, hypocretin
