neurologic disorders
Narcolepsy
Treatment of Narcolepsy
Modafinilorarmodafinil Oxybates Solriamfetol Pitolisant Narcolepsy may not require treatment if patients have occasional episodes of sleep paralysis or hypnagogic and hypnopompic hallucinations, infrequent and partial cataplexy, and mild EDS. For others, wake-promoting drugs and anticataplectic drugs are used. Patients should also get enough sleep at night and take brief naps (<30 minutes) at the same time every day (typically afternoon). Patients with cataplexy should avoid precipitating factors (eg, laughter, anger, fear). Fortype 1 narcolepsy,oxybates (sodium oxybateor a combination drug that contains calcium, magnesium, potassium, and sodium oxybates) orpitolisantshould be used for cataplexy, and if EDS persists,modafinilshould be added. Fortype 2 narcolepsy,modafinilshould be first-line treatment, withsolriamfetolas 2nd-line for EDS.Pitolisantcan also be used to treat EDS. Modafinil, a long-acting wake-promoting drug, can help patients with EDS. The mechanism of action is unclear. Typically,modafinil100 to 200 mg orally is given in the morning. Dose is increased to 400 mg as needed. If effects do not last into the evening, a small 2nd dose (eg, 100 mg) at noon or 1pmmay be used, although this dose sometimes interferes with nocturnal sleep. can lower the effectiveness of oral contraceptives and has abuse potential, although it is low. Rarely, serious rashes and Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) have developed in patients taking Armodafinil, theR-enantiomer ofmodafinil, has similar benefits and adverse effects but is longer-acting; dosage is 150 or 250 mg orally once in the morning. Solriamfetolis anorepinephrine-dopaminereuptake inhibitor. It is indicated to treat EDS (but not cataplexy) in patients with narcolepsy or obstructive sleep apnea (OSA). The starting dose is 75 mg orally once a day, which can be doubled every 3 days to a maximum 150 mg once a day. Dose adjustment is required for patients with renal impairment, andsolriamfetolshould not be used in patients with end-stage renal disease. In clinical trials,solriamfetolwas well-tolerated and significantly relieved symptoms of excessive sleepiness (documented by the Epworth Sleepiness Scale and maintenance of wakefulness testing) in adults with narcolepsy and in those with OSA and EDS. The most common adverse effects are insomnia, headache, nausea, decreased appetite, and diarrhea. There are no interactions with oral contraceptives. Pitolisantis a histamine-3 receptor inverse agonist, which is indicated for treatment of EDS and cataplexy in patients with narcolepsy. The dosage varies between 8.9 to 35.6 mg in the morning.Pitolisantis started at 8.9 mg orally once a day (taken on awakening) and increased to 17.8 mg once a day at week 2. The dose may be increased to a maximum of 35.6 mg once a day if needed. Dose adjustment is required for patients with renal or hepatic impairment, andpitolisantshould not be used in patients with end-stage renal disease. Adverse effects include headache, irritability, anxiety, and nausea. It interacts with oral contraceptives, making them less effective. Sodium oxybates or a combination drug that contains calcium, magnesium, potassium, andsodium oxybatesalts can also be used to treat EDS and cataplexy. The dose of both drugs is 2.25 g taken orally at bedtime while in bed, followed by the same dose 2.5 to 4 hours later. The maximum dose is 9 g a night. Adverse effects include headache, nausea, dizziness, nasopharyngitis, somnolence, vomiting, urinary incontinence, and sometimes sleepwalking. Oxybates are schedule III drugs and have the potential for abuse and dependence. They are contraindicated in patients with succinic semialdehyde dehydrogenase deficiency.Sodium oxybateshould be used cautiously in patients with untreated respiratory disorders, hypertension, or heart failure (becausesodium oxybatecontains more sodium than the combination drug that contains several different oxybate salts). Tricyclic antidepressants(particularlyclomipramine,imipramine, andprotriptyline) andSSRIs(eg,venlafaxine,fluoxetine) have been used in the past to treat cataplexy, sleep paralysis, and hypnagogic and hypnopompic hallucinations; however, data about the effectiveness of these drugs are limited. These drugs should be used only ifpitolisantand oxybates are ineffective. Methylphenidateoramphetaminederivativescan be used if patients do not respond to or cannot tolerate wake-promoting drugs. However, all stimulants should be considered 3rd- or 4th line aftermodafinil,armodafinil,solriamfetol, andpitolisant. If stimulants are prescribed for patients > 40 years, an exercise stress test should be done to determine whether patients have underlying cardiovascular disease. Dosages are Methylphenidate: 5 to 15 mg orally 2 or 3 times a day Methamphetamine: 5 to 20 mg orally 2 times a day Dextroamphetamine5 mg orally 2 times a day to 20 mg orally 3 times a day Methylphenidateandamphetaminederivatives are available in long-acting preparations and therefore can be dosed once a day in many patients. However, these stimulants have significant adverse effects, including agitation, hypertension, tachycardia, myocardial infarction (secondary to vasoconstriction), changes in appetite, and mood changes (eg, manic reactions). Abuse potential is high. 