Narcolepsy-cataplexy treatment

At the present time, there is no cure for narcolepsy, and treatment goals include control of EDS, cataplexy, hypnagogic hallucinations, and sleep paralysis improvement of nocturnal sleep and reduction of psychosocial problems. 

Broughton R, Mamelak M (1979) The treatment of narcolepsy-cataplexy with nocturnal gamma hydroxybutyrate. Can J Neurol Sci 6 1-6... 

The main risk factor appears to be a genetic susceptibility to the illness. The majority of narcolepsy patients, particularly those with cataplexy, have a genetic marker known as HLA-DQB1 0602. Recent evidence indicates that the key dysfunction in narcolepsy is diminished activity of a newly discovered neurotransmitter known as hypocretin. This new evidence has led to the development of a new diagnostic test for narcolepsy and may ultimately lead to new treatments that act directly on hypocretin systems in the brain. 

Other Hypersomnias. Narcolepsy is not the only hypersomnia, but it is by far the most common. Primary hypersomnia shares sleep attacks and excessive daytime sleepiness with narcolepsy but does not feature cataplexy or REM-associated abnormalities. Another rare hypersomnia is Kleine-Levin syndrome (KLS), which most often occurs in teenage boys. KLS consists of intermittent bouts of hypersomnia and bizarre behaviors including compulsive eating and sexual inappropriateness. Distinguishing these hypersomnias from narcolepsy may help clarify the patient s prognosis, but the treatment alternatives are very similar. 

Tricyclic Antidepressants (TCAs). TCAs were introduced in the 1950s and over the years have become the mainstay of treatment for cataplexy and the other REM-related symptoms. The doses used are usually less than the doses required in the treatment of depression. Imipramine (Tofranil) is the most widely used TCA for narcolepsy and is usually effective at doses from 10 to 75 mg given once a day. Some doctors prefer the TCA protriptyline (Vivactil) because it has mild stimulant effects, but it has not been as widely used or as thoroughly studied in narcolepsy. The common side effects of TCAs are drowsiness, dry mouth, and constipation, but these are usually not a problem at the lower doses used for narcolepsy. Patients should receive a baseline electrocardiograph (EKG) before starting a TCA and should have blood levels of the medication checked periodically. 

One change that is sometimes made during long-term treatment is the addition of a second medication to treat the auxiliary symptoms of narcolepsy. For many patients, these other symptoms do not occur often enough or are not severe enough to require treatment. However, the auxiliary symptoms (especially cataplexy) can be a big problem for some narcolepsy patients. The stimulants used to treat the sleep attacks can also provide some mild relief of cataplexy, but the benefit is often not sufficient. 

Unlabeled Uses Treatment of bulimia nervosa, cataplexy associated with narcolepsy, depression, neurogenic pain, panic disorder, ejaculatory disorders, pervasive developmental disorder... 

Sodium oxybate is effective and indicated for the treatment of cataplexy in patients with narcolepsy it could also be effective for general anesthesia, narcolepsy, fibromyalgia syndrome, insomnia, alcoholism and opiate withdrawal, but its potential for abuse is unacceptable... 

Some stimulants are approved for treatment of narcolepsy. Stimulants mainly improve excessive daytime sleepiness, and the effects may be dose related (Mitler et al. 1990). However, cataplexy usually does not respond to stimulants (Hyman et al. 1995). Stimulants are often administered in divided daily doses, and doses are often titrated weekly on the basis of clinical response. 

One of the oldest uses for dextroamphetamines is in the treatment of narcolepsy, a sleep disorder characterized by constant daytime fatigue and sleepiness, with a disturbance in nighttime REM sleep (the period of sleep when dreams occur). During the day or other periods of time when they would normaly be awake, people with narcolepsy often experience sudden episodes of REM sleep. They may also suffer from sleep paralysis and/or cataplexy, an abmpt, total loss of muscle control. Central nervous system stimulants like dextroamphetamine help to relieve these symptoms. 

With no effective treatment for narcolepsy currently available, the approximately 100,000 to 125,000 people in the United States afflicted with the often debilitating disease are eager for this research to yield a therapeutic drug. Narcolepsy causes excessive daytime sleepiness often accompanied by cataplexy, a sudden... 

In 2001, Orphan Medical filed a new drug application with the FDA for a drug called Xyrem (sodium oxy-bate, oral solution), which uses GHB as the active ingredient. In clinical trials, Xyrem has been shown to reduce cataplexy and restore normal sleep patterns. If approved, Xyrem would be the only treatment approved by the FDA as effective in managing cataplexy in people with narcolepsy. 

Cataplexy requires additional treatment, as stimulants are not effective. Medications for suppressing REM sleep improve other features of narcolepsy, i.e., use of ... 

Armodafinil was also evaluated at 150 or 250 mg/day in 196 narcolepsy patients,24 with or without cataplexy, with associated ES. For this particular trial, the MWT was conducted in standard fashion but extended later in the day to examine the potential for armodafinil to improve alertness. The MWT data at 09 00-15 00 h were combined for both treatment groups and showed an increase of 1.9 min for armodafinil compared with a decrease of 1.9 min for placebo (p < 0.01). MWT sleep latency showed significant improvement relative to placebo with a difference of 2.8 min. (p < 0.05). 

Narcolepsy is a rare disease characterized by excessive daytime sleepiness. It has a prevalence of 0.05% in the general population and affects an estimated 140,000 people in the United States. In 2002, the FDA approved sodium oxybate (Xyrem ) for the treatment of cataplexy in patients with narcolepsy. The active ingredient in this drug is gamma hydroxybutyrate, or GHB. The development and marketing of sodium oxybate was permitted after a revision of the Date Rape Prevention Act of 2000 (see Chapter 5) that allowed GHB to be legally administered for medical purposes. 

In June 2001, a government advisory panel convened by the FDA concluded that GHB could be useful as a treatment for cataplexy, a rare but dangerous complication of the sleep disorder narcolepsy. This panel was asked to consider whether prescription sales should be permitted for GHB under the brand name Xyrem . The committee concluded that the manufacturer of the drug (Orphan Medical) had shown that Xyrem is useful in treating cataplexy, a complication that can cause people to collapse suddenly when their muscles lose strength. 

This is a central nervous system depressant licensed for the treatment of narcolepsy with cataplexy. At recommended doses, it has been associated with confusion, depression and other neuropsychiatric effects. Sodium oxybate is related to gamma hydroxybutyrate, a known drug of abuse, which has been associated with seizures, respiratory depression, coma and death. 

Xyrem is used as an oral medication, available in solution form, for the treatment of cataplexy in patients with narcolepsy. Gamma hydroxybutyric acid (GHB) is also used as a drug of abuse. 

Doses of medications used to treat narcolepsy are summarized in Table 71-5. Pharmacologic management of narcolepsy is focused on two primary areas treatment of excessive daytime sleepiness (EDS) and treatment of cataplexy. 

The primary objective of pharmacologic treatment of narcolepsy is to reduce symptoms that adversely impact the quality of life. This includes alleviating daytime sleepiness with modaflnil or stimulants. The goal is to produce the fullest possible return of normal function for patients at work, school, home, and socially. Cataplexy, hypnagogic hallucinations, and sleep paralysis should be treated when they are present and troublesome. The health care provider should consider... 

Some clinicians believe that combinations of long- and shortacting stimulants are effective for the treatment of narcolepsy. Some stimulants have a short effective period, while others have a longer duration of activity and slower onset of action. By combining stimulants with different activities it may be possible to achieve alertness more rapidly and for a longer period. In addition, although published evidence is limited, combinations of stimulants and antidepressants may be of benefit for treatment of sleepiness and cataplexy. 

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