Insufficient Sleep Sleep Fragmentation Narcolepsy Recurrent Hypersomnias

Non-Pharmalogic Strategies Pharmalogic Treatment Sleep Disorder Summary

PHARMALOGIC TREATMENT OF PRIMARY DISORDERS OF SOMNOLENCE

Stimulants And Other Alerting Medications: Alerting agents provide a critical component of treatment for most patients with EDS resulting from primary disorders of somnolence. Clinically, the practice of combining two alerting agents of different chemical classes has been employed when a single agent is insufficient. This technique can be useful and has been evaluated in a large international trial with modafinil and sodium oxybate in narcolepsy.

Modafinil: Modafinil is a wake-promoting therapeutic somewhat comparable to traditional stimulants in promoting alertness, but with a different mechanism of action. This mechanism is unknown, but modafinil appears to act more selectively in the brain than do the traditional stimulants. After extensive evaluation, modafinil is viewed as first-line therapy for EDS in narcolepsy.

Sodium Oxybate (Gamma-Hydroxybutyrate): Another agent that has been found to enhance alertness in narcolepsy to a degree similar to or greater than modafinil is sodium oxybate, also known as gamma-hydroxybutyrate (GHB). These findings from a recent head-to-head trial suggest that this agent also should be viewed as first-line therapy for the EDS and cataplexy (see below) of narcolepsy. Clinical experience, but no controlled research, suggests that sodium oxybate may be useful in other conditions of primary EDS as well.

Traditional Stimulants: Commonly used traditional stimulants include methylphenidate, dextro-amphetamine, and methamphetamine. Other sympathomimetic amines and sustained-release preparations are available. Patients may experience negative effects with any alerting agent. Some patients report rebound hypersomnia (exacerbation of sleepiness) as the dose wears off, or tolerance (tachyphylaxis) to the alerting effect may occur with time in some patients. In cases of tolerance, switching to a different class of medication or providing a “drug holiday” can be useful.

Medications For Cataplexy (Anticataplectics): Medications useful in the treatment of cataplexy usually also improve hypnagogic/hypnopompic hallucinations and sleep paralysis.

Sodium Oxybate (GHB): In addition to its effect on EDS in narcolepsy, sodium oxybate, also known as gamma-hydroxybutyrate or GHB, is remarkably effective as an anticataplectic. It has been extensively evaluated as an anticataplectic agent over many years. Additionally, GHB is effective in reducing nocturnal sleep disruptions and in consolidating nocturnal sleep.

Antidepressants: Historically, antidepressants such as the tri-cyclic antidepressants (TCAs) and selective serotonin re-uptake inhibitors (SSRIs), especially those with CNS noradrenergic activity, have also been useful in temporizing cataplexy.Tolerance to these traditional cataplexy medications can occur, requiring medication switch or drug holiday. Recently, atomoxetine, venlafaxine and other newer non–SSRI/non-TCA antidepressants, have been reported in individual cases to provide effective treatment for cataplexy, although they have not yet been rigorously studied.

Immunotherapy: Although high-dose prednisone was unsuccessful in a child with new-onset narcolepsy, intravenous immunoglobulin treatment early in the course of narcolepsy has been reported to be beneficial in a few case reports . Additionally, plasmapheresis resulted in clear but very short-lived improvement in symptoms in a case of late-life onset narcolepsy.