In 1999, after successful clinical trial results, the U.S. Food and Drug Administration (FDA) approved a nonamphetamine wake-promoting drug called modafinil (Provigil) for the treatment of excessive daytime sleepiness. In clinical trials, this medicine proved to be effective in reducing excessive daytime sleepiness while producing fewer, less serious side effects than do amphetamines. Headache is the most commonly reported adverse effect. Long-term use of modafinil for narcolepsy treatment does not appear to lead to tolerance.
For cataplexy and other REM-sleep symptoms, antidepressant medications and other drugs that suppress REM sleep are prescribed. When treating narcolepsy, two classes of antidepressant drugs have proved effective in controlling cataplexy:
- Tricyclics (including imipramine, desipramine, clomipramine, and protriptyline)
- Selective serotonin reuptake inhibitors (including fluoxetine and sertraline).
In general, antidepressants produce fewer adverse effects than do amphetamines. But troublesome side effects still occur in some people, including impotence (erectile dysfunction), high blood pressure, and heart rhythm irregularities.
In 2002, the FDA approved Xyrem (sodium oxybate or gamma-hydroxybutyrate, also known as GHB) for treating people with narcolepsy who experience episodes of cataplexy. Due to safety concerns associated with the use of this medicine, the distribution of Xyrem is tightly restricted.
Caffeine and over-the-counter drugs have not been shown to be effective and are not recommended for treating narcolepsy.