Antidepressants to Treat Narcolepsy

Reviewed by: HU Medical Review Board | Last reviewed: March 2023

There are several antidepressants used to treat cataplexy. Cataplexy is a sudden loss of muscle tone, often in the face, but sometimes in the legs or whole body. Sometimes cataplexy is mild and only causes an eyelid or face droop for a few seconds. Not all people who experience cataplexy will need medicine. If they do, certain antidepressants can be used off-label to control symptoms.1,2

How antidepressants treat cataplexy

During normal sleep, humans lose muscle tone during the REM stage of sleep. In people with narcolepsy, the body has lost its ability to regulate sleep and awake stages. This means the person falls quickly into a REM state in the middle of the day, losing muscle tone without being asleep.1,2

Antidepressants that increase levels of the brain chemicals norepinephrine and serotonin suppress REM sleep and reduce cataplexy. These drugs begin working in a few days.1-3

Antidepressants used to treat cataplexy

When cataplexy control is necessary, antidepressants from 4 drug classes may be prescribed, including:3,4

  • Serotonin-norepinephrine reuptake inhibitors(SNRIs) – Effexor XR® (venlafaxine), Zoloft® (sertraline)
  • Dopamine/norepinephrine reuptake inhibitors – Sunosi® (solriamfetol)
  • Selective serotonin reuptake inhibitors (SSRIs) – Prozac® (fluoxetine)
  • Tricyclics – Anafranil® (clomipramine), Vivactil® (protripyline)

The SNRIs and SSRIs are generally prescribed first these days. That is because while tricyclic antidepressants work well to control cataplexy, tricyclics have more bothersome side effects such as dry mouth, sweating, and constipation.1-3

Side effects of SNRIs, SSRIs, and NRIs

SNRIs, NRIs, and SSRIs tend to be the first choice to control cataplexy. Depending on the drug taken, common side effects include:1,2

  • Nausea
  • Insomnia
  • Dry mouth
  • Headache
  • Increased blood pressure
  • Rash

Many SNRIs and SSRIs are used with caution in children, teens, and young adults with major depression because these drugs can cause suicidal thoughts in the first weeks.1

These are not all the possible side effects of SNRIs and SSRIs. Talk to your doctor about what to expect when taking SNRIs and SSRIs. You also should call your doctor if you have any changes that concern you when taking SNRIs and SSRIs.

Side effects of tricyclic antidepressants

Tricyclic antidepressants are an older class of antidepressants. While highly effective, many people do not like to take these drugs due to side effects. Common side effects of tricyclic antidepressants include:1,2

  • Dry mouth
  • Nausea or constipation
  • Sweating
  • Dizziness
  • Low pressure when standing
  • Daytime drowsiness
  • Disturbed nighttime sleep
  • Weight gain

Tricyclics may be a good option to take as needed before social events likely to trigger cataplexy, such as a party or wedding.1

These are not all the possible side effects of tricyclic antidepressants. Talk to your doctor about what to expect when taking tricyclic antidepressants. You also should call your doctor if you have any changes that concern you when taking tricyclic antidepressants.

Things to know about antidepressants and cataplexy

No antidepressant should be stopped suddenly. Stopping antidepressants too quickly can cause a serious rebound reaction called status cataplecticus. This is a severe, nearly constant cataplexy that can last several hours.1

People being treated for narcolepsy should see their doctor once or twice a year. If your doctor is adjusting your medicines, you should see the doctor more often. Many of the drugs taken for narcolepsy can interact with other drugs, including supplements and birth control pills. It is important to watch for drug side effects, changes in sleep or mood, and other health issues.1

Before beginning treatment for narcolepsy, tell your doctor about all your health conditions and any other drugs, vitamins, or supplements you are taking. This includes over-the-counter drugs.

Other treatments for narcolepsy

In addition to antidepressants, other drugs that are used to treat narcolepsy include stimulants and central nervous system depressants. Your doctor will decide which treatments are best for you based on your specific symptoms and how you respond to different drugs.

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