Unrefreshing Sleep in Chronic Fatigue Syndrome

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A key feature of chronic fatigue syndrome (ME/CFS) is poor-quality sleep that doesn't relieve fatigue. It's called unrefreshing or non-restorative sleep. No matter how much people with ME/CFS sleep, they never wake up feeling fresh and ready for the day.

Researchers are uncovering more about unrefreshing sleep in ME/CFS, including its clinical features, its impact, and how it can be treated.

What Is Unrefreshing Sleep?

Unrefreshing sleep is not the same thing as insomnia (which may also be present in people with this condition). It's not about how long you sleep or how hard it is to get there.

Instead, the term unrefreshing sleep is used to describe a light sleep that, even after a full night, doesn't leave you rested. People with ME/CFS often report waking up exhausted and feeling as if they haven't slept at all—no matter how long they were actually asleep.

The consequences of unrefreshing sleep go beyond mere tiredness. In studies, this symptom has been linked to:

  • Pain
  • Fatigue
  • Anxiety and depression
  • Low functional capacity
  • Poor quality of life

Unrefreshing sleep is believed to be caused by a problem with how your body regulates sleep, which is called sleep homeostasis. While people with ME/CFS may have sleep disorders as well, multiple studies support the theory that their constant, intense fatigue stems from impaired sleep homeostasis and not from other sleep disorders. In fact, a 2013 study published in Sleep Medicine Reviews found no evidence that treating comorbid sleep disorders relieves the fatigue of this condition.


Many symptoms of ME/CFS are theorized to stem, at least in part, from unrefreshing sleep. They include:

  • Unrelenting fatigue
  • Daytime sleepiness
  • Poor concentration and other cognitive impairment (brain fog)
  • Increased sensitivity to pain (hyperalgesia)
  • General disability

Why Is Sleep Unrefreshing in ME/CFS?

Numerous studies have reported measurable differences in how people with ME/CFS sleep, including:

  • Brain-wave abnormalities in several stages of sleep
  • Significantly shortened sleep duration
  • More time lying awake in bed
  • Less REM sleep & other REM-related abnormalities
  • Low nocturnal heart-rate variability, suggesting autonomic dysfunction

A growing body of research supports the hypothesis of autonomic dysfunction in ME/CFS, which is a problem with the autonomic nervous system (ANS).

The ANS is made up of the sympathetic and parasympathetic nervous systems, which work in balance with each other. When the sympathetic nervous system is activated, it puts you into fight-or-flight mode. Conversely, parasympathetic activation is referred to as a rest-and-digest mode.

If the sympathetic and parasympathetic are out of balance due to autonomic dysfunction, it could put you in a state of heightened arousal and awareness when you're trying to sleep. It's a lot like how a new parent is always on alert for a crying baby, never really getting into a good, deep sleep.

In a relatively new line of research, a 2017 study suggests people with ME/CFS may have structural changes in their brains that correlate with unrefreshing sleep. The brain region involved is the medial prefrontal cortex (mPFC), which is known to deal with memory and decision making (both of which are impaired in some people with ME/CFS) as well as facilitating long-term memory storage during sleep.


Researchers haven't made a lot of headway in finding effective ways to improve sleep, and therefore alleviate fatigue and other symptoms, in ME/CFS. To date, no drug has been FDA-approved for this disease.

A 2010 study in Pain Practice demonstrated positive results with the narcolepsy drug Xyrem (sodium oxybate). However, this drug is tightly controlled and it's often difficult to get a prescription for it.

Studies on the popular sleep supplement melatonin have been mixed, and a 2010 review of studies in Current Medicinal Chemistry states that more work is required to determine whether it's effective.

Some people with this condition report success with medications to help them sleep, including antidepressants and prescription or over-the-counter sleep aids. Others say supplements have helped them sleep better. Unfortunately, we have little-to-no quality research showing whether these treatments actually improve unrefreshing sleep in ME/CFS.

ME/CFS is believed to be similar to fibromyalgia, which also features unrefreshing sleep. The three FDA-approved drugs for fibromyalgia all have been shown to improve sleep in that condition. They are Lyrica (pregabalin), Cymbalta (duloxetine) and Savella (milnacipran). So far, only duloxetine has been studied for ME/CFS.

The small, double-blind trial included 60 people, half of whom received the drug while the other half got a placebo. Duloxetine didn't appear to improve physical fatigue significantly, but it did help with other symptoms, including mental fatigue and pain. This work, while somewhat promising, is preliminary and must be confirmed with larger and longer trials to gauge the drug's true effectiveness.

Doctors often recommend approaches such as learning relaxation techniques (which has some scientific backing), improving sleep habits, and getting help for any sleep disorders you may have.

If your ME/CFS involves pain, proper pain management may also help improve your sleep quality.

By working closely with your doctor and experimenting with different treatments, you may be able to find treatments that help alleviate unrefreshing sleep so that you can improve your health, functionality, and quality of life.

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