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Sleep Dysfunction in
Podell, MD, MPH
Many patients with chronic fatigue syndrome (CFS) feel sleepy
well as tired. Whether or not they have difficulty falling asleep (sleep onset
insomnia) or difficulty staying asleep (sleep maintenance insomnia), most CFS
patients feel that their sleep is not refreshing. They wake up in the morning
feeling as if they haven’t really rested.
Improving sleep is a realistic goal. As clinicians know, this is often a
complex and difficult task. Even modest improvement in sleep can have important
positive effects on the patient’s sense of well-being.1-6
Sleep studies will often disclose some abnormality. Pharmacologic and
non-pharmacologic measures can be of benefit, including cognitive therapies.
Complementary medications available over the counter may be of help to some
patients. When sleep dysfunction remains persistent and severe, a formal
consultation with a sleep physiologist should be obtained.
We only partly understand why people with
restorative sleep. For many, especially those with fibromyalgia, the EEG shows
alpha wave activity inappropriately intruding into the delta waves of deep
A significant minority have classic sleep disorders complicating their CFS:
periodic leg movement disorder (PLMD) or sleep apnea. Others suffer from
insomnia, hypersomnia or non-restorative sleep. The mechanisms for these aspects
of CFS are not clear (see table).
When either insomnia or poor sleep is chronic,
physician should consider whether a specific and treatable sleep disorder is
present. Occasionally, the diagnosis of CFS is mistaken, and a primary sleep
disorder is the main cause of fatigue. More often, CFS is the diagnosis, but
specific sleep disorders can complicate and exacerbate the illness. Sleep
disorders can be suspected by asking patients about key symptoms, specifically
about whether they snore, struggle for breath at night or have ever been told
that they stop breathing, or have muscle twitching often while asleep.
Teaching a family member or friend to observe the sleeping patient for at
least 30 minutes, on one or several nights, can be very useful. This is the
minimum that should be done for patients with chronic fatigue without a
clear-cut cause. The observer should look for severe snoring, episodes of not
breathing for 10 seconds or more, snorting or struggling for breath. Frequent
gross or fine muscle or limb movements or twitches should be noted.
One may observe PLMD if there is a restless legs syndrome during the day or
evening.7,8 However, lack of restless legs should not deter
evaluation for PLMD. Typically, patients are not aware of nocturnal muscle
twitches or limb jerks. This condition is often missed unless a sleep study is
We cannot exclude a sleep disorder with a very high degree of confidence
without professional monitoring, utilizing an overnight sleep study. We would
recommend that all patients with chronic insomnia or chronically non-restorative
sleep be evaluated in consultation with a sleep specialist whenever cost or
third-party payment is not an issue. It is important to note that some patients
with CFS have relatively normal overnight sleep tests. These patients also
describe their sleep as not restful. The patient’s subjective report should be
respected as valid and be taken seriously.
Treatment of Sleep Problems in CFS
Trial and error may be
productive. Often long-term rather than short-term treatment may be needed, with
all the trade-offs or potential medication side effects that that implies.
Even modest improvements in sleep quality can make a meaningful difference
for the quality of life. However, better sleep is not, by itself, a cure for
Sleep specialists recommend an important role for sleep hygiene and
behavioral techniques. Ideally, a nurse or patient educator would spend an hour
with each patient to review basic sleep hygiene and relaxation skills. Attention
to these details can often make a major difference. Additional and more complex
behavioral techniques can often help sleep problems of any kind, especially
those where the overnight sleep test fails to disclose specifically treatable
If chronic pain, sleep apnea, PLMD, anxiety or depression is a dominant
problem, these symptoms should be addressed with their standard treatments.
Whether or not these disorders complicate sleep, pharmacologic regimens
specifically for sleep can be very useful.
Sleep problems among many CFS patients are chronic, not intermittent. While
limiting sleep medicine to intermittent use is a desirable goal, there may be
good medical and psychological reasons to encourage chronic ongoing treatment.
If sleep medicines are to be used regularly, it is advantageous to use those
medicines which are less likely to disrupt sleep architecture or to induce
tolerance or addiction. The physician should be prepared to “test” a number of
different sleep medicines, each at a relatively low dose. A few may benefit by
rotating a different sleep medicine every night or every few nights. Patients
with CFS tend to be very sensitive to medicine side effects, so it is often wise
to start with new medicines with a very low dose.
For better sleep, the first choice should often be either anti-depressants
like trazadone (Desyrel) or the sedating tricyclic anti-depressants, e.g.,
amitriptyline. These medicines usually do not disrupt sleep, maintenance
insomnia or sleep architecture, and may improve sleep. They can be useful for
suppressing the alpha-delta sleep abnormality that is often seen with
fibromyalgia or with chronic pain. However, because of their long action, they
are often too sedating in the morning.9,10
When used for sleep, the tricyclics or trazadone usually do best at lower
doses than are needed for treating depression. The most commonly used
tricyclics, listed in order of sedation and increasing side effects:
nortriptyline (Pamelor), doxepin (Sinequan) and imipra-mine (Tofranil), as well
as amitriptyline (Elavil).
For the tricyclics, low doses, e.g. 10 mg, can be used at first. A few very
sensitive patients might start with 1–2 mg of doxepin suspension with stepwise
increases in dosage steps towards the 20–50 mg range. If also treating
depression, the increase can proceed to the usual full therapeutic dose (75–150
mg). For trazadone, a starting dose of 25–50 mg qhs is adequate. If necessary,
one can increase in steps toward the 150 mg range. When using these
antidepressant medicines, sleep benefits are often seen the first night. This
contrasts with relatively high dose range and 3–4 weeks typically needed to see
effects for depression.
Antidepressants can be useful sleep aids whether or not the patient is
depressed. However, some patients experience a paradoxical effect, becoming more
agitated and unable to sleep. For sleep onset insomnia, consider short-acting
agents such as zafeplon (Sonata) or triazolam (Halcion). For sleep maintenance
insomnia, consider zolpidem (Ambien) or one of these benzodiazepines: clonazepam
(Klonopin), temazepam (Restoril) or lorazepam (Ativan). Flurazepam (Dalmane), a
long-acting benzodiazepine, usually leaves patients too sedated in the morning.
Benzodiazepines have a relatively high potential for tolerance, habituation
and abuse. Ambien, a non-benzodiazepine, has less potential for tolerance and
perhaps also less for habituation. However, Ambien is not entirely free from the
risk of addiction. Transient amnesia has been reported for benzodiazepines as a
class, especially with triazolam.
In PLMD, employ a very brief diagnostic trial of dopaminergic agonist, which
is a moderately effective treatment for PLMD, e.g., Sinemet 25/100. If
subjective sleep quality improves, consider PLMD as fairly likely. Do not
continue to treat empirically. Confirm the diagnosis with an overnight sleep
study. Lack of improvement with Sinemet does not rule out PLMD. Various
antidepressants have been reported to exacerbate PLMD in some patients.
Almost all sleeping medicines should be used with caution for people who have
to be alert when they first wake or throughout the day. Most hypnotics will also
potentiate the sedating effects of alcohol and other sedating drugs. Use in
pregnancy should be coordinated with an obstetrician.
There are several over-the-counter medications
patients with CFS may use as sleep adjuncts. A few are listed below.
- Melatonin may be effective for a small minority of people with insomnia,
especially among the elderly. Little is known about the potential long-term
side effects or drug interactions. It may be useful for delayed phase sleep
- Valerian Root is a mediocre short-term sedative. However, at least three
double-blind studies from Germany show benefit for sleep and for mood after
3–4 weeks or taking Valerian, 300 mg twice daily. Valerian might also help
anxiety. It does not seem to be addictive. There are no substantial long-term
studies of safety or benefit.15,16
- Lavender extract used as aromatherapy has been studied, showing benefit
for sleep onset insomnia and accompanying anti-anxiety effects. No side
effects are expected.17
All of these natural products can potentially interact with selected drugs or
with specific nutrients or herbs. Books on complementary medicines and computer
data bases in health food stores and pharmacies are becoming
Richard Podell, MD, MPH, is clinical professor of family medicine in the
Department of Family Medicine at the University of Medicine and Dentistry of New
Jersey-Robert Wood Johnson Medical School. This article is reprinted with
permission from “A Consensus Manual for the Primary Care and Treatment of
Chronic Fatigue Syndrome,” published by The Academy of Medicine of New
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