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.

Pathophysiology
We only partly understand why people with CFS lack restorative sleep. For many, especially those with fibromyalgia, the EEG shows alpha wave activity inappropriately intruding into the delta waves of deep sleep.

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).

Diagnosis
When either insomnia or poor sleep is chronic, the 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 done.

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 CFS.

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 pathology.^9-11

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.

Other Therapies
There are several over-the-counter medications that 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 disorder.^12-14
  
• 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 available.¹⁸

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 Jersey.

References