Chronic Fatigue Syndrome: From Diagnosis to Management

Treating Specific Symptoms

Sleep problems. Recognize that unrefreshing sleep is a case-defining symptom, and the vast majority of CFS patients experiences some form of sleep-related symptoms.^[48,49] Sleep deprivation or disruption may cause or exacerbate other symptoms such as fatigue, impaired cognition, headaches, and pain, so treating sleep problems should occur early in the treatment program.

• Advise patients to practice standard sleep hygiene techniques and to avoid alcohol near bedtime.^[50]
• Advise patients to try light exercise and stretching at least 4 hours before bedtime, which may improve sleep in some patients.
• Recognize that pharmaceuticals are often needed to manage sleep problems in CFS. Initial medications to consider are simple antihistamines or over-the-counter sleep products. If this is not beneficial, then start with a prescription sleep medicine. A combination of medications -- including both sleep-initiating and sleep-sustaining drugs, and medication to relieve pain -- may be indicated for some CFS patients to help achieve restorative sleep.^[50,51]
• Prescribe the lowest effective dose because CFS patients are particularly sensitive to medications, and because sleep medications may change sleep architecture, alter daytime cognition, or worsen fatigue.^[52]
• Create an individualized treatment plan based on the patient's responses to a thorough sleep history and patient assessment. This helps clinicians avoid random use of sleep medications, which may prolong identification of a sleep disorder or induce additional problems. For instance, avoiding sleep medications that cause weight gain in patients with metabolic syndrome or a family history of type 2 diabetes and avoiding benzodiazepines or opioids in patients who have sleep apnea may be indicated.
• Set up a consultation with a sleep specialist or schedule polysomnography for CFS patients if sleep problems persist to determine the precise nature of the sleep dysfunction and identify any comorbid sleep conditions. Some clinicians recommend that patients see a neurologist rather than a pulmonologist for a sleep study because pulmonologists may only look for sleep apnea, and study results won't indicate other kinds of sleep dysfunction common to CFS.^[51]
• Treat any comorbid sleep disorders that are identified. Primary sleep disorders like obstructive sleep apnea, central sleep apnea, narcolepsy, and movement disorders like restless legs syndrome or myoclonus are exclusionary conditions for a diagnosis of CFS unless treatment of the disorder fails to resolve the CFS symptoms. Be aware that this is often the case. While treatment of comorbid sleep disorders often brings some symptom relief and is essential, it rarely resolves CFS or all associated sleep issues.

Pain. CFS patients may present with muscle and joint pain, sore throat and flu-like aches, tender or painful lymph nodes, visceral and neuropathic pain, headaches, and fibromyalgia tenderpoint pain. Pain can be substantially reduced in CFS patients with proper treatment, but it may not be eliminated.^[52]

• Conduct a thorough pain assessment to understand the cause and nature of the pain the patient is experiencing so treatment can be directed and effective. For instance, CFS patients experience different kinds of headaches -- including migraine, sinus, muscle-joint, dehydration, and sleep-deprivation headaches -- and the treatment for each varies.^[14]
• Advise patients that pain treatment in CFS is highly individualized and that a trial-and-error approach to finding the most effective pain relief may be needed. This reduces expectations that a single therapy will "fix" their pain and reduces the frustration that can lead to treatment noncompliance.
• Include nonpharmacologic modalities and alternative therapies in your pain management program. For some patients, nondrug treatments like heat (or cold), toning exercises, gentle stretching, massage, TENS, or acupuncture may reduce pain. For a patient who repeatedly reinjures muscles or joints, effective nondrug therapies would be counseling the patient to allow the injury to heal and developing an activity management plan to minimize the overexertion that leads to reinjury and the underexertion that leads to deconditioning.
• Use pain medications when indicated. Therapy may begin with simple analgesics like acetaminophen, aspirin, or NSAIDs. Opiates should be considered when pain is persistent and severe and has a significant impact on lifestyle and function, and when conservative pain management has proven inadequate. Clinicians report that CFS patients may be resistant to taking narcotics, causing symptom exacerbation and reducing quality of life.^[51] Educating patients about the role pain plays in their fatigue, poor sleep, mood, and overall well-being may help overcome this obstacle. Making them aware that research indicates it is very unusual to develop addictive behaviors to opioid pain medications while under the proper supervision of a clinician may also help overcome this barrier to effective treatment.^[53]
• Set appropriate time limits to assess the efficacy of specific drug therapies you are trying. Many pain medications have their full effect within 1 or 2 weeks, so the trial period should be set accordingly. Requiring patients to stay on a pain medication for longer than needed to determine efficacy exposes patients to unnecessary side effects and expense and delays prescribing another drug therapy if the first is not effective.^[53]
• Advise patients not to attempt vigorous exercise but that carefully controlled exercise is essential to avoid a downward spiral of weakness, stiffness, and further pain. Referrals to exercise therapists, physical therapists, massage therapists, and chiropractors may be indicated to help manage pain. Advise patients to sign up for 2-4 initial treatments to determine efficacy before committing to a longer term of therapy.^[54]
• Identify any comorbid focal pain conditions (such as osteoarthritis, peripheral neuropathy, or lumbar disc disease) and treat them with appropriate modalities when present.

Depression and mood disorders. There is now abundant scientific evidence that CFS is not a form of depression or hypochondria.^[9-11] Depression has been differentiated from CFS in both research and clinical settings. However, depression is a common comorbid illness in CFS, with as many as half of patients developing secondary depression as a result of the illness. Treating depression can reduce anxiety and stress and assist in relief of symptoms.

• Treat depression when it is present. Patients who have been traumatized by skepticism about the illness, or who have been told they are not sick, or that they are "just depressed" may fail to report depression to their clinicians and may be reluctant to be treated for it. This obstacle may be overcome by assuring such patients that you recognize that CFS is not caused by depression, and educating them about the role that untreated depression can play in perpetuating the illness and exacerbating symptoms.
• Conduct a careful patient assessment to determine if an exacerbation of symptoms is being caused by CFS or by depression. There are brief psychiatric screening tools available that can be administered and scored in the primary care setting.
• Refer patients to a mental health professional for counseling if indicated.
• Use caution in prescribing antidepressant drugs. Antidepressants of various classes may act on other CFS symptoms or cause side effects. However, they may serve as an important therapeutic intervention for some patients.
• When antidepressants are indicated, prescribe medications that treat multiple symptoms whenever possible. For instance, duloxetine may not only improve mood; it may also help with pain.

Orthostatic instability. Some CFS patients may present with symptoms indicative of orthostatic intolerance, including low blood pressure, low tolerance for standing, dizziness, lightheadedness, upright tachycardia, and vasovagal syncope.^[55,56] Some patients are diagnosed with neurally mediated hypotension (NMH) or postural orthostatic tachycardia syndrome (POTS), which is especially common in pediatric CFS.^[57]

• Be alert for symptoms of orthostatic instability. Patients may be referred to a cardiologist or a neurologist to confirm orthostatic problems before initiating treatment.
• Advise patients with orthostatic problems that they may experience some relief with lifestyle and diet changes such as cutting back on foods that are dehydrating (like alcohol and caffeine), wearing support hose, avoiding prolonged standing, avoiding getting overheated, and keeping feet elevated when possible. Prescribing high-pressure hose may be indicated for some patients.
• Use conservative treatment approaches first, like simple volume expansion (increasing both fluids and salt intake).
• Consider pharmacologic interventions like fludrocortisone or midodrine if volume expansion doesn't improve symptoms. Exercise caution with this therapy with patients who have high blood pressure.
• Consider adding a beta blocker or an adrenergic blocker if there's still no significant improvement in orthostatic symptoms.
• Be aware that orthostatic intolerance can cause headaches (activity-related orthostatic headaches), fatigue, and brain fog, so it's important to consider orthostatic problems as a contributing cause of those symptoms in CFS patients.
• Be especially alert for symptoms of orthostatic intolerance in adolescents who present with CFS symptoms. Treatment for POTS or NMH can sometimes resolve CFS altogether in adolescents or reduce symptomatology.

Cognitive problems. Memory and concentration problems, brain fog, confusion, word-finding difficulties, and many other cognitive problems have been reported in CFS patients.^[58,59] Cognitive deficits appear to be most common in patients who do not have a concurrent psychiatric disorder.^[60]

• Suggest coping and adaptive techniques for cognitive difficulties like memory and concentration problems. Memory aids, such as organizers, schedulers, and written resource manuals, are usually recommended.^[61]
• Advise patients to stimulate the mind with puzzles, word games, card games, and other activities.
• Refer CFS patients with disabling cognitive problems to behavioral health professionals for specific techniques to help them function better.
• Be aware of the interrelationship between cognitive problems and other symptoms of CFS. For instance, unrefreshing sleep can contribute significantly to cognitive dysfunction, but that may be ameliorated when sleep issues are addressed. Similarly, orthostatic instability can contribute to brain fog, so treatments that improve autonomic symptoms may also improve cognition.
• Consider pharmacologic treatments in cases of severe cognitive dysfunction. Stimulants like modafinil may be useful, particularly in low doses. Stronger stimulants should be used cautiously because they can adversely impact sleep and anxiety, and they can "trick" patients into thinking they have more energy than they do, cause them to overexert, and trigger a postexertional relapse.
• Remember that drugs used for pain, sleep, or mood may contribute indirectly to cognitive dysfunction.

Clinical Case Vignette: Managing Sleep

Case: Nancy, your CFS patient, complains of fatigue, aches and pains, problems concentrating, and sleep disturbance. She is particularly concerned about the sleep issues, reporting that it may take 1 or 2 hours to fall asleep, and then sleep is restless and shallow. No matter how much she sleeps, Nancy awakens feeling unrefreshed, and it takes an hour or 2 to get going in the morning. She frequently recalls vivid nightmarish dreams. As a result of her poor sleep, she finds it hard to get up for work in the morning, and she is somnolent during the day. Her Epworth Sleepiness Score is 14 out of 24 possible points, where 10 or more represents significant daytime somnolence.

Key Factors: Sleep disturbance occurs in 70% to 95% of CFS patients,^[48] and it is typically characterized by difficulty initiating and maintaining sleep, shallow or restless sleep, vivid or nightmarish dreams, nonrestorative sleep, and morning dysania (stiffness, soreness, and fogginess upon awakening). Most experts agree that sleep is foremost in the management of CFS because sleep dysfunction can significantly worsen other symptoms like muscle and joint pain, headaches, fatigue, cognitive problems, and mood.^[51]

The first step is to ensure good sleep hygiene. Advise the patient to: (1) provide a "wind-down" period before bedtime; (2) use the bed only for sleeping or sex; (3) avoid stimulant foods and beverages at night; (4) keep a sleep schedule by getting up every morning at the same time; (5) get up and read or listen to music if she cannot fall asleep within 30 minutes; (6) try not to take daytime naps (although short rest periods are fine); (7) refrain from watching TV or using the computer in the bed at night; and (8) hide the clock from view.

If sleep aids are needed, start with simple over-the-counter remedies such as melatonin or antihistamines. Dopamine agonists (ropinirole, pramipexole) or low-dose clonazepam may reduce periodic limb movements of sleep (PLMS) and restlessness. Reducing pain can reduce awakenings and improve sleep. Tricyclic drugs (amitriptyline, cyclobenzaprine or the tetracyclic trazodone) improve sleep onset and maintenance but may not reduce pain beyond 1 month. In more resistant cases, it may be necessary to try nonbenzodiazepine sleep aids such as zaleplon, eszopiclone, ramelteon, or zolpidem. Avoid sleep disturbers such as benzodiazepines (which may cause nonrestorative sleep) and SSRIs (which may cause restless legs or periodic leg movement disorder). If the patient is taking opiates for persistent, severe pain, these medications may need to be discontinued because they tend to reduce deep sleep.

Primary sleep disorders (such as sleep apnea and periodic leg movements) occur in more than half of CFS patients.^[62,63] If sleep is difficult to manage, refer the patient to a knowledgeable and empathetic sleep specialist to identify any comorbid sleep disorders.