Fibromyalgia (FM) is a widespread pain and fatigue syndrome without a known cause. The prevalence of FM ranges from 2% to 3% of the general population, with women affected six to nine times more frequently than men.¹ It is estimated that the prevalence increases in women as they age, from 4% at age 20 to 8% by age 70.¹⁻³
Most patients with FM complain of hurting all over—from head to toe. The neck, back, hips, and shoulders are typically prominent sites of pain. Patients also will frequently complain of poor sleep, burning and numb sensations, dry eyes and mouth, temperature sensitivity (feeling cold), headaches, fatigue, dizziness, abdominal and bladder problems, sensitivities to medications, restless leg syndrome, jaw discomfort, and difficulties with mood and memory.
From its earliest description in the literature, FM has been recognized as more than a pain syndrome. Researchers’ understanding that FM involves central nervous system sensitization and deep sleep dysregulation have changed the focus of FM diagnosis and treatment. Revised diagnostic criteria are illustrated in Table 1. As such, clinicians have begun to recognize that the treatment of sleep and fatigue comorbitities should be a major focus in the management of FM patients. The objective of this article is to review current diagnosis and treatment options for sleep-related problems in patients with FM, including a case presentation representative of a common FM patient.
Sleep Disturbances
According to a recent article, sleep and fatigue symptoms have surpassed pain as the most prominent complaints in FM patients.⁴ It is now known that FM patients suffer from a litany of sleep issues including nonrestorative sleep with alpha-wave intrusions, insomnia, restless leg syndrome, hypersomnia such as narcolepsy, and obstructive sleep apnea (OAS).
Perhaps the most common sleep problem seen in patients with FM is nonrestorative sleep. The majority of patients with FM will have alpha-wave intrusions during deep sleep. It is thought that this phenomenon contributes to sleep complaints among patients with FM. In the past, the diagnosis of alpha-wave intrusions could be very time consuming, with researchers counting the intrusions by hand over many hours. Today, diagnostic approaches, including the use of quantitative electroencephalography (qEEG), can easily demonstrate alpha-wave intrusions in deep sleep (see Figure 1).⁵
Figure 2 shows alpha-wave intrusion during delta waves on a sleep hypnogram from an overnight sleep study using polysomnography (PSG) in a patient with FM. More than 90% of patients with FM will have alpha-wave intrusions during their sleep and it is thought that this phenomenon contributes to pathology and complaints in patients with FM. Recent therapeutic approaches that target this phenomenon, such as the γ-aminobutyric acid (GABA)-type B agonist, sodium oxybate (Xyrem), has been shown to reduce alpha-wave intrusions, as well as improve symptoms of pain and fatigue.⁶˒⁷
In addition to alpha-wave intrusions that may impair the restorative aspect of sleep, FM patients usually have diminishment of the overall amount of deep sleep. In the normal population, slow-wave sleep (SWS) should account for 20% to 25% of sleep, but in the FM population it is typically much less. In Figure 3, a normal sleep hypnogram demonstrates normal deep sleep predominantly in the first 5 hours of sleep as compared to a FM patient who does not enter deep sleep for any significant period of time and has multiple unexplained arousals.
Patients with sleep disordered breathing (SDB) also can present with a number of complaints, including drowsiness, inability to sleep, cognitive dysfunction, fatigue, mood complaints, and decreased libido. A small case study demonstrated that treatment of SDB could improve symptoms in patients with FM.⁸ We also know that disruption of deep sleep in healthy individuals can predispose them to increases in pain perception and cognitive difficulties. A number of smaller trials have shown that when deprived of SWS, healthy volunteers developed pain and cognitive dysfunction similar to that seen in the FM population; findings that support the association between dysfunctional sleep and FM.⁹
Given the plethora of complaints common in both patients with FM and SDB, there has been new interest in ruling out SDB in patients with FM. Since we know that patients with FM can have poor quality sleep, the identification of a treatable sleep disorder such as SDB is something that can greatly benefit this patient population.
Patients with FM and SDB have added risk factors—prescription of sedative or narcotic agents, which can cause or worsen SDB. With the airway blocked, air cannot reach the lungs and oxygen levels drop. This causes the brain to slightly wake up; this is referred to as a microarousal. These brief repeated arousals cause sleep to be nonrestorative and put stress on the heart and other organs.
Sleep Apnea
One of the more serious SDBs is OSA. The condition is characterized by loud, frequent snoring and involves the partial or complete collapse of the airway during sleep. With OSA, muscles in the throat start to relax during sleep, which makes it more likely for the airway to collapse. An apnea is described as a cessation of airflow >10 seconds. A hypopnea is typically defined as a decrease in airflow of at least 30% associated with a decrease in oxygen saturation of >4%. Episodes can occur hundreds of times in one night. A large neck (greater than 18 inches in men or 16 inches in women), body mass index (BMI) >35 kg/m2, a retrusive jaw, or large tonsils in children can predispose patients to OSA.
Obstructive sleep apnea can cause excessive daytime drowsiness, which can affect performance at work and quality of life. When oxygen levels drop, numerous physiologic changes occur, including elevated cortisol levels, hyperglycemia, insulin resistance, and increase in sympathetic tone with increased heart rate and blood pressure. Because of this, OSA has been linked to a number of medical conditions, including high blood pressure, stroke, heart attack, atrial fibrillation, gastroesophageal reflux, diabetes, and glaucoma. Problems controlling weight, mood and memory problems, as well as diminished libido, also are common symptoms associated with OSA.
The incidence of moderate and severe OSA in the general population is estimated to range from 5% to 7% in men and 2% to 4% in women.¹⁰ However, in women who have been diagnosed with OSA, the incidence of FM is tenfold higher than in the normal population, indicating a profound association between SDB and FM.¹¹
Diagnosis: Sleep Testing
To evaluate for OSA, an overnight polysomnography that identifies the apnea-hypopnea index (AHI) should be ordered. An AHI of 5 to 15 times per hour is considered mild; more than 15 times per hour is considered moderate; and more than 30 times per hour is considered severe. Overnight PSG will also look for problems in sleep architecture such as decreased deep sleep or the presence of alpha-wave intrusions, which are common sleep findings in the FM population. Problems such as low-sleep efficiency and increased period limb movements also can be readily ascertained during a standard PSG, possibly leading to treatment interventions that can improve sleep quality in patients with FM.
Most sleep physicians will initiate therapy for patients with AHI in the moderate category. Patients who have mild sleep apnea and are drowsy or who have comorbid conditions (eg, hypertension, atrial fibrillation) also may be candidates for intervention.
Treatment of SDB in Fibromyalgia
The treatment of SDB in patients with FM may at times be more difficult than in the typical OSA population due to pain, hypervigilance, and non-restful sleep (see Algorithm). For patients with severe OSA (AHI >30), the only therapy that is indicated is continuous positive airway pressure (CPAP). The CPAP machine stops the cycle of OSA by delivering a stream of compressed air via a hose to a nasal pillow, nose mask, full-face mask, or hybrid, thereby creating a pneumatic splint that keeps the airway open. This promotes unobstructed breathing and often reduces and/or prevents apneas and hypopneas. Advancements in CPAP technology (eg, improvements that allow ambient air to be humidified without manual adjustment) can significantly reduce the amount of condensation that accumulates in the tubing that connects the machine to the mask.
Today, most CPAP machines are equipped with expiratory pressure relief that maintains positive pressure during inspiration, but reduces pressure during exhalation. The reduction in pressure during exhalation makes it easier for the patient to breathe. The titrated pressure is the pressure of air at which most (if not all) apneas and hypopneas have been prevented, and it is usually measured in centimeters of water (cm/H2O). A typical CPAP machine can deliver pressures between 4 and 20 cm/H2O.
The expiratory pressures usually are prescribed by the sleep physician. The newest autotitrating machines (AutoPAP), will titrate pressure according to snore vibrations and other internal algorithms that can help provide an adequate amount of pressure support when patients need more pressure—such as during rapid eye-movement (REM) sleep, when muscle relaxation is increased, or while the patient is supine. The AutoPAP also reduces the pressure automatically when the patient is in a light sleep or in a lateral decubitus position, greatly reducing the amount of awakenings patients experience as a result of therapy.
There also has been an increase in the types of mask interfaces available for those who require CPAP. These include small nasal pillow CPAP masks that resemble nasal cannulas (Swift FX for Her, ResMed). For patients who breathe through their mouths while sleeping and require a full-face mask, there are mouth-nasal pillow combinations that help to reduce claustrophobic complaints (Mirage Liberty, ResMed). In addition, there are masks that fit over the entire face, similar to a windshield (Fit Life, Respironics).
For patients with mild sleep apnea or moderate-severe OSA, oral appliance therapy with mandibular advancement (OAT) can be efficacious and is usually well tolerated (TAP 3, Dental Arts Laboratories; SomnoDent, SomnoMed). Oral appliances typically reduce AHI by 50% and are sometimes better tolerated than CPAP.
One drawback is that oral appliances can exacerbate tempromandibular joint (TMJ) symptoms, a frequent comorbidity in patients with FM. These devices work by advancing the mandible, which opens the airway, and are constructed specifically for the patient by dentists who are board-certified by the American Academy of Dental Sleep Medicine.
At times, patients may exhibit an elevated AHI while supine that may resolve when they assume a side-lying position. This is referred to as positional apnea. In these cases, instead of placing patients on CPAP, an ergonomic approach or a positional pillow (Sona Pillow) may be an effective, well-tolerated, and cost-efficient alternative.
A new and exciting experimental strategy for OSA that is currently under investigation is hypoglossal nerve stimulation (HGNS). A number of companies, including Apnex, ImTherma, and Medtropic, are already well into Phase II clinical trials. HGNS involves implantation of a neurostimulator in the anterior chest wall connected to a respiration sensing lead and a nerve cuff electrode that is attached to the hypoglossal nerve in the submandibular region.
When stimulated, the genioglossus muscle will contract and significantly increase the size of the retropharynx, thereby improving airflow and reducing apneas and hypopneas. After implantation, a programming system allows fine tuning of the device and a therapy controller will allow patients to activate the system prior to sleep and then turn it off when awake. This may end up being a viable option in the FM patient who requires treatment for OSA, but is intolerant of CPAP.
Conclusion
Fibromyalgia is the most common widespread pain condition in the world. The majority of patients with FM will have prominent sleep complaints that often surpass their pain complaints. A better understanding of sleep problems associated with FM, as well as improved testing and treatment, will enable the pain practitioner to care for patients and improve their symptoms, health, and quality of life. The tenfold increase of SDB in the FM patient population is not well understood, but is readily amenable to testing and the myriad treatment options now available.