Insomnia: Focus on New Dosing Concerns In Women
Sufficient sleep increasingly has been recognized as a key component of chronic disease prevention as well as overall health promotion.1 Insufficient sleep is associated with both the onset of, as well as difficulty in managing, chronic diseases. In fact, the increased number of motor vehicle crashes, industrial disasters, and occupational harm associated with sleep insufficiency raises it to the level of a public health concern.2 It is estimated that 50 to 70 million adults in the United States suffer from a sleep or wakefulness disorder.2,3 Of all the sleep disorders, insomnia is the most prevalent, accounting for 10% to 20% of complaints in primary care settings.4 The treatment approach for insomnia disorders has remained largely the same since the publishing of clinical guidelines in 2008; however, recent research on gender-related pharmacokinetic differences for some drugs has led to a change in the way physicians should prescribe certain agents in women.2,5 This review will highlight these new data and the resulting dosing considerations.
Types of Insomnia
Currently, classifications for insomnia are available in 2 references, the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition (DSM-V) and the International Classification of Sleep Disorders, Second Edition (ICSD-2).4,6 Both references identify various subtypes of insomnia, with the DSM-V classifying insomnia either as a primary disorder or as secondary to some underlying cause. The ICSD-2 is intended for use by sleep specialists and classifies insomnia into various categories; however, these specific categories are beyond the scope of this review.6 Insomnia is further classified based on its duration, with transient insomnia generally classified as symptoms lasting only a few (1-3) nights; acute insomnia, occurring when symptoms last 3 days to less than 4 weeks; and chronic insomnia, occurring when symptoms last more than 4 weeks.7
According to the DSM-V, patients with insomnia complain of difficulty initiating or maintaining sleep or having nonrestorative sleep; the specific diagnostic criteria are summarized in Table 1.4 Nonrestorative sleep is characterized as sleep that is restless, light, or of poor quality.
There are numerous secondary causes of insomnia, including underlying mental disorders, other general medical conditions, and illicit substance or medication use.2,7 Patients with chronic pain syndrome or degenerative diseases may have trouble sleeping because of their pain. Examples of chronic pain syndromes associated with insomnia include fibromyalgia, arthritis, back pain, and headache.8,9
Pain and Sleep
The relationship between pain and difficulty sleeping is complex and has been described as a vicious cycle.8,10-11 Pain intensity has been shown to increase the severity of sleep disturbances, and vice versa.11 Pain-related arousal has been shown to differ from somatic and cognitive arousal.10 In addition, pain is associated with the development of depression and anxiety, which can contribute to sleep difficulties and insomnia. Conversely, pain thresholds may be decreased as a response to disturbed sleep, and it has been observed that a disruption in sleep may actually directly affect nociceptors.12,13 Therefore, management of both pain and insomnia are required for the most benefit.
Insomnia also can be drug induced, especially by substances that result in central nervous system (CNS) stimulation. A list of medications and substances that may adversely affect sleep are summarized in Table 2.2,7,8,10
According to the National Institutes of Health (NIH), there are various risk factors for insomnia.14 The first is age, with rates of insomnia increasing in older patients. This primarily has been attributed to the high prevalence of medical and psychosocial conditions in this patient population, coupled with the frequent use of polypharmacy to treat these conditions.15 Higher rates of insomnia in this patient population also may be a result of older patients having a substantial decline in their arousal threshold (the mechanism that preserves sleep) compared with younger patients.16 Data suggest that older patients are more easily awakened by external noises such as traffic because of diminished sleep intensity.
The NIH also noted that women have a higher prevalence of insomnia, particularly in the postmenopausal years.14 These higher rates have been attributed to a multitude of factors, such as a more frequent occurrence of depression and anxiety in women compared with men, insomnia related to pregnancy, and sleep disorders occurring during the menopausal transition period.17 Furthermore, several studies and surveys have shown a link between pain syndromes and insomnia in women, making this group of patients especially difficult to manage.18 Other NIH-identified groups who have a higher prevalence of insomnia include patients with lower education and income and those who are divorced, separated, or widowed.14 The data for differences in insomnia rates among various racial or ethnic groups are inconclusive.
Insomnia also is commonly observed in patients with comorbid mental disorders.4 In a cohort of the general American population, it was reported that 40% to 60% of patients with insomnia showed symptoms of depression, including 10% to 25% of cases with diagnosed clinical depression; anxiety disorders were diagnosed in 20% to 30% of patients with insomnia.19
A 2008 Clinical Guideline for the Evaluation and Management of Chronic Insomnia provides recommendations for the assessment and treatment of patients with insomnia.2 Patients presenting with insomnia should have a detailed history taken to identify any medical, psychiatric, or substance-related factors that may be contributing to their insomnia. In addition, a thorough sleep history should be obtained. Some elements of the sleep history include characterization of the primary complaint (eg, difficulty falling asleep vs awakenings vs poor sleep), the frequency and duration of insomnia, nocturnal symptoms, impact on daytime activities and functioning, and any past or current treatments and the patient’s responses to them. A physical exam also is recommended to identify risk factors for other sleeping disorders (eg, sleep apnea), such as obesity, increased neck circumference, and upper airway anatomical changes. At minimum, the guideline recommends that clinicians perform the general medical assessment as described above in addition to having patients complete a sleep questionnaire and a 2-week sleep log/diary to help identify sleep patterns. An example of a sleep questionnaire is the Insomnia Severity Index, a 7-item rating to assess patient’s perception of insomnia.