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18 Articles in Volume 11, Issue #9
Pain and Sleep: A Delicate Balance
Management of Insomnia: Considerations For Patients With Chronic Pain
PPM Editorial Board Outlines Management Strategies for Chronic Pain Patients With Insomnia
Attention Deficit Hyperactivity Disorder And Patients With Pain
Dry Needling Offers Relief From Chronic Low Back Pain
Etiology of Chronic Pain and Mental Illness: How To Assess Both
Temporomandibular Disorder: Examining the Cause And Treatments
Highlights From PAINWeek 2011
Is Your Patient Using Heroin?
Medications For Low Back Pain
Nonpharmacologic Treatments for Patients With Sleep Disorders and Pain
Man With Constant, Daily Headache Pain, Photophobia, Phonophobia, and Nausea
Successful Nonoperative Treatment of Persistently Painful Knees Following Total Knee Arthroplasty—A Case Series
Insomnia in Chronic Pain Patients
What Is Going Wrong With Research? Finding the Right Answer
Testing Positive for Marijuana in Urine
Hydrocodone, Carisoprodol, and Alprazolam—A Most Lethal Combination
Pro-inflammatory Diet

Management of Insomnia: Considerations For Patients With Chronic Pain

Sleep is a vital physiologic process, and notable reductions in sleep can have negative physiologic, cognitive, and emotional effects.1 Primary insomnia is estimated to occur in 1% to 10% of the general adult population and in up to 25% in older adults.2 Many patients who suffer from insomnia have impairments in their quality of life as a result of decreased energy, difficulty concentrating, memory impairment, and increased fatigue.2,3 The incidence of insomnia among patients with chronic pain is significantly higher than that in the general population.4 According to data from the National Sleep Foundation, about two-thirds of patients with chronic pain report problems with sleep.

Types of Insomnia
Currently, classifications for insomnia are available in two references, the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and the International Classification of Sleep Disorders, Second Edition (ICSD-2).2,5 Both identify various subtypes of insomnia, with the DSM-IV classifying insomnia as either a primary disorder or secondary to some underlying cause. The ICSD-2 classifies insomnia into various categories; however, these specific categories are beyond the scope of this review.5 Insomnia is further classified based on its duration, with transient insomnia generally classified as symptoms lasting only a few (1-3) days, acute insomnia occurring when symptoms last 3 days to less than 4 weeks, and chronic insomnia occurring when symptoms last more than 4 weeks.6

According to the DSM-IV, patients with primary insomnia complain of difficulty initiating or maintaining sleep or nonrestorative sleep for at least 1 month; the specific diagnostic criteria are summarized in Table 1.2 Nonrestorative sleep is characterized as sleep that is restless, light, or of poor quality.

There are numerous secondary causes of insomnia ranging from underlying mental disorders, other general medical conditions, or those that are related to a substance or medication.6,7 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 headaches.4,8

The relationship between pain and difficulty sleeping is complex and has been described as a vicious cycle.4,9,10 Pain intensity has been shown to increase the severity of sleep disturbances, and vice versa.10 Pain-related arousal has been shown to differ from somatic and cognitive arousal.9 In addition, pain is associated with development of depression and anxiety, which can contribute to sleep difficulties and insomnia.

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 2.4,6,7,9

Risk Factors
In a National Institutes of Health (NIH) statement on insomnia, various risk factors for insomnia were highlighted.11 The first was 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.12 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.13 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.11 These higher rates have been attributed to a multitude of factors, such as 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.14 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.11 Currently, the data for differences in insomnia rates among various racial or ethnic groups are inconclusive.

Assessment
A 2008 Clinical Guideline for the Evaluation and Management of Chronic Insomnia provides recommendations for the assessment and treatment of patients with insomnia.7 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), frequency and duration of insomnia, identification of nocturnal symptoms, impact on daytime activities and functioning, and any past or current treatments and responses. 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 patients’ perceptions of insomnia.

In patients experiencing pain or those with chronic pain, careful assessment is required in order to determine how well the pain itself is being managed.9 The presence of comorbid psychiatric disorders also should be considered. As previously mentioned, depression and anxiety are common in patients with chronic pain and may further exacerbate sleep disturbances and insomnia.

Treatment of Insomnia
Insomnia should be treated when the condition affects daytime functioning, the patient’s overall health, or sleep quality.7 The first step for treatment is the identification and management of comorbid conditions that are associated with insomnia, such as depression or chronic pain, followed by the modification of behaviors or medications (see Table 2) that can worsen insomnia. If medications that are associated with insomnia cannot be discontinued or switched, consideration should be given to adjusting the timing of administration. The main goals for treating insomnia include improving sleep time and/or quality and reducing daytime impairments. The recommended treatment approach involves pharmacologic and nonpharmacologic interventions.

Nonpharmacologic Therapy For Insomnia
There are numerous cognitive and behavioral interventions for patients with insomnia.7 Some of these interventions include stimulus control, relaxation training, cognitive-behavioral therapy for insomnia (CBT-I), sleep restriction, paradoxical intention, biofeedback, sleep hygiene, and multicomponent therapy. The guidelines recommend stimulus control, relaxation training, and CBT-I with or without relaxation therapy as the standards of care for nonpharmacologic management of chronic insomnia. The other interventions also are noted to be useful, but with less evidence supporting their efficacy.

Stimulus control focuses on having patients go to bed only when sleepy and avoid staying awake in bed for prolonged periods of time.7 Patients are instructed to remove themselves from bed if they are not asleep within 20 minutes and to engage in a relaxing activity until they are drowsy again. Relaxation training can include techniques such as progressive muscle relaxation, guided imagery, or abdominal breathing. Finally, the last standard, CBT-I treatment, combines cognitive therapy with behavioral interventions such as stimulus control or sleep restriction. Cognitive therapy is designed to help patients change their beliefs and unrealistic expectations about sleep. Specifically, for patients with chronic pain who are experiencing insomnia, a hybrid approach involving CBT-I combined with pain management programs has been suggested.10

Educating patients with insomnia on proper sleep hygiene techniques is a common nonpharmacologic intervention used by many general practitioners.6,15 The guideline recommends that sleep hygiene education be performed in conjunction with stimulus control, relaxation training, sleep restriction, or cognitive therapy.7 Elements of good sleep hygiene education are summarized in Table 3 (see page 50).

Pharmacologic Therapy for Insomnia
According to the guidelines, choice of drug therapy depends on many factors, such as specific symptoms and sleep patterns, previous response to treatment, patient preference, cost, comorbid conditions, and drug–drug interactions.7 Several classes of medications have been used to treat insomnia; however, only three classes have FDA-approved labeling for insomnia. These are the benzodiazepine receptor agonists (benzodiazepines and nonbenzodiazepine hypnotics), the antidepressant doxepin (Silenor), and the melatonin receptor agonist ramelteon.16 Table 4 summarizes the FDA-approved medications as well as other prescription products that have evidence for use in managing insomnia.7,9,11,16-19

Prescription Medications
First-line therapy is a short- or intermediate-acting benzodiazepine receptor agonist such as zaleplon (Sonata), zolpidem (Ambien), eszopiclone (Lunesta), triazolam (Halcion), or temazepam (Restoril), or the melatonin receptor agonist ramelteon (Rozerem).7 Benzodiazepines have sedative, anxiolytic, muscle relaxant, and anticonvulsant properties through agonistic effects at the γ-aminobutyric acid (GABA) receptor.19 The newer nonbenzodiazepine sedative-hypnotics have only sedative properties. The guidelines do not give preference to a specific medication. Zaleplon and ramelteon are effective in reducing sleep latency, but because of their short half-lives, they are not as effective in reducing wakefulness after sleep onset. Intermediate-acting agents such as temazepam and eszopiclone can be used to improve sleep maintenance. One caveat is that longer-acting agents have a greater potential to lead to residual sedation or next-day effects.

Patients with chronic pain managed with opioids should avoid benzodiazepines because of overlapping CNS effects that can lead to increased sedation and confusion.9 Other side effects associated with benzodiazepines include anterograde amnesia and rebound insomnia when the agents are discontinued.19 These agents should be used with caution in elderly patients because of the increased risk for falls in this population. Tolerance to benzodiazepines can develop after 1 month of use. Nonbenzodiazepine sedative-hypnotic agents have demonstrated similar efficacy to benzodiazepines but have the advantage of less residual sedation.

Patients with comorbid depression may be managed with low-dose sedating antidepressant therapy.7 Examples of agents include trazodone, mirtazapine, doxepin, and amitriptyline. The guidelines do not give preference to any specific antidepressant. It has been suggested that patients with chronic pain can be successfully managed with sedating antidepressants because there is a high prevalence of comorbid depression, and antidepressants have some analgesic effects.9 Daytime side effects can be problematic because of the prolonged half-life of many of the antidepressants (see Table 4). Tricyclic antidepressants (TCAs) have been associated with anticholinergic effects (urinary retention, constipation, dry mouth) and cardiac conduction abnormalities. Trazodone is not associated with significant anticholinergic effects to the extent that the TCAs are, and it is not associated with dependence; therefore, it may be a valuable option for patients with a history of substance abuse.7,19 However, trazodone has been associated with orthostatic hypotension and priapism in men.6,19 Of note, the low doses of antidepressants (commonly trazodone) used for insomnia are inadequate to manage depression but can have additive efficacy for depression when used in combination with another antidepressant given at full-dose for depression.7

Once an agent has been selected, it is reasonable to treat acute insomnia for 2 to 4 weeks.7,9,17,19 The lowest effective dose of the agent should be used for the shortest duration of time necessary. Consideration may be given to treating chronic insomnia intermittently, for example, two to five times per week.7 There is a lack of data on chronic use of sedative-hypnotics; however, such use is noted to occur in practice.7,19 Open-label extension trials have been conducted for eszopiclone and zolpidem for up to 12 months.7 Patients receiving long-term sedative-hypnotics should be followed and reevaluated at least as often as every 6 months. For patients who do not respond to initial therapy, it is reasonable to try another agent from the same class with careful consideration of specific sleep disturbances. Insomnia is treated in the same manner in patients with or without chronic pain. However, pain control must be optimized and any comorbid psychiatric disorders should be identified and managed when treating patients with chronic pain and insomnia. The guidelines suggest the use of gabapentin or pregabalin (Lyrica) for pain control for selected patients as appropriate because these agents are associated with somnolence.

Over-the-Counter (OTC) Agents/Dietary Supplements
Sedating antihistamines and certain dietary supplements have been used for the management of insomnia.7,19 Antihistamines are generally safe and effective for mild insomnia; however, definitive evidence of efficacy is lacking. Similar to TCAs, anticholinergic side effects occur with antihistamines, and these effects are likely to be more problematic in elderly patients. Diphenhydramine (Tylenol PM) and doxylamine (Unisom) are the agents used. Dietary supplements including valerian, melatonin, and l-tryptophan also have been used to treat insomnia.11 Dietary supplements are not regulated by the FDA, and there may be variations in the content of the product compared with the labeling. The OTC agents, including dietary supplements, used for insomnia are summarized in Table 5.7,11,19

Summary
Insomnia is a common medical problem associated with significant quality of life impairments for affected patients, including difficulty concentrating, memory impairment, decreased productivity at work, and an increased risk for accidents. The economic burden of insomnia is substantial in terms of direct and indirect costs to the US healthcare system. Patients with chronic pain have an increased incidence of insomnia compared with the healthy population. The underlying mechanisms between chronic pain and insomnia are complex, but it is believed that emotional arousal plays a role in addition to somatic arousal.

Treatment of insomnia employs both nonpharmacologic interventions and drug therapy. Management of patients with chronic pain and insomnia should first be directed at adequate pain control and assessment for concurrent depression. Clinicians should be aware of the potential for additive sedation in patients receiving opioid analgesics and sedative-hypnotic agents.

Sedative-hypnotic agents should be used at the lowest effective dose and shortest duration possible with close follow-up of the patient to assess response.

Last updated on: December 28, 2011
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