Journal of Psychosocial Nursing and Mental Health Services

Psychopharmacology 

Insomnia: Will Medication Bring Rest?

Barbara J. Limandri, PhD, PMHNP, BC

Abstract

Acute and chronic insomnia are common and difficult clinical problems that contribute to and are consequences of other mental and physical health problems. It is tempting to treat insomnia with medications for rapid relief; however, these medications have significant side effects that add health burden and may cause tolerance and dependency. First-line treatment for insomnia is cognitive-behavioral therapy for insomnia (CBT-I); however, this is less frequently prescribed than benzodiazepine and non-benzodiazepine sedative hypnotic agents. Prudent primary care and mental health clinicians should screen for insomnia using valid and reliable tools when clients report sleep difficulties. When screening is positive, further assessment with a sleep diary is warranted. The primary treatment for insomnia is CBT-I, and pharmacological treatment may provide temporary support for no more than 2 to 4 weeks. Non-benzodiazepine hypnotic agents, histamine blocking medications, dual orexin receptor antagonists, and over-the-counter herbal supplements may serve as adjuncts. [Journal of Psychosocial Nursing and Mental Health Services, 56(7), 9–14.]

Abstract

Acute and chronic insomnia are common and difficult clinical problems that contribute to and are consequences of other mental and physical health problems. It is tempting to treat insomnia with medications for rapid relief; however, these medications have significant side effects that add health burden and may cause tolerance and dependency. First-line treatment for insomnia is cognitive-behavioral therapy for insomnia (CBT-I); however, this is less frequently prescribed than benzodiazepine and non-benzodiazepine sedative hypnotic agents. Prudent primary care and mental health clinicians should screen for insomnia using valid and reliable tools when clients report sleep difficulties. When screening is positive, further assessment with a sleep diary is warranted. The primary treatment for insomnia is CBT-I, and pharmacological treatment may provide temporary support for no more than 2 to 4 weeks. Non-benzodiazepine hypnotic agents, histamine blocking medications, dual orexin receptor antagonists, and over-the-counter herbal supplements may serve as adjuncts. [Journal of Psychosocial Nursing and Mental Health Services, 56(7), 9–14.]

In 2013, Americans slept an average 6.8 hours per day, with 40% sleeping <6 hours per day, even though the American Academy of Sleep Medicine recommends at least 7 hours of sleep per day for individuals ages 18 to 60 (Howe, 2017). These statistics indicate that approximately 35% of U.S. adults are sleep deprived to some degree every day (Centers for Disease Control and Prevention, 2016).

Consequences of poor sleep include missed days from work, loss of productivity, vehicle crashes, and increased health care use for depression, alcohol abuse, cardiovascular disease, diabetes, obesity, and cancer (Howe, 2017). When sleep disturbance continues for days to months and is accompanied by other symptoms, the problem can be redefined as insomnia. This term, however, is frequently misunderstood and has different meanings for lay people as well as health care professionals. To lay people, it can mean difficulty falling asleep or finding time to sleep due to excess work and leisure activity. Polysomnographic evidence of disturbed sleep includes long sleep latency, frequent awakenings, prolonged periods of wakefulness during the sleep period, and/or frequent transient arousals (Roth, 2007). In addition, patients describe difficulty falling asleep, staying asleep, or not feeling rested upon awakening despite adequate opportunity to sleep. These symptoms and signs continue for at least 3 times per week for a duration of 1 month to be classified as insomnia (Roth, 2007). Patients usually seek help from primary care providers who likely prescribe a sedative hypnotic agent in the benzodiazepine or nonbenzodiazepine class as a first-line intervention, and that prescription may be refilled several times (Kaufman, Spira, Alexander, Rutkow, & Mojtabai, 2016). To complicate the matter, individuals with sleep disorders are more likely to misuse hypnotic prescriptions than those with anxiety or depressive disorders (Guina & Merrill, 2018). Although sedative hypnotic agents are approved for short-term use only (i.e., 2 to 4 weeks), with no studies on long-term use, 53% of patients continue to use these medications sporadically for 3 to 5 years and 60.4% continue to use them regularly for an average of 10 years (Reynolds & Ebben, 2017).

Defining the Problem

Insomnia is the most common sleep disorder and includes acute insomnia, chronic insomnia, primary insomnia, and secondary insomnia, all of which are referred to as insomnia disorder in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association [APA], 2013; Jungquist, 2011). The diagnosis of insomnia disorder requires either difficulty initiating or maintaining sleep or early morning awakening with the inability to return to sleep that causes clinically significant distress or occupational impairment and persists at least 3 nights per week for at least 3 months and cannot be explained by any other sleep–wake disorder, physiological effects of a substance, or coexisting mental or physical disorder (APA, 2013). The pathophysiology is likely attributable to hypothalamic dysfunction and/or melatonin production (Jungquist, 2011), hyperarousal of the hypothalamic pituitary adrenal axis, and negatively toned cognitive activity (e.g., worry, ruminations) (Roth, 2007). Factors that contribute to developing insomnia include stress, high arousability, poor self-rated general health, higher bodily pain, positive family history of insomnia, menopause, depression, anxiety, and substance abuse (LeBlanc, 2009). In addition, the likelihood of sleep disturbance increases with age (Manjavong, Limpawattana, Mairiang, & Anutrakulchai, 2016; Skottheim, Lövheim, Isaksson, Sandman, & Gustafsson 2018). Chronic insomnia is associated with physical illnesses, including heart disease, cancer, hypertension, neurological diseases, autoimmune disorders, and gastrointestinal disorders (Jungquist, 2011).

Many psychiatric disorders include the symptom of sleep disturbance, which can be either a consequence or cause of the psychiatric disorder, especially depressive, anxiety, and bipolar disorders (Roth, 2007). Lack of sleep and poor quality sleep are manifested by impaired cognitive and physical functioning, daytime drowsiness, persistent fatigue, poor memory, impaired learning, and suppressed immunity (Jungquist, 2011).

Screening and Assessment

Because sleep disturbance is a pervasive problem in the United States with serious health consequences, all health care providers should be advised to screen patients, especially when comorbid health problems are present. The Epworth Sleepiness Scale (access http://yoursleep.aasmnet.org/pdf/Epworth.pdf), Brief Insomnia Questionnaire (access https://www.hcp.med.harvard.edu/wmh/ftpdir/affiliatedstudies_BIQ.pdf), and Insomnia Screening Questionnaire (access https://centreforsleep.com/archive/assets/images/pdf/insomnia_assessment_guideline07.pdf) are all valid and reliable tools that are easy to administer to adults in any clinical setting. A positive screen necessitates deeper assessment to clarify specifics of the sleep disorder, which includes asking clients to maintain a sleep diary. A sleep diary helps identify patterns and habits and motivates clients to solve the sleep problem. The diary provides a structured format that is easy for clients to keep for at least 1 month and up to 6 months. Several formats are available online (e.g., access https://sleepfoundation.org) or as smartphone applications. Information that clients record every day includes:

  • time to bed,
  • time spent out of bed after initially going to bed,
  • amount of time to fall asleep,
  • number of awakenings during the sleep period,
  • total hours of sleep, and
  • feeling upon awakening.

In addition, at the end of the day before going to bed, clients record:

  • amount of caffeine consumed during the day and last consumption,
  • duration of exercise and time,
  • nap times and frequency,
  • times/circumstances of feeling drowsy,
  • mood, and
  • bedtime routine.

With this information, clinicians can target problem behaviors and clarify whether and when medication can complement the treatment approach.

Treatment Strategies

The first-line approach to treating insomnia is cognitive-behavioral therapy for insomnia (CBT-I) as recommended by the National Institutes of Health, American Academy of Sleep Medicine, and American College of Physicians (Burman, 2017; Reynolds & Ebben, 2017). CBT-I requires special training to conduct this 6-week intervention and can be done on an individual or group level. Training is available to generalist and advanced practice psychiatric–mental health nurses online (access http://www.myshuti.com) or through educational institutions, such as University of North Carolina or Duke University. CBT-I provides significant improvement in duration and quality of sleep with sustainable effectiveness for at least 6 months and has demonstrated effectiveness with sleep disturbances of many kinds, including posttraumatic stress disorder and nightmares (Reynolds & Ebben, 2017). This therapy is especially beneficial in improving cognitive functioning with long-term improvements after treatment (Herbert, Kyle, & Pratt, 2018). The Table describes the elements of CBT-I.

Strategies For Cognitive-Behavioral Therapy for Insomnia

Table:

Strategies For Cognitive-Behavioral Therapy for Insomnia

Clinicians may refer clients for CBT-I as well as teach them basic sleep hygiene skills, such as: going to bed at the same time every night and awakening at the same time every day, no caffeine within 5 hours before bedtime, moderate exercise no later than 4 hours before bedtime, use of bedroom for sleep and sex only, no blue light screens within 1 hour of bedtime, and no heavy food intake within 4 to 5 hours of bedtime (Jungquist, 2011).

Pharmacotherapy for Sleep Disturbance

Benzodiazepine Receptor Agonists

In addition to CBT-I, clinicians may prescribe a sedative-hypnotic agent for short-term use while clients participate in more sustainable treatment. Prior to 2000, benzodiazepine receptor agonist agents (BZD; e.g., triazolam, flurazepam, temazepam, estazolam, quazepam) were the mainstay in treating insomnia (Kaufman et al., 2016) and then non-BZD were introduced with the promise of equal efficacy and less tolerance or dependence (Krystal, 2017). BZD are GABA-A modulators that bind on the GABA-A benzodiazepine binding site to enhance GABA inhibition of the wake-promoting areas of the brain and promote sleep. They are effective for sleep-onset and sleep maintenance problems with significant half-lives of at least 8 hours, thereby contributing to hangover and daytime sleepiness (Krystal, 2017). They are approved by the U.S. Food and Drug Administration (FDA) for the short-term treatment of acute insomnia with the recommended limit of 2 to 4 weeks of daily or regular use. There are no studies to indicate long-term use of BZD for insomnia (Guina & Merrill, 2018). Side effects include dizziness, ataxia, psychomotor agitation, dependence, poor concentration, fatigue, memory impairments, nightmares, suicidal ideation, delirium, depression, emotional numbness, anxiety, irritability, weight gain, and rebound insomnia (Guina & Merrill, 2018). BZD are contraindicated in individuals with substance abuse disorders, depression, suicidal ideation or behaviors, bipolar disorder, and neurocognitive disorders including traumatic brain injuries (Guina & Merrill, 2018). The most significant problems with BZD for insomnia are tolerance, dependence, and rebound insomnia. Many clients who have been taking this class of drugs will state they cannot sleep without them; however, what they are experiencing is rebound insomnia that long-term use will cause and disguise. When clients with long-term use of BZD for insomnia present, clinicians must educate them about the need for a withdrawal program and concurrent alternative treatments for insomnia. Initially, alternative treatments will be relatively ineffective but will improve within a few weeks depending on the extent of BZD dependence. Therefore, clinicians need to be particularly supportive of clients, compassionate to their drug-related irritability and frustration, and patient with the process of recovery.

Non-Benzodiazepine Receptor Agonists

With the introduction of non-BZD, it was possible to improve sleep onset without next-day persistent drowsiness. These drugs, often referred to as “Z drugs,” have a much shorter half-life of between 2 and 4 hours and could bring about sedation within 20 to 30 minutes yet diminish within 8 hours to allow a refreshed awakening. Non-BZD also target the GABA-A receptors but are chemically different from BZD. Non-BZD agents approved by the FDA include: zolpidem, zaleplon, and eszopiclone (Krystal, 2017). They have the same efficacy as BZD but are more limited to the broad inhibitory effects of BZD, and therefore were assumed to have minimal effect on anxiety and lower tolerance and dependence potential. Non-BZD target sleep-onset problems with less benefit to sleep maintenance. Eventually, however, pharmaceutical companies introduced long-acting formulations for zolpidem, and eszopiclone has a longer half-life to provide effective sleep maintenance (Krystal, 2017). The side effect profiles are similar to BZD, with the most serious adverse reactions including depression exacerbation, suicidal ideation, aggressive behavior, hallucinations, impaired next-day mental alertness and judgment, anterograde amnesia, and parasomnias (e.g., sleep walking, talking, eating, driving). Less serious and common side effects include headache, dizziness, nausea, and unpleasant taste with eszopiclone. Zaleplon may contribute to dependence (Jungquist, 2011; Krystal, 2017).

Melatonin Receptor Agonists

There are two hypnotic agents that target melatonin, the hormone secreted by the pineal gland to regulate circadian rhythm. Melatonin binds to the G protein-coupled melatonin 1 receptor that inhibits activity at the suprachiasmatic nucleus of the hypothalamus to bring about changes in phases of the circadian cycle in response to light (Krystal, 2017). When taken at doses exceeding naturally occurring melatonin (i.e., >1 mg), it induces the sleep cycle. However, this mechanism is easily overridden voluntarily by individuals viewing blue light screens at bedtime. Curiously, melatonin does not cause drowsiness, except as experienced as placebo (Rose & Bourguignon, 2011). Instead, it turns off the reticular activating system to ready the brain for sleep (Jungquist, 2011; Krystal, 2017). Because melatonin is an over-the-counter (OTC) medication and not FDA regulated, dosing varies widely between 1 mg and 10 mg, with 2 mg to 3 mg found to be effective for sleep onset. Melatonin is reasonably safe with dose-related side effects of headache, dizziness, nausea, and irritability (Jungquist, 2011).

Ramelteon (Rozarem®) is a FDA–approved prescription drug for treating insomnia. It is a melatonin 1 and melatonin 2 receptor–specific agonist for naturally occurring melatonin and is more potent than exogenous melatonin. Ramelteon is effective in inducing sleep onset with little evidence of effectiveness in maintaining sleep. It has relatively few side effects like melatonin and no evidence of abuse potential (Krystal, 2017).

Selective Histamine Receptor Antagonists

Antihistamine agents, such as diphenhydramine and doxylamine, block the histamine 1 receptor to induce drowsiness (Krystal, 2017). Although not FDA approved for treating insomnia, they are frequently used as self-medication by clients to help with sleep onset. When combined with an OTC nonsteroidal anti-inflammatory drug (e.g., Excedrin® PM), they serve to relieve minor pain that interferes with sleep as well as induce drowsiness.

Other histamine prescription drugs may be used off-label to induce sleep onset due to the side effect of drowsiness. These medications include doxepin, trazodone, and amitriptyline. Given in lower doses than used for treating depression, these medications serve as effective hypnotic agents without the potential for tolerance or dependence (Jaffer et al., 2017; Wichniak, Wierzbicka, Walecka, & Jernajczyk, 2017) .

Of interest is the use of quetiapine (Seroquel®) in low doses for insomnia in the absence of psychotic symptoms. Quetiapine has been used with adolescents and adults to induce sleep onset by virtue of significant histamine receptor antagonism. It is given at lower dosages (25 mg to 100 mg) but often requires increased dosing when used long term. Side effects include hyperlipidemia, extrapyramidal symptoms, tardive dyskinesia, dystonia, neuroleptic malignant syndrome, QT prolongation, hyperglycemia, orthostatic hypotension, weight gain, and hypertension (Chow et al., 2017). These significant side effects need to be weighed against the benefits of sleep induction, especially with safer alternatives available (Chow et al., 2017; Cornelis et al., 2017). Similarly, mirtazapine (Remeron®) is often prescribed in low doses (7.5 mg to 15 mg) for its sedating effect. Quetiapine and mirtazapine increase sleep onset, duration of deep sleep, and non-REM sleep for improved sleep quality. However, both have been found to cause daytime sleepiness, reduced sustained attention, and impaired learning (Karsten, Hagenauw, Kamphuis, & Lancel, 2017). Consequently, they need to be used with caution in the short term until alternative treatments can help.

Dual Orexin Receptor Antagonists

The newest drug on the market to treat insomnia and sleep disorders is suvorexant (Belsomra®), a drug that blocks orexin. Orexin, also known as hypocretin, is a neuropeptide that selectively regulates wakefulness and appetite in the lateral hypothalamus. By blocking the orexin receptor, suvorexant promotes sleep by diminishing wakefulness. In doing so, it avoids altering the overall sleep architecture and permits cognitive functioning upon awakening (Lee-Iannotti & Parish, 2016). Therefore, if sleep is necessarily interrupted, individuals can perform cognitive tasks and respond to stimuli without impairment. Suvorexant is given at 10 mg within 30 minutes of bedtime with a maximum dosage of 20 mg (Tannenbaum et al., 2016). Side effects of suvorexant include drowsiness, dizziness, headache, unusual dreams, and dry mouth (Tannenbaum et al., 2016). Although it is a schedule IV drug, there is little evidence of tolerance, dependence, or abuse potential (Born, Gauvin, Mukherjee, & Briscoe, 2017; Schoedel et al., 2016).

Herbals and Nutraceuticals

In addition to FDA–approved drugs, Chinese herbs and nutraceuticals have shown modest effectiveness in treating insomnia. Three Chinese herbs, suanzaoren decoction, fuling, and gancao, act on the GABA-A receptor similar to BZD without tolerance and dependence (Singh & Zhao, 2017). These agents are prescribed by a professional herbalist. OTC herbals, such as valerian, verbena, lavender, and passionflower, have modest effect on sleep onset and little effect on sleep maintenance; however, the side effect profile is neutral with no evidence of tolerance or dependence (Taslaman, 2014; Yarnell, 2015).

Summary

Acute and chronic insomnia are common and difficult clinical problems that contribute to and are a consequence of other mental and physical health problems. It is tempting to treat insomnia with medications for rapid relief; however, these medications have significant side effects that add health burden and may have tolerance and dependency. First-line treatment for insomnia is CBT-I; however, this is less frequently prescribed than BZD and non-BZD sedative hypnotic agents. Based on a review of the literature, a prudent course of action clinicians should take with clients who report sleep difficulties includes:

  • Screening for insomnia using the Epworth Sleepiness Scale, Brief Insomnia Questionnaire, or Insomnia Screening Questionnaire.
  • Following a positive screen with further assessment by having clients keep a sleep diary for at least 1 month.
  • Ordering a sleep study if more complex sleep disturbance is apparent in the sleep diary (e.g., snoring, night terrors or nightmares, apnea).
  • Recommending CBT-I or referral to a therapist trained in this modality.
  • Instructing clients in sleep hygiene practices and monitoring effective use.
  • Parsimoniously prescribing sedative hypnotic agents for no longer than 2 to 4 weeks while initiating other treatment strategies.
  • Monitoring effectiveness of treatment for at least 6 months, with annual visits in primary care for relapse.

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Strategies For Cognitive-Behavioral Therapy for Insomnia

Strategy Explanation
Stimulus control Identifies stimuli that interfere with sleep and benefits sleep
Sleep restriction Sets strict limits on the time spent in bed. Initial limit is the amount of time the client is spending currently (e.g., 5 hours) and increases gradually to the amount needed for quality sleep.
Relaxation training and biofeedback Teaches the client how to relax the mind and body
Cognitive control and psychotherapy Identifies the attitudes and beliefs that keep the client awake and introduces approaches to block negative thoughts and beliefs
Sleep hygiene training Teaches specific patterns and habits for healthy sleep
Authors

Dr. Limandri is Professor Emerita, Linfield College, School of Nursing, McMinnville, Oregon.

The author has disclosed no potential conflicts of interest, financial or otherwise.

Address correspondence to Barbara J. Limandri, PhD, PMHNP, BC, Professor Emerita, 9136 SW 36th Avenue, Portland, OR 97219; e-mail: limandribj@gmail.com.

10.3928/02793695-20180619-03

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