To view this article in PDF form, click here.

The ZZZs to success: A good night’s sleep is more than beauty rest

Insomnia is more complex than just not getting a good night’s sleep. If left untreated, the condition can compromise quality of life. Patients may also develop more serious conditions.

Clint Bastible, MPAS, PA-C; Natasha Cha, MPAS, PA-C

Clint Bastible is a physician assistant at Wellness in Sleep, Fort Worth, Texas. Natasha Cha is a physician assistant in the Department of Internal Medicine, University of North Texas Health Science Center, Fort Worth. The authors have indicated no relationships to disclose relating to the content of this article.

Any PA on call through the night or student cramming for finals can verify the importance of sleep and the effects of a lack of sleep. The American Academy of Sleep Medicine (AASM) defines insomnia as difficulty initiating sleep or remaining asleep, waking up too early, or having nonrestorative sleep despite adequate circumstances and opportunity for sleep.¹ In addition, the patient must experience at least one of the following: fatigue or malaise; focus or memory difficulty; poor performance at work, school, or home; mood disturbance or irritability; daytime somnolence; decrease in energy or motivation; increased susceptibility to errors or accidents at work or while driving; increased concerns about sleep; or tension headaches or GI symptoms in response to sleep loss.¹

When insomnia lingers, it can severely impact daily functioning and quality of life. Limited sleep can quickly lead to a depressed mood, slowed working memory, reduced cognitive processing, and lapses of attention. Sleep restriction can also lead to an increased risk of obesity, cardiovascular events, traffic accidents, and death.² Sleeping only 4 hours at night has been shown to be equivalent to a blood alcohol concentration of 0.095%.³ This article reviews the epidemiology, etiology, classification, clinical presentation, diagnosis, and treatment of insomnia.

EPIDEMIOLOGY

Sleep is divided into nonrapid eye movement (NREM) and rapid eye movement (REM) states. In adults, REM sleep constitutes approximately 20% to 25% of sleep and NREM the remaining 75% to 80%. NREM is further divided into stages 1 to 4 during which lower pulse, ventilation, arterial BP, and cardiac output occur compared to the awake state.⁴ REM-NREM sleep cycles last approximately 90 minutes, with an average of 4 to 6 cycles per night. Each REM state varies in duration but increases in length through the night. In polysomnography, REM states are marked by a tone decrease on electromyography, desynchronized waves on electroencephalography (EEG), and the hallmark finding of paroxysmal rapid eye movements recorded by electrooculography.^4,5

Insomnia is the most common sleep complaint; approximately 30% to 40% of adults suffer from the disorder. Insomnia with daytime impairment or marked distress affects approximately 10% of the adult population.⁶ A recent study found that health care costs for patients with insomnia were $3,200 higher than for patients without insomnia.⁷ Prescription drug costs, sick leave costs, short- and long-term disability costs, and workers’ compensation also were higher in patients with insomnia compared to patients without the disorder.⁷

ETIOLOGY/PATHOLOGY

Insomnia is classified by duration; transient lasts days to weeks and chronic lasts a month or longer.⁸ Insomnia is further classified by cause. In primary insomnia, no distinct etiology is found; in secondary insomnia, the condition develops as a result of a specific cause.

Parkinson’s disease, stroke, incontinence, arthritis, heart failure, pulmonary disorders that cause dyspnea when supine, hyperthyroidism, renal failure, and GI disorders such as reflux disease or heartburn increase the prevalence of insomnia.^4,8 Patients with insomnia have a high prevalence of other psychiatric disorders such as anxiety, obsessive-compulsive disorder, and depression.⁹

Insomnia can be more specifically defined by its cause or trigger. Adjustment or acute insomnia is caused by a psychologic, physiologic, interpersonal, environmental, or physical stressor. This type of insomnia resolves with removal of or adaptation to the stressor. Inadequate sleep hygiene insomnia is the result of poor sleep habits. Idiopathic insomnia has no identifiable cause, begins in childhood, and is lifelong. Paradoxical insomnia is when no objective evidence of a sleep disturbance can be found. Psychophysiologic insomnia occurs with an excessive amount of worry and anxiety about sleep. Insomnia caused by drug or substance abuse, a medical condition, or a mental disorder are forms of secondary insomnia.^1,10

CLINICAL PRESENTATION

Patients often present complaining of having difficulty falling asleep at night, waking up during the night, waking up too early in the morning, having daytime fatigue/sleepiness, or having daytime irritability. Including the patient’s sleeping partner in the discussion of possible causes is often helpful. Important components of the history are insomnia duration and triggers. Patients should be questioned about their night-time behaviors such as snoring, night sweats or hot flushes, palpitations, choking for air, leg movement, sleep-walking, sleep-eating, acting out dreams, or any other behaviors that occur during or shortly before sleeping. Daytime functioning is also important. Impairments such as falling asleep while driving or while at work should be documented.¹¹

Current medications the patient is taking, including prescription drugs, OTC supplements, herbs, caffeine, nicotine, alcohol, and illicit drugs, should be reviewed. The effects of caffeine can last up to 14 hours; alcohol can promote the onset of sleep but interferes with sleep as the night progresses; and OTC herbal supplements with valerian root extract, cava-cava, chamomile, and ginseng may either cause insomnia or their withdrawal or wearing-off affects sleep.⁵ In general, some medications that treat depression, hypertension, asthma, allergic rhinitis, attention-deficit/ hyperactivity disorder, or narcolepsy may cause insomnia directly or during withdrawal.⁵ Oftentimes it is difficult for the patient or the bed partner to recall specific night-time events. A sleep diary can often help qualify and quantify sleep; however, correlation between subjective and objective reports can be poor to modest.¹¹

AASM states the physical examination is an important element in the evaluation of patients with insomnia and other medical symptoms.⁹ However, few physical examination findings point to a definitive diagnosis of a sleep disorder unless a cataplectic episode, an emotional state that causes some degree of paralysis in the patient, is witnessed.⁵ Physical examination findings such as weight and height evaluation for obesity, neck girth, nasal or pharyngeal obstruction, receding jaw, and hypertension can rule out causes such as sleep apnea.⁵ A joint and muscle evaluation can determine if osteoarthritis pain or fibromyalgia—which often causes fatigue and tenderness at specific muscle points—is causing the patient’s insomnia.⁵

DIAGNOSIS

Generally, insomnia is diagnosed by a combination of the history, physical examination, and information from the patient and his or her bed partner. In a routine evaluation of insomnia, polysomnography is not indicated unless a comorbid sleep disorder such as apnea is suspected.⁹ A multiple sleep latency test is not indicated unless narcolepsy is suspected.⁹ Actigraphy, a test performed by the patient wearing a device on the wrist that measures movement, has not been fully validated for evaluating insomnia.⁸

Insomnia can have many underlying causes. A crawling, restless, uncomfortable sensation in the legs may suggest restless leg syndrome.¹¹ Snoring, choking, or gasping for air, night sweats, and palpitations, as well as obesity, increased neck girth, and small airway size, suggest obstructive sleep apnea.^4,5,11 Early morning awakenings may suggest depression; difficulty falling asleep may suggest anxiety issues.⁵ Narcolepsy can manifest as suddenly falling into a deep sleep, daytime sleepiness with frequent naps throughout the day, episodes of muscle group paralysis while awake, or hallucinations while falling asleep. Advanced phase and delayed phase syndromes manifest when the patient’s sleep schedule has changed to earlier or later than the average person’s bedtime. Advanced phase syndrome is more common in the elderly because they go to bed early in the evening and awake early in the morning. Delayed phase syndrome is more common in teenagers and young adults who have later bedtimes and then sleep in until late in the morning.¹ An enlarged prostate and incontinence may cause frequent awakenings during the night.⁵ Although occurring less frequently than other causes, parasomnias, such as sleep-walking, sleep-eating, and REM behavioral sleep disorder (the patient acts out his or her dreams), may lead to poor sleep quality.

PHARMACOLOGIC TREATMENT

OTC agents Patients frequently try OTC sleep aids containing antihistamines before presenting for evaluation. Systematic evidence of the efficacy of antihistamines is not available, and side effects such as decreased cognitive processing and remaining sedation the next day are major concerns.⁸ Melatonin, a hormone believed to play a role in the sleep-wake cycle, is available as an OTC herbal supplement. Montes and colleagues compared melatonin 0.3 mg, 1 mg, and placebo and found no significant difference in sleep EEG or improvement in subjective sleep quality.¹² This study included only 10 patients who took each dose for 1 week. Larger studies are needed to verify this finding.

Nonbenzodiazepine hypnotics These drugs are preferred over traditional benzodiazepines because of their selectivity for the benzodiazepine type 1 receptor subtype on the gamma-aminobutyric acid (GABA_A) receptor complex. Nonbenzodiazepine hypnotics are associated with fewer side effects and less addictive potential compared to benzodiazepines. Glass and colleagues concluded that the sleep-inducing benefits of benzodiazepines may not justify the increased risk of adverse effects, especially in patients with existing cognitive or psychomotor risks.¹³

Zolpidem resulted in less somnolence the next day, longer stage 3 and 4 periods, and equal efficacy in improving sleep quality and decreasing nocturnal awakenings than was experienced with a short-acting benzodiazepine.¹⁴ A newer form of zolpidem combines an immediate- and prolonged-release formulation and was shown to be superior to placebo in decreasing sleep latency and duration and nightly awakenings; however, a short rebound insomnia was observed in patients after abrupt discontinuation of the medication.¹⁵

Zaleplon, another short-acting nonbenzodiazepine hypnotic, did not show residual sedation when administered in the middle of the night or when checked 5 to 6¹/₂ hours later.¹⁶ Allain and colleagues compared zaleplon, 10 mg, with zolpidem, 10 mg. In diurnal wakefulness and quality-of-day life, patients rated both drugs similarly; however, zolpidem was rated significantly higher in quality of sleep and onset of sleep.¹⁷

Eszopiclone was shown to decrease onset of sleep and increase sleep efficiency and total sleep time compared to placebo. Dosages of 3 mg and 3.5 mg showed decreased night-time awakenings compared to placebo.¹⁸ In a 12-month study of patients on eszopiclone, patients continued to show improvement from baseline in sleep latency, number of awakenings and wake time after sleep onset, sleep time, and sleep quality.¹⁹

Benzodiazepines Short-acting benzodiazepines were the traditional treatment of choice for insomnia; however, these drugs are now used as a second-line treatment for patients who do not respond to other medications because of an increased risk of dependence. In a randomized, controlled trial, patients were given temazepam, 20 mg, or zolpidem, 10 mg, for 4 weeks and then the drug was stopped. There was no significant difference in rebound insomnia between the two medications, and both agents significantly improved total sleep time and decreased time to onset of sleep.²⁰ In another study, flurazepam showed significant residual sedative effects 5 to 6½ hours after administration compared to zaleplon.¹⁶

In 2007, the FDA requested a label change on medications commonly used to treat insomnia to warn of potential adverse events such as angioedema, anaphylaxis, and complex sleep-related behaviors such as driving, making phone calls, and preparing and eating food while asleep. This warning specifically lists some benzodiazepines, nonbenzodiazepine hypnotics, ramelteon, ethchlorvynol, and barbiturates. Further clinical studies to assess the frequency of these events and which medications cause these effects more readily are recommended.²¹

Antidepressants Many antidepressants are used off label for insomnia; however, potentially significant adverse events are possible. Trazodone has been shown to improve several sleep parameters for 2 weeks, but longer studies are not available.⁸ Data on amitriptyline is also lacking.⁸

Other prescription agents Differing from the other prescription treatments for insomnia, ramelteon is an agonist for the melatonin receptors MT₁ and MT₂, as opposed to GABA_A. With ramelteon not working on GABA, it does not have addictive potential. Ramelteon was shown to statistically reduce time to sleep onset and increase total sleep time compared with placebo. There was also no significant difference in next-day somnolence compared to placebo.²² Because of its low abuse potential, ramelteon may play a role in treating patients with a history of chemical dependency; however, no studies of this use have been published.²³ Table 1 lists the dosages, contraindications, and warnings for the pharmacologic agents discussed above.

BEHAVIORAL TREATMENT

Behavioral interventions can be an important treatment option for patients (see Table 2); however, there are a limited number of therapists who are qualified to provide this treatment option.²⁴ Behavioral intervention often involves a combination of cognitive behavior therapy (CBT), relaxation therapy, sleep hygiene, sleep restriction, and stimulus control techniques.

CBT modifies hindered beliefs and attitudes. Patients are taught techniques to relax their body and mind during relaxation therapy. Sleep hygiene adjusts poor sleep habits. Sleep restriction therapy consolidates and limits sleep and then gradually adds back sleep. Stimulus control includes avoiding naps, using the bed only for sleep and sex, going to bed only when sleepy, awakening each morning at the same time, and exiting the bedroom when unable to sleep.¹⁰ Relaxation, sleep restriction, CBT with or without relaxation therapy, multi-component therapy without CBT, and stimulus control therapies have been shown to be individually effective.²⁵ Insufficient evidence exists for recommending one single therapy over another or a single therapy over combination therapy.²⁵

ALTERNATIVE/HERBAL MEDICINE

Evidence of efficacy in treating insomnia is lacking for most alternative therapies. Evening bright light therapy showed short-term improvement in elderly patients, but morning bright light therapy did not.^26,27 In patients with anxiety-related insomnia, acupuncture showed improvement in sleep onset, decreased arousals, sleep time, and efficiency, but not next day sedation.²⁸ Tai chi improved sleep quality, latency, duration, and efficiency in the elderly.²⁹ Soft music with relaxation exercises also improved sleep quality, duration, efficiency, and latency in the elderly.³⁰ Valerian supplements showed no benefit over placebo in limited studies, and hepatotoxicity is a possible adverse effect.⁸ Systematic evidence supporting the use of L-tryptophan is extremely limited, and toxic effects are possible when used with some psychiatric medications.⁸

CONCLUSION

Insomnia, a disorder of difficulty going to sleep, staying asleep, or both, is a common condition seen in primary care. If left untreated, insomnia can lead to decreased quality of life, depression and/or anxiety, and difficulty maintaining employment. Sleep restriction can lead to an increased risk of cardiovascular morbidity and mortality.² A thorough history and physical examination often rule out other causes of decreased quality of sleep, such as sleep apnea. Effective treatment and adherence can help patients function and have a better quality of life. A multifaceted treatment approach combining medication, CBT, and alternative treatments can improve the quality and quantity of sleep for patients with insomnia. Treating and improving insomnia can ameliorate patients’ performance throughout the day, overall mood, and general medical health. JAAPA

DRUGS MENTIONED

Amitriptyline (Elavil, Endep)
Cimetidine (Tagamet)
Disulfiram (Antabuse)
Eszopiclone (Lunesta)
Ethchlorvynol (Placidyl)
Flurazepam (Dalmane)
L-tryptophan (Tryptan)
Quanethidine
Quinidine
Ramelteon (Rozerem)
Temazepam (Restoril)
Triazolam (Halcion)
Trazodone
Zaleplon (Sonata)
Zolpidem (Ambien)

REFERENCES

	1.	Nosology Committee of the American Academy of Sleep Medicine, eds. The International Classification of Sleep Disorders Pocket Version Diagnostic & Coding Manual. 2nd ed. Westchester, IL: American Academy of Sleep Medicine; 2006.
	2.	Banks S, Dinges DF. Behavioral and physiological consequences of sleep restriction. J Clin Sleep Med. 2007;3(5):519-528.
	3.	Roehrs T, Burduvali E, Bonahoom A, et al. Ethanol and sleep loss: a “dose” comparison of impairing effects. Sleep. 2003;26(8):981-985.
	4.	Lee-Chiong T. Sleep: A Comprehensive Handbook. Hoboken, NJ: John Wiley & Sons, Inc; 2006.
	5.	Douglas NJ. Clinicians’ Guide to Sleep Medicine. London, England: Arnold Publishers; 2002.
	6.	National Institutes of Health, US Department of Health and Human Services. 2003 National Sleep Disorders Research Plan. Bethesda, MD: National Institutes of Health; 2004. NIH publication 03-5209. http://www.nhlbi.nih.gov/health/prof/sleep/res_plan/section5/section5b.html. Accessed June 4, 2008.
	7.	Susman E. APSS: extra health cost of insomnia reaches $3,200 an employee. Medpage Today Web site. http://www.medpagetoday.com/tbprint.cfm?tbid=5909&topicid=273. Accessed June 4, 2008.
	8.	NIH State-of-the-Science Conference Statement on Manifestation and Management of Chronic Insomnia in Adults. NIH Consens Sci Statements. 2005;22(2):1-30.
	9.	Chesson A Jr, Hartse K, Anderson WM, et al. Practice parameters for the evaluation of chronic insomnia. An American Academy of Sleep Medicine report. Standards of Practice Committee of the American Academy of Sleep Medicine. Sleep. 2000;23(2):237-241. http://www.aasmnet.org/Resources/PracticeParameters/PP_ChronicInsomnia.pdf. Accessed June 4, 2008.
	10.	Insomnia. American Academy of Sleep Medicine Web site. http://www.aasmnet.org/Resources/FactSheets/Insomnia.pdf. Accessed June 4, 2008.
	11.	Sateia MJ, Doghramji K, Hauri PJ, Morin CM. Evaluation of chronic insomnia. Sleep. 2000;23(2): 243-308. http://www.aasmnet.org/Resources/PracticeParameters/Review_ChronicInsomnia.pdf. Accessed June 4, 2008.
	12.	Suhner AG, Murphy PJ, Campbell SS. Failure of timed bright light exposure to alleviate age-related sleep maintenance insomnia. J Am Geriatr Soc. 2002;50(4):617-623.
	13.	Glass J, Lanctôt KL, Hermann N, et al. Sedative hypnotics in older people with insomnia: meta-analysis of risks and benefits. BMJ. 2005;331(7526):1169. http://www.bmj.com/cgi/content/full/331/7526/1169. Accessed June 4, 2008.
	14.	Uchimura N, Nakajima T, Hayash K, et al. Effect of zolpidem on sleep architecture and its next-morning residual effect in insomniac patients: a randomized crossover comparative study with brotizolam. Prog Neuropsychopharmacol Biol Psychiatry. 2006;30(1):22-29.
	15.	Roth T, Soubrane C, Titeux L, Walsh JK; Zoladult Study Group. Efficacy and safety of zolpidem-MR: a double-blind, placebo-controlled study in adults with primary insomnia. Sleep Med. 2006; 7(5):397-406.
	16.	Walsh JK, Pollak CP, Scharf MB, et al. Lack of residual sedation following middle-of-the-night zaleplon administration in sleep maintenance insomnia. Clin Neuropharmacol. 2000;23(1):17-21.
	17.	Allain H, Bentué-Ferrer D, Le Breton SL, et al. Preference of insomniac patients between a single dose of zolpidem 10 mg versus zaleplon 10 mg. Hum Psychopharmacol. 2003;18(5):369-374.
	18.	Rosenberg R, Caron J, Roth T, Amato D. An assessment of the efficacy and safety of eszopiclone in the treatment of transient insomnia in healthy adults. Sleep Med. 2005;6(1):15-22.
	19.	Roth T, Walsh JK, Krystal A, et al. An evaluation of the efficacy and safety of eszopiclone over 12 months in patients with chronic primary insomnia. Sleep Med. 2005;6(6):487-495.
	20.	Voshaar RC, van Balkom AJ, Zitman FG. Zolpidem is not superior to temazepam with respect to rebound insomnia: a controlled study. Eur Neuropsychopharmacol. 2004;14(4):301-306.
	21.	FDA requests label change for all sleep disorder drug products. US Food and Drug Administration Web site. http://www.fda.gov/bbs/topics/NEWS/2007/NEW01587.html. Accessed June 4, 2008.
	22.	Erman M, Seiden D, Zammit G, et al. An efficacy, safety, and dose-response study of ramelteon in patients with chronic primary insomnia. Sleep Med. 2006;7(1):17-24.
	23.	Curry DT, Eisenstein RD, Walsh JK. Pharmacologic management of insomnia: past, present, and future. Psychiatr Clin North Am. 2006;29(4):871-893.
	24.	Adams MP, Judd CR, Neubauer D, Zee P. Management of chronic insomnia: individualized assessment and interventions to ensure a safe sleep. JAAPA. 2007;20(9)(suppl):1-20.
	25.	Morgenthaler T, Kramer M, Alessi C, et al; American Academy of Sleep Medicine. Practice parameters for the psychocological and behavioral treatment of insomnia: an update. An American Academy of Sleep Medicine report. Sleep. 2006;29(11):1415-1419. http://www.aasmnet.org/Resources/PracticeParameters/PP_BTInsomnia_Update.pdf. Accessed June 4, 2008.
	26.	Suhner AG, Murphy PJ, Campbell SS. Failure of timed bright light exposure to alleviate age-related sleep maintenance insomnia. J Am Geriatr Soc. 2002;50(4):617-623.
	27.	Kirisoglu C, Guilleminault C. Twenty minutes versus forty-five minutes morning bright light treatment on sleep onset insomnia in elderly subjects. J Psychosom Res. 2004;56(5):537-542.
	28.	Spence DW, Kayumov L, Chen A, et al. Acupuncture increases nocturnal melatonin secretion and reduces insomnia and anxiety: a preliminary report. J Neuropsychiatry Clin Neurosci. 2004;16(1):19-28.
	29.	Li F, Fisher KJ, Harmer P, et al. Tai chi and self-rated quality of sleep and daytime sleepiness in older adults: a randomized controlled trial. J Am Geriatr Soc. 2004;52(6):892-900.
	30.	Lai HL, Good M. Music improves sleep quality in older adults. J Adv Nurs. 2005;49(3):234-244.