Assessment and Management of Insomnia 6-8 Carlos H

CONTEMPO UPDATES LINKING EVIDENCE AND EXPERIENCE

Assessment and Management of Insomnia 6-8 Carlos H. Schenck, MD pression, and suicidality. Insomnia is plored. The bedpartner’s input can pro- associated with enormous direct and in- vide important information regarding Mark W. Mahowald, MD direct costs, as much as $14 billion in snoring and breathing patterns, un- Robert L. Sack, MD the United States in 1995.7 Physicians usual sleep motor activity, and day- should therefore establish an effective time consequences from suboptimal NSOMNIA IS A COMMON TREATABLE clinical strategy for eliciting and man- sleep. Use of caffeine, alcohol, and drugs disorder of insufficient or poor- aging insomnia complaints.9-11 Use of a (prescription, over-the-counter, herbal quality sleep, with adverse daytime I 1 sleep-trained nurse, psychologist, or products, illicit agents) should also be consequences. Insomnia presents as both on a consultation basis or as a mem- discussed. Reliving a typical day with the trouble falling asleep (long-sleep ber of the physician’s medical practice patient can be helpful. latency), trouble staying asleep (exces- should be considered. One study has re- A sleep log (diary), completed for at sive or prolonged awakenings), or feel- ported on the benefit of behavioral treat- least 7 consecutive days, is important for ing nonrestored from sleep. Insomnia ment of insomnia provided by a trained evaluating an insomnia complaint11 and can be a primary disorder emerging in clinic nurse in a general medical prac- is especially useful in identifying circa- childhood or later, a conditioned (psy- tice.12 However, the cost-effectiveness of dian rhythm disorders as a cause of in- chophysiological) disorder, or comor- incorporating a sleep-trained nurse or somnia. A sleep questionnaire is also use- bid with a psychiatric, medical, or other psychologist into a medical practice has ful; a commonly used one is the sleep disorder.1 Insomnia can be tran- yet to be reported. Pittsburgh Sleep Quality Index13 that has sient (related to stress, illness, travel) 19 items yielding data on the severity of or chronic (occurring nightly for Ͼ6 Assessment insomnia. Urine toxicology screening months). Persistent untreated insom- may be needed in selected cases to de- nia is a strong risk factor for major de- Assessment of insomnia complaints tect use of stimulant drugs (ephedrine, pression.2 Insomnia must be distin- should begin with a history obtained cocaine, amphetamines). guished from sleep-state misperception from the patient and bedpartner, then Psychological screening should as- and short sleep states without symp- continue with a physical examination. sess the presence and severity of depres- toms.1 The primary focus should be on the sion and anxiety, which are the most More than 50 epidemiological stud- functional impact and severity, and chro- common psychiatric conditions associ- ies have shown that one third of vari- nicity of the complaints, with rapid iden- ated with insomnia. The Beck Depres- ous general populations have insom- tification of target symptoms for use in sion and Beck Anxiety Inventories are nia symptoms and that 9% to 21% have formulating a management strategy. simple, validated, self-administered tests insomnia with serious daytime conse- Questioning should be directed at de- with easy guidelines for physician in- quences, such as bodily fatigue, dimin- termining age of onset, predisposing fac- terpretation.11 Such tests should be ad- ished energy, difficulty concentrating, tors and traits (family history, habitual ministered to insomnia patients with memory impairment, low motivation, light sleeper, sensitivity to noise and suspected depression and anxiety or to loss of productivity, irritability, inter- other stimuli, deviant circadian sleep and patients with no identified cause of in- personal difficulties (with family, friends, wake rhythm), precipitating events somnia. Formal psychological or psy- coworkers), increased worrying, anxi- (stress, illness, medication, or bedpart- chiatric referral can be considered on a ety, and depression.3-5 Chronic sleep loss, ner’s sleep problem), duration and spe- case-by-case basis. Patients with a past which occurs in untreated insomnia, is cific characteristics (nightly, intermit- a major risk factor for fatigue-related au- tent, or situation-specific: weekday vs weekend, with vs without bedpartner, tomobile crashes and industrial acci- Author Affiliations: Departments of Psychiatry (Dr dents, loss of jobs, marital and social sleep at home vs away, time-of-night pat- Schenck) and Neurology (Dr Mahowald), Minnesota tern, and daytime consequences). Life- Regional Sleep Disorders Center, Hennepin County problems, poor health, metabolic and Medical Center and University of Minnesota Medical endocrine dysregulation with im- style, daily activity patterns, and mal- School, Minneapolis; and Department of Psychiatry, adaptive behaviors must be addressed, Oregon Health Sciences University, Portland (Dr Sack). paired ability to maintain weight con- Corresponding Author and Reprints: Carlos H. trol, coronary heart disease, major de- including the frequency, timing, and Schenck, MD, Department of Psychiatry (844), Hen- type of meals consumed. Timing of nepin County Medical Center, 701 Park Ave S, Min- sexual activity and exercise, and any neapolis, MN 55415. See also Patient Page. Contempo Updates Section Editor: Sarah Pressman other effect on sleep, should also be ex- Lovinger, MD, Fishbein Fellow.

Downloaded from www.jama.com at Sanofi-Aventis, on September 11, 2007 ASSESSMENT AND MANAGEMENT OF INSOMNIA or current history of psychiatric disor- commonly associated with insomnia adults who must care for spouses or der who present with an insomnia com- include asthma, chronic obstructive pul- family members with medical disor- plaint should most likely be referred to monary disease, congestive heart fail- ders associated with sleep disruption of- a psychiatrist to assess whether a psy- ure, ischemic heart disease, gastro- ten complain of insomnia with day- chiatric disorder is contributing to the esophageal reflux, rheumatologic or time consequences. The physician must insomnia complaint. other pain-related disorders, hyperthy- assess the value of various treatment Actigraphy is an objective test that is roidism, end-stage renal disease, and modalities for a particular patient: a useful in identifying sleep-state mis- neurodegenerative disorders.7,14,15 Noc- low-dose sedative (0.125/0.25 mg of al- perception, sleep-interruption insom- turnal gastroesophageal reflux can be an prazolam; 0.5 mg of lorazepam) at bed- nia, and circadian rhythm disorders. Ac- epiphenomenon of obstructive sleep ap- time may facilitate the prompt resump- tigraphy uses a wrist monitor that nea, improving with treatment of the lat- tion of sleep throughout multiple records movement during successive ter condition.16 caretaking-related awakenings; zale- 1-minute time bins on a microcom- The most common sleep disorder as- plon (5-10 mg) as occasion requires can puter chip. The movement and non- sociated with sleep-onset and sleep- help control any tendency for pro- movement pattern can correlate closely maintenance insomnia is restless legs longed awakenings; strategic daytime with wakefulness and sleep.11 Never- syndrome, which at times is linked with naps (15-45 minutes), depending on the theless, there can be substantial error disruptive periodic limb movements of napping capabilities of the individual in some insomniacs who lie quietly in sleep, obstructive sleep apnea, and para- and the schedule of daily activities; and bed for prolonged periods of time.11 somnias (sleep behavior disorders).17,18 judicious use of caffeine in the morn- Polysomnography (formal physiologi- Restless legs syndrome affects up to 10% ing or early afternoon to increase alert- cal monitoring of sleep) should be re- of the general population and more than ness. However, prolonged naps or naps served for cases of insomnia with a sus- 25% of pregnant women and often re- taken late in the day could aggravate in- pected organic sleep disorder. The use sults in severe insomnia.17 Restless legs somnia, as could excessive amounts or of actigraphy and polysomnography syndrome manifests as peculiar, dis- ill-timed use of caffeine. Regular exer- should be decided during a consulta- tressing, and painful leg sensations cise should also be encouraged, pro- tion with a sleep specialist. during drowsiness that are relieved by vided that the timing of the exercise walking or other measures that are in- does not interfere with sleep. Conditioned Insomnia compatible with falling asleep. Dopa- A common cause of persistent insom- minergic or opiate therapy, or both (and Management Guidelines nia is conditioned (learned or psycho- at times use of benzodiazepines, par- The diagnostic and management strat- physiological) insomnia. This disor- ticularly clonazepam) at bedtime is usu- egies of insomnia are linked. The phy- der usually arises from an episode of ally effective, safe, and well-tolerated sician should promptly place an insom- acute situational insomnia (triggered by during long-term nightly use.17-20 The nia complaint into 1 of 4 categories (not pain, illness, medication, stress, travel, common and quite treatable parasom- mutually exclusive): related to stress, bereavement). The patient soon asso- nias include abnormal behaviors asso- bad habits, or improperly timed activi- ciates the bed with not sleeping and be- ciated with obstructive sleep apnea17; dis- ties; related to a sleep disorder (chronic comes hyperaroused at night at a time orders of arousal from non–rapid eye insomnia, circadian rhythm disorder, when he/she would ordinarily feel re- movement sleep (sleepwalking, sleep obstructive sleep apnea, restless legs laxed and sleepy. After the original pre- terrors); rapid eye movement sleep be- syndrome and periodic limb move- cipitant recedes, a conditioned insom- havior disorder (acting-out of violent ments disorder, parasomnia); related to nia persists that will often not resolve dreams, usually in older men); and noc- a medical, neurological, psychiatric dis- spontaneously. turnal sleep-related eating disorders order; and nonclinical complaint, with- (consumption of high-calorie foods dur- out daytime consequence (short sleeper; Insomnia Associated ing partial nocturnal arousals, usually in some cases of sleep-state mispercep- With Clinical Disorders women). Screening questions for para- tion). The physician can then decide Insomnia is very common in psychiat- somnias are available for physician use.18 whether to further evaluate and treat the ric disorders, particularly mood and A related phenomenon involves bed- insomnia or refer the patient to a spe- anxiety disorders.2,4,7 In 1 large study, in- partner-induced or aggravated insom- cialist. somnia appeared before the onset of a nia, due to snoring, body jerking, peri- Transient insomnia can be con- mood disorder in more than 40% of af- odic leg movements, or parasomnias. trolled with short-term use of a hyp- fected persons, whereas insomnia ap- notic medication. Management of per- peared concurrently or after the onset Caretaker Insomnia sistent or chronic insomnia can be of an anxiety disorder in more than 72% Caretaker insomnia can emerge in vari- separated into primary and secondary in- of affected persons.4 Medical disorders ous contexts. Parents of newborns who terventions (BOX). Sleep hygiene aims and sometimes their treatment most have repeated nocturnal awakenings or to establish proper daily habits that pro-

Downloaded from www.jama.com at Sanofi-Aventis, on September 11, 2007 ASSESSMENT AND MANAGEMENT OF INSOMNIA mote sleep and minimize daily habits chronic insomnia patients,9,20 al- that interfere with sleep (eg, drinking though systematic studies on long- Box. Management of coffee or engaging in stressful activities term use have yet to be published. A Persistent or Chronic in the evening).2,7 Relaxation training can referral to a sleep specialist is recom- Insomnia take various forms (progressive muscle mended for patients being considered Primary Interventions relaxation, guided imagery, hypnosis, for long-term treatment with benzodi- Sleep hygiene training meditation, yoga, biofeedback), with the azepines or related agents that at times Relaxation training goal being the reduction of psychic and can cause morning sedation, memory Stimulus-control therapy muscular tension causing hyper- dysfunction, dosage tolerance, or mis- arousal and interference with sleep on- use. Close physician monitoring is thus Secondary Interventions set.2,7 Stimulus-control therapy is di- encouraged. The following can also be Pharmacologic rected both to reducing arousing stimuli effective for short-term use and possi- Zolpidem and zaleplon Benzodiazepine hypnotics and in the bedroom that interfere with fall- bly long-term use in controlling insom- Ͼ anxiolytics ing asleep and reinforcing associations nia: doxepin or amitriptyline ( 10-50 Antidepressants between the bed/bedroom and falling mg); triimpramine (25-100 mg); imip- Combined pharmacotherapies 2,7 asleep. Various unproven interven- ramine (Ͼ10-75 mg); and trazodone Nonpharmacologic tions are widely promoted and some, (Ͼ25-100 mg). Cognitive-behavioral therapy such as white noise machines, may For patients with insomnia associ- Sleep restriction and sleep con- be helpful in selected cases (noise- ated with depression, various pharma- solidation therapy sensitive insomnia). cologic strategies exist2: sedating anti- When primary interventions are in- depressants; combination of sedating effective or partially effective in con- and nonsedating antidepressants; ben- nia in the United States, with the former trolling insomnia, secondary interven- zodiazepine or related hypnotic in mild- being more rigorously evaluated. A re- tions should be considered. Depending moderate depression treated with cent randomized, double-blind study of on patient interest and physician train- psychotherapy; combination of an an- 202 patients with nonorganic insom- ing, either pharmacologic or nonphar- tidepressant with a benzodiazepine or nia found that after 6 weeks of treat- macologic interventions can be suc- related hypnotic. Cognitive-behav- ment, valerian was as effective as the cessfully used. Zolpidem and zaleplon ioral therapy, which requires specially benzodiazepine oxazepam.26 Hepato- (imidazopydridine and pyrazolopyrimi- trained clinicians, can be quite effec- toxicity, cardiotoxicity, and delirium dine agents, respectively) act as ago- tive in treating chronic insomnia.23 This occur sporadically with use of val- nists at the benzodiazepine receptor therapy is directed at altering dysfunc- erian; dermatotoxicity and interac- component of the ␥-aminobutyric re- tional beliefs about sleep that perpetu- tions with sedatives and alcohol may oc- ceptor complex.21,22 They are rapidly ab- ate insomnia.2,23 Sleep restriction and cur with use of kava. sorbed, do not have active metabo- sleep consolidation therapy aim to mini- lites, and are well-tolerated with low mize the amount of wakefulness in bed Circadian Rhythm Sleep Disorders risk for tolerance and a low abuse po- by limiting the total time in bed.2 This In circadian rhythm sleep disorders, in- tential. Zolpidem has been exten- therapy requires a high level of pa- somnia results from a mismatch be- sively studied, with an excellent thera- tient motivation, because the patient tween the endogenous sleep and alert- peutic profile with nightly use for up must stay out of the bedroom until a ness rhythm and the desired (or to 6 months, the longest duration stud- late hour (3 AM) and then go to bed 15 required) time for sleep and wake.27 The ied.21,22 At our centers, patients with minutes earlier on successive nights, mismatch can result from external chal- chronic insomnia are usually well- until the target bedtime is achieved.2 lenges to the circadian system, such as controlled during nightly zolpidem Over-the-counter drugs containing night-shift work and jet travel; vulner- treatment of more than 6 months’ du- sedating antihistamines (diphenhy- abilities in the endogenous circadian ration (C.H.S., unpublished data, 2003). dramine) are widely used by the pub- mechanisms, such as having a circa- The usual dose is 5 to 10 mg at bed- lic for insomnia. However, the effi- dian clock with an overly short intrin- time. Zaleplon is an ultrashort-acting cacy of these agents in treating insomnia sic period (as in familial advanced agent that is effective in promptly re- has not been established. Although US sleep-phase syndrome); or a lack of en- storing sleep in patients with problem- patients have shown a growing inter- vironmental time cues, as in the case atic nocturnal awakenings. The usual est in alternative therapies,24 there is of individuals who are blind and whose dose is 5 to 10 mg. Benzodiazepine hyp- currently insufficient scientific knowl- rhythms free-run on a non–24-hour notics can also be safely and effec- edge on the efficacy and safety of herbal cycle. tively used for short-term therapy,9 and treatments of insomnia.25 Valerian and The circadian clock is located in the possibly also for long-term nightly use kava are probably the most commonly suprachiasmatic nucleus of the hypo- in carefully diagnosed, refractory, promoted herbal remedies of insom- thalamus, and its intrinsic period gen-

Downloaded from www.jama.com at Sanofi-Aventis, on September 11, 2007 ASSESSMENT AND MANAGEMENT OF INSOMNIA erated by a gene-protein feedback loop pacemaker is signaling sleep. Sleep dur- Treatment in humans is slightly longer than 24 ing the day is typically foreshortened, Treatments involve resetting the circa- hours; consequently, precise synchro- and after a few days, a cumulative sleep dian clock so that it is more congruent nization to a 24-hour day (entrain- debt may build that compounds night- with the desired or required sleep- ment) depends on input from the en- time sleepiness. Some night workers wake schedule. Bright light exposure in vironment, especially the solar light and are able to synchronize their internal the morning can shift circadian rhythms dark cycle. The effect of light expo- rhythms to their work schedules, but earlier and has been shown to be effec- sure on circadian rhythms is critically many never do. Bright light exposure tive for the treatment of DSPS.29 The dependent on its timing: in the morn- on the job may promote adaptation by treatment can be as simple as having the ing, light shifts the clock earlier but, in shifting circadian rhythms but sun- person go for a walk outside in the the evening, it shifts the clock later. light on the commute home from work morning (even cloudy days can pro- Nonphotic time cues (scheduled sleep may block it. vide sufficient sunlight), although ar- and activity) may have some influ- Delayed and Advanced Sleep Phase tificial bright light fixtures may be nec- ence on the clock, but the effects are Syndromes. Patients with delayed sleep essary in the winter. Bright light in the weak compared with light exposure. phase syndrome (DSPS) are extreme evening shifts rhythms later and is ef- During the day, the circadian clock night owls who prefer to stay awake late fective for treating advanced sleep phase generates an alerting signal that coun- into the night and wake up at midday, syndrome and possibly also elderly teracts the normal accumulation of a schedule that conflicts with employ- people with insomnia who have early sleep drive related to duration of time ment or school obligations. Many ado- morning awakening based on circa- awake, and thereby maintains a rela- lescents have a tendency toward DSPS, dian mechanisms. Dark goggles worn tive balance toward wakefulness. As even if they do not meet strict criteria on the morning commute from work bedtime approaches, the circadian alert- for the syndrome. Delayed sleep phase have been shown to improve adapta- ing process recedes, allowing for sleep syndrome may result from an intrin- tion of night workers. and the dissipation of sleep drive. In cir- sic circadian period that is signifi- Melatonin is a hormone secreted at cadian rhythm sleep disorders, the cir- cantly longer than 24 hours, making en- night by the pineal gland that can shift cadian alerting process is misaligned trainment to a conventional schedule the circadian pacemaker in an opposite and overlaps the desired time for sleep, very difficult. direction from light (considered a dark- resulting in insomnia. Advanced sleep phase syndrome is ness signal). When administered in the rare. However, a tendency toward evening, it shifts rhythms earlier but, in Common Circadian Rhythm advanced sleep phase syndrome is the morning, shifts rhythms later. It is Sleep Disorders common in older people who doze off important to take melatonin at the ap- Jet Lag. After rapid travel across time in the evenings and awaken prema- propriate time to promote the desired zones, endogenous circadian rhythms turely. The syndrome may be related clock-resetting effect. In clinical trials, become out of phase with local time. to an intrinsic circadian period that is melatonin has been shown to acceler- Symptoms include insomnia, daytime significantly shorter than 24 hours. ate adaptation to night work and to al- sleepiness, and gastrointestinal distur- Other kinds of insomnia include Sun- leviate DSPS and jet lag.30 The com- bances that gradually resolve as the in- day night insomnia that results from monly available doses of 0.5 and 3 mg ternal body clock catches up to local staying up late on the preceding nights, appear to be safe. Effective strategies ex- time and circadian harmony is re- thereby delaying the peak of circadian ist for scheduling bright light exposure stored. Besides circadian desyn- alertness so that it coincides with bed- and for using melatonin to induce cir- chrony, other contributors to jet lag in- time. Also, insomnia may occur dur- cadian adaptation in permanent night- clude poor sleep due to uncomfortable ing the winter months, because morn- shift workers.31 airline seats, disruption by other pas- ing light is insufficient to maintain It is difficult to induce a large circa- sengers, liberal use of alcohol and caf- normal entrainment. dian phase shift in 1 or 2 cycles; rather, feine, and a shortened sleep opportu- persistent small adjustments are more nity. After arrival, insomnia can persist Evaluation of Circadian likely to succeed. For example, pa- and be exacerbated by sleeping in a Sleep Disorders tients with DSPS can be treated with novel environment. A sleep diary can provide a clear pic- gradual advances in their sleep times, Night-Shift Work. A more persis- ture of the temporal patterns of from 15 to 30 minutes every 2 to 3 days. tent form of circadian desynchrony un- sleep. The Horne-Ostberg scale28 The schedule is reinforced with bright derlies the insomnia of night-shift work- assesses the tendency for people to light exposure in the morning, mela- ers. The nonadapted night worker must prefer the morning hours (larks) vs tonin in the evening, and if necessary, sleep when the circadian pacemaker is the evening hours (owls). Actigraphy sleeping medication at night. promoting wakefulness and must stay is invaluable for helping diagnose Intermittent use of hypnotic medi- awake and alert when the circadian circadian disorders. cations can benefit a night worker who

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What is the hardest task in the world? To think. —Ralph Waldo Emerson (1803-1882)

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