Dr. Martinez-Gonzalez is fellow, Dr. Obermeyer is associate scientist, and Dr. Benca is professor, all in the Department of Psychiatry at the University of Wisconsin–Madison.  Reprinted from TEN. 2001;3(9):48-57. 



Why is the recognition and treatment of insomnia important? Insomnia is highly prevalent and associated with significant costs and morbidities, although it is seldom a focus of medical attention. Patients with insomnia have an increased incidence of health problems and reduced quality of life; they also are at greater risk for developing depression. There has been increasing evidence for a causal relationship between insomnia and health. Appropriate diagnosis and treatment of insomnia may lessen its associated morbidities and ultimately reduce healthcare costs.



Insomnia is one of the most common medical symptoms in industrialized countries, with significant associated costs and comorbidities. Individuals with insomnia complain of difficulties falling asleep, staying asleep, and/or the perception of disturbed or nonrestorative sleep. They also may report fatigue and impairment of daytime functioning. Chronic insomnia affects up to 40% of adults over the course of a year, and 10% of adults complain of moderate to severe sleep problems.1-6 Insomnia is more prevalent with aging and in women. Sleep disturbance is also strongly associated with medical, and particularly, psychiatric illnesses, with up to half of adults with insomnia having concomitant psychiatric disorders.


Costs of Insomnia

The costs associated with insomnia are enormous. The direct costs of treatment include visits to physicians, prescription and nonprescription medications, and nursing home care. In 1995, it was estimated that these costs totaled approximately $13.9 billion in the United States7; whereas in France, with a population approximately one fifth the size of US, the 1995 costs for insomnia treatment were slightly over $2 billion.8 These numbers exemplify the significant direct costs of insomnia in industrialized societies. Since most individuals do not discuss their sleep problems with a physician, and only a minority of patients receives treatment, the potential costs of treating insomnia may be even higher.

The indirect costs related to insomnia, though more difficult to quantify, are likely to be far greater in magnitude. Sleep disturbance is correlated with fatigue-related accidents, decreased productivity, poorer health, reduced quality of life, and medical and psychiatric disorders. It is not clear, however, whether these associations are causes or results of insomnia, although evidence is emerging that both types of relationships exist.

In general, people with insomnia use more medical and psychiatric services than good sleepers.5,9,10 Simon and VonKorff5 reported a 10% prevalence of severe insomnia in primary care patients, and they found that insomnia was associated with significantly greater disability from medical disorders and with increased rates of healthcare utilization and depression. In another large survey of the general population, people with insomnia had higher rates of utilization of general medical services.1 A study using data (1980–1984) from the National Institute of Mental Health Epidemiological Catchment Area Study compared morbidity and mortality of insomnia in subjects with or without a history of psychiatric illness during the previous year.9 Both groups of insomniacs showed greater utilization of general medical and psychiatric services, although rates were even higher in subjects with a prior history of psychiatric disorders.

Subjective reports of poorer quality of life have been consistent with incidence of insomnia in various populations, including a National Sleep Foundation/ Gallup poll,6 a survey of US primary care patients in California and Hawaii,11 and a Japanese study.12 Insomnia is also correlated with decreased work productivity, increased absenteeism, higher rate of accidents, and complaints of daytime fatigue.13,14 Deficits in cognitive and psychomotor functioning, including memory, concentration, attention, reasoning, problem-solving, and reaction time, have also been demonstrated in people with insomnia.6,11,13,15

Insomnia and Medical Disorders

In addition to their subjective sense of poorer health quality, insomniacs show increased rates of medical disorders. Mellinger and colleagues2 reported that over half of individuals with serious insomnia had two or more health problems, in comparison to only about one quarter of those with no trouble sleeping. Not only do insomniacs have more medical problems, but medically ill patients also have more sleep complaints. A survey of patients in primary care clinics in Hawaii and California found a total prevalence of insomnia of 69%, with 19% reporting chronic insomnia.11 In a study of medical outpatients, Katz and McHorney16 found that half complained of sleep disturbance, with severe insomnia reported by 16%. Sleep problems were associated with a variety of medical conditions, including cardiopulmonary disease, musculoskeletal conditions, prostate problems, and depression.

Sleep disturbance may also contribute to medical disorders. A recent meta-analysis by Schwartz and colleauges17 demonstrated that trouble falling asleep was associated with coronary events, independent of other risk factors for cardiac disease.17 Several studies of the associations between insomnia and medical illness have demonstrated that sleep disturbance tends to change in relation to health status. In geriatric subjects, resolution of insomnia was significantly associated with improvement in self-perceived health.18 Severity of symptoms in patients with irritable bowel disorder was predicted by the prior night’s sleep, suggesting a potential causal relationship.19 Thus, sleep disturbance may be both a cause and a result of medical disorders, and treatment of insomnia may decrease the need for utilization of other medical services.

Insomnia and Psychiatric Disorders

Insomnia is most strongly associated with psychiatric disorders, particularly anxiety and depression. Psychiatric patients commonly report sleep difficulties, and polysomnographic studies show objective sleep abnormalities in association with all major psychiatric disorders (Table 1).20,21 Sleep complaints are a primary or associated diagnostic criteria for most psychiatric illnesses, which disrupt sleep through a variety of mechanisms, including the increased anxiety and arousal that accompany most acute episodes of illness and the secondary effects of psychotropic medications.


Chronic insomnia is also strongly associated with psychiatric symptomatology and psychiatric disorders. Increased rates of psychological stress and poorer ability to cope with stress have been connected with insomnia in several surveys.6,12 Insomniacs also show more abnormalities on psychological testing. Almost 80% show significant increases on one or more clinical scales on the Minnesota Multiphasic Personality Inventory (MMPI).22 These results may not have been due solely to an increase in psychiatric disorders, since even people whose insomnia was due to identified medical factors showed elevations on the MMPI, suggesting a direct effect of sleep disturbance on psychological symptomatology.

Epidemiologic studies of the general adult population have shown that one third to one half of people with chronic insomnia suffer from primary psychiatric disorders, predominantly anxiety and mood disorders. Mellinger and colleagues2 noted that among adults reporting “a lot” of trouble falling asleep or staying asleep over the past year (17% of the population), almost half of them had high levels of psychiatric distress with symptoms consistent with depression and anxiety disorders.2 In a large-scale survey of almost 8,000 individuals, Ford and Kamerow1 reported that 40% of those with significant insomnia met criteria for psychiatric disorders, whereas only 16% of those without sleep complaints had psychiatric illnesses. Breslau23 found a strong correlation between lifetime prevalences of sleep problems and psychiatric disorders in a study of young adults. Anxiety, depression, and substance abuse were the most common disorders in this population.

The comorbidity between insomnia and psychiatric disorders may be even higher in clinical populations. In one study, over half of insomnia patients presenting to general medical or sleep disorders clinics were reported to have psychiatric symptoms.24 At least three quarters of insomnia patients in sleep or general medical clinics were diagnosed with a psychiatric illness in another study.25 Katz and Horney16 found that, in medical outpatients, major depressive disorder and depressive symptoms were more strongly associated with insomnia than were other chronic illnesses.

Most psychiatric patients complain of sleep disturbance, not only during periods of acute illness but also during periods of remission.26 Virtually all psychiatric patient groups show changes in sleep architecture that are associated with insomnia. These changes include reduced sleep efficiency, prolonged latency to sleep onset, increased time awake during the sleep period, and reduced amounts of total sleep.21 Thus, the increase in subjective complaints of insomnia among psychiatric patients is based on objective changes in sleep, and are not a consequence of a simple reporting bias or misperception of sleep state related to their psychiatric illness.

Mood Disorders

Depression has been studied more extensively than any other psychiatric disorder. Patients with depression frequently report insomnia, although a minority complain of hypersomnia. Hypersomnia is more common in those with bipolar disorder or winter depression,27 often characterized by symptoms of prolonged nocturnal sleep and daytime napping. Depressed people may also complain of intense or distressing dreams and daytime fatigue. Manic patients may have severe insomnia during episodes of acute illness, accompanied by the sense of a decreased need for sleep. Insomnia often precedes mania and has been identified as a precipitant or perpetuating factor. The relationship between sleep loss and mania is one of the most robust associations between sleep disturbance and resulting illness.

Patients with major depression show the most robust and consistent changes in sleep architecture versus other psychiatric disorders.21 These sleep abnormalities are usually grouped into three categories28:

(1) Decreased sleep continuity, consisting of prolonged sleep-onset latency, increased wakefulness during the sleep period, and early morning awakening, resulting in reduced sleep efficiency and total time spent asleep.

(2)  Decreased slow-wave sleep (SWS), including reductions in SWS as percentage of total sleep, total time spent in SWS, and decreased δ-wave activity during sleep versus age-matched normal control subjects.

(3)  Rapid eye movement (REM) sleep abnormalities, including reduced latency to REM sleep onset, increased REM sleep as percentage of total sleep, increased proportion of REM sleep in the first third of the night, and increased total number or density of REMs across the night.

Sleep is generally most disturbed during acute episodes of depression, although certain sleep abnormalities tend to persist during periods of clinical remission. These persistent “trait” abnormalities are reduced REM sleep latency and loss of SWS, which have been considered markers for depression. Other sleep changes, such as REM density and sleep continuity, may reflect the state of depression because they have been reported to fluctuate with the illness.29

While bipolar patients in an episode of acute mania show the same sleep abnormalities as depressives,30,31 patients with dysthymia or subclinical depression seem to be indistinguishable from normal control subjects.

Cause and Effect Between Insomnia and Depression

There is increasing evidence supporting causal relationships between sleep and mood disorders. In prospective studies, complaints of insomnia were found to have a positive predictive value for subsequent development of depression. Ford and Kamerow1 found that subjects with insomnia had a greatly increased risk of developing a new episode of major depression 1 year later, compared to individuals with no insomnia. A prospective study of community-dwelling, elderly over a 2-year period, found that sleep disturbance was the best predictor for development of depression.32 Another study assessed the sleep habits of over 1,000 men while they were medical students and followed them for a median of 34 years. Individuals with insomnia during medical school had an increased risk of depression later in life (relative risk 2.0), as did those reporting difficulty sleeping under stress (relative risk 1.8), versus those with no sleep problems.33 Breslau23 assessed the incidence of depression over a 3.5-year period in young adults with a history of insomnia compared to those with no prior history of insomnia. Even though controlling for the prior history of other depressive symptoms would naturally have reduced the odds ratio, the risk for developing depression with a history of insomnia remained high (odds ratio 2.1). Another study that controlled the independent contributions of various depressive symptoms was performed in older adults.34 In this population, other depressive symptoms were found to have higher predictive values; insomnia ranked third among women, but last among men. These data suggest that sleep disturbance is an important risk factor and possibly a precipitant for depression.

Anxiety Disorders

Anxiety disorders, including generalized anxiety disorder, panic disorder, posttraumatic stress disorder (PTSD), and obsessive-compulsive disorder (OCD), are commonly associated with insomnia. In general, sleep studies performed in patients with any of these disorders report prolonged latency to sleep onset, increased time awake during the sleep period, early morning awakening, reduced sleep efficiency, and decreased total sleep.

Patients with generalized anxiety disorder experience chronic and persistent anxiety and, not surprisingly, most report problems with insomnia. Sleep studies have shown prolonged sleep latency, reduced sleep efficiency, early morning awakening, and reduced total sleep time.35,36

Sleep-related panic attacks affect most patients with panic disorders; one third or more of patients with panic disorder suffer recurrent nocturnal panic attacks.37 Symptomatology of sleep panic attacks is similar to wake panic attacks and they occur more commonly at transitions from stage 2 to SWS.38,39 Nocturnal panic attacks are characterized by waking in a state of intense fear or anxiety associated with palpitations, shortness of breath, choking sensation, chest discomfort, and chills or hot flushes. In contrast to night terrors, which are characterized by incomplete arousal from sleep, in a sleep panic attack, patients are awake and alert immediately after the attack begins. Patients with recurrent sleep panic attacks may become fearful of going to sleep, which can contribute further to their insomnia.

Individuals with PTSD have a history of experiencing a traumatic event and reexperiencing the event in flashbacks, intrusive recollections of the event, or recurrent dreams of the event. This has led to investigation of possible REM sleep abnormalities in PTSD.40 PTSD patients exhibit a higher percentage of REM sleep, fewer arousals from non-REM sleep, and perceptions of poorer sleep quality.41

Patients with OCD may have reduced sleep continuity, increased wake percent during sleep period, and decreased REM latency.42-44 Further, the obsessions and compulsions of OCD patients may directly disturb their sleep.


Schizophrenic patients suffer significant sleep disruption, particularly during acute exacerbations of illness.21,45 They typically report increased nocturnal wakefulness, daytime fatigue and napping, and frightening dreams. Objective studies performed in schizophrenics show reduced REM sleep latency46-48 and decreased amounts of SWS; this loss of SWS appears to be correlated with negative symptoms and abnormalities in the prefrontal cortex.49,50

Eating Disorders

Patients with eating disorders may have a variety of sleep complaints and objective sleep abnormalities.51 Those with anorexia nervosa typically report excess energy and symptoms of insomnia, particularly during periods of weight loss, whereas those with bulimia nervosa may experience hypersomnia following eating binges. Polysomnographic studies have documented sleep abnormalities generally similar to those seen in depression, such as sleep continuity disruption, loss of SWS, and reduced REM sleep latency.52,53

Binge eating in bulimics occurs in the evening or during the night, and some patients may binge-eat during sleep54; they typically get up sometime after sleep onset and consume large amounts of high-calorie foods. Polysomnographic studies have shown SWS parasomnias in about half of patients studied, and many have prior histories of sleepwalking.55,56 Sleep-related eating has also been reported in patients with other sleep disorders (eg, periodic limb movements, narcolepsy, and obstructive sleep apnea), substance abuse (eg, benzodiazepine and alcohol abuse), and other psychiatric disorders (mood and anxiety disorders).55,57


Most alcoholic patients have significant insomnia symptoms. In a study of patients receiving treatment for alcohol dependence, 61% complained of insomnia during the preceding 6 months.58 Chronic alcoholics tend to show loss of SWS and sleep disruption, particularly if they abstain from drinking.59 Sleep during withdrawal from alcohol is characterized by reduced total sleep, even greater prolongation of sleep latency, and a relative loss of SWS. Increased REM density and/or increased REM sleep amount may also be seen. Both subjective sleep disturbance and objective changes in sleep architecture may predict increased risk for relapse of alcoholism.58,60

Development and Aging

Sleep is profoundly affected by age; not surprisingly, the prevalence of particular kinds of sleep problems clearly varies with age. For example, infants and toddlers have more difficulty falling asleep compared with preadolescent school-age children.61,62 Younger children show increased incidence of parasomnias, such as sleepwalking, nightmares, bruxism, and enuresis, whereas adolescents and adults have more problems with insomnia and daytime sleepiness. Even in children, however, there are significant associations between insomnia and behavioral problems and/or psychiatric disorders.21,63-65

Children with various medical disorders (eg, allergies, asthma, upper respiratory infections, otitis media) also have increased rates of sleep problems.64,66 Overall, sleep problems in children are significantly associated with psychopathology, behavioral problems, and other medical disorders similar to associations in adults.21,64,67

In the elderly, sleep is more shallow and disrupted, with reduction of total sleep, decreased sleep efficiency, prolonged sleep latency, increased arousals during sleep, loss of SWS, and increase in daytime napping. In addition, some primary sleep disorders, such as sleep apnea, periodic movements in sleep, and REM sleep behavior disorder, are more prevalent among the elderly.1,68 The circadian rhythm tends to advance in older people, causing early morning awakening.69

Insomnia is common in the elderly and strongly associated with depressed mood and physical disease.68-70 Sleep disturbance is frequently seen in persons with dementia and Parkinson’s disease, which are often associated with old age. In dementia, the degree of sleep disturbance is likely related to the severity of the disease.71 “Sundowning” refers to episodes of confusion and agitation during the sleep period in patients with dementia.72 In addition, dementia has been associated with prolongation of sleep latency, reduced sleep efficiency, and loss of total sleep time in comparison to age-matched normal subjects.21 Individuals with Alzheimer’s disease may also show decrements in SWS and REM sleep, perhaps related to loss of cholinergic neurons.73-75 Insomnia should be considered a significant symptom in the elderly and not simply assumed to be part of normal aging.76

Drug Effects on Sleep

Most psychotropic medications have significant effects on sleep patterns that may either improve or worsen sleep problems (Table 2).77 The newer antidepressants, including the selective serotonin reuptake inhibitors (SSRIs) (eg, fluoxetine, paroxetine, sertraline) and venlafaxine, may induce insomnia, which may lead to exacerbation of sleep difficulties in some patients. The older tricyclic antidepressants tend to cause sedation, which is why they have typically been administered in a single bedtime dose. Most antidepressants, particularly tricyclics and SSRIs, are associated with higher rates of some primary sleep disorders, including restless legs syndrome, periodic leg movements, and REM sleep behavior disorder.78-80 Increased eye movements during non-REM sleep have also been reported in patients taking SSRIs; the clinical significance of this finding is unknown.80


Given the importance of brainstem monoaminergic systems in REM sleep regulation, it is not surprising that most antidepressants have profound effects on sleep architecture, probably related to their effects on increasing monoaminergic transmission (norepinephrine and/ or serotonin) in the central nervous system. Most antidepressants suppress REM sleep, prolong REM latency, and reduce total amounts of REM sleep.81 Monoamine oxidase inhibitors can lead to profound suppression of REM sleep,82,83 but tricyclics and SSRIs also reduce REM sleep amounts significantly. REM sleep rebound consisting of increases in REM sleep amounts, reduced REM sleep latency, and sleep disruption, may occur following discontinuation of REM sleep-suppressing antidepressants. Several effective antidepressants, including nefazodone,84 trimipramine, iprindole, and amineptine,81 appear to have no REM sleep-suppressing properties.

Although all mood stabilizers typically used in bipolar patients have sedative effects, they have few other effects on sleep architecture. Lithium, however, may increase SWS and can have REM sleep-suppressing effects.85

Antipsychotic medications tend to have sedative effects, and objective sleep studies have demonstrated reduced sleep latency and increases in total sleep.86-88

Treatment of Insomnia

Treatment of insomnia depends on accurate assessment of the underlying causes. Medical illnesses, psychiatric disorders, and primary sleep disorders need to be addressed specifically. Most patients with insomnia, however, may also benefit from attention to sleep hygiene, behavioral therapy, and/or symptomatic treatment with hypnotic medications, regardless of the underlying cause.

Treatment of primary insomnia and sleep disturbance related to psychiatric illness should begin with a careful review of sleep-related habits and practices. Insomnia patients frequently engage in activities that interfere with sleep, and the development of good sleep habits is an important first step in behavioral treatment. The principles of sleep hygiene, outlined in Table 3, include establishment of a regular sleep-waking schedule to reinforce the circadian or daily sleep-waking rhythm, avoidance of sleep-disrupting activities, elimination of stimulants, and maintenance of a sleep-conducive environment. Sleep hygiene is particularly important for psychiatric patients, many of whom may lack daily structure due to their illness.


Other more focused behavioral treatments have been developed, particularly for patients with primary insomnia. These may also be effective for many patients with chronic sleep disturbance from other causes. Several different types of behavioral interventions have been found to be effective in chronic insomnia, but there is not yet a clear consensus as to which specific types or schedules of treatments are more effective. Various types of relaxation techniques have also been used in insomnia. These include progressive muscle relaxation, guided imagery, meditation, and biofeedback, all of which may decrease physiologic and/or cognitive arousal and thus promote sleep.

Stimulus control therapy, developed by Bootzin and Nicassio,89 was primarily designed to reestablish a positive association between the bed and falling asleep; most chronic insomniacs actually become aroused in the sleeping environment after repeated experiences of insomnia. With stimulus control, time spent awake in bed is minimized since patients are only allowed to remain in bed if they are drowsy or fall asleep. Patients are instructed to go to bed only when they are sleepy and not to engage in activities other than sleep or sexual activity in bed. If they do not fall asleep in about 10 minutes, or find themselves becoming aroused or anxious, they are to get out of bed, go to another room, and engage in quiet or relaxing activities until they feel sleepy, at which point they may return to bed. If they cannot fall asleep, they are to get out of bed again and repeat the process until they successfully fall asleep within 10 minutes. Napping is not allowed during the day, and patients must have a fixed waking time in the morning.

Sleep restriction therapy,90 like stimulus control, may also work in part by creating more consistent experiences of falling asleep quickly in bed. Sleep restriction attempts to increase homeostatic pressure for sleep by limiting the hours spent in bed. Patients are instructed to restrict the time spent in bed to the actual hours that they sleep, but not less than 4.5 hours; a set wake-up time is established at the beginning of treatment. If sleep efficiency increases to an average of 90% or more for 5 days, the patient increases the time in bed by 15 minutes. Conversely, if sleep efficiency decreases below 85%, time in bed is reduced to the average sleep time from the previous 5 days.

In general, behavioral therapies, alone or in combination with medication, have been shown to be more effective in treating chronic insomnia than medications alone. Many medications with hypnotic properties, however, are frequently used in the treatment of insomnia (Table 4). The most commonly prescribed medications are benzodiazepine-receptor agonists. They tend to be relatively safe and effective in comparison with other available agents, particularly the barbiturates, which they have largely replaced. Benzodiazepines tend to promote sleep onset, increase total time asleep, and suppress SWS. Some of the newer nonbenzodiazepine drugs that act as benzodiazepine-receptor agonists, such as zolpidem and zaleplon, have been reported not to have SWS suppressive effects.91-93


Low doses of antidepressants are commonly prescribed for insomnia.94 Generally tricyclic antidepressants improve sleep latency and sleep continuity in insomnia patients with depression.95 Trazodone, a nontricyclic antidepressant with sedating properties, also increases total sleep time in depressed patients with insomnia.96 The drug has shown efficacy as a hypnotic in patients with chronic insomnia even in the absence of depression.97 Trazodone, along with other newer antidepressants with sleep-inducing properties, such as nefazodone and mirtazapine, is frequently combined with other antidepressants to improve sleep.98

Histamine-receptor type 1 antihistamines are frequently used as hypnotics. Antihistamine constitutes the primary active ingredient in most over-the-counter sleeping aids. Although studies have shown that antihistamines increase sleepiness in healthy normal individuals, no studies have clearly established the dose range over which hypnotic effects in people with insomnia might be found.99 They are also associated with potentially significant side effects, such as daytime sedation, orthostatic hypotension, and other anticholinergic effects. In some cases, they can have paradoxic activating effects.

Melatonin, a natural hormone, is frequently self-administered for insomnia. Unlike the benzodiazepine hypnotics, melatonin is not a tranquilizer in the classic sense or even a particularly sedating drug. Melatonin has sometimes been referred to as a soporific (to make drowsy) rather than a hypnotic per se.100 Little data are available on melatonin’s effects as a hypnotic in people with insomnia. One study, using very large doses of melatonin (75 mg orally) for 14 consecutive days, showed a significant increase in subjective total sleep time and daytime alertness.101 Studies in which wrist motor activity was used as an outcome variable have reported that elderly insomniacs have reduced motor activity at night after taking both low and high doses of melatonin just before bedtime.102-104

This has raised the hope that melatonin may prove to be effective in the treatment of disrupted sleep, particularly in the elderly. However, there are no positive polysomnographic data to document that melatonin improves sleep maintenance insomnia comparable to the demonstrated efficacy of the short-acting benzodiazepines.105 Melatonin may be useful, however, as a chronobiotic to help with resetting or entraining circadian rhythms in shiftworkers or others with sleep schedule disorders.

Treatment of Sleep Problems in Psychiatric Patients

When insomnia is related to a psychiatric disorder, primary treatment should be directed at the disorder itself. In patients with mood disorders, the choice of antidepressant is usually influenced by the sleep complaints; sedating antidepressants are often prescribed for patients with insomnia (eg, tricyclics, trazodone, nefazodone, or mirtazapine), whereas more activating medications (eg, SSRIs or bupropion) are given to patients with fatigue and/or hypersomnia. When an SSRI or other activating antidepressant is used in patients with insomnia, sedating antidepressants and/or hypnotics may be added to improve sleep. Interestingly, antidepressant response does not appear to depend on eliminating insomnia, as indicated by a comparison of fluoxetine and nefazodone; both were effective, although patients treated with fluoxetine continued to show evidence of insomnia whereas nefazodone improved sleep quality.106 Insomnia should be monitored carefully in bipolar patients and treated aggressively, since sleep loss can trigger or exacerbate mania.

Antianxiety drugs often have sedative-hypnotic effects. Benzodiazepines are often given to patients with anxiety disorders in a larger dose at bedtime, for sleep induction and maintenance.

In schizophrenic patients, most antipsychotic drugs have sleep-promoting effects, particularly the low-potency neuroleptics (eg, chlorpromazine) and clozapine, and hypersomnolence is a significant side effect of these medications. Behavioral disorganization is frequently a significant contributing factor to sleep disturbance in schizophrenics, and should be addressed through improved sleep hygiene.

In general, sedative-hypnotic drugs should not be given to patients with histories of substance abuse. Treatment must be based on substance withdrawal and maintenance of abstinence. Patients should be educated in principles of sleep hygiene and comorbid psychiatric disorders should be treated. Sedating antidepressants may be helpful for those who continue to suffer from significant sleep disruption.


Although insomnia is widely prevalent and associated with significant negative health outcomes, it is generally underdiagnosed and undertreated.4 To date, insomnia research and treatment have concentrated on careful description and symptomatic relief, respectively.

Symptomatic relief has been achieved via both behavioral and pharmacologic means. Studies have shown that this symptomatic relief may have broader benefits. Quality of life has been reported to improve following the treatment of insomnia.107,108 On the other hand, at least one recent study has been unable to demonstrate an effect of insomnia treatment on reported health (both physical and emotional), anxiety, depression, optimism, and absenteeism,13 although the study was limited by lack of information regarding resolution of insomnia.

The functional relationship between insomnia and the wide variety of associated medical and psychiatric disorders has been difficult to clarify. Studies have suggested that insomnia may precede or exacerbate medical and psychiatric disorders. Perhaps more to the point, treatment of insomnia may or may not reduce associated sequelae.

It has been difficult to tease out the effects of available treatments from the putative effects of insomnia. Many hypnotics have residual effects that can impair daytime functioning. For example, a recent meta-analysis of the effects of benzodiazepines in the treatment of insomnia found that they increased both sleep duration and daytime drowsiness and light-headedness.91 Other studies have reported increased impairment in cognitive function with benzodiazepine use, particularly with longer-acting compounds. Thus, it is possible that treating insomnia actually reduces the sequelae of insomnia while at the same time replaces them with drug side effects displaying a similar constellation of daytime symptoms.

It is now possible to sidestep that problem. Newer agents, especially those with ultra-short half-lives, appear to have less tendency to impair cognitive and psychomotor performance the morning after use.92 Together with behavioral and environmental intervention, we can now see the results of insomnia treatment in a clearer light.

Appropriate recognition and treatment of insomnia will ultimately depend on a better appreciation of its true costs and morbidities and the demonstration that the costs can be reduced through medical intervention.  PP


1.    Ford DE, Kamerow DB. Epidemiologic study of sleep disturbance and psychiatric disorders: an opportunity for prevention? JAMA. 1989;262:1479-1484.
2.    Mellinger GD, Balter MB, Uhlenhuth EH. Insomnia and its treatment. Prevalence and correlates. Arch Gen Psychiatry. 1985;42:225-232.
3.    Bixler EO, Kales A, Soldatos CR, Kales JD, Healey S. Prevalence of sleep disorders in the Los Angeles metropolitan area. Am J Psychiatry. 1979;136:1257-1262.
4.    Ancoli-Israel S, Roth T. Characteristics of insomnia in the United States: results of the 1991 National Sleep Foundation Survey. I. Sleep. 1999;22(suppl 2):S347-S53.
5.    Simon GE, VonKorff M. Prevalence, burden, and treatment of insomnia in primary care. Am J Psychiatry. 1997;154:1417-1423.
6.    Roth T, Ancoli-Israel S. Daytime consequences and correlates of insomnia in the United States: results of the 1991 National Sleep Foundation Survey. II. Sleep. 1999;22(suppl 2):S354-358.
7.    Walsh JK, Engelhardt CL. The direct economic costs of insomnia in the United States for 1995. Sleep. 1999;22(suppl 2):S386-393.
8.    Leger D, Levy E, Paillard M. The direct costs of insomnia in France. Sleep. 1999;22(suppl 2):S394-401.
9.    Weissman MM, Greenwald S, Nino-Murcia G, Dement WC. The morbidity of insomnia uncomplicated by psychiatric disorders. Gen Hosp Psychiatry. 1997;19:245-250.
10.    Chevalier H, Los F, Boichut D, et al. Evaluation of severe insomnia in the general population: results of a European multinational survey.
J Psychopharmacol. 1999;13:S21-24.
11.    Shochat T, Umphress J, Israel AG, Ancoli-Israel S. Insomnia in primary care patients. Sleep. 1999;22(suppl 2):S359-365.
12.    Kim K, Uchiyama M, Okawa M, Liu X, Ogihara R. An epidemiological study of insomnia among the Japanese general population. Sleep. 2000;23:41-47.
13.    Zammit GK, Weiner J, Damato N, Sillup GP, McMillan CA. Quality of life in people with insomnia. Sleep. 1999;22(suppl 2):379-385.
14.    Balter MB, Uhlenhuth EH. New epidemiologic findings about insomnia and its treatment. J Clin Psychiatry. 1992;53(suppl):34-39; discussion 40-42.
15.    Hauri PJ. Cognitive deficits in insomnia patients. Acta Neurol Belg. 1997;97:113-117.
16.    Katz DA, McHorney CA. Clinical correlates of insomnia in patients with chronic illness. Arch Intern Med. 1998;158:1099-1107.
17.    Schwartz S, McDowell Anderson W, Cole SR, Cornoni-Huntley J, Hays JC, Blazer D. Insomnia and heart disease: a review of epidemiologic studies. J Psychosom Res. 1999;47:313-333.
18.    Foley DJ, Monjan A, Simonsick EM, Wallace RB, Blazer DG. Incidence and remission of insomnia among elderly adults: an epidemiologic study of 6,800 persons over three years. Sleep. 1999;22(suppl 2):S366-372.
19.    Goldsmith G, Levin JS. Effect of sleep quality on symptoms of irritable bowel syndrome. Dig Dis Sci. 1993;38:1809-1814.
20.    Benca RM. Sleep in psychiatric disorders. In: Aldrich MS, ed. Sleep Disorders. Philadelphia, Pa: W.B. Saunders; 1996:739-764.
21.    Benca RM, Obermeyer WH, Thisted RA, Gillin JC. Sleep and psychiatric disorders: a meta-analysis. Arch Gen Psychiatry. 1992;49:651-668.
22.    Kalogjera-Sackellares D, Cartwright RD. Comparison of MMPI profiles in medically and psychologically based insomnias. Psychiatry Res. 1997;70:49-56.
23.    Breslau N, Roth T, Rosenthal L, Andreski P. Sleep disturbance and psychiatric disorders: a longitudinal epidemiological study of young adults. Biol Psychiatry. 1996;39:411-418.
24.    Charon F, Dramaix M, Mendlewicz J. Epidemiological survey of insomniac subjects in a sample of 1,761 outpatients. Neuropsychobiology. 1989;21:109-110.
25.    Buysse DJ, Reynolds CF III, Kupfer DJ, et al. Clinical diagnoses in 216 insomnia patients using the International Classification of Sleep Disorders (ICSD), DSM-IV and ICD-10 categories: a report from the APA/NIMH DSM-IV Field Trial. Sleep. 1994;17:630-637.
26.    Rush AJ, Erman MK, Giles DE, et al. Polysomnographic findings in recently drug-free and clinically remitted depressed patients. Arch Gen Psychiatry. 1986;43:878-884.
27.    Rosenthal NE, Sack DA, Gillin JC, et al. Seasonal affective disorder. A description of the syndrome and preliminary findings with light therapy. Arch Gen Psychiatry. 1984;41:72-80.
28.    Reynolds CF, III, Kupfer DJ. Sleep research in affective illness: state of the art circa 1987. Sleep. 1987;10:199-215.
29.    Thase ME, Fasiczka AL, Berman SR, Simons AD, Reynolds CFr. Electroencephalographic sleep profiles before and after cognitive behavior therapy of depression. Arch Gen Psychiatry. 1998;55:138-144.
30.    Hudson JI, Lipinski JF, Keck PE, et al. Polysomnographic characteristics of young manic patients: comparison with unipolar depressed patients and normal control subjects. Arch Gen Psychiatry. 1992;49:378-383.
31.    Linkowski P, Kerkhofs M, Rielaert C, Mendlewicz J. Sleep during mania in manic-depressive males. Eur Arch Psychiatry Neurol Sci. 1986;235:339-341.
32.    Livingston G, Blizard B, Mann A. Does sleep disturbance predict depression in elderly people? A study in inner London. Br J Gen Pract. 1993;43:445-448.
33.    Chang PP, Ford DE, Mead LA, Cooper-Patrick L, Klag MJ. Insomnia in young men and subsequent depression. The Johns Hopkins Precursors Study. Am J Epidemiol. 1997;146:105-114.
34.    Dryman A, Eaton WW. Affective symptoms associated with the onset of major depression in the community: findings from the US National Institute of Mental Health Epidemiologic Catchment Area Program. Acta Psychiatr Scand. 1991;84:1-5.
35.    Papadimitriou GN, Linkowski P, Kerkhofs M, Kempenaers C, Mendlewicz J. Sleep EEG recordings in generalized anxiety disorder with significant depression. J Affect Disord. 1988;15:113-118.
36.    Reynolds CF, III, Shaw DH, Newton TF, Coble PA, Kupfer DJ. EEG sleep in outpatients with generalized anxiety: a preliminary comparison with depressed outpatients. Psychiatry Res. 1983;8:81-89.
37.    Mellman TA, Uhde TW. Sleep panic attacks: new clinical findings and theoretical implications. Am J Psychiatry. 1989;146:1204-1207.
38.    Hauri PJ, Friedman M, Ravaris CL. Sleep in patients with spontaneous panic attacks. Sleep. 1989;12:323-337.
39.    Mellman TA, Uhde TW. Electroencephalographic sleep in panic disorder. Arch Gen Psychiatry. 1989;46:178-184.
40.    Ross RJ, Ball WA, Sullivan KA, Caroff SN. Sleep disturbance as the hallmark of posttraumatic stress disorder. Am J Psychiatry. 1989;146:697-707.
41.    Engdahl BE, Eberly RE, Hurwitz TD, Mahowald MW, Blake J. Sleep in a community sample of elderly war veterans with and without posttraumatic stress disorder. Biol Psychiatry. 2000;47:520-524.
42.    Insel TR, Gillin JC, Moore A, Mendelson WB, Loewenstein RJ, Murphy DL. The sleep of patients with obsessive-compulsive disorder. Arch Gen Psychiatry. 1982;39:1372-1377.
43.    Rapoport J, Elkins R, Langer DH, et al. Childhood obsessive-compulsive disorder. Am J Psychiatry. 1981;138:1545-1554.
44.    Hohagen F, Lis S, Krieger S, et al. Sleep EEG of patients with obsessive-compulsive disorder. Eur Arch Psychiatry Clin Neurosci. 1994;243:273-278.
45.    Keshavan MS, Reynolds CF, III, Kupfer DJ. Electroencephalographic sleep in schizophrenia: a critical review. Comprehensive Psychiatry. 1990;31:34-47.
46.    Benson KL, Zarcone VP, Jr. Rapid eye movement sleep eye movements in schizophrenia and depression. Arch Gen Psychiatry. 1993;50:474-482.
47.    Hudson JI, Lipinski JF, Keck PE, Jr., et al. Polysomnographic characteristics of schizophrenia in comparison with mania and depression. Biol Psychiatry. 1993;34:191-193.
48.    Zarcone VP, Benson KL, Berger PA. Abnormal rapid eye movement latencies in schizophrenia. Arch Gen Psychiatry. 1987;44:45-48.
49.    Ganguli R, Reynolds CF III, Kupfer DJ. Electroencephalographic sleep in young never-medicated schizophrenics. Arch Gen Psychiatry. 1987;44:36-44.
50.    van Kammen DP, van Kammen WB, Peters J, Goetz K, Neylan T. Decreased slow-wave sleep and enlarged lateral ventricles in schizophrenia. Neuropsychopharmacology. 1988;1:265-271.
51.    Benca RM, Casper RC. Sleep in eating disorders. In: Kryger MH, Roth T, Dement WC, eds. Principles and Practice of Medicine. 2nd ed. Philadelphia, Pa: W.B. Saunders Company; 1994:927-933.
52.    Delvenne V, Kerkhofs M, Appelboom Fondu J, Lucas F, Mendlewicz J. Sleep polygraphic variables in anorexia nervosa and depression: a comparative study in adolescents. J Affect Disord. 1992;25:167-172.
53.    Levy AB, Dixon KN, Schmidt H. Sleep architecture in anorexia nervosa and bulimia. Biol Psychiatry. 1988;23:99-101.
54.    Gupta MA. Sleep-related eating in bulimia nervosa: an underreported parasomnia disorder. Sleep Res. 1991;20:182.
55.    Schenck CH, Hurwitz TD, Bundlie SR, Mahowald MW. Sleep-related eating disorders: polysomnographic correlates of a heterogeneous syndrome distinct from daytime eating disorders. Sleep. 1991;14:419-431.
56.    Winkelman JW. Clinical and polysomnographic features of sleep-related eating disorder. J Clin Psychiatry. 1998;59:14-19.
57.    Spaggiari MC, Granella F, Parrino L, Marchesi C, Melli I, Terzano MG. Nocturnal eating syndrome in adults. Sleep. 1994;17:339-344.
58.    Brower KJ, Aldrich MS, Robinson EA, Zucker RA, Greden JF. Insomnia, self-medication, and relapse to alcoholism. Am J Psychiatry. 2001;158:399-404.
59.    Obermeyer W, Benca R. Effects of drugs on sleep. Otolaryngol Clin North Am. 1999;32:289-302.
60.    Gillin JC, Smith TL, Irwin M, Butters N, Demodena A, Schuckit M. Increased pressure for rapid eye movement sleep at time of hospital admission predicts relapse in nondepressed patients with primary alcoholism at 3-month follow-up. Arch Gen Psychiatry. 1994;51:189-197.
61.    Rosen C, Mahowald M, Ferber R. Sleepwalking, confusional arousals, and sleep terrors in the child. In: Ferber T, Kryer M, eds. Principles and Practices of Sleep Medicine in Children. New York, NY: W. B. Saunders; 1995:99-106.
62.    Broughton R. NREM arousal parasomnias. In: Kryer M, Roth T, Dement W, eds. Principles and Practices of Sleep Medicine. New York, NY: W. B. Saunders; 2000:693-706.
63.    Minde K, Popiel K, Leos N, Falkner S, Parker K, Handley-Derry M. The evaluation and treatment of sleep disturbances in young children. J Child Psychol Psychiatry. 1993;34:521-533.
64.    Stein MA, Mendelsohn J, Obermeyer WH, Amromin J, Benca R. Sleep and behavior problems in school-aged children. Pediatrics. 2001;107:E60.
65.    Kahn A, Van de Merckt C, Rebuffat E, et al. Sleep problems in healthy preadolescents. Pediatrics. 1989;84:542-546.
66.    Owens JA, Spirito A, McGuinn M, Nobile C. Sleep habits and sleep disturbance in elementary school-aged children. J Dev Behav Pediatr. 2000;21:27-36.
67.    Sadeh A, McGuire JPD, Sachs H, et al. Sleep and psychological characteristics of children on a psychiatric inpatient unit. J Am Acad Child Adolesc Psychiatry. 1995;34:813-819.
68.    Beneto A. Sleep disorders in the elderly. Epidemiology. Rev Neurol. 2000;30:581-586.
69.    Martin J, Shochat T, Ancoli-Israel S. Assessment and treatment of sleep disturbances in older adults. Clin Psychol Rev. 2000;20:783-805.
70.    Ancoli-Israel S. Insomnia in the elderly: a review for the primary care practitioner. Sleep. 2000;23(suppl 1):S23-S30. Discussion S36-38.
71.    Bliwise DL. Sleep in normal aging and dementia. Sleep. 1993;16:40-81.
72.    Vitiello MV, Bliwise DL, Prinz PN. Sleep in Alzheimer’s disease and the sundown syndrome. Neurology. 1992;42:83-93. Discussion 93-94.
73.    Bliwise DL, Tinklenberg J, Yesavage JA, et al. REM latency in Alzheimer’s disease. Biol Psychiatry. 1989;25:320-328.
74.    Prinz PN, Vitaliano PP, Vitiello MV, et al. Sleep, EEG and mental function changes in senile dementia of the Alzheimer’s type. Neurobiol Aging. 1982;3:361-370.
75.    Vitiello MV, Prinz PN, Williams DE, Frommlet MS, Ries RK. Sleep disturbances in patients with mild-stage Alzheimer’s disease. J Gerontol. 1990;45:M131-138.
76.    Henderson S, Jorm AF, Scott LR, Mackinnon AJ, Christensen H, Korten AE. Insomnia in the elderly: its prevalence and correlates in the general population. Med J Aust. 1995;162:22-24.
77.    Obermeyer WH, Benca RM. Effects of drugs on sleep [review]. Neurol Clin North Am. 1996;14:827-840.
78.    Bakshi R. Fluoxetine and restless legs syndrome. J Neurol Sci. 1996;142:151-152.
79.    Dorsey CM, Lukas SE, Cunningham SL. Fluoxetine-induced sleep disturbance in depressed patients. Neuropsychopharmacology. 1996;14:437-442.
80.    Schenck CH, Mahowald MW, Kim SW, O’Connor KA, Hurwitz TD. Prominent eye movements during NREM sleep and REM sleep behavior disorder associated with fluoxetine treatment of depression and obsessive-compulsive disorder. Sleep. 1992;15:226-235.
81.    Vogel GW, Buffenstein A, Minter K, Hennessey A. Drug effects on REM sleep and on endogenous depression. Neurosci Biobehav Rev. 1990;14:49-63.
82.    Bowers M, Kupfer DJ. Central monoamine oxidase inhibition and REM sleep. Brain Res. 1971;35:561-564.
83.    Wyatt RJ, Fram DH, Kupfer DJ, Snyder F. Total prolonged drug-induced REM sleep suppression in anxious-depressed patients. Arch Gen Psychiatry. 1971;24:145-155.
84.    Armitage R, Rush AJ, Trivedi M, Cain J, Roffwarg HP. The effects of nefazodone on sleep architecture in depression. Neuropsychopharmacology. 1994;10:123-127.
85.    Kupfer DJ, Reynolds CF, III, Weiss BL, Foster G. Lithium carbonate and sleep in affective disorders: further considerations. Arch Gen Psychiatry. 1974;30:79-84.
86.    Brannen JO, Jewett RE. Effects of selected phenothiazines on REM sleep in schizophrenics. Arch Gen Psychiatry. 1969;21:284-290.
87.    Kaplan J, Dawson S, Vaughan T, Green R, Wyatt RJ. Effect of prolonged chlorpromazine administration on the sleep of chronic schizophrenics. Arch Gen Psychiatry. 1974;31:62-66.
88.    Kupfer DJ, Wyatt RJ, Greenspan K, Scott J, Snyder F. Lithium carbonate and sleep in affective illness. Arch Gen Psychiatry. 1970;23:35-40.
89.    Bootzin RR, Nicassio PM. Behavioral treatments for insomnia. In: Hersen M, Eissler R, Miller P, eds. Progress in Behavior Modification. New York, NY: Academic Press; 1978:1-45.
90.    Spielman AJ, Saskin P, Thorpy MJ. Treatment of chronic insomnia by restriction of time in bed. Sleep. 1987;10:45-56.
91.    Holbrook AM, Crowther R, Lotter A, Cheng C, King D. Meta-analysis of benzodiazepine use in the treatment of insomnia. CMAJ. 2000;162:225-233.
92.    Walsh JK, Pollak CP, Scharf MB, Schweitzer PK, Vogel GW. Lack of residual sedation following middle-of-the-night zaleplon administration in sleep maintenance insomnia. Clin Neuropharmacol. 2000;23:17-21.
93.    Troy SM, Lucki I, Unruh MA, et al. Comparison of the effects of zaleplon, zolpidem, and triazolam on memory, learning, and psychomotor performance. J Clin Psychopharmacol. 2000;20:328-337.
94.    Benca RM. Eating disorders. In: Kryer M, Roth T, Dement W, eds. Principles and Practices of Sleep Medicine. New York, NY: W. B. Saunders; 2000:1169-1175.
95.    Kupfer DJ, Spiker DG, Rossi A, Coble PA, Shaw DH, Ulrich RF. Nortriptyline and EEG sleep in depressed patients. Biol Psychiatry. 1982;17:535-546.
96.    Scharf MB, Sachais BA. Sleep laboratory evaluation of the effects and efficacy of trazodone in depressed insomniac patients. J Clin Psychiatry. 1990;51(suppl):13-17.
97.    Parrino L, Spaggiari MC, Boselli M, Di Giovanni G, Terzano MG. Clinical and polysomnographic effects of trazodone CR in chronic insomnia associated with dysthymia. Psychopharmacology. 1994;116:389-395.
98.    Nierenberg AA, Adler LA, Peselow E, Zornberg G, Rosenthal M. Trazodone for antidepressant-associated insomnia. Am J Psychiatry. 1994;151:1069-1072.
99.    Roth T, Roehrs T, Koshorek G, Sicklesteel J, Zorick F. Sedative effects of antihistamines.
J Allergy Clin Immunol. 1987;80:94-98.
100.    Wirz-Justice A, Armstrong SM. Melatonin: nature’s soporific? J Sleep Res. 1996;5:137-141.
101.    MacFarlane JG, Cleghorn JM, Brown GM, Streiner DL. The effects of exogenous melatonin on the total sleep time and daytime alertness of chronic insomniacs: a preliminary study. Biol Psychiatry. 1991;30:371-376.
102.    Garfinkel D, Laudon M, Nof D, Zisapel N. Improvement of sleep quality in elderly people by controlled-release melatonin. Lancet. 1995;346:541-544.
103.    Haimov I, Lavie P, Laudon M, Herer P, Vigder C, Zisapel N. Melatonin replacement therapy of elderly insomniacs. Sleep. 1995;18:598-603.
104.    Wurtman RJ, Zhdanova I. Improvement of sleep quality by melatonin. Lancet. 1995;346:1491.
105.    Czeisler CA, Cajochen C, Turek FW. Melatonin in regulation of sleep and circadian rhythms. In: Kryer M, Roth T, Dement W, eds. Principles and Practices of Sleep Medicine. New York, NY: W.B. Saunders; 2000:693-706.
106.    Rush AJ, Armitage R, Gillin JC, et al. Comparative effects of nefazodone
and fluoxetine on sleep in outpatients with major depressive disorder. Biol Psychiatry. 1998;44:3-14.
107.    Hindmarch I, Fairweather DB. Assessing the residual effects of hypnotics. Acta Psychiatr Belg. 1994;94:88-95.
108.    Leger D, Quera-Salva MA, Philip P. Health-related quality of life in patients with insomnia treated with zopiclone. Pharmacoeconomics. 1996;10:39-44.