Sleep Medicine Reviews, Vol. 1, No. 1, pp 45-56, 1997 MEDICINE
Sleep and mood disorders Ruth M. Bencal, Masako Okawa’, Makoto Uchiyama*, Shigeru Ozaki*, Toru Nakajima*, Kayo Shibui* and William H. Obermeyer’ 1 Department of Psychiatry, University of Wisconsin-Madison, 6001 Research Pavk Blvd., Madison, WI 53719-1179, USA; 2 Department of Psychophysiology, National Institute of Mental Health, NCNP lchikawa-City, 272 Japan
Mood disorders arefound in one-tkiud to one-half of patients with ckvonic sleep problems. Likewise, most patients with mood disorders experience insomnia, but a minority obtain significantly increased amounts of sleep. Although mood disorders cause significant morbidity and mortality, they often go undiagnosed. Attention to sleep complaints could lead to better identification of mood disorders. Management of sleep problems in patients with mood disorders should focus on treating underlying mood disordevs with attention to the nature of the sleepcomplaint. Patients with depressionshow characteristicabnormalities in sleep continuity, slow-wave sleep and REM sleep patterns. Differences in sleep patterns cannot reliably distinguish patients with depression from those with otkev psychiatric disorders, but sleep changes may provide a window on neuvobiological abnormalities in depression.
Key words: Sleep, mood disorders, depression, insomnia, sleep deprivation, light therapy
Sleep disturbances occur in almost all patients suffering from mood disorders, and sleep complaints are often among the most problematic symptoms for these individuals. Similarly, mood disorders are more likely to be found among people with abnormal sleep. Two community-based epidemiological studies showed that adults with insomnia were far more likely to be suffering from major depression (rates from 14% to 21%) than those without sleep complaints (rates of depression less than 1% in both studies).l, ’ Sleep abnormalities associated with mood disorders are not limited to insomnia as even individuals with complaints of hypersomnia showed an increased prevalence of mood disorders (9.9%).2 The likelihood of mood disorders may be even greater among patients with insomnia who present for medical treatment. A study of patients presenting to general medical clinics found that the symptoms of sleep disturbance and fatigue had the greatest positive predictive values (61% and 69%, respectively) for significant depressive symptoms3 In a multi-center survey of patients seen in sleep disorders clinics, the International Classification of Sleep Disorders (ICSD) diagnosis, “sleep disorder associated with mood disorders”, was the primary diagnosis in 32.2% of patients and the primary or secondary diagnosis in 53.7% of patients, making it the most common diagnosis associated with insomnia.4 1087-0792/97/010045+12
0 1997 W.B. Saunders Company Ltd
R. M. Benca et al.
Although sleep abnormalities are usually easily identified in patients known to have depression, the converse seems not to be true: mood disorders often go undiagnosed in non-psychiatric settings. It has been estimated that the diagnosis of depression is missed in up to half of affected patients in primary care settings. Given the strong association between sleep complaints and mood disorders, it is essential that any patient with chronic insomnia be thoroughly evaluated for a mood disorder. Mood disorders are serious medical problems, in that up to one-quarter of patients will make suicide attempts and up to 15% will eventually complete a suicide. The disability related to mood disorders is comparable to that associated with other chronic medical conditions, and patients with mood disorders have much higher rates of utilization of other medical services. In addition to these overriding considerations, identification and treatment of mood disorders is important for the successful treatment of associated sleep problems.
Major depressive disorder (MDD) is the most prevalent mood disorder, affecting up to 25% of women and half as many men across the lifespan. Patients with MDD may have one or more major depressive episodes across their lifetimes. The criteria for diagnosis of major depressive episodes are the presence of depressed mood and/or loss of interest or pleasure for a period of at least 2 weeks, along with four or more of the following additional criteria: (1) significant gain or loss of weight; (2) insomnia or hypersomnia; (3) psychomotor agitation or retardation; (4) decreased energy or fatigue; (5) feeling guilty or worthless; (6) decreased concentration; and (7) thoughts of death or suicidal ideation.5 Patients with dysthymia have depressive symptoms which do not meet full criteria for a major depressive episode and persist for periods of at least 2 years. They may also suffer from MDD superimposed on a chronic dysthymic state, sometimes referred to as “double depression”. Bipolar disorder affects l-2% of the population and consists of manic, hypomanic or mixed episodes; bipolar patients often suffer from major depressive episodes as well. Manic episodes consist of periods of at least 1 week in which mood is abnormally elevated or irritable. Three or more additional diagnostic criteria must be present; including: (1) grandiosity; (2) decreased need for sleep; (3) increased pressure of speech; (4) racing thoughts; (5) distractibility; (6) increase in goal-directed activities; and (7) increase in pleasure-seeking activities, often with negative consequences5 Hypomanic episodes are less severe than manic episodes, and mixed episodes have elements of both mania and depression.
Insomnia is the most common complaint in patients with depression and may consist of a variety of specific symptoms, including prolonged latency to sleep, frequent and/ or extended awakenings during the night, and early morning awakening. Depressives may also complain of vivid dreams, often with more negative emotional content. They
Sleep and mood Table
Class Monoamine oxidase inhibito&
Tricyclics and tetr&yclics
Imipramine Nortryptiline Despramine Protriptyline Fluoxetine Sertraline Paroxetine Venlafaxine Buproprion Trazodone Nefazodone
Selective serotonin re-uptake inhibitors
150-300 mg Sedation 75-200 mg REM sleep suppression loo-250 mg Increased total sleep 150-300 mg Decreased sleep latency 150-3010% 50-151Orng 75-200 rng 20-60 mg 20-60 mg Insomnia 50-200mg REM sleep suppression 2050 mg NREM eye movements 75-300 mg Insomnia or sedation 300-450 mg Increased REM sleep 150-400 mg Sedation, increased SWS 300-600 mg Sedation
&mpathomimetics, agitation, edema, Anticholinergic effects (orthostatic, hypotension, dry mouth, constipation, urinary retention, sweating, cognitive deficits), tremor, weight gain, tachycardia, slowing of cardiac conduction Nausea, diarrhea, . 1*1--welgnc loss, nervousness, headache, sexual dysfunction Nausea, headache, dry mouth, constipation, nervousness Lowered seizure threshold, weight loss Orthostatic hypotension, priapism Dizziness, nausea, dry mouth, headache, constipation
describe their sleep as “less deep” than previously, and often do not feel well rested upon awakening. Although patients with depression and insomnia frequently report significant daytime tiredness, objective testing usually does not demonstrate increased sleep tendency. In some cases, depression is accompanied by hypersomnia rather than insomnia. Such patients report increased duration of nocturnal sleep, often with difficulty waking up in the morning and increased napping. Hypersomnia tends to occur in bipolar patients during major depressive episodes and has been commonly described in seasonal affective disorder (SAD) or winter depression. In addition to hypersomnia, patients with SAD frequently report cravings for foods with high fat and carbohydrate content. SAD is more prevalent at extreme latitudes, and symptoms appear in the fall and winter months and diminish or vanish in the spring. In some cases, patients experience spring/summer mania or hypomania.
R. M. Benca et al.
Patients experiencing hypomanic or manic episodes usually have significant decreases in their sleep amounts. In contrast to patients with depression, manic patients usually report a decreased need for sleep and may not complain about insomnia when their mood and energy are elevated.
Depressives have been studied with polysomnography more frequently than any other category of psychiatric patients. A variety of sleep abnormalities have been described, and have been reviewed elsewhere. &’ In comparison to age-matched normal control subjects, groups of depressed patients show sleep abnormalities which can be grouped into three categories: 1. Problems with initiation and maintenance of sleep. Depressives take longer to fall asleep (prolonged sleep latency), have more frequent arousals during sleep, and are more likely to awaken early in the morning. This fragmentation produces decreased sleep efficiency and reduced amounts of sleep. 2. Loss of slow-wave sleep (SWS). SWS processes appear to be abnormal in depression as indicated by both the absolute (SWS minutes) and relative (SWS% of total sleep) losses. The results of quantitative analysis of the sleeping EEG have been mixed, but in general, fewer waves in the delta (0.54 Hz) band are seen in depressives, particularly early in the night.‘,” 3. Rapid-eye-movement (REM) sleep changes. Abnormalities in REM sleep are perhaps the most characteristic sleep changes in patients with mood disorders. For depressives, in comparison to healthy subjects: less time elapses from sleep onset to the first REM sleep period (reduced REM latency); more REM sleep occurs in the first part of the night; and, there are more frequent eye movements during REM sleep. Most investigations of sleep in mood disorders have focused on acutely depressed patients with underlying MDD. Studies of other groups of mood disorders patients have generally yielded similar findings. Sleep patterns in depressed bipolar subjects were not distinguishable from those seen in patients with MDD. A study of bipolar patients during manic episodes also demonstrated sleep abnormalities similar to those seen in MDD, particularly reduced REM latency. l1 Dysthymic subjects, on the other hand, tended not to show significant sleep abnormalities compared to normal controls. Few data are available on depressed patients with significant hypersomnia, such as those with SAD, but they appeared to show similarities to patients with MDD as welll* It has been suggested that sleep changes, particularly REM sleep and/or SWS abnormalities may be biological markers for mood disorders. Although sleep disturbances worsen during acute episodes of illness, they often do not normalize completely during periods of clinical remission. Thus patients with previous episodes of depression report more subjective sleep disturbance than those with no prior history, and objective parameters, particularly reduced REM latency, may remain abnormal. It has been theorized that sleep abnormalities represent either a “scar” related to prior episodes of illness or, alternatively, a “trait” related to an underlying vulnerability to mood disorders. At the present time, polysomnographic changes related to mood disorders are of greater importance from a research perspective than from a clinical standpoint.
Sleep and mood
Although sleep studies may have some ability to discriminate between depressed patients and healthy control subjects, even measures such as REM sleep latency have limited utility for distinguishing patients with mood disorders from other psychiatrically ill patients.7 There have been suggestions of potential clinical applications for sleep studies in the treatment of mood disorders. In particular, several studies have indicated that early effects of antidepressants on sleep architecture may relate to their ultimate therapeutic efficacy13,14 and that sleep parameters may be predictive of relapse (reviewed by Kupfer’), but these possibilities have not been systematically explored. Furthermore, sleep studies may be important to rule out other sleep disorders. There is increasing evidence that sleep abnormalities may provide important clues about the underlying pathophysiological mechanisms of mood disorders. Deficits in central catecholaminergic systems as well as increased cholinergic activity and/or hypersensitivity have been associated with depression and may explain the observed sleep abnormalities observed in association with mood disorders. It is critically important to understand the relationship between sleep problems and mood disorders, i.e. whether sleep abnormalities exacerbate mood disorders or vice versa. In the case of mania, both situations occur. Not only does acute mania lead to dramatic curtailment of sleep, but sleep loss can precipitate or exacerbate mania in those with bipolar disorder. Wehr has postulated that sleep loss, by increasing central catecholamine levels, may act via a feed-forward mechanism to prolong the manic state.15 The potential impact of sleep loss on the genesis of depression is less clear. An important public health question is whether the increasing sleep deprivation and sleep schedule disruption incurred by our society is related to the increasing incidence of depression and other mood disorders. A better understanding of the relationship between sleep and mood regulatory mechanisms could have major impact on our clinical approach to treating sleep problems in mood disorders.
Treatment Treatment should first be aimed at correcting underlying mood disorders, if present, in patients with sleep disturbance. Sleep will generally improve along with the illness; specific attention to the sleep complaints will usually result in a more rapid resolution of sleep difficulties and, possibly, the mood disorder as well. Medication is usually indicated in the treatment of depressive episodes and may be helpful for subsyndromal symptoms in some individuals as well. The choice of antidepressant is usually based on consideration of potential side effects. In the treatment of depression with significant sleep complaints, the side effect profile can often be used to advantage. The major classes of antidepressants include the monoamine oxidase inhibitors (MAOIs), tricyclic and tetracyclic antidepressants (TCAs), selective serotonin re-uptake inhibitors (SSRIs), as well as others which do not fit into the previous categories. Most antidepressants enhance central monoaminergic activity, and some of them also have anticholinergic properties; these properties, when considering current theories of sleep physiology, seem to form the basis of their REM sleep-suppressing capabilities. It has been suggested by Vogel that antidepressant effects may in fact be related to the ability of medications to suppress REM sleep.16
R. M. Benca et al.
MAOIs are the most potent REM sleep-suppressing agents of all the antidepressants. They are the oldest available antidepressants, and although effective in the treatment of depression and panic disorder, their use is greatly limited by their side effect profile and toxicity. Side effects include orthostatic hypotension, constipation, tachycardia, sexual dysfunction and agitation. Patients taking MAOIs may experience hypertensive crises if they ingest tyramine-containing foods (such as aged cheese, red wine, dark beer) or take sympathomimetic medications or other antidepressants. Effects on sleep more commonly include insomnia, but sedation can occur as well. MAOI-induced insomnia may be treated with benzodiazepines, or cautious administration of trazodone. TCAs are among the most efficacious medications in the treatment of depression and have often been used to treat insomnia because of their sedating properties. Sedative effects are most pronounced with amitriptyline, doxepin and clomipramine; desipramine and protriptyline produce the least sedation. Some patients may complain of oversedation, which can include prolonged sleep duration and/or impairments of cognition and performance in the daytime. It has been reported that TCAs may exacerbate periodic leg movements,17 which could explain persistent sleep problems in patients treated with TCAs. However, the relationship between antidepressants and periodic leg movements is unclear, and little has been published on this topic. With the exception of trimiprimine, the TCAs suppress REM sleep and prolong REM latency. Unfortunately, TCAs also have significant side effects which make them difficult to tolerate, such as anticholinergic effects (dry mouth, constipation, flushing/sweating, blurred vision, urinary retention, cognitive dysfunction, etc.), orthostatic hypotension and weight gain. Their cardiac effects make them highly toxic in overdose. Anticholinergic properties are suspected as the main cause of cognitive impairment and development of delirium, especially in elderly depressed patients (mianserin has been reported to be useful in the treatment of delirium in the agedl’). Adverse effects may also occur upon abrupt cessation of anticholinergic compounds. One should therefore be cautious in discontinuing TCAs; careful and slow withdrawal is indicated. The SSRIs are currently considered first-line agents in the treatment of depression, based on their efficacy (which is similar to TCAs) along with their greatly reduced toxicity and side effects. Like MAOIs and TCAs, SSRIs also lead to REM sleep suppression. The major side effects of SSRIs include anorexia/G1 upset, nervousness or agitation, sexual dysfunction and insomnia. Treatment with fluoxetine and sertraline has been reported to be related to the occurrence of nocturnal bruxism. Bupropion may relieve such SSRI-related nocturnal bruxism. Fluoxetine-induced nightmares, oculomotor abnormalities occurring during NREM sleep, and REM sleep behavior disorders (RBD) have also been reported. I9 It should be noted that RBD can be a consequence of any of the REM-suppressing antidepressants. Insomnia and agitation resulting from SSRI use can be problematic in patients already suffering from severely disturbed sleep, but the overall advantages of the SSRIs in alleviating depression may still make it worthwhile to use them in these cases, especially in conjunction with a sedating antidepressant such as trazodone (see below). Because of their activating effects in most patients, SSRIs are usually administered in the morning. Although data comparing SSRI effects on sleep is not available, fluoxetine is thought to be the most activating of the group. In the minority of patients, for whom SSRIs lead to sedation, these medications may be taken at bedtime.
Sleep and mood
Newer agents unrelated to the above compounds include trazodone, buproprion, venlafaxine and nefazodone. Venlafaxine is similar to the SSRIs in its activating properties and can also lead to significant insomnia. Buproprion and nefazodone are among the few antidepressants reported to increase REM sleep rather than suppress iCzorzlthis suggests that the hypothesis regarding the relationship between REM sleep suppression and antidepressant effects may need to be modified. Both trazodone and nefazodone are sedating. Trazodone is often used in the treatment of insomnia in depressed patients and can be useful in combination with SSRIs; it has also been shown to be effective in the treatment of insomnia in non-depressed subjects.22 In addition to mild REM-sleep suppression, trazodone may actually increase SWS, unlike most other antidepressants. Patients experiencing hypomanic or manic episodes are usually treated with mood stabilizers, which include lithium, carbamazepine and sodium valproate. All can lead to increased drowsiness. Lithium has been reported to have multiple effects on sleep architecture, including mild REM suppression and increased NREM sleep, but the latter two agents appear to have little impact on sleep parameters. For depressed or manic patients with insomnia, short-term use of hypnotics may be helpful, particularly during periods of acute illness. Although many antidepressants have beneficial effects on anxiety symptoms, patients with significant anxiety may require additional treatment with benzidiazepines or other anxiolytic drugs. As stated above, treatment of insomnia is particularly important in manic patients because of the role of sleep loss in exacerbating mania. Antipsychotics are generally used to treat symptoms such as hallucinations and delusions or in the acute phase of a manic episode for rapid symptom control. Electroconvulsive therapy (ECT) is used for both severe depression and mania in individuals who do not respond to medication and/or are acutely suicidal. ECT also has been reported to normalize REM sleep.” Hypersomnic patients, such as those with SAD, often benefit from the more activating antidepressants. In severe cases, stimulant medications may be needed. Other adjunctive treatments include light therapy, described below. Most individuals with chronic sleep disorders develop a psychophysiological component to their insomnia (i.e. aversive conditioning to their sleep environment). In addition to the somatic treatments outline above, patients with sleep problems and mood disorders should also receive instruction on behavioral management of their sleep. This would include education on sleep hygiene as well as specific behavioral techniques, such as relaxation training, stimulus control and/or sleep restriction.
Over the past two decades, light therapy has come to be recognized as one of the more effective non-drug therapies for sleep disorders. This treatment was first administered to patients with seasonal affective disorder (SAD), but its clinical application was later extended to patients with non-seasonal mood disorders and sleepwake schedule disorders. Following the identification of SAD, the winter depression was reported to be successfully treated by a prolongation of day length using exposure to artificial bright
R. M. Benca et al.
light.24 In the early trials of light therapy for SAD, fluorescent lamps (providing at least 2500 lux) were used; patients with winter depression were exposed to artificial bright light in the early morning and in the early evening to prolong day length by more than 2 h. In most cases, therapeutic responses including decrease in hypersomnia and improvement in mood emerged within days. Early discussions focused on the timing of the light therapy. Lewy has suggested that the antidepressant effect of light might be result from a phase shift of the circadian rhythm.25 The onset of melatonin secretion under dim light conditions (DLMO) was reported to be delayed in SAD patients compared with controls. Exposure to bright light in the morning was found to advance the timing of DLMO in SAD patients. This finding supported the notion that the phase advancing effect of light might be responsible for its therapeutic efficacy. Subsequent comparative studies,26,27 however, revealed that light therapy in the morning, midday and evening improved the depressive symptoms to the same extent in patients with SAD, regardless of the circadian phase changes provoked by light therapy. It is not clear that either circadian phase-shifting effects or suppression of melatonin play a major role in the antidepressant effect of bright light therapy.*’ The intensity of light needed to obtain a therapeutic response has also been investigated. Early reports stressed the importance of high light intensity, whereas more recent evidence suggests that very bright light is not always necessary to improve the depressive symptoms of SAD. 29 Light therapy has also been used in patients with mood disorders not featuring a seasonal pattern; it was reported to be effective in bipolar depressives, 3obut seemed to have variable effects on non-seasonal, unipolar depression3i It has been suggested that light therapy was particularly effective for “atypical symptoms”, especially hyperphagia and carbohydrate craving, which was suggested as a marker for a responder of light therapy in SAD. Serotonin depletion seems to be responsible for these changes in eating behavior, since selective serotonergic antagonists (e.g. d-fenfluramine) were reported to suppress hyperphagia in SAD.32 A recent study demonstrated that untreated SAD patients displayed abnormal hormonal responses to serotonergic agonists in winter as well as summer, but that these abnormal responses were normalized with light therapy. These findings suggest that the therapeutic effects of light exposure in SAD may involve a serotonergic mechanism.33 Recent placebo-controlled studies have indicated that, when treatment expectations are matched, light therapy does not produce a measurable effect on depression until after the second week of treatment. Early studies were not placebo controlled and usually did not measure treatment response beyond two weeks. As a consequence, many of the issues raised by the pioneering studies in the use of light for the treatment of affective disorders remain unanswered. These studies raised many important issues regarding the relationships among light, affective disorders, sleep and biological rhythms. Light treatment has now been shown to be effective, but the precise mechanism is not fully understood.
It is intriguing that although insomnia is one of the most troublesome symptoms associated with depression, sleep deprivation has been shown to alleviate depression.
Sleep and mood
Sleep deprivation (SD) was introduced as a treatment for depression in the late 1960s and has been used for nearly 30 years. I5 Although SD therapy has not been a mainstream antidepressant therapy, it seems an attractive treatment because of its rapid antidepressant effect, inexpensiveness and clinical safety. The rapid improvement following SD may be encouraging to depressed patients by showing them the possibility of improvement. Total sleep deprivation (TSD), in which patients are encouraged to stay awake throughout the night, was the first procedure described. Sleep obtained after sleep deprivation is likely to be depressogenic, even though it is still unclear whether REM or NREM sleep is responsible for this phenomenon. TSD has not been widely used; relapses occur after even brief recovery sleep, and the consequent exhaustion does not allow repeated use. Subsequent studies have revealed that partial sleep deprivation (PSD) during the latter part of the night was just as effective as TSD. An advantage of the development of PSD as a therapy is that it can be used repeatedly. Recent studies have shown that relapses that accompany PSD can be prevented by its combination with antidepressant medication or lithium. PSD may provoke or intensify drug responses to antidepressants, even in seemingly drug-resistant depressive patients. Selective REM sleep deprivation, a subtype of PSD, was first used to test the hypothesis that REM sleep-suppressing capacity was related to the therapeutic effects of antidepressants. Although REM sleep deprivation did show antidepressant effects, its clinical use has been limited by the difficulty of performing selective arousals during REM sleep outside of the sleep laboratory. Another sleep manipulation suggested for the treatment of depression and its associated sleep problems is phase advance therapy.34 This treatment was devised to correct the putative abnormalities between circadian rhythms and the timing of sleep; some studies have suggested that the circadian rhythms of depressed patients, including those of core body temperature and serum cortisol levels, might be phase advanced relative to sleep. In phase advance therapy, the patient is instructed to retire and then wake up several hours earlier than their usual schedule. Like PSD, phase advance therapy also deprives the patient of early morning sleep. Phase advance therapy, however, has the advantage of permitting normal sleep. More recently, to minimize the chance of relapse after the recovery sleep, a combination of sleep deprivation with consecutive sleep phase advance35 was found to be beneficial in patients with MDD. After TSD, the subsequent recovery sleep was scheduled 6 hours earlier than patient’s conventional retiring and waking times. The advanced sleep schedule was gradually delayed 1 hour per day until it returned to their conventional sleep schedule. Sleep deprivation therapies have also been reported to be effective in patients with late luteal phase dysphoric disorder (LLPDD)/p remenstrual syndrome (PMS).36 Sleep deprivation may also be an effective and safe alternative to drug therapy for depressed female patients who are, or may be pregnant. Attempts to clarify the mechanism of the antidepressant effect of sleep deprivation has been made by using PET (positron emission tomography) or SPECT (single-photon emission computed tomography). A PET study using (18F) deoxyglucose (FDG) revealed that sleep deprivation may normalize the abnormally elevated glucose metabolism in the cingulate cortex of depressive patients.37 A dopamine D2 receptor ligand SPECT study has suggested that sleep deprivation may enhance the release of dopamine.38
R. M. Benca et al.
Practice Points Chronic insomnia is more strongly associated with depression than with any other medical or psychiatric illness. Depression leads to significant morbidity and mortality and is underdiagnosed in primary medical settings. Symptoms of depression include depressed mood, insomnia or hypersomnia, fatigue, change in appetite, psychomotor agitation or retardation, guilt, poor concentration, and suicidal ideation. Sleep changes in depression include disturbed sleep continuity, loss of slow wave sleep, and changes in REM sleep, particularly shortened latency to REM sleep onset. Sleep abnormalities associated with mood disorders often persist in between episodes of illness, but are usually more severe during episodes of mood disorders. Sleep studies cannot reliably diagnose mood disorders. Treatment of mood disorders usually leads to improvement in the associated sleep abnormalities. Antidepressant therapy tends to normalize sleep architecture in patients with depression. In treating patients with sleep problems and mood disorders, side effect profile should guide the choice of an antidepressant. For treatment of insomnia associated with mood disorders, sedating antidepressants, adjunctive hypnotics and/or behavioral therapy may be helpful. Most antidepressants suppress REM sleep and are associated with REM sleep rebound upon withdrawal. Such REM loss is not a contraindication for use of an antidepressant, and may even be related to its effectiveness. Antidepressant medications can exacerbate or induce periodic leg movements and REM sleep behavior disorder. Light therapy may be useful in treatment of depression, particularly SAD and atypical symptoms of depression, such as hypersomnia and increased appetite. Light and sleep deprivation therapies may be useful adjunctive treatments for depression.
Conclusion Given the significant rate of mood disorders, particularly depression, among patients who report chronic sleep problems, screening for mood disorders should be a routine component in the evaluation of any patient with a sleep complaint. Patients are much more likely to endorse somatic rather than emotional symptoms, particularly in general medical settings, and sleep complaints provide an important clue to the clinician regarding the presence of depression or other psychiatric illness. Similar mechanisms seem to be involved in the regulation of mood and sleep, which may explain the high incidence of sleep abnormalities in patients with mood disorders as well as the effects of antidepressants on both mood and sleep. Antidepressant treatment can improve sleep, particularly when drugs are chosen with an eye to the side effect profile. Similarly, light therapy and sleep manipulations may provide relief for the symptoms of depression including sleep abnormalities, particularly when drugs are contraindicated.
Sleep and mood disorders
Acknowledgements This work was supported by grants MH01224 National Institute of Mental Health.
to R.M.B. from
References *l Mellinger GD, Balter MB, Uhlenhuth EH. Insomnia and its treatment. Prevalence and correlates. Arch Gen Psychiatry 1985; 42: 225-232. “2 Ford DE, Kamerow DB. Epidemiologic study of sleep disturbance and psychiatric disorders: an opportunity for prevention? JAMA 1989; 262: 1479-1484. “3 Gerber I’D, Barrett JE, Barrett JA et al. The relationship of presenting physical complaints to depressive symptoms in primary care. I Gen Int Med 1992; 7: 170-173. “4 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. *5 Task Force on DSM-IV. First MB, ed. Diagnostic and Statistical Manual of Mental Disorders. 4th edn. Washington, DC: American Psychiatric Association, 1994. 6 Reynolds CF, III, Kupfer DJ. Sleep research in affective illness: state of the art circa 1987. Sleep 1987; 10: 199-215. *7 Benca RM, Obermeyer WH, Thisted RA et al. Sleep and psychiatric disorders: a metaanalysis. Arch Gen Psyckiat 1992; 49: 651-668. *8 Benca RM, Kryger MH, Roth T, Dement WC, eds. Principles and Practice of Sleep Medicine. 2nd edn. Philadelphia: W.B. Saunders Co. 1994; 85, Mood Disorders. p. 899-913. *9 Kupfer DJ. Sleep research in depressive illness: clinical implications-a tasting menu. [Review]. Biol Psychiatry 1995; 38: 391403. 10 Armitage R. Microarchitectural findings in sleep EEG in depression: diagnostic implications. Biol Psyckiaty 1994; 36: 1-12. 11 Hudson JI, Lipinski JF, Keck PE et al. Polysomnographic characteristics of young manic patients: copmparison with unipolar depressed patients and normal control subjects. Arch Gen Psych& 1991; (in press). 12 Anderson JL, Rosen LN, Mendelson WB et al. Sleep in fall/winter seasonal affective disorder: effects of light and changing seasons. J Psyckosom Res 1994; 38: 323-337. 13 Gillin JC, Wyatt RJ, Fram DH et al. The relationship between changes in REM sleep and clinical improvement in depressed patients treated with amitriptyline. Psychopharmacology 1978; 59: 267-272. 14 Kupfer DJ, Foster FG, Reich L et al. EEG sleep as predictors in depression. Am ] Psyckiatvy 1976; 133: 622-626. *15 Leibenluft E, Wehr TA. Is sleep deprivation useful in the treatment of depression? Am J Psychiatry 1992; 149: 1599168. *16 Vogel GW. Evidence for REM sleep deprivation as the mechanism of action of antidepressant drugs. Prog Neuvopkavmacol Biol Psyckiahy 1983; 7: 343-349. 17 Ware JC, Brown FW, Moorad PJ et al. Nocturnal myoclonus and tricyclic antidepressants. Sleep Res 1984; 13: 72. 18 Uchiyama M, Tanaka K, Isse K et al. Efficacy of mianserin on symptoms of delirium in the aged: an open trial study. Prog Neuro-Psyckopkarmacol Biol Psychiatry 1996; 20: 651-656. 19 Schenck CH, Mahowald MW, Kim SW et al. 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. 20 Nofzinger EA, Reynolds CF, III, Thase ME et al. REM sleep enhancement by bupropion in depressed men. Am J Psyckiaty 1995; 152: 274-276.
The most important
by an asterisk.
R. M. Benca et al.
21 Ware JC, Rose FU, McBrayer RH. The acute effects of nefazodone, trazodone and buspirone on sleep and sleep-related penile tumescence in normal subjects. Sleep 1994; 17: 544-550. 22 Nierenberg AA, Adler LA, Peselow E et al. Trazodone for antidepressant-associated insomnia. Am J Psyckiatvy 1994; 151: 1069-1072. 23 Grunhaus L, Tiongco D, Pande A et al. Monitoring of antidepressant response to ECT with polysomnographic recordings and dexamethasone suppression test. Psychiatry Res 1988; 24: 177-185. 24 Lewy AJ, Kern HA, Rosenthal NE, Wehr TA. Bright artificial light treatment of a manicdepressive patient with a seasonal mood cycle. Am ] Psyckiatvy 1982; 139: 1496-1498. 25 Lewy AJ, Sack RL, Miller LS, Hoban TM. Antidepressant and circadian phase-shifting effects of light. Science 1987; 235: 352-354. “26 Wirz-Justice A, Graw P, Krauchi K et al. Light therapy in seasonal affective disorder is independent of time of day or circadian phase. Arch Gen Psychiatry 1993; 50: 929-937. 27 Meesters Y, Jansen JH, Beersma DG et al. Light therapy for seasonal affective disorder. The effects of timing. BY J Psychiatry 1995; 166: 607-612. 28 Wirz-Justice A. Light therapy for depression: present status, problems, and perspectives. Psychopathology 1986; 19 (Suppl. 2): 136-141. 29 Terman M, Schlager DS. Sleep and biological rhythms. New York: 1990; 7 Twilight Therapeutics, Winter depression, Melatonin, and Sleep. pp. 113-128. 30 Deltito JA, Moline M, Pollak C et al. Effects of phototherapy on non-seasonal unipolar and bipolar depressive spectrum disorders. J Affect Disord 1991; 23: 231-237. 31 Mackert A, Volz HP, Stieglitz RD et al. Phototherapy in nonseasonal depression. Biol Psychiatry 1991; 30: 257-268. 32 Terman M. Principles and practice of sleep medicine. Philadelphia: 1994; 95. Light treatment, Clinical strategy. pp. 1013-1014. 33 Garcia-Borreguero D, Jacobsen FM, Murphy DL et al. Hormonal responses to the administration of m-chlorophenylpiperazine in patients with seasonal affective and controls. Biol Psyckiafvy 1995; 37: 740-749. 34 Wehr TA, Wirz-Justice A, Goodwin FK et al. Phase advance of the circadian sleep-wake cycle as an antidepressant. Science 1979; 206: 710-713. 35 Vollmann J, Berger M. Sleep deprivation with consecutive sleep-phase advance therapy in patients with major depression: a pilot study. Biol Psychiatry 1993; 33: 54-57. 36 Severino SK, Wagner DR, Moline ML et al. High nocturnal body temperature in premenstrual syndrome and late luteal phase dysphoric disorder. Am 1 Psychiatry 1991; 148: 1329-1335. 37 Wu JC, Gillin JC, Buchsbaum MS et al. Effect of sleep deprivation on brain metabolism of depressed patients. Am J Psychiatry 1992; 149: 538-543. 38 Ebert D, Feistel H, Kaschka W et al. Single photon emission computerized tomography assessment of cerebral dopamine D2 receptor blockade in depression before and after sleep deprivation-preliminary results. Biol Psychiatry 1994; 35: 880-885.