insomnia and psychiatric disorders

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Introduction

During the past several years, the relationship between insomnia and psychiatric disorders has come to be

viewed as circular and synergistic. Psychiatric illnesses, particularly anxiety and mood disorders, have long

been recognized as a frequent cause of insomnia symptoms. In some instances, this association is even

formalized in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV ) diagnostic

criteria. Clinical experience shows that almost all patients with mood and anxiety disorders have sleep

disturbances either chronically or during exacerbations of their psychiatric illnesses. However, it has become

clear that insomnia also increases the risk of future relapse or the development of new onset anxiety, mood, and

substance abuse disorders. This relationship can promote a downward spiral of symptom severity and quality of

life for patients that further complicates treatment efforts. On the other hand, the close association of insomnia,

depression, and anxiety symptoms can be viewed as an opportunity for targeted therapies that may provide

significant benefits for patients.

Introduction

Epidemiology

An analysis of data from the large-scale Epidemiologic Catchment Area (ECA) project[1]

demonstrates the

relatively high percentage of individuals in the general population who suffer from significant insomnia

symptoms and meet the criteria for mood, anxiety, or substance abuse disorders. In all, 10% of the sample met

the stringent criteria for insomnia, and 40% of these insomnia sufferers met the criteria for at least 1 psychiatric

disorder. Major depression or dysthymia was diagnosed in 23%; anxiety disorder was diagnosed in 24%;

alcohol abuse was found in 7%; and drug abuse was discovered in 4%. Furthermore, if insomnia was present

both at baseline and 1 year later, the risk of the individual having a new onset mood or anxiety disorder at the

time of the follow-up interview increased significantly.

This general conclusion has been replicated in longitudinal studies with subjects ranging from adolescents to

the elderly.[2,3]

Indeed, any history of persistent insomnia augments the lifetime risk of major depression.[4]

It is

unclear whether the insomnia represents a prodrome, shared genetic vulnerability, or a causative process

promoting depressive symptoms. Nevertheless, this association emphasizes the need for early recognition and

treatment of insomnia, and an evaluation for potential psychiatric disorders.

Insomnia and Bipolar Disorder

In addition to major depression and dysthymic disorder, insomnia commonly occurs with bipolar disorder during

depressive and manic episodes. Although some manic patients will describe a decreased need for sleep, others

complain of being distressed by an inability to sleep. Sleep loss from any reason, including jet lag and workschedules, may contribute to the onset or progression of manic episodes in patients with bipolar disorder.

[5,6]

Insomnia and Psychiatric DisordersDavid N. Neubauer, MD

Posted: 06/21/2004

Insomnia and Psychiatric Disorders (printer-friendly) http://www.medscape.org/viewarticle/480681_print

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Early sleep-targeted interventions may prevent or limit exacerbations for these patients.

Anxiety Disorders

Among anxiety disorders, insomnia is particularly problematic for patients with panic disorder, posttraumatic

stress disorder, generalized anxiety disorder, and social phobia. Most patients with panic disorder at times will

experience distressing panic episodes that awaken them from sleep. This may lead to considerable anticipatory

anxiety about going to sleep, which may lead to sleep insufficiency and more anxiety.[7]

Patients withposttraumatic stress disorder frequently experience poor sleep quality and vivid nightmares.

[8]The chronic

anxiety of patients with generalized anxiety disorder often affects these patients throughout the night with

resulting difficulty falling asleep and repeated awakenings. Patients with social phobia report significantly worse

sleep quality and difficulty falling asleep as compared with healthy controls.[9]

Management of Insomnia in Patients With Psychiatric Comorbidities

Managing the insomnia complaints of patients with concurrent psychiatric disorders is a 2-pronged approach.

Specific therapeutic interventions should address the primary psychiatric condition. These interventions may

include psychotherapeutic, behavioral, and pharmacologic strategies. Optimizing the treatment of the underlying

disorder ultimately should improve sleep.

Medications for patients with mood and anxiety disorders include an assortment of antidepressants, anxiolytics,

and mood stabilizers. The selective serotonin reuptake inhibitor (SSRI) antidepressants and venlafaxine (a

combination SSRI and norepinephrine reuptake inhibitor) often are effective for these patients, although they

rarely improve insomnia symptoms rapidly. Furthermore, some patients will develop insomnia as a side effect

from these medications.

A sedating antidepressant, such as amitriptyline, trazodone, or mirtazapine, may help with sleep, but also may

cause residual sedation the following day. If trazodone is prescribed, further caution is advised regarding

hypotension, priapism (men and women), and the potential contribution to the serotonin syndrome when

combined with other serotonergic medications. Although selected medications work well for certain patients,

there currently is no antidepressant that reliably and rapidly promotes improved nighttime sleep and daytimealertness.

General approaches to insomnia are those applicable to a broad range of patients and include sleep hygiene

and behavioral interventions, cognitive behavioral therapy, and hypnotic medications. These approaches may

be used concurrently with specific treatment strategies for the psychiatric disorders. There are several

advantages to this 2-pronged approach. First, there is greater choice in selecting medications for the psychiatric

symptoms, rather than restricting the options to sedating agents. There also can be flexibility in the dosage,

timing, and duration of use of medications targeting different symptoms. Second, hypnotic medications may

provide immediate relief and, subsequently, decreased distress and improved quality of life. A hypnotic can

offset the stimulating effect of some antidepressants. Third, these general insomnia treatment approaches can

directly address the perpetuating factors that reinforce chronic insomnia.

Currently available hypnotic agents include 5 benzodiazepines (estazolam, flurazepam, quazepam, temazepam,

and triazolam) and 2, newer nonbenzodiazepine agents (zaleplon and zolpidem). All of these medications are

positive allosteric modulators at the gamma-aminobutyric acid (GABA)-A receptor complex. The inhibitory

GABA-A system functions through membrane hyperpolarization as negative chloride ions enter the cells.

Benzodiazepine receptor agonists enhance this normal process. The traditional benzodiazepines appear to

interact with most subunit configurations of the GABA-A receptor, whereas the newer agents are more selective

for a particular configuration. This selectivity and the relatively short elimination half-lives of these

nonbenzodiazepine hypnotics help explain the good efficacy, safety, and tolerance of these newer-generation

agents.

In clinical practice, hypnotics often are prescribed concurrently with antidepressants for patients with mood and


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anxiety disorders. Pharmacokinetic and pharmacodynamic studies of fluoxetine and sertraline combined with

zolpidem have been performed in healthy, nondepressed women.[10,11]

These studies found no clinically

significant interactions. Another trial evaluated the sleep of patients prescribed an SSRI concurrently with

zolpidem or a placebo.[12]

The study population included individuals successfully treated for depression with an

SSRI, but who were complaining of persistent insomnia. The hypnotic-treated patients reported significantly

improved sleep and daytime functioning.

New Agents

A variety of pharmacologic agents is being evaluated in clinical trials for the treatment of insomnia. These

include new nonbenzodiazepine medications and modified-release preparations as well as melatonin agonists,

presynaptic and postsynaptic GABA-A modulators, and corticotropin-releasing factor antagonists.

On the near horizon is eszopiclone, a moderately short-acting, nonbenzodiazepine agent derived from

zolpiclone, which has been available outside the United States for several years. The newest development with

the nonbenzodiazepine hypnotics is the modified-release formulation. The rationale behind the development of

this formulation is that the immediate-release component promotes rapid sleep onset, whereas the extended-

release component helps maintain sleep through the night. Ideally, short medication half-lives will allow a rapid

decline of the sedating effects to prevent residual daytime effects. Formulations of this type are being evaluatedfor zaleplon and zolpidem. Indiplon is a new, very short half-life nonbenzodiazepine hypnotic that likely will be

available in both immediate- and modified-release formulations.

Looking for Other Causes of Sleeplessness

Although it is important to identify and treat the insomnia symptoms that may result from psychiatric illnesses, it

is equally important to evaluate psychiatric patients for other possible contributing causes of their sleep

disturbances. These may include stimulating effects of psychotropic and other medications, medical disorders

and underlying primary sleep disorders, circadian rhythm disorders, irregular schedules, and maladaptive habits

and routines. Patients with sleep apnea can present solely with insomnia complaints. Restless legs syndrome

and periodic limb movements, which can be exacerbated by most antidepressants, can cause difficulty falling

asleep and repeated awakenings. Withdrawn or agoraphobic patients may spend excessive time at home, sleepat irregular times, and be deprived of the photoperiod that normally reinforces the sleep-wake cycle.

Although the clinical history is the cornerstone of the evaluation of sleep disturbances, patients' descriptions of

their sleep problems can be supplemented with a sleep log or diary maintained for at least several weeks. This

may offer a more accurate representation of exactly when they are awake or sleeping (nighttime and daytime)

as compared with their summary given at a clinic appointment. It also can be helpful when monitoring the

effectiveness of treatment approaches. Consultation with a sleep medicine specialist and sleep laboratory

testing may be appropriate for patients with excessive daytime sleepiness, when patients are suspected of

having disorders, such as sleep apnea and narcolepsy, and when insomnia is persistent and not responsive to

standard treatments.

The effective treatment of insomnia in patients with psychiatric disorders may require a constellation of

strategies involving proper sleep habits, schedule manipulations, cognitive behavioral interventions, and

adjustments of psychiatric medications. Hypnotic medications may play a valuable role for selected patients.

Improving sleep can be an important catalyst to more general clinical recovery.

References

Ford DE, Kamerow DB. Epidemiologic study of sleep disturbances and psychiatric disorders. An

opportunity for prevention? JAMA. 1989;262:1479-1484.

1.

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. Abstract

2.

Roberts RE, Shema SJ, Kaplan GA, Strawbridge WJ. Sleep complaints and depression in an aging3.


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Medscape Neurology. 2004;6(1) © 2004 Medscape

cohort: a prospective perspective. Am J Psychiatry. 2000;157:81-88. Abstract

Ford DE, Cooper-Patrick L. Sleep disturbances and mood disorders: an epidemiologic perspective.

Depress Anxiety. 2001;14:3-6. Abstract

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Leibenluft E, Albert PS, Rosenthal NE, Wehr TA. Relationship between sleep and mood in patients with

rapid-cycling bipolar disorder. Psychiatry Res. 1996;63:161-168. Abstract

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Young DM. Psychiatric morbidity in travelers to Honolulu, Hawaii. Compr Psychiatry. 1995;36:224-228.

Abstract

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Uhde TW. Anxiety disorders. In: Principles and Practice of Sleep Medicine. Kryger MH, Roth T, Dement

WC, eds. WB Saunders: Philadelphia, Pa; 2000.

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Green B. Post-traumatic stress disorder: symptom profiles in men and women. Curr Med Res Opin.

2003;19:200-204. Abstract

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Stein MB, Kroft CDL, Walter JR. Sleep impairment in patients with social phobia. Psychiatry Res.

1993;49:251-256. Abstract

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Allard S, Sainati SM, Roth-Schechter BF. Coadministration of short-term zolpidem with sertraline in

healthy women. J Clin Pharmacol. 1999;39:184-191. Abstract

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Allard S, Sainati SM, Roth-Schechter BF, MacIntyre J. Minimal interaction between fluoxetine and

multiple-dose zolpidem in healthy women. Drug Metab Dispos. 1998;26:617-622. Abstract

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Asnis GM, Chakraburtty A, DuBoff EA, et al. Zolpidem for persistent insomnia in SSRI-treated depressed

patients. J Clin Psychiatry. 1999;60:668-676. Abstract

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