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Abstract

Sleep disturbances-particularly insomnia - are highly prevalent in anxiety disorders and complaints such as insomnia or nightmares have even been incorporated in some anxiety disorder definitions, such as generalized anxiety disorder and posttraumatic stress disorder. In the first part of this review, the relationship between sleep and anxiety is discussed in terms of adaptive response to stress. Recent studies suggested that the corticotropin-releasing hormone system and the locus ceruleus-autonomic nervous system may play major roles in the arousal response to stress. It has been suggested that these systems may be particularly vulnerable to prolonged or repeated stress, further leading to a dysfunctional arousal state and pathological anxiety states, Polysomnographic studies documented limited alteration of sleep in anxiety disorders. There is some indication for alteration in sleep maintenance in generalized anxiety disorder and for both sleep initiation and maintenance in panic disorder; no clear picture emerges for obsessive-compulsive disorder or posttraumatic stress disorder. Finally, an unequivocal sleep architecture profile that could specifically relate to a particular anxiety disorder could not be evidenced; in contrast, conflicting results are often found for the same disorder. Discrepancies between studies could have been related to illness severity, diagnostic comorbidity, and duration of illness. A brief treatment approach for each anxiety disorder is also suggested with a special focus on sleep.
249
nxiety is an experience of everyday life. It typ-
ically functions as an internal alarm bell that warns of
potential danger and, in mild degrees, anxiety is service-
able to the individual. In anxiety disorders, however,the
individual is submitted to false alarms that may be
intense, frequent, or even continuous. These false alarms
may lead to a state of dysfunctional arousal that often
leads to persistent sleep–wake difficulties. Indeed, popu-
lation surveys indicate that the prevalence of anxiety dis-
order is about 24% to 36% in subjects with insomnia
complaints and about 27% to 42% for those with hyper-
somnia.1,2 Another point further underpinning the rela-
tionship between anxiety and sleep is that sleep distur-
bance is a diagnostic symptom for some anxiety disorders,
such as generalized anxiety disorder (GAD) and post-
traumatic stress disorder (PTSD).
Anxiety states may be focused upon some particular sit-
uation or may be generalized. Usually, there is a combi-
nation and most people suffering from severe phobic dis-
order will have some degree of generalized anxiety.
Likewise, patients with generalized anxiety often experi-
Clinical research
Sleep and anxiety disorders
Luc Staner, MD
Keywords:
sleep; insomnia; anxiety disorder; sleep–wake regulation; panic
disorder; generalized anxiety disorder; obsessive-compulsive disorder; posttrau-
matic stress disorder
Author affiliations: Sleep Laboratory, FORENAP, Rouffach, France
Address for correspondence: Sleep Laboratory, FORENAP, Institute for
Research in Neuroscience and Neuropsychiatry, BP29, 68250 Rouffach, France
(e-mail: luc.staner@forenap.asso.fr)
A
Sleep disturbances—particularly insomnia—are highly prevalent in anxiety disorders and complaints such as insomnia
or nightmares have even been incorporated in some anxiety disorder definitions, such as generalized anxiety disorder
and posttraumatic stress disorder. In the first part of this review, the relationship between sleep and anxiety is discussed
in terms of adaptive response to stress. Recent studies suggested that the corticotropin-releasing hormone system and
the locus ceruleus–autonomic nervous system may play major roles in the arousal response to stress. It has been sug-
gested that these systems may be particularly vulnerable to prolonged or repeated stress, further leading to a dys-
functional arousal state and pathological anxiety states. Polysomnographic studies documented limited alteration of
sleep in anxiety disorders. There is some indication for alteration in sleep maintenance in generalized anxiety disorder
and for both sleep initiation and maintenance in panic disorder; no clear picture emerges for obsessive-compulsive dis-
order or posttraumatic stress disorder. Finally, an unequivocal sleep architecture profile that could specifically relate to a
particular anxiety disorder could not be evidenced; in contrast, conflicting results are often found for the same disorder.
Discrepancies between studies could have been related to illness severity, diagnostic comorbidity, and duration of illness.
A brief treatment approach for each anxiety disorder is also suggested with a special focus on sleep.
© 2003, LLS SAS Dialogues Clin Neurosci. 2003;5:249-258.
Copyright © 2003 LLS SAS. All rights reserved www.dialogues-cns.org
ence increase in anxiety in certain situations. Moreover,
the various anxiety disorders share many biological and
clinical similarities, and are highly comorbid. Therefore,
in this article, we will first discuss common features of the
neurobiological basis of anxiety and its relationships with
sleep physiology. Next, sleep disturbances and its treat-
ment will be discussed; for clinical convenience, each of
the different anxiety disorders will be discussed sepa-
rately. Indeed, the treatment of the anxiety disorder sig-
nificantly improves sleep; however,when the sleep dis-
turbance predominates, its treatment may improve the
management of the anxiety disorder.
A brief survey of sleep physiology
Human sleep consists of two qualitatively different brain
states,non–rapid eye movement (NREM) and rapid eye
movement (REM) sleep. NREM sleep is further subdi-
vided into stages 1 through 4, with stage 1 being the light-
est and stage 4 being the deepest sleep. Since slow “delta”
waves distinguish stages 3 and 4, the stages are often
defined as delta sleep or slow-wave sleep (SWS). REM
sleep is also called paradoxical sleep because of the close
resemblance with the electroencephalogram (EEG) of
active wakefulness combined with a “paradoxical”active
inhibition of major muscle groups that seems to reflect a
heavy sleep. Normal sleep is characterized electrograph-
ically as recurrent cycles of NREM and REM sleep of
about 90 min. In the successive cycles during the night,
the duration of stages 3 and 4 decrease, and the propor-
tion of the cycle occupied by REM sleep tends to
increase with REM episodes occurring late in the night
having more eye movement bursts than REM episodes
occurring early in the night.3
Most models of sleep regulation have implicated the
monoaminergic and cholinergic systems and the impor-
tance of inhibitory GABAergic (GABA, γ-aminobutyric
acid) mechanisms in sleep regulation is well established.4
Since dysfunction of these neurotransmitter systems have
been implicated in anxiety disorders,5it is no wonder that
one of the chief complaints of anxiety disorder patients
relates to sleep alteration.
Sleep–wake regulation is classically viewed as resulting
from the interaction of two regulating processes (circa-
dian [C] and homeostatic [S]).6The propensity to sleep
or be awake at any given time is a consequence of a sleep
debt (process S), and its interaction with signals coming
from the circadian clock located in the suprachiasmatic
nucleus (process C). Process S is supposed to reflect the
activity of a somnogenic substance that progressively
accumulates with prolonged wakefulness,with adenosine
being one of the most cited candidates.7Both homeosta-
tic and circadian mechanisms are thought to influence
the opposite action of neurons promoting wakefulness
and neurons promoting sleep.Wake-active neurons are
cholinergic (located in the basal forebrain and in the
tegmentum) and monoaminergic (noradrenergic in the
locus ceruleus, serotonergic in the dorsal raphe, and his-
taminergic in the tuberomammillary nucleus), whereas
sleep-active neurons are GABAergic and located in the
preoptic area of the hypothalamus.4
The discovery of the hypocretin (also called orexin) sys-
tem has brought new inroads into understanding the
sleep-regulatory neural circuit.8Hypocretin neurons are
located in the lateral hypothalamus and have dense exci-
tatory projections to all monoaminergic and cholinergic
cell groups. Recent studies suggested that monoaminer-
gic and hypocretin neurons play a different and comple-
mentary role in wakefulness maintenance.4For example,
the dual effects of hypocretins on arousal and food intake
(orexin from “appetite-stimulating”) suggest a more
important role for hypocretins in the control of arousal
maintenance related to energy homeostasis.8In the same
way, data summarized in the following section suggest a
role for the norepinephrine (NE)–containing neurons of
the locus ceruleus (LC) in stress-induced arousal and
concomitant anxiety.
Clinical research
250
Selected abbreviations and acronyms
ACTH adrenocorticotropic hormone
AN autonomic nervous (system)
BZD benzodiazepine
CNA central nucleus of the amygdala
CRH corticotropin-releasing hormone
GAD generalized anxiety disorder
HPA hypothalamic-pituitary-adrenal (axis)
LC locus ceruleus
NE norepinephrine
NREM non–rapid eye movement
OCD obsessive-compulsive disorder
PTSD posttraumatic stress disorder
PVN paraventricular nucleus
REM rapid eye movement
SSRI selective serotonin reuptake inhibitor
SWS slow-wave sleep
TCA tricyclic antidepressant
Interactions between stress,
anxiety, and sleep
Anxiety and stress
Anxiety is a universal emotion and it would at times be
maladaptive not to experience it; it is a necessary part of
the response of the organism to a stress,ie,a threat to the
psychological or the physiological integrity of an indi-
vidual. Anxiety may be polarized between a state and a
trait. It may supervene at some point in the course of life,
in which case anxiety is referred as a state.Anxiety trait
is a long-term feature of a person’s experience, present
throughout life and considered to be a key feature of the
avoidant or anxious personality disorder. It probably
reflects a lifetime maladaptive response to stress due to
individual differences in biogenetic background, devel-
opmental influences, and early life experiences.There is
no hard and fast distinction between anxiety that may be
considered as a normal, acceptable accompaniment of
stress and the pathological state that warrants classifica-
tion as a psychiatric disorder. In the latter, the nature of
the stress is not always clearly discernible. In other words,
pathological anxiety could be characterized by a sense of
fear, but it is differentiated from fear in that the threat is
not immediate or always obvious. Whether normal or
pathological, the constituent features of anxiety always
comprise indices of increased arousal or alertness that
could lead to sleep–wake alterations. Indeed, anxiety is
only one part of the arousal response to stress, whether
the stress is real, implied, or overvalued.
Arousal and stress
Response to stress implicates two systems that both play
a key role in physiological responses to stressful situation
by promoting arousal, the corticotropin-releasing hor-
mone (CRH) system and the LC–autonomic nervous
(AN) system. This topic has recently been reviewed by
several authors9-11 and will be only briefly described here.
Before going further, it should be emphasized that pro-
moting arousal is essential for identifying a given situa-
tion as important, as well as for maintaining the central
nervous system (CNS) in states that most favor survival
during stressful situations. Arousal response to stress
comprises three components (hormonal, behavioral,and
autonomic) in which CRH and LC-AN systems have
been diversely implicated (Figure 1). Different stressors
activate different components of the stress system, eg,the
LC-AN system will be more implicated in the response
to physiological stressors such as hypoxia, while the CRH
system will be recruited for more complex environmen-
tal dangers such as emotional stress. However, there are
several connections between the two systems which are
continuously in close interaction (see next section).
The stress system
During these last years, a series of studies in rodents
established the role of CRH as a key neurotransmitter in
the stress response, beside its stimulating effect on the
hypothalamic-pituitary-adrenal (HPA) axis.9,11 It has been
shown that hypothalamic CRH neurons activate the LC-
AN system and inhibit a variety of neurovegetative func-
tions, such as food intake, sexual activity, growth, and
reproduction. CRH-containing neurons located in the
central nucleus of the amygdala (CNA) play a key role
by activating fear-related behavior, while inhibiting
exploration behavior. Like the CRH system,the NE-con-
taining neurons of the LC promote arousal, inhibit the
parasympathetic system as well as several vegetative
functions such as feeding and sleep, and contribute to
HPA axis stimulation.12 It has been shown that stress
increases NE turnover in many terminal projections of
the LC and that the activity of LC neurons is monoton-
ically related to increased arousal.9
There is also evidence that NE stimulates the release of
CRH in the paraventricular nucleus (PVN) of the hypo-
thalamus and in the CNA.9These NE-CRH influences
suggest a potential feed-forward system between the
Sleep and anxiety disorders - Staner Dialogues in Clinical Neuroscience - Vol 5 .No. 3 .2003
251
Figure 1. Arousal response to stress. CRH, corticotropin-releasing hor-
mone; PVN, paraventricular nucleus; CNA, central nucleus of
the amygdala; LC-AN, locus ceruleus–autonomic nervous; NE,
norepinephrine.
LC-AN system
CRH system Hormonal
response
Autonomic
response
Behavioral
response
Emotional
stressors
Physiological
stressors
Hypothalamus (PVN)
Amygdala (CNA)
CRH
CRH
NE
NE
LC-AN system and the CRH system, and both systems
have stimulating properties on its counterpart. It has
been suggested that such a feed-forward mechanism may
be particularly vulnerable to dysfunction during which
the arousal reaction is maintained despite the removal of
the stressful situation.9,10 The same authors have proposed
that, if prolonged,such dysfunctional arousal state could
lead to anxiety and depressive disorder.
Stress and sleep–wake regulation
Animal and human studies showed that both acute and
chronic stress have pronounced effects on sleep that are
mediated through the activation of the HPA axis and the
sympathetic system.13 For instance, in rats, effects of acute
stress on sleep are primarily manifested by changes in
REM sleep.These alterations seem to involve CRH-medi-
ated mechanisms: CRH acts as a neurotransmitter in the
LC to increase activity of the NE neurons, which leads to
an increase in REM sleep.14 Rats exposed to various mod-
els of chronic stress have shown sleep disruption, increase
in REM sleep, and decrease in SWS.15,16 There are also indi-
cations that CRH could contribute to the regulation of
spontaneous waking even in the absence of stressors.17
In humans,there is a close temporal relationship between
HPA activity and sleep structure.The HPA axis is subject
to a pronounced inhibition during the early phase of noc-
turnal sleep, during which SWS predominates. In contrast,
during late sleep, when REM sleep predominates, HPA
activity increases to reach a diurnal maximum shortly after
morning awakening. During SWS, sympathetic activity is
reduced and there is positive correlation among the
amount of REM sleep and activities of the HPA axis and
the sympathetic system.18,19 More generally, a close coupling
has been shown between adrenocorticotropic, autonomic,
and EEG indices of arousal during the sleep–wake cycle.20-
22 Exogenous administration of CRH, adrenocorticotropic
hormone (ACTH), or cortisol produces either prolonged
sleep onset, reduced SWS, and increased sleep fragmenta-
tion.13 Accordingly, patients with complaints of insomnia
show electrophysiological and psychomotor evidence of
increased daytime arousal,23-25 as well as indications of
increased HPA activity26 and increased sympathetic tone.27
Sleep complaints and anxiety disorder
Anxiety disorders are considered as the most frequently
occurring category of mental disorder in the general
population. Estimates of the lifetime prevalence of anxi-
ety disorders have ranged between 10% and 25%.28
Epidemiological studies have also demonstrated the high
prevalence of sleep complaints.As much as one third of
the adult population reports difficulty sleeping29-31 and
sleep disturbance is considered as the second most com-
mon symptom of mental distress.32 Some epidemiological
studies investigated the relationship between the occur-
rence of sleep disturbances and anxiety disorder in the
general population.1,2,33 In a longitudinal study of young
adults, Breslau et al2found that lifetime prevalence was
16.6% for insomnia alone, 8.2% for hypersomnia alone,
and 8% for insomnia plus hypersomnia. Odds ratios for
various anxiety disorder diagnoses associated with life-
time sleep disturbance varied from 1.2 to 13.1. Table I
shows that the odds ratios associated with insomnia alone
varied little from those associated with hypersomnia
alone.The three highest odds ratios were those for obses-
sive-compulsive disorder (OCD) and for panic disorder
associated with both insomnia and hypersomnia, and that
for GAD associated with insomnia alone.
These findings were replicated for chronic insomnia in a
recent study,33 which further showed that insomnia
appeared before the anxiety disorder in 18% of cases,
anxiety and insomnia appeared about in the same time
in 38.6% of cases,and anxiety appeared before insomnia
in 43.5% of cases.These authors concluded that psychi-
atric history, including anxiety disorder,is closely related
to the severity and chronicity of current insomnia.
Panic disorder and agoraphobia
The essential features of panic disorder are recurrent
attacks of severe anxiety (panic attacks), which are not
restricted to any particular situation or set of circum-
stances and are therefore unpredictable.According to
Clinical research
252
Table I. Odds ratios for specific anxiety disorders associated with lifetime
sleep disturbances (adapted from Breslau et al2). GAD, general-
ized anxiety disorder; OCD, obsessive-compulsive disorder.
Insomnia Hypersomnia Both
alone alone
GAD 7.0 (2.817.2) 4.5 (1.515.3) 4.8 (1.515.2)
Panic disorder 5.3 (2.013.6) 4.3 (1.314.8) 8.5 (3.123.5)
OCD 5.4 (2.014.8) 1.2 (0.19.7) 13.1 (4.835.7)
Phobic disorder 1.5 (1.02.3) 2.9 (1.84.8) 4.0 (2.56.5)
Any anxiety 2.4 (1.63.5) 3.3 (2.05.4) 4.5 (2.87.3)
disorder
the Diagnostic and Statistical Manual of Mental Disorders,
Fourth Edition (DSM-IV)34 criteria of panic disorder,
unexpected panic attacks have to be followed by at least
1 month of persistent concern about having another
panic attack. The dominant symptoms of a panic attack
vary from individual to individual. Typically, it includes
autonomic symptoms with marked psychic anxiety. The
most prominent autonomic symptoms are palpitations,
sweating, trembling, shortness of breath, dizziness,chest
pain, nausea, and paresthesias.There is almost always a
secondary fear of dying, losing control, or going mad.
Most individual attacks last only for a few minutes, but
a common complication is the development of anticipa-
tory fear of helplessness or loss of control during a panic
attack, so that the individual may progressively develop
avoidant behavior leading to agoraphobia or specific
phobias. In this respect, most, if not all, patients with
agoraphobia also have a current diagnosis (or history)
of panic disorder.34 Accordingly, sleep disturbances of
panic disorder and agoraphobia are discussed in the
same section.
Subjective sleep
Sleep disturbances, predominantly insomnia, are
extremely common in panic disorder. Sheehan et al35
reported a prevalence of 68% for difficulties in falling
asleep and of 77% for restless and disturbed sleep. In a
self-report sleep survey, Mellman and Uhde36 found that,
compared with healthy subjects, patients with panic dis-
order reported more complaints of middle night insom-
nia (67% versus 23%) and late night insomnia (67%
versus 31%); the two groups did not differ with regard
to early night insomnia. Many patients with panic disor-
der experience occasional sleep panic attacks, but only
about 20% to 45% of patients with panic disorder have
repeated nocturnal panic attacks.37-39 Some evidence sug-
gests that patients experiencing regular nocturnal panic
attacks represent a specific version of panic disorder
characterized by fearful associations with sleep and
sleep-like states.40 Therefore, nocturnal panic attacks will
be discussed in a separate section.
Sleep EEG recording
Most polysomnographic studies indicate that patients
with panic disorder have impaired sleep initiation and
maintenance characterized by increased sleep latency
and increased time awake after sleep onset resulting in a
reduced sleep efficiency (the ratio between total sleep
time and time in bed),41-47 but there are also negative
reports showing no difference compared with controls in
these variables.48,49 Concerning sleep architecture, NREM
sleep was found differently affected across studies; some
reported a decreased in stage 2 sleep duration42,43 with a
concomitant increase in SWS.47 Time spent in SWS was
found reduced by Arriaga et al46 and Stein et al,49 but
unchanged by other authors.36,42,45 Controversial results
were also obtained regarding REM sleep.Although most
studies agreed on the fact that REM sleep time is
unchanged in panic disorder, some authors found a short-
ening of REM sleep latency,36,48 while others did not.41,44
To summarize, most studies suggest that the subjective
sleep continuity disturbances reported by patients with
panic disorder could be objectively demonstrated by
polysomnographic recordings. Findings regarding sleep
architecture are more controversial (although REM
sleep seems to be preserved). These discrepancies could
relate to sampling differences (some studies having
included patients with a comorbid depressive disorder)
and to the influence of nocturnal panic attack during the
sleep EEG recording.
Treatment
Sleep disturbances linked to panic disorder respond to a
number of antipanic pharmacological agents including
selective serotonin reuptake inhibitors (SSRIs), tricyclic
antidepressants (TCAs), benzodiazepines (BZDs),and
monoamine oxidase inhibitors (MAOIs). Some patients
could have an initial increased anxiety or insomnia in
response to antidepressant medications, which should
alert the clinician to the need to increase the dosage quite
slowly. A BZD can also be used to reduce anxiety and aid
sleep in the early phases of treatment.
Nocturnal panic
The majority of patients with panic disorder experience
nocturnal panic attacks. However, in a subgroup of
patients,sleep-related panic is the predominant symptom,38
with up to 18% of all panic attacks occurring during
sleep.50 Nocturnal panic refers to waking from sleep in a
state of panic and should be distinguished from nighttime
arousal induced by nightmares or environmental stimuli
(such as unexpected noise). It has often been mistaken for
Sleep and anxiety disorders - Staner Dialogues in Clinical Neuroscience - Vol 5 .No. 3 .2003
253
sleep apnea, sleep terrors, and nocturnal epilepsy.
Nocturnal panic generally occurs during late stage 2 to
early stage 3 sleep, and can therefore be distinguished
from sleep terrors,which mostly occur during stage 4 sleep,
and from nightmares, which mostly occur during REM
sleep.51 Moreover,nocturnal panic could be differentiated
from nocturnal seizures by the fact that no EEG abnor-
mality was demonstrated during nocturnal panic attacks
and from sleep apnea because sleep apnea occurs mostly
during stages 1 and 2, as well as during REM sleep, and is
more repetitive than nocturnal panic.40
There are limited indications that subjects with frequent
sleep panic attacks have a severe form of panic disor-
der.37,38,52 More recent studies suggest that there are only
few differences on measures of psychopathology and on
sleep EEG between panic-disordered patients with and
without sleep-related panic attacks.40,53 However, differ-
ences may be more subtle and evidenced by techniques
such as measurement of the autonomic nervous system
(ANS) activity. For instance, Sloan et al54 used a lactate
infusion panicogenic challenge and heart rate variability as
a measurement of ANS activity to demonstrate that ANS
dysregulation during sleep is more pronounced in noctur-
nal panic patients than in daytime panic patients.This sug-
gests a more increased arousal level in nocturnal panic.
On the basis of several observations,38,40,51 it has been pro-
posed that nocturnal panic is characterized by height-
ened distress to situations that involve loss of vigilance,
such as sleep and relaxation, and that it may represent
one particular version of panic disorder that responds
just as well as other forms of panic disorder to usual
antipanic treatment.40 In this regard, the adjunction of
cognitive-behavioral therapy to pharmacological agents
will be particularly beneficial in patients with nocturnal
panic, since some patients can develop a conditioned fear
or even an avoidance of sleep, which may cause further
sleep deprivation and thus aggravate the condition.
Generalized anxiety disorder
A persistent state of anxiety, ie, lasting for at least 6
months, characterizes GAD. Anxiety and apprehensive
expectation (“worry”) need to relate to a certain number
of events and to be accompanied by additional symptoms
belonging to a motor tension cluster (muscle tension;
restlessness; and easy fatigability) or to a vigilance and
scanning cluster (difficulty falling or staying asleep; rest-
less, unsatisfying sleep; difficulty concentrating; and irri-
tability). According to DSM-IV,34 the diagnosis is not
made if the symptoms exclusively relate to another Axis I
disorder.As sleep disturbances are part of the diagnosis
requirement, a high prevalence of these symptoms is
expected in GAD. For instance, in mental health epi-
demiological surveys, Ohayon et al55 found that, among
subjects complaining of insomnia and having a primary
diagnosis of mental disorder, GAD was the most preva-
lent diagnosis. It has been estimated that about 60% to
70% of patients with GAD have insomnia complaint,
whose severity parallels that of the anxiety disorder,56,57
suggesting that insomnia could represent one of the core
symptoms of GAD.
Sleep EEG recording
Monti and Monti58 have extensively reviewed six selected
studies investigating polysomnographic recording of
patients with GAD.The sleep EEG recordings following
an adaptation night of 130 patients were compared to
those of 147 normal controls in the age range 20 to 65
years (mean 37 years). Regarding sleep continuity, the
results indicate that GAD is mostly associated with sleep
maintenance insomnia, and to a lesser extent with sleep
initiation difficulties. Five studies found a significant
decrease in total sleep time, four an increase of waking
after sleep onset, while only two studies showed a signif-
icant prolongation of sleep onset latency. As regards
NREM and REM sleep structures, results are inconsis-
tent. Stage 4 was significantly decreased in three studies,
all six studies showed nonsignificant decrease in REM
sleep, and one study a significant shortening of REM
latency.
Treatment
GAD is often responsive to BZDs, buspirone, and anti-
depressants.Anxiolytic BZDs provide a prompt relief of
the GAD symptoms belonging to the motor and the vig-
ilance-scanning clusters. However, psychic symptoms
such as worry and ruminations are less affected by these
compounds and respond better to antidepressants such
as TCAs, SSRIs, or norepinephrine and serotonin selec-
tive antidepressant (NaSSA), such as venlafaxine.58
Adjunctive psychotherapy with a cognitive focus can be
beneficial. In this regard, studies have shown that cog-
nitive-behavioral techniques are better than control con-
ditions or to either cognitive or behavior therapy alone.58
Clinical research
254
The alleviation of the sleep disturbance can often greatly
improve the condition: therefore a low-dose, intermedi-
ate-acting BZD at bedtime may be temporarily indicated
early in the treatment. Sedative antidepressant could also
help improve sleep.
Obsessive-compulsive disorder
According to DSM-IV,34 the essential features of the OCD
are recurrent obsessions or compulsions that are suffi-
ciently severe to cause a signification disruption of a per-
son’s daily routine. The most common obsessional
thoughts are fears of contamination, of being aggressive,
and of a sexual nature; the most common compulsions
relate to checking, cleaning, and counting. The sufferer
knows that it is his or her own thought (or act), that it
arises from within him- or herself, and that it is subject to
the sufferer’s own will.Anxiety is provoked by the fear of
what may happen if the compulsive rituals are disturbed,
the need to both perform the action and preserve social
acceptability, or the fearful nature of the obsessional
thoughts themselves.The person usually functions satis-
factorily in other areas of life not contaminated by the
obsessional thoughts, but as the obsessions become more
severe there is increasing social incapacity.
Patients often complain of disrupted sleep and sleep
delay due to compulsive behaviors. In one epidemiolog-
ical survey,55 insomnia related to OCD had a prevalence
of 0.2% (ie, insomnia complaints sufficiently severe to
warrant an Axis I diagnosis in addition to OCD), while
the prevalence of OCD with insomnia (not sufficiently
severe to warrant a separate diagnosis) was 1.2%.These
data should be compared with the 2.5% of OCD preva-
lence in the general population.34
Sleep EEG recording
Studies comparing polysomnographic sleep EEG record-
ings from OCD patients with those of normal volunteers
are scanty and bring divergent results.Most of these stud-
ies contained a large number of patients with a comorbid
mood disorder, leaving doubt about the specificity of
their findings.59-61 The three studies found various degrees
of sleep continuity disturbances, mainly regarding sleep
maintenance. REM latency was found shortened in two
out of the three studies. Robinson et al62 investigated a
group of OCD patients free of major depression and
could not evidence any significant difference in sleep
continuity and architecture variables between patients
and healthy controls. However, slight negative correla-
tions were found between severity of obsessive-compul-
sive symptoms and total sleep time or sleep efficiency. In
summary, except for sleep maintenance disturbances,
there is at yet no clear pattern of polysomnographic find-
ings in OCD.
Treatment
Treatment is generally a combination of pharmacotherapy
with serotonin-potentiating agents and behavioral therapy.
In contrast to other anxiety disorder, only drugs inhibiting
serotonin reuptake have proven their efficacy in OCD.63
According to a recent meta-analysis, clomipramine has
been demonstrated to be superior to the other drugs,64 but
poor tolerance and the lethal risk of overdose can limit
their utilization. Accordingly, SSRIs are now considered
to be first-line treatment for OCD.65 Placebo-controlled
studies have shown the efficacy of paroxetine, fluoxetine,
fluvoxamine, citalopram, and sertraline.66 Since SSRIs can
act as stimulants, especially at the doses required to treat
OCD, and induce insomnia, the concurrent use of tra-
zodone or a low-dose sedative TCA is often prescribed,
particularly for patients with a history of sleep complaints
prior pharmacotherapy.
Posttraumatic stress disorder
Neuropsychological problems following experience of a
traumatic event characterize patients suffering from
PTSD.The stressful event must have been exceptionally
threatening or catastrophic in nature, such as a natural
disaster, combat,serious accident, witnessing the violent
death of someone, or being the victim of torture or rape.
The typical features of PTSD are commonly grouped
into three catergories34: (i) reexperiencing the traumatic
event (comprising preoccupation of reliving the trauma,
intrusive memories or flashbacks,and vivid nightmares);
(ii) persistent avoidance of stimuli associated with the
trauma and numbing of general responsiveness; and (iii)
signs of increased arousal, such as hypervigilance, insom-
nia, and difficulty concentrating.Patients with PTSD may
become socially isolated and, at times, may resort the use
of drugs or alcohol to suppress the traumatic memories
and tormented wakefulness.The lifetime prevalence of
the disorder is between 1% and 9%.67 Sleep disturbances
in terms of nightmares and insomnia are a very promi-
Sleep and anxiety disorders - Staner Dialogues in Clinical Neuroscience - Vol 5 .No. 3 .2003
255
nent complaint of subjects who have undergone trauma;
for instance, it has been estimated that 96% of Holocaust
survivors complained of insomnia and 83% reported
recurrent nightmares.68 Pillar et al67 reported that patients
with PTSD frequently described very prolonged sleep
latencies (ie, more than 2 h), and estimate being awake
more than half of the time in bed during the night (ie, a
subjective sleep efficiency of less than 50%). More gen-
erally, it must be underlined that recurrent distressing
dreams of a traumatic event are pathognomonic of
PTSD,in the sense that they are not observed in other
disorders, contrary to complaints such as insomnia.
Sleep EEG recording
Results of studies investigating polysomnographic
recordings of patients with PTSD have been previously
reviewed67 and contrast somewhat with the prevalence of
subjective sleep complaints. Pillar et al67 concluded that
PTSD itself does not dramatically adversely affect objec-
tive sleep. Some studies found longer sleep latencies,
reduced total sleep time, and lower efficiencies among
patients with PTSD,but numerous other studies failed to
replicate this finding. SWS did not seem to be affected
during PTSD, while inconsistent results have been
reported for REM sleep: both shortening and prolonga-
tion of REM latency and lower and higher time spent in
REM were reported in PTSD.Most relevant studies in
PTSD reported on increased REM density, ie,more rapid
eye movements per REM time, a finding that could
relate to the hostile and threatening characteristics of a
dream. Some of the positive findings could be related to
comorbid psychiatric illness, such as major depression.67
Treatment
Patients with PTSD generally benefit from some form of
individual or group psychotherapy, especially early in the
course of the disorder.With regard to pharmacotherapy,
SSRIs appear to be the treatment of choice and their effi-
cacy and safety have been demonstrated by meta-analysis,
while TCAs have a more modest effect on PTSD symp-
toms.66 Early in treatment, for severe cases, sedative anti-
depressant could bring relief to night terror activity. BZDs
may be helpful, but tolerance may develop because of the
chronicity of the disorder and it should be kept in mind that
the risk of associated dependence is high in these patients.
Conclusions
Although sleep disturbances, and particularly severe
insomnia complaints, are often encountered in patients
with anxiety disorders, polysomnographic studies docu-
mented limited alteration of sleep continuity, ie,sleep ini-
tiation and sleep maintenance. Regarding sleep architec-
ture, no clear picture emerges for specific anxiety
disorders.Discrepancies between studies could have been
related to illness severity, diagnostic comorbidity, and
duration of illness. It should be stressed that anxiety in
itself is present in many psychiatric disorders and that
therefore the assessment of anxiety as a single influence
on sleep is quite difficult. Our current preclinical under-
standing of arousal responses to aversive stress and some
confirmation that similar mechanisms may play a role in
human stress,should open the way to the development of
more specific therapeutic tools in sleep medicine, partic-
ularly for anxiety-induced sleep alterations.
Clinical research
256
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... One of the novel findings of this study is the role of early sleep difficulties as risk factors for persistent high levels of anxiety disorders. Sleep disturbances are highly prevalent in anxiety (Staner, 2003). Further, sleep problems in childhood associate with anxiety in adulthood (Gregory et al., 2005). ...
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