Dialogues in Clinical Neuroscience

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Sleep and anxiety disorders

Luc Staner

To cite this article: Luc Staner (2003) Sleep and anxiety disorders, Dialogues in Clinical
Neuroscience, 5:3, 249-258, DOI: 10.31887/DCNS.2003.5.3/lstaner
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Clinical research
Sleep and anxiety disorders
Luc Staner, MD

A 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-

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.

Keywords: sleep; insomnia; anxiety disorder; sleep–wake regulation; panic Address for correspondence: Sleep Laboratory, FORENAP, Institute for
disorder; generalized anxiety disorder; obsessive-compulsive disorder; posttrau- Research in Neuroscience and Neuropsychiatry, BP29, 68250 Rouffach, France
matic stress disorder (e-mail: [email protected])

Author affiliations: Sleep Laboratory, FORENAP, Rouffach, France

Copyright © 2003 LLS SAS. All rights reserved

249 www.dialogues-cns.org
Clinical research
Selected abbreviations and acronyms the duration of stages 3 and 4 decrease, and the propor-
ACTH adrenocorticotropic hormone tion of the cycle occupied by REM sleep tends to
AN autonomic nervous (system) increase with REM episodes occurring late in the night
BZD benzodiazepine having more eye movement bursts than REM episodes
CNA central nucleus of the amygdala occurring early in the night.3
CRH corticotropin-releasing hormone Most models of sleep regulation have implicated the
GAD generalized anxiety disorder monoaminergic and cholinergic systems and the impor-
HPA hypothalamic-pituitary-adrenal (axis) tance of inhibitory GABAergic (GABA, γ-aminobutyric
LC locus ceruleus acid) mechanisms in sleep regulation is well established.4
NE norepinephrine Since dysfunction of these neurotransmitter systems have
NREM non–rapid eye movement been implicated in anxiety disorders,5 it is no wonder that
OCD obsessive-compulsive disorder one of the chief complaints of anxiety disorder patients
PTSD posttraumatic stress disorder relates to sleep alteration.
PVN paraventricular nucleus Sleep–wake regulation is classically viewed as resulting
REM rapid eye movement from the interaction of two regulating processes (circa-
SSRI selective serotonin reuptake inhibitor dian [C] and homeostatic [S]).6 The propensity to sleep
SWS slow-wave sleep or be awake at any given time is a consequence of a sleep
TCA tricyclic antidepressant
debt (process S), and its interaction with signals coming
from the circadian clock located in the suprachiasmatic
ence increase in anxiety in certain situations. Moreover, nucleus (process C). Process S is supposed to reflect the
the various anxiety disorders share many biological and activity of a somnogenic substance that progressively
clinical similarities, and are highly comorbid. Therefore, accumulates with prolonged wakefulness, with adenosine
in this article, we will first discuss common features of the being one of the most cited candidates.7 Both homeosta-
neurobiological basis of anxiety and its relationships with tic and circadian mechanisms are thought to influence
sleep physiology. Next, sleep disturbances and its treat- the opposite action of neurons promoting wakefulness
ment will be discussed; for clinical convenience, each of and neurons promoting sleep. Wake-active neurons are
the different anxiety disorders will be discussed sepa- cholinergic (located in the basal forebrain and in the
rately. Indeed, the treatment of the anxiety disorder sig- tegmentum) and monoaminergic (noradrenergic in the
nificantly improves sleep; however, when the sleep dis- locus ceruleus, serotonergic in the dorsal raphe, and his-
turbance predominates, its treatment may improve the taminergic in the tuberomammillary nucleus), whereas
management of the anxiety disorder. sleep-active neurons are GABAergic and located in the
preoptic area of the hypothalamus.4
A brief survey of sleep physiology The discovery of the hypocretin (also called orexin) sys-
tem has brought new inroads into understanding the
Human sleep consists of two qualitatively different brain sleep-regulatory neural circuit.8 Hypocretin neurons are
states, non–rapid eye movement (NREM) and rapid eye located in the lateral hypothalamus and have dense exci-
movement (REM) sleep. NREM sleep is further subdi- tatory projections to all monoaminergic and cholinergic
vided into stages 1 through 4, with stage 1 being the light- cell groups. Recent studies suggested that monoaminer-
est and stage 4 being the deepest sleep. Since slow “delta” gic and hypocretin neurons play a different and comple-
waves distinguish stages 3 and 4, the stages are often mentary role in wakefulness maintenance.4 For example,
defined as delta sleep or slow-wave sleep (SWS). REM the dual effects of hypocretins on arousal and food intake
sleep is also called paradoxical sleep because of the close (orexin from “appetite-stimulating”) suggest a more
resemblance with the electroencephalogram (EEG) of important role for hypocretins in the control of arousal
active wakefulness combined with a “paradoxical” active maintenance related to energy homeostasis.8 In the same
inhibition of major muscle groups that seems to reflect a way, data summarized in the following section suggest a
heavy sleep. Normal sleep is characterized electrograph- role for the norepinephrine (NE)–containing neurons of
ically as recurrent cycles of NREM and REM sleep of the locus ceruleus (LC) in stress-induced arousal and
about 90 min. In the successive cycles during the night, concomitant anxiety.

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Interactions between stress, activate different components of the stress system, eg, the
anxiety, and sleep LC-AN system will be more implicated in the response
to physiological stressors such as hypoxia, while the CRH
Anxiety and stress system will be recruited for more complex environmen-
tal dangers such as emotional stress. However, there are
Anxiety is a universal emotion and it would at times be several connections between the two systems which are
maladaptive not to experience it; it is a necessary part of continuously in close interaction (see next section).
the response of the organism to a stress, ie, a threat to the
psychological or the physiological integrity of an indi- The stress system
vidual. Anxiety may be polarized between a state and a
trait. It may supervene at some point in the course of life, During these last years, a series of studies in rodents
in which case anxiety is referred as a state. Anxiety trait established the role of CRH as a key neurotransmitter in
is a long-term feature of a person’s experience, present the stress response, beside its stimulating effect on the
throughout life and considered to be a key feature of the hypothalamic-pituitary-adrenal (HPA) axis.9,11 It has been
avoidant or anxious personality disorder. It probably shown that hypothalamic CRH neurons activate the LC-
reflects a lifetime maladaptive response to stress due to AN system and inhibit a variety of neurovegetative func-
individual differences in biogenetic background, devel- tions, such as food intake, sexual activity, growth, and
opmental influences, and early life experiences. There is reproduction. CRH-containing neurons located in the
no hard and fast distinction between anxiety that may be central nucleus of the amygdala (CNA) play a key role
considered as a normal, acceptable accompaniment of by activating fear-related behavior, while inhibiting
stress and the pathological state that warrants classifica- exploration behavior. Like the CRH system, the NE-con-
tion as a psychiatric disorder. In the latter, the nature of taining neurons of the LC promote arousal, inhibit the
the stress is not always clearly discernible. In other words, parasympathetic system as well as several vegetative
pathological anxiety could be characterized by a sense of functions such as feeding and sleep, and contribute to
fear, but it is differentiated from fear in that the threat is HPA axis stimulation.12 It has been shown that stress
not immediate or always obvious. Whether normal or increases NE turnover in many terminal projections of
pathological, the constituent features of anxiety always the LC and that the activity of LC neurons is monoton-
comprise indices of increased arousal or alertness that ically related to increased arousal.9
could lead to sleep–wake alterations. Indeed, anxiety is There is also evidence that NE stimulates the release of
only one part of the arousal response to stress, whether CRH in the paraventricular nucleus (PVN) of the hypo-
the stress is real, implied, or overvalued. thalamus and in the CNA.9 These NE-CRH influences
suggest a potential feed-forward system between the
Arousal and stress

Response to stress implicates two systems that both play

Hormonal
a key role in physiological responses to stressful situation CRH system CRH response
by promoting arousal, the corticotropin-releasing hor- Hypothalamus (PVN)
Amygdala (CNA)
mone (CRH) system and the LC–autonomic nervous Emotional
(AN) system. This topic has recently been reviewed by stressors NE Behavioral
response
several authors9-11 and will be only briefly described here. Physiological CRH
Before going further, it should be emphasized that pro- stressors
NE
moting arousal is essential for identifying a given situa- LC-AN system
Autonomic
tion as important, as well as for maintaining the central response
nervous system (CNS) in states that most favor survival
during stressful situations. Arousal response to stress
Figure 1. Arousal response to stress. CRH, corticotropin-releasing hor-
comprises three components (hormonal, behavioral, and mone; PVN, paraventricular nucleus; CNA, central nucleus of
autonomic) in which CRH and LC-AN systems have the amygdala; LC-AN, locus ceruleus–autonomic nervous; NE,
been diversely implicated (Figure 1). Different stressors norepinephrine.

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Clinical research
LC-AN system and the CRH system, and both systems 22
Exogenous administration of CRH, adrenocorticotropic
have stimulating properties on its counterpart. It has hormone (ACTH), or cortisol produces either prolonged
been suggested that such a feed-forward mechanism may sleep onset, reduced SWS, and increased sleep fragmenta-
be particularly vulnerable to dysfunction during which tion.13 Accordingly, patients with complaints of insomnia
the arousal reaction is maintained despite the removal of show electrophysiological and psychomotor evidence of
the stressful situation.9,10 The same authors have proposed increased daytime arousal,23-25 as well as indications of
that, if prolonged, such dysfunctional arousal state could increased HPA activity26 and increased sympathetic tone.27
lead to anxiety and depressive disorder.
Sleep complaints and anxiety disorder
Stress and sleep–wake regulation
Anxiety disorders are considered as the most frequently
Animal and human studies showed that both acute and occurring category of mental disorder in the general
chronic stress have pronounced effects on sleep that are population. Estimates of the lifetime prevalence of anxi-
mediated through the activation of the HPA axis and the ety disorders have ranged between 10% and 25%.28
sympathetic system.13 For instance, in rats, effects of acute Epidemiological studies have also demonstrated the high
stress on sleep are primarily manifested by changes in prevalence of sleep complaints. As much as one third of
REM sleep.These alterations seem to involve CRH-medi- the adult population reports difficulty sleeping29-31 and
ated mechanisms: CRH acts as a neurotransmitter in the sleep disturbance is considered as the second most com-
LC to increase activity of the NE neurons, which leads to mon symptom of mental distress.32 Some epidemiological
an increase in REM sleep.14 Rats exposed to various mod- studies investigated the relationship between the occur-
els of chronic stress have shown sleep disruption, increase rence of sleep disturbances and anxiety disorder in the
in REM sleep, and decrease in SWS.15,16 There are also indi- general population.1,2,33 In a longitudinal study of young
cations that CRH could contribute to the regulation of adults, Breslau et al2 found that lifetime prevalence was
spontaneous waking even in the absence of stressors.17 16.6% for insomnia alone, 8.2% for hypersomnia alone,
In humans, there is a close temporal relationship between and 8% for insomnia plus hypersomnia. Odds ratios for
HPA activity and sleep structure. The HPA axis is subject various anxiety disorder diagnoses associated with life-
to a pronounced inhibition during the early phase of noc- time sleep disturbance varied from 1.2 to 13.1. Table I
turnal sleep, during which SWS predominates. In contrast, shows that the odds ratios associated with insomnia alone
during late sleep, when REM sleep predominates, HPA varied little from those associated with hypersomnia
activity increases to reach a diurnal maximum shortly after alone. The three highest odds ratios were those for obses-
morning awakening. During SWS, sympathetic activity is sive-compulsive disorder (OCD) and for panic disorder
reduced and there is positive correlation among the associated with both insomnia and hypersomnia, and that
amount of REM sleep and activities of the HPA axis and for GAD associated with insomnia alone.
the sympathetic system.18,19 More generally, a close coupling These findings were replicated for chronic insomnia in a
has been shown between adrenocorticotropic, autonomic, recent study,33 which further showed that insomnia
and EEG indices of arousal during the sleep–wake cycle.20- appeared before the anxiety disorder in 18% of cases,
anxiety and insomnia appeared about in the same time
Insomnia Hypersomnia Both in 38.6% of cases, and anxiety appeared before insomnia
alone alone in 43.5% of cases. These authors concluded that psychi-
GAD 7.0 (2.8–17.2) 4.5 (1.5–15.3) 4.8 (1.5–15.2) atric history, including anxiety disorder, is closely related
Panic disorder 5.3 (2.0–13.6) 4.3 (1.3–14.8) 8.5 (3.1–23.5) to the severity and chronicity of current insomnia.
OCD 5.4 (2.0–14.8) 1.2 (0.1–9.7) 13.1 (4.8–35.7)
Phobic disorder 1.5 (1.0–2.3) 2.9 (1.8–4.8) 4.0 (2.5–6.5) Panic disorder and agoraphobia
Any anxiety 2.4 (1.6–3.5) 3.3 (2.0–5.4) 4.5 (2.8–7.3)
disorder The essential features of panic disorder are recurrent
Table I. Odds ratios for specific anxiety disorders associated with lifetime
attacks of severe anxiety (panic attacks), which are not
sleep disturbances (adapted from Breslau et al2). GAD, general- restricted to any particular situation or set of circum-
ized anxiety disorder; OCD, obsessive-compulsive disorder. stances and are therefore unpredictable. According to

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Sleep and anxiety disorders - Staner Dialogues in Clinical Neuroscience - Vol 5 . No. 3 . 2003

the Diagnostic and Statistical Manual of Mental Disorders, and increased time awake after sleep onset resulting in a
Fourth Edition (DSM-IV)34 criteria of panic disorder, reduced sleep efficiency (the ratio between total sleep
unexpected panic attacks have to be followed by at least time and time in bed),41-47 but there are also negative
1 month of persistent concern about having another reports showing no difference compared with controls in
panic attack. The dominant symptoms of a panic attack these variables.48,49 Concerning sleep architecture, NREM
vary from individual to individual. Typically, it includes sleep was found differently affected across studies; some
autonomic symptoms with marked psychic anxiety. The reported a decreased in stage 2 sleep duration42,43 with a
most prominent autonomic symptoms are palpitations, concomitant increase in SWS.47 Time spent in SWS was
sweating, trembling, shortness of breath, dizziness, chest found reduced by Arriaga et al46 and Stein et al,49 but
pain, nausea, and paresthesias. There is almost always a unchanged by other authors.36,42,45 Controversial results
secondary fear of dying, losing control, or going mad. were also obtained regarding REM sleep. Although most
Most individual attacks last only for a few minutes, but studies agreed on the fact that REM sleep time is
a common complication is the development of anticipa- unchanged in panic disorder, some authors found a short-
tory fear of helplessness or loss of control during a panic ening of REM sleep latency,36,48 while others did not.41,44
attack, so that the individual may progressively develop To summarize, most studies suggest that the subjective
avoidant behavior leading to agoraphobia or specific sleep continuity disturbances reported by patients with
phobias. In this respect, most, if not all, patients with panic disorder could be objectively demonstrated by
agoraphobia also have a current diagnosis (or history) polysomnographic recordings. Findings regarding sleep
of panic disorder.34 Accordingly, sleep disturbances of architecture are more controversial (although REM
panic disorder and agoraphobia are discussed in the sleep seems to be preserved). These discrepancies could
same section. relate to sampling differences (some studies having
included patients with a comorbid depressive disorder)
Subjective sleep and to the influence of nocturnal panic attack during the
sleep EEG recording.
Sleep disturbances, predominantly insomnia, are
extremely common in panic disorder. Sheehan et al35 Treatment
reported a prevalence of 68% for difficulties in falling
asleep and of 77% for restless and disturbed sleep. In a Sleep disturbances linked to panic disorder respond to a
self-report sleep survey, Mellman and Uhde36 found that, number of antipanic pharmacological agents including
compared with healthy subjects, patients with panic dis- selective serotonin reuptake inhibitors (SSRIs), tricyclic
order reported more complaints of middle night insom- antidepressants (TCAs), benzodiazepines (BZDs), and
nia (67% versus 23%) and late night insomnia (67% monoamine oxidase inhibitors (MAOIs). Some patients
versus 31%); the two groups did not differ with regard could have an initial increased anxiety or insomnia in
to early night insomnia. Many patients with panic disor- response to antidepressant medications, which should
der experience occasional sleep panic attacks, but only alert the clinician to the need to increase the dosage quite
about 20% to 45% of patients with panic disorder have slowly. A BZD can also be used to reduce anxiety and aid
repeated nocturnal panic attacks.37-39 Some evidence sug- sleep in the early phases of treatment.
gests that patients experiencing regular nocturnal panic
attacks represent a specific version of panic disorder Nocturnal panic
characterized by fearful associations with sleep and
sleep-like states.40 Therefore, nocturnal panic attacks will The majority of patients with panic disorder experience
be discussed in a separate section. nocturnal panic attacks. However, in a subgroup of
patients, sleep-related panic is the predominant symptom,38
Sleep EEG recording with up to 18% of all panic attacks occurring during
sleep.50 Nocturnal panic refers to waking from sleep in a
Most polysomnographic studies indicate that patients state of panic and should be distinguished from nighttime
with panic disorder have impaired sleep initiation and arousal induced by nightmares or environmental stimuli
maintenance characterized by increased sleep latency (such as unexpected noise). It has often been mistaken for

253
Clinical research
sleep apnea, sleep terrors, and nocturnal epilepsy. tability). According to DSM-IV,34 the diagnosis is not
Nocturnal panic generally occurs during late stage 2 to made if the symptoms exclusively relate to another Axis I
early stage 3 sleep, and can therefore be distinguished disorder. As sleep disturbances are part of the diagnosis
from sleep terrors, which mostly occur during stage 4 sleep, requirement, a high prevalence of these symptoms is
and from nightmares, which mostly occur during REM expected in GAD. For instance, in mental health epi-
sleep.51 Moreover, nocturnal panic could be differentiated demiological surveys, Ohayon et al55 found that, among
from nocturnal seizures by the fact that no EEG abnor- subjects complaining of insomnia and having a primary
mality was demonstrated during nocturnal panic attacks diagnosis of mental disorder, GAD was the most preva-
and from sleep apnea because sleep apnea occurs mostly lent diagnosis. It has been estimated that about 60% to
during stages 1 and 2, as well as during REM sleep, and is 70% of patients with GAD have insomnia complaint,
more repetitive than nocturnal panic.40 whose severity parallels that of the anxiety disorder,56,57
There are limited indications that subjects with frequent suggesting that insomnia could represent one of the core
sleep panic attacks have a severe form of panic disor- symptoms of GAD.
der.37,38,52 More recent studies suggest that there are only
few differences on measures of psychopathology and on Sleep EEG recording
sleep EEG between panic-disordered patients with and
without sleep-related panic attacks.40,53 However, differ- Monti and Monti58 have extensively reviewed six selected
ences may be more subtle and evidenced by techniques studies investigating polysomnographic recording of
such as measurement of the autonomic nervous system patients with GAD. The sleep EEG recordings following
(ANS) activity. For instance, Sloan et al54 used a lactate an adaptation night of 130 patients were compared to
infusion panicogenic challenge and heart rate variability as those of 147 normal controls in the age range 20 to 65
a measurement of ANS activity to demonstrate that ANS years (mean 37 years). Regarding sleep continuity, the
dysregulation during sleep is more pronounced in noctur- results indicate that GAD is mostly associated with sleep
nal panic patients than in daytime panic patients.This sug- maintenance insomnia, and to a lesser extent with sleep
gests a more increased arousal level in nocturnal panic. initiation difficulties. Five studies found a significant
On the basis of several observations,38,40,51 it has been pro- decrease in total sleep time, four an increase of waking
posed that nocturnal panic is characterized by height- after sleep onset, while only two studies showed a signif-
ened distress to situations that involve loss of vigilance, icant prolongation of sleep onset latency. As regards
such as sleep and relaxation, and that it may represent NREM and REM sleep structures, results are inconsis-
one particular version of panic disorder that responds tent. Stage 4 was significantly decreased in three studies,
just as well as other forms of panic disorder to usual all six studies showed nonsignificant decrease in REM
antipanic treatment.40 In this regard, the adjunction of sleep, and one study a significant shortening of REM
cognitive-behavioral therapy to pharmacological agents latency.
will be particularly beneficial in patients with nocturnal
panic, since some patients can develop a conditioned fear Treatment
or even an avoidance of sleep, which may cause further
sleep deprivation and thus aggravate the condition. GAD is often responsive to BZDs, buspirone, and anti-
depressants. Anxiolytic BZDs provide a prompt relief of
Generalized anxiety disorder the GAD symptoms belonging to the motor and the vig-
ilance-scanning clusters. However, psychic symptoms
A persistent state of anxiety, ie, lasting for at least 6 such as worry and ruminations are less affected by these
months, characterizes GAD. Anxiety and apprehensive compounds and respond better to antidepressants such
expectation (“worry”) need to relate to a certain number as TCAs, SSRIs, or norepinephrine and serotonin selec-
of events and to be accompanied by additional symptoms tive antidepressant (NaSSA), such as venlafaxine.58
belonging to a motor tension cluster (muscle tension; Adjunctive psychotherapy with a cognitive focus can be
restlessness; and easy fatigability) or to a vigilance and beneficial. In this regard, studies have shown that cog-
scanning cluster (difficulty falling or staying asleep; rest- nitive-behavioral techniques are better than control con-
less, unsatisfying sleep; difficulty concentrating; and irri- ditions or to either cognitive or behavior therapy alone.58

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Sleep and anxiety disorders - Staner Dialogues in Clinical Neuroscience - Vol 5 . No. 3 . 2003

The alleviation of the sleep disturbance can often greatly continuity and architecture variables between patients
improve the condition: therefore a low-dose, intermedi- and healthy controls. However, slight negative correla-
ate-acting BZD at bedtime may be temporarily indicated tions were found between severity of obsessive-compul-
early in the treatment. Sedative antidepressant could also sive symptoms and total sleep time or sleep efficiency. In
help improve sleep. summary, except for sleep maintenance disturbances,
there is at yet no clear pattern of polysomnographic find-
Obsessive-compulsive disorder ings in OCD.

According to DSM-IV,34 the essential features of the OCD Treatment

are recurrent obsessions or compulsions that are suffi-
ciently severe to cause a signification disruption of a per- Treatment is generally a combination of pharmacotherapy
son’s daily routine. The most common obsessional with serotonin-potentiating agents and behavioral therapy.
thoughts are fears of contamination, of being aggressive, In contrast to other anxiety disorder, only drugs inhibiting
and of a sexual nature; the most common compulsions serotonin reuptake have proven their efficacy in OCD.63
relate to checking, cleaning, and counting. The sufferer According to a recent meta-analysis, clomipramine has
knows that it is his or her own thought (or act), that it been demonstrated to be superior to the other drugs,64 but
arises from within him- or herself, and that it is subject to poor tolerance and the lethal risk of overdose can limit
the sufferer’s own will.Anxiety is provoked by the fear of their utilization. Accordingly, SSRIs are now considered
what may happen if the compulsive rituals are disturbed, to be first-line treatment for OCD.65 Placebo-controlled
the need to both perform the action and preserve social studies have shown the efficacy of paroxetine, fluoxetine,
acceptability, or the fearful nature of the obsessional fluvoxamine, citalopram, and sertraline.66 Since SSRIs can
thoughts themselves. The person usually functions satis- act as stimulants, especially at the doses required to treat
factorily in other areas of life not contaminated by the OCD, and induce insomnia, the concurrent use of tra-
obsessional thoughts, but as the obsessions become more zodone or a low-dose sedative TCA is often prescribed,
severe there is increasing social incapacity. particularly for patients with a history of sleep complaints
Patients often complain of disrupted sleep and sleep prior pharmacotherapy.
delay due to compulsive behaviors. In one epidemiolog-
ical survey,55 insomnia related to OCD had a prevalence Posttraumatic stress disorder
of 0.2% (ie, insomnia complaints sufficiently severe to
warrant an Axis I diagnosis in addition to OCD), while Neuropsychological problems following experience of a
the prevalence of OCD with insomnia (not sufficiently traumatic event characterize patients suffering from
severe to warrant a separate diagnosis) was 1.2%. These PTSD. The stressful event must have been exceptionally
data should be compared with the 2.5% of OCD preva- threatening or catastrophic in nature, such as a natural
lence in the general population.34 disaster, combat, serious accident, witnessing the violent
death of someone, or being the victim of torture or rape.
Sleep EEG recording The typical features of PTSD are commonly grouped
into three catergories34: (i) reexperiencing the traumatic
Studies comparing polysomnographic sleep EEG record- event (comprising preoccupation of reliving the trauma,
ings from OCD patients with those of normal volunteers intrusive memories or flashbacks, and vivid nightmares);
are scanty and bring divergent results. Most of these stud- (ii) persistent avoidance of stimuli associated with the
ies contained a large number of patients with a comorbid trauma and numbing of general responsiveness; and (iii)
mood disorder, leaving doubt about the specificity of signs of increased arousal, such as hypervigilance, insom-
their findings.59-61 The three studies found various degrees nia, and difficulty concentrating. Patients with PTSD may
of sleep continuity disturbances, mainly regarding sleep become socially isolated and, at times, may resort the use
maintenance. REM latency was found shortened in two of drugs or alcohol to suppress the traumatic memories
out of the three studies. Robinson et al62 investigated a and tormented wakefulness. The lifetime prevalence of
group of OCD patients free of major depression and the disorder is between 1% and 9%.67 Sleep disturbances
could not evidence any significant difference in sleep in terms of nightmares and insomnia are a very promi-

255
Clinical research
nent complaint of subjects who have undergone trauma; Treatment
for instance, it has been estimated that 96% of Holocaust
survivors complained of insomnia and 83% reported Patients with PTSD generally benefit from some form of
recurrent nightmares.68 Pillar et al67 reported that patients individual or group psychotherapy, especially early in the
with PTSD frequently described very prolonged sleep course of the disorder. With regard to pharmacotherapy,
latencies (ie, more than 2 h), and estimate being awake SSRIs appear to be the treatment of choice and their effi-
more than half of the time in bed during the night (ie, a cacy and safety have been demonstrated by meta-analysis,
subjective sleep efficiency of less than 50%). More gen- while TCAs have a more modest effect on PTSD symp-
erally, it must be underlined that recurrent distressing toms.66 Early in treatment, for severe cases, sedative anti-
dreams of a traumatic event are pathognomonic of depressant could bring relief to night terror activity. BZDs
PTSD, in the sense that they are not observed in other may be helpful, but tolerance may develop because of the
disorders, contrary to complaints such as insomnia. chronicity of the disorder and it should be kept in mind that
the risk of associated dependence is high in these patients.
Sleep EEG recording
Conclusions
Results of studies investigating polysomnographic
recordings of patients with PTSD have been previously Although sleep disturbances, and particularly severe
reviewed67 and contrast somewhat with the prevalence of insomnia complaints, are often encountered in patients
subjective sleep complaints. Pillar et al67 concluded that with anxiety disorders, polysomnographic studies docu-
PTSD itself does not dramatically adversely affect objec- mented limited alteration of sleep continuity, ie, sleep ini-
tive sleep. Some studies found longer sleep latencies, tiation and sleep maintenance. Regarding sleep architec-
reduced total sleep time, and lower efficiencies among ture, no clear picture emerges for specific anxiety
patients with PTSD, but numerous other studies failed to disorders. Discrepancies between studies could have been
replicate this finding. SWS did not seem to be affected related to illness severity, diagnostic comorbidity, and
during PTSD, while inconsistent results have been duration of illness. It should be stressed that anxiety in
reported for REM sleep: both shortening and prolonga- itself is present in many psychiatric disorders and that
tion of REM latency and lower and higher time spent in therefore the assessment of anxiety as a single influence
REM were reported in PTSD. Most relevant studies in on sleep is quite difficult. Our current preclinical under-
PTSD reported on increased REM density, ie, more rapid standing of arousal responses to aversive stress and some
eye movements per REM time, a finding that could confirmation that similar mechanisms may play a role in
relate to the hostile and threatening characteristics of a human stress, should open the way to the development of
dream. Some of the positive findings could be related to more specific therapeutic tools in sleep medicine, partic-
comorbid psychiatric illness, such as major depression.67 ularly for anxiety-induced sleep alterations. ❏

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Sleep and anxiety disorders - Staner Dialogues in Clinical Neuroscience - Vol 5 . No. 3 . 2003

Sueño y trastornos de ansiedad Sommeil et troubles anxieux

Los trastornos del sueño particularmente el insom- Les perturbations du sommeil, et en particulier l’in-
nio son altamente prevalentes en los trastornos de somnie, sont très fréquentes dans les troubles
ansiedad, e incluso molestias como el insomnio o anxieux, et les plaintes comme l’insomnie et les cau-
las pesadillas han sido incorporadas en las defini- chemars font même partie de la définition de cer-
ciones de algunos trastornos de ansiedad, como el tains troubles anxieux, comme le trouble anxieux
trastorno de ansiedad generalizada y el trastorno généralisé et l’état de stress posttraumatique. Dans
por estrés postraumático. En la primera parte de la première partie de cette revue de la littérature,
esta revisión se discute la relación entre el sueño y les relations entre sommeil et anxiété sont présen-
la ansiedad en términos de una respuesta de adap- tées dans un contexte de réaction d'adaptation au
tación al estrés. Estudios recientes sugieren que el stress. Des études récentes suggèrent que le sys-
sistema que implica la hormona liberadora de cor- tème impliquant la corticolibérine et le système
ticotrofina y el sistema que implica el locus ceruleus impliquant le locus ceruleus et le système nerveux
y el sistema nervioso autónomo pueden jugar un autonome joueraient un rôle majeur dans la réac-
papel importante en la respuesta de alerta al estrés. tion d'activation suite à un stress. Ces systèmes
Se ha sugerido que estos sistemas pueden ser par- pourraient être particulièrement vulnérables à des
ticularmente vulnerables al estrés prolongado o stress prolongés ou répétés, ce qui serait à l’origine
repetido, lo que conduciría a un estado de alerta d’un état d'activation dysfonctionnel et d’états
disfuncional y estados de ansiedad patológica. Los anxieux pathologiques. Les études polysomnogra-
estudios polisomnográficos han documentado phiques n’identifient que peu d’anomalies du som-
pocas alteraciones del sueño en los trastornos de meil dans les troubles anxieux. Certains éléments
ansiedad. Hay ciertos elementos a favor de una sont en faveur d’une perturbation du maintien du
alteración del sueño en el trastorno de ansiedad sommeil dans le trouble anxieux généralisé et d’une
generalizada, y del inicio y en el mantenimiento del perturbation de l’endormissement et du maintien
sueño en el trastorno de pánico; en cambio, los du sommeil dans le trouble panique ; les données
datos son contradictorios en el trastorno obsesivo sont contradictoires pour le trouble obsessionnel-
compulsivo o en el trastorno por estrés postraumá- compulsif et l’état de stress posttraumatique. Enfin,
tico. Finalmente, no se ha podido determinar que les études n’ont pu mettre en évidence des ano-
alguna anormalidad del sueño se relacione de malies de l’architecture du sommeil spécifiques d’un
manera específica con algún trastorno ansioso, y a trouble anxieux particulier et, inversement, des
la inversa, se han encontrado resultados contradic- résultats contradictoires ont été rapportés pour un
torios para el mismo trastorno. Las discrepancias même trouble anxieux. Ces discordances entre les
entre los estudios pudieran deberse a la severidad études proviennent probablement des différents
de la enfermedad, la comorbilidad diagnóstica o la niveaux de sévérité de la maladie, de la comorbi-
duración de la enfermedad. Además se sugiere una dité psychiatrique et de la durée de la maladie. Une
breve aproximación terapéutica para cada tras- brève approche thérapeutique est également pro-
torno ansioso con especial atención sobre el sueño. posée pour chaque trouble anxieux avec une atten-
tion particulière au sommeil.

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