Annotated Bibliography

Sleep disturbance in anxiety disorders

GEORGE N. PAPADIMITRIOU 1 & PAUL LINKOWSKI

2

1 Athens University Medical School, Department of Psychiatry, Eginition Hospital, Athens, Greece, and

2 Free University of Brussels, Department of Psychiatry, Erasme Hospital, Brussels, Belgium

Summary Many patients suffering from the majority of anxiety disorders complain about their sleep by reporting difficulties in initiating and maintaining it. Polysomnographic studies have shown that, in comparison to normal subjects, the sleep of patients with panic disorder is characterized by longer sleep latency, increased time awake and reduced sleep efficiency. Sleep architecture is normal and there are no significant changes in REM sleep measures. Nocturnal panic attacks are non-REM-related events and occur without an obvious trigger in 18–45% of panic disorder patients. Regarding generalized anxiety disorder, the patients complain of ‘trouble sleeping’ in 60–70%, while polysomnography has shown increased sleep latency and decreased sleep continuity measures. The findings in REM sleep and sleep architecture generally do not show any aberration to exist. In patients with obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD), results from the sleep laboratory do not seem to support the subjective complaints of poor sleep. The early reports of shortened REM latency in OCD could not be replicated by recent studies. A dysregulation of the REM sleep control system has been reported for patients with PTSD. Finally, no significant differences were found in all sleep parameters between social phobia patients and controls.

Introduction

Anxiety disorders have an estimated lifetime pre-

valence ranging between 15 and 25% in the general

population (Kessler et al., 1994). On the other hand,

in spite of the fact that sleep problems are considered

to be a common symptom of mental distress, sleep

disturbance in patients with anxiety disorders has

been the focus of relatively little research, in contrast

to the attention given to sleep disturbances in the

course of mood disorders.

Anxiety disorders are often associated with diffi-

culties in initiating and maintaining sleep and the

etiopathogenetic issues regarding the association of

the two groups of symptoms are not well elucidated

(American Psychiatric Association [APA], 1994;

Benca, Obermeyer, Thisted & Gillin, 1992;

Soldatos & Dikeos, 2003). In a meta-analysis based

on 177 studies with 7151 psychiatric patients,

including those suffering from anxiety disorders,

compared to normal subjects it was demonstrated

that there was disrupted sleep continuity with

significant reduction of total sleep time (TST) and

sleep efficiency (SE, the ratio between total sleep

time and time in bed), while sleep latency (SL) was

prolonged. In sleep architecture, slow wave sleep

(SWS) variables were found to be normal, while the

non rapid eye movement (NREM) time was reduced

in anxiety disorders (Benca et al., 1992).

In a recent study on comorbid anxiety and

insomnia by Ohayon and Roth (2003), it was

shown that in 18% of cases insomnia appeared

before the anxiety disorder, anxiety and insomnia

appeared at about the same time in 39% of cases, and

anxiety appeared before insomnia in 43% of cases.

The authors conclude that psychiatric history,

including anxiety disorder, is closely related to the

severity and chronicity of current insomnia

(Ohayon & Roth, 2003).

The present article is a review of sleep disturbance

among patients with various anxiety disorders. Data,

which pertain to specific differences in sleep char-

acteristics and the effects of sleep deprivation

between anxiety disorders and depression are also

discussed.

Panic disorder

Sleep disturbance, predominantly insomnia, restless

or broken sleep and nocturnal panic attacks are

common complaints in patients with panic disorder

(PD). A prevalence of 68% for difficulties in falling

asleep and of 77% for restless and disturbed sleep

Correspondence: George N. Papadimitriou, MD, Associate Professor of Psychiatry, Athens University Medical School, Department of Psychiatry, Eginition Hospital, 74 Vas Sophias Ave, 115 28, Athens, Greece. Tel: þ30 210 7289 324. Fax: þ30 210 7289 324. E-mail: [email protected]

International Review of Psychiatry, August 2005; 17(4): 229–236

ISSN 0954–0261 print/ISSN 1369–1627 online � 2005 Institute of Psychiatry DOI: 10.1080/09540260500104524

has been reported (Sheehan, Ballenger & Jacobsen,

1980).

Most studies indicate that patients with PD,

compared to normal subjects, complain of perceived

difficulties in the initiation and maintenance of sleep,

characterized by longer SL and increased time awake

after sleep onset resulting in a reduced SE (Arriaga

et al., 1996; Hauri, Friedman & Ravaris, 1989; Lauer

et al., 1992; Saletu-Zyhlarz et al., 2000). However,

there are also negative reports showing no differences

compared with controls (Stein, Enns & Kryger,

1993; Uhde, Roy-Byrne & Gillin, 1984). In sleep

architecture, Stein et al. (1993), reported a ‘remark-

able normality’ of sleep EEG characteristics in 16

non-depressed patients with PD, in comparison with

16 healthy controls. Nevertheless, they found

a reduction of TST, along with an increase of stage

1 percentage and a decrease of SWS percentage, and

difficulties in maintaining sleep. In another study

with 14 PD patients and 14 controls, the patients

presented a higher percentage of wake, a reduced

sleep efficiency and a lower percentage of SWS,

mainly due to diminished amounts of stage 4 sleep

(Arriaga et al., 1996). In relation to sleep duration

and latency as well as in the percentages of stages 1, 2

and 3 no significant differences were observed

(Arriaga et al., 1996). Recently, it has been reported

that PD patients have EEG documented evidence of

difficulty falling asleep and reduced sleep efficiency,

while the sleep architecture is surprisingly ‘normal’

(Uhde, 2000).

Regarding REM sleep measures, controversial

results were obtained. Patients with panic disorder

compared to normals, presented shortened REM

latency, less REM density, and increased movement

time (Lauer et al., 1992; Mellman & Uhde, 1989a;

Uhde et al., 1984), while other studies did not find

similar changes (Dube et al., 1986; Pecknold &

Luthe, 1990; Stein et al., 1995). More recently, in

REM sleep latency and percentage, no differences

between patients and controls were found (Arriaga

et al., 1996). Finally, in one study it was noted that

PD patients, compared with a healthy control group,

have an increased rate of micro-apnoeas (5–10 s)

during sleep (Stein et al., 1995).

Sleep panic attacks

Panic attacks may also occur during sleep (National

Institutes of Health Consensus Development

Conference, 1991). The patients usually waking

from sleep in a state of panic, defined as an abrupt

and discrete period of intense fear or discomfort

accompanied by cognitive and physical symptoms of

arousal (APA, 1994).

Nocturnal panic attacks, as with unexpected day-

time panic attacks, occur without an obvious trigger,

repeatedly (i.e., nightly or weekly) among 18–45%

of panic disorder patients (Craske & Barlow, 1989;

Mellman & Uhde, 1989a, b; Stein et al., 1993; Uhde,

1994). In one of these studies, 45 PD patients and 26

normal control subjects were surveyed regarding

their histories of insomnia and sleep panic attacks.

Among the patients, 69% of them (n ¼ 31) experi-

enced sleep panic at some time in their lives, and

33% (n ¼ 15) experienced recurrent sleep panic

(Mellman & Uhde, 1989b). Panic attacks during

the night are similar in quality, severity and duration

to wake panic attacks, although dyspnea may be

more common in nocturnal than in wake panic

attacks. The majority of PD patients in clinical

treatment have experienced nocturnal panic attacks,

and for a subgroup of patients, sleep related panic is

the predominant symptom (Mellman & Uhde,

1989a), with up to 18% of all panic attacks occurring

during sleep (Taylor et al., 1986). In a review by

Uhde (2000), 33% of a PD outpatient sample

‘commonly’ experienced nocturnal panic attacks.

This kind of attack occurs within three hours of sleep

onset, are short lived, lasting approximately 2–8 min,

and are not associated with dreams, cognition or

imagery (Uhde, 2000).

Patients with PD with nocturnal panic attacks

report higher rates of insomnia, especially non-

restorative sleep and frequent awakenings (Hauri

et al., 1989), as well as depression than do panic

disorder patients without sleep panic (Mellman &

Uhde, 1989a). It is possible that in response to

nocturnal panic attacks, many patients develop a

conditioned fear and avoidance of sleep and the

chronic intermittent sleep deprivation is an impor-

tant complication of nocturnal panic attacks

(Craske & Barlow, 1989). Sloan et al. (1999) in a

study on 12 patients who suffered from panic attacks

during sleep, 12 from daytime panic attacks and 12

control subjects, have shown that PD patients had

lower sleep efficiency and less stage 4 sleep than the

controls. In addition, the patients with nocturnal

panic attacks, in comparison to those with daytime

panic attacks, reported more frequent daytime panic

attacks and had more somatic sensations (Sloan et al.,

1999). In the most recent studies based on sleep

EEG and on characteristics of psychopathology in

panic patients with and without sleep-related panic

attacks, only a few differences between them have

been reported (Craske et al., 2002; Landry et al.,

2002). Patients experiencing regular nocturnal panic

attacks have been suggested as representing a specific

version of panic disorder characterized by fearful

associations with sleep and sleep-like states (Craske

et al., 2002).

Nocturnal panic attacks should be distinguished

from night-time arousals induced by nightmares or

environmental stimuli and other sleep-related events

230 G. N. Papadimitriou & P. Linkowski

(Craske & Barlow, 1989; Mellman & Uhde, 1989b).

Sleep-related panic attacks are, however, often

mistaken for sleep apnoea, parasomnias, post-

traumatic stress disorder, and nocturnal epilepsy

(Craske & Barlow, 1989).

Sleep panic attacks are NREM-related events,

usually emerging from late stage 2 or early stage 3

sleep (Stein et al., 1995). They can, therefore, be

distinguished from sleep terrors, which mostly occur

during stage 4 sleep and from nightmares or PTSD

related anxiety dreams, which mostly occur during

REM sleep (Craske & Rowe, 1997; Uhde, 2000).

However, descriptions of adults experiencing night

terrors do suggest some areas of overlap with panic

disorder (Kales et al., 1980). Sleep panic attacks can

also be differentiated from sleep apnoea because

sleep apnoea occurs mostly during stages 1 and 2,

as well as during REM sleep, and is more repetitive

than nocturnal panic and from nocturnal seizures by

the fact that during nocturnal panic attacks no EEG

abnormalities were found (Craske et al., 2002).

Various hypotheses regarding the occurrence of

sleep panic attacks have been reported. Increase in

movement time among PD patients has been

proposed as a possible explanation (Roy-Byrne,

Uhde & Post, 1986; Uhde et al., 1984). Other

researchers believe that altered arousability might

explain the propensity of patients with PD to

experience sleep panic attacks (Craske & Barlow,

1989). Since excessive arousability is not a char-

acteristic feature of sleep in PD (Stein et al., 1993),

and sleep panic attacks typically arise during the

transition toward early delta sleep, that is, during

a state of diminishing arousal (Mellman & Uhde,

1989b), it is possible that it is decreased arousal

which contributes to the pathogenesis of nocturnal

panic (Uhde, 1994). On the other hand, autonomic

nervous system dysregulation during sleep is more

pronounced in nocturnal panic than in daytime panic

patients, suggesting that a more increased autonomic

arousal level might be the mechanism leading to

nocturnal panic attacks (Sloan et al., 1999).

Respiratory polysomnography, conducted on 14 PD

patients and 14 healthy controls showed that the

patients had evidence of abnormal sleep breathing as

indicated by increased irregularity in tidal volume

during REM and an increased rate of micro-apnoea

pauses in breathing (Stein et al., 1995). This may be

due to respiratory dysregulation, such as centrally

based carbon dioxide receptor hypersensitivity,

chronic hyperventilation, or sleep deprivation-

induced increases in carbon dioxide (Craske &

Rowe, 1997).

A possible connection between sleep paralysis and

sleep-related panic attacks has been also noted.

About 35% of subjects with isolated sleep paralysis

also reported a history of wake panic attacks

unrelated to the experience of paralysis and 16% with

isolated sleep paralysis met full criteria of panic

disorder (Bell, Dixie-Bell & Thompson, 1986). It is

possible that patients with sleep paralysis have an

increased rate of panic disorder, but that panic

disorder itself is not associated with an increased risk

of sleep paralysis (Uhde, 2000).

Finally, it has been argued that the occurrence of

panic attacks during sleep cannot be considered

evidence in favour of a biologic over a cognitive

model of panic disorder (Stein et al., 1993).

Recently, by evaluating the role of pre-sleep attribu-

tions regarding physiological events during sleep

in nocturnal panic attacks, Craske et al. (2002)

concluded that their findings are consistent with a

cognitive model of nocturnal panic attacks and that

attributions and beliefs may be one pathway for

nocturnal panic (Craske et al., 2002).

Generalized anxiety disorder

Among subjects complaining of insomnia and having

a primary diagnosis of mental disorder, generalized

anxiety disorder (GAD) was the most prevalent

symptomatology (J.M. Monti & D. Monti, 2000;

Monti & Papadimitriou, 2002; Ohayon, 1997). This

complaint of ‘trouble sleeping’, estimated to be

present in about 60–70% of patients with GAD,

represents one of the more core symptoms of the

disorder (Anderson, Noyes & Crowe, 1984; Monti &

Papadimitriou, 2002; Ohayon, 1997; Papadimitriou,

Kerkhofs, Kempenaers & Mendlewicz, 1988a; Uhde,

2000).

In sleep continuity, GAD patients, compared with

normal subjects, have problems initiating and main-

taining sleep (Akiskal et al., 1984) and had increased

time awake (Sitaram, Dube & Jones, 1984). They

also report poor quality of sleep characterized by

initial or middle insomnia and restless broken sleep

(Uhde, 2000). In a study on 44 outpatients with

GAD and 34 normal subjects, the patients signifi-

cantly presented increased wake time during the total

sleep period and more early morning awakening,

decreased total sleep and SE. Insomniac GAD

patients demonstrated decreased SE and TST and

increased middle and late insomnia. These results

are taken to suggest that CNS hyper-vigilance and

hyperarousal, as actual symptoms of GAD, lead to

nocturnal insomnia (Saletu-Zyhlarz et al., 1997).

In sleep architecture, higher percentages of stage 2,

as well as diminished amounts of SWS, have been

reported in GAD patients (Arriaga & Paiva, 1990;

Papadimitriou et al., 1988a; Reynolds et al., 1983).

In another study, stage 2 was minimally decreased

and stages 1, 3 and 4 were increased, while in REM-

related parameters there were no significant differ-

ences between the GAD patients and the controls

Sleep disturbance in anxiety disorders 231

(Saletu-Zyhlarz et al., 1997). On the contrary, lower

REM percentage, longer REM latency, and less

REM activity have been found in GAD patients

(Reynolds et al., 1983).

Papadimitriou et al. (1988a) for the first time

performed sleep polygraphic recordings during three

consecutive nights in three groups of individuals

(12 inpatients with pure GAD in comparison with two

age- and sex-matched groups of patients with major

depressive disorder [MDD] and normal subjects).

The GAD patients differed significantly from those

with MDD. A lower number of awakenings and stage

shifts in night 1 and the mean of the three nights and a

shorter REM duration in night 1 but longer REM

latency in the mean of the three nights were observed

in GAD in comparison to MDD patients. In sleep

continuity, GAD patients also showed a significantly

longer sleep onset latency and shorter duration of

TST and in sleep architecture less stage 2 times than

control subjects. Regarding REM sleep parameters,

no difference in REM latency between the two groups

was found. In another study from the same group of

investigators, ten drug-free inpatients suffering from

GAD with significant depression were compared with

an age- and sex-matched group of patients with pure

GAD and a group of primary MDD patients. The

GAD patients with depression did not differ from

the GAD patients in any sleep variable. Patients with

MDD showed more stage shifts and a greater number

of awakenings than the GAD patients. The REM

latency was significantly shorter in MDD patients

than in other groups, and this may help to differentiate

anxious from depressed patients (Papadimitriou et al.,

1988b). The GAD patients with or without depres-

sion show a better accommodation to the sleep

laboratory than patients with MDD (Papadimitriou

et al., 1988a, b). Similarly, clinical anxiety disorder

samples (including GAD and PTSD) showed

relatively few changes from the first to the second

nights spent in a sleep laboratory (Reynolds et al.,

1983; Rosa, Bonnet & Kramer, 1983).

Recently, the analysis of polysomnography

variables on 15 GAD patients and 15 controls, has

demonstrated that the patients took longer to fall

asleep, had a smaller percentage of SWS and more

frequent transitions into stage 1 NREM sleep (Fuller,

Waters, Binks & Anderson, 1997). Regarding REM

sleep, no significant differences between the two

groups in REM latency or percentage of REM sleep

have been found (Fuller et al., 1997).

Benca et al. (1992), in a review of 11 studies with

159 patients, concluded that a decreased TST and

sleep efficiency index, as well as an increased sleep

latency can be considered as typical for insomnia in

GAD, while findings regarding SWS, REM latency,

REM density, and percentage REM were rather

variable.

Obsessive-compulsive disorder

Polysomnographic sleep EEG recordings from

obsessive-compulsive disorder (OCD) patients

compared with those from normal subjects have

produced inconsistent results with various degrees of

sleep continuity disturbances, mainly regarding sleep

maintenance. Rapaport et al. (1981) found that TST

was significantly decreased in nine inpatient children

with OCD. In another study at the same period by

Insel et al. (1982), on 14 adult inpatients with OCD

compared to controls, the patients were also found

to have significantly decreased TST, less stage 4

sleep, decreased REM efficiency and shortened

REM latency. Both adult and adolescent patients

with OCD tended to have poor quality of sleep as

indicated, in addition to the significantly decreased

total sleep time, by more awakenings, increased

awake movement time and non-significant increases

and decreases, respectively, in sleep latency and sleep

efficiency (Insel et al., 1982; Rapaport et al., 1981).

These early results were supported by a lower sleep

efficiency and a concomitant increase in the number

of awakenings in OCD patients compared to normal

volunteers (Hohagen et al., 1994). All these three

studies, however, contained a large number of

patients with major depression (three in the study

by Rapaport et al., and seven in the studies by Insel

et al. and Hohagen et al.) and involved inpatients. In

a recent study on 13 outpatients with pure OCD

compared to 13 age- and sex-matched volunteers, no

differences between groups were found on sleep

latency, sleep time, minutes of movement and sleep

efficiency, suggesting that many OCD patients have

essentially normal sleep EEG findings (Robinson,

Walsleben, Pollack & Lerner, 1998).

Based on epidemiological findings, insomnia

related to OCD had a prevalence of 0.2%, while

the prevalence of OCD with insomnia was 1.2%,

compared with 2.5% of OCD prevalence in the

general population (Ohayon, 1996). It seems, thus,

that there is great variation in the severity of sleep

disturbance associated with OCD. Many patients

with OCD have little or no problems with sleep and

others relate significant distress with initiating and

maintaining sleep (Uhde, 2000). Delayed sleep onset

or multiple awakenings are related to the obsessions

(Uhde, 2000). Patients often complain of

disrupted sleep and sleep delay due to compulsive

behaviours.

Regarding sleep architecture and REM measures,

REM latency has been reported to be shortened in

adult patients with OCD, independent of the

coexisting presence of depressive symptomatology

(Insel et al., 1982). Similar findings were reported

among children with OCD (Rapaport et al., 1981).

Both studies also found a significant decrease in the

232 G. N. Papadimitriou & P. Linkowski

total time in stage 2, but data regarding SWS were

inconsistent (Insel et al., 1982; Rapaport et al.,

1981). Other REM characteristics, such as REM

density, number of REM periods and total REM

time, were not significantly different between

the OCD patients and the normal subjects (Insel

et al., 1982). The early reports of shortened REM

latency in OCD could not be replicated by two

independent research teams by Hohagen et al.

(1994) in 22 adult inpatients with OCD and by

Robinson et al. (1998) on 13 outpatients with OCD

compared to 13 age- and sex-matched volunteers. In

both of these studies, no evidence of any significant

differences in sleep architecture variables was found

between patients and healthy controls, suggesting

that the most probable explanation for the earlier

findings was the comorbidity with depression among

OCD patients of those studies (Hohagen et al., 1994;

Robinson et al., 1998).

Post-traumatic stress disorder

Sleep disturbances in terms of insomnia, anxious

arousals or nightmares are very prominent com-

plaints of some patients with post-traumatic stress

disorder (PTSD) (Defazio, Rustin & Diamond,

1975; Mellman & Davis, 1985; Mellman, Kulick-

Bell, Ashlock & Nolan, 1995; Pillar, Malhotra &

Lavie, 2000; Ross, Ball, Sullivan & Caroff, 1989;

Starker & Jolin, 1982; Van der Kolk et al., 1984).

DeFazio et al. (1975), for the first time, reported

the presence of anxiety dreams as well as other forms

of sleep disturbances in Vietnam combat veterans.

These findings were replicated later by Starker and

Jolin (1982). Nightmares have been found to be

frequent in 59–68% of patients with PTSD

(Mellman & Davis, 1985; Ross et al., 1989; Van

der Kolk et al., 1984). They seem to occur earlier in

the sleep cycle, may arise out of varying stages of

sleep and are not confined to REM sleep alone

(Van der Kolk et al., 1984). The anxiety arousals in

patients with PTSD are REM-related nightmares

(Ross et al., 1989), although anxious awakenings

may also occur during NREM stages of sleep

(Van der Kolk et al., 1984). Sometimes, as with

night terrors, the post-traumatic anxiety dreams

occur early in the night, and are often accompanied

by gross body movements (Van der Kolk et al.,

1984).

In a study of 21 medication-free combat veterans

with PTSD compared to eight controls, the most

prevalently reported sleep-related symptoms of

patients were the recurrent awakenings, the threa-

tening dreams, the thrashing movements during sleep

and the awakenings with startle or panic features

(Mellman, Kulick-Bell, Ashlock & Nolan, 1995).

Insomnia and non- restorative sleep were endorsed

as significant problems by 59–73% of the subjects

with PTSD versus 19–38% of the subjects without

PTSD. Middle insomnia, recurrent awakenings and

excessive body movement during sleep were asso-

ciated most specifically with having PTSD (Mellman

et al., 1995). Another study reported that very

prolonged sleep latencies and estimates of being

awake more than half of the time in bed during the

night were among the complaints of PTSD patients

(Pillar et al., 2000). The most recent studies which

actigraphically recorded sleep, however, failed to

distinguish PTSD patients from controls (Dagan,

Zinger & Lavie, 1997). In addition, PTSD, comor-

bid panic disorder and trauma-related nightmare

complaints were all associated with significant and

systematic reductions of sleep movement time

(Woodward, Leskin & Sleikh, 2002).

Inconsistent results have been reported for REM

sleep. Both shortening and prolongation of REM

latency and lower and higher time spent in REM have

been described to occur (Cartright, 1983; Kramer,

Schoen & Kinney, 1987). In a more recent study, the

percentage of sleep time in REM sleep and the mean

REM period duration were elevated in 11 Vietnam

combat veterans with current PTSD compared to

eight controls on the second night of recorded sleep.

Increased REM sleep activity persisted in the PTSD

group on the subsequent night. A dysregulation of the

REM sleep control system was thus proposed to be

involved in the pathogenesis of PTSD (Ross et al.,

1994). Regarding other sleep stages, SWS was not

found to be significantly reduced among PTSD

patients (Ross et al., 1994).

Social phobia

Subjective complaints of insomnia and idiosyncratic

sleep disturbances are common in patients with

social phobia (Uhde, 1994). On the other hand,

polysomnography is by in large normal, with total

sleep time, sleep latency and sleep efficiency being

similar among patients and normal control subjects

(Brown, Black & Uhde, 1994; Uhde, 2000).

Regarding REM measures, REM latency, REM

distribution, REM progression and REM density,

these were also found to be normal (Uhde, 2000).

General comments and conclusions

As much as one third of the adult population reports

a difficulty in sleeping (Mellinger, Balter &

Uhienhut, 1985; Ohayon, 1996) and there seem to

be a strong causal link of insomnia to both depres-

sion and anxiety (Soldatos, 1994). Patients with

complaints of insomnia show electrophysiological

and psychomotor evidence of increased daytime

Sleep disturbance in anxiety disorders 233

arousal (Regenstein et al., 1993), as well as indica-

tions of increased hypothalamic-pituitary-adrenal

(HPA) activity (Vgontzas et al., 2001), and increased

sympathetic tone (Bonnet & Arand, 1998). On the

other hand, a close relation exists between adreno-

corticotropic, autonomic, and EEG indices of

arousal during the sleep–wake cycle (Gronfrier

et al., 1999), and animal and human studies have

shown that both acute and chronic stress have

pronounced effects on sleep, mediated through the

activation of the HPA axis and the sympathetic

system (Van Reeth et al., 2000). Based on these

observations, one would expect that sleep distur-

bance would be very prominent among patients with

anxiety disorders.

The findings of the studies which have been

conducted to date and which are presented in this

review show that many patients suffering from the

majority of anxiety disorders complain about their

sleep, by reporting difficulties in initiating and

maintaining it. Subjective sleep disturbance, actually,

is a diagnostic symptom for a few anxiety disorders

such as GAD and PTSD. On the other hand,

objective polysomnographic data show that only for

patients with GAD are the subjective complaints

evident in the laboratory. For patients with panic

disorder, reduction of sleep efficiency is objectively

recorded, but longer sleep latency is not. Findings on

OCD and PTSD do not show sleep laboratory

evidence of the reported complaints. Almost all

studies, however, on which polysomnographic

findings are based, include a limited number of

individuals. Thus, it is possible that the observed

differences between patients and normal volunteers

cannot be shown due to this fact, as well as to the

substantial heterogeneity of sleep disturbance in

patients suffering from anxiety disorders.

Earlier studies had shown sleep architecture to be

impaired in various anxiety disorders, with lower

SWS and shortened REM latency. These findings,

however, are not replicated in more recent studies in

which the selection of subjects is done more

rigorously. In addition, this is possibly related to

the fact that a high number of patients with comorbid

depression were included in the older studies.

Akiskal et al. (1984) compared the sleep EEG

characteristics of primary dysthymics with those of

anxious-depressives and normal controls. The

anxious group had a high degree of insomnia

(82%) and sleep continuity difficulties, while the

depressed group had the highest REM sleep percen-

tage and the shortest REM latency. Normal REM

parameters contrasting with the well-replicated

findings of reduced REM latency and increased

REM percentage in depression are usually the case

for anxiety disorder patients (Benca et al., 1992;

Kupfer et al., 1986). Although patients with anxiety

disorders are often similar to those with affective

disorders in terms of sleep continuity measures, they

do not show decrements in SWS time, SWS

percentage, REM latency, and REM percentage,

which are usually normal (Benca et al., 1992).

It seems thus, that anxiety disorder patients do

not show any particular characteristics of sleep

architecture and that, based on this may by

differentiated from patients with mood disorders.

In addition, increasing evidence indicates that the

anxiety disorders can be distinguished from mood

disorders on the basis, also, of differential responses

to sleep deprivation. While depressed patients

experience marked, albeit transient, symptomatic

improvement after sleep deprivation (Papadimitriou,

Christodoulou, Katsougianni & Stefanis, 1993;

Wu & Bunney, 1990), patients with different types

of anxiety disorders report either a lack of improve-

ment or significant worsening after the application of

this method. It is believed that sleep deprivation and

its attendant drowsiness may play a role in exacer-

bating symptoms in some panic disorder patients

with sleep panic attacks (Craske & Barlow, 1989;

Roy-Byrne et al., 1986). Lack of improvement after

sleep deprivation has also been reported for OCD

patients (Joffee & Swinson, 1988), as well as for

patients with GAD and social phobia (Labbate et al.,

1998).

In conclusion, subjective sleep disorders are quite

frequent among patients with anxiety disorders, for

some of which objective measures of sleep initiation

and continuity are also impaired. Sleep architecture,

particularly REM parameters, and response to sleep

deprivation seem to differentiate anxiety from mood

disorders.

References

Akiskal, H. S., Lemmi, H., Dickson, H., King, D., Yelevanian, B.,

& Van Valkenburg, C. (1984). Chronic depressions. Part 2.

Sleep EEG differentiation of primary disorders from anxious

depressions. Journal of Affective Disorders, 6, 287–295.

American Psychiatric Association (1994). Diagnostic and

statistical manual of mental disorders. American Psychiatric

Association (4th Edn), Washington, DC: American Psychiatric

Association.

Anderson, D. J., Noyes, R., & Crowe, R. R. (1984). A comparison

of panic disorder and generalized anxiety disorder. American

Journal of Psychiatry, 141, 572–575.

Arriaga, F., & Paiva, T. (1990). Clinical and EEG sleep changes

in primary dysthymia and generalized anxiety: A comparison

with normal controls. Neuropsychobiology, 24, 109–114.

Arriaga, F., Paiva, T., Matos-Pires, A., Cavaglia, F., Lara, E., &

Bastos, L. (1996). The sleep of non-depressed patients with

panic disorder: A comparison with normal controls. Acta

Psychiatrica Scandinavica, 93, 191–194.

Bell, C. C., Dixie-Bell, D. D., & Thompson, B. (1986). Panic

attacks: Relationship to isolated sleep paralysis. American

Journal of Psychiatry, 143, 1484.

234 G. N. Papadimitriou & P. Linkowski

Benca, R. M., Obermeyer, W. H., Thisted, R. A., & Gillin, J. C.

(1992). Sleep and psychiatric disorders. A meta-analysis.

Archives of General Psychiatry, 49, 651–668.

Bonnet, M. H., & Arand, D. L. (1998). Heart rate variability in

insomniacs and matched normal sleepers. Psychosomatic

Medicine, 60, 610–615.

Brown, T. M., Black, B., & Uhde, T. W. (1994). The sleep

architecture of social phobia. Biological Psychiatry, 35, 420–421.

Cartright, R. D. (1983). Rapid eye movement sleep characteristics

during and after mood-disturbing events. Archives of General

Psychiatry, 40, 197–201.

Craske, M. G., & Barlow, D. H. (1989). Nocturnal panic:

Response to hyperventilation and carbon dioxide challenges.

Journal of Abnormal Psychology, 3, 302–307.

Craske, M. G., & Rowe, M. K. (1997). Nocturnal panic. Clinical

Psychology: Science and Practice, 2, 153–174.

Craske, M. G., Lang, A. J., Rowe, M., et al. (2002). Pre-sleep

attributions about arousal during sleep: Nocturnal panic.

Journal of Abnormal Psychology, 3, 53–62.

Dagan, Y., Zinger, Y., & Lavie, P. (1997). Actigraphic sleep

monitoring in post-traumatic stress disorder (PTSD) patients.

Journal of Psychosomatic Research, 42, 577–581.

Defazio, V., Rustin, S., & Diamond, A. (1975). Symptom

development in Vietnam era veterans. American Journal

of Orthopsychiatry, 45, 158–163.

Dube, S., Jones, D. A., Bell, J., Davies, A., Ross, E., & Sitaram, N.

(1986). Interface of panic and depression: Clinical and sleep

EEG correlates. Psychiatry Research, 10, 119–133.

Fuller, K. H., Waters, W. F., Binks, P. G., & Anderson, T.

(1997). Generalized anxiety and sleep architecture: A

polysomnographic investigation. Sleep, 20, 370–376.

Gronfrier, C., Simon, C., Piguard, F., Erhart, S., &

Branbenberger, G. (1999). Neuroendocrine processes under-

lying ultradian sleep regulation in man. Clinical Endocrinology

and Metabolism, 84, 2686–2690.

Hauri, P. J., Friedman, M., & Ravaris, C. L. (1989).

Electroencephalographic sleep in panic disorder. Archives

of General Psychiatry, 46, 178–184.

Hohagen, F., Lis, S., Krieger, S., et al. (1994). Sleep EEG of

patients with obsessive-compulsive disorder. European Archives

of Psychiatry and Clinical Neurosciences, 243, 273–278.

Insel, T. R., Gillin, J. C., Moore, A., et al. (1982). The sleep

of patients with obsessive-compulsive disorder. Archives of

General Psychiatry, 39, 1372–1377.

Joffee, R. T., & Swinson, R. P. (1988). Total sleep deprivation in

patients with obsessive-compulsive disorder. Acta Psychiatrica

Scandinavica, 77, 484–487.

Kales, J. D., Kales, A., Soldatos, C. R., Caldwell, A. B., Charney,

D. S., & Martin, E. D. (1980). Night terrors: Clinical

characteristics and personality patterns. Archives of General

Psychiatry, 37, 1413–1417.

Kessler, R. C., Mcgoagle, K. A., Zhao, S., et al. (1994). Lifetime

and 12-month prevalence of DSM-III-R psychiatric disorders in

the United States. Results from the National Comorbidity

Survey. Archives of General Psychiatry, 51, 8–19.

Kramer, M., Schoen, L. S., & Kinney, L. (1987). Nightmares

in Vietnam veterans. Journal of the American Academy

of Psychoanalysis, 15, 67–81.

Kupfer, D. J., Reynolds, C. F., Grochocinski, V. J., Ulrich, R. F.,

& Mceachran, A. (1986). Aspects of short REM latency in

affective states: A revisit. Psychiatry Research, 17, 49–59.

Labbate, L. A., Johnson, M. R., Lydiard, R. B., et al. (1998).

Sleep deprivation in social phobia and generalized anxiety

disorder. Biological Psychiatry, 43, 840–842.

Landry, P., Marchant, L., Mainguy, N., Marchand, A., &

Montplaisir, J. (2002). Electroencephalography during sleep of

patients with nocturnal panic disorder. Journal of Nervous and

Mental Diseases, 190, 559–562.

Lauer, C. J., Krieg, J. C., Garcia-Borreguero, D., Ozoaglar, A., &

Holsboer, P. (1992). Panic disorder and major depression: A

comparative electroencephalographic sleep study. Psychiatry

Research, 44, 41–54.

Mellinger, G. D., Balter, M. B., & Uhienhut, E. H. (1985).

Insomnia and its treatment. Prevalence and correlates. Archives

of General Psychiatry, 42, 225–232.

Mellman, T. A., & Davis, G. C. (1985). Combat-related flashbacks

in post-traumatic stress disorder: Phenomenology and similarity

to panic attacks. Journal of Clinical Psychiatry, 46, 379–382.

Mellman, T. A., & Uhde, T. W. (1989a). Electroencephalographic

sleep in panic disorder. Archives of General Psychiatry, 46,

178–184.

Mellman, T. A., & Uhde, T. W. (1989b). Sleep panic attacks:

New clinical findings and theoretical implications. American

Journal of Psychiatry, 146, 1204–1207.

Mellman, T. A., Kulick-Bell, R., Ashlock, L. E., & Nolan, B.

(1995). Sleep events among veterans with combat-related

posttraumatic stress disorder. American Journal of Psychiatry,

152, 110–115.

Monti, J. M., & Monti, D. (2000). Sleep disturbance in general-

ized anxiety disorder and its treatment. Sleep Medicine Reviews,

4, 263–276.

Monti, J. M., & Papadimitriou, G. N. (2002). Sleep disturbances

in generalized anxiety disorder. XII World Congress of

Psychiatry, Yokohama, Japan, Book of Abstracts, 1, 140.

National Institutes of Health Consensus Development Conference

(1991). Panic: Consensus statement. Bethesda, MD.

Ohayon, M. M. (1996). Epidemiological study on insomnia in

a general population. Sleep, 19(Suppl. 3), 7–15.

Ohayon, M. M. (1997). Prevalence of DSM-IV diagnostic

criteria for insomnia distinguishing insomnia related to

mental disorders from sleep disorders. Psychiatric Research, 31,

333–346.

Ohayon, M. M., & Roth, T. (2003). Place of chronic insomnia

in the course of depressive and anxiety disorders. Journal

of Psychiatry Research, 37, 9–15.

Papadimitriou, G. N., Christodoulou, G. N., Katsougianni, K., &

Stefanis, C. N. (1993). Therapy and prevention of affective

illness by total sleep deprivation. Journal of Affective Disorders,

27, 107–116.

Papadimitriou, G. N., Kerkhofs, M., Kempenaers, C., &

Mendlewicz, J. (1988a). EEG sleep studies in patients with

generalized anxiety disorder. Psychiatry Research, 26, 183–190.

Papadimitriou, G. N., Linkowski, P., Kerkhofs, M., Kempenaels,

C., & Mendlewicz, J. (1988b). Sleep EEG recordings in

generalized anxiety disorder with significant depression.

Journal of Affective Disorders, 15, 113–118.

Pecknold, J. C., & Luthe, L. (1990). Sleep studies and

neurochemical correlates in panic disorder and agoraphobia.

Progress in Neuropsychopharmacology & Biological Psychiatry, 14,

753–758.

Pillar, G., Malhotra, A., & Lavie, P. (2000). Post-traumatic stress

disorder and sleep—what a nightmare. Sleep Medicine Review,

4, 183–200.

Rapaport, J., Elkins, R., Langer, D. H., et al. (1981). Childhood

obsessive-compulsive disorder. American Journal of Psychiatry,

138, 1545–1554.

Regenstein, Q. H., Dambrosia, J., Hailett, M., Muwarski, B., &

Paine, M. (1993). Daytime alertness in patients with primary

insomnia. American Psychiatry, 150, 1529–1534.

Reynolds, C. F., Shaw, D. H., Newton, T., Coble, P. A., &

Kupfer, D. J. (1983). EEG sleep in outpatients with generalized

anxiety: A preliminary comparison with depressed outpatients.

Psychiatry Research, 8, 81–89.

Robinson, D., Walsleben, J., Pollack, S., & Lerner, G. (1998).

Nocturnal polysomnography in obsessive-compulsive disorder.

Psychiatry Research, 80, 257–263.

Sleep disturbance in anxiety disorders 235

Rosa, R. R., Bonnet, M. H., & Kramer, M. (1983). The

relationship of sleep and anxiety in anxious patients. Biological

Psychiatry, 16, 119–126.

Ross, R. J., Ball, W. A., Dinges, D. F., et al. (1994). Rapid eye

movement sleep disturbance in posttraumatic stress disorder.

Biological Psychiatry, 35, 195–202.

Ross, R. J., Ball, W. A., Sullivan, K. A., & Caroff, S. N. (1989).

Sleep disturbance as the hallmark of posttraumatic stress

disorder. American Journal of Psychiatry, 146, 697–707.

Roy-Byrne, P., Uhde, T. W., & Post, R. M. (1986). Effects of one

night’s sleep deprivation on mood and behavior in panic

disorder patients compared with depressed and normal

controls. Archives of General Psychiatry, 43, 895–899.

Saletu-Zyhlarz, G., Saletu, B., Anserer, P., et al. (1997).

Non-organic insomnia in generalized anxiety disorder.

Neuropsychobiology, 36, 117–129.

Saletu-Zyhlarz, G. M., Anderer, P., Berger, P., Gruber, G.,

Oberndorfer, S., & Saletu, B. (2000). Non-organic insomnia in

panic disorder: Comparative sleep laboratory studies with

normal controls and placebo-controlled trials with alprazolam.

Human Psychopharmacology Clinical and Experimental, 15, 241–

254.

Sheehan, D. V., Ballenger, J., & Jacobsen, G. (1980).

Treatment of endogenous anxiety with phobic, hysterical

and hypochondrial symptoms. Archives of General Psychiatry,

37, 51–59.

Sitaram, N., Dube, S., & Jones, D. (1984). Acetylcholine and

alpha-adrenergic sensitivity in the separation of depression

and anxiety. Psychopathology, 17, 24–39.

Sloan, E. P., Natarajan, M., Baker, B., et al. (1999). Nocturnal

and daytime panic attacks: Comparison of sleep architecture,

heart rate variability, and response to sodium lactate challenge.

Biological Psychiatry, 45, 1313–1320.

Soldatos, C. R. (1994). Insomnia in relation to depression and

anxiety: Epidemiologic considerations. Journal of Psychosomatic

Research, 38(Suppl. 1), 3–8.

Soldatos, C. R., & Dikeos, D. G. (2003). An integrative approach

to the management of insomnia. Current Opinion in Psychiatry,

16(Suppl. 2), 93–99.

Starker, S., & Jolin, A. (1982). Imagery and fantasy in Vietnam

veteran psychiatric inpatients. Imagination, Cognition and

Personality, 2, 15–22.

Stein, M. B., Enns, M. W., & Kryger, M. H. (1993). Sleep in non-

depressed patients with panic disorder: II. Polysomnographic

assessment of sleep architecture and sleep continuity. Journal

of Affective Disorders, 28, 1–6.

Stein, M. B., Millar, T. W., Larsen, D. K., & Kryger, M. H.

(1995). Irregular breathing during sleep in patients with panic

disorder. American Journal of Psychiatry, 152, 1168–1173.

Taylor, C. B., Shreiber, J., Agras, W. S., et al. (1986). Ambulatory

heart rate changes in patients with panic attacks. American

Journal of Psychiatry, 143, 478–482.

Uhde, T. W. (1994). The anxiety disorders: Phenomenology and

treatment of core symptoms and associated sleep disturbance.

In M. H. Kruger, T. Roth & W. C. Dement (Eds), Principles and

practice of sleep medicine (pp. 871–898). Philadelphia: W. B.

Saunders Company.

Uhde, T. W. (2000). Anxiety disorders. In M. H. Kryger, T. Roth

& W. C. Dement (Eds), Principles and practice of sleep medicine

(pp. 1123–1139). Philadelphia: W. B. Saunders Company.

Uhde, T. W., Roy-Byrne, P., & Gillin, J. C. (1984). The sleep of

patients with panic disorder: A preliminary report. Psychiatric

Research, 12, 251–259.

Van Der Kolk, B., Blitz, R., Burr, W., Sherry, S., & Hartmann, E.

(1984). Nightmares and trauma: A comparison of nightmares

after combat with lifelong nightmares in veterans. American

Journal of Psychiatry, 141, 187–190.

Van Reeth, O., Wiebel, L., Spiegel, K., Leproult, R., Dugovic, C.,

& Maccari, S. (2000). Interactions between stress and sleep:

From basic research to clinical situations. Sleep Medicine Review,

4, 201–219.

Vgontzas, A. N., Bixler, E. O., Lin, H. M., et al. (2001).

Chronic insomnia is associated with nyctohemeral activation

of the hypothalamic-pituitary-adrenal axis: Clinical implica-

tions. Journal of Clinical Endocrinology and Metabolism, 86,

3787–3794.

Woodward, S. H., Leskin, G. A., & Sleikh, J. I. (2002). Movement

during sleep: Associations with posttraumatic stress

disorder, nightmares, and comorbid panic disorder. Sleep, 25,

681–688.

Wu, J. C., & Bunney, W. E. (1990). The biological basis of an

antidepressant response to sleep deprivation and relapse:

Review and hypothesis. American Journal of Psychiatry,

147, 14–21.

236 G. N. Papadimitriou & P. Linkowski