In Review

Sleep in Psychiatric Disorders: Where Are We Now?

Elliott Kyung Lee, MD, FRCPC, D ABPN Sleep Medicine, Addiction Psychiatry, D ABSM1,2;
Alan B Douglass, MD, FRCPC, D ABSM1,3

Although the precise function of sleep is unknown, decades of research strongly

implicate that sleep has a vital role in central nervous system (CNS) restoration,
memory consolidation, and affect regulation. Slow-wave sleep (SWS) and rapid
eye movement (REM) sleep have been of significant interest to psychiatrists; SWS
because of its putative role in CNS energy recuperation and cognitive function, and
REM sleep because of its suggested involvement in memory, mood regulation,
and possible emotional adaptation. With the advent of the polysomnogram,
researchers are now beginning to understand some of the consequences of
disrupted sleep and sleep deprivation in psychiatric disorders. The same
neurochemistry that controls the sleep–wake cycle has also been implicated in the
pathophysiology of numerous psychiatric disorders. Thus it is no surprise that
several psychiatric disorders have prominent sleep symptoms. This review will
summarize normal sleep architecture, and then examine sleep abnormalities and
comorbid sleep disorders seen in schizophrenia, as well as anxiety, cognitive, and
substance abuse disorders.
Can J Psychiatry. 2010;55(7):403–412.

Clinical Implications

· REM sleep and SWS may have significant roles in memory consolidation, cognitive
function, affect regulation, and diminishing the emotional valence of memories; these
roles may have significant implications for several psychiatric disorders.
· Sleep is influenced by neurochemistry that is also implicated in the pathophysiology of
numerous psychiatric disorders, which may explain why so many psychiatric disorders
have sleep complaints as a primary symptom; an understanding of these mechanisms
may lead to rational manipulation of these relations and lead to improved clinical care
of numerous psychiatric disorders.
· Psychiatrists should maintain a high index of suspicion for several sleep disorders,
including obstructive sleep apnea, restless legs syndrome, periodic limb movement
disorder, REM behaviour disorder, and even narcolepsy, all of which may be
comorbid or possibly mimic numerous psychiatric disorders, and can even occur as a
consequence of psychiatric care; these disorders may exacerbate underlying
psychiatric symptoms if left untreated.

Limitations

· The precise function of sleep is not known; consequently, efforts to understand and
rationally manipulate sleep are limited.
· There is a paucity of psychiatrists involved in sleep medicine and sleep research; as a
result, an understanding of the role of sleep in psychiatric disorders, and the
psychiatric symptoms of sleep disorders remains limited.

Key Words: sleep, psychiatric disorders, antipsychotic, alcohol, antidepressant,

anxiety, schizophrenia, REM sleep, slow-wave sleep, opioid

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In Review

S leep is divided into 2 main types: REM sleep and NREM

sleep. NREM sleep is further subdivided; Stages 1 and 2
are light stages of sleep (now referred to as N1 and N2), while
is compromised. PTSD would be a classic example of a mal-
function of this putative emotional adaptation process, where
the emotional content of a previous traumatic event persists.
Stages 3 and 4 are deeper stages (now referred to as N3), col- REM sleep abnormalities are seen in numerous psychiatric
lectively referred to as SWS. SWS is important in CNS energy disorders, some of which will be examined below.
restoration and declarative memory (memory for facts and
[or] events),1,2 which has significant consequences for psychi- Insomnia, defined as difficulty initiating or maintaining sleep
atric disorders with cognitive dysfunction. For example, SWS resulting in daytime consequences, is common among psy-
deficits are seen in schizophrenia3 and Alzheimer disease.4 chiatric disorders. Several potential comorbid sleep disor-
REM sleep likely has a significant role in memory consolida- ders, including OSA, RLS, PLMD, and RBD may modulate
tion and affect regulation. The “mood regulatory function of psychiatric symptom expression. This review will examine
dreaming”5, p 261 hypothesis suggests that the function of the sleep abnormalities and comorbid sleep disorders in schizo-
transition from SWS to REM sleep is to mitigate the affect of phrenia, anxiety, cognitive, and substance abuse disorders.
the previous waking experience.5,6 One model advanced by
Walker7 is that sleep modulates the emotional tone of mem-
ory. In what he called the “sleep to remember” and “sleep to
forget” hypotheses, Walker7 speculates that “emotional mem- Sleep and Schizophrenia
ories” are formed in a “milieu of high adrenergic [emotional] Insomnia in schizophrenia is common, having been objec-
tone.”p 190 Using some elegant experiments, Walker’s data tively validated in 2 large meta-analyses.8,9 Severe insomnia
suggest that while sleep plays a role in enhancing declarative can be a prodromal symptom to psychotic decompensation
memory, sleep (especially REM sleep) may also play a role in and (or) relapse to psychosis following antipsychotic discon-
stripping the emotional valence of a memory over time. For tinuation.10 The sleep abnormality most consistently found in
instance, after an emotionally traumatic event, with multiple patients with schizophrenia is a short REM latency, defined
iterations of sleep, the emotional tone of the memory dimin- as the time from sleep onset to the first REM period.3,11 This
ishes, while the factual memory of the events remains intact. short REM latency is likely secondary to SWS deficits, which
In this hypothesis, several psychiatric disorders may be may passively reduce REM latency.12 SWS deficits have
impacted if this emotional adaptation function of REM sleep been seen frequently in schizophrenia,13 even in first-episode
neuroleptic-naive patients.3 SWS is believed to provide a
cortical restorative recovery from wakefulness1,14 and to
enhance declarative memory consolidation.15 Therefore,
Abbreviations used in this article SWS deficiency in schizophrenia may play a significant role
5-HT serotonin in cognitive and negative symptoms.16 Both short REM
AHI Apnea Hypopnea Index latency17 and SWS deficits18,19 are positively correlated with
CBT cognitive-behavioural therapy
negative symptoms and cognitive dysfunction. Additional
studies illustrate a relation between SWS deficits and CNS
CNS central nervous system
structural abnormalities seen in schizophrenia, including
CPAP continuous positive airway pressure increased ventricular volume.20,21 However, whether this is a
CRF corticotrophin releasing factor cause or an effect of the underlying disorder is unknown.
GAD generalized anxiety disorder
MDD major depressive disorder Shortened REM latency is also seen in narcolepsy and sev-
NREM nonrapid eye movement eral psychiatric disorders,22 limiting the use of this finding. In
severe narcolepsy, the hypnagogic and hypnopompic hallu-
OSA obstructive sleep apnea
cinations, believed to be REM intrusion phenomena of
OSA–HS obstructive sleep apnea–hypopnea syndrome
dreaming into wakefulness, can be misdiagnosed as psy-
PLMD periodic limb movement disorder chotic symptoms of schizophrenia.23,24 This has significant
PLMs periodic limb movements in sleep treatment implications, as stimulant therapy may ameliorate
PTSD posttraumatic stress disorder hypnagogic and hypnopompic hallucinations25 but would
exacerbate schizophrenia. Although challenging, narcoleptic
RBD rapid eye movement behaviour disorder
hallucinations can be distinguished from schizophrenic hal-
REM rapid eye movement
lucinations by their holistic presentation. Narcoleptic hallu-
RLS restless legs syndrome cinations are often characterized by a multimodal perceptual
SNRI serotonin and norepinephrine reuptake inhibitor experience including visual, auditory, and tactile elements,
SSRI selective serotonin reuptake inhibitor whereas in schizophrenia, hallucinations are often unimodal
and frequently auditory.26 Additionally, narcoleptic halluci-
SWS slow-wave sleep
nations are not accompanied by delusional symptoms or loss
TST total sleep time
of touch with reality.26

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Table 1 Polysomnographic effects of antipsychotic medicationsa
Antipsychotic Tmax, hours t½, hours TST
Clozapine 3 16 +++
Quetiapine 1 7 +++
Ziprasidone 5 4–10 +++
Olanzapine 5 30 +++
Risperidone 1 3–20 + +++
Thiothixene 2–4 34 +++
Haloperidol 4–6 12–36 +++
0 = no effect; + = mild effect; ++ = moderate effect; +++ = strong effect; Tmax = time to peak plasma concentration; t ½ = half-life;
WASO = wake time after sleep onset
a
Reprinted with permission from Krystal et al30
Antipsychotics and Sleep
Antipsychotics are currently the mainstay of schizophrenia
treatment.27 First-generation (typical) antipsychotics are pri-
marily dopaminergic antagonists, with antihistaminergic and
anticholinergic effects. Second-generation (atypical)
antipsychotics have the added effect of blocking serotonergic
receptors and are associated with improvement of negative
and cognitive symptoms.28 The central H1 (histaminergic
one) antihistaminergic effects of antipsychotics have signifi-
cant sedating properties, which may be beneficial for patients
with schizophrenia and insomnia. Olanzapine is the most
sedating of the atypical antipsychotics.29 However, excessive
daytime sedation can facilitate a reversal of the sleep–wake
cycle, as daytime naps may enhance nighttime wakefulness,
p a r a d o x i c a l l y e x a c e r b a t i n g in s o mn i a . 3 0 A n o th e r
antihistaminergic effect is increased appetite and weight gain,
which can increase the risk of developing OSA.31 OSA may
often go unrecognized in these patients and can contribute to
several problems including aggressive behaviours. Anecdotal
reports of severely aggressive patients with schizophrenia and
unrecognized OSA have shown that, once treated with CPAP,
aggressive tendencies diminished dramatically.32
Dopaminergic antagonism also has significant sleep effects.
Dopamine antagonism has been linked to exacerbation of
RLS and PLMs, which can fragment sleep and contribute to
daytime sleepiness. This has been demonstrated in case
reports for olanzapine,33 risperidone,34 and quetiapine.35
Serotonergic actions also play a role in sleep architecture
changes. 5-HT1A agonist effects suppress REM sleep.30 For
instance, ziprasidone has strong 5-HT1A agonism effects and
significantly suppresses REM sleep.30 Increased SWS is cor-
related significantly with 5-HT2 antagonism. Olanzapine36
and risperidone37 have high 5-HT2 antagonism and are
reported to increase SWS the most among antipsychotics.
Ziprasidone also increases SWS, but quetiapine does not
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Sleep in Psychiatric Disorders: Where Are We Now?
Decreases
REM Shortens sleep awakenings and
suppression Increases SWS onset latency (or) WASO
0 ++ + +++
++ 0 +++ +++
+++ +++ + +++
0 +++ + +++
+++ + ++
+ ++ +++ +++
+ ++ +++ +++
increase SWS in healthy patients, likely because of less
5-HT2 antagonism.30 Paliperidone has not been shown to
increase SWS.38 For a summary of these effects, see Table 1.
Interpreting these findings can be challenging because these
effects are studied in different populations, from control sub-
jects to patients with different psychiatric conditions, leading
to conflicting findings. Additionally, it is unclear that simply
reversing the SWS abnormalities results in clinical improve-
ment of schizophrenia symptoms. However, there is clinical
utility in understanding sleep architecture changes that occur
with antipsychotics. For instance, quetiapine is an appropri-
ate choice for sleep-onset insomnia, as it reaches peak blood
levels quickly, has a relatively short half-life compared with
the other atypical antipsychotics, and significantly shortens
sleep latency. Other atypical antipsychotics including
olanzapine, risperidone, or clozapine may take up to 1 week
for blood levels to peak. 30 Conversely, ziprasidone,
olanzapine, or risperidone may be more suitable for sleep
maintenance insomnia, owing to their relatively powerful
potential to increase SWS; however, daytime sedation can be
a side effect.30
Sleep in Anxiety Disorders
Patients with anxiety disorders, including GAD, PTSD, and
panic disorder, often have disturbed sleep. Insomnia is the
most common sleep complaint in these disorders. A large
cross-sectional study by Ohayon and Roth39 showed 61% of
panic disorder patients and 44% of patients with GAD had
insomnia. Insomnia can have several etiologies, including
RLS, or an underlying common neurochemical abnormality.
RLS and Anxiety Disorders
RLS is often described as a creepy-crawly or tingling sensa-
tion in the lower limbs associated with a strong desire to
move, usually worsened by rest and worse in the evenings.40
Because symptoms frequently occur in late evening, they
405
In Review
often cause initial insomnia. RLS is strongly related to PLMD,
in which the legs move periodically in the night, usually at 20-
to 40-second intervals, causing fragmented sleep and middle
insomnia. CNS dopamine deficiency is strongly implicated in
RLS and PLMD.41 RLS prevalence estimates indicate 5% to
10% of the population may be affected.42 Several recent stud-
ies highlight a strong preponderance of anxiety disorders in
RLS patients, especially panic disorder.43 The relation may lie
in a common dopaminergic abnormality.43 Antidepressant use
is also linked to RLS, including the tricyclics and SSRIs,44
venlafaxine,45 and, particularly, mirtazapine.44 Recent studies
suggest an average 5% to 10% increase in incidence of RLS
symptoms with SSRI or SNRI antidepressant use, but up to a
30% increase with mirtazapine and no increase with
reboxetine use.44 Although SSRIs and SNRIs may exacerbate
RLS, bupropion has been suggested to be neutral for RLS
symptoms and possibly even helpful for RLS because of its
dopaminergic activity.46 As untreated RLS is associated with
insomnia47 and poor quality of life,48 it behooves psychiatrists
to recognize this disorder. Many patients with anxiety disor-
ders may have unrecognized RLS. If RLS symptoms occur
more than 3 times per week, treatment with a dopamine ago-
nist such as pramipexole or ropinirole 2 hours before bed-
time49 can be beneficial.
GAD and Sleep
GAD is commonly associated with insomnia. Although GAD
has a high comorbidity with MDD, polysomnography studies
of these patients do not consistently demonstrate the reduction
in REM latency seen in MDD.50 These studies also showed
that GAD patients have less SWS and more awakenings than
control subjects.51 Daytime vigilance and attention remain
stable despite SWS deprivation and fragmented sleep, but fine
motor control and reaction time are diminished, suggesting
some deficits from sleep disturbances.52 Benca et al8 per-
formed a large review of sleep findings in patients with GAD
and concluded that while studies consistently reported an
increased sleep latency and decreased sleep efficiency in these
patients, findings in SWS, REM latency, REM density, and
REM quantity were variable.
Panic Disorder and Sleep
Several surveys show an association between insomnia and
panic disorder, with up to 68% of patients with panic disorder
identifying problems falling asleep and 77% of patients with
panic disorder endorsing difficulties maintaining adequate
sleep.50 Panic attacks evolving from sleep (sleep panic attacks
or nocturnal panic attacks) may result in insomnia because
sleep may become regarded as a fearful panicogenic state.53
Between 44% and 71% of patients with panic disorder experi-
ence sleep panic attacks,54 with 18% to 45% of panic attacks
arising from sleep.50,55 Sleep evaluations have established that
nocturnal panic attacks typically occur at the transition
between Stages 2 and 3 of sleep56 and are distinct from night
terrors and other parasomnias, as well as from panic attacks
occurring after nocturnal awakening. Recent studies show
406
patients with nocturnal panic attacks have reduced heart rate
variability and a “qualitatively different cardio-
physiology,”55, p 461 possibly suggesting that these patients
have a distinct variant of panic disorder. Evaluation should
consist of a sleep evaluation to screen for other diagnoses
such as night terrors, sleep paralysis, seizures, PLMD, and, in
particular, OSA, as apneic events can trigger nocturnal panic
attacks.54
PTSD and Sleep
Studies evaluating sleep in PTSD have shown frequent
arousals, fragmented sleep, and increased motor activity.57
Although reports on sleep architecture changes are inconsis-
tent, a large recent meta-analysis showed PTSD patients have
more Stage 1 sleep, less SWS, and higher REM density.58
The losses in SWS may be mediated by increases in
cerebrospinal fluid CRF, which is known to inhibit SWS.59
CRF dysregulation may be a core feature of PTSD; as a
result, CRF receptor antagonists are being developed as ther-
apeutic targets for treatment of PTSD symptoms.59,60
REM sleep abnormalities in PTSD have attracted significant
attention. Several studies show higher REM density and
increased REM latency61 in these patients. Multiple lines of
evidence suggest REM sleep continuity is disrupted in
chronic PTSD. 62,63 Some studies have demonstrated
increased muscle tone in REM sleep, further suggesting a
dysfunction of REM sleep mechanisms, as REM sleep nor-
mally has skeletal muscle atonia.57,64 PLMs also occur fre-
quently in PTSD.57 Dream enactment behaviour has also
been evaluated in patients with PTSD,64,65 though surpris-
ingly few studies have evaluated this comorbidity, given how
often parasomnia behaviours occur, including yelling, shout-
ing, and kicking.
Nightmares and PTSD
Nightmares occur in up to 96% of PTSD patients,66 predomi-
nantly emerging from REM sleep.63 Mellman51 has observed
that in patients exposed to trauma, those who develop PTSD
describe dream content that is “highly replicative”p 1052 of the
trauma; whereas those who do not develop PTSD describe
dreams with a significant fear component but that are not
replicative of the traumatic events. Mellman theorizes that
these replicative dreams in PTSD represent a “failure of
adaptive emotional memory that is a normal functioning of
REM sleep and dreaming.”51, p 1052 This theory is consistent
with Walker’s “sleep to forget hypothesis”7, p 190 (discussed
earlier), as PTSD is envisioned as a failure of the normal
function of REM sleep to remove the emotional content of a
memory, leading some to speculate that PTSD symptoms
may represent a form of sleep disorder,67 in contrast to the tra-
ditional view that sleep disturbances are a symptom of PTSD.
Several nonpharmacologic measures have been shown to be
beneficial for nightmares, including imagery rehearsal ther-
apy and CBT, either alone or in combination.68 Eye move-
ment desensitization and reprocessing may also help with
sleep efficiency in PTSD.69 Another nonpharmacologic
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intervention for PTSD is CPAP. Some studies have demon-
strated frequencies of OSA in PTSD patients of more than
90%,70 while another study of community patients with PTSD
showed no increase in OSA.62 Treatment of underlying OSA
in PTSD patients may significantly improve nightmares and
insomnia symptoms.71 Patients with PTSD and OSA may not
report the typical sleepiness reported by classic OSA patients,
as this may be masked by heightened anxiety; instead, they
may report fatigue or tiredness. Krakow et al72 demonstrated
that these patients report nocturia, morning headaches, and
dry mouth, which may be better indicators of comorbid OSA
in this population. For excellent reviews of sleep abnormali-
ties in PTSD, see Spoormaker and Montgomery67 and
Germain et al.73
The heightened arousal and disturbing dreams in PTSD likely
originate from an overactive noradrenergic system, with
involvement of the limbic system including the amygdala and
medial prefrontal cortex.73 Prazosin, an alpha-1 adrenergic
antagonist, has significant nightmare attenuation properties.
This agent diminishes noradrenergic activity of the locus
coeruleus, thereby decreasing nightmare frequency and inten-
sity.74,75 Studies used between 1 and 20 mg/day, with a mean
effective dosage of 2 to 13 mg/day.75 The 5-HT2A receptors
also play an important role in nightmare experiences and sleep
disturbances in PTSD. Other medications that have demon-
strated efficacy for sleep in PTSD include 5-HT2 antagonists,
many with antiadrenergic activity, including trazodone,76
mirtazapine,77 olanzapine,78 risperidone,79 quetiapine,80
aripiprazole,81 as well as the anticonvulsants topiramate82 and
gabapentin.83 The latter 2 agents may reduce kindling–
hyperreactivity of the limbic system. Other recently studied
medications with demonstrated sleep benefits in PTSD
include nabilone84 and dehydroepiandrosterone-sulphate.85
For further details regarding use of these medications, and
anecdotal reports of other medications with some demon-
strated benefits in sleep parameters for patients with PTSD,
see the review by Berger et al.86 Among the SSRIs, only
fluvoxamine87 has demonstrated improvement in sleep
parameters, although SSRIs are still first-line medications for
other PTSD symptoms.86 While benzodiazepines are fre-
quently used, there is sparse literature on their efficacy for
sleep in PTSD, with only temazepam demonstrating improve-
ments.88 Although this paucity of literature has led several
investigators to argue against benzodiazepine use in this pop-
ulation,75,86 one exception may be when a parasomnia is
observed, as clonazepam is highly effective for parasomnias
such as sleepwalking89 and RBD.89
Sleep and Cognitive Disorders
Normal Sleep Changes in the Elderly
Aging is associated with several changes in sleep architecture.
Large studies indicate that percentages of REM sleep and
SWS decrease with age.90 However, there is consensus that
the need for sleep does not change with aging, but the ability to
sleep diminishes.91 The consequences of poor-quality sleep
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Sleep in Psychiatric Disorders: Where Are We Now?
include depression,92 cognitive dysfunction,93 poorer quality
of life, and increased mortality.94 Prevalence estimates of
sleep complaints in the elderly approach 30% to 50%,95 mak-
ing sleep important to address in this population.
Insomnia in the Elderly
Insomnia is the most common sleep difficulty reported in
elderly adults, especially elderly women.96 The prevalence of
insomnia increases sharply with the number of medical and
psychiatric conditions present, the most common being
depression, chronic pain, cancer, chronic obstructive pulmo-
nary disease, and cardiovascular disease. In an extensive
review of 6800 elderly patients with insomnia, only 7% of
those with incident insomnia did not have one of these condi-
tions, leading the authors to conclude that medical conditions
associated with aging lead to insomnia, rather than aging
itself.97 Many medications also have insomnia as a side
effect.
Circadian Rhythm Disturbances in the Elderly
The sleep–wake cycle is controlled by the suprachiasmatic
nucleus, located in the anterior hypothalamus. Together with
external time cues (zeitgebers), particularly exogenous light
and endogenous melatonin, the suprachiasmatic nucleus
entrains the body’s circadian rhythms, including the
sleep–wake cycle. This system becomes less robust with age,
and more prone to phase advancing. Therefore, the elderly
may have a tendency to retire early and arise early. Conse-
quently, 2 patterns may emerge that exacerbate insomnia.98
Some elderly may stay awake longer, to more socially
accepted norms but then wake up early in the morning unable
to return to sleep because their bodily rhythm is entrained to
an early morning rising. Alternatively, the elderly can feel
more fatigued earlier in the day and take daytime naps, caus-
ing initial and middle insomnia because of less nocturnal
sleep debt.
Sleep Disorders in the Elderly
Obstructive Sleep Apnea–Hypopnea Syndrome. OSA is
characterized by repeated pharyngeal obstructions resulting
in airflow cessation (apnea) or reduction (hypopnea) during
sleep; these lead to sleep deprivation, fragmentation, and
hypoxemia. The AHI and Respiratory Disturbance Index
(commonly referred to by its acronym, RDI) are 2 measures
used to quantify OSA severity. These indices measure the
frequencies of sleep-disordered breathing events per hour of
sleep, with higher values indicating more severe distur-
bances. CPAP is usually the optimal treatment for OSA, but
surgery (uvulopalatopharyngoplasty) or an oral appliance
can be considered for milder cases, although these are used
infrequently in OSA in the elderly.
Among adults aged 30 to 60 years, the prevalence of OSA,
defined as an AHI of greater than 5, is 9% for women and
24% for men.99 The prevalence of OSA–HS, defined as an
AHI of greater than 5 and daytime hypersomnolence, is 2%
for women and 4% for men.99 For people aged 61 years and
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In Review
older, prevalence rates of OSA may rise sharply. The Sleep
Heart Health Study,100 one of the largest studies evaluating
OSA in the elderly, showed stable prevalence rates across age
groups from 60 to 98 years, with 51% to 66% having an AHI
of more than 5. Several medical conditions predispose the
elderly to developing OSA, including stroke, diabetes (with
autonomic neuropathy possibly altering ventilatory control
mechanisms), renal failure (possibly owing to excess fluid
accumulation), hypothyroidism, obesity, and heart disease.
However, other studies show an increased risk of OSA in geri-
atric patients in the absence of these conditions (reviewed by
Norman and Loredo101). Multiple mechanisms have been sug-
gested to explain this increased vulnerability to developing
OSA, including decreased pharyngeal dilator activity, and
excess pharyngeal fat deposits (reviewed by Norman and
Loredo101). Additionally, postmenopausal women not on hor-
mone replacement therapy may lose the protective effect of
estrogen on the upper airway.101 Further, patients with
dementias may have progressive deterioration of brain stem
structures involved in maintaining airway patency and conse-
quently are at higher risk of developing OSA. 102
Although snoring and daytime sleepiness are common OSA
symptoms in elderly patients, other symptoms include insom-
nia, nocturia, irritability, morning headaches, depression, and
cognitive impairment.101 Clinicians may overlook these clues,
ascribing these symptoms to aging or medical issues.103
Patients with more severe OSA perform worse on dementia
rating scales, suggesting a correlation between dementia and
OSA severity.104 Other studies highlight the strong associa-
tion between OSA and increased risk of cardiovascular dis-
ease including heart disease, and hypertension in the elderly
population.101,105
As there are significant consequences for OSA in the geriatric
population, the psychiatrist should maintain a high index of
suspicion, as OSA is common and often undiagnosed. Refer-
ral should be considered if there are symptoms suggestive of
OSA with comorbid nocturia, cardiovascular disease, hyper-
tension, or cognitive dysfunction.106 CPAP is the treatment of
choice, and has been shown to improve cognitive
functioning.104 Although CPAP compliance may be challeng-
ing, contrary to what clinicians may believe, patients with
dementia can adapt to CPAP use with proper assistance. A
study by Ayalon et al107 showed that neither age, severity of
dementia, nor severity of OSA correlated with poor CPAP
adherence; only comorbid depression predicted poorer
compliance.
RLS and PLMD in the Elderly
The prevalence of RLS and PLMD rises sharply with age,108
with women twice as likely to be affected as men. RLS exacer-
bates initial insomnia, as symptoms usually occur before sleep
onset. PLMD may exacerbate middle insomnia because noc-
turnal leg movements can fragment sleep. Both respond to
dopaminergic therapy, including ropinirole or pramipexole,
considered first-line pharmacologic recommendations.49
408
These agents may be problematic for patients with psychotic
symptoms and (or) impulse control difficulties, including
pathological gambling and hypersexuality.109 Another option
is gabapentin.49 Benzodiazepines and opioids are considered
third- and fourth-line options. 49
RBD in the Elderly
In RBD, the normal skeletal muscle atonia of REM sleep is
intermittently absent, resulting in complex motor behaviours
during REM sleep; dream content is then enacted, often
involving themes of aggression or self-defence. Almost 90%
of affected patients are male, often presenting in their 60s.110
These patients are at high risk for developing alpha
synucleinopathies, including Parkinson disease, Lewy Body
Dementia, and Multisystem Atrophy.111 Recent research sug-
gests RBD patients have a 20% risk of developing Parkinson
disease or dementia within 5 years, and a 40% risk in 10
years,112,113 suggesting RBD is an early clinical marker of
these disorders. Several case reports have identified medica-
tions that exacerbate RBD, including tricyclic antidepres-
sants, 64 monoamine oxidase inhibitors, 114 SSRIs, 115
mirtazapine, 116 and venlafaxine. 115 RBD responds to
clonazepam (0.5 to 2.0 mg at bedtime) in 80% of patients.117
However, clonazepam can increase fall risk and worsen
OSA; in these patients, melatonin may be beneficial.118
Sleep in Dementia
Sleep is frequently disturbed in patients with dementia.
Often, they are institutionalized and consequently have little
ambient light exposure. They may also have high exposure to
nocturnal noise and medications affecting sleep. 119
Suprachiasmatic nucleus neurons may degenerate more
quickly in patients with progressive dementias.120 Melatonin,
a hormone normally produced by the pineal gland to regulate
sleep cycles, has been shown to be diminished by up to 80%
in elderly patients with dementia.121 Investigators have
examined melatonin use for insomnia in dementia patients,
with benefit in some,122 but not all studies.123 A synthetic
melatonin receptor agonist, ramelteon, has been developed
and approved for treatment of insomnia in the United
States.124 For a review on other medications used for insom-
nia in the elderly population, see Bloom et al.124
Additionally, the elderly may have insomnia related to pain,
medications, depression, or a primary sleep disorder such as
OSA, RLS, PLMD, or RBD. Treatment should begin by
addressing all the aforementioned disorders. Several studies
demonstrated that increasing bright light exposure, minimiz-
ing ambient noise, and addressing sleep hygiene are effective
at improving sleep quality and consolidating the sleep–wake
cycle.125,126 CBT, which includes a combination of sleep
hygiene, relaxation techniques, stimulus control, and sleep
restriction, was more effective at maintaining improvements
in insomnia than temazepam at 2-year follow-up.127
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Substance Use and Sleep
Alcohol and Sleep
Acute alcohol use results in decreased sleep latency, modest
increases in SWS, and a reduction of REM sleep in the first 2
to 4 hours of the night.128 These properties make alcohol an
appealing hypnotic; up to 67% of insomniacs report alcohol as
an effective hypnotic.129 However, during the second half of
the night, REM sleep rebounds and is associated with intense
dreaming and nightmares, leading to sleep fragmentation and
decreased sleep efficiency.128 These disruptive effects can
even be seen 6 hours after happy hour drinking (about 5 PM);
that is, when blood alcohol levels are zero.130
However, the effects of chronic alcohol use are quite different
from acute use. Tolerance to alcohol’s sleep-enhancing
effects develops within 3 to 9 nights of daily alcohol use.130
Chronic use leads to increased sleep latency and decreased
sleep efficiency, SWS, REM sleep, and TST.128 These distur-
bances can persist months after alcohol cessation, even up to 2
years, although gradual improvement is generally noted.130,131
Sleep disturbances persisting in early recovery from alcohol
dependence are associated with higher relapse risk.132,133
Benzodiazepines for the treatment of insomnia are avoided
because of their abuse potential in abstinent alcoholics. Very
little work has been done on evaluating other related pharma-
cologic agents for insomnia in these patients, such as
zopiclone, zolpidem, or zaleplon, because of similar con-
cerns. Medications shown to improve sleep disturbances in
this population include trazodone,134 carbamazepine,135
acamprosate,136 and gabapentin.137
Alcohol use may exacerbate several sleep disorders, includ-
ing OSA, PLMD, and RLS, as well as parasomnias such as
sleepwalking and RBD. OSA and snoring are worsened by
alcohol, even after a single drink.130 PLMD and RLS preva-
lence increases 2- to 3-fold in patients having 2 or more drinks
per day. 130 The exacerbation of parasomnias, such as
sleepwalking, may also have distinct forensic implications,128
including “sexsomnia,” 138, p 272 a potentially violent
parasomnia where sexual behaviours are enacted in sleep.138
Opiates and Sleep
Most studies of opioid effects on sleep have examined heroin,
morphine, and methadone. Acute opioid administration
causes reductions in TST, REM sleep, and SWS.139 With
chronic opioid use, these changes are minimized. In opioid
withdrawal, insomnia frequently occurs, with reduced SWS
and markedly diminished REM sleep.140 Maximal REM and
SWS suppression occurs 2 to 3 days into abstinence for
chronic heroin users, and some suppression persists for 5 to 7
days into abstinence.141 With protracted abstinence, TST,
REM sleep, and SWS subsequently increase (rebound). The
time course for changes in sleep architecture have not been
studied for each opioid; however, for methadone, REM and
SWS rebound occurs 13 to 22 weeks after methadone with-
drawal.139 These sleep changes may explain some behavioural
changes seen during this withdrawal phase, including initial
The Canadian Journal of Psychiatry, Vol 55, No 7, July 2010 W
Sleep in Psychiatric Disorders: Where Are We Now?
irritability,140 which may be connected to REM and (or) SWS
deficits. REM sleep deprivation may be hyperalgesic,142
leading to speculation that opioids paradoxically reduce the
pain threshold by reducing REM sleep, possibly resulting in a
vicious cycle of excess opioid requirements.143 However,
pain itself also reduces REM and NREM sleep, and disrupts
sleep continuity, thereby making this a complex relation
requiring further study.
Several sleep complications occur with chronic opioid use,
especially methadone. Chronic opioid use is associated with
the development of central sleep apnea occurring as a conse-
quence of chronic suppression of ventilatory drive. This
dose-dependent phenomenon has been seen in 30% of
patients on stable methadone maintenance.144 An increase in
OSA has also been observed in 39% of patients receiving
chronic opioid therapy145; these phenomena may play a role
in the sleep disturbances and increased mortality seen in
these patients.146
Cannabinoids and Sleep
Studies on the main active ingredient of marijuana, delta-9
tetrahydrocannabinol, show decreases in sleep latency,147,148
making marijuana potentially appealing as a sedative. Both
increases and decreases in SWS have been seen with mari-
juana use.149 Tolerance to sleep-induction effects of mari-
juana has been demonstrated in studies of chronic marijuana
users.149 Marijuana’s sleep effects can be variable149 because
it contains numerous compounds, some with sedative effects
and others with wakefulness-promoting properties such as
cannabidiol.147,148 Marijuana also decreases REM sleep and
REM density.149 These findings have led investigators to use
nabilone, a synthetic cannabinoid, for mitigating PTSD
nightmares with some reported success.84 Cannabis with-
drawal has been associated with sleep disturbances, with dis-
turbing dreams most consistently reported.150 Withdrawal
symptoms begin 2 to 3 days after the last cannabis use and
generally last up to 2 weeks, although they can persist up to
7 weeks.149 Sleep onset latency increases, with reduced SWS
and increased REM sleep,149 consistent with the disturbing
dreams reported by patients.150
Summary
Sleep and sleep disorders are intimately tied to psychiatric ill-
ness. This is true at both the clinical–behavioural and the
neurochemical levels. Most psychiatric medications target
receptors involved in the control of sleep. Additionally, it
appears that physical sleep disorders are pathoplastic to psy-
chiatric disorders, and need to be suspected by every practis-
ing psychiatrist when evaluating the sleep complaints of their
parents. Future research may change the way psychiatric dis-
orders are viewed, with a growing understanding of the
bidirectional relation between sleep disturbances and psychi-
atric symptoms. There is an opportunity to develop new treat-
ment strategies for psychiatric disorders based on a broader
understanding of sleep physiology and pathophysiology.
409
In Review
Acknowledgements
The Canadian Psychiatric Association proudly supports the
In Review series by providing an honorarium to the authors.
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Manuscript received, revised, and accepted October 2009.
1
Assistant Professor, Faculty of Medicine, University of Ottawa,
Department of Psychiatry and Psychology, Ottawa, Ontario.
2
Sleep Specialist, Sleep Disorders Clinic, Royal Ottawa Mental Health
Centre, Ottawa, Ontario.
3
Medical Director, Sleep Disorders Clinic, University of Ottawa Institute
of Mental Health Research and Royal Ottawa Mental Health Centre,
Ottawa, Ontario.
Address for correspondence: Dr EK Lee, Sleep Disorders Clinic, Royal
Ottawa Mental Health Centre, 1145 Carling Avenue, Ottawa, ON
K1Z 7K4; elliott.lee@rohcg.on.ca

Résumé : Le sommeil dans les troubles psychiatriques : où en

sommes-nous?
Bien que la fonction précise du sommeil soit inconnue, des décennies de recherche suggèrent
fortement que le sommeil a un rôle essentiel dans la restauration du système nerveux central (SNC),
la consolidation de la mémoire, et la régulation de l’affect. Le sommeil à onde lente (SOL) et le
sommeil paradoxal (SP) présentent un intérêt significatif pour les psychiatres; le SOL en raison de
son rôle présumé dans la récupération d’énergie et la fonction cognitive du SNC, et le SP à cause de
sa participation suggérée à la mémoire, à la régulation de l’humeur, et à une possible adaptation
émotionnelle. Avec l’arrivée du polysomnograph, les chercheurs commencent maintenant à
comprendre certaines conséquences du sommeil perturbé et de la privation de sommeil dans les
troubles psychiatriques. La même neurochimie qui contrôle le cycle sommeil-éveil est également
impliquée dans la pathophysiologie de nombreux troubles psychiatriques. Il n’est donc pas étonnant
que plusieurs troubles psychiatriques aient des symptômes de sommeil dominants. Cette étude
résumera l’architecture normale du sommeil, puis examinera les anomalies du sommeil et les
troubles du sommeil comorbides observés dans la schizophrénie, ainsi que dans les troubles
anxieux, cognitifs, et liés à l’abus de substances.

412 W La Revue canadienne de psychiatrie, vol 55, no 7, juillet 2010