Delirium phenomenology: What can we learn from

the symptoms of delirium?

Nitin Gupta
a,

, Jos de Jonghe
b
, Jan Schieveld
c
, Maeve Leonard
d
, David Meagher
e
a
South Staffordshire and Shropshire Healthcare NHS Foundation Trust, Burton on Trent, United Kingdom
b
Department of Geriatic Medicine, Medical Center Alkmaar, Alkmaar, The Netherlands
c
Department of Psychiatry and Neuropsychology, Division of Child and Adolescent Psychiatry, Maastricht University Medical Center, Maastricht,
The Netherlands
d
Limerick Regional Hospital, Limerick, Ireland
e
Department of Psychiatry, Midwestern Regional Hospital, Health Systems Research Centre, University of Limerick, Limerick, Ireland
Received 9 March 2008; received in revised form 11 May 2008; accepted 15 May 2008
Abstract
Objectives: This review focuses on phenomenological studies
of delirium, including subsyndromal and prodromal concepts,
and their relevance to other elements of clinical profile.
Methods: A Medline search using the keywords delirium, phe-
nomenology, and symptoms for new data articles published in
English between 1998 and 2008 was utilized. The search was
supplemented by additional material not identified by Medline
but known to the authors. Results: Understanding of prodromal
and subsyndromal concepts is still in its infancy. The
characteristic profile can differentiate delirium from other
neuropsychiatric disorders. Clinical (motoric) subtyping holds
potential but more consistent methods are needed. Studies are
almost entirely cross-sectional in design and generally lack
comprehensive symptom assessment. Multiple assessment tools
are available but are oriented towards hyperactive features and
few have demonstrated ability to distinguish delirium from
dementia. There is insufficient evidence linking specific
phenomenology with etiology, pathophysiology, management,
course, and outcome. Conclusions: Despite the major advance-
ments of the past decade in many aspects of delirium research,
further phenomenological work is crucial to targeting studies of
causation, pathophysiology, treatment, and prognosis. We
identified eight key areas for future studies.
2008 Elsevier Inc. All rights reserved.
Keywords: Delirium; Phenomenology
Introduction
Delirium is a complex neuropsychiatric syndrome of
multifactorial etiology and protean manifestations. Its
phenomenological presentation is highly variable and
differs according to etiological causation, underlying
pathophysiology, management, and course [1]. This review
focuses on how studies of the past decade have illuminated
our understanding of delirium and considers methodologi-
cal issues for phenomenological studies including instru-
mentation and study design. Key areas for further study
are highlighted.
Method
A Medline search for English language articles using
the keywords delirium, symptoms, or phenomenology
published during the 10 years since the previous review
by Meagher and Trzepacz [1] identified 1267 articles.
When only those reporting new data about either DSM-III-
R and subsequent versions or ICD-10 delirium were
considered, 195 articles remained, of which 47 were
selected for the review (see Fig. 1). Fifteen additional
Journal of Psychosomatic Research 65 (2008) 215222

Corresponding author.
E-mail address: nitingupta659@yahoo.co.in (N. Gupta).
0022-3999/08/$ see front matter 2008 Elsevier Inc. All rights reserved.
doi:10.1016/j.jpsychores.2008.05.020
articles were not identified by this search method but were
known to the authors due to their interest in the area.
The phenomenological complexity of delirium
Delirium involves a wide range of cognitive disturbances
and noncognitive neuropsychiatric symptoms across the
domains of motor behavior, sleepwake cycle, affective
expression, perception, and thinking. This broad phenom-
enological range reflects generalized disruption of brain
function and can mimic many other neuropsychiatric
disorders. Despite the variety of causes, delirium has a
consistent presentation that reflects dysfunction of a final
common neural pathway [2]. Understanding particular
symptom frequencies and patterns can provide important
clues regarding neurobiological underpinnings [3]. Delir-
ium includes essential diagnostic symptoms (e.g., inatten-
tion, disorganized thinking) as well as core features that
are consistent in presentation (e.g., sleepwake cycle
disturbances, motor activity changes), as well as other
features that are more variable (e.g., psychosis, affective
changes) and reflect the influence of particular etiologies,
comorbidities, medical treatments, or individual patient
vulnerabilities (see Table 1).
Historically, clouding of consciousness has been used to
describe cognitive impairment in delirium but is a vague
concept that reflects impairment in a number of cognitive
domains including attention, alertness, vigilance, and
comprehension. Attention is impaired in all of its aspects
such that delirious patients have difficulty in mobilizing,
shifting, and sustaining attention [25]. Inattention is a
consistent feature, crucial to diagnosis, and is highly
prevalent in patients who have subsyndromal illness or
syndromal delirium with few symptoms [26]. It correlates
highly with other elements of cognition but is disproportio-
nately affected [4]. Short- and long-term memory, orienta-
tion, comprehension, vigilance, visuospatial ability, and
executive function are also impaired. Both short- and long-
term memory are impaired but with particular disruption of
recent memory due to diminished capacity to incorporate
new experience. Disorientation to time, place, and identity of
others is common and often used to screen for disturbed
cognition in clinical settings but prone to inaccuracy due to
its fluctuating nature. Visuospatial disturbances impair
patient functionality in ward environments. Constructional
apraxia measured on the Clock Drawing Test is sensitive to
cognitive impairment in general but lacks specificity for
delirium [27].
Speech and language disturbances (abnormal semantic
content, dysnomia, paraphasias, incoherence, word-finding
difficulties) are common [28]. Disorganization of thinking
(tangentiality, loosened associations, circumstantiality) is a
key diagnostic indicator, but the frequency of different forms
of thought disorder is less well studied. Various forms of
dysgraphia (spelling errors, jagged writing, and construc-
tional dyspraxia) may assist delirium detection [29]. Sleep
wake cycle disturbances range from napping and nocturnal
disruptions to severe disintegration of the normal circadian
cycle. Motoric disturbances range from hyperactive to
hypoactive [30].
Psychotic features complicate approximately 50% of
cases [5,31] and are more common in hyperactive presenta-
tions but may occur in hypoactive patients as well [6,32].
Hallucinations are commonly visual, while delusional
content involves misidentifications, themes of imminent
danger, or bizarre happenings in the immediate environment
[7]. Affective lability is typical of delirium, but recent studies
Fig. 1. Process of article selection.
Table 1
Frequency of phenomenological manifestations in delirium [424]
Core diagnostic features
Attentional deficits (97100%)
Thought process abnormalities (5479%)
Other core symptoms
Disorientation (7696%)
Memory deficits (8896%)
Sleepwake cycle disturbances (9297%)
Motoric alterations (2494%)
Language disturbances (5767%)
Non-core symptoms
Perceptual disturbances (5063%)
Delusions (2131%)
Affective changes (4386%)
216 N. Gupta et al. / Journal of Psychosomatic Research 65 (2008) 215222
have highlighted the frequency of more sustained mood
disturbances that complicate differentiation from hypomania
in agitated cases and depression in hypoactive presentations
[31,33].
Clinical subtypes
Disturbances of motor behavior in delirium are almost
invariably present [4,26] and highly visible. Almost 30 studies
exist and suggest that motorically defined clinical subtypes of
delirium differ with regard to presence of nonmotoric
symptoms [6], etiology [8,34], pathophysiology [35,36],
detection rates [37], treatment experience [38,39], episode
duration, and outcome [9,40,41]. However, findings have
been inconsistent with better prognosis variously identified
in hypoactive patients [42], hyperactive presentations
[40,43], or patients without disturbed motor behavior [44].
Various definitions for motor subtypes exist; Lipowski
[45] described hyperactive and hypoactive psychomotoric
presentations and later added a third mixed category where
elements of both occur within short time frames [46]. Liptzin
and Levkoff [41] specified criteria based on activity and
associated psychomotoric behaviors. O'Keeffe [47] adapted
items from the Brief Psychiatric Rating Scale to describe
subtypes according to activity within the first 48 h of
delirium. Other approaches include the use of symptom
items from the Memorial Delirium Assessment Scale
(MDAS) [48], the Delirium Rating Scale (DRS) [49], and
its recent revision (DRS-R-98) [50], as well as visual analog
scales [8] and clinical impression [43].
The comparability of existing studies of motorically
defined subtypes is limited. Recent work identified only 34%
concordance between four commonly used subtyping
methods [51]. Greater focus on pure motor features and
correlation with independent measures of motor behavior
can validate subtyping methods. Electronic motion analysis
(accelerometry) concurs with observed gross movement and
distinguishes subtypes with regard to quantitative and
qualitative movement [52].
There is little information about the longitudinal course of
motor profile in delirium, and to date, studies have not
assessed subtype stability over time. Marcantonio et al. [10]
studied delirium symptom persistence over a week in elderly
patients and found that both lethargy and restlessness
remained stable in most (95%) patients. Fann et al. [11]
found great consistency in psychomotor disturbance in the
30 days after stem cell transplantation.
Subsyndromal illness
Accumulating evidence points towards a diagnostic
spectrum of delirium. Subsyndromal delirium (SSD) was
first described by Lipowski [45], and subsequently, it has
been defined by the presence of any core delirium symptoms
or severity scores on rating scales that are below diagnostic
threshold [5357]. Prevalence rates of 3050% have been
reported in intensive care unit and post-acute nursing home
facilities with SSD subjects having intermediate outcomes
(in terms of morbidity, mortality, and length of hospital stay)
between those with and without delirium [56,57].
SSD may reflect the impact of different predisposing
(e.g., dementia) and precipitating factors (e.g., trauma) upon
neuropsychiatric profile. Hypoactive patients may be over-
represented because they are too ill to present the overactive
behaviors that are scored on severity rating scales. Greater
clarity regarding the diagnosis of SSD, including the
relevance of individual symptoms, is needed.
Prodromal phase
Aprodromal phase can occur before full syndromal illness
becomes evident. This varies from hours to days or even
weeks and includes difficulty concentrating, sleep distur-
bances, vivid dreams, disorientation, tiredness, irritability,
restlessness, anxiety, depression, or noise sensitivity. Sirois
[12] reported that headaches and general uneasiness were
common prior to manifesting delirium. Duppils and Wikblad
[58] found that anxiety, frequent calls for assistance,
disorientation, psychomotor restlessness, and inattention
were prevalent in 62% of hip fracture patients for 48 h
before developing delirium. de Jonghe et al. [59] studied
delirium symptom emergence in postoperative hip-surgery
patients using the DRS-R-98; memory impairment, disor-
ientation, and formal thought disorder predicted delirium
independent of baseline risk factors. Greater awareness of the
early signs of delirium can inform our understanding of
neuropathogenesis and allowearlier detection of those at risk.
Assessment tools
Assessment tools can facilitate improved recognition and
differential diagnosis, monitor symptom severity, and assess
treatment response. Delirium diagnosis is based on a clinical
interview with the patient, discussion with relatives and
nursing staff, and medical note review. This can be
supplemented by specific symptom assessment tools.
Electroencephalography typically shows slow wave activity
in delirium patients [60] and can assist diagnosis in difficult
cases, including the differentiation of delirium comorbid
with dementia from dementia alone [61].
Delirium symptom rating scales have advantages over
clinical observations in terms of objectivity, standardization,
and the availability of normative data. Screening scales
include the Confusion Assessment Method [62], the
Delirium Symptom Interview [63], the NEECHAM Confu-
sion Scale [64], the Cognitive Test for Delirium (CTD) [65],
and the Delirium Observation Scale [66]. The DRS revised
version (DRS-R-98) [50] is the most frequently used severity
measure. Other valid and reliable severity measures include
the MDAS [48], Confusional State Evaluation [67], Delirium
217 N. Gupta et al. / Journal of Psychosomatic Research 65 (2008) 215222
Severity Scale [68], Delirium Index [69], and the Delirium-
O-Meter [13]. One criticism of these scales is the bias
towards hyperactive delirium symptomatology. Moreover,
only three tools have been validated for their ability to
distinguish delirium from dementia: the DRS [49], DRS-R-
98 [50], and CTD [65].
Differential diagnosis
The phenomenological complexity of delirium brings
with it a wide differential diagnosis that includes the
dementias, functional psychosis, and depression. The
distinction from dementia is complicated by high comorbid-
ity, with 2289% cases of dementia complicated by delirium
[70]. In general, the characteristic features of delirium
(abrupt onset, fluctuating course, disturbed consciousness,
and inattention) are absent in Alzheimer's dementia where
memory impairment is the cardinal feature. Sleepwake
cycle disruption, psychotic symptoms, and thought dis-
turbances are more suggestive of delirium [71,72], while
studies exploring the influence of comorbid dementia on
delirium presentation indicate that delirium symptoms
dominate but with greater cognitive disturbance and
disorganized thinking in comorbid cases [1416,73]. There
is a paucity of studies comparing neuropsychiatric profile in
delirium versus dementia complicated by behavioral and
psychological symptoms. Differentiation from Lewy Body
dementia (DLB) is particularly challenging because dis-
turbed attention, visual hallucinations, and symptom fluctua-
tion are common features of DLB but neuroleptic sensitivity,
autonomic dysfunction, and systematized delusions are
infrequent in delirium compared with DLB [74]. Because
delirium represents a medical emergency, acute alterations of
mental state should be assumed to be delirium until proven
otherwise [28].
Depression is a common differential for hypoactive
delirium. In major depression, symptom onset is less acute
and mood disturbances are more sustained and typically
dominate the clinical picture, with cognitive impairments
indicative of pseudodementia. Symptoms of major depres-
sion occur in delirium (e.g., psychomotor slowing, sleep
disturbances, thoughts of death), but affective lability is the
characteristic disturbance [33]. Hyperactive delirium can
mimic agitated depression or mania, but the widespread and
profound cognitive changes characteristic of delirium along
with the context of illness usually allow differentiation.
In contrast to the complex, often systematized delu-
sional beliefs characteristic of schizophrenia, delusions in
delirium tend to be simple or fragmented and first-rank
symptoms are uncommon [7]. In delirium, illusions,
depersonalization, and derealization are common and
hallucinations tend to be visual (and/or tactile) rather
than auditory. Disorganized thinking may help in distin-
guishing from psychosis [7,17,75], though well-designed
studies are lacking.
Relevance of phenomenology to other elements of
clinical profile
Delirium presentation varies across age groups. Younger
patients experience a similar range of symptoms as in adults
but with less frequent delusions and greater symptom
fluctuation, sleepwake cycle disturbance, affective lability,
and agitation [18]. Conversely, Leentjens et al. [19] found
more acute onset, more severe perceptual disturbances and
delusions, lability of mood, and agitation but with less severe
cognitive deficits, sleepwake cycle disturbance, and
symptom fluctuation in childhood delirium compared with
adults, while adult and geriatric delirium differed in
relation to more severe cognitive symptoms in geriatric
delirium. This may reflect differences in brain function
across the age span with developmental immaturity in
children, functional decline in old age, differences in
expression of distress, and differences in etiology, medical
treatments, and reaction to hospitalization.
Delirium typically involves multiple causes interacting to
produce a fluctuating clinical presentation. The classical
stereotype of agitated delirium with psychotic features is
linked to substance withdrawal but psychotic symptoms
occur with many etiologies, including those associated with
quieter presentations. Hyperactivity is more common with
substance-related delirium, and hypoactivity is more com-
mon with metabolic causes and organ failure [8,20,
35,40,43]. The temporal relationship between etiology and
phenomenology is unstudied despite its potential to
illuminate pathogenesis and improve management.
Although delirium is a unitary syndrome, particular
phenomenological profiles may reflect differing pathophy-
siological underpinnings. Localized neuroanatomical lesions
are linked with particular presentations; for example, marked
inattention is associated with disturbances in the nondomi-
nant posterior parietal and prefrontal cortices, brainstem, and
anteromedial thalamus [28]. Simple visual hallucinations
suggest dysfunction of the primary visual cortex whereas
more complex ones implicate the temporal or fusiform
regions [3]. Sleep disturbances may be related to disturbed
melatonin metabolism [76,77]. Hyperactivity has been
linked with middle temporal gyrus damage, and hypoactivity
has been linked with frontostriatal injury [78].
The phenomenological presentation of alcohol-related
delirium may be influenced by genetic factors. Visual
hallucinations during alcohol-withdrawal delirium are more
common in subjects with polymorphisms of genes coding for
the dopamine transporter [79], CCK-A receptor [80], COMT
[81], and NRHquinone oxidoreductase-2 [82]. Future work
should consider such factors in non-alcohol-related illness.
CSF homovanillic acid levels correlate with delusions and
hallucinations [83]. Future studies of delirium pathophysiol-
ogy should incorporate assessment of individual symptoms
and/or symptom clusters.
Pharmacological management varies with phenomenolo-
gical presentation, with greater use of antipsychotic agents in
218 N. Gupta et al. / Journal of Psychosomatic Research 65 (2008) 215222
agitated patients despite evidence indicating usefulness in
hypoactive patients [32,8486], and effectiveness is not
limited to patients with psychotic features [87]. The extent to
which particular symptoms indicate greater treatment
responsiveness is unclear, but the typical criterion for
response (50% improvement in DRS-R-98 scores) requires
improvement across a broad range of symptoms, and
therefore, improvements cannot be merely due to improve-
ments in sleep, psychosis, or motor activity.
Delirium duration is predicted by severity of cognitive
disturbance, mood lability, and sleepwake cycle disruption
[21,22]. Recovery at 4 weeks was predicted by greater
hyperactivity and inattention but less severe disorientation
[88]. Treloar and Macdonald [9] found the reversibility of
delirium predicted by severity of motor activity, speech and
thought disturbances, and fluctuating course. Fann et al. [11]
found that psychomotor changes, sleepwake cycle dis-
turbance, and psychotic symptoms dominated early on while
cognitive impairment peaked at 1 week and dominated
thereafter. Kiely et al. [44] studied elderly patients with
delirium in post-acute facilities and found that 1 year
mortality was predicted by severity of motor disturbance.
The prognostic relevance of individual symptoms across
different populations followed over the course of delirium
episodes requires further study.
Existing studies of delirium phenomenology
An important shortcoming of existing work is that the
majority of studies have not used instrumentation that
captures the breadth of delirium as a syndrome. However, the
development of standardized and validated tools such as the
MDAS, the DRS-R-98, and the CTD has allowed better
understanding of the importance of particular features; the
sleepwake cycle disturbance is almost invariable in
delirium, and the severity and type of disturbances
(fragmentation, cycle reversal) differ considerably from the
milder sleep disturbances common in nondelirious hospita-
lized elderly, prompting some to advocate delirium as a
disorder of circadian rhythm [89]. More detailed phenom-
enological studies can clarify suitable features for diagnosis
and detection; Bosisio et al. [90] compared delirium and
nondelirious patients with a variety of psychiatric diagnoses
and found that most DRS and MDAS items were more
common in delirium, especially general cognitive function,
sleep, and psychomotor disturbance, while perceptual
disturbances and delusions were least discriminating.
Studies are almost entirely cross-sectional in design and,
thus, cannot account for the complex and varying nature of
delirium phenomenology over time. The fluctuating nature
of delirium is a key diagnostic criterion in both ICD-10
and DSM-IV definitions [91,92]. Some existing work
indicates that individual symptoms follow separate
trajectories. A prospective study of stem cell transplanta-
tion patients found that noncognitive features dominated
in the early stages of delirium while cognitive impairment
peaked after 1 week and dominated thereafter [11]. Meagher
et al. [4] found disorientation much less consistent than other
cognitive elements over a 24-h period in a palliative care
population. Subsequent work involving biweekly assess-
ments demonstrated considerable symptom variation, with
inattention being the most consistent feature over episode
course [93]. Key outstanding issues for longitudinal
studies are whether early presentation predicts course
and whether symptoms follow a unitary or more varied
trajectory over time. Such work can identify features that
are more consistent (and therefore useful for detection
purposes) and provide clues regarding shared pathophy-
siological underpinnings.
The usefulness of factor analysis in exploring the
relationship between symptoms in complex disorders is
predicated on adequately accounting for the phenomenolo-
gical breadth of the syndrome. Studies to date (see Table 2)
have identified two to three factor solutions with typically a
composite cognitive and one or more neurobehavioral
Table 2
Factor analytic studies of delirium symptoms
Study n Population Instruments Findings
van der Mast [23] 36 Post-cardiotomy inpatients DRS Three-factor solution
Trzepacz and Dew [94] 20 General hospital inpatients DRS Two-factor solution
Trzepacz et al. [14] 18 and 43 Consecutive admissions to
geriatric unit
DRS Two-factor solution for both delirious
and deliriousdemented populations
Camus et al. [95] 154 Psychogeriatric consultations Medical Confusion Scale Five-factor solution
Lawlor et al. [96] 56 Consecutive admissions to a
palliative care unit
MDAS Two-factor solution
Grassi et al. [97] 105 Neuropsychiatric referrals of
cancer patients
DRS Three-factor solution for DRS
MDAS Two-factor solution for MDAS
Johansson et al. [98] 73 Postoperative hip fracture patients NEECHAM Three-factor solution
Saravay et al. [99] 109 Mixed delirium and dementia patients MMSE, DRS Two-factor solution
Blessed Dementia Rating Scale
Fann et al. [11] 64 Stem cell transplantation patients DRS Three-factor solution
MDAS
de Jonghe et al. [13] 92 Elderly general hospital patients Delirium-O-Meter (DOM) Two-factor solution for DOM
219 N. Gupta et al. / Journal of Psychosomatic Research 65 (2008) 215222
factors. However, no single study has included a compre-
hensive assessment of the range of cognitive, neuropsychia-
tric, and behavioral symptoms that can occur, and as such,
existing studies may have oversimplified the factor structure
of delirium phenomenology.
Future directions
Phenomenological work is crucial to targeting studies of
causation, pathophysiology, treatment needs, and prog-
nosis. A decade ago, Meagher and Trzepacz [1] outlined a
plan for phenomenological studies of delirium and
although there has been progress, there remains a need
for studies that
1. document the course of individual delirium symptoms
with longitudinal studies.
2. delineate prodromal and subsyndromal concepts.
3. identify features that can assist detection across
different populations.
4. clarify the clinical relevance and stability of motor
subtypes with longitudinal studies.
5. identify correlates between symptom profile and
etiology, pathophysiology, treatment, and course.
6. explore the relevance of comorbidity (e.g., dementias)
and medication exposure.
7. investigate the impact of genetic factors on symptom
profile in non-alcohol-related delirium.
8. explore variations in presentation across different
patient populations, treatment settings, and cultures.
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