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Management of Delirium in Palliative Care: a Review

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Curr Psychiatry Rep (2015) 17:13
DOI 10.1007/s11920-015-0550-8

COMPLEX MEDICAL-PSYCHIATRIC ISSUES (MB RIBA, SECTION EDITOR)

Management of Delirium in Palliative Care: a Review

Luigi Grassi & Augusto Caraceni & Alex J. Mitchell &
Maria Giulia Nanni & Maria Alejandra Berardi &
Rosangela Caruso & Michelle Riba

# Springer Science+Business Media New York 2015

Abstract Delirium is a complex but common disorder in pal-
liative care with a prevalence between 13 and 88 % but a
particular frequency at the end of life (terminal delirium). By
reviewing the most relevant studies (MEDLINE, EMBASE,
PsycLit, PsycInfo, Cochrane Library), a correct assessment to
make the diagnosis (e.g., DSM-5, delirium assessment tools),
the identification of the possible etiological factors, and the
application of multicomponent and integrated interventions
were reported as the correct steps to effectively manage delir-
ium in palliative care. In terms of medications, both conven-
tional (e.g., haloperidol) and atypical antipsychotics (e.g.,
olanzapine, risperidone, quetiapine, aripiprazole) were shown
to be equally effective in the treatment of delirium. No recom-
mendation was possible in palliative care regarding the use of
other drugs (e.g., α-2 receptors agonists, psychostimulants,
cholinesterase inhibitors, melatonergic drugs). Non-
pharmacological interventions (e.g., behavioral and
educational) were also shown to be important in the manage-
ment of delirium. More research is necessary to clarify how to
more thoroughly manage delirium in palliative care.
Keywords Delirium . Palliative care . Psychiatry .
Psycho-oncology . Psychopharmacotherapy
Introduction
Delirium is a complex neurocognitive syndrome, particularly
seen in hospitalized medically ill patients, which is extremely
common in patients in advanced phases of illness, and one of
the most frequent complication encountered in palliative care
[1••]. In these settings, recent data from the literature indicate a
prevalence of delirium between 13 and 88 % and an incidence

This article is part of the Topical Collection on Complex Medical-

Psychiatric Issues
L. Grassi (*) : M. G. Nanni : R. Caruso A. J. Mitchell
Institute of Psychiatry, Department of Biomedical and Specialty Department of Psycho-Oncology, Cancer Studies and Molecular
Surgical Sciences, University of Ferrara, Corso Giovecca 203, Medicine, University of Leicester, Leicester, UK
44121 Ferrara, Italy
e-mail: luigi.grassi@unife.it M. A. Berardi
Psycho-Oncology Unit, Istituto Scientifico per lo Studio e la Cura dei
L. Grassi : M. G. Nanni : R. Caruso
Tumori (IRST) S.r.l., IRCCS, Meldola, FC, Italy
University Hospital Psychiatry Unit, Program on Psycho-Oncology
M. Riba
and Psychiatry in Palliative Care, S. Anna University Hospital
Department of Psychiatry, University of Michigan, Ann Arbor, MI,
and Health Authorities, Ferrara, Italy
USA
A. Caraceni
M. Riba
Palliative Care, Pain Therapy and Rehabilitation Fondazione IRCCS
University of Michigan Comprehensive Depression Center, Ann
Istituto Nazionale dei Tumori, Milan, Italy
Arbor, MI, USA

A. Caraceni M. Riba
European Palliative Care Research Center, Norwegian University of Psycho-Oncology Program, University of Michigan Comprehensive
Science and Technology, Trondheim, Norway Cancer Center, Ann Arbor, MI, USA
13 Page 2 of 9
between 3 and 45 % [2•]. Thirty to 50 % of the cases occurring
in palliative care are reversible, while, in terminal disease, it is
typically irreversible (terminal delirium) [3, 4].
Despite its prevalence and prognostic importance, delirium
is often overlooked. In one study in an inpatient hospice, only
30 % of cases were identified clinically [5]. Use of the term
delirium is infrequent in both hospital and hospice palliative
care settings, and routine screening for delirium is rare [5].
Even clinicians working in high-risk settings admit low con-
fidence in dealing with delirium [6]. Patients with hyperactive
delirium may be recognized more often as they are more likely
to attract medical attention.
In consideration of the development of multidisciplinary
teams in palliative care and the special role that psychiatry
has with this respect [7, 8•], the primary aim of this review
is to summarize the data relative to the management of delir-
ium in palliative care. Since a thorough diagnostic assessment,
the identification of the possible etiological factors, and the
application of pharmacological and non-pharmacological in-
tervention are the hallmarks of appropriate management, the
most relevant studies and major databases (MEDLINE,
EMBASE, PsycLit, PsycInfo, Cochrane Library) were
consulted. Alcohol or substance withdrawal deliria were not
taken into consideration in the present review.
Definition and Assessment of Delirium
Delirium is an acute syndrome involving a global cerebral
dysfunction of the brain, with a complex neuropathogenesis
[9••] and multiple causes. From the clinical point of view, it is
mainly a disorder of attention (i.e., reduced ability to direct,
focus, sustain, and shift attention) and awareness (i.e., reduced
orientation to the environment), with a series of other symp-
toms as part of the syndrome, including rapid development
and fluctuation of symptoms, abnormalities of cognition (e.g.,
memory recall, calculations, writing-drawing, language), dis-
orders of perception and thought, of the sleep–wakefulness
cycle, and of motility. Motor abnormalities in delirium have
been the object of significant research [10, 11], with classifi-
cation traditionally indicating hypoactive, hyperactive, and
mixed forms. Hypoactive delirium, which has a various prev-
alence—68–86 % in certain studies, 20 % in others [5]—and
also been associated with early mortality [12], may receive
late diagnoses or be misdiagnosed with other disorders (e.g.,
depression). Studies in palliative care patients indicated that
motor profile of delirium tended to be relatively consistent
over episode courses and to relate more closely to delirium
phenomenology than to etiology [11] with comparable levels
of cognitive impairment but different in non-cognitive symp-
toms [13, 14]. The conception that hypoactive delirium has
low prevalence rates of perceptual and thought disturbances is
not confirmed by studies in palliative care settings that
Curr Psychiatry Rep (2015) 17:13
demonstrated a higher prevalence of these symptoms (40–
50 %) in hypoactive delirium than previously reported [15].
For these reasons, the assessment of delirium should be
based on a careful clinical evaluation, usually based on the
current psychiatric nosography criteria, which are the gold
standard for the diagnosis. These include the recent Diagnos-
tic and Statistical Manual of Mental disorders, 5th edition
(DSM-5) [16], which classifies delirium within the chapter
of neurocognitive disorders, and the upcoming International
Classification of Diseases in its 11th edition (ICD-11) [17,
18•]. However, in the specific setting of palliative care, the
problems and challenges for a more comprehensive classifi-
cation, diagnosis, and treatment of delirium have been repeat-
edly pointed out, particularly as far as the subsyndromal and
psychomotor manifestations of delirium [19].
For the purposes of besides clinical evaluation or screen-
ing, a number of instruments have been reviewed [20]. Many
instruments (e.g., the Delirium Rating Scale-98, the Memorial
Delirium Assessment Scale, the Confusion assessment Meth-
od, the Nursing Delirium Screening Scale) have also been
developed for assessing and screening delirium both for epi-
demiological, research, and clinical purposes [21–23], al-
though the need for an improvement of the assessment tools
in delirium by more detailed operationalization of the diag-
nostic criteria has been indicated [24]. Only a handful of in-
struments are quick and simple to administer, perhaps the best
example is the Nursing Delirium Screening Scale (Nu-DESC)
which takes about 2 min. Non-specific scales such as the Mini
Mental State Examination (MMSE) are widely used but not
recommended beyond initial screening [25].
Identification of the Etiology
Since delirium in palliative care is the direct consequence of
different factors acting often together, such as a medical con-
dition (e.g., advanced stage of cancer) and consequent meta-
bolic imbalances and organ failures or substance intoxication
or withdrawal (e.g., opioids), it is of paramount importance to
identify these causes for a correct management of the syn-
drome in palliative care (Table 1). As for other fields of med-
icine, some acrostics and acronyms may help as mnemonics in
palliative care clinical practice, in the task to rule out the
possible causes of delirium [1••]:
& I WATCH DEATH (Infections, Withdrawal, Acute meta-
bolic causes, Trauma, CNS pathology, Hypoxia, Deficien-
cies, Endocrinopathies, Acute vascular, Toxins or drugs,
Heavy metals);
& DELIRIUM (Drugs, Electrolyte disturbances, Lack of
drugs withdrawals, Infection, Reduced sensory input, In-
tracranial infection, Urinary/fecal retention, Myocardial/
pulmonary causes);
Curr Psychiatry Rep (2015) 17:13
Table 1 Etiological factors to be part of the assessment for a correct management of delirium (from [1••] adapted and modified)
• Medical disorder (e.g., cancer, neurological, cardiac disease, lung disease)
• Systemic complications of the medical disorder (e.g., anemia, infections, sepsis, electrolyte abnormalities, glycemic derangements, metabolic disorders,
encephalopathy due to hepatic, renal, or pulmonary failure)
• CNS disorders (e.g., cerebrovascular disease, infection, vasculitis, CNS tumor, and brain and meningeal metastases)
• Nutritional deficiency (e.g., thiamine, folic acid, vitamin B12 deficiency)
• Toxicity of drugs (e.g., chemotherapy, biological therapy, opioids, steroids, anticholinergic drugs, psychoactive drugs) and treatment (e.g., radiation)
& THINK (Toxic Situations such as CHF, shock, dehydra-
tion, deliriogenic medications, organ failure, e.g., liver,
kidney; Hypoxemia; Infection/sepsis (nosocomial), Im-
mobilization; Non-pharmacological interventions such as
hearing aids, glasses, reorient, sleep protocols, music,
noise control, ambulation; K+ or electrolyte problems);
& DIMES (Drugs, Infections, Metabolic, Environmental,
Structural)
Careful clinical examination and laboratory tests are
thus a mandatory part of the clinical intervention and
include complete blood cell count, electrolytes, renal
and liver function tests, analysis of urine, arterial blood
gasses, chest X-ray, EKG and appropriate cultures, as
well as a careful evaluation of the drugs administered
and the possible interactions and side effects at a cognitive
level [26].
Treatment of Delirium
The American College of Physicians-American Society
of Internal Medicine End-of-Life Care Consensus Panel
[27], the American Psychiatric Association (APA) [28],
the Canadian Coalition for Seniors’ Mental Health [29],
the European Delirium Association (EDA) [30], and the
National Institute of Clinical Excellence (NICE) [31,
32], just to cite some, have published clinical guidelines
for the treatment of delirium. These may be helpful for
palliative care health professionals, although a signifi-
cant need for the development and implementation of
more high-quality guidelines has been underlined [33••].
Etiological Interventions
The primary goal of treatment is the reversal of etiological
factors, once identified. In palliative care, opioid rotation, re-
moval of any drug that is contributing to delirium, and man-
agement of clinical situations, such as dehydration (also to
reduce the likelihood of accumulation of toxic drug or metab-
olites levels) and hypercalcemia, are the most common as-
pects of the intervention [34•] (Table 1).
Page 3 of 9 13
Pharmacological Intervention
Psychotropic drugs, such as antipsychotics and other medica-
tions, are an important pillar for the treatment of delirium.
Some systematic reviews are available in patients in an ad-
vanced stage of medical illness [35, 36•], including oncology
and palliative care [37••, 38••, 39] (Table 2).
Antipsychotics (APs)
APs are a broad class of different drugs and several sub-clas-
ses, usually classified as first-generation antipsychotics (APs),
also known as typical or conventional APs, which include
phenothiazines (e.g., chlorpromazine, fluphenazine),
tioxanthenes (e.g., tiothixene, flupentixol), butyrophenones
(e.g., haloperidol, droperidol), and dibenzoxazepines (e.g.,
loxapine); second-generation APs (e.g., olanzapine,
paliperidone, quetiapine, risperidone, ziprasidone); and third-
generation APs (e.g., aripiprazole). APs are also known as
atypical APs.
APs are commonly used in the management of delirium in
clinical settings [40], including palliative care. Several meta-
analyses show that APs are effective for the treatment of
delirium [41] and may prevent future deliria in high-risk
patients [42]. Their inhibiting action on dopamine (DA)
D2 receptors are considered the main reason for their
use, because of the hypothesis that an excess of DA and
a deficiency in acetylcholine (Ach) are involved in the
pathophysiology of the syndrome [43]. Other hypotheses
on the use of APs in delirium relate to possible neuropro-
tective effect via σ-1 receptor antagonism, reduction of
oxidative stress, as well as immunomodulation via indirect
antagonism of interleukin-1.
Among the first generation (conventional or typical) APs,
haloperidol is one of the most common drug used [44, 45],
with randomized clinical trials [46] showing its benefit in
improving delirium symptoms in palliative care settings. In a
recent Delphi survey among 135 palliative care clinicians in
nine countries, haloperidol is considered one of the four es-
sential drugs that should be made available in all settings
caring for dying patients with cancer [47•]. Chloropromazine
has shown to be effective in the treatment of delirium, al-
though its significant side effects (e.g., orthostatic
 13

Table 2 Antipsychotics for the management of delirium (adapted, modified, and expanded from [36•])
Page 4 of 9

Drug Mechanism of action Dosing per day/Route of administration Clinical characteristics and pearls Side effects and precautions

Typical APs
Haloperidol DA 0.5–10 PO, IV, IM, SC 1st choice in delirium (recommended by guidelines) Monitor QTc
RCTs available Extrapyramidal effects common
Antiemetic properties
Chlorpromazine DA 12.5–200 mg IV, IM, SC Anxiolytic and sedative effects Monitor QTc
RCTs available Sedation, hypotension
Methotrimeprazine PR 6.25–12.25 PO, IV, SC Analgesic, antiemetic, and sedating effects Anticholinergic side effects common (constipation,
dry mouth, blurred vision, tachycardia): NB in
patients in opioid treatment and poly-drug therapy
Atypical APs
Olanzapine MARTA 2.5–20 PO, IM, SC Sedating effects Monitor QTc
Appetite stimulant and antiemetic properties Anticholinergic side effects (constipation, dry mouth)
RCT available (vs risperidone)
Quetiapine MARTA 25–300 PO Sedative effects Monitor QTc
Hypotension Sedation
RCT available (vs haloperidol; vs amisulpride)
Risperidone SDA 0.25–6 mg PO Less side effects vs typical APs if in low Monitor QTc
doses (otherwise as haloperidol) Possible extrapyramidal effects
RCT available (vs olanzapine)
Ziprasidone SDA 40–160 PO, IM Sedating profile Monitor QTc and EKG
No RCT Few research in delirium
Other atypical APs
Aripiprazole DPA 5–20 PO, IM Less side effects of typical APs Monitor QTc
Data on efficacy in hypoactive delirium Agitation, possible extrapyramidal symptoms
Perospirone SDA 5–15 PO Effective in 86.8 % of cases Reported low incidence of side effects (fatigue,
Effect within several days sleepiness, akathisia, hypotension)
No RCT Few data in delirium and drug available only in Japan
Amisulpride DA (D2 and D3); GA 150 PO Effective in delirium RCT available (vs quetiapine) Few side effects

DA dopamine antagonist, SDA serotonin-dopamine antagonist, MARTA multi-acting receptor-targeted antipsychotics, DPA dopamine partial agonist, GA γ-hydroxybutyrate agonist
a. Recommendations in oncology and palliative care settings [34•]
1. Neurological symptoms (e.g., extrapyramidal symptoms, including dystonias, akathisia, and Parkinsonian symptoms; reduction of seizure threshold): monitor at baseline and daily; 2. Cardiological
symptoms: blood pressure and pulse at baseline and at least daily (closer or continuous monitoring for at risk or medically unstable patients); EKG at baseline and with every AP dose increase or daily if high
Curr Psychiatry Rep (2015) 17:13

doses of AP are used (closer attention to patients with underlying unstable cardiac disease, electrolyte disturbances, on other QTc prolonging medications for the increased risk of torsades des pointes)
Curr Psychiatry Rep (2015) 17:13
hypotension, cardiovascular effects) call for caution in its use,
particularly in patients receiving opioid therapy [22].
Methotrimeprazine has also been used in palliative care, with
a recent study carried out in infants and children experiencing
symptoms of agitation, delirium, or restlessness, showing that
different dosages of the drug (0.02–0.5 mg/kg/dose) and dif-
ferent routes (intravenous, oral/gastrostomy tube, or subcuta-
neous) appeared to be effective and safe [48].
Atypical or second-generation APs are a class of drugs with
a 5HT2A-D2 antagonism that conventional APs do not have,
although the receptor-binding profiles of the atypical APs vary
consistently between the single drugs [49]. The use of atypical
APS is becoming more common in the treatment of delirium
[50, 51] with studies indicating that at least 50 % of patients
receive atypical rather than typical APs [52] and supporting
their use in palliative care [53]. Among these drugs,
olanzapine has been shown to be useful and safe in delirium
in several palliative care studies [54, 55•], with some variables
(e.g., age >70 years, history of dementia, CNS spread of can-
cer and hypoxia as delirium etiologies, Bhypoactive^ delirium,
and Bsevere^ intensity of delirium) predicting a poor response
to olanzapine [56]. Risperidone is also used in the treatment of
delirium [57], with comparative efficacy with respect to halo-
peridol and olanzapine [58] and independent of the severity of
the underlying illness [59]. Data have also accumulated on the
use of quetiapine [60•], with recent reports indicating a com-
parable efficacy and safety as haloperidol for controlling de-
lirium symptoms [61] and an increase of its use in general
hospital settings [44]. Ziprasidone, a further atypical AP,
showed to be as effective as haloperidol in the treatment of
delirium in intensive care unit [62], also when used intrave-
nously [63], although no study is available in palliative care
settings. Data exist on perospirone, an atypical AP used for
schizophrenia [64], with no serious adverse effects in delirious
patients [65]. Perospirone has been reported to be the fourth
AP (after risperidone, quetiapine, haloperidol, and followed
by olanzapine and aripiprazole) in a large study of 2453 pa-
tients treated for delirium [44]. Aripiprazole, which has D2
and 5-HT1A partial agonist properties, has been successfully
used in delirium [66, 67], particularly in the hypoactive sub-
type [68], with a low rate of adverse side effect [69, 70].
Amisulpride, also an antipsychotic with atypical properties,
showed a comparable efficacy and tolerability with quetiapine
in one study [71] and a significant improvement of delirium
symptoms in another study of medically ill patients with de-
lirium [72].
The different action of atypical APs has been reported to be
related to a safer profile (e.g., little or no propensity to cause
EPS, reduced capacity to elevate prolactin levels, and reduc-
tion of negative symptoms of schizophrenia) and better toler-
ability than typical APS, although controversies still exist
about this issue [73]. Data regarding the use of APs in delirium
indicated no difference between haloperidol in low-dosage
Page 5 of 9 13
and atypical APs (e.g., olanzapine and risperidone) both in
terms of efficacy and frequency of adverse drug effects [74,
75], with haloperidol considered as a first-line drug in cancer
patients [32]. Data are also quite controversial about the dos-
ages of APs, however. A study exploring APs prescription
patterns for 100 patients treated for delirium with haloperidol,
olanzapine, and chlorpromazine documented that the median
haloperidol equivalent daily dose (HEDD) was 3.2 mg, indi-
cating a decrease of HEDD as compared with previous data
[76] and with HEDD influenced more by health care profes-
sional distress and preoccupation than by actual delirium
symptoms [77]. These findings underline the need for further
prospective trials to better identify optimal doses of APs, con-
sidering the complexity of clinical conditions (e.g.,
polypharmacotherapy, organ failures) among patients with ad-
vanced disease and the risk of drugs’ side effects that thus
should always be carefully monitored in palliative care set-
tings (Table 2). Drug-drug interaction via cytochrome P450
system exists and may occur with the association of other
drugs, such as dexamethasone, antibiotics, and anticonvul-
sants [78].
Other Drugs
A series of data have accumulated on the use of other drugs in
the management of delirium in the elderly or critical care, with
mixed results [79, 80•].
Dexmedetomidine, a potent α-2 receptors agonist, with
sedative, analgesic, sympatholytic, and anxiolytic effects,
has been proposed as a viable alternative in managing
treatment-refractory delirium in the critical care population
[81], but no study exists in palliative care settings.
Since impaired cholinergic function has been implicated as
one of the final common pathways in the neuropathogenesis
of delirium, reviews on the use of cholinesterase inhibitors
(e.g., donepezil and rivastigmine) showed that there is no ev-
idence supporting the use of these medications in the treat-
ment of delirium [82].
Also, the use of psychostimulants (e.g., methylphenidate)
in the treatment of delirium, namely hypoactive delirium, has
been considered, but no systematic or RCT study is available
[83]. Likewise, the possible use of modafinil in management
of delirium is yet to be assessed [84].
Because of the dysregulation of 24-h circadian cycles, in-
cluding melatonin secretion or activity, the potential therapeu-
tic use of melatonergic drugs for delirium has been tested, in
which the data indicate that melatonin and melatonin agonists
(e.g., ramelteon) are useful in the prevention and management
of delirium in older adults [85, 86•]. No study has been carried
out in palliative care, however.
A few clinical reports, but no RCTs, exist on the possible
use of other agents, such as trazodone [87] and ondasentron
[88], which are thus not recommended drugs.
13 Page 6 of 9 Curr Psychiatry Rep (2015) 17:13

Table 3 Behavioral and educational intervention as a part of the management of delirium (from [1••], adapted and modified)

Patient
• Environment: having the patient in a single room, reduction of the noises—nursing activity, beeps, alarms, ringing bells, respirators, etc.—keeping the
room quiet and well lit, to improve confusion and decrease frightening illusions; availability of objects—photographs, pictures, personal objects—that
are familiar to the patient; returning aids—eyeglasses, hearing aids—in order to ameliorate the quality of sensory input and in decreasing
misinterpretation of the surroundings)
• Orientation: reorienting the patients to time and space by repeating the date and the time, in having a room with a calendar and a big clock; reorientation
to space, context, and persons by repeating where the patient is, why he is there, and the identity of the people assisting him
• Information: regular explanation of the procedures the staffs are applying (e.g., blood exams, pharmacological treatment and route, restraints when
needed) and reassurance about what is happening; after delirium is cleared, information about the symptoms and their meaning as a reassurance
Family
• Allow company: family members and close relatives or friends should be permitted to visit the patient and stay with him/her both to reassure the patient,
to reduce his/her feelings of abandonment and strangeness determined by unknown persons, to help the staff in reorienting him/her to time and space,
and to give the staff information about fluctuation of symptoms
• Information and support: explanation to the family of the causes and characteristics of delirium and its symptoms as a reassurance to what family
members are witnessing to; explanation about procedures the staff are applying; elicit and respond to the family concerns, problems, and needs and
identify and accept the family emotional reactions
Staff
• Schedule: when possible, avoid that the patient is attended by new, unknown, and unfamiliar health care professionals, by maintaining them in their
rotation scheme
• Training: train the staff on communication skills (e.g., maintaining the communication channels open, active listening, give meaning to symptoms);
training to the use of delirium assessment tools (e.g., CAM), implementation of application of protocols for delirium management

Benzodiazepines should be used with care in delirium that Conclusions

is not due to alcohol or drug withdrawal (unless sedation is
considered necessary) because of paradoxical agitation that
can occur particularly with low-medium doses [23].
Non-pharmacological Management
Besides psychopharmacological treatment, research in pallia-
tive care has provided evidence of the importance and the
efficacy of multicomponent and integrated intervention. Mod-
ifications of key clinical factors that may precipitate delirium,
including cognitive impairment or disorientation, constipa-
tion, immobility or limited mobility, pain, poor nutrition, sen-
sory impairment, and sleep disturbance, are part of the treat-
ment [89, 90••]. Also, behavioral and educational interven-
tions are an important part of the treatment of delirium, since
high levels of distress were reported by spouses and by the
nurses caring for patients with delirium [91–93]. The presence
of delusions was shown to be the most significant predictor of
patient distress, poor Karnofsky Performance Status as the
most significant predictor of spouse/caregiver distress, and
delirium severity and the presence of perceptual disturbances
as the most significant predictors of nurse distress [80•]. Al-
though multicomponent preventive interventions seem to be
ineffective in decreasing delirium incidence and severity
among cancer patients receiving end-of-life care [94], aware-
ness of the importance of delirium in palliative care and train-
ing of the staff through interprofessional practice intervention
and interprofessional education are key elements in the man-
agement of the syndrome [95, 96•] (Table 3).
Delirium is a common and at the same time very demanding
clinical condition in palliative care, with significant impact for
the patients, their family caregivers, and the staff as well. In a
careful diagnostic assessment, an appropriate care should be
combined to meet the needs of patients with different clinical
perspectives and disease burden. In spite of significant advance-
ments in many aspects of delirium research, more effort is nec-
essary to reach an agreement between the varying definitions in
internationally recognized classification systems [97]. Also
there is an unrgent need to clarify in a more detailed way the
causation, pathophysiology, assessment, treatment, and progno-
sis of this syndrome in both the general hospital [98] and pal-
liative care [99] as well as the relationship between phenome-
nology of the clinical subtypes and course. The need for further
studies, especially double-blind, randomized, placebo-
controlled trials, is also extremely recommended, for a better
understanding of the management of delirium in all medical
settings, [100] including palliative care.
Acknowledgments The staff of the Psycho-Oncology and Psychiatry
in palliative care program at the University of Ferrara is acknowledged for
their support
Compliance With Ethics Guidelines
Conflict of Interest Luigi Grassi, Alex J Mitchell, Maria Giulia Nanni,
Maria Alejandra Berardi, Rosangela Caruso, and Michelle Riba declare
that they have no conflict of interest.
Augusto Caraceni has received board membership payments
from Gruennethal and Pfizer; grants from Molteni, Gruenenthal,
Curr Psychiatry Rep (2015) 17:13
Prostrakan, Mundipharma, and Teva; and honoraria payments
from Molteni.
Human and Animal Rights and Informed Consent This article does
not contain any studies with human or animal subjects performed by any
of the authors.
References
Papers of particular interest, published recently, have been
highlighted as:
• Of importance
•• Of major importance
1.•• Caraceni A, Grassi L. Delirium: acute confusional states in palli-
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This book is specifically devoted to examine all the aspects related
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agement and treatment in palliative care.
2.• Hosie A, Davidson PM, Agar M, Sanderson CR, Phillips J.
Delirium prevalence, incidence, and implications for screening
in specialist palliative care inpatient settings: a systematic review.
Palliat Med. 2013;27:486–98. The study examines the incidence
and prevalence of delirium in palliative settings according to the
DSM-IV and specific tools when correctly employed.
3. Breitbart W, Strout D. Delirium in the terminally ill. Clin Geriatr
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4. Moyer DD. Review article: terminal delirium in geriatric patients
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