SPECIAL ISSUE PAPER

Debate article: Antipsychotic medications are clinically

useful for the treatment of delirium
David Meagher1,2, Meera R. Agar3,4,5,6 and Andrew Teodorczuk7,8
1
Cognitive Impairment Research Group, Graduate Entry Medical School, University of Limerick, Ireland
2
Department of Psychiatry, University Hospital Limerick, Ireland
3
Faculty of Health, University of Technology Sydney, New South Wales, Australia
4
South West Sydney Clinical School, University of New South Wales, New South Wales, Australia
5
Ingham Institute of Applied Medical Research, New South Wales, Australia
6
Discipline, Palliative and Supportive Services, Flinders University, South Australia, Australia
7
School of Medicine, Griffith University, Gold Coast, Australia
8
Health Institute for the Development of Education and Scholarship (Health IDEAS), Griffith University, Queensland, Australia
Correspondence to: A. Teodorczuk, MD, DipClin Ed, FRCPsych, E-mail: a.teodorczuk@griffith.edu.au

Prescribing of antipsychotic medications for patients with delirium remains controversial. Concerns ex-
ist that these vulnerable and frail patients may be prescribed antipsychotics inappropriately as a substi-
tute for non-pharmacological approaches when identifiable causes are not found or they challenge ward
processes. Moreover, recent evidence suggests that antipsychotics may cause more harm than good in
the palliative care patient group with delirium. On the other hand, guidelines in the United Kingdom
and the Netherlands support prescribing of antipsychotics in certain circumstances, and a large Euro-
pean survey has revealed that antipsychotics tend to be prescribed first line for hyperactive delirium.
Never before, therefore, is there a greater need to examine whether indeed these medications are clin-
ically useful for the treatment of delirium. With this in mind, evidence-based arguments for and against
prescribing antipsychotics for the treatment of delirium are presented in this debate article. The paper
concludes with a moderation piece to help guide clinical practice. Copyright # 2017 John Wiley &
Sons, Ltd.
Key words: delirium; antipsychotics; prescribing; psychopharmacology
History: Received 15 May 2017; Accepted 01 June 2017; Published online in Wiley Online Library (wileyonlinelibrary.com)
DOI: 10.1002/gps.4759

The case for antipsychotic treatment in
delirium
David Meagher.
Email: (david.meagher@ul.ie).
Introduction
Treatment with antipsychotic agents is the norm in the
everyday management of delirium across elderly med-
ical, surgical, palliative and critical care settings
(Tropea et al., 2008; Salluh et al., 2009; Briskman
et al., 2010; Hui et al., 2010). This practice is supported
by a sizeable number of prospective studies (Meagher
et al., 2013). However, delirium is highly fluctuating,
typically multifactorial and frequently remits with res-
olution of the primary insult. Placebo-controlled
studies are therefore crucial to establishing the impact
of interventions. To date, these constitute two small
studies in ICU (Devlin et al., 2010) and elderly medicine
populations (Tahir et al., 2010) both suggesting more
rapid resolution of symptoms with quetiapine use, a
negative study of haloperidol and ziprasidone in an
ICU (Girard et al., 2010), and a recent study (Agar
et al., 2017) in palliative care indicating no positive
impact with either haloperidol or risperidone and poorer
survival in the groups exposed to antipsychotics. More-
over, a recent meta-analysis of 19 studies found no
impact upon delirium severity or duration (Neufeld
et al., 2016). Consequently, there is more confusion than
ever regarding the optimal management of delirium.

Copyright # 2017 John Wiley & Sons, Ltd. Int J Geriatr Psychiatry 2017

Treatment practices in delirium
Treatment practices for delirium are highly inconsis-
tent—partly to allow tailoring of treatment to the
needs of individual patients, but also due to uncer-
tainties around effectiveness and safety. Although
delirium is primarily characterised by generalised
cognitive impairment, it also includes a variety of neu-
ropsychiatric disturbances which prompt a response
directed towards symptom control rather than core
neurocognitive disturbances. Many clinicians perceive
the therapeutic action of neuroleptics as sedative or
antipsychotic, even though response is not closely
linked to these actions (Meagher, 2010). Consequently,
antipsychotic treatment is more frequent in patients
with behavioural difficulties and hyperactivity.
Similarly, the decision to withhold treatment relates
to concerns about adverse effects and a perceived
effectiveness of non-pharmacological interventions.
Non-pharmacological measures can be effective in
the prevention of delirium, but these interventions
have limited impact upon established delirium
(Abraha et al., 2015). Their use is thus better under-
stood in terms of perceived safety compared to
pharmacological interventions. However, for some
patients, interventions such as cognitive remediation
and early mobilisation may be overwhelming and
potentially aggravate agitation and distress. Although
there is no good evidence for deleterious effects with
non-pharmacological interventions, evidence that
antipsychotics are regularly associated with unman-
ageable adverse effects is also lacking. For the latter,
this has been scrutinised but has been overlooked with
non-pharmacological approaches. Evidence-based
criticisms must be applied with equal rigor to all
interventions, with recent studies in other mental
disorders emphasising how it can be erroneous to
presume that non-drug therapies are devoid of adverse
effects (Crawford et al., 2016).
Limitations of the unitary syndrome
As a syndrome, delirium includes a variety of cognitive
and neuropsychiatric symptoms that reflect widespread
disturbance of CNS function. This unitary concept has
promoted research effort within a cohesive community
of deliriumologists (European Delirium Association and
American Delirium Society (2014)). However, this uni-
tary syndrome includes considerable heterogeneity—in
palliative care, delirium is especially prevalent,
pharmacological intervention is often directed towards
short-term symptom alleviation and is complicated by
Copyright # 2017 John Wiley & Sons, Ltd.
D. Meagher et al.
concepts such as ‘terminal cognitive failure’ that are
particular to palliative care and underline the need for
caution when extrapolating to other settings.
At the core of our efforts to manage this complex
syndrome is a growing need to fundamentally revisit
the conceptualisation of neurocognitive disturbance.
DSM-5 emphasises delirium as a unitary concept and
does little to distinguish patients in terms of etiology,
clinical subtype and background cognitive function,
even though these differences are highly relevant to
therapeutic need and prognosis. As such, there is lim-
ited information regarding which patients are most
likely to benefit from interventions as existing studies
focus almost exclusively upon efficacy in terms of the
unitary syndrome of delirium, rather than how it
relates to factors such as clinical subtype, age and
comorbid dementia.
Complex problems, complex solutions
One concern is how antipsychotic use may impact
upon application of non-pharmacological strategies.
In particular, a simple pharmacological response may
sometimes occur without a comprehensive
consideration of the range of non-pharmacological
interventions. How pharmacotherapy operates in
collaboration with non-pharmacological factors is
understudied, but complex problems rarely respond
to simple solutions and often require multifaceted
interventions. In support, a recent meta-analysis
found that interventions for delirium in ICU patients
involving six or more strategies are most likely to
reduce length of stay and mortality (Trogrlic et al.,
2015). Evidence from treatment-resistant depression
indicates that achieving best outcomes requires a
variety of interventions to capture incremental gains
in recovery—the complexity of delirium suggests that
a similar philosophy to treatment may be the most
effective.
The Australian palliative care study
Agar et al. (2017) recently conducted the most detailed
placebo-controlled study of antipsychotic treatment of
delirium to date. The sample size, flexible dosing
strategies and careful monitoring of rescue and other
medications allow for persuasive conclusions regard-
ing the efficacy of the antipsychotic agents. However,
there are caveats; the haloperidol group had more
severe baseline delirium and greater opioid use, both
of which may reflect characteristics that impact upon
response and survival. Also, the greater use of (rescue)
Int J Geriatr Psychiatry 2017
Antipsychotic prescribing in delirium
benzodiazepines in the antipsychotic-exposed group
may relate to adverse effects of antipsychotics or
factors relevant to the general morbidity of these
patients. The longer duration of delirium in the
antipsychotic-treated groups is unexpected because,
in contrast to benzodiazepines, antipsychotics are not
typically associated with deliriogenic potential.
A further consideration is the cognitive status of the
study population. While 20% were deemed to have
prior cognitive impairment, the mean IQCODE scores
(≥4) indicate that longstanding cognitive decline was
highly prevalent. In keeping with prior work in pallia-
tive care (Breitbart et al., 2002b), this can influence the
impact of antipsychotics. Also, the use of items (inap-
propriate behavior, inappropriate communication and
illusions/hallucinations) from the Nursing Delirium
Screening Scale (NuDESC) allowed examination of
the impact upon important target symptoms of
delirium rather than just delirium syndromal status,
but the exclusion of psychomotor retardation is
surprising because a key strength of the NuDESC
derives from its emphasis of this common feature of
delirium. Of note, recent Dutch delirium guidelines
emphasise hypoactive presentations as an important
treatment target, advocating reserved use of antipsy-
chotics (Leentjens et al., 2014).
A particularly concerning finding is the elevated
mortality in the antipsychotic-exposed groups, which
reached statistical significance for the haloperidol
group. This is unexpected in terms of previous work,
including a detailed study of antipsychotic use and
mortality in delirious elderly general hospital
inpatients (Elie et al., 2009). Antipsychotics can cause
a variety of adverse effects, including altered cardiac
conduction, extrapyramidal effects (EPS) and cerebro-
vascular incidents in those with dementia. It is unclear
how these mechanisms might relate to the elevated
mortality in the Australian study where exposure was
short term, using modest dosing, and no serious EPS
were noted. Moreover, although non-placebo-
controlled studies have limited capacity for examining
efficacy, they provide important information about
adverse effects and suggest that cardiac, cerebrovascular
and EPS are uncommon with antipsychotic treatment
of delirium (Meagher et al., 2013).
In a retrospective analysis of haloperidol and
quetiapine used in a CCU for delirium treatment,
Naksuk et al. (2015) found no evidence for changes
to mean QTc interval duration. Moreover, the elevated
mortality in delirium was unrelated to antipsychotic
use. Cardiac effects are rare where cumulative daily
doses of intravenous haloperidol are lower than
2 mg, unless patients have additional risk factors for
Copyright # 2017 John Wiley & Sons, Ltd.
QTc prolongation (Meyer-Massetti et al., 2010). Stud-
ies indicate significant benefit where care of delirious
patients is protocolised to include dose titration with
regular monitoring of arousal, cardiac status and for
EPS (Skrobik et al., 2010; Dale et al., 2014; Sullinger
et al., 2016). However, implementation is challenging
—a survey of ICU specialists found that QTc monitor-
ing was highly variable, not routinely measured in 20%
of ICUs and haloperidol continued in 60% cases where
QTc interval exceeded 500 ms (Devlin et al., 2011).
Similarly, a review of prospective studies of delir-
ium treatment with antipsychotics concluded that
the frequency of EPS is low, rising to 8% in studies
that included a validated instrument (Meagher et al.,
2013). Extrapyramidal effects include involuntary
movements, parkinsonism and akathisia, with the
latter difficult to reliably distinguish from the agitation
of hyperactive delirium. Espi Forcen et al. (2015)
reviewed ten studies of antipsychotic treatment in
delirium and found that akathisia occurred in less than
10% with the exception of one study (Girard et al.,
2010) where an unusually elevated rate of EPS in
patients receiving haloperidol and ziprasidone was
matched in the placebo group, suggesting limited
relationship to antipsychotic exposure. Other effects
are poorly studied with no systematic reports of the fre-
quency of cerebrovascular incidents or metabolic effects.
Conclusions
The interpretation of evidence around use of antipsy-
chotics for delirium treatment in everyday practice is
more challenging than ever. While prospective studies,
including some placebo-controlled work, indicate that
many delirious patients recover in the context of anti-
psychotic treatment, recent work in palliative care and
ICU suggests that the actual response may not be
greater than placebo. Moreover, the largest study iden-
tified reduced survival in antipsychotic-exposed pallia-
tive care patients. Although the mechanisms for this
finding are unclear, the study highlights how antipsy-
chotic use requires careful consideration of therapeu-
tic targets supported by systematic monitoring for
adverse effects. In real world practice, antipsychotic
treatment frequently continues for extended periods
including beyond hospital discharge (Tomichek
et al., 2016) emphasising the need to clarify treatment
duration, including the merits of ongoing use. The
NICE guidelines (2010) support targeted use of
antipsychotics for delirium where behavioural distur-
bance, psychosis and distress warrant intervention.
These recommendations remain pertinent to
Int J Geriatr Psychiatry 2017

everyday practice where the safety, distress and dignity
of patients frequently present a compelling argument
for intervention and non-pharmacological techniques
are not always effective. Even where antipsychotics
do not impact delirium incidence or duration, they
do reduce agitation (Page et al., 2013). However, the
merits of antipsychotic use in less urgent circum-
stances or prophylaxis are unclear and relate to factors
such as comorbid dementia status and adverse effect
risk. In the absence of evidence to support routine
use, we must avoid therapeutic nihilism and shift
attentions to identifying those patients most likely to
benefit from antipsychotics while developing treat-
ment protocols to guide dose titration and optimise
identification of adverse effects.
Antipsychotics for the treatment of delirium—
the argument against use
Meera Agar.
Email: meera.agar@uts.edu.au
Delirium is an acute medical condition
characterised by changes in attention, awareness and
cognition, in the setting of one or more causes: general
medical condition(s), an intoxicating substance or
medication (American Psychiatric Association, 2013).
Delirium pathophysiology is complex, and although
understanding is increasing, it remains poorly under-
stood. There are many putative neuro-transmitter,
metabolic and inflammatory pathways where empiri-
cal data exist, which may all contribute to delirium
(MacLullich et al., 2008; Maldonado, 2013). There is
increasing interest in the role aberrant stress responses
and neuro-inflammation in delirium pathophysiology
(MacLullich et al., 2008; Cunningham and Maclullich,
2013). To date, no unifying pathophysiological process
has been identified (Maldonado, 2013). It is possible
different mechanisms may come into play for different
individuals, dependent on predisposing conditions
and precipitants. There are several commonly de-
scribed neurotransmitter abnormalities in delirium
with increased dopamine only one of them, with
others including reduced acetylcholine, norepineph-
rine, glutamate, and both increased/decreased hista-
mine, gamma-aminobutyric acid (GABA) and
serotonin (Van Der Mast, 1998; Maldonado, 2013).
The role for antipsychotics in delirium was extrap-
olated from their benefits in psychiatric disorders with
psychotic symptoms, and based on some pharmaco-
logical and neuro-anatomical evidence of dopamine
excess and cholinergic deficiency contributing to delir-
ium. For example, dopamine agonists (such as D-
Copyright # 2017 John Wiley & Sons, Ltd.
D. Meagher et al.
amphetamine) and hypoxia leading to dopamine
surges that decrease acetylcholine release causing de-
lirium (Hshieh et al., 2008). However, dysfunction in
dopamine receptors can impart a range of responses
in acetylcholine receptors (Hshieh et al., 2008). Dopa-
mine blockage using antipsychotics aims to counter
the proposed dopamine excess in delirium (Inouye
et al., 2014). It is important to consider that dopamine
blockage is only one component of antipsychotics ac-
tion, and side effects due to anticholinergic activity
and α-receptor blockade include cognitive impair-
ment, functional decline, sedation, hypotension, dizzi-
ness, falls and extrapyramidal side effects (Inouye
et al., 2014). Anti-psychotics also have been associated
with increased mortality, in particular in people with
dementia (Schneider et al., 2005).
There are multiple goals that pharmacological treat-
ment of delirium should aim to achieve. Immediate
outcomes relate to ensuring the safety of the patient
and others, and reducing symptomatic and psycholog-
ical/emotional distress. Early in treatment, we also
need to be able to deliver the medical care needed
for the delirium precipitant, which may need patient
cooperation with intravenous therapies and investiga-
tions. In the medium term, the aim is to reduce the se-
verity and duration of delirium, which will hopefully
lead to complete resolution. Longer-term outcomes
are to minimise functional and cognitive sequelae,
and psychological impacts from recall of the experi-
ence for both the patient and caregiver. Impacts on
both immediate and subsequent mortality (Witlox
et al., 2011) are also important.
National Institute for Health and Clinical Excel-
lence (NICE) delirium clinical guidelines (2010) rec-
ommendation is that antipsychotics are reserved for
severe distress or behavioral disturbance, and only
when other strategies have been ineffective or are in-
appropriate, also considering if there are risks to the
patient safety. There are no registered medications
for the treatment of delirium with the U.S Food and
Drug Administration (FDA), European Medicines
Agency (EMA) or similar international bodies. There
are also significant variations in practice, even among
specialists in the field, with lack of clinical consensus on
whether antipsychotics change outcomes, choice of anti-
psychotics and wide variation in dose and duration of
treatment (Carnes et al., 2003; Agar et al., 2008; Morandi
et al., 2013). Often starting doses are not low, and evi-
dence of regular review is lacking (Tropea et al., 2009).
There is a wealth of qualitative data which gives in-
sight into the distress experienced by patients during a
delirium episode, with fear, anxiety and feeling threat-
ened common emotions, with perceptual disturbance
Int J Geriatr Psychiatry 2017
Antipsychotic prescribing in delirium
a common cause (Breitbart et al., 2002a; O’Malley
et al., 2008). Patients also report that it felt like a
dream-like state, in a situation they could not control,
and distress when they could not communicate with
their loved ones (O’Malley et al., 2008). There is a
range of symptoms that are reported as distressing by
caregivers, which include hyperactive delirium presen-
tations, perceptual disturbance, functional decline and
somnolence (Breitbart et al., 2002, Namba et al., 2007,
O’Malley et al., 2008). One study of 99 cancer patients
with delirium found 74% remembered being deliri-
ous, and 81% reported the experience distressing
(Bruera et al., 2009). This seems to be despite patients
receiving antipsychotic treatment, as haloperidol 2 mg
every 6 h, (and as needed) was used for psychomotor
agitation, delusions or hallucinations up to 30 mg/
day (Bruera et al., 2009). It is also difficult to suggest
a biologically plausible mechanism for antipsychotics
improving all elements of the negative patient experi-
ence, unless they significantly reduce the time with
delirium.
There have been several randomised controlled tri-
als (RCTs) of antipsychotics for managing established
delirium; in AIDS (Breitbart, 1996), medical patients
(Tahir et al., 2010a, Hu et al., 2004, Maneeton et al.,
2013), cancer (Kim et al., 2010) and intensive care
(Devlin et al., 2010b). Three were placebo controlled,
reflecting the natural history of delirium (Tahir et al.,
2010b). All these trials have various methodological is-
sues including flawed allocation concealment (Hu
et al., 2004), treatment-limiting adverse effects leading
to early termination of one study arm (lorazepam)
(Breitbart, 1996) and no a priori power calculation
(Breitbart, 1996; Han and Kim, 2004; Kim et al.,
2010), with three studies ceased prematurely
(Maneeton et al., 2013, Tahir et al., 2010a, Devlin
et al., 2010a). Outcomes in all but one of these trials
were by assessment of changes in total delirium sever-
ity score over time, and overall these studies suggested
potential for antipsychotics to improve delirium sever-
ity. One trial demonstrated shorter time to first delir-
ium resolution (Devlin et al., 2010). There are several
issues with these trials. First, without adequately
powered comparisons to placebo, it is not possible to
evaluate if antipsychotics provided additional benefits
to the resolution of delirium that can be achieved by
providing medical treatment of the underlying precip-
itants. Using delirium severity measures means a range
of symptoms are included in the primary outcome.
For example, the Memorial Delirium Assessment Scale
(Breitbart et al., 1997) captures changes in awareness
and attention, disorientation, short-term memory
impairment, disorganised thinking, sleep–wake and
Copyright # 2017 John Wiley & Sons, Ltd.
perceptual disturbances and psychomotor changes.
This does not assist in evaluating the symptomatic
outcomes of treatment (if the treatment is aiming to
reduce specific target symptoms), no minimally
important or clinical important difference has been
defined to inform power calculations, nor does this
clearly evaluate impacts of antipsychotics on important
universal abnormalities (such as inattention). There
may also be other confounding factors which influence
changes in score over time, for example if a person has
increased sedation then determining presence of
perceptual symptoms may be more difficult, artificially
reducing delirium severity scores. There also has been
limited assessment of adverse effects, for example
validated systematic measures of sedation or extrapyra-
midal toxicity has been rarely included. Comparisons
of antipsychotics with placebo have not been evalua-
tion for complications such as falls, and longer-term
outcomes, such as mortality, cognition and function.
By contrast, two adequately powered placebo-
controlled studies of intravenous haloperidol in criti-
cally ill adults (Page et al., 2013), and oral haloperidol
or ziprasidone in ventilated intensive care patients with
either altered consciousness or in receipt of sedative or
analgesic medications (Girard et al., 2010), found no
difference in delirium-free nor coma-free days; how-
ever, study inclusion did not require the presence of
delirium and does not provide insight into the impact
of treatment on symptomatic treatment.
A recent meta-analysis of antipsychotic medication
for the treatment of delirium has been conducted,
included data from 12 studies in mixed samples of
surgical and nonsurgical hospitalised adults, with five
studies focusing on ICU populations (Neufeld et al.,
2016). This meta-analysis also did not find supportive
evidence for antipsychotics improving outcomes, with
no reduction in delirium duration (in the seven
studies reporting this outcome) or severity (in eight
studies) demonstrated (Neufeld et al., 2016). There
was considerable heterogeneity among studies, and
data from both prevention and treatment studies were
combined (Neufeld et al., 2016).
An adequately powered randomised controlled trial
(n = 247) by our team in the palliative care setting also
did not demonstrate a benefit of antipsychotics, with
dose-titrated oral haloperidol and risperidone groups
having higher delirium symptoms after 72 h of treat-
ment than the placebo group (Agar et al., 2017).
Are there alternative treatment options? Delirium
remains under-detected and under-diagnosed, and
investment is needed to have improved systems in
place to ensure all people with delirium receive a
timely diagnosis and treatment of precipitating
Int J Geriatr Psychiatry 2017

medical causes (Kakuma et al., 2003; O’Hanlon et al.,
2014). Non-pharmacological interventions and com-
prehensive geriatric assessment may also play a role.
A targeted nurse-led, multi-component intervention
of systematic screening and target risk factor manage-
ment (dehydration/nutrition, pain and medication
management) with nurse training and support from
geriatric nurse specialists, reduced delirium duration
in the intervention group using a before/after design
(n = 120) (Milisen et al., 2001). A RCT showed that
a multi-component geriatric intervention that in-
cluded recognition of delirium and underlying precip-
itants targeted risk factor management (orientation,
dehydration/nutrition, early mobilisation, medication
management) (Pitkala et al., 2006) and comprehensive
geriatric assessment alleviated delirium symptoms ear-
lier and increased the number with improved delirium
at eight days (n = 174). These studies did not restrict
antipsychotics and also undertook medication review
(adjustment of other medications which may have
been implicated in delirium) making it difficult to
assess the benefit of non-pharmacological therapies
on their own (Pitkala et al., 2006). Incident delirium
also seems to be less severe and shorter in duration
when multicomponent interventions were in place
aiming to prevent delirium prior to the delirium
occurring (Inouye and Charpentier, 1996; Inouye
et al., 1999; O’Hanlon et al., 2014). This evidence
suggests that non-pharmacological strategies poten-
tially offer benefit in delirium treatment, but further
studies are needed to determine which elements of
multi-component strategies make the most differ-
ence, and how they are best delivered.
Present evidence does not support a role for the
treatment of delirium with antipsychotics, if delirium
severity, specific delirium symptoms or delirium-free
days are the outcomes. Given the broad range of treat-
ment goals for antipsychotics in this setting, establish-
ing net clinical benefit needs outcomes to be
considered more carefully, and also safety measured
more robustly. Treatment driven to ensure safety of
the patient (risk of falls, aggression to others) needs
to be compared with the safety outcomes seen with
treatment of antipsychotics including mortality out-
comes. Equally, qualitative work that has explored
the delirium experience, including participants where
it is known that they received antipsychotic treatment,
still had recall of the experience and distress. As our
understanding of delirium pathophysiology increases,
dopamine excess seems to be one player in a complex
array of abnormalities, and other targets may emerge
which have stronger biological plausibility and chance
of better impact in delirium treatment. Delirium is a
Copyright # 2017 John Wiley & Sons, Ltd.
D. Meagher et al.
significant medical condition, with substantial costs
to the patient, their family and the health care system.
People with delirium deserve the best quality evidence
to guide their care, and antipsychotic use in delirium
should be limited to use in robust adequately powered
and carefully designed randomised controlled clinical
trials (Ely, 2011).
Moderation
Andrew Teodorczuk.
a.teodorczuk@griffith.edu.au
To prescribe or not to prescribe antipsychotics in
delirium, that is seemingly the question. From various
perspectives, this is an increasingly important
dilemma that healthcare professionals are likely to face
on a daily basis as they wrestle with delirium manage-
ment in a system that struggles to accommodate the
needs of the acutely confused patient (MacLullich
and Hall, 2011).
Economically, any pharmacological intervention
that is able to reduce the impact of the delirium on
length of stay and readmissions is attractive to clini-
cians, hospital managers and systems alike. Ethically,
a treatment approach that potentially may reduce
patient distress, mortality, cognitive decline and func-
tional loss is much needed, especially now that we are
acutely aware of the negative long-term health impact
of delirium (Witlox et al., 2010). From a cultural per-
spective, there also exists a pertinent need to determine
the best way forward. Reports of junior medical staff
being pressured to prescribe in clinical situations by
other healthcare staff, whom are challenged by the
needs of the patient with delirium, may resonate with
today’s clinical workforce (Teodorczuk et al., 2015).
Furthermore, an international survey of practice sug-
gests that prescribing first line is the norm for hyperac-
tive delirium (Morandi et al., 2013). With this in mind,
the debate article is both timely and clinically relevant.
For the nays, Meera Agar puts forward a persuasive
argument not to prescribe drawing on the central
tenets that biologically a narrow focus on dopamine
blockade makes little sense and is at odds with our, al-
beit limited, understanding of the pathophysiology of
delirium. Put another way, it is a Band-Aid solution
to a complex pathophysiological multifactorial prob-
lem borne out of the need to do something medically
and may even do more harm than good given the well-
known side effects of antipsychotics. This argument is
supported by growing evidence in the field, both RCT
(Agar et al., 2017) and systematic review (Neufeld
et al., 2016). Furthermore in the presence of robust
Int J Geriatr Psychiatry 2017
Antipsychotic prescribing in delirium
non-pharmacological approaches, the need to reach
for a pharmacological solution may not be necessary
or evidence based.
In defence of antipsychotics in delirium manage-
ment and prevention, David Meagher argues in
essence that a false dichotomy has been created and
the proposal not to prescribe over simplifies a complex
problem. The crux of the argument being that in the
absence of a unitary concept of delirium, a one size fits
all approach never to prescribe is not the answer.
Moreover, the evidence for non-pharmacological
approaches traditionally pertains more towards
prevention than management of delirium (Inouye,
2000). Lending from the psychiatric literature, where
clinicians and researchers also wrestle with managing
other similarly poorly understood heterogeneous
complex syndromes, Meagher suggests that complex
solutions are needed to complex problems. Specifically,
an incremental improvement approach combining
both pharmacological and non-pharmacological strate-
gies is necessary, tailored to patients with delirium
delineated by sub type, setting, age and co-morbidity.
So who wins, the yays or the nays? Both arguments
are well articulated and point to the complexity of
delirium, lack of robust research studies and faults in
those studies conducted leading to serious challenges
in interpreting and implementing the evidence. What
emerges is no clear winner but a need to establish
essentially why we are prescribing antipsychotics.
Perhaps, this should be the central question before
deciding what works.
If the goal is to prevent delirium then, in the ab-
sence of clear evidence for and presence of evidence
supporting non-pharmacological approaches, it is
reasonable to advocate not prescribing antipsychotics
for prevention. Rather, the focus should be on ensur-
ing early screening and identification of those at risk
of delirium and detailed formulation to lead towards
a complex non-pharmacological approach. Effective
interprofessional collaboration here is key.
If the goal is to manage simple or so-called “rou-
tine” delirium in a patient without risks and distress,
then arguably it may be sensible to advocate avoiding
antipsychotics as the tide of evidence is moving against
their use in these contexts. It also appears that the
more robust a study is in a challenging delirium
research arena the stronger the emergent signal against
prescribing.
However, if the goal is to treat a complex delirium
with distress and or risk, then the answer is less clear.
Unfortunately, as stated by Neufeld et al. (2016), we
simply do not have the studies that focus on symp-
tomatic relief and reducing agitation as a treatment
Copyright # 2017 John Wiley & Sons, Ltd.
target. In this context, judicious prescribing together
with effective implementation of non-pharmacologi-
cal approaches may be necessary.
What do we mean by judicious use? Essentially, if
prescribing is necessary for reasons of severe distress
or risk, then antipsychotics should be only com-
menced if non-pharmacological strategies have been
found to be ineffective or may be inappropriate. Fur-
ther, each patient should be considered on a case by
case basis and evaluated for significant comorbidities.
When prescribing, low dose antipsychotic treatment
with careful consideration of side effects and ongoing
monitoring of ECGs, extrapyramidal side effects, BP
and sedation should be routinely undertaken. Last,
any pharmacological treatment beyond one week
would appear especially difficult to justify given the
propensity for side effects and risk of leaving a patient
on an antipsychotic long term.
Ultimately, though any decisions that are made
should be decided by a combination of best available
evidence and crucially in conjunction with patient
and carer preferences. With this in mind and in the
context of delirium occurring as a consequence of de-
compensation in a vulnerable brain, sensible pharma-
cological advice may be to inform carers (and staff) of
the risk of prescribing, emerging evidence base for not
prescribing in certain contexts and shifting the discus-
sion from prescribing to deprescribing. Only once staff
and carers are satisfied that there is still a need to pre-
scribe should pharmacological approaches be initiated.
To prescribe antipsychotics or not in delirium does
not lend itself unfortunately to simple answers.
Complex decisions need to be proceeded by complex
discussions informed by best evidence in an ever chang-
ing delirium research arena. A score draw is declared.
Conflict of interest
None declared.
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