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Age and Ageing 2015; 44: 318–321
doi: 10.1093/ageing/afu152
Published electronically 4 December 2014
© The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society.
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SHORT REPORTS
Defining ‘recovery’ for delirium research:
a systematic review
DIMITRIOS ADAMIS1,2, AMANDA DEVANEY2, ELAINE SHANAHAN3, GERALDINE MCCARTHY2,4, DAVID MEAGHER5
1
Research and Academic Institute of Athens, Athens, Greece
Department of Psychiatry, Sligo Mental Health Services, Sligo, Ireland
3
Department of Elderly Medicine, University Hospital Limerick, Limerick, Ireland
4
Sligo Medical Academy, National University of Ireland, Galway, Sligo, Ireland
5
Department of Psychiatry, Medical School, University of Limerick, Limerick, Ireland
2
Address correspondence to: D. Adamis. Tel: (+353) 719142111; Fax: (+353) 719144177. Email: [email protected]
Abstract
Background: delirium is a common neuropsychiatric disorder. The natural course is of an acute, fluctuating and often transient condition; however, accumulating evidence suggests that delirium can be associated with incomplete recovery. Despite a
growing body of research, a lack of clarity exists regarding definition and outcomes.
Objective: to clarify the definition of recovery of delirium used in the literature.
Methods: a Medline search was performed using relevant keywords. Studies were included if they were in English, provided
any definition of recovery and were longitudinal. Excluded articles were duplicated studies, case studies, review articles or
articles related to alcohol, children, subsyndromal delirium only or those investigating core symptoms such as function.
Results: fifty-six studies met the inclusion criteria. Only two studies used clinical criteria alone for the diagnosis of delirium;
most studies used at least one validated scale—either categorical or continuous severity scales. A variety of 16 different terms
were used to define the ‘recovery of delirium’. The definitions of each term also varied. Studies using severity scales used either
cut-off points or percentage reduction between assessments, while others using dichotomous scales (yes/no) defined recovery
as one or more days of negative delirium.
Conclusion: an agreed terminology to define recovery in delirium is required. A distinction should also be made between
symptomatic and overall recovery, as well as between long- and short-term outcomes. It is proposed that cognitive recovery
should be central to defining recovery in delirium.
Keywords: delirium, outcome, recovery, remission, response, older people
Introduction
Delirium has been defined as a syndrome of acute onset, typically over hours or days, followed by a fluctuating course with
impaired attention, altered awareness and a variety of cognitive
and neuropsychiatric disturbances [1]. Although the natural
history of delirium is that of an often acute and frequently reversible condition, evidence suggests that delirium can be associated with incomplete recovery [2], particularly, in elderly
individuals and individuals with co-existing dementia [3]. The
naturally fluctuating course of delirium and the impact from
treatment of underlying precipitating factors complicate efforts
to identify a meaningful definition of recovery. To define recovery, Trzepacz et al. [4], suggested a definition of delirium
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resolution or response as a significant reduction in delirium
symptoms below a specified value (often a percent change
from baseline) as measured with a severity scale. Closely related
to the concept of ‘recovery’ are issues of ‘response’ (which typically relates to initial reduction in symptom load), ‘remission’
(which typically refers to a sustained initial period without
major symptoms) and ‘resolution’ (which usually refers to complete symptom reduction) [5, 6]. Inherent to these concepts are
issues of degree of change from baseline, duration of observed
improvements, extent of residual symptoms and which aspects
of any condition should be considered the primary determinant of therapeutic effect. Thus, the definition of recovery in
mental disorders, many of which have a propensity for chronicity, is influenced by the specific disorder, e.g. bipolar,
Defining ‘recovery’ for delirium research
schizophrenia and anxiety disorders, and may emphasise temporal or symptomatic elements [5–9].
Despite the growing delirium literature, there is a lack of
clarity and rigor with respect to the terminology pertaining to
both definition and recovery. Thus, in an effort to clarify terminology and definitions of recovery in delirium that have
been used in the literature, we conducted a systematic literature
review, with the aim of investigating approaches to the definition of recovery that have been applied in studies of delirium.
CINAHL Plus and PsyInfo databases from 1954 until
December 2013. Also, a manual search was performed of
reference lists from identified studies. The literature search
yielded a total of 1,050 studies in the English language.
(Figure 1). The abstracts of these studies were inspected for
the inclusion of relevant studies independently by two investigators (D.A. and A.D.). In cases of discrepancies between
the investigators, the full text article was reviewed. Predefined
data were extracted by one of the authors.
Methods
Results
Inclusion criteria for studies
Fifty-six studies met the inclusion/exclusion criteria and they
are summarised in Supplementary data, Appendix S1 available in Age and Ageing online.
Studies were included if:
(i) they provide explicitly any definition of recovery or
remission or relevant information.
(ii) they include at least two assessment points in time.
Exclusion of studies
(i) Duplicated studies.
(ii) Studies that investigate recovery in one of the core symptoms or outcomes of delirium (cognition, adaptive function and quality of life) as recovery of one symptom/
element not necessarily means recovery of the whole.
(iii) Studies that investigate only subsyndromal delirium.
(iv) Studies that investigated delirium in children/adolescents.
(v) Alcohol-related delirium studies.
(vi) Case studies.
(vii) Review articles/commentaries.
(viii) Non-English language studies.
Description of studies
Five were retrospective [10–14], five were secondary analyses
of data already collected [15–19] and the rest (n = 46) had a
prospective design. Three were case–control studies [10, 20,
21] but with longitudinal designs. Twenty-four of the
included studies were trials of different medications or interventions while 32 measured clinical characteristics and outcomes of delirium. The settings in which each study
conducted, the study duration, the scales used, the number
of delirious patients and the recovery rates of each definition
are shown in Supplementary data, Appendix S1 available in
Age and Ageing online. Most of the studies examined older
populations (minimum mean age of 39.3 in AIDS patients;
maximum mean age of 87.4 in long-term facilities).
Search keywords/strategy
Nomenclature
The search keywords used were ‘Delirium’ or ‘acute confusion’ AND ‘recovery’ or ‘reversibility’ or ‘reversible’ or
‘recoverable’ or ‘resolution’ or ‘remission’ or ‘response’ or
‘outcome’ or ‘treatment’. The search included Medline,
A variety of terms have been used to describe the outcome
of delirium. The most often used was ‘recovery’ (15 studies),
but other terminologies included ‘response’ (5), ‘resolution’
(10) ‘improvement’ (3) or ‘sufficient effect of treatment’ (1).
Figure 1. Flow chart of included studies.
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D. Adamis et al.
Definitions of outcome
Similarly, the definitions of each term varied. Studies that used
severity scales such as the MDAS, DRS and DRS-R98 required
either cut-off points, which varied even for the same scale
across studies (e.g. MDAS ≤10 or <13; DRS-R98 severity
scores <15.25 or <10) or percentage reduction in total scores
between assessments. Some applied dichotomous scales (yes/
no) such as the CAM with the first day of negative delirium
used as the end point [20] while in other studies a longer
period ‘delirium-free’ was required (Supplementary data,
Appendix S1 available in Age and Ageing online).
Discussion
From the studies included in this review, it is apparent that a
variety of definitions of ‘recovery’ or other similar terms like
‘response’ or ‘remission’ have been used to describe the
outcome of delirium in observational and clinical trial studies.
The search strategy may have missed some relevant articles, but
it is unlikely that markedly different definitions have been used.
This inconsistency in terminology can, in part, be explained
by the inherent heterogeneity of delirium as a condition
(whereby what is considered a ‘good’ response in one population or setting may not be so viewed in others). However, it
serves to seriously obfuscate the literature pertaining to outcomes in delirium. Although delirium can have an acute onset
with florid symptomatology (e.g. including delusions, hallucinations and psychomotor disturbances), more often the presentation is much quieter with so-called hypoactive delirium which is
less phenomenologically compelling or intense but is a more
severe form of delirium in terms of many outcomes. Thus,
even though acute symptoms may resolve (with reduction in severity scale scores), persistent difficulties can occur such that
full resolution of symptoms is not possible. In the existing literature, ‘response’ most often refers to a reduction of clinical
symptoms. This term is frequently used in clinical trials and
includes a 50% or more reduction in severity of symptoms.
However, delirium is caused by physical illness, and in some
cases, a perceived response may reflect the impact of treatment
of the underling medical condition. Similarly, by using response
as an outcome both inclusion criterion and baseline measurement are measured as a single assessment by the same scale. As
a consequence, in statistical analysis, the regression to the mean
will contribute to an invalid finding of clinical improvement
[22]. Moreover, greater baseline severity predicts greater efficacy
of medications versus placebo [23], as the magnitude of change
is highly dependent upon the initial severity of the symptoms.
Remission in other psychiatric disorders (e.g. depression)
equates with the symptoms and the signs of the disorder no
longer being present. Resolution has also been used as a
synonym of remission. In such cases, the use of scales with
binary rating (yes/no) is preferable. Of note, the use of
remission as an outcome could penalise those with more delirium symptoms and includes a presumption that the cut-off
point of scales applied for diagnosis is accurate.
Recovery implies an extended period of remission and a
return to previous status. However, optimal outcomes for
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many patients with delirium do not always extend to full
recovery as for some, delirium is a marker of deteriorating
function, while for others it can act as an accelerating or aggravating factor for underlying dementia [24, 25]. Given that,
especially in elderly people, a full recovery may never be
achieved, it is perhaps better to define recovery according to
a symptomatic status that can be measured by a variety of
diagnostic instruments.
Recommendations
By reviewing the relevant literature, we can suggest that an
agreed terminology to define recovery in delirium is required,
and that a distinction should be made between symptomatic
and general recovery as well as between short- and longterm outcomes. Increasingly, studies have highlighted that
although many patients experience symptomatic improvement,
others continue to experience significant delirium symptoms for
prolonged periods with some ultimately transitioning into persistent states of cognitive impairment and dementia [3].
Psychiatric disorders are chronic and disabling conditions with
fluctuations and relapses. However, historically, many of the
major advances in psychiatric understanding have followed longitudinal observations. Kraepelin [26], for instance, distinguished
manic depression from schizophrenia mainly based on the
course of illness and the outcome. Ignoring outcome makes it
difficult to distinguish delirium from other cognitive disorders,
especially dementia which share many common characteristics
[27, 28]. It has been proposed that reversibility of cognition
should be a criterion for the definition of delirium [29, 30]; although other work has highlighted the central nature of cognitive impairments to phenomenological profile in delirium [28],
we propose that sustained improvement in cognitive function
should be a core element in defining therapeutic outcomes in
delirium, including ‘response’ where baseline cognitive function
is re-established for at least one full day of assessment, ‘recovery’
where this is sustained for more prolonged periods (e.g. at least
a week) and that both should be distinguished from ‘symptomatic improvement’ that reflects symptom reduction—including
reduction of agitation and related problems with sedative psychotropics. More consistent use of these terms can allow for
more meaningful comparison of outcome across studies with
better clarity as to the nature of therapeutic response in the
complex neuropsychiatric syndrome that is delirium.
Key points
• There is not a consist terminology to define recovery in delirium.
• A distinction should be made between symptomatic and
general recovery.
• Similarly a distinction needs to be made between short and
long term outcomes.
• Well defined, practical and feasible criteria for delirium recovery such as cognitive recovery would give a standard
upon which to examine factors against.
Defining ‘recovery’ for delirium research
Conflicts of interest
None declared.
Supplementary data
Supplementary data mentioned in the text are available to
subscribers in Age and Ageing online.
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Received 22 February 2014; accepted in revised form
11 September 2014
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