Non-pharmacological interventions for agitation in dementia: systematic review of randomised controlled trials

The number of people with dementia is rising rapidly with
increased longevity. Although dementia’s core symptom is
cognitive deterioration, agitation is common, persistent and
distressing. Nearly half of all people with dementia have agitation
symptoms every month, including 30% of those living at home. 1
Four-fifths of those with clinically significant symptoms remain
agitated over 6 months, 2 and 20% of those initially symptom-free
develop symptoms over 2 years.2 Agitation in dementia is
associated with poor quality of life, 3 because it is unpleasant,
impedes activities and relationships, causes helplessness and anger
in family and paid caregivers,4 and predicts nursing home
admission, 5 where the agitated behaviour adversely influences
the environment.4 Several reviews, including our previous
systematic review, 6 considered all neuropsychiatric symptoms’
management together. We found direct behavioural management
therapies (BMT) with the person with dementia and specific staff
education had lasting effectiveness, but this may be limited to
affective symptoms. 7 A recent meta-analysis of family caregiver
interventions for overall neuropsychiatric symptoms in dementia
found an effect size of 0.23, but did not consider which symptoms
improved.8
Neuropsychiatric symptoms in dementia are heterogeneous,
therefore symptoms should be considered individually as success-
ful strategies may differ. The one published, well-conducted
systematic review of non-pharmacological management of
agitation in dementia included only randomised controlled trials
(RCTs) published before 2004 in English or Korean; it found just
14 papers and evidence of effectiveness only for sensory inter-
ventions.9 The review did not consider whether interventions were
effective only during the intervention or whether the effect lasted
longer; the settings in which the intervention had been shown to
be effective (e.g. in the community or in care homes); or whether
the intervention reduced levels of agitation symptoms and was
preventive or treated clinically significant agitation.
Psychotropic medication was routinely used to treat agitation
but is now discouraged since benzodiazepines and antipsychotics
increase cognitive decline, 10 and antipsychotics cause excess
mortality and are of limited efficacy. 11 Similarly, citalopram has
some efficacy but has cardiac side-effects and reduces cognition. 12
Cholinesterase inhibitors and memantine appear ineffective. 13,14
Preliminary evidence suggests mirtazapine may reduce agitation. 15
One RCT (not placebo-controlled) found analgesics improved
agitation in people with dementia, with an effect size comparable
to antipsychotics.16
Effective agitation management could in theory improve the
quality of life of people with dementia and their caregivers, reduce
distress, decrease inappropriate medication, enable positive
relationships and activities, delay institutionalisation and be
cost-effective. We aimed therefore to review systematically the
evidence for non-pharmacological interventions for agitation in
people with dementia, both immediately and longer-term; the
costs of the successful interventions are reported in a separate
paper. 17
Method
We registered our protocol with the Prospero International
Prospective Register of Systematic Reviews (http://www.crd.york.
ac.uk/PROSPERO/display_record.asp?ID = CRD42011001370). We
began electronic searches on 9 August 2011, repeating them on
12 June 2012. We searched PubMed, Web of Knowledge, British
Nursing Index, the Health Technology Assessment (HTA)
Programme Database, PsycINFO, NHS Evidence, System for
Information on Grey Literature, The Stationery Office Official
Publications website, the National Technical Information Service,
INAHL and the Cochrane Library. Search terms were agreed in
consultation with caregiver representatives, older adults and
436
Non-pharmacological interventions for agitation
in dementia: systematic review of randomised
controlled trials
Gill Livingston, Lynsey Kelly, Elanor Lewis-Holmes, Gianluca Baio, Stephen Morris,
Nishma Patel, Rumana Z. Omar, Cornelius Katona and Claudia Cooper
Background
Agitation in dementia is common, persistent and distressing
and can lead to care breakdown. Medication is often
ineffective and harmful.
Aims
To systematically review randomised controlled trial evidence
regarding non-pharmacological interventions.
Method
We reviewed 33 studies fitting predetermined criteria,
assessed their validity and calculated standardised effect
sizes (SES).
Results
Person-centred care, communication skills training and
adapted dementia care mapping decreased symptomatic and
severe agitation in care homes immediately (SES range
0.3–1.8) and for up to 6 months afterwards (SES range
0.2–2.2). Activities and music therapy by protocol (SES range
0.5–0.6) decreased overall agitation and sensory intervention
decreased clinically significant agitation immediately.
Aromatherapy and light therapy did not demonstrate
efficacy.
Conclusions
There are evidence-based strategies for care homes. Future
interventions should focus on consistent and long-term
implementation through staff training. Further research is
needed for people living in their own homes.
Declaration of interest
None.
The British Journal of Psychiatry (2014)
205, 436–442. doi: 10.1192/bjp.bp.113.141119
Review article

professionals. We hand-searched included papers’ reference lists
and contacted all authors about other relevant studies. We
translated eight non-English papers.
Inclusion and exclusion criteria
We included studies in any language that met the following
criteria:
(a) the participants all had dementia, or those with dementia were
analysed separately;
(b) the study evaluated non-pharmacological interventions for
agitation, defined as inappropriate verbal, vocal or motor
activity not judged by an outside observer to be an outcome
of need, 18 encompassing physical and verbal aggression and
wandering;
(c) agitation was measured quantitatively;
(d) a comparator group was reported or agitation was compared
before and after the intervention.
We excluded studies if every individual was given psychotropic
drugs or some participants received medication as the sole
intervention. In this paper we report the highest-quality studies
– randomised controlled trials (RCTs) with more than 45
participants – since none of the trials with a smaller sample size
provided a full and appropriate sample size calculation.
Data extraction
The first 20 search results were independently screened by G.L.
and L.K. to assess exclusion procedure reliability. No paper was
excluded incorrectly. All other papers were screened by L.K. and
E.L.H. If exclusion was unclear, L.K., E.L.H. and G.L. discussed
and reached consensus. Data extracted from the papers (by L.K.
and E.L.H.) included methodological characteristics; description
of the intervention; whether the intervention was applied to the
person with dementia, family caregivers or staff; statistical
methods; length of follow-up; diagnostic methods; and summary
outcome data (immediate and longer-term). Paper quality,
including bias, was scored independently by L.K. and E.L.H.,
discussing discrepancies with G.L. and/or G.B. They used Centre
for Evidence-Based Medicine (CEBM) RCT evaluation criteria
(http://www.cebm.net/index.aspx?o = 1025); this approach gives
points for randomisation and its adequacy, participant and rater
masking, outcome measures validity and reliability, power
calculations and achievement, follow-up adequacy, accounting
for participants, and whether analyses were intention to treat
and appropriate. Possible scores range from 0 to 14 (highest
quality). Where a randomised design was used but the inter-
vention was not compared with the control group, we considered
this a within-subject design, for example the study by Raglio et
al. 19 We assigned CEBM evidence levels as follows:
(a) level 1b: high-quality RCTs (these were at least single-blind,
had follow-up rates of at least 80%, were sufficiently
powered, used intention-to-treat analysis, had valid outcome
measures and findings reported with relatively narrow
confidence intervals);
(b) level 2b: lower-quality RCTs.
Intervention categories
The authors L.K., E.L.H. and G.L. categorised the interventions
independently and then by consensus. The interventions were
activities; music therapy (protocol-driven); sensory interventions
(all involved touch, and some included additional sensory
stimulation such as light); light therapy; training paid caregivers
in person-centred care or communication skills (interventions
focused on improving communication with the person with
dementia and finding out what they wanted), with and without
supervision; dementia care mapping; aromatherapy; training
family caregivers in behavioural management therapies or
cognitive–behavioural therapy (CBT); exercise; cognitive
stimulation therapy; and simulated presence therapy.
Agitation level
We separated studies according to the inclusion criteria of
participants in terms of level of symptoms of agitation: 1, no
agitation symptom necessary for inclusion; 2, some agitation
symptoms necessary for inclusion; 3, clinically significant
agitation level; 4, level unspecified. We used the usual thresholds:
a score above 39 on the Cohen-Mansfield Agitation Inventory
(CMAI),20 and a score above 4 on the Neuropsychiatric Inventory
(NPI) agitation scale, 1 to denote significant agitation.
Statistical analysis
We decided a priori to meta-analyse when there were three or
more RCTs investigating sufficiently homogeneous interventions
using the same outcome measure, but no intervention met these
criteria. To facilitate comparison across interventions and
outcomes, where possible, we estimated interventions’
standardised effect sizes (SES) with 95% confidence intervals. 21
In some studies the outcome was measured and reported at several
time-points during the intervention. We used data from the last
time-point to estimate the SES, since individual patient data were
not available to incorporate repeated measures in the calculation.
We also recalculated results for studies not directly comparing
intervention and control groups but reporting only within-group
comparisons and with one-tailed significance tests, so some of our
results differ from the original analysis.
Results
We found 1916 records, including 33 relevant RCTs with at least
45 participants (Fig. 1). Online Tables DS1 and DS2 list
methodological characteristics, SES and quality ratings; Table
DS1 contains the findings from interventions for which there
appeared to be adequate evidence, and Table DS2 contains those
for which there was not adequate evidence (either evidence that
they were not effective or where there was simply insufficient
evidence).
Efficacious interventions
Working with the person with dementia
Activities. Five of the included RCTs implemented group
activities; those with standard activities reduced mean agitation
levels, and decreased symptoms in care homes while they were
in place.22,23 One high-quality RCT found no additional effect
on agitation of individualising activities according to functional
level and interest, 24 although two lower-quality RCTs did. 25,26
All studies were in care homes except one, in which some
participants attended a day centre and others lived in a care
home. 27 None specified a significant degree of agitation for
inclusion. Only one study measured agitation after the
intervention finished, and did not show effects at 1-week and
4-week follow-up. 24
Although activities in care homes reduced levels of agitation
significantly while in place, there is no evidence regarding
longer-term effect, and it is unclear whether individualising
437
Non-pharmacological studies of agitation in dementia

Livingston et al
activities further reduces agitation. There is no evidence for
activities in severe agitation or outside care homes.
Music therapy. Three RCTs, all in care homes, evaluated music
therapy by trained therapists using a specific protocol – typically
involving warming up with a well-known song, listening to and
then joining in with the music. 28–30 The largest study, which
included participants irrespective of agitation level, found music
therapy twice a week for 6 weeks was effective compared with
the usual care group. 28 A second study found a significant effect
in comparison with a reading group, 30 and the third found a
borderline significant effect. 29 Reduction in symptoms of agitation
was immediate (SES = 0.5–0.9). There is little evidence longer-
term, and no evidence for people with severe agitation or outside
care homes.
Sensory interventions
Five RCTs of sensory interventions, all in care homes, targeted
perceived understimulation of people with dementia. Some
focused on touch, such as massage; others were multisensory
interventions of tactile, light and auditory stimulation, such as
Snoezelen therapy. 22,31–34 Studies comparing touch found a
significant improvement in symptomatic and clinically significant
agitation compared with usual care.22,34 We report three
‘therapeutic touch’ studies; defined as a healing-based touch inter-
vention focusing on the whole person. 31–33 Despite therapeutic
touch being efficacious in before-and-after analyses, in between-
group analyses therapeutic touch tended towards being less
efficacious than ordinary massage or usual treatment. Sensory
interventions significantly improved symptomatic agitation and
clinically significant agitation during the intervention, but
therapeutic touch did not demonstrate added advantage, and
there is insufficient evidence about long-term effects or in settings
outside care homes.
Working through care-home staff
Person-centred care, communication skills training and dementia
care mapping all seek to change the caregiver’s perspective,
communication with and thoughts about people with dementia,
encouraging the caregiver to see and treat them as individuals
rather than being task-focused. Training paid caregivers in these
techniques was investigated in five RCTs. 35–39 All interventions
included supervision during training and implementation.
Person-centred care. One high-quality study of person-centred
care training found severe agitation significantly improved during
the intervention and 8 weeks later.35 Two studies of improving
communication skills or person-centred care for participants with
symptomatic agitation found significant improvements compared
with the control group during the intervention,37,38 and up to 6
months afterwards.37 A large study including participants without
high agitation levels found agitation improved significantly during
8 weeks of person-centred care training and 20 weeks later. 36 One
small study, where participants’ agitation levels were unspecified,
showed immediate improvement in agitation during bathing
compared with the control group. 39
438
102 additional records
found from
other sources
Initial screening
1916 records
284 full papers reviewed
160 papers included
and scored for quality
including bias
33 RCTs with at least
45 participants:
CEBM score 1b: 8
CEBM score 2b: 25
133 records
identified from
second search
1632 abstracts excluded:
Not only dementia: 681
Not primary research: 360
Not intervention study: 318
Not psychological, or behavioural or sensory
or environmental intervention: 236
Protocol only: 16
No comparator group: 9
No agitation or behavioural outcome: 11
Conference paper only: 1
124 excluded
No agitation or behavoural outcome: 35
Not only dementia: 23
Not primary research: 15
No comparator: 12
No quantitative outcome: 17
Conference paper only: 8
Not psychological, behavioural, sensory
or environmental intervention: 3
Multidisciplinary team approach including drug prescription: 4
Not intervention study: 3
Participants under 50: 2
No outcome: 1
Protocol only: 1
127 not considered in this review
CEBM score 2c or less: 107
CEBM score 2b or more: 545 participants: 19
CEBM score 2b 445 participants not RCT: 1
1681 unique records
identified from
original search
6
7
6
7
6
7
6
Fig. 1 Study search profile (CEBM, Centre for Evidence-Based Medicine; RCT, randomised controlled trial).

Non-pharmacological studies of agitation in dementia
Dementia care mapping. One large, high-quality care home
study evaluated dementia care mapping. The researchers observed
and assessed each resident’s behaviour, factors improving well-
being and potential triggers; explained the results to caregivers,
and supported proposed change implementation. Severe agitation
decreased during the intervention and 4 months afterwards.35
Effect sizes. Training paid care-home staff in communication
skills, person-centred care or dementia care mapping with
supervision during implementation was significantly effective for
symptomatic and severe agitation immediately (SES = 0.3–1.8)
and for up to 6 months (SES = 0.2–2.2). There was no evidence
in other settings.
Interventions without evidence of efficacy
Working with the person with dementia
Light therapy. Light therapy hypothetically reduces agitation
through manipulating circadian rhythms, typically by 30–60 min
daily bright light exposure. We included three RCTs, all in care
homes. 40–42 Among participants with some or significant
agitation, light therapy either increased agitation or did not
improve it. The SES was 0.2 (for improvement) to 4.0 (for
worsening symptoms) compared with the control group. There
is therefore no evidence that light therapy reduces symptomatic
or severe agitation in care homes and it may worsen it.
Aromatherapy. The two RCTs of aromatherapy both took place
in care homes. 43,44 One large, high-quality blinded study found no
immediate or long-term improvement relative to the control group
for participants with severe agitation. 44 The other, non-blinded,
study found significant improvement compared with the control
group.43 When assessors are masked to the intervention,
aromatherapy has not been shown to reduce agitation in care
homes.
Training family caregivers in BMT. Two high-quality studies
found no immediate or longer-term effect (at 3 months, 6 months
or 12 months) of either four or eleven sessions training family
caregivers in BMT for severe or symptomatic agitation in people
with dementia living at home. 45,46 Two studies training family
caregivers in CBT for people with severe agitation also found no
improvement compared with controls.47,48 There is thus high-
quality evidence that teaching family caregivers BMT or CBT is
ineffective for severe agitation, but insufficient evidence to draw
conclusions regarding symptomatic agitation.
Interventions with insufficient evidence
For the following interventions there was insufficient evidence to
make a definitive recommendation.
Exercise
There is no evidence that exercise is effective. The one sufficiently
sized exercise RCT was conducted in a care home and found no
effect on agitation levels either immediately or 7 weeks later.
Training caregivers without supervision
Training in communication skills and person-centred care without
supervision was ineffective. 49,50
Other interventions
One study found that simulated presence therapy – playing a
recording mimicking a telephone conversation with a relative
when the participant was agitated – was not effective.51 One study
testing a mixed psychosocial intervention, including massage and
promoting residents’ activities of daily living skills, did not find
agitation improved significantly compared with the control
group. 52
Standardised effect sizes
Figure 2 illustrates the effect of person-centred care, communication,
dementia care mapping, music therapy and activities in reducing
agitation. Long-term effects (in months) of changing the way care-
givers interact with residents are at least as good as the short-term
effects. 35,38
Discussion
This is the first up-to-date systematic review to focus on agitation.
It uniquely analyses whether the intervention was potentially
preventive, by reducing mean levels of agitation symptoms
including those not clinically significant at baseline or managed
clinically significant agitation; whether effects were observed only
while the intervention was in place or lasted longer; and the
settings in which the intervention had been shown to be effective:
the community or in care homes.
Effective interventions
Effective interventions seem to work through care staff, partic-
ularly in the long term. There is convincing evidence that
when implementation is supervised, interventions that aim to
communicate with people with dementia, helping staff to
understand and fulfil their wishes, reduce symptomatic and severe
agitation during the intervention and for 3–6 months afterwards.
This suggests that training paid caregivers in communication,
person-centred care skills or dementia care mapping are clinically
important interventions, as shown by a 30% decrease in
agitation 43 or a standardised effect size of 0.2, which is clinically
small, 0.5 medium and 0.8 large.53
Sensory interventions significantly improved agitation of all
severities while in place. Therapeutic touch had no added
advantage. We also found replicated, good-quality evidence that
activities and music therapy by protocol reduce overall and
symptomatic agitation in care homes while in place. Although
we were surprised that individualised activities were no more
effective than prescribed activities, the low numbers in the activity
intervention groups may suggest that it was only those who were
particularly suited to the activity who participated. There is
no evidence for severe agitation. Theory-based activities
(neurodevelopmental and Montessori) were no more effective
than other pleasant activities.
Other interventions
Light therapy does not appear to be effective and may be harmful.
Non-blinded interventions with aromatherapy appeared effective,
possibly owing to rater bias, but masked raters do not find it
effective. Training family caregivers in BMT and CBT interventions
for the person with dementia was not effective. Learning complex
theories and skills and maintaining fidelity to an intervention may
be almost impossible to combine with looking after a family
member with dementia and agitation on a 24-hour basis.
Strengths and weaknesses of the study
This is an exhaustive systematic review; two raters independently
evaluated studies to ensure reliability in study inclusion and
quality ratings. We searched all health and social sciences
439