Ageing Research Reviews 11 (2012) 78–86

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Ageing Research Reviews

journal homepage: www.elsevier.com/locate/arr

Review

Systematic appraisal of dementia guidelines for the management of

behavioural and psychological symptoms
Majda Azermai a,∗ , Mirko Petrovic a,b , Monique M. Elseviers a,c , Jolyce Bourgeois a ,
Luc M. Van Bortel a , Robert H. Vander Stichele a
a
Ghent University, Heymans Institute of Pharmacology, Ghent, Belgium
b
Ghent University Hospital, Service of Geriatrics, Ghent, Belgium
c
University of Antwerp, Nursing Science, Antwerp, Belgium

a r t i c l e i n f o a b s t r a c t

Article history: Background: Within the treatment of dementia, management of behavioural and psychological symptoms
Received 1 July 2011 (BPSD) is a complex component.
Accepted 8 July 2011 Purpose: We wanted to offer a pragmatic synthesis of existing specific practice recommendations for
Available online 10 August 2011
managing BPSD, based on agreement among systematically appraised dementia guidelines.
Data sources: We conducted a systematic search in MEDLINE and guideline organisation databases, sup-
Keywords:
plemented by a hand search of web sites.
Behavioural and psychological symptoms
Study selection: Fifteen retrieved guidelines were eligible for quality appraisal by the Appraisal of Guide-
of dementia
Antipsychotics
lines Research and Evaluation instrument (AGREE), performed by 2 independent reviewers.
Clinical practice guidelines Data extraction: From the 5 included guidelines, 18 specific practice recommendations for BPSD were
extracted and compared for their level of evidence and strength.
Data synthesis: No agreement was found among dementia guidelines for the majority of specific practice
recommendations with regard to non-pharmacological interventions, although these were recom-
mended as first-line treatment. Pharmacological specific practice recommendations were proposed as
second-line treatment, with agreement for the use of a selection of antipsychotics based on strong
supporting evidence, but with guidance for timely discontinuation.
Limitations: The appraisal of the level of agreement between guidelines for each specific practice recom-
mendation was complicated by variation in grading systems, and was performed with criteria developed
a posteriori.
Conclusion: Despite the limited number of recommendations for which agreement was found,
guidelines did agree on careful antipsychotic use for BPSD. Adverse events might outweigh the
supporting evidence of efficacy, weakening the recommendation. More pivotal trials on the effective-
ness of non-pharmacological interventions, as well as guidelines specifically focusing on BPSD, are
needed.
© 2011 Elsevier B.V. All rights reserved.

1. Introduction ponent within the treatment of dementia, due to risk of serious

Behavioural and psychological symptoms of dementia (BPSD)
comprise a broad spectrum of non-cognitive symptoms including
physical aggression, agitation, hallucinations, depression, delu-
sions, wandering and sleep disturbances (Petrovic et al., 2007;
Liperoti et al., 2008). Up to 80% of patients with Alzheimer’s demen-
tia may develop periodic episodes or chronic behavioural and
psychological symptoms in their course of illness (Lyketsos et al.,
2002). Management of BPSD is an important but complex com-
∗ Corresponding author at: Ghent University, Heymans Institute of Pharmacology,
De Pintelaan 185, 1 Blok B, 9000 Ghent, Belgium.
E-mail address: majda.azermai@ugent.be (M. Azermai).
adverse effects associated with antipsychotic treatment and to the
absence of credible alternatives. Additionally, BPSD are important
risk factors for care giver burden and institutionalisation (Fersch
and Falzgraf, 2007).
The Institute of Medicine defines clinical practice guidelines
as ‘systematically developed statements to assist practitioner
and patient decisions about appropriate health care for spe-
cific clinical circumstances’ (Field, 1990). Several clinical practice
guidelines on the management of dementia are available, but
their quality is unclear. A standard methodology such as
the Appraisal of Guidelines Research and Evaluation (AGREE,
2003a,b) instrument is available for the quality assessment of
clinical practice guidelines, with a focus on the development
process.

1568-1637/$ – see front matter © 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.arr.2011.07.002
 M. Azermai et al. / Ageing Research Reviews 11 (2012) 78–86
For the management of BPSD, clinical practice guidance is par-
ticularly scarce. Additionally, to assess the quality of evidence and
strength of recommendations, a variety of grading systems exists
(Atkins et al., 2004), which further complicates the task of inter-
pretation for the practitioner (Guyatt et al., 2006).
To our knowledge, no systematic attempts have been made
to compare recommendations from existing dementia guidelines
with regard to BPSD.
Therefore, the aim of this study was to offer a pragmatic
synthesis of existing specific practice recommendations for the
management of BPSD. We collected and appraised the quality of
existing clinical practice guidelines on management of dementia,
focusing on or mentioning BSPD; extracted specific practice rec-
ommendations for BPSD from selected guidelines; and selected key
practice recommendations for which there is sufficient agreement
among guidelines.
2. Methods
2.1. Data sources
A systematic search for existing clinical practice guidelines
on dementia or BPSD was performed in electronic databases.
We searched Medline with Pubmed, the Database of Reviews of
Effects (DARE) and Health Services/Technology Assessment Texts
(HSTAT). Also, we searched web sites of guideline organisations
such as New Zealand Guidelines group, National Guideline Clear-
inghouse (NGC), National Institute of Health and Clinical Excellence
(NICE), Scottish Intercollegiate Guidelines (SIGN), and Guidelines
International Network (GIN). Additionally, we hand searched web
sites of relevant medical societies. The following search string
was used in Pubmed, with Medical Subject Headings (MeSH):
(“Dementia”[Mesh] AND (“Behavioural Symptoms”[Mesh] OR “Aggres-
sion”[Mesh])) AND “Aged”[Mesh]. The limits were: practice guideline
as publication type, published between 2003 and 2010, English or
Dutch language.
A flowchart of the search is presented in Fig. 1.
2.2. Guideline selection
The retrieved guidelines were scrutinised in the title and in the
abstract for mentioning of management of Alzheimer’s dementia or
BPSD, and if so, read in full to confirm whether they were fully or
partly dedicated to the management of BPSD. Dementia guidelines
were not selected if the scope was screening, diagnosis, evaluation
of dementia or cognitive decline, care for families, and if manage-
ment of BPSD was not addressed. The remaining guidelines were
considered and selected as eligible for quality appraisal by AGREE.
MEDLINE
12 962 citations
12 942 excluded based on
predefined filter practice
guidelines (as publication type)
20 guidelines
retrieved
13 guidelines excluded
based on exclusion criteria
7 relevenant
guidelines selected
15 practice guidelines
included for quality appraisal
Fig. 1. Flowchart of the systematic search.
79
2.3. Guideline quality appraisal
Quality of selected clinical practice guidelines regarding man-
agement of dementia was appraised by 2 independent reviewers
(MA and MP), using the standardised AGREE instrument. Differ-
ences were resolved by mutual consensus.
The AGREE instrument consists of 23 items covering 6 domains:
scope and purpose (overall aim, clinical questions and target popu-
lation), stakeholder involvement (representation of the view of the
intended users), rigour of development (process of obtaining evi-
dence and formulating recommendations), clarity and presentation
(language and format), applicability (organizational, behavioural
and cost implications), and editorial independence (conflict of
interest and independence of the recommendations). Each item
rated on a 4-point scale, ranging from strongly disagree (score 1) to
strongly agree (score 4) (AGREE, 2003a,b). Rigour of development
is the largest domain scored by 7 items, while editorial indepen-
dence is the smallest domain scored by 2 items. For each domain a
standardised domain score can be calculated by:
obtained items score − minimum possible items score
maximum possible items score − minimum possible items score
The 6 domain scores are independent and not intended for
aggregation into a summarising overall single quality score.
Based on these standardised domain scores guidelines can be
classified in 4 categories: high overall quality guideline (most
domain scores >60%), moderate overall quality guideline (most
domain scores between 30% and 60%), low overall quality guide-
line (most domain scores <30%), or a guideline with unclear result
regarding its quality (AGREE manual, 2003; Watine et al., 2006).
Only the guidelines labelled as high quality guidelines with
AGREE were included and submitted to the next process.
2.4. Recommendation extraction process
Included guidelines were analysed in depth by one reviewer
(MA) for the extraction of specific practice recommendations,
using the conceptual frameworks of a document-centric approach
(Shiffman et al., 2004), with the intention to model rec-
ommendations extracted from clinical practice guidelines into
computer-interpretable and -executable formats (Kaiser et al.,
2007). The chapters regarding management of BPSD within each
guideline were first identified and then screened for specific prac-
tice recommendations. The BPSD spectrum includes a variety of
non-cognitive symptoms, but we focused on those symptoms
most addressed by guidelines i.e. agitation, aggression, psychotic
symptoms and depression. Finally, specific practice recommen-
dations for BPSD were listed per guideline into a summarising
table and classified into non-pharmacological and pharmacological
hand search of web sites
15 guidelines retrieved
7 guidelines
excluded based on
exclusion criteria
8 relevenant
guidelines selected
80 M. Azermai et al. / Ageing Research Reviews 11 (2012) 78–86
interventions, supplemented by the results of their grading process
of the quality of the supporting evidence and the strength of the
recommendation, as indicated by each guideline.
2.5. Appraisal of the level of agreement
In case several guidelines were available for one specific prac-
tice recommendation, we assessed the level of agreement between
those guidelines with regard to the appraisal of quality of evi-
dence and strength of recommendation. If ¾ or more guidelines
addressing the specific practice recommendation supported the
recommendation (i.e. no conflict), and if no inconsistency was
observed in quality appraisal of supporting evidence with maxi-
mum one guideline indicating insufficient evidence, then the level
of agreement among guidelines for a specific practice recommen-
dation was found to be sufficient. These criteria were defined a
posteriori. Only specific practice recommendations for which the
level of agreement was sufficient, were selected as key recommen-
dations.
3. Results
3.1. Systematic search for guidelines
The broad Pubmed search profile for MEDLINE resulted in 12 962
citations, which were reduced by the filter to 20 practice guide-
lines in English or in Dutch, published between 2003 and November
2010. The hand search of web sites of medical societies and guide-
line organisations resulted in an additional 15 practice guidelines.
Hence, 35 potentially relevant guidelines on dementia were
retrieved, and analysed in full.
Of the 20 guidelines retrieved in MEDLINE, 13 were not selected
(9 did not focus on the management of Alzheimer’s dementia, 4
did not address the management of BPSD). The remaining 7 guide-
lines were retained. In the analysis of the 15 eligible guidelines
retrieved from the web, 7 were excluded (because not address-
ing the management of BPSD). None of the remaining 8 guidelines
were retrievable in MEDLINE. In total, 15 (7 from Medline: AGS
& AAGP, 2003; DCGP, 2005; Caltagirone et al. (IAP), 2005; AAN,
2005; EFNS, 2006; CCC, 2007; APA, 2007 and 8 from the web: MOH
Malaysia, 2009; Group Health, 2009; BCMA, 2008; MOH Singapore,
2007; NICE, 2006; SIGN, 2006; CCSMH, 2006; RACGP, 2003) clinical
practice guidelines on the management of dementia with attention
to BPSD were selected, and appraised for quality with AGREE. Only
one guideline was exclusively focused on management of mental
and behavioural problems in residential care (CCSMH, 2006).
The search was repeated in January 2011 and yielded no new
clinical practice guidelines on management of dementia.
A description of the selected clinical practice guidelines is pre-
sented in Table 1.
3.2. Quality appraisal of the selected guidelines by the AGREE
instrument
The 15 selected clinical practice guidelines on management of
dementia scored well on scope/purpose, with 12 guidelines scor-
ing over 60%; and on clarity/presentation with 9 guidelines scoring
over 60%. For rigour of development, 8 guidelines scored over 60%.
Domain scores were not as good for stakeholder involvement, with
3 scoring over 60%, and worse for editorial independence and appli-
cability with respectively 5 guidelines and 1 guideline scoring over
60%.
Five clinical practice guidelines were appraised as high qual-
ity guidelines and therefore included, because in their evaluation
with the AGREE instrument most of the standardised domain scores
were 60% or higher (see Section 2 and Table 2).
The 5 high quality guidelines were subjected to the next process.
3.2.1. Extraction of specific practice recommendations
From 5 high quality guidelines, we extracted 18 specific practice
recommendations on the management of BPSD in terms of agita-
tion, aggression, psychotic symptoms and depression. All of these
recommendations were proposed by more than one guideline. In
Box 1, the different grading systems used by these 5 guidelines are
outlined.
The 18 specific practice recommendations for management of
BPSD were classified into non-pharmacological and pharmacolog-
ical interventions (see Table 3).
Recommendations with regard to non-pharmacological treat-
ment included aroma therapy, multisensory stimulation, music,
bright light therapy, and behaviour management.
Recommendations with regard to pharmacological treatment
included drug classes such as antipsychotics, benzodiazepines,
antidepressants and acetylcholinesterase inhibitors (A-ChI).
3.2.1.1. Non-pharmacological treatment. In general, clinical prac-
tice guidelines on management of dementia recommended to start
non-pharmacological interventions first, and initiate medication
only in case of failure of these non-pharmacological treatments.
Some dementia guidelines stated that non-pharmacological inter-
ventions should be started in combination with medication.
Non-pharmacological approaches for the management of BPSD
were addressed by 4 out of 5 included dementia guidelines.
Aroma therapy (addressed by 4 guidelines, recommended by 2)
The majority of dementia guidelines concluded that aroma ther-
apy may be of some benefit, but that a strong evidence base was
lacking. The use of aromatherapy was only supported by 2 guide-
lines (NICE, CCC) and judged by others (SIGN, MOH (M)) as having
too weak evidence to recommend its use. There was insufficient
level of agreement among dementia guidelines to support the use
of aroma therapy for management of BPSD.
Multisensory stimulation (addressed by 4 guidelines, recom-
mended by 2)
There was clear inconsistency among guidelines in the grading
of the recommendation for multisensory stimulation. The recom-
mendation of NICE and CCC was based on low quality evidence,
while SIGN only recommended multisensory stimulation in mild
and not in severe dementia. The recommendation was strongly
rejected by MOH (M). There was insufficient agreement among
dementia guidelines to support the use of multisensory stimula-
tion for management of BPSD.
Music therapy (addressed by 4 guidelines, recommended by 3)
The therapeutic use of music for BPSD was recommended by
NICE, CCC, and MOH (M). Their appraisal of the quality of evidence
ranged from moderate to high. SIGN appraised the evidence as
insufficient to make a recommendation.
We estimated that the level of agreement among dementia
guidelines to support the use of music therapy for management
of BPSD was sufficient.
Massage (addressed by 3 guidelines, recommended by 2)
Two guidelines (NICE, CCC) recommended the use of massage
for BPSD but differed in their quality appraisal of supporting evi-
dence, while another guideline (SIGN) concluded that there was
insufficient evidence to recommend its use.
We estimated that the level of agreement among dementia
guidelines to support the use of massage for management of BPSD
was insufficient.
Bright light therapy (addressed by 3 guidelines, recommended by
1)
SIGN rejected bright light therapy based on expert opinion,
while CCC recommended its use based on low quality evidence
and MOH (M) concluded that there was insufficient evidence.
Table 1
Description of the selected dementia guidelines for quality appraisal.

Guideline Abbreviation Country Year Diagnosis Management Management No. of references Grading Funding
development dementia dementia BPSD evidence
group

1. Ministry of Health MOH (M) Malaysia 2009 x x 333 Yes Yes (pharmaceutical)
Malaysia
2. Group Health GH America 2009 x x x 31 No Not stated
3. British Columbia BMCA Canada 2008 x x x 18 No Not stated
Medical
Association
4. American APA America 2007 x x 289 Yes Yes (pharmaceutical)
Psychiatric

M. Azermai et al. / Ageing Research Reviews 11 (2012) 78–86

Association
5. 3rd Canadian CCC Canada 2007 x x x 18 Yes Yes (pharmaceutical)
Consensus
Conference
6. Ministry of Health MOH (S) Singapore 2007 x x x 162 Yes Not stated
Singapore
7. European EFNS Europe 2006 x x x 253 Yes Yes (non-pharmaceutical)
Federation of
Neurological
Societies
8. National Institute NICE United Kingdom 2006 x x x 768 Yes Yes (non-pharmaceutical)
for Health and
Clinical Excellence
9. Scottish SIGN 2006 x x 183 Yes Not stated
Intercollegiate
Guideline Network
10. Canadian Coalition CCSMH Canada 2006 x 36 Yes Yes (non-pharmaceutical)
for Seniors Mental
Health
11. American Academy AAN America 2005 x x 175 Yes Not stated
of Neurology
12. Italian Association IAP Italy 2005 x x 276 Yes Yes (pharmaceutical)
of Psychogeriatrics
13. Dutch College of DCGP The Netherlands 2005 x x x 265 Yes Yes (non-pharmaceutical)
Clinical Geriatrics
14. American Geriatric AGS&AAGP America 2003 x 57 Yes Yes (pharmaceutical)
Society and
American
Association for
Geriatric
Psychiatry
15. Royal Australian RACGP Australia 2003 x x 29 No Yes (non-pharmaceutical)
College of General
Practitioners

81
82 M. Azermai et al. / Ageing Research Reviews 11 (2012) 78–86
Box 1: Summary of grading systems used in included clinical practice guidelines for the management of dementia.
Level of evidence
Dutch college of clinical geriatrics
A1 Systematic reviews that include some studies of A2 level, of which
results of individual studies are consistent
A2 Randomized clinical trials of good quality (randomized, double-blind
controlled trials) of sufficient size and consistency
B Randomized clinical trials of moderate quality or insufficient size or
other competition (non-randomized, comparative cohort studies,
case-control studies)
C Non-comparative research
D Expert opinion, e.g. working group members
National Institute for Health and Clinical Excellence
High Further research is very unlikely to change our confidence in the
estimate of the effect
Moderate Further research is likely to have an important impact on our
confidence in the estimate of the effect and may change the estimate
Low Further research is very likely to have an important on our confidence in
the estimate of the effect and is likely to change the estimate
Very low Any estimate of the effect is very uncertain
Scottish intercollegiate guideline network
1++ High quality systematic reviews of RCTs, or RCTs with very low risk of
bias
1+ Well conducted meta-analyses, systematic reviews of RCTs, or RCTs
with a low risk of bias
1- Meta-analyses, systematic reviews of RCTs, or RCTs with high risk of
bias
2++ High quality systematic reviews of case control or cohort studies; high
quality case control studies or cohort studies with very low risk of bias
and a high probability that the relationship is causal
2+ Well conducted case control or cohort studies with low risk of bias and
a significant risk that the relationship is not causal
3 Non-analytic studies (case reports, case series)
4 Expert opinion
Canadian consensus conference (3rd)
1 Evidence obtained from at least 1 properly RCT
2.1 Evidence obtained from well-designed controlled trials without
randomization, or
2.2 Evidence obtained from well-designed cohort or case-control analytic
studies preferably from more than 1 centre or research group, or
2.3 Evidence obtained from comparisons between time or places with or
without the intervention. Dramatic results in uncontrolled experiments
are included in this category
3 Opinions of respected authorities based on clinical experience,
descriptive studies or expert committees
Academy of medicine of Malaysia and ministry of health
1 Evidence obtained from at least 1 properly RCT
II-1 Evidence obtained from well-designed controlled trials without
randomization, or
II-2 Evidence obtained from well-designed cohort or case-control analytic
studies preferably from more than 1 centre or research group, or
II-3 Evidence obtained from comparisons between time or places with or
without the intervention. Dramatic results in uncontrolled experiments
are included in this category
III Opinions of respected authorities based on clinical experience,
descriptive studies or expert committees
There was insufficient agreement among dementia guidelines to
support the use of bright light therapy for management of BPSD.
Behaviour management (addressed and recommended by 3 guide-
lines)
The term ‘behaviour management’, is used to reflect ‘structured,
systematically applied and normally time-limited interven-
tions usually carried out by carers or care home staff under
Level of recommendations
1 A systematic review (A1) or at least two independent other studies
conducted at level A1 or A2
2 At least two independently conducted studies level B
3 At least one study of level A2 or B, or studies of level C level
4 Expert opinion, for example, the working group members
No explicit grading of the strength of recommendation
A At least 1 meta-analysis, systematic review of RCTs, or RCT rated as
1++ and directly applicable to the target population; or A body of
evidence consisting principally of studies rated as 1+, directly
applicable to the target population, and demonstrating overall
consistency of results
B A body of evidence including studies rated as 2++, directly
applicable to the target population, and demonstrating overall
consistency of results; or Extrapolated evidence from studies rated as
1++ or 1+
C A body of evidence including studies rated as 2+, directly
applicable to the target population and demonstrating overall
consistency of results; or Extrapolated evidence from studies rated as
2++
D Evidence level 3 or 4; or extrapolated evidence from studies rated
as 2+
Good practice points (GPP):
Recommended best practice based on clinical experience
A There is good evidence to support this manoeuvre
B There is fair evidence to support this manoeuvre
C There is insufficient evidence to recommend for or against this
manoeuvre but recommendations may be made on other grounds
D There is fair evidence to recommend against this procedure
E There is good evidence to recommend against this procedure
A At least 1 meta-analysis, systematic review, or RCT, or evidence
rated as good and directly applicable to the target population
B Evidence from well conducted clinical trials, directly applicable to
the target population, and demonstrating overall consistency of
results, or evidence extrapolated from meta-analysis, systematic
review, or RCT
C Evidence of expert opinion in the absence of applicable good
clinical studies
the supervision of a professional with expertise in this area’
(SIGN, 2006). Quality appraisal of supporting evidence and
strength of recommendation was consistent among the 3
guidelines.
There was sufficient agreement among dementia guidelines to
support the use of behaviour management for management of
BPSD, in particular for depression.
 M. Azermai et al. / Ageing Research Reviews 11 (2012) 78–86 83

Table 2
Quality appraisal by the AGREE instrument of dementia guidelines.

Guideline development group Abbreviation Domains of appraisal*

Scope and Stakeholder Rigour of Clarity and Applicability Editorial independence

purpose involvement development presentation

Included guidelines
Dutch College of Clinical Geriatrics DCCG 94 79 90 87 33 8
National Institute for Health and Clinical NICE 89 88 81 96 72 83
Excellence
Scottish Intercollegiate Guideline Network SIGN 61 58 92 92 39 8
3rd Canadian Consensus Conference CCC 83 58 71 63 8 92
Ministry of Health Malaysia MOH (M) 100 58 96 92 33 58
Excluded guidelines
Group Health GH 17 37 35 38 22 8
British Columbia Medical Association BCMA 50 37 22 79 17 8
American Psychiatric Association APA 78 54 71 42 8 75
Ministry of Health (Singapore) MOH 67 58 57 88 8 8
European Federation of Neurological EFNS 61 42 67 58 17 83
Societies
Canadian Coalition for Seniors Mental Health CCSMH 78 58 57 88 33 67
American Academy of Neurology AAN 61 21 76 38 17 8
Italian Association of Psychogeriatrics IAP 39 50 48 46 33 8
American Geriatric Society and American AGS&AAGP 83 29 31 50 11 33
Association for Geriatric Psychiatry
Royal Australian College of General RCGP 61 71 26 67 17 8
Practitioners

Moderate quality: most domain scores 30–60%.

Low quality: most domain scores < 30%.
*
High quality: most domain scores > 60%.

3.2.1.2. Pharmacological treatment. BPSD in Alzheimer’s dementia. However, guidelines differed in

Antipsychotics (addresses and recommended by 5 guidelines)
The use of antipsychotics was addressed by all guidelines.
Sufficient level of agreement was found for the efficacy of
antipsychotics (risperidone, olanzapine, haloperidol) in case of
agitation/aggression/psychosis (recommendation addressed and
recommended by 4 guidelines).
No agreement among guidelines was found for a clear choice
between typical or atypical antipsychotic agents. Four guidelines
(DCCG, SIGN, CCC, MOHM) recommended atypical antipsychotics,
of which 2 guidelines (DCCG, SIGN) additionally recommended
typical antipsychotics. Two guidelines (NICE, MOH (M)) addition-
ally concluded that the choice of an antipsychotic agent should
be based on an individual risk/benefit analysis.
Three guidelines (DCCG, CCC, MOH (M)) recommenced the
time-limited use of antipsychotics and regular periods of re-
assessment, but with varying appraisals of supporting evidence.
Only 2 guidelines (CCC, MOH (M)) addressed discontinua-
tion of antipsychotics. Both recommended discontinuation in a
standardised fashion after a period of behavioural stability (3-6
months), but with varying appraisals of supporting evidence.
Benzodiazepines (addressed and recommended by 3 guidelines)
There was sufficient agreement among dementia guidelines
to support the short-term use of benzodiazepines in case of
acute agitation or agitation based on anxiety, but with varying
appraisals of supporting evidence.
Antidepressants (addressed and recommended by 5 guidelines)
The use of antidepressants (i.e. Selective Serotonine Reuptake
Inhibitors) was addressed and recommended by 5 guidelines, but
with varying appraisal of the quality of the supporting evidence.
We considered the level of agreement for the use of antidepres-
sants for co-morbid depression in BSPD patients to be sufficient.
Acetylcholinesterase inhibitors (A-ChI) (addressed by 4 guidelines
with divergent recommendations)
The oldest guideline (DCCG, 2005) concluded that there was
insufficient evidence to support the use of A-ChI for management
of BPSD. More recent guidelines supported the use of A-ChI for
their recommendations when separating A-ChI into donepezil,
galantamine or rivastigmine.
- NICE recommended donepezil for BPSD, while galantamine and
rivastigmine were not recommended because of insufficient
evidence for BPSD in Alzheimer’s dementia.
- SIGN recommended all A-ChI (donepezil, galantamine and
rivastigmine) in specified dosages for the management of BPSD.
- CCC recommended the use of A-ChI without a further specifica-
tion of active substances.
- MOH (M) recommended the use of A-ChI for BPSD, but
donepezil as first choice in Alzheimer’s dementia.
A superficial agreement with varying appraisal of the quality
of the supporting evidence exists among dementia guidelines for
the use of A-ChI for management of BPSD, with no agreement as
to the choice of A-ChI.
Therefore, we estimated that the level of agreement among
guidelines to support the use of A-ChI for BPSD is insufficient.
- Memantine (addressed by 4, recommended by 2 guidelines)
Memantine was recommended by 2 guidelines (CCC, MOH (M)),
while 2 other guidelines (NICE, SIGN) concluded that there was
insufficient evidence to recommend its use. There was an insuf-
ficient level of agreement among dementia guidelines to support
the use of memantine for BPSD.
3.3. Key recommendations
An overview of 9 specific practice recommendations, selected
as key recommendations, because the level of agreement among
guidelines was considered as sufficient, is given in Box 2 .
4. Discussion
To our knowledge, this study the first systematic review where
an effort was made to systematically appraise specific practice
recommendations of several guidelines on the clinical topic of
behavioural and psychological symptoms of dementia (BPSD).
84 M. Azermai et al. / Ageing Research Reviews 11 (2012) 78–86

Table 3
Recommendations for management of BPSD extracted from included dementia guidelines.

Recommendations (grading)b Included guidelinesa Sufficient agreement?

DCCG (2005) NICE (2006) SIGN (2006) CCC (2007) MOH (M) (2009)

Non-pharmacological treatment
Use of aroma therapy
Use of multisensory stimulation
Use of music
Use of massage and touch
interventions
Use of bright light therapy
Use of behaviour management
/ * * *
· + (moderate) ? + (C2) ? No
· + ? (gpp) + (C2) −(A) No
· + (moderate) ? + (B1) + (A) Yes
· + (moderate) · + (C2) ? No
· · − (gpp) + (C2) ? No
· + (moderate) + (B) + (B1) · Yes

Pharmacological treatment * * / * *
After trial of non-pharmacological + (4) + · + (C1) +(C) Yes
interventions or in combination
with non-pharmacological
interventions or when
non-pharmacological
interventions have failed
Antipsychotics * * * * *
For (severe) psychosis and/or + (1) + · + (A1) + (A) Yes
aggression/agitation
Use of atypical antipsychotics + (1) · + (gpp) + (A1) + (A) Yes
(risperidone, olanzapine)
Use of conventional antipsychotics + (1) · + (A) · · Yes
(haloperidol)
Choice based on individual · + · · + (C) Yes
risk/benefit analysis
Start at low dose and titrate upwards · + · + (B3) + (C) Yes
Time-limited use and regular + (4) + · +(B3) +(C) Yes
reassessment (every 3 months or
according to clinical need)
Withdrawal after behavioural · · · + (A1) +(C) Yes
stability
Benzodiazepines * * / * /
For acute agitation or agitation based + (3,4) + · + (B1) · Yes
on anxiety (short-term use)
Antidepressants * * * *
For comorbid depression use of + (2) + (moderate) + (D) + (B3) + (A) Yes
selective serotonine reuptake
inhibitors
Acetylcholinesterase inhibitors (A-ChI) * * * * *
Use of A-ChI ? + (moderate) + (B) + (B3) + (B) No
Memantine / * * * *
Use of memantine · ? ? + (B3) B No

Symbols: *: Addressed in the guideline; /: not addressed in the guideline; +: recommended for management of behavioural and psychological symptoms of dementia (BPSD);
–: not recommended for management of BPSD; ?: insufficient evidence to formulate a recommendation; ·: missing.
a
Abbreviations of included guidelines are explained in Tables 1 and 2.
b
Grading levels of each guideline are presented in Box 1.

Our systematic Pubmed search for clinical practice guidelines
on management of dementia was highly efficient to find guidelines
available in bibliographic databases. Efficiency was achieved using
the limit feature, and the search performance showed a recall of
100% and a precision of 7/20. However, it was necessary to sup-
plement the search in databases by a hand search of web sites, as
this resulted in a surprisingly high number of additional relevant
guidelines. We retrieved a total of 15 clinical practice guidelines
with regard to management of dementia, of which 14 were partly
and only 1 was fully dedicated to the management of BPSD. Four
out of 5 included guidelines were retrieved through the Web,
indicating that a search in Medline will miss too much valuable
information.
The appraisal of dementia guidelines with the AGREE instru-
ment revealed an overall moderate quality, but with a wide vari-
ation in quality domain scores. In general, the domains of applica-
bility and editorial independence need more attention, as was also
previously observed by others (Lopez-Olivo et al., 2008). Potential
costs and organisation barriers were significant flaws in the appli-
cability domain, while low scores for editorial independence were
more often the result of lack of information regarding the influence
of funding, rather than actually confirmed conflict of interest.
In this study we extracted specific practice recommendations
for management of BPSD from tertiary information sources (guide-
lines), without considering secondary sources (systematic reviews)
and primary evidence (RCTs). We included 5 rigorously devel-
oped clinical practice guidelines on management of dementia for
extraction of specific practice recommendations. We examined the
divergent methods for the appraisal of the quality of supporting
evidence and strength of these recommendations, and compared
the differences in appraisal. Additionally, we attempted to develop
a systematic approach to synthesize the quality appraisal of spe-
cific practice recommendations in different guidelines. However,
variation in use of grading system complicated interpretation, com-
parison and generalisability of recommendations among guidelines
(Box 1). Grading systems consisted of 2 axes, 1 for the level of
evidence and 1 for the strength of recommendation. Included
guidelines (n = 5) used 3 different grading systems for the level
of evidence and 4 different grading systems for the strength of
recommendations. Recommendations were usually in the positive
direction, except for 1 guideline (CCC) that used bipolar recommen-
dations for or against an intervention.
We tried to resolve the problem of different grading systems
by assessing the level of agreement among guidelines regarding
 M. Azermai et al. / Ageing Research Reviews 11 (2012) 78–86
Box 2: Summary of 9 key specific practice recommen-
dations for management of BPSD.
If a person with dementia shows distressing behavioural symptoms
Then → consider non-pharmacological interventions first with most evidence
for music and behavioural management for depression
If non-pharmacological approaches have failed
Then → consider psychotropic medication
If a person with dementia shows co-morbid depression
Then → consider antidepressants (preferably SSRIs)
If a person with dementia shows distressing acute agitation or agitation based
on anxiety
Then → consider the short-term use of benzodiazepines (with caution)
If a person shows severe agitation/aggression and/or psychosis
Then → consider antipsychotic medication
If antipsychotic medication is considered
Then → carefully evaluate the individual risks (e.g. cardiovascular) and
benefits to make a choice for typical or atypical agents
If an antipsychotic is started
Then → initiate a low starting dose and titrate upwards in function of the
resident’s response and presence of adverse events
If an antipsychotic is started
Then → treatment should be time-limited and regularly reviewed (every 3
months or according to clinical need)
If there is a period of behavioural stability
Then → periodical attempts of antipsychotic discontinuation should be
considered
specific practice recommendations, based on criteria a posteriori
defined by the reviewers. These criteria need to be further listed,
elaborated and validated.
Our goal was to select key recommendations for behavioural and
psychological symptom management from rigorously developed
dementia guidelines. For a specific practice recommendation to be
a key recommendation, the level of agreement among the different
guidelines with regard to the quality of the supporting evidence and
the strength of the recommendation needed to be sufficient. We
found that non-pharmacological interventions as first-step treat-
ment for BPSD are discussed at length in dementia guidelines.
However, individual interventions are often not supported by a
majority of guidelines, and the recommending guidelines acknowl-
edge the low quality of supporting evidence.
The question whether atypical over typical antipsychotics
should be preferred, remains unanswered after comparing guide-
lines. Individual risk-benefit analysis of each class for a specific
indication by the treating physician remains crucial when prescrib-
ing an antipsychotic agent. There was agreement among guidelines
for the use of risperidone, olanzapine and haloperidol since claims
for efficacy are more supported with high quality studies. When
looking closer into primary evidence for the efficacy of antipsy-
chotics for BPSD, we found that there is modest efficacy for
haloperidol in terms of aggression (Lonergan et al., 2002). As for
the atypical antipsychotics (i.e. the most researched risperidone
and olanzapine), there is a modest efficacy for aggression and psy-
chosis, but the evidence with regard to efficacy for other BPSD
symptoms is not convincing (Ballard and Waite, 2006; Ballard et al.,
2008). There is insufficient evidence for the efficacy of other atypi-
cal antipsychotics (Ballard et al., 2008). Also, credible head-to-trials
on comparative efficacy of typical and atypical antipsychotics on
specific manifestations of BPSD are needed.
Atypical antipsychotics have almost completely replaced typi-
cal antipsychotics, because they were perceived as having a better
side-effect profile (Briesacher et al., 2005). However, more recently,
warnings (FDA, 2005, 2008; MHRA, 2008, 2009) have been issued
that all antipsychotics have increased risk of stroke and a (smaller)
risk of mortality, and are not recommended for the off-label treat-
ment of BPSD.
85
Additionally, there is more to risk-benefit analysis than
appraisal of evidence of efficacy alone, especially when, adverse
events might outweigh the benefits (as in the case of antipsy-
chotics). This is the reason why our study, nor guidelines offer a
clear choice of antipsychotic agents.
Guidelines also agreed on the time-limited use of antipsy-
chotics for severe non-cognitive symptoms defined as agitation,
aggression, and psychotic symptoms. Planned discontinuation was
addressed by 2 guidelines, and both recommended discontinu-
ation of antipsychotics in a standardised fashion after a period
of behavioural stability. A Cochrane review (De Clercq et al., in
preparation) investigates whether antipsychotics can be promptly
stopped in older patients with dementia without having a signif-
icant effect on behavioural outcome measures objectivised by the
use of a standardised behavioural scoring instrument.
Most dementia guidelines superficially agree, with varying
appraisal of the quality of the supporting evidence, that acetyl-
cholinesterase inhibitors (A-ChI) may be used for treatment of
BPSD. Although some trials have indeed shown statistically signif-
icant efficacy for A-ChI in the BPSD treatment, the relevance of the
clinical effect remains questionable (Sink et al., 2005; Rodda et al.,
2009).
Antidepressants can not consistently be recommended for BPSD
other than depression. Benzodiazepines may be used (short-term)
for acute agitation or agitation based on anxiety. Caution is even
required when prescribing benzodiazepines in older adults with
dementia since adverse events may include increased agitation,
confusion and consecutive risk of falling and fractures (Woolcott
et al., 2009), and finally potential cognitive decline (Eggermont
et al., 2009).
In general, guidance on the management of BPSD in existing
dementia guidelines was superficial, without further elaboration
on specific indications, pharmacotherapeutic dosages, and discon-
tinuation programs. The use of physical restraints was seldom
addressed, although still often used in the approach of disruptive
behaviour caused by dementia (Hamers and Huizing, 2005; Meyer
et al., 2009).
Our study has some limitations. The validated and frequently
used AGREE instrument judges the overall quality of the guideline
focusing on the development process, not the quality of the rec-
ommendations within the guidelines. Because low methodological
domain scores in AGREE are a risk factor for suboptimal guideline
and therefore suboptimal recommendations within the guideline,
it is necessary to avoid inclusion of low quality guidelines with erro-
neous recommendations, only adding to the general confusion of
conflicting recommendations.
Included guidelines dated from 2005 to 2009. This time lap
might lead to divergent recommendations based on collections of
evidence of a different age or different interpretations by the devel-
opment group of the same evidence. The evaluation of the level
of agreement among dementia guidelines for specific practice rec-
ommendations was based on a posteriori defined and not-validated
criteria, which might seem arbitrary. To our knowledge, no other
systematic attempts have been made to compare recommenda-
tions from existing dementia guidelines with regard to BPSD, and
we hope our proposal can evolve into a priori criteria for future
research.
None of the included guidelines used a complete GRADE (Grades
of Recommendation, Assessment, Development, and Evaluation)
systematic approach. We first tried to adopt GRADE as an over-
arching instrument in the appraisal of what several guidelines tell
on one specific practice guideline. However, after consulting the
GRADE working group it appeared that use of GRADE to synthesise
strength of recommendations as appraised by different guideline
development groups would be methodologically incorrect without
the re-appraisal of supporting studies. We therefore restricted our-
86 M. Azermai et al. / Ageing Research Reviews 11 (2012) 78–86
selves to an appraisal of the level of agreement between guidelines
and to those specific practice recommendations for which the level
of agreement was judged as sufficient.
Further research is needed to explore whether valid methods
can be developed to appraise quality of supporting evidence and
strength of extracted specific practice recommendations, when the
level of agreement between guidelines is insufficient, without hav-
ing to resort to laborious re-appraisal of primary evidence.
Finally, there is need for more elaborated guidelines focusing
on management of BPSD and for more substantial research on the
various details of initiating, monitoring and tapering of therapy.
Specific practice recommendations for the management of BPSD
in existing dementia guidelines should be more specifically for-
mulated, with further efforts to synchronise the reporting of the
appraisal of level of supporting evidence, and of the appraisal of
the strength and clinical relevance of recommendations for the
practitioner.
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