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Ageing Research Reviews 11 (2012) 78–86

Contents lists available at ScienceDirect

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


adverse effects associated with antipsychotic treatment and to the
Behavioural and psychological symptoms of dementia (BPSD) absence of credible alternatives. Additionally, BPSD are important
comprise a broad spectrum of non-cognitive symptoms including risk factors for care giver burden and institutionalisation (Fersch
physical aggression, agitation, hallucinations, depression, delu- and Falzgraf, 2007).
sions, wandering and sleep disturbances (Petrovic et al., 2007; The Institute of Medicine defines clinical practice guidelines
Liperoti et al., 2008). Up to 80% of patients with Alzheimer’s demen- as ‘systematically developed statements to assist practitioner
tia may develop periodic episodes or chronic behavioural and and patient decisions about appropriate health care for spe-
psychological symptoms in their course of illness (Lyketsos et al., cific clinical circumstances’ (Field, 1990). Several clinical practice
2002). Management of BPSD is an important but complex com- 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,
∗ Corresponding author at: Ghent University, Heymans Institute of Pharmacology,
2003a,b) instrument is available for the quality assessment of
De Pintelaan 185, 1 Blok B, 9000 Ghent, Belgium.
clinical practice guidelines, with a focus on the development
E-mail address: majda.azermai@ugent.be (M. Azermai). 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 79

For the management of BPSD, clinical practice guidance is par- 2.3. Guideline quality appraisal
ticularly scarce. Additionally, to assess the quality of evidence and
strength of recommendations, a variety of grading systems exists Quality of selected clinical practice guidelines regarding man-
(Atkins et al., 2004), which further complicates the task of inter- agement of dementia was appraised by 2 independent reviewers
pretation for the practitioner (Guyatt et al., 2006). (MA and MP), using the standardised AGREE instrument. Differ-
To our knowledge, no systematic attempts have been made ences were resolved by mutual consensus.
to compare recommendations from existing dementia guidelines The AGREE instrument consists of 23 items covering 6 domains:
with regard to BPSD. scope and purpose (overall aim, clinical questions and target popu-
Therefore, the aim of this study was to offer a pragmatic lation), stakeholder involvement (representation of the view of the
synthesis of existing specific practice recommendations for the intended users), rigour of development (process of obtaining evi-
management of BPSD. We collected and appraised the quality of dence and formulating recommendations), clarity and presentation
existing clinical practice guidelines on management of dementia, (language and format), applicability (organizational, behavioural
focusing on or mentioning BSPD; extracted specific practice rec- and cost implications), and editorial independence (conflict of
ommendations for BPSD from selected guidelines; and selected key interest and independence of the recommendations). Each item
practice recommendations for which there is sufficient agreement rated on a 4-point scale, ranging from strongly disagree (score 1) to
among guidelines. 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
2. Methods
standardised domain score can be calculated by:
2.1. Data sources obtained items score − minimum possible items score
maximum possible items score − minimum possible items score
A systematic search for existing clinical practice guidelines
The 6 domain scores are independent and not intended for
on dementia or BPSD was performed in electronic databases.
aggregation into a summarising overall single quality score.
We searched Medline with Pubmed, the Database of Reviews of
Based on these standardised domain scores guidelines can be
Effects (DARE) and Health Services/Technology Assessment Texts
classified in 4 categories: high overall quality guideline (most
(HSTAT). Also, we searched web sites of guideline organisations
domain scores >60%), moderate overall quality guideline (most
such as New Zealand Guidelines group, National Guideline Clear-
domain scores between 30% and 60%), low overall quality guide-
inghouse (NGC), National Institute of Health and Clinical Excellence
line (most domain scores <30%), or a guideline with unclear result
(NICE), Scottish Intercollegiate Guidelines (SIGN), and Guidelines
regarding its quality (AGREE manual, 2003; Watine et al., 2006).
International Network (GIN). Additionally, we hand searched web
Only the guidelines labelled as high quality guidelines with
sites of relevant medical societies. The following search string
AGREE were included and submitted to the next process.
was used in Pubmed, with Medical Subject Headings (MeSH):
(“Dementia”[Mesh] AND (“Behavioural Symptoms”[Mesh] OR “Aggres-
2.4. Recommendation extraction process
sion”[Mesh])) AND “Aged”[Mesh]. The limits were: practice guideline
as publication type, published between 2003 and 2010, English or
Included guidelines were analysed in depth by one reviewer
Dutch language.
(MA) for the extraction of specific practice recommendations,
A flowchart of the search is presented in Fig. 1.
using the conceptual frameworks of a document-centric approach
(Shiffman et al., 2004), with the intention to model rec-
2.2. Guideline selection ommendations extracted from clinical practice guidelines into
computer-interpretable and -executable formats (Kaiser et al.,
The retrieved guidelines were scrutinised in the title and in the 2007). The chapters regarding management of BPSD within each
abstract for mentioning of management of Alzheimer’s dementia or guideline were first identified and then screened for specific prac-
BPSD, and if so, read in full to confirm whether they were fully or tice recommendations. The BPSD spectrum includes a variety of
partly dedicated to the management of BPSD. Dementia guidelines non-cognitive symptoms, but we focused on those symptoms
were not selected if the scope was screening, diagnosis, evaluation most addressed by guidelines i.e. agitation, aggression, psychotic
of dementia or cognitive decline, care for families, and if manage- symptoms and depression. Finally, specific practice recommen-
ment of BPSD was not addressed. The remaining guidelines were dations for BPSD were listed per guideline into a summarising
considered and selected as eligible for quality appraisal by AGREE. table and classified into non-pharmacological and pharmacological

MEDLINE hand search of web sites


12 962 citations 15 guidelines retrieved
12 942 excluded based on 7 guidelines
predefined filter practice excluded based on
guidelines (as publication type) exclusion criteria
20 guidelines
retrieved
13 guidelines excluded
based on exclusion criteria
7 relevenant 8 relevenant
guidelines selected guidelines selected

15 practice guidelines
included for quality appraisal

Fig. 1. Flowchart of the systematic search.


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

interventions, supplemented by the results of their grading process 3.2.1. Extraction of specific practice recommendations
of the quality of the supporting evidence and the strength of the From 5 high quality guidelines, we extracted 18 specific practice
recommendation, as indicated by each guideline. recommendations on the management of BPSD in terms of agita-
tion, aggression, psychotic symptoms and depression. All of these
2.5. Appraisal of the level of agreement recommendations were proposed by more than one guideline. In
Box 1, the different grading systems used by these 5 guidelines are
In case several guidelines were available for one specific prac- outlined.
tice recommendation, we assessed the level of agreement between The 18 specific practice recommendations for management of
those guidelines with regard to the appraisal of quality of evi- BPSD were classified into non-pharmacological and pharmacolog-
dence and strength of recommendation. If ¾ or more guidelines ical interventions (see Table 3).
addressing the specific practice recommendation supported the Recommendations with regard to non-pharmacological treat-
recommendation (i.e. no conflict), and if no inconsistency was ment included aroma therapy, multisensory stimulation, music,
observed in quality appraisal of supporting evidence with maxi- bright light therapy, and behaviour management.
mum one guideline indicating insufficient evidence, then the level Recommendations with regard to pharmacological treatment
of agreement among guidelines for a specific practice recommen- included drug classes such as antipsychotics, benzodiazepines,
dation was found to be sufficient. These criteria were defined a antidepressants and acetylcholinesterase inhibitors (A-ChI).
posteriori. Only specific practice recommendations for which the
level of agreement was sufficient, were selected as key recommen-
dations. 3.2.1.1. Non-pharmacological treatment. In general, clinical prac-
tice guidelines on management of dementia recommended to start
3. Results non-pharmacological interventions first, and initiate medication
only in case of failure of these non-pharmacological treatments.
3.1. Systematic search for guidelines Some dementia guidelines stated that non-pharmacological inter-
ventions should be started in combination with medication.
The broad Pubmed search profile for MEDLINE resulted in 12 962
Non-pharmacological approaches for the management of BPSD
citations, which were reduced by the filter to 20 practice guide-
were addressed by 4 out of 5 included dementia guidelines.
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. Aroma therapy (addressed by 4 guidelines, recommended by 2)
Hence, 35 potentially relevant guidelines on dementia were The majority of dementia guidelines concluded that aroma ther-
retrieved, and analysed in full. apy may be of some benefit, but that a strong evidence base was
Of the 20 guidelines retrieved in MEDLINE, 13 were not selected lacking. The use of aromatherapy was only supported by 2 guide-
(9 did not focus on the management of Alzheimer’s dementia, 4 lines (NICE, CCC) and judged by others (SIGN, MOH (M)) as having
did not address the management of BPSD). The remaining 7 guide- too weak evidence to recommend its use. There was insufficient
lines were retained. In the analysis of the 15 eligible guidelines level of agreement among dementia guidelines to support the use
retrieved from the web, 7 were excluded (because not address- of aroma therapy for management of BPSD.
ing the management of BPSD). None of the remaining 8 guidelines Multisensory stimulation (addressed by 4 guidelines, recom-
were retrievable in MEDLINE. In total, 15 (7 from Medline: AGS mended by 2)
& AAGP, 2003; DCGP, 2005; Caltagirone et al. (IAP), 2005; AAN, There was clear inconsistency among guidelines in the grading
2005; EFNS, 2006; CCC, 2007; APA, 2007 and 8 from the web: MOH of the recommendation for multisensory stimulation. The recom-
Malaysia, 2009; Group Health, 2009; BCMA, 2008; MOH Singapore, mendation of NICE and CCC was based on low quality evidence,
2007; NICE, 2006; SIGN, 2006; CCSMH, 2006; RACGP, 2003) clinical while SIGN only recommended multisensory stimulation in mild
practice guidelines on the management of dementia with attention and not in severe dementia. The recommendation was strongly
to BPSD were selected, and appraised for quality with AGREE. Only rejected by MOH (M). There was insufficient agreement among
one guideline was exclusively focused on management of mental dementia guidelines to support the use of multisensory stimula-
and behavioural problems in residential care (CCSMH, 2006). tion for management of BPSD.
The search was repeated in January 2011 and yielded no new Music therapy (addressed by 4 guidelines, recommended by 3)
clinical practice guidelines on management of dementia. The therapeutic use of music for BPSD was recommended by
A description of the selected clinical practice guidelines is pre- NICE, CCC, and MOH (M). Their appraisal of the quality of evidence
sented in Table 1. ranged from moderate to high. SIGN appraised the evidence as
insufficient to make a recommendation.
3.2. Quality appraisal of the selected guidelines by the AGREE We estimated that the level of agreement among dementia
instrument guidelines to support the use of music therapy for management
of BPSD was sufficient.
The 15 selected clinical practice guidelines on management of Massage (addressed by 3 guidelines, recommended by 2)
dementia scored well on scope/purpose, with 12 guidelines scor- Two guidelines (NICE, CCC) recommended the use of massage
ing over 60%; and on clarity/presentation with 9 guidelines scoring for BPSD but differed in their quality appraisal of supporting evi-
over 60%. For rigour of development, 8 guidelines scored over 60%. dence, while another guideline (SIGN) concluded that there was
Domain scores were not as good for stakeholder involvement, with insufficient evidence to recommend its use.
3 scoring over 60%, and worse for editorial independence and appli- We estimated that the level of agreement among dementia
cability with respectively 5 guidelines and 1 guideline scoring over guidelines to support the use of massage for management of BPSD
60%. was insufficient.
Five clinical practice guidelines were appraised as high qual- Bright light therapy (addressed by 3 guidelines, recommended by
ity guidelines and therefore included, because in their evaluation 1)
with the AGREE instrument most of the standardised domain scores SIGN rejected bright light therapy based on expert opinion,
were 60% or higher (see Section 2 and Table 2). while CCC recommended its use based on low quality evidence
The 5 high quality guidelines were subjected to the next process. 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 Level of recommendations

Dutch college of clinical geriatrics


A1 Systematic reviews that include some studies of A2 level, of which 1 A systematic review (A1) or at least two independent other studies
results of individual studies are consistent conducted at level A1 or A2
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 2 At least two independently conducted studies level B
other competition (non-randomized, comparative cohort studies,
case-control studies)
C Non-comparative research 3 At least one study of level A2 or B, or studies of level C level
D Expert opinion, e.g. working group members 4 Expert opinion, for example, the working group members

National Institute for Health and Clinical Excellence


High Further research is very unlikely to change our confidence in the No explicit grading of the strength of recommendation
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 A At least 1 meta-analysis, systematic review of RCTs, or RCT rated as
bias 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
1+ Well conducted meta-analyses, systematic reviews of RCTs, or RCTs consistency of results
with a low risk of bias
1- Meta-analyses, systematic reviews of RCTs, or RCTs with high risk of B A body of evidence including studies rated as 2++, directly
bias applicable to the target population, and demonstrating overall
consistency of results; or Extrapolated evidence from studies rated as
1++ or 1+
2++ High quality systematic reviews of case control or cohort studies; high C A body of evidence including studies rated as 2+, directly
quality case control studies or cohort studies with very low risk of bias applicable to the target population and demonstrating overall
and a high probability that the relationship is causal consistency of results; or Extrapolated evidence from studies rated as
2++
2+ Well conducted case control or cohort studies with low risk of bias and D Evidence level 3 or 4; or extrapolated evidence from studies rated
a significant risk that the relationship is not causal as 2+
3 Non-analytic studies (case reports, case series) Good practice points (GPP):
4 Expert opinion Recommended best practice based on clinical experience

Canadian consensus conference (3rd)


1 Evidence obtained from at least 1 properly RCT A There is good evidence to support this manoeuvre
2.1 Evidence obtained from well-designed controlled trials without B There is fair evidence to support this manoeuvre
randomization, or
2.2 Evidence obtained from well-designed cohort or case-control analytic C There is insufficient evidence to recommend for or against this
studies preferably from more than 1 centre or research group, or manoeuvre but recommendations may be made on other grounds
2.3 Evidence obtained from comparisons between time or places with or D There is fair evidence to recommend against this procedure
without the intervention. Dramatic results in uncontrolled experiments
are included in this category
3 Opinions of respected authorities based on clinical experience, E There is good evidence to recommend against this procedure
descriptive studies or expert committees
Academy of medicine of Malaysia and ministry of health
1 Evidence obtained from at least 1 properly RCT A At least 1 meta-analysis, systematic review, or RCT, or evidence
rated as good and directly applicable to the target population
II-1 Evidence obtained from well-designed controlled trials without B Evidence from well conducted clinical trials, directly applicable to
randomization, or the target population, and demonstrating overall consistency of
results, or evidence extrapolated from meta-analysis, systematic
review, or RCT
II-2 Evidence obtained from well-designed cohort or case-control analytic C Evidence of expert opinion in the absence of applicable good
studies preferably from more than 1 centre or research group, or clinical studies
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 the supervision of a professional with expertise in this area’
support the use of bright light therapy for management of BPSD. (SIGN, 2006). Quality appraisal of supporting evidence and
Behaviour management (addressed and recommended by 3 guide- strength of recommendation was consistent among the 3
lines) guidelines.
The term ‘behaviour management’, is used to reflect ‘structured, There was sufficient agreement among dementia guidelines to
systematically applied and normally time-limited interven- support the use of behaviour management for management of
tions usually carried out by carers or care home staff under 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


their recommendations when separating A-ChI into donepezil,
galantamine or rivastigmine.
Antipsychotics (addresses and recommended by 5 guidelines) - NICE recommended donepezil for BPSD, while galantamine and
The use of antipsychotics was addressed by all guidelines. rivastigmine were not recommended because of insufficient
Sufficient level of agreement was found for the efficacy of evidence for BPSD in Alzheimer’s dementia.
antipsychotics (risperidone, olanzapine, haloperidol) in case of - SIGN recommended all A-ChI (donepezil, galantamine and
agitation/aggression/psychosis (recommendation addressed and rivastigmine) in specified dosages for the management of BPSD.
recommended by 4 guidelines). - CCC recommended the use of A-ChI without a further specifica-
No agreement among guidelines was found for a clear choice tion of active substances.
between typical or atypical antipsychotic agents. Four guidelines - MOH (M) recommended the use of A-ChI for BPSD, but
(DCCG, SIGN, CCC, MOHM) recommended atypical antipsychotics, donepezil as first choice in Alzheimer’s dementia.
of which 2 guidelines (DCCG, SIGN) additionally recommended A superficial agreement with varying appraisal of the quality
typical antipsychotics. Two guidelines (NICE, MOH (M)) addition- of the supporting evidence exists among dementia guidelines for
ally concluded that the choice of an antipsychotic agent should the use of A-ChI for management of BPSD, with no agreement as
be based on an individual risk/benefit analysis. to the choice of A-ChI.
Three guidelines (DCCG, CCC, MOH (M)) recommenced the Therefore, we estimated that the level of agreement among
time-limited use of antipsychotics and regular periods of re- guidelines to support the use of A-ChI for BPSD is insufficient.
assessment, but with varying appraisals of supporting evidence. - Memantine (addressed by 4, recommended by 2 guidelines)
Only 2 guidelines (CCC, MOH (M)) addressed discontinua- Memantine was recommended by 2 guidelines (CCC, MOH (M)),
tion of antipsychotics. Both recommended discontinuation in a while 2 other guidelines (NICE, SIGN) concluded that there was
standardised fashion after a period of behavioural stability (3-6 insufficient evidence to recommend its use. There was an insuf-
months), but with varying appraisals of supporting evidence. ficient level of agreement among dementia guidelines to support
Benzodiazepines (addressed and recommended by 3 guidelines) the use of memantine for BPSD.
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 3.3. Key recommendations
appraisals of supporting evidence.
Antidepressants (addressed and recommended by 5 guidelines) An overview of 9 specific practice recommendations, selected
The use of antidepressants (i.e. Selective Serotonine Reuptake as key recommendations, because the level of agreement among
Inhibitors) was addressed and recommended by 5 guidelines, but guidelines was considered as sufficient, is given in Box 2 .
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. 4. Discussion
Acetylcholinesterase inhibitors (A-ChI) (addressed by 4 guidelines
with divergent recommendations) To our knowledge, this study the first systematic review where
The oldest guideline (DCCG, 2005) concluded that there was an effort was made to systematically appraise specific practice
insufficient evidence to support the use of A-ChI for management recommendations of several guidelines on the clinical topic of
of BPSD. More recent guidelines supported the use of A-ChI for 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 · + (moderate) ? + (C2) ? No
Use of multisensory stimulation · + ? (gpp) + (C2) −(A) No
Use of music · + (moderate) ? + (B1) + (A) Yes
Use of massage and touch · + (moderate) · + (C2) ? No
interventions
Use of bright light therapy · · − (gpp) + (C2) ? No
Use of behaviour management · + (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 In this study we extracted specific practice recommendations
on management of dementia was highly efficient to find guidelines for management of BPSD from tertiary information sources (guide-
available in bibliographic databases. Efficiency was achieved using lines), without considering secondary sources (systematic reviews)
the limit feature, and the search performance showed a recall of and primary evidence (RCTs). We included 5 rigorously devel-
100% and a precision of 7/20. However, it was necessary to sup- oped clinical practice guidelines on management of dementia for
plement the search in databases by a hand search of web sites, as extraction of specific practice recommendations. We examined the
this resulted in a surprisingly high number of additional relevant divergent methods for the appraisal of the quality of supporting
guidelines. We retrieved a total of 15 clinical practice guidelines evidence and strength of these recommendations, and compared
with regard to management of dementia, of which 14 were partly the differences in appraisal. Additionally, we attempted to develop
and only 1 was fully dedicated to the management of BPSD. Four a systematic approach to synthesize the quality appraisal of spe-
out of 5 included guidelines were retrieved through the Web, cific practice recommendations in different guidelines. However,
indicating that a search in Medline will miss too much valuable variation in use of grading system complicated interpretation, com-
information. parison and generalisability of recommendations among guidelines
The appraisal of dementia guidelines with the AGREE instru- (Box 1). Grading systems consisted of 2 axes, 1 for the level of
ment revealed an overall moderate quality, but with a wide vari- evidence and 1 for the strength of recommendation. Included
ation in quality domain scores. In general, the domains of applica- guidelines (n = 5) used 3 different grading systems for the level
bility and editorial independence need more attention, as was also of evidence and 4 different grading systems for the strength of
previously observed by others (Lopez-Olivo et al., 2008). Potential recommendations. Recommendations were usually in the positive
costs and organisation barriers were significant flaws in the appli- direction, except for 1 guideline (CCC) that used bipolar recommen-
cability domain, while low scores for editorial independence were dations for or against an intervention.
more often the result of lack of information regarding the influence We tried to resolve the problem of different grading systems
of funding, rather than actually confirmed conflict of interest. by assessing the level of agreement among guidelines regarding
M. Azermai et al. / Ageing Research Reviews 11 (2012) 78–86 85

Additionally, there is more to risk-benefit analysis than


Box 2: Summary of 9 key specific practice recommen- appraisal of evidence of efficacy alone, especially when, adverse
dations for management of BPSD. events might outweigh the benefits (as in the case of antipsy-
If a person with dementia shows distressing behavioural symptoms chotics). This is the reason why our study, nor guidelines offer a
Then → consider non-pharmacological interventions first with most evidence clear choice of antipsychotic agents.
for music and behavioural management for depression
If non-pharmacological approaches have failed
Guidelines also agreed on the time-limited use of antipsy-
Then → consider psychotropic medication chotics for severe non-cognitive symptoms defined as agitation,
If a person with dementia shows co-morbid depression aggression, and psychotic symptoms. Planned discontinuation was
Then → consider antidepressants (preferably SSRIs) addressed by 2 guidelines, and both recommended discontinu-
If a person with dementia shows distressing acute agitation or agitation based
ation of antipsychotics in a standardised fashion after a period
on anxiety
Then → consider the short-term use of benzodiazepines (with caution) of behavioural stability. A Cochrane review (De Clercq et al., in
If a person shows severe agitation/aggression and/or psychosis preparation) investigates whether antipsychotics can be promptly
Then → consider antipsychotic medication stopped in older patients with dementia without having a signif-
If antipsychotic medication is considered icant effect on behavioural outcome measures objectivised by the
Then → carefully evaluate the individual risks (e.g. cardiovascular) and
benefits to make a choice for typical or atypical agents
use of a standardised behavioural scoring instrument.
If an antipsychotic is started Most dementia guidelines superficially agree, with varying
Then → initiate a low starting dose and titrate upwards in function of the appraisal of the quality of the supporting evidence, that acetyl-
resident’s response and presence of adverse events cholinesterase inhibitors (A-ChI) may be used for treatment of
If an antipsychotic is started
BPSD. Although some trials have indeed shown statistically signif-
Then → treatment should be time-limited and regularly reviewed (every 3
months or according to clinical need) icant efficacy for A-ChI in the BPSD treatment, the relevance of the
If there is a period of behavioural stability clinical effect remains questionable (Sink et al., 2005; Rodda et al.,
Then → periodical attempts of antipsychotic discontinuation should be 2009).
considered 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,
specific practice recommendations, based on criteria a posteriori confusion and consecutive risk of falling and fractures (Woolcott
defined by the reviewers. These criteria need to be further listed, et al., 2009), and finally potential cognitive decline (Eggermont
elaborated and validated. et al., 2009).
Our goal was to select key recommendations for behavioural and In general, guidance on the management of BPSD in existing
psychological symptom management from rigorously developed dementia guidelines was superficial, without further elaboration
dementia guidelines. For a specific practice recommendation to be on specific indications, pharmacotherapeutic dosages, and discon-
a key recommendation, the level of agreement among the different tinuation programs. The use of physical restraints was seldom
guidelines with regard to the quality of the supporting evidence and addressed, although still often used in the approach of disruptive
the strength of the recommendation needed to be sufficient. We behaviour caused by dementia (Hamers and Huizing, 2005; Meyer
found that non-pharmacological interventions as first-step treat- et al., 2009).
ment for BPSD are discussed at length in dementia guidelines. Our study has some limitations. The validated and frequently
However, individual interventions are often not supported by a used AGREE instrument judges the overall quality of the guideline
majority of guidelines, and the recommending guidelines acknowl- focusing on the development process, not the quality of the rec-
edge the low quality of supporting evidence. ommendations within the guidelines. Because low methodological
The question whether atypical over typical antipsychotics domain scores in AGREE are a risk factor for suboptimal guideline
should be preferred, remains unanswered after comparing guide- and therefore suboptimal recommendations within the guideline,
lines. Individual risk-benefit analysis of each class for a specific it is necessary to avoid inclusion of low quality guidelines with erro-
indication by the treating physician remains crucial when prescrib- neous recommendations, only adding to the general confusion of
ing an antipsychotic agent. There was agreement among guidelines conflicting recommendations.
for the use of risperidone, olanzapine and haloperidol since claims Included guidelines dated from 2005 to 2009. This time lap
for efficacy are more supported with high quality studies. When might lead to divergent recommendations based on collections of
looking closer into primary evidence for the efficacy of antipsy- evidence of a different age or different interpretations by the devel-
chotics for BPSD, we found that there is modest efficacy for opment group of the same evidence. The evaluation of the level
haloperidol in terms of aggression (Lonergan et al., 2002). As for of agreement among dementia guidelines for specific practice rec-
the atypical antipsychotics (i.e. the most researched risperidone ommendations was based on a posteriori defined and not-validated
and olanzapine), there is a modest efficacy for aggression and psy- criteria, which might seem arbitrary. To our knowledge, no other
chosis, but the evidence with regard to efficacy for other BPSD systematic attempts have been made to compare recommenda-
symptoms is not convincing (Ballard and Waite, 2006; Ballard et al., tions from existing dementia guidelines with regard to BPSD, and
2008). There is insufficient evidence for the efficacy of other atypi- we hope our proposal can evolve into a priori criteria for future
cal antipsychotics (Ballard et al., 2008). Also, credible head-to-trials research.
on comparative efficacy of typical and atypical antipsychotics on None of the included guidelines used a complete GRADE (Grades
specific manifestations of BPSD are needed. of Recommendation, Assessment, Development, and Evaluation)
Atypical antipsychotics have almost completely replaced typi- systematic approach. We first tried to adopt GRADE as an over-
cal antipsychotics, because they were perceived as having a better arching instrument in the appraisal of what several guidelines tell
side-effect profile (Briesacher et al., 2005). However, more recently, on one specific practice guideline. However, after consulting the
warnings (FDA, 2005, 2008; MHRA, 2008, 2009) have been issued GRADE working group it appeared that use of GRADE to synthesise
that all antipsychotics have increased risk of stroke and a (smaller) strength of recommendations as appraised by different guideline
risk of mortality, and are not recommended for the off-label treat- development groups would be methodologically incorrect without
ment of BPSD. the re-appraisal of supporting studies. We therefore restricted our-
86 M. Azermai et al. / Ageing Research Reviews 11 (2012) 78–86

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