Home' Australian Pharmacist : Australian Pharmacist June 2013 Contents 36 Australian Pharmacist June 2013 I ©Pharmaceutical Society of Australia Ltd.
Dr Hanan Khalil is the Director of the
Centre for Chronic Disease Management, a
collaborating centre of the Joanna Briggs
Institute, Faculty of Medicine, Nursing and
Health Sciences, Monash University, and
a reviewer for the consumer group of the
Antipsychotics in older
people with dementia
By Dr Hanan Khalil
The purpose of this evidence summary is to
provide the best available information on the
efficacy of withdrawal versus continuation
of antipsychotics in older people with
dementia. For the full Cochrane review,
refer to Declercq T, Petrovic M, Azermai M,
et al. Withdrawal versus continuation of
chronic antipsychotic drugs for behavioural
and psychological symptoms in older
people with dementia. Cochrane Database
of Systematic Reviews 2013, Issue 3. Art.
No.: CD007726. DOI: 10.1002/14651858.
Age related chronic diseases represent
a significant health issue globally.
Neurological disorders such as dementia
in particular appear mostly in the older
age population. A recent study in the
Lancet estimates the global prevalence of
dementia to triple by 2040 reaching a total
of 81.1 million sufferers.2
Both cognitive deficits and non-cognitive
impairments are common in the disease
presentation. Non-cognitive symptoms
include agitation, aggression, hallucinations,
anxiety, apathy, depression, delusions,
wandering and shouting. These symptoms
occur in up to 98% of people with dementia.1
cholinesterase inhibitors and neuroleptics
are used to treat the non-cognitive
symptoms with mixed results regarding their
long term efficacy. Treatment often relies on
expert opinions and consensus guidelines.
There is evidence to support the benefit
of antipsychotic treatments on symptoms
of agitation, aggression and psychotic
symptoms in people with dementia.
The downside of their use includes their
increased risk of mortality and stroke with
long term use. Studies on the clinical benefit
of withdrawal versus continuous treatment
of these medications when patients are
stabilised remain limited.3
Characteristics of the studies
The studies selected for the systematic
review mentioned above were randomised
controlled trials. Withdrawal trials that were
not placebo controlled trials were only
included if the assessors were blinded to the
Quality of the research
All studies included in the report were of
low to moderate methodological quality.
Biases such as random sequence generation,
allocation concealment, incomplete
outcome data, blinding of participants and
outcome assessment were not adequately
addressed in only a few studies.
• The following databases were searched:
ALOIS, the Specialised Register of the
Cochrane Dementia and Cognitive
Improvement Group (CDCIG),
The Cochrane Library, MEDLINE, EMBASE,
PsycINFO, CINAHL, LILACS, clinical trials
registries and grey literature sources were
searched on 23 November 2012.
• A total of nine trials with 606 randomised
patients were included. Seven trials
took place in nursing homes, one in an
outpatient setting and the last one took
place in both settings.
• The primary outcome measures included
success of withdrawal from antipsychotics
over short term (four weeks or less) and
long term (more than four weeks) follow
up. The success rate was defined as the
ability to complete the study, which is
defined by no dropouts of the trial due to
worsening of the symptoms or no relapse
due to antipsychotic treatment, presence
or absence of withdrawal symptoms and
• Seven of the nine studies showed that
withdrawal of antipsychotics could be
done in patients with dementia without
significant effect on behavioural outcomes.
Withdrawal symptoms were not reported in
any of the studies.
• Subgroup analysis of patients with severe
symptoms in one study was significantly
more likely to develop marked behaviour
problems upon discontinuation of
• A recent study showed a significantly
increased risk of relapse in those people
who previously responded well to
risperidone and discontinued it as part of
• The secondary outcomes measures
included: cognitive function measures,
quality of life, use of physical restraints
• Quality of life and use of physical restraints
were only reported in one study and were
found to be non-significant in both groups.
• Mortality was only reported in two
studies and there was no significant
difference between the withdrawal and
Implications for research and
The results of this review reinforce the
need to establish safe alternatives to both
pharmacological and non-pharmacological
management of psychotic symptoms in older
people with dementia.
The current evidence supports that older
people with dementia on long term
antipsychotics can be withdrawn without
deterioration of their behaviour. Exceptions
include people with severe non-cognitive
symptoms and those who respond well to
1. Declercq T, Petrovic M, Azermai M, et al. Withdrawal versus
continuation of chronic antipsychotic drugs for behavioural and
psychological symptoms in older people with dementia. Cochrane
Database of Systematic Reviews 2013, Issue 3. Art. No.: CD007726.
2. Ferri CP, Prince M, Brayne C, et al. Global prevalence of dementia: a
Delphi consensus study. Lancet 2005;366(9503):2112--7.
3. Ballard CG, Thomas A, Fossey J, et al. A 3-month, randomized,
placebo-controlled, neuroleptic discontinuation study in 100 people
with dementia: the Neuropsychiatric Inventory median cutoff is a
predictor of clinical outcome. J Clin Psychiatry 2004;65:114--9.
Links Archive Australian Pharmacist May 2013 Australian Pharmacist July 2013 Navigation Previous Page Next Page