Past Issues

Behavioral and psychological symptoms of
dementia (BPSD) is common in clinical psychiatry.
BPSD which is the major source of caregiver
and family burnout, may provoke elderly abuse,
cause premature institutionalization, increase cost
of care, and decrease quality of life. It is also associated
with poorer prognosis, more rapid rate of
cognitive decline, and greater impairment in activities
of daily living [1]. However, BPSD can be
treated effectively and safety, compared to its
counterpart of cognitive impairment, and may result
in increasing quality of life of patients and
their family, reducing caregiver distress as well as
lower the risk of premature institutionalization
[1].
Second-generation (SGA or atypical) antipsychotics
have been recommended to treat psychosis
and agitation in patients with BPSD, and it
is rated as standard level in evidence-based pharmacological
treatment of dementia [2].
In 2003, an Australian study was fi rst reported
higher risk of cerebrovascular adverse events
(CVAEs) in older patients with BPSD who receive
risperidone compared with those treated with placebo
in a randomized study [3]. Subsequently, increased
risks of CVAEs were noted for olanzapine
[4]. The CVAEs include strokes, transient ischemic
events and undetermined events thought to
be vascular in origin. In 2004, the U.K. Committee
of Safety of Medicine (CSM) informed their clinicians
that risperidone and olanzapine should not be used to treat patients with BPSD due to increased
risk of strokes with both drugs and increased
risk of mortality with olanzapine [5]. In
2005, a meta-analysis of 17 placebo-controlled
studies of risperidone, olanzapine, quetiapine and
aripiprazole for the treatment of patients with
BPSD (n=5106), revealed a 4.5% mortality rate
among the drug-treated group compared with a
2.6% mortality rate among the placebo group, an
increased mortality about nearly two times in SGA
antipsychotics-treated patients with BPSD [6].
The causes of death varied, most were related to
cardiovascular problems, including heart failure
and sudden death or infection with dementia. The
U.S. Food and Drug Administration (FDA) issued
a warning about new safety information regarding
all SGA antipsychotics [6].
In Taiwan, only risperidone had been approved
by Department of Health, Executive Yuan
in 2006 for treatment of patients with BPSD, So
far, there is no any other information from
Department of Health, Executive Yuan about other
atypical antipsychotics use in patients with
BPSD.
The exact mechanism for increased risk of
CVAEs and mortality has not been indentifi ed, the
possible biological mechanisms have been proposed
as anticholinergic effect of antipsychotics
causing conduction delays with ventricular tachycardia
and torsades de pointes; deep sedation of
antipsychotics plus benzodiazepines causing in-creased risk of aspiration pneumonia; drug-drug
interaction, especially with furosemide; and drugdisease
interaction, especially in demented patients
with Lewy body [7].
If SGA agents are withdrawn for BPSD, then
how about conventional agents or other alternative
drugs would in reducing the safety risk ? A
series of meta-analyses and large pharmacoepidemiologic
studies is found that conventional
antipsychotics have comparable risks for stroke
[8] or death [9]. Currently there is an absence of
consistent evidence supporting the effi cacy or
safety of alternative drugs for the treatment of
BPSD due to the uncertainty regarding the safety
of both conventional and atypical antipsychotics
[6].
Recently there have been reported from some
studies which contradict those of the U.K. CSM
and U.S. FDA. They found no different risk/benefi
t ratio between drugs treatment and placebo [10]
and no increased risk for mortality and CVAEs in
the atypical antipsychotic treatment [11, 12].
There is no evidence that the risk of CVAEs or
mortality is increased in older patients with psychiatric
disorders other than dementia [13]. In addition,
the most study samples are heterogeneous
and previous CVAEs risk factors such as diabetes
mellitus, smoking, cardiac diseases and hypertension,
can infl uence the outcome. More or fewer
patients with CVAEs risk factors could have been
randomized into the active treatment group [13].
The policy of American Psychiatric
Association (APA) about antipsychotic use in the
treatment of BPSD, is that antipsychotics should
be used only if there is clear, acute danger of
BPSD that may place the patient or others at risk
or do cause severe and signifi cant distress to the
patients and their family [14]. The treatment with
low doses of antipsychotics is indicated if the
drugs provide benefi t, its use should be reassessed
after several months and considered dose reduction
[14]. The American Association for Geriatric
Psychiatry (AAGP) policy gives similar recommendation
concerning antipsychotics in the treatment
of BPSD as that of the APA [15].The CSM
provided the prescribing advice that risperidone
should not be used to treat BPSD, however, CSM
also recommended that use of risperidone for the
management of acute psychotic condition should
be limited to short-term use [5].
In summary, the use of atypical antipsychotics
for BPSD is not contraindicated, and conventional
antipsychotics are at least as likely as atypical
agents to increase the risk of death and CVAEs
among patients with BPSD and should not be used
to replace atypical antipsychotics in response to
the FDA warning. When using atypical antipsychotics
for the treatment of patients with BPSD,
clinicians need to consider their risk-benefi t ratio
for each individual patient, especially patient with
current vascular risk factors and a previous history
of stroke, in addition to using the lowest effective
dose and careful monitoring to avoid or reduce
hypotension, gait disturbance, and oversedation.
To use SGA antipsychotics for patients with BPSD
in a time-limited period needs reasonable precautions
to reduce the risk of CVAEs and mortality.