RISK OF ISCHEMIC STROKE

ASSOCIATED WITH THE USE OF

ANTIPSYCHOTIC DRUGS IN
ELDERLY PATIENTS: A
RETROSPECTIVE COHORT STUDY
IN KOREA
Journal Reading
Anatria Amyrra Iqlima, Nisa Khinanty, Irene Olivia Salim,
Agus Hendra, Kevin Leonardo

Kepaniteraan Klinik Ilmu Kedokteran Jiwa

RSJ Prof. Dr. Soerojo, Magelang
Program Studi Pendidikan Dokter
Fakultas Kedokteran Universitas Tanjungpura, Pontianak
Periode 17 Oktober - 19 November 2016

Journal Identity
Title

Risk of Ischemic Stroke Associated with the Use of

Antipsychotic Drugs in Elderly Patients: A Retrospective
Cohort Study in Korea

Author

Ju-Young Shin, Nam-Kyong Choi, Joongyub Lee, Jong-Mi

Seong, Mi-Ju Park, Shin Haeng Lee, Byung-Joo Park.

Editor

M Maria Glymour

Publish

PLoS One. 2015; 10(3)

Published
Online
2015
doi:10.1371/journal.pone.0119931

March

19

Clinical Questions
nterventio Compariso
Population Ins
O
utcome
n
Elderly
Patients
Ischemic
Stroke
patients
after their
psychiatric
first
admission

Secondary
data
analysis

Antipsychot
ic drugs
and risk of
Ischemic
Stroke

Antipsychot
ic drugs
could have
a
potentially
elevated
risk of
developing
Ischemic
Stroke

Background
Conventional antipsychotics (CAPs) in the year 1960s
schizophrenia, acute mania, bipolar disorder, behavioral and
psychological symptoms of dementia (BPSD), and delirium.
Atypical antipsychotics (AAPs) in the year 1990s effective
for both positive and negative psychotic symptoms, including
extrapyramidal symptoms, hypotension, and anticholinergic
like syndromes.
Study to compare the risk of hospitalization for ischemic
stroke among elderly patients taking antipsychotics.

Background (contd)
Study

Results

Sung S-K, Lee S-G, CAPs & AAPs increased risk of cerebrovascular
Lee K-S, Kim D-S, adverse events (CVAEs) based on clinical trials
Kim K-H, Kim K-Y with elderly demented patients.
(2009)
Zhang J-P, Gallego Recommended not using risperidone and
JA, Robinson DG, olanzapine in older patients with dementia, due
Malhotra AK, Kane to a three-fold increase of the risk of stroke
JM,
Correll
CU
(2013)
Douglas IJ, Smeeth Higher risk of stroke with atypical antipsychotics
L.
(2008); than with conventional antipsychotics
Huybrechts K et al.
(2012); Wu SC et
al. (2012)
Gill et al. (2005)

Atypical antipsychotics are associated with a

similar risk of ischemic stroke as compared with
conventional antipsychotics

Subjects and Methods

A retrospective cohort study with observational methods
Source : The Korean Health Insurance Review and Assesment
Service (HIRA) database.
A nationwide cohort of 71,594 elderly patients at the ages of
65 years and above who were prescribed at least one
antipsychotic medication whose records were enrolled in the
Korean Health Insurance Review and Assessment Service
(HIRA) in Korea from January 1 2005 through December 31,
2009.

Sample Criteria
Inclusion :
1. Patients aged 65 years and above who visited at least one
hospital or clinic located in Korea.
2. Patients with no history of taking antipsychotic medications in
the 12 months prior to the study entry date.

Exclusion :
1. Patients with prior cerebrovascular diseases (I60- I69) or TIA
(G45) during the prior 365 days,
2. Patients with a diagnosis of ischemic stroke recorded on the
first day of antipsychotic prescription.
3. Patients older than 100 years old
4. Patients who received non-oral antipsychotics such as
injectable or depot preparation.

Results

Results

10

Results

11

Results

12

Results

13

Discussion
A very strong risk of ischemic stroke associated with chlorpromazine and
haloperidol compared to risperidone.
AAPs may be preferred to CAPs in elderly patients based on the improved
safety profile.
Chlorpromazine showed a tripling of the ischemic stroke risk among longterm users (more than 150 days), female and demented patients showed
an almost 5-fold in- creased risk with chlorpromazine compared with
risperidone use.
A previous population-based case-control study in elderly patients showed
a 1.83-fold (95% CI, 1.572.14) increased rate of cerebrovascular accidents
after the use of conventional antipsychotics compared with atypicals.
Another retrospective cohort study in the elderly patients with dementia
reported that the odds ratio of incident cerebrovascular events for
haloperidol was 1.91 (95% CI, 1.023.60) compared with risperidone.
A retrospective cohort study using a Canadian claims database showed no
significantly increased risk of ischemic stroke with atypicals compared with
conventional drugs had a small sample size with insufficient power.

14

Discussion
Conventional antipsychotics cause more extrapyramidal motor symptoms than
atypical antipsychotics, whereas atypical antipsychotics generally cause more
weight gain and the metabolic syndrome
The comparative risk of ischemic stroke among haloperidol, chlor- promazine,
risperidone, quetiapine, and olanzapine the highest risk with chlorpromazine is newsworthy, as many of previous studies did not cover
chlorpromazine, with one exception
One retrospective cohort study showed that the risk of stroke was six times
higher for phenothiazines (the class containing chlorpromazine) and 3.6 times
for butyrophenones (the class containing haloperidol) compared with non-users
Pre- scribing CAPs, particularly chlorpromazine, should be done with more
caution in demented female geriatric patients females are more prone to
hyperprolactinemia risk than males [42, 44], which may explain our results
demonstrating the highest risk in female chlorpromazine users.
Hyperprolactinemia has mostly been seen with CAPs, and this implies that
drug-induced hyperprolactinemia, which may promote platelet aggregation
[43], might be the biological mechanism responsible for increased risk of
ischemic stroke.
15

Critical Appraisal
The structure and content of the journal :
The title of the journal
- Describe the whole journal : Yes
- Interesting
: Yes
- The Structure
: 18 words
The author and Institution
- Appropriate with The Guideline : Yes

16

Critical Appraisal
Abstract
- The structure
Consist of 4 part
background, material/method,
result, conclusion.
- Informative Yes
- Less than 350 words
Yes (210)
Background
- Explain background of the research
- Explain hypothesis
No
- Objective
Yes

Yes

17

Critical Appraisal
Method
Design of The Research
A nested case control study
Inclusion and Exclusion Criteria
: Mentioned
Sampling Technique
: Secondary data analysis
Blind Method
: Yes
Analytic Computer Programs :
Univariate and Multivariate logistic regression

18

Critical Appraisal
Results
Characteristic subject table : Included
Characteristic subject before intervention that was compared with
the result : No Result
Total subject in intervention : Was written
Accuracy of numeric data : Trusted
Accuracy and compability of analytic computer program : Trusted
Include the result of the analysis, degree of freedom and p-value :
Included

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Critical Appraisal
A. Are the results of the study valid?
Question

Indicator
Yes

1. Did the study address a clearly focused issue?

2. Did the authors use an appropriate method to

answer their
question?

3. Were the cases recruited in acceptable way?

4. Was the exposure accurately measured to minimize

bias?

5. Were all articles who entered the study accounted

for
appropriatedly at the end?

No

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B. What were the results?

1. How large was the article effect?
From this study we can conclude that:
Chlorpromazine and Haloperidol increasing the risk of Ischemic
Stroke in Female Geriartry patients with Dementia.
Long term users (>150days) of first generation antipsychotics,
Chlorpromazine and Haloperidol does increase the risk of Ischemic
Stroke compared to Risperidone Users.
The risk of Ischemic Stroke were decreased for usage <150 days for
both 1st generation antipsychotics (Chlorpromazine and
Haloperidol) compared to risperidone users.
2. How precise was the estimate result of the study effect?
The result is doubtly accurate because the pathophysiology of
underlying association
between the use of antipsychosis drugs with increasing Ischemic
Stroke risk is remain speculative hyperprolactinemia and hypotension
among individual antipsychotics.
21

C. Can the results be applied to your patients?

Indicat
or

Question

Ye
s

1. Can the results be applied to my patient (care)?

The result of this study can be applied to the clinical care
because theres a significant correlation between the use of
some antipsychotic drugs with an increased risk of Ischemic
Stroke

2. Were all clinically important outcomes reported?

Were the most important outcomes used?
The most important outcome is the increased risk of
Ischemic Stroke n female elderly patient received
current antipsychosis (Chlorpromazine, Haloperidol, and
Risperidone).
How the quality of life outcomes after knowing this
article? Asessment of adverse effect?

No

V
22

Conclusions
The results or reccomendations are valid (form A)

Yes

The results are clinically important (form B)

Yes

The result are rellevant to my practice (form C)

Yes

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