Critical Appraisal Journal :

Withdrawal or continuation of cholinesterase

inhibitors or memantine or both, in people with
dementia (Review)

Presentant : dr. Huseikha Velayazulfahd

Pembimbing : Prof. Dr. dr. Salim Harris, Sp.S(K), FICA

The Journal
Introduction
DEMENTIA
Progressive syndrome characterised by deterioration in memory, thinking and
behaviour, and by impaired ability to perform daily activities.

DRUGS IN DEMENTIA
Cholinesterase Inhibitor and Memantine

Uncertainties about the benefits and adverse effects

of these drugs in the long term and in severe
dementia
 Objective
To evaluate  The effects of withdrawal or continuation of cholinesterase inhibitors or
memantine, or both, in people with dementia on:
● Cognitive
● Neuropsychiatric and functional outcomes
● Rates of institutionalization
● Adverse events
● Dropout from trials
● Mortality
● Quality of life
● Career-related outcomes.
 Critical Appraisal
F A I
Did the search find all the Have the studies been Did they only include high
relevant evidence? critically appraised? quality studies?

T H
Heterogeneity between studies assessed
Have the results been totalled up with
and explained?
appropriate summary tables and plots?
 Yes

Cochrane Dementia and Cognitive Improvement Group’s Specialised Register

P: up to 17 October 2020

I : Withdrawal of Cholinesterase inhibitors or memantine

C: Continuation of cholinesterase inhibitor or memantine, or both,

beyond the time of randomisation.

O: Cognitive, functional and global outcomes, neuropsychiatric symptoms, quality

of life and safety, tolerability and adverse effects, and mortality
 Yes

Type of the Study

Selection Criteria
Randomised, controlled clinical trials.
Included all randomised, controlled clinical
Type of the Participants trials (RCTs) which compared withdrawal of
cholinesterase inhibitors or memantine, or both,
with continuation of the same drug
Participants had dementia of any severity, diagnosed
using a recognised and validated tool or by clinical
assessment, and were taking a cholinesterase
inhibitor or memantine, or both, at baseline.
F Find All Relevant Evidence?

Yes
Result

Data Collection
Two review authors independently assessed citations
and full-text articles for inclusion

Extracted data from included trials

Assessed risk of bias using the Cochrane risk of bias

tool.
Risk Of Bias
 Have the studies been critically
A appraised?
Yes

Qualification of The Study

This review assessed the overall certainty of the evidence for each
outcome using GRADE methods.
 I Did they only include high quality studies?

No

They included all the study that

matched with their selection
criteria.
 I
Did they only include
high quality studies?
 I
Did they only include
high quality studies?
 I
Did they only include
high quality studies?
T Have the results been totalled up with appropriate summary tables and plots
and Heterogeneity between studies assessed and explained?
H
This journal assessed potential differences between the included studies
Yes in the types of participants, interventions or controls used before
pooling data.

I2 values over 50%

suggesting substantial
heterogeneity
T Have the results been totalled up with appropriate summary tables and plots
and Heterogeneity between studies assessed and explained?
H

We conducted a sensitivity analysis, excluding

data from Johannsen 2006 which had included When these data were omitted, the
only participants with a poor response to heterogeneity was reduced (I2 = 24%)
donepezil, who might be expected to show less
effect of discontinuation.
T Have the results been totalled up with appropriate summary tables and plots
and Heterogeneity between studies assessed and explained?
H
T Have the results been totalled up with appropriate summary tables and plots
and Heterogeneity between studies assessed and explained?
H
 Critical Appraisal
F A I
Did the search find all the Have the studies been Did they only include high
relevant evidence? critically appraised? quality studies?

T H
Heterogeneity between studies assessed
Have the results been totalled up with
and explained?
appropriate summary tables and plots?
Discussion

• Compared to continuing cholinesterase inhibitors, discontinuing treatment may

be associated with worse cognitive function in the short term
• Discontinuation may make little or no difference to functional status in the short
term
• Discontinuation may be associated with a worsening of neuropsychiatric
symptoms over the short term and medium term
• We found no clear evidence of an effect of discontinuation on dropout due to lack
of medication efficacy or deterioration in overall medical condition, number of
adverse events, serious adverse events, and on mortality
Conclusion
Discontinuing cholinesterase inhibitors may result in worse
cognitive, neuropsychiatric and functional status than continuing
treatment
Limitation and Suggestion

This is supported by limited evidence, almost all of low or very

low certainty.

There is a need for further well-designed RCTs, across a

range of dementia severities and setting
THANK YOU