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International Journal of Stroke 18(3)
Figure 2. Confirmatory factor analysis of the Montgomery-Åsberg Depression Rating Scale. (a) One-factor model of
depression and (b) three-factor model assessing apathy, depression, and anhedonia. For both indices, lower values indicate
a better fit to the data, with differences over 10 being considered significant. The three-factor model demonstrated lower
AIC and BIC values, suggesting it was a better fit to the data. Single-headed arrows indicate the factor loadings while doubleheaded
arrows indicate the correlations. All paths are significant at p < 0.05. AIC: Akaike information criterion; BIC: Bayesian
information criterion.
The depressive construct we investigated excluded
anhedonia. Research suggests that SSRIs can ameliorate
depressive symptomatology in general, but specific effects
for treating anhedonia are mixed.19 Our results supported
this, with anhedonic symptoms not differing between
groups or decreasing in the fluoxetine group over time. We
did, however, observe an increase in anhedonia in the placebo
group. Theoretical work suggests that apathy and
anhedonia may increase over time due to similar pathophysiological
mechanisms.6 If this is the case, then it is possible
that fluoxetine prevented an increase in anhedonia in
patients who received it.
A strength of this study is that it used a large randomized
controlled trail data set. A limitation is that it was a post hoc
analysis. Rather than using individual scales for apathy and
depression, both measures had to be derived from the
MADRS. Our results should therefore be replicated in
future studies, which can be designed around assessing
fluoxetine-related changes in apathy and depression as a
International Journal of Stroke, 18(3)
primary outcome. Three large trials have examined the
effect of fluoxetine post-stroke, but only the EFFECTS trial
had data collected which allowed comparison of fluoxetine
on apathetic and depressive symptoms.20 This study also
has a number of limitations primarily related to the tools we
had available to assess apathy. Apathy and anhedonia were
only assessed using a single item. This limits our conclusions
to symptomatic apathy and anhedonia, rather than
broader syndromes. Item 7 of the MADRS, which we used
to assess apathy, primarily measures slowness or difficulty
initiating activities and therefore is best seen as an index of
behavioral apathy, but is not a good indicator of the motivation
aspect of apathy. The use of single items may also
reduce sensitivity to detect effect; of note, depressive
symptoms were in contrast assessed using eight items.
Furthermore, we cannot make conclusions about the apathy
severity from the one item we used. Another related limitation
is that recent studies have suggested apathy is a multidimensional
concept, including different facets, such as

WSO - March 2023

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Contents
WSO - March 2023 - Cover1
WSO - March 2023 - Cover2
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WSO - March 2023 - Contents
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WSO - March 2023 - Cover3
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https://europe.nxtbook.com/nxteu/sageuk/wso_202404
https://europe.nxtbook.com/nxteu/sageuk/ukstrokeforum_202402_supp
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