WSO - March 2023 - 289

Tay et al.
289
Table 1. Baseline characteristics of the modified intention-to-treat population in EFFECTS.
Fluoxetine (n = 681)
Age, mean (SD)
Sex, female, n (%)
NIHSS, median (IQR)
Stroke type
Ischemic, n (%)
Hemorrhagic, n (%)
Ischemic stroke cause*
Large artery disease, n (%)
Small-vessel disease, n (%)
Cardioembolism, n (%)
Other, n (%)
Unknown or uncertain, n (%)
MADRS variables
Total score, mean (SD)
Apathy, mean (SD)
Depression, mean (SD)
Anhedonia, mean (SD)
70 (11.2)
270 (39.6)
3.0 (2-6)
599 (88.0)
82 (12.0)
95 (14.0)
199 (29.2)
120 (17.6)
25 (3.7)
164 (24.1)
2.8 (3.6)
0.4 (0.8)
2.1 (2.7)
0.1 (0.4)
Placebo (n = 688)
71.4 (10.4)
253 (36.8)
3.0 (2-6)
595 (86.5)
91 (13.2)
0.27
81 (11.8)
196 (28.5)
134 (19.5)
14 (2.0)
172 (25.0)
2.7 (3.0)
0.3 (0.7)
2.1 (2.3)
0.1 (0.3)
NIHSS: National Institute of Health Stroke Scale; MADRS: Montgomery-Åsberg Depression Rating Scale.
*Assessed using modified TOAST criteria.
apathetic and depressive symptoms when examining treatment
effects.
Apathetic symptoms increased over time in both groups
consistent with some studies reporting increased apathy
over time following stroke.15 In addition, there was an
increase in the proportion of patients reporting apathy
symptoms after 6 months in the placebo group. This was
not observed in the fluoxetine group, although this may be
explained by that group having higher rates of apathy at
baseline. These results suggest that post-stroke patients
experience a greater burden of motivational deficits over
time, although overall severity may be mild. Research on
1 year trajectories suggests that the majority of post-stroke
patients can be categorized into high (7%), moderate (33%),
or low/no (50%) levels of apathy from the acute phase,
which remains stable for up to a year.16 A small group of
patients will spontaneously improve (7%) or worsen
(7%).14 Over the course of 5 years following stroke, the
prevalence of apathy was reported to increase by about
10%.15 Theoretical work suggests that increases in poststroke
apathy can be explained by anterograde neurodegeneration,
which can propagate from the initial infarct to
large-scale brain networks underlying motivation.17 These
networks may also be affected by ischemic white matter
disease,2,18 which was supported by our finding that apathy
increased in the SVD subgroup.
Decreases in depressive symptoms in the fluoxetine
group were observed in patients with age ⩽70 years, SVD,
and NIHSS ⩽5, suggesting that fluoxetine may be more
effective in treating depressive symptoms in stroke patients
with less severe disease. Why this may be the case is
unclear. One explanation could be that the pathogenesis
and development of depressive symptoms are different in
SVD compared to other stroke types, and that these are
more amenable to SSRI treatment. Regardless of the reasons,
future treatment studies should replicate and further
investigate the possibility that fluoxetine can alleviate
depressive symptoms in participants with mild disease. It is
important to emphasize that these claims pertain to symptomatic,
rather than syndromic, depression (e.g. major
depression). All patients enrolled in EFFECTS were free
from depression upon entry to the trial. Therefore, the
decrease in depressive symptoms observed in the fluoxetine
group should be interpreted as a decrease in subthreshold
depressive symptomatology, rather than the treatment
of a pre-existing depressive disorder.
International Journal of Stroke, 18(3)
0.87
0.007
0.71
0.28
p
0.37
0.32
0.61
0.55
WSO - March 2023

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