Twelve-Month Outcomes of the AFFINITY Trial of Fluoxetine for Functional Recovery After Acute Stroke: AFFINITY Trial Steering Committee on Behalf of the AFFINITY Trial Collaboration.

BACKGROUND AND PURPOSE: The AFFINITY trial (Assessment of Fluoxetine in Stroke Recovery) reported that oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and seizures. After trial medication was ceased at 6 months, survivors were followed to 12 months post-randomization. This preplanned secondary analysis aimed to determine any sustained or delayed effects of fluoxetine at 12 months post-randomization. METHODS: AFFINITY was a randomized, parallel-group, double-blind, placebo-controlled trial in adults (n=1280) with a clinical diagnosis of stroke in the previous 2 to 15 days and persisting neurological deficit who were recruited at 43 hospital stroke units in Australia (n=29), New Zealand (4), and Vietnam (10) between 2013 and 2019. Participants were randomized to oral fluoxetine 20 mg once daily (n=642) or matching placebo (n=638) for 6 months and followed until 12 months after randomization. The primary outcome was function, measured by the modified Rankin Scale, at 6 months. Secondary outcomes for these analyses included measures of the modified Rankin Scale, mood, cognition, overall health status, fatigue, health-related quality of life, and safety at 12 months. RESULTS: Adherence to trial medication was for a mean 167 (SD 48) days and similar between randomized groups. At 12 months, the distribution of modified Rankin Scale categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio, 0.93 [95% CI, 0.76-1.14]; P=0.46). Compared with placebo, patients allocated fluoxetine had fewer recurrent ischemic strokes (14 [2.18%] versus 29 [4.55%]; P=0.02), and no longer had significantly more falls (27 [4.21%] versus 15 [2.35%]; P=0.08), bone fractures (23 [3.58%] versus 11 [1.72%]; P=0.05), or seizures (11 [1.71%] versus 8 [1.25%]; P=0.64) at 12 months. CONCLUSIONS: Fluoxetine 20 mg daily for 6 months after acute stroke had no delayed or sustained effect on functional outcome, falls, bone fractures, or seizures at 12 months poststroke. The lower rate of recurrent ischemic stroke in the fluoxetine group is most likely a chance finding. Registration: URL: http://www.anzctr.org.au/; Unique identifier: ACTRN12611000774921.

Similar cognitive deficits in mice and humans in the chronic phase post-stroke identified using the touchscreen-based paired-associate learning task.

For many chronic stroke survivors, persisting cognitive dysfunction leads to significantly reduced quality of life. Translation of promising therapeutic strategies aimed at improving cognitive function is hampered by existing, disparate cognitive assessments in animals and humans. In this study, we assessed post-stroke cognitive function using a comparable touchscreen-based paired-associate learning task in a cross-sectional population of chronic stroke survivors (≥ 5 months post-stroke, n = 70), age-matched controls (n = 70), and in mice generated from a C57BL/6 mouse photothrombotic stroke model (at six months post-stroke). Cognitive performance of stroke survivors was analysed using linear regression adjusting for age, gender, diabetes, systolic blood pressure and waist circumference. Stroke survivors made significantly fewer correct choices across all tasks compared with controls. Similar cognitive impairment was observed in the mice post-stroke with fewer correct choices compared to shams. These results highlight the feasibility and potential value of analogous modelling of clinically meaningful cognitive impairments in chronic stroke survivors and in mice in chronic phase after stroke. Implementation of validated, parallel cross-species test platforms for cognitive assessment offer the potential of delivering a more useful framework for evaluating therapies aimed at improving long-term cognitive function post-stroke.

Incidence and predictors of post-traumatic stress symptoms in a cohort of patients with intracerebral hemorrhage.

OBJECTIVES: Examine the incidence and predictors of PTSD symptoms in a cohort of patients with ICH. PATIENTS AND METHODS: This study uses a prospective cohort of 108 patients with complete follow-up data including a questionnaire regarding stress symptoms (PCL-S: PTSD checklist specific for a stressor) at 3, 6, and 12 months. RESULTS: The incidence of novel stress symptoms following ICH was approximately 6.5%. Age was negatively associated with PTSD symptoms with only trend-level significance (3 months: OR = 0.83, p = 0.087; 6 months: OR = 0.70, p = 0.015; 12 months: OR = 0.88, p = 0.087). Gender did not affect PTSD symptom development, (t = 1.34, p = 0.18). Pre-morbid functioning, initial stroke prognosis, total number of complications, and length of hospital/ICU stay were not associated with PTSD symptoms; however, each was significantly correlated with poorer functional outcomes. Yet, poorer functional outcomes were observed in those with higher reports of PTSD symptoms (r = 0.24, p = 0.01). CONCLUSION: Functional outcomes in ICH are correlated with PTSD symptoms, however the mechanism and relationship are difficult to elucidate. Further research is needed to determine possible mechanisms by which a stroke patient may develop PTSD.