Following a stroke around two-thirds of patients suffer long-term disability. Many preclinical and clinical studies have suggested that selective serotonin reuptake inhibitors (SSRIs) might improve functional outcomes after stroke, including a number of small randomised trials.
The present trial was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were 18 or older, had a clinical diagnosis of acute stroke with brain imaging compatible with intracerebral haemorrhage or ischaemic stroke. Further, eligible patients were randomised between 2 and 15 days from stroke onset and had a persisting focal neurological deficit at the time of randomisation to warrant 6 months treatment. Patients were excluded if they had subarachnoid haemorrhage except where secondary to a primary intracerebral haemorrhage.
Patients were randomly assigned in a 1:1 ratio to either receive fluoxetine or placebo for 6 months. The primary outcome measure was functional status assessed using the simplified modified Rankin scale. Secondary outcomes were survival at 6 and 12 months, functional status at 12 months measured with the simplified modified Rankin scale and health status assessed using the Stroke Impact Scale.
A total of 3,127 patients were enrolled comprising 1,564 allocated to fluoxetine and 1,563 allocated to placebo. Baseline characteristics were well balanced between the two groups and were similar to unselected stroke patients admitted to UK hospitals. The primary outcome, an ordinal comparison of the distribution of patients across the modified Rankin Scale categories at 6 months, adjusted for variables included in the minimisation algorithm, was similar in the two groups (common OR 0·951 [95% CI 0·839–1·079]; p=0·439). The unadjusted analysis showed a similar result (common OR 0·961 [95% CI 0·848–1·089]; p=0·531). Analysis of the modified Rankin Scale dichotomised into 0-2 versus 3-6 was also similar between the two groups (adjusted OR 0·955 [95% CI 0·812–1·123], p=0·576).
Secondary outcomes and adverse events at 6 months were generally similar between the groups, with the exception of new onset depression at 6 months which was significantly lower in the fluoxetine group (210 [13·4%] patients vs 269 [17·2%]; difference in proportions 3·78% [95% CI 1·26–6·30]; p=0·0033). Mood as assessed using the Mental Health Inventory (MHI-5) was significantly higher in the fluoxetine group (median 76 [IQR 60–88] vs 72 [56–88]; p=0·0100). Further, bone fractures were significantly higher in the fluoxetine group (45 [2·88%] patients vs 23 [1·47%]; difference in proportions 1·41% [95% CI 0·38–2·43]; p=0·0070)
In summary, the results of the FOCUS trial show that fluoxetine 20 mg given daily for 6 months after an acute stroke did not influence patients’ functional outcomes but did decrease the occurrence of depression and increase the occurrence of bone fractures.
The full report is available here.