Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial

Background Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects. Methods FOCUS 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 aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762. Findings Between Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months. Interpretation Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function. Funding UK Stroke Association and NIHR Health Technology Assessment Programme

Intratympanic steroid therapy using the Silverstein Microwick for refractory sudden sensorineural hearing loss increases speech intelligibility.

OBJECTIVE: To determine whether delivery of methylprednisolone to the round window (administered for 10 days after the onset of the hearing loss) can improve hearing and, in particular, speech intelligibility, after the failure of conventional treatment for idiopathic sudden sensorineural hearing loss. RESULTS: Of the 26 patients enrolled in this non-randomized retrospective study, 14 patients (54%) showed an improvement in the pure tone average (PTA) and 12 remained unchanged. The topical steroid therapy brought about an overall improvement in PTA of 13.5 +/- 7.3 dB for the 26 patients enrolled. The auditory capacity index, defined as the mean speech discrimination score obtained at 40, 55 and 70 dB, improved by 24.2 +/- 8.7% in 26 patients. Among the 12 patients with a stable PTA, 9 showed an increase in speech intelligibility. CONCLUSION: Local administration of steroids to the inner ear through the round window route improves hearing and speech intelligibility in patients after failure of conventional therapy