Fluoxetine and fractures after stroke: exploratory analyses from the FOCUS trial

Abstract

Background and purpose
The FOCUS trial showed that fluoxetine did not improve modified Rankin scale scores (mRS) but increased the risk of fractures. We aimed to describe the fractures, their impact on mRS and factors associated with fracture risk

Methods
A UK, multicentre, parallel group, randomised, placebo-controlled trial. Patients ≥18yrs with a clinical stroke and persisting deficit assessed two to 15 days after onset were eligible.
Consenting patients were allocated fluoxetine 20mg or matching placebo for six months. The primary outcome was the mRS at six months and secondary outcomes included fractures.

Results
Sixty five of 3127(2.1%) patients had 67 fractures within six months of randomisation; 43 assigned fluoxetine and 22 placebo. Fifty nine (90.8%) had fallen and 26(40%) had fractured their neck of femur. The effect of fluoxetine on mRS (Common odds ratio (COR)=0.951) was not significantly altered by excluding fracture patients (COR=0.961). Cox proportional hazards modelling showed that only age >70yr (Hazard Ratio (HR)=1.97(95% CI 1.13 to 3.45;p=0.017), female sex (HR=2.13(1.29 to 3.51;p=0.003) and fluoxetine (HR=2.00(1.20 to 3.34;p=0.008) were independently associated with fractures.

Conclusions
Most fractures resulted from falls. Although many fractures were serious, and likely to impair patients’ function, the increased fracture risk did not explain the lack of observed effect of fluoxetine on mRS. Only increasing age, female sex and fluoxetine were independent predictors of fractures.

Clinical trial registration
URL:http://www.controlled-trials.com. ISRCTN83290762