Randomized controlled trial of Fluoxetine or placebo on quality of life after

Abstract

Introduction:  Acute ischemic stroke is a leading cause of life-altering disability and death among the Thai population. Depression is a significant sequela of stroke which negatively impacts not only physical recovery, but also the quality of life of stroke survivors.  Fluoxetine has been involved in numerous studies in improving functional recovery and preventing post-stroke depression, but with limited findings on the quality of life of stroke patients receiving fluoxetine.  This current study strived to ascertain the effects of fluoxetine on the quality of life of patients with acute ischemic stroke following discharge.  

Methods:  A prospective, double blinded, randomized controlled trial was conducted at Bhumibol Adulyadej Hospital (Bangkok, Thailand) among 60 patients of consenting age admitted with acute ischemic stroke between April 2019 – March 2020.  Patients with a diagnosed mental illness, complications following ischemic stroke, inability to communicate, or had high scores on depression screening tools were excluded.  Enrolled patients were given either fluoxetine or a matching placebo upon discharge to take once daily for 90 days.  They were also scheduled for assessments of quality of life, depression screening, and stroke evaluation at one month and three months following discharge.  As of December 2019, 34 patients have been enrolled and followed up at the outpatient department. The primary outcome is the proportion of patients who have a clinically significant improvement (≥0.1) of quality of life at 3 months as measured by EQ-5D-5L.  Quality of life as measured by the modified Rankin score (mRS) and incidence of depression as monitored by the 9Q questionnaire were studied as secondary outcomes.  Proportional variables were compared using Chi-squared test and Fisher’s exact test and continuous variables were compared using T-test or Mann Whitney U test where appropriate.  Statistical analyses were carried out using SPSS version 19.  

Results:  An interim analysis was planned after the complete follow up of 30 patients.  A total of 34 patients were enrolled in which 3 patients were lost to follow up (1 from the fluoxetine group and 2 from the placebo group).  Patient baseline characteristics including age, sex, body mass index, and alcohol and tobacco usage were not significantly different between the two groups.  Baseline EQ-5D-5L, EQ-VAS, hospital anxiety and depression scale (Thai-HADS), and modified Rankin score (mRS) were similar between the two groups, while 9Q scores in the placebo group (mean=4) was significantly greater although not exceeding the cut-off point for a positive screening of depression (p=0.015).  Improvements of EQ-5D-5L scores at the final follow up for patients receiving fluoxetine were higher than those receiving placebo (75% vs. 46.7%), but were not statistically significant (p=0.106).  Proportions of patients with mRS ≤ 2 at 3 months were not significantly different between the placebo and the Fluoxetine group (p=1.0).  A greater proportion of patients in the placebo group had a 9Q score of > 7 at the final visit as compared to the Fluoxetine group (33.5% vs. 18.75%).  No major adverse effects accountable to fluoxetine were observed.      

Conclusion: In this interim analysis, prescribing fluoxetine to patients after acute ischemic stroke revealed a potential for positive improvement of quality of life compared to placebo, although improvements of functional outcomes were equivocal.  The incidence of higher depression screening scores was greater in patients who received placebo, suggesting fluoxetine as a potential agent for the prevention of post-stroke depression.