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Fluoxetine for stroke recovery improvement – the doubleblind, randomised placebo-controlled FOCUS-Poland trial
- Department of Clinical Neurophysiology, Institute of Psychiatry and Neurology, Sobieskiego 9, 02-957 Warsaw, Poland
- Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, Poland, Żwirki i Wigury 61, 02-091 Warsaw, Poland
- 2nd Department of Neurology, Institute of Psychiatry and Neurology, Sobieskiego 9, 02-957 Warsaw, Poland
open access
Abstract
Aim of study. The Fluoxetine Or Control Under Supervision (FOCUS)-Poland trial tested in a Polish cohort the hypothesis that fluoxetine improves recovery after stroke.
Clinical rationale for study. Some studies have suggested that fluoxetine may improve functional outcomes after stroke, but these results needed confirmation. Between 2012 and 2014, large clinical trials were initiated by the FOCUS Trial Collaboration. Recently, results from the UK, Sweden, Australia, New Zealand and Vietnam have been published. We here present the results of the FOCUS trial conducted in Poland.
Material and methods. This was a randomised, double-blind, placebo-controlled study based on the FOCUS trial protocol. Patients who had a persisting neurological deficit were randomly assigned 2-15 days after stroke onset to receive for six months either fluoxetine 20 mg/day or a placebo. The primary outcome was functional status measured using the modified Rankin Scale (mRS) at six months after randomisation. Functional status at 12 months was also assessed, as was neurological deficit at six and 12 months. Data was also collected on adverse events.
Results. Between 19 December 2014 and 13 March 2018, 30 patients were given fluoxetine and 31 were given a placebo. For the primary outcome, the distribution across mRS categories was similar for the fluoxetine and placebo groups at six months (common odds ratio 0.88; 95% confidence interval 0.31–2.50; p = 0.81), and there was no difference at 12 months (p = 0.864). There were no differences between groups in stroke recovery or in motor function recovery of the affected hand. There were no significant differences in any other secondary outcomes at six or 12 months. Patients given fluoxetine were less likely than those given the placebo to receive new antidepressant medication within six months (2 [6.67%] vs. 4 [12.90%]).
Conclusions and clinical implications. Consistent with other trials based on the FOCUS protocol, fluoxetine did not improve motor recovery or general stroke outcome at six and 12 months in the Polish cohort studied. However, patients receiving fluoxetine required therapy with additional antidepressant medication less frequently.
Abstract
Aim of study. The Fluoxetine Or Control Under Supervision (FOCUS)-Poland trial tested in a Polish cohort the hypothesis that fluoxetine improves recovery after stroke.
Clinical rationale for study. Some studies have suggested that fluoxetine may improve functional outcomes after stroke, but these results needed confirmation. Between 2012 and 2014, large clinical trials were initiated by the FOCUS Trial Collaboration. Recently, results from the UK, Sweden, Australia, New Zealand and Vietnam have been published. We here present the results of the FOCUS trial conducted in Poland.
Material and methods. This was a randomised, double-blind, placebo-controlled study based on the FOCUS trial protocol. Patients who had a persisting neurological deficit were randomly assigned 2-15 days after stroke onset to receive for six months either fluoxetine 20 mg/day or a placebo. The primary outcome was functional status measured using the modified Rankin Scale (mRS) at six months after randomisation. Functional status at 12 months was also assessed, as was neurological deficit at six and 12 months. Data was also collected on adverse events.
Results. Between 19 December 2014 and 13 March 2018, 30 patients were given fluoxetine and 31 were given a placebo. For the primary outcome, the distribution across mRS categories was similar for the fluoxetine and placebo groups at six months (common odds ratio 0.88; 95% confidence interval 0.31–2.50; p = 0.81), and there was no difference at 12 months (p = 0.864). There were no differences between groups in stroke recovery or in motor function recovery of the affected hand. There were no significant differences in any other secondary outcomes at six or 12 months. Patients given fluoxetine were less likely than those given the placebo to receive new antidepressant medication within six months (2 [6.67%] vs. 4 [12.90%]).
Conclusions and clinical implications. Consistent with other trials based on the FOCUS protocol, fluoxetine did not improve motor recovery or general stroke outcome at six and 12 months in the Polish cohort studied. However, patients receiving fluoxetine required therapy with additional antidepressant medication less frequently.
Keywords
acute stroke, fluoxetine, stroke outcome, motor recovery
Title
Fluoxetine for stroke recovery improvement – the doubleblind, randomised placebo-controlled FOCUS-Poland trial
Journal
Neurologia i Neurochirurgia Polska
Issue
Article type
Research Paper
Pages
544-551
Published online
2020-12-17
Page views
1437
Article views/downloads
1183
DOI
Pubmed
Bibliographic record
Neurol Neurochir Pol 2020;54(6):544-551.
Keywords
acute stroke
fluoxetine
stroke outcome
motor recovery
Authors
Jan P. Bembenek
Maciej Niewada
Bożena Kłysz
Anna Mazur
Katarzyna Kurczych
Marcin Głuszkiewicz
Anna Członkowska
- Katan M, Luft A. Global Burden of Stroke. Semin Neurol. 2018; 38(2): 208–211.
- Robinson RG, Jorge RE. Post-Stroke Depression: A Review. Am J Psychiatry. 2016; 173(3): 221–231.
- Lim CM, Kim SW, Park JY, et al. Fluoxetine affords robust neuroprotection in the postischemic brain via its anti-inflammatory effect. J Neurosci Res. 2009; 87(4): 1037–1045.
- Wang JW, David DJ, Monckton JE, et al. Chronic fluoxetine stimulates maturation and synaptic plasticity of adult-born hippocampal granule cells. J Neurosci. 2008; 28(6): 1374–1384.
- McCann SK, Irvine C, Mead GE, et al. Efficacy of antidepressants in animal models of ischemic stroke: a systematic review and meta-analysis. Stroke. 2014; 45(10): 3055–3063.
- Chollet F, Tardy J, Albucher JF, et al. Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial. Lancet Neurol. 2011; 10(2): 123–130.
- Gu SC, Wang CD. Early Selective Serotonin Reuptake Inhibitors for Recovery after Stroke: A Meta-Analysis and Trial Sequential Analysis. J Stroke Cerebrovasc Dis. 2018; 27(5): 1178–1189.
- Legg LA, Tilney R, Hsieh CF, et al. Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery. Cochrane Database Syst Rev. 2019; 2019(11): e142–e143.
- FOCUS Trial Collaboration. Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial. Lancet. 2019; 393(10168): 265–274.
- AFFINITY Trial Collaboration. Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2020; 19(8): 651–660.
- EFFECTS Trial Collaboration. Safety and efficacy of fluoxetine on functional recovery after acute stroke (EFFECTS): a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2020; 19(8): 661–669.
- Mead G, Hackett ML, Lundström E, et al. The FOCUS, AFFINITY and EFFECTS trials studying the effect(s) of fluoxetine in patients with a recent stroke: a study protocol for three multicentre randomised controlled trials. Trials. 2015; 16: 369.
- Brott T, Adams HP, Olinger CP, et al. Measurements of acute cerebral infarction: a clinical examination scale. Stroke. 1989; 20(7): 864–870.
- Bamford J, Sandercock P, Dennis M, et al. Classification and natural history of clinically identifiable subtypes of cerebral infarction. Lancet. 1991; 337(8756): 1521–1526.
- Adams HP, Bendixen BH, Kappelle LJ, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993; 24(1): 35–41.
- Broderick JP, Adeoye O, Elm J. Evolution of the Modified Rankin Scale and Its Use in Future Stroke Trials. Stroke. 2017; 48(7): 2007–2012.
- Duncan PW, Wallace D, Lai SM, et al. The stroke impact scale version 2.0. Evaluation of reliability, validity, and sensitivity to change. Stroke. 1999; 30(10): 2131–2140.
- Dyck PJ, Boes CJ, Mulder D, et al. History of standard scoring, notation, and summation of neuromuscular signs. A current survey and recommendation. J Peripher Nerv Syst. 2005; 10(2): 158–173.
- Brunnstrom S. Movement therapy in hemiplegia: A neurophysiological approach. New York: Harner and Row Publish. ; 1970.
- Mahoney FI, Barthel DW. Functional evaluation: The Barthel Index. Md State Med J. 1965; 14: 61–65.
- Hoeymans N, Garssen AA, Westert GP, et al. Measuring mental health of the Dutch population: a comparison of the GHQ-12 and the MHI-5. Health Qual Life Outcomes. 2004; 2: 23.
- McCabe CJ, Thomas KJ, Brazier JE, et al. Measuring the mental health status of a population: a comparison of the GHQ-12 and the SF-36 (MHI-5). Br J Psychiatry. 1996; 169(4): 516–521.
- Herdman M, Gudex C, Lloyd A, et al. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res. 2011; 20(10): 1727–1736.
- Tsapakis EM, Gamie Z, Tran GT, et al. The adverse skeletal effects of selective serotonin reuptake inhibitors. Eur Psychiatry. 2012; 27(3): 156–169.
- Wadhwa R, Kumar M, Talegaonkar S, et al. Serotonin reuptake inhibitors and bone health: A review of clinical studies and plausible mechanisms. Osteoporos Sarcopenia. 2017; 3(2): 75–81.
- Myint PK, Poole KES, Warburton EA. Hip fractures after stroke and their prevention. QJM. 2007; 100(9): 539–545.
- Douros A, Dell'Aniello S, Dehghan G, et al. Degree of serotonin reuptake inhibition of antidepressants and ischemic risk: A cohort study. Neurology. 2019; 93(10): e1010–e1020.
- Jensen MP, Ziff OJ, Banerjee G, et al. The impact of selective serotonin reuptake inhibitors on the risk of intracranial haemorrhage: A systematic review and meta-analysis. Eur Stroke J. 2019; 4(2): 144–152.