Fluoxetine and recovery after stroke

Worp, H. Bart van der

doi:10.1016/s0140-6736(18)32983-0

Cited by 12 publications

(12 citation statements)

References 7 publications

(12 reference statements)

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“…The estimates for upper limb FMA scales takes into consideration mRS score changes as part of the equation to define how many points of improvement of FMA would be considered as clinical important changes; changes in these scales are therefore associated with meaningful clinical differences. 53 To date, the mechanisms by which fluoxetine may potentially favor motor function remain uncertain 12 and despite the increase in fluoxetine prescriptions poststroke, the accumulated evidence has not been compelling enough to definitively alter stroke management. Our initial hypothesis was that fluoxetine could modulate the excitatory-inhibitory network balance, thus promoting motor recovery in later stroke phases.…”

Section: Discussionmentioning

confidence: 99%

“…However, they did not perform an ITT analysis, and they did not report how many patients in each group received open-label fluoxetine for depression during the trial; that is, some of the patients in the fluoxetine and placebo groups may have received 40 and 20 mg of fluoxetine respectively; the correlation between mood changes and motor improvement was unclear as well. 12 In the FOCUS trial, fluoxetine also reduced the occurrence of depression in the first 6 months after stroke; however, no correlations with functional or motor outcomes were presented 47 and the trial results did not support the use of fluoxetine to prevent post-stroke depression or to improve functional outcomes. Thus far, there is only one randomized clinical trial showing positive effects of fluoxetine on stroke motor function, 13 and the available meta-analysis evaluated dependency and disability scales (such as mRS) rather than sensorimotor function scales relating to impairment such as FMA.…”

Section: Fluoxetine Motor Function Effectsmentioning

confidence: 94%

“…10,11 While previous studies showed that SSRIs, especially fluoxetine, could improve motor function and reduce stroke-related disability, the evidence remains insufficient to modify stroke treatment guidelines or reduce concerns regarding serious adverse effects. 11,12 Early prescriptions of fluoxetine (20 mg/d 5-10 days after stroke onset) combined with physiotherapy enhanced motor function recovery (FLAME trial) and decreased stroke-related disability 13 ; a Cochrane review on SSRI effects on poststroke rehabilitation also demonstrated improved dependency and disability. 14 However, this review and a previous meta-analysis 15 concluded that motor deficits did not significantly benefit from SSRIs (including fluoxetine) when comparing motor scales, potentially due to SSRI nonfocality.…”

Section: Introductionmentioning

confidence: 99%

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Combining Fluoxetine and rTMS in Poststroke Motor Recovery: A Placebo-Controlled Double-Blind Randomized Phase 2 Clinical Trial

Pinto

Morales-Quezada

Piza

et al. 2019

Neurorehabil Neural Repair

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Background. Although recent evidence has shown a new role of fluoxetine in motor rehabilitation, results are mixed. We conducted a randomized clinical trial to evaluate whether combining repetitive transcranial magnetic stimulation (rTMS) with fluoxetine increases upper limb motor function in stroke. Methods. Twenty-seven hemiparetic patients within 2 years of ischemic stroke were randomized into 3 groups: Combined (active rTMS + fluoxetine), Fluoxetine (sham rTMS + fluoxetine), or Placebo (sham rTMS + placebo fluoxetine). Participants received 18 sessions of 1-Hz rTMS in the unaffected primary motor cortex and 90 days of fluoxetine (20 mg/d). Motor function was assessed using Jebsen-Taylor Hand Function (JTHF) and Fugl-Meyer Assessment (FMA) scales. Corticospinal excitability was assessed with TMS. Results. After adjusting for time since stroke, there was significantly greater improvement in JTHF in the combined rTMS + fluoxetine group (mean improvement: −214.33 seconds) than in the placebo (−177.98 seconds, P = 0.005) and fluoxetine (−50.16 seconds, P < 0.001) groups. The fluoxetine group had less improvement than placebo on both scales (respectively, JTHF: −50.16 vs −117.98 seconds, P = 0.038; and FMA: 6.72 vs 15.55 points, P = 0.039), suggesting that fluoxetine possibly had detrimental effects. The unaffected hemisphere showed decreased intracortical inhibition in the combined and fluoxetine groups, and increased intracortical facilitation in the fluoxetine group. This facilitation was negatively correlated with motor function improvement (FMA, r2 = −0.398, P = 0.0395). Conclusion. Combined fluoxetine and rTMS treatment leads to better motor function in stroke than fluoxetine alone and placebo. Moreover, fluoxetine leads to smaller improvements than placebo, and fluoxetine’s effects on intracortical facilitation suggest a potential diffuse mechanism that may hinder beneficial plasticity on motor recovery.

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Section: Discussionmentioning

confidence: 99%

Section: Fluoxetine Motor Function Effectsmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Combining Fluoxetine and rTMS in Poststroke Motor Recovery: A Placebo-Controlled Double-Blind Randomized Phase 2 Clinical Trial

Pinto

Morales-Quezada

Piza

et al. 2019

Neurorehabil Neural Repair

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“…83 Although there were some differences in the study design between these two large studies, utility of fluoxetine to aid in the motor recovery of adult patients with stroke is not completely clear. 84 Investigators need to study the effectiveness and safety of pharmacologic interventions such as fluoxetine in pediatric stroke directly, as clinical practice varies widely based on patient age and physician preference regarding this potential therapy.…”

Section: What Therapies Can Be Utilized To Promote Recovery In Pediatmentioning

confidence: 99%

Pediatric Stroke: Unique Implications of the Immature Brain on Injury and Recovery

Malone

Felling

2020

Pediatric Neurology

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Pediatric stroke causes significant morbidity for children resulting in lifelong neurological disability. Although hyperacute recanalization therapies are available for pediatric patients, most patients are ineligible for these treatments. Therefore the mainstay for pediatric stroke treatment relies on rehabilitation to improve outcomes. Little is known about the ideal rehabilitation therapies for pediatric patients with stroke and the unique interplay between the developing brain and our models of stroke recovery. In this review, we first discuss the consequences of pediatric stroke. Second, we examine the scientific evidence that exists between the mechanisms of recovery and how they are different in the pediatric developing brain. Finally, we evaluate potential interventions that could improve outcomes.

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“…Recent large-scale RCTs in stroke patients such as the TALOS 34 and FOCUS trials 35 , involving over 642 and 3,000 patients, respectively, however, do not suggest beneficial effects of SSRIs on functional recovery. Critically, however 36 , these RCTs were conducted against the backdrop of routinely available rehabilitation and did not combine SSRI administration with a clearly defined motor learning paradigm, nor did they assess functional brain responses to SSRI intake. As a result, no previous study, either in healthy participants or in patients, has successfully leveraged prolonged training on an established motor learning paradigm in combination with SSRI-administration and fMRI in an adequately powered sample.…”

Section: Introductionmentioning

confidence: 99%

Modulation of premotor cortex response to sequence motor learning during escitalopram-intake

Molloy¹,

Mueller²,

Beinhoelzl³

et al. 2020

Preprint

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The contribution of selective serotonin reuptake inhibitors (SSRIs) to motor learning by inducing motor cortical plasticity remains controversial given diverse findings from positive preclinical data to negative findings in recent clinical trials. To empirically address this translational disparity, we use functional magnetic resonance imaging (fMRI) in a double-blind, randomized controlled study powered to assess whether 20 mg escitalopram improves sequence-specific motor performance and modulates cortical motor response in 64 healthy female participants. We found decreased left premotor cortex responses during sequence-specific learning performance comparing single dose and steady escitalopram state. Escitalopram plasma-levels negatively correlated with the premotor cortex response. We did not find evidence in support of improved motor performance after a week of escitalopram-intake. These findings do not support the conclusion that 1-week escitalopram intake increases motor performance but could reflect early adaptive plasticity with improved neural processing underlying similar task performance when steady peripheral escitalopram levels are reached.

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Fluoxetine and recovery after stroke

Abstract: I am Co-Chief Investigator of two multicentre randomised trials in patients with acute stroke, both related to repositioning of drugs: PRECIOUS (ISRCTN82217627) and MR ASAP (ISRCTN99503308).

Cited by 12 publications

References 7 publications

Combining Fluoxetine and rTMS in Poststroke Motor Recovery: A Placebo-Controlled Double-Blind Randomized Phase 2 Clinical Trial

Combining Fluoxetine and rTMS in Poststroke Motor Recovery: A Placebo-Controlled Double-Blind Randomized Phase 2 Clinical Trial

Pediatric Stroke: Unique Implications of the Immature Brain on Injury and Recovery

Modulation of premotor cortex response to sequence motor learning during escitalopram-intake

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