SSRI vs NDRI: Which Is Better for Post-Stroke Depression?

 Your competent? doctor has already summarized this research right? I've got nothing on NDRIs. If your doctor is talking depression meds IT MEANS THEY ARE FUCKING INCOMPETENT IN GETTING YOU 100% RECOVERED!

• SSRIs (31 posts to January 2013) Benefits and problems in here.

SSRI vs NDRI: Which Is Better for Post-Stroke Depression?

SAN FRANCISCO — The selective serotonin reuptake inhibitor (SSRI) fluoxetine and the norepinephrine-dopamine reuptake inhibitor (NDRI) bupropion are each effective for different psychiatric symptoms of post-stroke depression (PSD), new research suggests. 

In a large retrospective cohort study with data for more than 100,000 patients with PSD, bupropion was associated with a significantly lower risk for suicidal ideation — the primary outcome — compared to treatment with fluoxetine.

However, for the secondary outcome of decreased demoralization and apathy, fluoxetine was the winner. (No 100% recovery protocols is the cause of demoralization! GET THERE!)

The results highlight the importance of customizing PSD treatment to the patient, said investigator Jaime Villa, an incoming first-year medical student at Reading Hospital, Tower Health System. 

Article Key Points

Fluoxetine and bupropion show distinct benefits for post-stroke depression, with bupropion reducing suicidal ideation risk and fluoxetine alleviating demoralization and apathy. Customizing treatment based on symptoms is crucial for effective management.

“For clinicians, the take-away message is that each of these antidepressants have a different effect on transmitters in the body,” Villa told Medscape Medical News. “So I’d say: focus on the symptoms and just treat each with the appropriate antidepressant.” The findings were presented May 17 at the American Psychiatric Association (APA) 2026 Annual Meeting. 

Large Cohort 

Depression is a common complication of stroke, affecting about 1 in 3 survivors, and is associated with poor recovery and increased morbidity. Most PSD cases occur within the first year post-stroke.

Fluoxetine is considered a first-line treatment for PSD, with both SSRIs and serotonin-norepinephrine reuptake inhibitors often prescribed for the condition. Caution has been urged for bupropion use in this population because it lowers the seizure threshold, and some studies have suggested a slightly higher risk for bleeding events. 

The new retrospective cohort study aimed to address the lack of head-to-head data for secondary psychiatric outcomes between antidepressant classes. 

“We wanted to look at the effect SSRIs and NDRIs had on the body for specific symptoms of depression,” Villa noted. 

For the analysis, investigators included 2005-2025 data for 108,664 adult patients (mean age, 64 years; 59% women; 73% White) from the TriNetX Research Network database. All had been diagnosed with PSD within a year previously, with half receiving treatment with fluoxetine and the other half receiving bupropion.

Individualized Treatment Needed 

Results showed a significantly lower suicidal ideation risk for the bupropion-treated group compared to the fluoxetine group (odds ratio [OR], 0.76; P < .05), as well as a lower percentage of recurrence (2.04% vs 2.66%, respectively). 

However, bupropion was linked to greater increased risk for demoralization and apathy vs fluoxetine (OR, 1.54; P < .05), with a higher percentage of recurrence (0.13% vs 0.08%). 

NDRIs increase the concentration of dopamine and norepinephrine and are known to regulate energy, motivation, and reward pathways, which Villa said could account for its efficacy for suicidal ideation prevention in patients with PSD. 

Fluoxetine acts as a mood stabilizer and stress reliever, which makes it effective for such symptoms as apathy. However, it has a lower likelihood of affecting other neurotransmitters, including dopamine and norepinephrine, which may explain why it was less effective at preventing suicidal ideation, Villa added. 

“These findings highlight differential psychiatric effects across antidepressant classes and underscore the importance of individualized treatment selection in PSD management,” he said. 

The findings also underscore that clinicians have options depending on their patient's symptoms, he added.

Potentially Practice Changing? 

The results offer some unexpected findings, said Charles S. Nguyen, MD, clinical professor of psychiatry at the University of California, Riverside, who was not part of the study.

“I always thought with bupropion, because it can lower the seizure threshold, maybe there’s a higher risk for seizures post-stroke. So I would not have thought that it would be a good choice to make” for this patient population, Nguyen told Medscape Medical News. 

“We all knew that it could potentially be helpful, and after I look at this data showing it can help, I may be more inclined to consider it in my own practice in the future,” Nguyen added. 

One question the research doesn’t answer, he noted, is whether there was an increased risk of stroke recurrence in the study participants. 

Asked later about this concern, Villa said that while that outcome was not assessed in the current study, it would be an important topic to look into in the future. 

Comparative Efficacy of Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) in the Management of Post-stroke Depression: A Systematic Review of Randomized Controlled Trials

 You wouldn't need depression meds if you had 100% recovery protocols! Or are you that blitheringly stupid you can't see solving the primary problem negates the need for working on the secondary problem? Well, ARE YOU STUPID OR NOT? Your patients would like to know your intelligence level.

Comparative Efficacy of Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) in the Management of Post-stroke Depression: A Systematic Review of Randomized Controlled Trials 

Zarin Nudar Rodoshi • Sharen Shibu • Osman Omer • Hamza Tallal • Muhammad Zubair Dawud Gondal • Zayam Shahid • Ayesha Azam • Noor Abbas

Published: May 25, 2025 DOI: 10.7759/cureus.84784 Peer-Reviewed Cite this article as: Rodoshi Z, Shibu S, Omer O, et al. (May 25, 2025) Comparative Efficacy of Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) in the Management of Post-stroke Depression: A Systematic Review of Randomized Controlled Trials. Cureus 17(5): e84784. doi:10.7759/cureus.84784

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Abstract

Post-stroke depression (PSD) is a common neuropsychiatric complication that adversely affects rehabilitation outcomes, cognitive recovery, and quality of life in stroke survivors. While selective serotonin reuptake inhibitors (SSRIs) are widely used as first-line treatment, serotonin-norepinephrine reuptake inhibitors (SNRIs) have emerged as potential alternatives with broader neurochemical targets. This systematic review aimed to compare the efficacy of SSRIs and SNRIs in the treatment and prevention of PSD. A comprehensive literature search was conducted across PubMed, Embase, Scopus, and Google Scholar in accordance with PRISMA guidelines, applying filters for English-language clinical trials. Five randomized controlled trials met the inclusion criteria and were analyzed. The findings revealed that both SSRIs and SNRIs significantly improved depressive symptoms, with escitalopram showing early and superior antidepressant effects compared to sertraline. SNRIs like duloxetine and reboxetine demonstrated added benefits in cognitive outcomes, prevention of PSD, and symptom subtype-specific efficacy, particularly in retarded depression. While the overall risk of bias was low in most studies, limitations such as small sample sizes and limited direct head-to-head comparisons were noted. These results support the clinical utility of both drug classes and emphasize the need for individualized pharmacologic strategies based on patient characteristics and symptom profiles.

More at link.

SSRIs May Speed Up Cognitive Decline

 Your competent? doctor should not have to treat depression at all if they have EXACT 100% RECOVERY PROTOCOLS! No need to even treat depression then from your stroke.

SSRIs May Speed Up Cognitive Decline

Summary: A new study based on data from 18,740 dementia patients suggests that antidepressants may accelerate cognitive decline. Researchers found that patients taking antidepressants, particularly SSRIs like escitalopram, citalopram, and sertraline, experienced faster deterioration compared to those not on medication.

While depression itself can worsen dementia symptoms, the findings highlight the need for more tailored antidepressant choices in dementia care. Future research will explore whether specific dementia types or biomarkers influence how patients respond to different antidepressants.

Key Facts

• Faster Cognitive Decline: Dementia patients on antidepressants showed greater cognitive deterioration over time.
• SSRI Impact: Escitalopram, citalopram, and sertraline were linked to the fastest decline, while mirtazapine had a milder effect.
• Need for Individualized Care: Researchers aim to identify patient subgroups that may respond better or worse to specific antidepressants.

Source: Karolinska Institute

New research suggests that antidepressants can accelerate cognitive decline in people with dementia. At the same time, some drugs appear to be less harmful than others, which can help doctors make better treatment decisions, according to the study published in BMC Medicine.

Antidepressants are often used to relieve symptoms such as anxiety, depression, aggressiveness, and sleep disturbances in dementia sufferers.

Credit: Neuroscience News

However, a new observational study based on data from the Swedish Dementia Registry (SveDem) shows that patients with dementia who are treated with antidepressants experience an increased cognitive decline compared to patients who do not receive this medication.

The study is based on a comprehensive analysis of registry data from 18,740 patients, of whom approximately 23 percent were treated with antidepressants. During the course of the study, a total of 11,912 prescriptions of antidepressants were registered, with selective serotonin reuptake inhibitors (SSRIs) accounting for 65 percent.

“Depressive symptoms can both worsen cognitive decline and impair quality of life, so it is important to treat them. Our results can help doctors and other healthcare professionals choose antidepressants that are better adapted for patients with dementia,” says Sara Garcia Ptacek, researcher at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, and the study’s last author.

The researchers from Karolinska Institutet and Sahlgrenska University Hospital in Gothenburg have followed the patients’ cognitive development over time and compared both medicated and non-medicated groups as well as different types of antidepressants.

Although it is not currently possible to determine whether the cognitive impairment is due to the drugs or to the depressive symptoms themselves, the researchers were able to see that antidepressants were associated with increased cognitive decline.

Differences between drugs

The study also points to differences between different drugs. The SSRI escitalopram was associated with the fastest cognitive decline, followed by the SSRIs citalopram and sertraline.

The researchers now want to investigate whether certain patient groups, such as people with specific dementia types or biomarkers, respond better or worse to different antidepressants. Credit: Neuroscience News

Mirtazapine, which has a different mechanism of action, had less negative cognitive impact than escitalopram.

The researchers now want to investigate whether certain patient groups, such as people with specific dementia types or biomarkers, respond better or worse to different antidepressants.

“The goal is to find these subgroups to create more individualised care,” says Sara Garcia Ptacek.

Funding: The study has been funded by the Swedish Research Council, Region Stockholm, the Swedish Dementia Research Foundation, the Alzheimer’s Foundation and New Innovative Roads Call – a private initiative from the Leif Lundblad family and others. The researchers report no conflicts of interest.

About this psychopharmacology and cognition research news

Author: Press Office
Source: Karolinska Institute
Contact: Press Office – Karolinska Institute
Image: The image is credited to Neuroscience News

Original Research: The findings will appear in BMC Medicine

Evaluating the Effectiveness of Neuroprotective Strategies in Enhancing Post-stroke Recovery: A Systematic Review of Meta-Analyses and Clinical Trials

 First of all, stop using the term, neuroprotection! Neuronal cascade of death is the correct term! It gives absolutely NO SENSE OF URGENCY! If you tell your patients, you know nothing about stopping  the 5 causes of the neuronal cascade of death in the first week thus letting die hundreds of millions to billions of neurons.  They might just get angry with your incompetence!

Send me hate mail on this: oc1dean@gmail.com. I'll print your complete statement with your name and my response in my blog. Or are you afraid to engage with my stroke-addled mind? I would like to know why you aren't solving stroke to 100% recovery, because this doesn't solve stroke recovery at all!

Evaluating the Effectiveness of Neuroprotective Strategies in Enhancing Post-stroke Recovery: A Systematic Review of Meta-Analyses and Clinical Trials 

Published: October 12, 2024

DOI: 10.7759/cureus.71343 

 Peer-Reviewed

Cite this article as: Hassan B, Dabas M M, Kanemitsu K, et al. (October 12, 2024) Evaluating the Effectiveness of Neuroprotective Strategies in Enhancing Post-stroke Recovery: A Systematic Review of Meta-Analyses and Clinical Trials. Cureus 16(10): e71343. doi:10.7759/cureus.71343

Abstract

This systematic review evaluates the effectiveness of various neuroprotective strategies in enhancing recovery following acute ischemic stroke, focusing on interventions such as normobaric oxygen (NBO), lithium, selective serotonin reuptake inhibitors (SSRIs), and Cerebrolysin. Drawing upon data from six primary studies, including randomized controlled trials (RCTs) and meta-analyses, we assessed these therapies' impact on functional outcomes, motor recovery, and neurological improvement. Normobaric oxygen, across 12 RCTs, demonstrated limited efficacy in improving recovery outcomes or reducing mortality. Lithium, supported by animal models but with inconclusive human data, showed potential in reducing stroke volume but did not significantly enhance functional recovery in clinical trials. SSRIs, particularly fluoxetine, showed moderate success in improving motor recovery, as evidenced by the FLAME (Fluoxetine for Motor Recovery after Acute Ischaemic Stroke) trial and meta-analyses. Cerebrolysin demonstrated consistent improvement in early neurological function and motor recovery, with a number-needed-to-treat (NNT) of 7.1 for early NIHSS (National Institutes of Health Stroke Scale) score improvements. Our Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided search covered PubMed, Medline, Embase, and the Cochrane Library up to September 2024. These findings emphasize the mixed efficacy of these neuroprotective interventions and underscore the necessity for personalized treatment protocols and further large-scale, controlled trials to clarify their roles in clinical practice. This review contributes to the ongoing dialogue on optimizing post-stroke recovery and highlights the critical need for evidence-based neuroprotective strategies.

Introduction & Background

Stroke remains one of the leading causes of death and disability worldwide, with ischemic stroke accounting for the majority of cases. The pathophysiology of stroke involves a cascade of events, including excitotoxicity, oxidative stress, inflammation, and apoptosis, all contributing to brain injury and long-term neurological deficits [1]. Early intervention with neuroprotective therapies has the potential to limit such damage and enhance functional recovery [2]. Despite significant advancements in acute stroke care, such as thrombolysis and thrombectomy, there is still an unmet need for effective neuroprotective strategies that can be implemented during the subacute phase of stroke recovery [3].

We selected normobaric oxygen (NBO), lithium, selective serotonin reuptake inhibitors (SSRIs), and Cerebrolysin for review due to their unique mechanisms of action and their emerging roles in neuroprotection and post-stroke recovery. These therapies have shown varying degrees of promise in both preclinical studies and early-phase clinical trials. NBO has been explored for its ability to increase oxygen delivery to ischemic brain tissue, though meta-analyses suggest that it may not significantly improve functional outcomes [4,5]. Lithium, widely known for its mood-stabilizing effects, has demonstrated potential in reducing stroke volume and improving post-stroke function in animal models, but human data remain inconclusive. SSRIs, particularly fluoxetine, have garnered attention for their ability to enhance motor recovery post-stroke, independent of their antidepressant effects, as supported by the FLAME (Fluoxetine for Motor Recovery After Acute Ischemic Stroke) trial and subsequent meta-analyses [6]. Cerebrolysin, a neuropeptide preparation, has been the subject of multiple randomized controlled trials (RCTs) and meta-analyses, with studies suggesting its potential for early neurological improvement, though evidence of long-term benefits remains limited [7].

These four interventions were selected based on their clinical relevance, availability of substantial data from RCTs and meta-analyses, and their distinct neuroprotective mechanisms. Compared to other emerging interventions, such as hypothermia, neurotrophic factors, and stem cell therapies, NBO, lithium, SSRIs, and Cerebrolysin have garnered the most clinical attention and research, making them well-suited for a focused systematic review. The objective of this review is to evaluate the efficacy of these neuroprotective strategies in improving post-stroke recovery, particularly in terms of functional outcomes, motor recovery, and neurological improvement. By synthesizing data from clinical trials and meta-analyses, this review aims to provide a clearer understanding of the benefits and limitations of these therapies in stroke rehabilitation.

More at link.

SSRI No Help for Depression After Stroke

Depression is the result of having NO PROTOCOLS LEADING TO 100% RECOVERY.  Fix that and you wouldn't have to treat this secondary problem. 

SSRI No Help for Depression After Stroke

— Does AFFINITY completely shut the door on a possible benefit?

by Kate Kneisel, Contributing Writer, MedPage Today August 2, 2021

Daily treatment with a selective serotonin reuptake inhibitor (SSRI) had no effect on stroke survivors' risk of depression, which decreased on its own by 6 months, a secondary analysis of the AFFINITY trial found.

Among study participants who had experienced a recent stroke, fluoxetine (Prozac) use did not reduce clinically significant symptoms of depression, which at baseline affected 18.9% of the fluoxetine group and 18.5% of the placebo group and dropped at 26 weeks to 7.0% and 8.2% (P=0.41), respectively, according to the study published in JAMA Neurology.

Cumulative prevalence of clinically significant symptoms during the study was 20.2% of the fluoxetine group and 21.1% of the placebo group (P=0.70), reported Osvaldo Almeida, PhD, of University of Western Australia in Perth, and colleagues.

Likewise, rates of newly developed, self-assessed depression during the study were similar in both fluoxetine- and placebo-treated groups (13.0% vs 14.8%, P=0.43).

"The results of the AFFINITY trial showed that the prevalence of clinically significant symptoms of depression decreases steadily during the first 6 months after a stroke associated with minimal to moderate neurologic deficits, and such a decrease is not affected by the routine daily use of 20 mg of fluoxetine hydrochloride," the group concluded.

Thus, their analysis failed to replicate the positive findings from other fluoxetine trials in the setting of stroke.

Interest in potential benefits of fluoxetine's role post-stroke depression -- affecting one in every three patients within a year of the stroke -- had been fueled a decade ago when the FLAME trial reported that 20 mg daily of fluoxetine enhanced motor recovery and decreased the proportion of stroke survivors with depression at 3 months. While functional improvement was not replicated in subsequent trials, benefits in depression were observed again in the FOCUS and EFFECTS trials.

The main finding of AFFINITY had been fluoxetine's lack of a improvement on functional outcome after stroke -- but an increase in falls, bone fractures, and epileptic seizures.

For now, "use of fluoxetine to prevent post-stroke depression should be considered only if the evidence of benefit outweighs the potential risk of harm," the investigators said.

In an accompanying editorial, Michael Hill, MD, MSc, and Sean Dukelow, MD, PhD, both of the University of Calgary in Alberta, noted that in clinical practice, "pharmacologic treatments for depression are started a bit (or much) later than the 15 days after stroke used in the AFFINITY trial and after clinician-administered assessments of depression are conducted."

For their secondary analysis, Almeida and colleagues assessed the prevalence of depression in 1,221 patients enrolled in AFFINITY within 2-15 days of experiencing a stroke. Participants had been recruited from centers in Australia, New Zealand, and Vietnam between January 2013 and June 2019, with 614 randomly assigned to 20 mg of fluoxetine hydrochloride daily, and 607 to placebo.

The groups were balanced in baseline demographic and clinical measures. Participants in each study arm averaged 64 years of age, and approximately 63% were men; median stroke severity was moderate, with an NIH Stroke Scale score of 6.

Notably, in contrast to earlier studies using a non-structured clinician diagnosis of depression, AFFINITY investigators relied on the self-administered Patient Health Questionnaire (PHQ)-9 to assess for signs and symptoms of depression.

"That our ... repeated assessments with a valid depression instrument failed to replicate [previous fluoxetine trial] results showed that agreement between the PHQ-9 definition of depression and participant-reported diagnosis of depression is poor," Almeida and coauthors noted.

Indeed, of the AFFINITY participants with PHQ-9 scores below 9 at baseline, there was a trend toward less clinician-diagnosed depression in the fluoxetine group (4.3% vs 7.0%, P=0.05).

"Diagnosing major depression in the first 15 days after stroke likely has lower specificity than waiting longer and allowing time for [a more comprehensive assessment]," study authors added.

Fluoxetine also did not reduce the secondary outcome of proportion of participants who were prescribed a non-trial antidepressant or nonpharmacologic treatment.

Interaction with time was not significant, nor were results affected by patient factors including type of stroke, sex, history of depression, and country.

Almeida and colleagues cautioned that these results apply primarily to patients with stroke who had mild to moderate neurologic deficits, thus were able to complete the PHQ-9. They acknowledged that the loss of one-third of participants by week 26 may have rendered the study underpowered to show a modest reduction in depression risk.

"It may also be worthy to consider that, like any major illness, stroke will be commonly associated with an adjustment disorder as patients go through a process of grieving, before adapting and compensating," according to Hill and Dukelow.

"The implication is that the effect size sought may have been too large -- the authors calculated that the study had adequate power to detect a 7% risk difference. Clinically smaller changes, measured using this instrument or perhaps with a combination of existing instruments, could still be important to stroke recovery," the editorialists said.

• 

  Kate Kneisel is a freelance medical journalist based in Belleville, Ontario.

Disclosures

AFFINITY was funded by the Australian National Health and Medical Research Council.

Almeida disclosed grants from National Health and Medical Research Council of Australia.

Hill reported grant support to the University of Calgary from NoNO Inc, Boehringer-Ingelheim, and Medtronic; owning stock in PureWeb; being a director of the Canadian Federation of Neurological Sciences, Canadian Stroke Consortium, and Circle NeuroVascular; and receiving grant support from Alberta Innovates Health Solutions, Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada, and National Institutes of Neurological Disorders and Stroke.

Dukelow reported grants from Brain Canada and personal fees from Prometheus Medical, Sinntaxis, Ipsen, and Allergan.

Primary Source

JAMA Neurology

Source Reference: Almeida OP, et al "Depression outcomes among patients treated with fluoxetine for stroke recovery: the AFFINITY randomized clinical trial" JAMA Neurol DOI: 10.1001/jamaneurol.2021.2418.

Secondary Source

JAMA Neurology

Source Reference: Hill MD, Dukelow SP "Poststroke selective serotonin reuptake inhibitors -- do they work for anything?" JAMA Neurol; DOI:10.1001/jamaneurol.2021.1907.

 

Risk of Fractures in Stroke Patients Treated With a Selective Serotonin Reuptake Inhibitor

Just in case your doctor did not get the memo that SSRIs originally thought to help rehab do not really help. Good thing I was only on these for a couple of months because I fell a lot on my left hip in order to strengthen it and prevent breaking my hip when I really get old. Don't listen to me, I'm not medically trained.

A while ago SSRIs were considered helpful in recovery.

Common antidepressant can help stroke patients improve movement and coordination Sept. 2015 

 

Antidepressants may help people recover from stroke even if they are not depressed Jan. 2013

  

 Have your doctor explain why  this discrepancy occurred between the upper two and this lower one.

 Then further research disproved that. 

 

Is there a suitable drug for stroke recovery?

The latest here:

Risk of Fractures in Stroke Patients Treated With a Selective Serotonin Reuptake Inhibitor

A Systematic Review and Meta-Analysis

Joshua S. Jones

,

Rina Kimata

,

Osvaldo P. Almeida

,

Graeme J. Hankey

Originally published25 Jun 2021https://doi.org/10.1161/STROKEAHA.120.032973Stroke. ;0:STROKEAHA.120.032973

Abstract

Background and Purpose:

Stroke survivors have an increased risk of depression and bone fractures. Selective serotonin reuptake inhibitors (SSRIs) have been associated with an increased risk of fractures in observational studies. Several randomized controlled trials (RCTs) reporting the effect of SSRIs on the risk of fractures in stroke survivors have been published recently but have not been subject to a meta-analysis. We aimed to determine the risk of fractures associated with the use of SSRIs, and the risk of falls, seizures, and recurrent strokes as possible mediators of fractures, in stroke survivors.

Methods:

We conducted a systematic review and meta-analysis of RCTs of SSRIs in stroke survivors according to a protocol registered in PROSPERO (CRD42020192632). Web of Science, EMBASE, PsycINFO, and Ovid Medline/PubMed bibliographic databases, clinical trial registers, and grey literature sources were searched. RCTs of SSRIs versus placebo or no intervention that report the risk of fractures in adult survivors of hemorrhagic or ischemic stroke were included. Two reviewers independently screened search results and extracted data. Meta-analyses were conducted for each outcome using the Mantel-Haenszel random-effects models.

Results:

The searches yielded 683 records, of which 4 RCTs of 6 months duration with a total of 6549 participants were included in the meta-analysis: 3 studies of fluoxetine and 1 study of citalopram. Treatment with an SSRI for 6 months increased the risk of fractures with a risk ratio of 2.36 (95% CI, 1.64–3.39) compared with placebo. The risk of falls, seizures, and recurrent stroke was not statistically significantly increased. Only studies of fluoxetine and citalopram were available for inclusion in the review, and hence the generalizability of the findings to other SSRIs is uncertain.

Conclusions:

Based on available RCTs of fluoxetine and citalopram, SSRIs used for 6 months doubled the risk of fractures in stroke survivors.(So unless your doctors and therapists have a perfect fall prevention protocol you probably don't want this.)

Registration:

URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42020192632.

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Serotonin Levels and Cognitive Recovery in Patients with Subacute Stroke after Rehabilitation Treatment

A while ago SSRIs were considered helpful in recovery.

Common antidepressant can help stroke patients improve movement and coordination Sept. 2015 

 

Antidepressants may help people recover from stroke even if they are not depressed Jan. 2013

  

 Have your doctor explain why  this discrepancy occurred between the upper two and this lower one.

 Then further research disproved that. 

 

Is there a suitable drug for stroke recovery?

The latest here with a lot of big words:

Serotonin Levels and Cognitive Recovery in Patients with Subacute Stroke after Rehabilitation Treatment

t
Mariacristina Siotto 1
, Marco Germanotta 1,* , Massimo Santoro 2
, Valeria Cipollini 1
, Giulia Guardati 1
,
Dionysia Papadopoulou 1
, Elisa Bray 1
, Alessia Mastrorosa 1 and Irene Aprile 1





Citation: Siotto, M.; Germanotta, M.;
Santoro, M.; Cipollini, V.;
Guardati, G.; Papadopoulou, D.;
Bray, E.; Mastrorosa, A.; Aprile, I.
Serotonin Levels and Cognitive
Recovery in Patients with Subacute
Stroke after Rehabilitation Treatment.
Brain Sci. 2021, 11, 642. https://
doi.org/10.3390/brainsci11050642
Academic Editors: Stefano Paolucci,
Giovanni Morone and Marco Iosa
Received: 22 March 2021
Accepted: 11 May 2021
Published: 15 May 2021
Publisher’s Note: MDPI stays neutral
with regard to jurisdictional claims in
published maps and institutional affiliations.
Copyright: © 2021 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
1
IRCCS Fondazione Don Carlo Gnocchi ONLUS, 50143 Florence, Italy; msiotto@dongnocchi.it (M.S.);
vcipollini@dongnocchi.it (V.C.); gguardati@dongnocchi.it (G.G.); dpapadopoulou@dongnocchi.it (D.P.);
ebray@dongnocchi.it (E.B.); amastrorosa@dongnocchi.it (A.M.); iaprile@dongnocchi.it (I.A.)
2 Division of Health Protection Technologies ENEA-Italian National Agency for New Technologies,
Energy and Sustainable Economic Development, 00123 Rome, Italy; massimo.santoro@enea.it
* Correspondence: mgermanotta@dongnocchi.it; Tel.: +39-0633086550

Abstract: 

Post-stroke depression and cognitive impairment are common conditions affecting patients after stroke. Serotonin is a neurotransmitter involved in modulating, among others, mood, cognition, learning, and memory. Sub-optimal serotonin activity may be in part responsible for cognitive deficits seen in depression. In this pilot study serotonin levels were evaluated in 29 patients withsub-acute stroke before and after a rehabilitation treatment (consisting of a program of upper limb robotic rehabilitation in addition to conventional physical therapy treatment). We employed the Back Depression Inventory scale to evaluate symptoms of depression, and specific tools to evaluate cognitive functions. We found a significant reduction of the serotonin levels after rehabilitation in the whole group (T0: 85.9 ± 92.4 ng/mL; T1: 61.9 ± 58.4 ng/mL; p = 0.0018), as well as in the subgroup of patients untreated with Selective Serotonin Reuptake Inhibitors (SRRI), (mean serotonin at T0: 154.0 ± 102.3 ng/mL; mean serotonin at T1: 92.9. ± 68.7 ng/mL at T1; p = 0.005). We also found a correlation with cognitive assessment: in particular, the change from baseline of the serotonin(∆Serotonin) was correlated with the changes from baseline of the Rey’s Figure (∆ROCF) (r = 0.535; p < 0.05), the Tower of London (∆ToL) (subscore point: r = 0.621; p < 0.005; subscore time: r = −0.619; p < 0.005) meaning that a serotonin levels decrease is associated with a worsening of cognitive functions. Considering patients treated and untreated with SSRIs separately, in patients treated with SSRIs (n = 16) we found only a positive correlation between ∆Serotonin and ∆ToL (subscore point: r= 0.587; p = 0.045), whereas in patients untreated with SSRIs (n = 13) we found a positive correlations between ∆Serotonin and ∆ROCF (r = 0.700; p = 0.036), ∆Stroop (subscore time: r = 0.750; p = 0.020) and ∆Tol (subscore point: r = 0.740; p = 0.023) and a negative correlation between ∆Serotonin and ∆Tol (subscore time: r= −0.833; p = 0.005). These results suggest that variation of serotonin levels should be monitored in patients during a rehabilitation program, not only for their relationship with depression symptoms, but also for the correlation with cognitive performance.
Keywords: post-stroke depression; post-stroke cognitive impairment; serotonin; 5-HT; stroke; rehabilitation; cognitive functions; SSRIs.

Do commonly prescribed antidepressants(SSRIs) increase the risk of bleeding stroke? NO

A while ago SSRIs were considered helpful in recovery.

Common antidepressant can help stroke patients improve movement and coordination Sept. 2015 

 

Antidepressants may help people recover from stroke even if they are not depressed Jan. 2013

  

 Have your doctor explain why  this discrepancy occurred between the upper two and this lower one.

 Then further research disproved that. 

 

Is there a suitable drug for stroke recovery?

The latest here:

Do commonly prescribed antidepressants(SSRIs) increase the risk of bleeding stroke? NO

There is good news for people who take antidepressants called selective serotonin reuptake inhibitors (SSRIs), the most commonly prescribed antidepressants in the United States. A new preliminary study has found that they are not associated with an increased risk of intracerebral hemorrhage, the deadliest kind of stroke. The preliminary study released today, February 25, 2021, will be presented at the American Academy of Neurology’s 73^rd Annual Meeting being held virtually April 17 to 22, 2021.

An intracerebral hemorrhage is when a blood vessel bursts in the brain sending blood into the surrounding tissue. The most common causes are high blood pressure and head trauma, but some studies have also suggested that SSRIs may increase a person’s risk of this type of bleeding stroke.

“Selective serotonin reuptake inhibitors work by preventing reabsorption of the chemical serotonin, which regulates mood, into the cells, making more of it available in the brain,” said study author Mithilesh Siddu, MD, of the University of Miami in Florida and member of the American Academy of Neurology. “However, by interfering with serotonin, which also plays a role in blood clotting, SSRIs may increase the risk of bleeding. Therefore, to determine if these antidepressants increase the risk of bleeding strokes, we looked at a large population of people with stroke.”

For the study, researchers identified 127,915 people who had a stroke between 2010 to 2019. A total of 17,009 people had been prescribed antidepressants prior to their stroke and the other 110,906 had never had an SSRI prescription.

Researchers found that 11% of people who had been prescribed antidepressants had an intracerebral hemorrhage, compared to 14% of the people who had not. After adjusting for other factors that could affect stroke risk, such as age, high blood pressure and diabetes, researchers found that people who took antidepressants were just as likely to have an intracerebral hemorrhage as people not taking such medications.

“These findings are important, especially since depression is common after stroke and selective serotonin reuptake inhibitors are some of the first drugs considered for people,” said Siddu. “More research is needed to confirm our findings and to also examine if SSRIs prescribed after a stroke may be linked to risk of a second stroke.”

A limitation of the study was that some details regarding the length, dosage and type of antidepressants were not available to be included in the study.

To read more, click here

 

 

Stroke neurorehabilitation: what future (if any) for fluoxetine?(type of antidepressant known as an SSRI)

My confidence level is zero that any stroke hospital will be following this. But surprise me.

Stroke neurorehabilitation: what future (if any) for fluoxetine?(type of antidepressant known as an SSRI)

17/07/2020/in ESO, Stroke Research /by Jennifer Thomsen

by Giuseppe Reale, MD – Department of Neurosciences, Università Cattolica del Sacro Cuore – Rome
Nine years ago, the FLAME trial burst in the stroke neurorehabilitation panorama¹. This trial (n=118) showed that ischemic stroke patients with hemiparesis/hemiplegia who had started fluoxetine 20 mg die within 5-10 days had better 3-months functional outcomes, if compared to placebo. The primary endpoint was Fugl-Meyer Motor Scale (FMMS); among secondary endpoints, modified Rankin Scale (mRS) and NIHSS motor sub-scores were lower too in the fluoxetine group. Noticeably, the median baseline NIHSS of both groups was about 13 and all patients received physiotherapy.
Putting together the results of the FLAME trial and the previous works on fluoxetine efficacy in animal models², three large randomized controlled trials were soon started: FOCUS, EFFECTS and AFFINITY.
However, the results of the FOUCS trial (n= 3127), published in 2019, quite dampened the enthusiasm³. This trial included patients with ischemic and hemorrhagic stroke and a persistent neurological deficit (87% and 29% had a motor deficit or aphasia, respectively, in both arms), median baseline NIHSS was 6. Fluoxetine 20 mg die was started within 2-15 days after stroke and continued for three months, while the primary outcome was 6-months mRS score. The trial did not show any benefit of fluoxetine on 6-months disability, while it documented a reduced risk of post-stroke depression and an increased risk of bone fracture.
FOCUS and FLAME trials had some differences, such as baseline severity (NIHSS 6 vs 13), population (ischemic vs ischemic + hemorrhagic stroke, hemiparesis/hemiplegia vs persistent neurological deficit), enrolment timing (5-10 days vs 2-15 days), follow-up (three-months vs six-months, mRS vs FMMS), ancillary rehabilitation (not defined additional physiotherapy vs standard physiotherapy), so great expectations were addressed towards EFFECTS and AFFINITY, who were supposed to be presented at ESO-WSO Conference 2020 in Vienna. However, because of the SARS-CoV-2 pandemic, both trials were presented respectively by Prof. Erik Lündstrome and Prof. Hankey J. Graeme during a Webinar on May 13^th (link here).
The EFFECTS trial was conducted in Sweden and enrolled 1500 patients. Treatment, inclusion criteria and primary outcome were the same of the FOCUS trial. Median baseline NIHSS was 3. Fluoxetine had a neutral effect on six-months disability, while reduced the risk of post-stroke depression and increased the risk of hyponatremia and bone fractures.
The AFFINITY trial enrolled 1280 patients from Australia, New Zealand and Vietnam. Patients with recent diagnosis of stroke (2-15 days) were randomized to receive fluoxetine 20 mg die or placebo. The primary endpoint was the mRS score distribution at six months. Baseline median NIHSS was 6. Once again, fluoxetine did not show any efficacy in reducing six-months disability. However, fluoxetine had a slight effect on patients’ mood, but increased the risk of seizures and bone fractures.
As showed above, these trials differed from the FLAME regarding the enrolled population, as they included patients with both ischemic and hemorrhagic stroke and less severe symptoms. Patients with mild symptoms would have probably had a good outcome independently from the experimental drug. In this view, subgroup analyses per stroke etiology, symptom severity and time of enrollment might shed new light on this topic. Furthermore, the possible efficacy of fluoxetine on post-stroke depression is potentially interesting for future trials. As well, the risk of bone fractures and of seizures should be carefully taken in account.
To definitely answer to these questions, a pooled metanalysis of FOCUS, AFFINITY and EFFECTS is already planned. Until then, in the future of fluoxetine there is still a FLAME of hope.

References

1. Chollet F, Tardy J, Albucher J-F, Thalamas C, Berard E, Lamy C, Bejot Y, Deltour S, Jaillard A, Niclot P, et al. Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial. Lancet Neurol. 2011;10:123–130.
2. McCann SK, Irvine C, Mead GE, Sena ES, Currie GL, Egan KE, Macleod MR, Howells DW. Efficacy of antidepressants in animal models of ischemic stroke: a systematic review and meta-analysis. Stroke. 2014;45:3055–3063.
3. Dennis M, Mead G, Forbes J, Graham C, Hackett M, Hankey GJ, House A, Lewis S, Lundström E, Sandercock P, et al. Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial. The Lancet. 2019;393:265–274.

Study provides new understanding of how the brain recovers from damage caused by stroke - vision

Interesting that SSRIs have just been described as not helpful in motor recovery. 

Common antidepressant can help stroke patients improve movement and coordination Sept. 2015 

 

Antidepressants may help people recover from stroke even if they are not depressed Jan. 2013

  

 Have your doctor explain why  this discrepancy occurred between the upper two and this lower one..

 

Is there a suitable drug for stroke recovery?

 

Study provides new understanding of how the brain recovers from damage caused by stroke - vision

• Download PDF Copy

Reviewed by James Ives, MPsychMar 21 2019

Each year, approximately 265,000 Americans have a stroke that causes visual impairment. New research, which appears in the journal Proceedings of the Royal Society B, sheds light on how the damage in the brain caused by a stroke can lead to permanent vision impairment. The findings could provide researchers with a blueprint to better identify which areas of vision are recoverable, facilitating the development of more effective interventions to encourage vision recovery.
"This study breaks new ground by describing the cascade of processes that occur after a stroke in the visual center of the brain and how this ultimately leads to changes in the retina," said senior study author Brad Mahon, an associate professor at Carnegie Mellon University and the University of Rochester. "By more precisely understanding which connections between the eye and brain remain intact after a stroke, we can begin to explore therapies that encourage neuroplasticity with the ultimate goal of restoring more vision in more patients."
When a stroke occurs in the primary visual cortex, the neurons responsible for processing vision can be damaged. Depending upon the extent of the damage, this can result in blind areas in the field of vision. While some patients spontaneously recover vision over time, for most the loss is permanent. A long-known consequence of damage to neurons in this area of the brain is the progressive atrophy of cells in the eyes, called retinal ganglion cells.
"While the eye is not injured in the stroke, cells in the retina that send projections to parts of the brain that are damaged will degenerate over time," Mahon said. "Once this occurs, it becomes more and more unlikely for vision to recover at that location."
The new research sought to understand the mechanisms of vision loss after stroke and whether it was possible to identify areas in the field of vision that could be recovered. The study involved 15 patients treated at Strong Memorial and Rochester General hospitals for a stroke that affected the primary visual processing area of the brain. The participants took vision tests, underwent scans in an MRI to identify areas of brain activity and were administered a test that evaluated the integrity of cells in their retina.
The team found that the survival of the retinal ganglion cells depended upon whether or not the primary visual area of the brain to which they are connected remained active. Eye cells that were connected to areas of visual cortex that were no longer active would atrophy and degenerate, leading to permanent visual impairment.
However, the researchers observed that some cells in the eye remained healthy, even though the patient could not see at the corresponding field of vision. This finding suggests that these eye cells remain connected to unscathed neurons in the visual cortex and that visual information was making its way from the eyes to the visual cortex, even though this information was not being interpreted by the brain in a manner that allowed sight.
"The integration of a number of cortical regions of the brain is necessary in order for visual information to be translated into a coherent visual representation of the world," said study co-author Dr. Bogachan Sahin, an assistant professor in the University of Rochester Medical Center (URMC) Department of Neurology. "And while the stroke may have disrupted the transmission of information from the visual center of the brain to higher order areas, these findings suggest that when the primary visual processing center of the brain remains intact and active, clinical approaches that harness the brain's plasticity could lead to vision recovery."

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The research has formed the basis of a new clinical trial for stroke patients with vision loss that is now under way at URMC and lead by Sahin. The study involves a class of drugs called selective serotonin reuptake inhibitors, the most common of which is the antidepressant Prozac, which are known to enhance neuroplasticity - the brain's ability to rewire itself and form new connections to restore function after damage. The hypothesis is that the drug will help restore vision by fostering the development of new connections between areas of the brain necessary for interpreting signals from the healthy eye cells.
The study also suggests new clinical approaches to maximize the potential for recovery by more effectively targeting blind regions in the field of vision. URMC researchers Krystel Huxlin and Dr. James V. Aquavella have developed a visual training regime that has been shown to help with vision recovery after stroke and the new study could help refine how this technology is employed.
"These findings suggest a treatment protocol that involves a visual field test and an eye exam to identify discordance between the visual deficit and retinal ganglion cell degeneration," said Colleen Schneider, an M.D./Ph.D. student at the University of Rochester School of Medicine and Dentistry and the first author of the study. "This could identify areas of vision with intact connections between the eyes and the brain and this information could be used to target visual retraining therapies to regions of the blind field of vision that are most likely to recover."
Data from this study is openly available in KiltHub, CMU's comprehensive institutional repository hosted within figshare. In the future, it will be incorporated into The Open Brain Project, a new, digital platform for exploration of the human brain. Ana Van Gulick, research liaison for psychology and brain sciences and program director for Open Science at Carnegie Mellon University Libraries, is a key contributor to this joint effort of CMU and the University of Rochester.
"The field of neuroscience is currently undergoing a dramatic shift toward open science that will encourage new collaborations and methods of research inspired by data science," Van Gulick said. "A cornerstone of this is providing open access to datasets in a standard format so that they can be aggregated and reused to extend scientific discovery. The data currently available in KiltHub and the larger collection that will later be discoverable through The Open Brain Project will provide a rich open access resource for education and research in neuroscience."
This study also is part of a larger research program being carried out by the Translational Brain Mapping Program at the University of Rochester Medical Center. Mahon and Sahin were recently awarded a $1.7 million grant from National Eye Institute to continue their investigations into vision loss after stroke. The funding will support a multi-institution research effort that includes CMU, URMC, Rochester Regional Health and the University of Pittsburgh Medical Center.

Source:

https://www.cmu.edu/

Is there a suitable drug for stroke recovery?

So it seems antidepression meds do not increase motor recovery. Ask your doctor to analyze all sets of research to determine which way to go. Well, fuck, the Rankin scale has nothing objective in it at all except for 6 - death. Using the Rankin scale is stupid, it has very limited discriminatory power and is not objective. 

Common antidepressant can help stroke patients improve movement and coordination Sept. 2015 

 

Antidepressants may help people recover from stroke even if they are not depressed Jan. 2013

  

 Have your doctor explain why  this discrepancy occurred between the upper two and this lower one.

 

Is there a suitable drug for stroke recovery?

In this study, researchers examine the effects of a drug, fluoxetine, in improving the functional ability of those facing stroke recovery.

Stroke affects many worldwide. Disability is one of the debilitating effects after a stroke.  It is estimated that 6.5 million people worldwide are affected by post-stroke disability. Usually, post-stroke recovery involves treating depression and other factors. One drug used for this treatment is in the class of selective serotonin reuptake inhibitors (SSRI), known specifically as fluoxetine, though other SSRIs have been suggested to help in stroke recovery.
Previous trials have suggested that fluoxetine may improve motor ability. Other studies also suggested fewer instances of depression in those using fluoxetine during stroke recovery. Yet, stroke guidelines do not strongly recommend fluoxetine because of the fear of potential adverse reactions.
The researchers, part of the FOCUS Trial Collaboration, sought to determine whether those facing stroke recovery would benefit from fluoxetine used over a six-month period. This study, published in The Lancet, was a double-blind randomized controlled trial, which involved 103 hospitals in the United Kingdom.
Adults with acute stroke diagnosis were included in the study. A total of 1564 adults were randomized to receive fluoxetine (20 mg) and 1563 were randomized to receive placebo and were examined for their ability to function at the six-month mark. Using the modified Rankin Scale (mRS), which is a scale used to determine disability level in those who have faced a stroke, the researchers found that there were no significantly different scores between those who took fluoxetine and those who took the placebo.
At the six-month mark, depression and a negative mood were less likely to occur in those in the fluoxetine group compared to those in the placebo group. Yet, bone fracture risk was higher in the fluoxetine group. Unfortunately, at the 12-month mark, there was no longer a significant difference in mood and depression between the fluoxetine and placebo group.
Overall, those facing stroke recovery showed no improved functional ability at the six or 12-month mark. In addition, in the short term at six months, depression seemed to be less evident in the fluoxetine group, but overall, this significance did not remain after more time had passed (i.e. at the 12-month mark in the study).
Limitations in this study include the fact that some of the characteristics of their recruited patients were not completely representative of the UK population. The authors also suggested that the effect of the treatment had the potential to be underestimated since they had some issues with adherence to the use of the medication. Also, the outcome score, a modified mRS, may not be the strongest measure to use, but it was deemed the most relevant. In addition, any face-to-face interaction with the patients could have led to bias.
Overall, more research should be done to confirm these results. This study reinforces the idea that fluoxetine may not be beneficial for those facing stroke recovery. Additional studies are needed to see if fluoxetine may be more harmful than beneficial or vice versa.
Written by Olajumoke Marissa Ologundudu B.Sc. (Hons)
Reference: FOCUS Trial Collaboration.Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised,controlled trial. The Lancet. 2018; 1–10. doi: http://dx.doi.org/10.1016/S0140-6736(18)32823-X

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

 So it seems antidepression meds do not increase motor recovery. Ask your doctor to analyze all sets of research to determine which way to go. Well, fuck, the Rankin scale has nothing objective in it at all except for 6 - death. Using the Rankin scale is stupid, it has very limited discriminatory power and is not objective. 

Common antidepressant can help stroke patients improve movement and coordination Sept. 2015 

 

Antidepressants may help people recover from stroke even if they are not depressed Jan. 2013

• fluoxetine (10)

 

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

The Lancet | January 10, 2019

In this FOCUS trial collaboration, researchers assessed the effects fluoxetine on functional outcomes after stroke. Overall, they did not observe any benefits of providing fluoxetine 20 mg daily for 6 months after acute stroke in terms of functional outcomes. The treatment reduced the occurrence of depression but increased the frequency of bone fractures. Thus, the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function was not supported.

Methods

• This multicenter, parallel group, double-blind, randomized, placebo-controlled trial was conducted at 103 UK hospitals.
• Study participants included adults with a clinical stroke diagnosis who were randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits.
• Participants received either fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimization algorithm.
• Functional status, measured with the modified Rankin Scale (mRS), at 6 months was assessed as the primary outcome.
• Treatment allocation was not revealed to patients, care givers, healthcare staff, or the trial team.
• Assessment of functional status was done at 6 months and 12 months after randomization.
• As per the treatment allocation, analysis of the patients was done.

Results

• A total of 3,127 patients were recruited between September 10, 2012, and March 31, 2017.
• Researchers allocated 1,564 patients to receive fluoxetine and 1,563 to receive placebo.
• In each treatment group, 1,553 (99.3%) patients had mRS data available at 6 months.
• The fluoxetine and placebo groups had similar distribution across mRS categories at 6 months.
• Patients who received fluoxetine displayed less tendency for developing new depression by 6 months vs those who received placebo; however, these patients had more bone fractures.
• No significant differences in any other event at 6 or 12 months was noted.

Read the full article on The Lancet

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

So it seems antidepression meds do not increase motor recovery. Ask your doctor to analyze all sets of research to determine which way to go. Well, fuck, the Rankin scale has nothing objective in it at all except for 6 - death. Using the Rankin scale is stupid, it has very limited discriminatory power and is not objective. 

Common antidepressant can help stroke patients improve movement and coordination Sept. 2015 

 

Antidepressants may help people recover from stroke even if they are not depressed Jan. 2013

 

 

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

• FOCUS Trial Collaboration ^†
• Show footnotes

Open AccessPublished:December 05, 2018DOI:https://doi.org/10.1016/S0140-6736(18)32823-X

Open access funded by Department of Health UK

PlumX Metric

Summary

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.

Introduction

Each year, stroke affects around 9 million people worldwide for the first time and results in long-term disability for around 6·5 million people.

¹

Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), is used to treat depression and emotional lability after stroke. Many clinical and preclinical studies have suggested that SSRIs might improve outcomes after stroke through a range of mechanisms, which include enhancing neuroplasticity and promoting neurogenesis. In 2011, the results of the FLAME (FLuoxetine for motor recovery After acute ischaeMic strokE) trial indicated that fluoxetine enhanced motor recovery.

²

In this double-blind, placebo-controlled, multicentre trial, 118 patients with ischaemic stroke and unilateral motor weakness, and a median National Institutes of Health Stroke Scale (NIHSS) score of 13, were randomly allocated between 5 and 10 days after stroke onset to receive fluoxetine 20 mg daily or placebo for 3 months. At day 90, the improvement from baseline in the Fugl-Meyer motor score was significantly greater in the fluoxetine group than in the placebo group. Additionally, the proportion of patients who were independent in daily living (with a modified Rankin Scale [mRS] score of 0–2) was significantly higher in the fluoxetine group than in the placebo group (26% vs 9%, p=0·015). More participants were free from depression at 3 months in the fluoxetine group than in the placebo group (93% vs 71%; p=0·002). A subsequent Cochrane systematic review

³

of SSRIs for stroke recovery identified 52 randomised controlled trials of SSRIs versus controls (in 4060 patients), but no others tested the effect of fluoxetine on functional outcomes measured with the mRS. The findings of the Cochrane review suggested that SSRIs might reduce post-stroke disability, although this estimate was based on a meta-analysis done across various measures of function and greater effects were seen if studies with increased risk of bias were retained and patients with depression were included. Although promising, data from the FLAME trial and the Cochrane review were not sufficiently compelling to alter stroke treatment guidelines or to alleviate concerns that any possible benefits might be offset by serious adverse reactions.

⁴