Mike: Hello, I'm Mike Clarke, podcast editor for the Cochrane Library. Cochrane Stroke has produced more than 70 systematic reviews of pharmacological interventions that might improve the recovery of patients after stroke. In this podcast, co-authors Simiao Wu and Xing Hua, both from the West China Hospital at Sichuan University, in Chengdu, China, talk about the November 2021 update for one of these, which looks at the effects of selective serotonin uptake inhibitors on recovery from stroke.

Simiao: Hello Xing, first of all, could you tell us a little about selective serotonin uptake inhibitors, or SSRIs. What are they and what do they do?

Xing: SSRIs are a class of drug usually used to treat mood disorders, including those occurring after stroke, such as depression and anxiety. They do this by changing the level of chemicals in the brain.

Simiao: So why is it important to have a review of their effectiveness when they are used for patients recovering from a stroke, and why did you update the review?

Xing: As well as their benefits for mood, there have also been some small studies suggesting that SSRIs might promote motor recovery by direct effects on the brain. And in the 2019 version of our Cochrane Review we did find a benefit on recovery but this benefit was not apparent when low-quality studies were excluded from the meta-analysis. Since then, two large studies, AFFINITY and EFFECTS, have been completed, making it important to perform this further update to see if they would change our conclusion. This up-to-date account of the scientific evidence will help inform patients and physicians making decisions about the routine use of SSRIs for stroke.

Simiao: Did you find the evidence you needed, and what does it say about SSRIs for treating stroke?

Xing: In addition to the 63 studies we had in the 2019 version, the two large studies I mentioned and the other studies we found, there are now 76 clinical trials in the review, with just over 13,000 stroke survivors within one year after their stroke. All of these were randomised to an SSRI versus placebo or usual care. 

Simiao: And, what do these trials tell us about the effects of SSRIs and how reliable are they?

Xing: Of these 76 included studies, six studies that recruited a total of nearly 6000 participants were at low risk of bias across all domains. These six studies all tested a SSRI called fluoxetine and did not require participants to have depression to enter. These high-quality studies suggested that fluoxetine did not improve recovery after stroke, which was consistent with the 2019 version of the review but we found new evidence that fluoxetine did reduce the risk of future depression by about a quarter and also the severity of depression. However, it did not reduce disability or dependency after stroke. 

Simiao: What about the safety aspects? What evidence was there about complications and adverse events among patients using SSRIs?

Xing: Fluoxetine increased the risk of bone fractures, probably increased the risk of seizures, and may increase the risk of gastrointestinal problems. For other adverse events, the risks were similar between the SSRI and the control groups.

Simiao: Overall, what’s the take-home message about the use of SSRIs for patients who have had a stroke?

Xing: Put simply, there is currently no indication for the routine prescription of fluoxetine in order to reduce disability and increase independence after stroke.  Although fluoxetine reduced depression risk, it also increased the risk of bone fractures. 

Simiao: Thanks Xing. If people would like to read the review, how can they get hold of it?

Xing: It’s available online. People just need to go to Cochrane Library dot com and type 'SSRIs for stroke recovery' in the search box to get the link to the review.