The Daily Telegraph today reports that “A commonly prescribed anti-depressant could help stroke victims recover physical control over their bodies.” The newspaper says that a study of 118 stroke patients found that taking the drug fluoxetine (also known as Prozac) in the days following a stroke led to greater restoration of movement than a dummy “placebo” drug.
During the study, stroke patients left with paralysis or muscle weakness were given fluoxetine or a placebo for three months, starting 5-10 days after their stroke. On average, they showed greater improvements in their movement than patients receiving placebo capsules, and were more likely to be able to carry out the usual activities of daily living independently by the end of three months.
Although this study is the largest of its kind to date, even larger studies will be needed to confirm its findings, and to determine whether the effects last after the drug is discontinued. This study used robust methods and suggests that the use of fluoxetine after a stroke to improve movement merits further investigation.
Where did the story come from?
The study was carried out by researchers from the University of Toulouse and other research centres in France, and was funded by the French Ministry of Health. It was published in the peer-reviewed medical journal, The Lancet Neurology.
This study was covered by BBC News, The Daily Telegraph and the Daily Mail. Press coverage was generally accurate and well balanced. The Daily Mail’s headline that “Prozac 'gives movement back to stroke victims left paralysed'” may suggest that all paralysed stroke patients can benefit, but this study did not include those with the most severe paralysis.
What kind of research was this?
This was a double-blind, randomised controlled trial looking at whether giving people the antidepressant drug fluoxetine (brand name Prozac) after a stroke would improve their movement to a greater extent than a dummy “placebo” drug. Earlier brain imaging studies in people with stroke have shown that a single dose of fluoxetine increased activity in areas of the brain involved in controlling movement compared with placebo.
A few small trials of post-stroke use of selective serotonin-reuptake inhibitors (the family of drugs to which fluoxetine belongs) have suggested that they may have a positive effect on movement. The researchers therefore wanted to carry out a larger trial to test whether giving fluoxetine to people who had experienced a stroke might improve their movement.
The study design used is ideal for investigating questions about the benefits and harms of treatments as it uses randomisation of participants, the best way of ensuring that the groups being compared are as similar as possible. This means that any differences in outcomes seen between the groups should be due to differences in the treatment received. The double-blind nature of the trial means that neither the doctors nor patients knew which treatment they were receiving, fluoxetine or placebo. This means that the results should not be affected by the doctors’ or patients’ preconceptions about whether the drug would have an effect or not.
What did the research involve?
The researchers enrolled 118 adults aged between 18 and 85 who were either paralysed down one side of their body or had weakness down one side of their body as a result of a stroke which occurred in the previous 5-10 days. All of the participants had a type of stroke called ischaemic stroke, which is due to a blood clot in the brain. Patients who had a severe disability either from before the stroke or because of the stroke were not included. Patients who had been diagnosed with depression, had high levels of depressive symptoms or were taking antidepressants were not eligible to take part in the study.
Participants were randomly assigned to receive either fluoxetine (20 mg once a day) or “dummy” (placebo) capsules which looked the same as the fluoxetine capsules, but contained no active ingredients. They took the capsules once a day for three months, and they all received physiotherapy.
The participants’ mobility on their affected side was measured at the start of the study and at the end of the three-month treatment period using the Fugl-Meyer motor scale (FMMS).
The FMMS scale is a standard scale that ranges from 0 (no movement ability) to 100 (normal movement). Participants can score up to 66 points for arm movement and up to 34 points for leg movement. The scores are based on whether the patient can fully perform, partially perform or not perform these movements.
At the start of the study, all the patients scored 55 or less in their FMMS test, indicating moderate-to-severe movement problems. The researchers also used two other scales which assessed independence and disability (the modified Rankin scale and the National Institutes of Health stroke scale, or NHSS). The modified Rankin scale ranges from 0 to 5, where 0 indicates no symptoms and 5 indicates severe disability. A score of 0 to 2 was taken as indicating independence, as individuals with scores in this range do not require help in activities of daily living. None of the participants had modified Rankin scale scores of 0 to 2 at the start of the study.
At the end of the study, the researchers compared the change in motor ability between those patients receiving fluoxetine and those receiving placebo. They also compared the level of depressive symptoms and any side effects between the groups.
What were the basic results?
Two patients died during the study and a further three withdrew from the study, so the researchers analysed data from the remaining 113 patients.
Fluoxetine improved movement on the side of the body affected by the stroke more than placebo. Participants in the fluoxetine group improved their FMMS score by 34 points on average, compared to an average of about 24 points in the placebo group. When splitting the score into its components, fluoxetine caused larger improvements of both arm and leg movement scores than the placebo. More participants in the fluoxetine group (26%) could independently carry out activities of daily living at the end of the study than those in the placebo group (9%).
The level of depressive symptoms at the start of the study was similar in both groups. Over the course of the study the placebo group showed an increase in depressive symptoms, while symptoms in the fluoxetine group stayed roughly the same. Participants in the group treated with fluoxetine were also less likely to be diagnosed with depression during the study than those in the placebo group.
Digestive problems such as nausea, diarrhoea and abdominal pain were more common in the fluoxetine group, with a quarter of patients affected, compared with 11% of those receiving placebo. This difference is not statistically significant.
How did the researchers interpret the results?
The researchers concluded “in patients with ischaemic stroke and moderate to severe motor [movement] deficit, the early prescription of fluoxetine with physiotherapy enhanced motor recovery after three months”.
This study used a robust design for assessing whether fluoxetine could improve movement in people who have suffered a stroke. Its use of randomisation means that the comparison groups were likely to have been well balanced, and blinding reduced the chance that preconceptions about the effects of treatment could have affected how patients’ or doctors’ rated movement. There are a few points to note:
- Although larger than previous studies, this study was still relatively small at 118 patients. Larger randomised controlled trials will be needed to confirm the results.
- It is not possible to say whether the improvements in movement seen with fluoxetine would be maintained in the longer term after treatment with fluoxetine stopped.
- As with most randomised controlled trials, the patients included in this trial were specially selected and had very specific characteristics. For example, the most severely affected patients were excluded, as were patients with haemorrhagic stroke (the cause of around one in five strokes). This means that study would not be representative of all patients with stroke.
- Studies with less stringent selection criteria would be needed to determine whether fluoxetine would have similar effects in all stroke patients. Analyses of different groups of patients could identify whether any specific groups are most likely to benefit.
- It is not clear whether fluoxetine is having a direct effect on movement, or whether it may be having an indirect effect by lifting patients’ mood, which may, for example, allow them to engage more fully in their physiotherapy or other activities.
Overall, this trial suggests that the use of fluoxetine after a stroke to improve movement is worth investigating further.
Analysis by Bazian
Edited by NHS Website
Links to the headlines
BBC News, 10 January 2011
The Daily Telegraph, 10 January 2011
Daily Mail, 10 January 2011
Links to the science
The Lancet Neurology, Early Online Publication, January 10 2011