A recent study named “Fluoxetine in Motor Recovery of Patients with Acute Ischemic Stroke (FLAME)” was published online last January. The study reported that stroke subjects who take the antidepressant medication fluoxetine after experiencing an ischemic stroke have a more improved mobility. It also reported that the stroke subjects receiving fluoxetine are more independent with their activities of daily living (ADL) compared with stroke victims who received placebo. Researchers of the clinical study are suggesting that fluoxetine, a selective serotonin reuptake inhibitor (SSRI), could signify a new approach to treating stroke patients.
Fluoxetine (also known by the tradenames Prozac, Sarafem, Fontex, among others) is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class used to treat depression obsessive-compulsive behavior, a number of eating disorders and panic attacks. SSRIs are the most commonly prescribed antidepressant medication. SSRIs are relatively safe and generally cause fewer side effects than any other type of antidepressant. They work by blocking the reabsorption or the reuptake of the neurotransmitter serotonin increasing its levels in the brain. This increase seems to help brain cells send and receive chemical messages which in turn boosts a person’s moods. They are called selective because they only affect serotonin and not the other neurotransmitters in the brain. Side effects of SSRIs may include:
- Dry mouth
- Nervousness, agitation or restlessness
- Reduced sexual desire or difficulty reaching orgasm
- Inability to maintain an erection (erectile dysfunction)
- Increased sweating
- Weight gain
About the study
Dr. François Chollet, MD, the study’s lead author, a professor of neurology at the Toulouse University Hospital in France said that their team thinks that fluoxetine encourages an increase in the brain’s capacity to reorganize – it acts by helping in rewiring the brain. He added that using fluoxetine is like opening another capacity, another target and another pathway for treating patients who had experienced a stroke.
Currently, ischemic stroke patient are being treated with tissue plasminogen activator (tPA), a thrombolytic drug approved by the US Food and Drug Administration. Dr. Chollet’s team hopes that, in the near future, fluoxetine or other SSRIs can also be a treatment option for these stroke patients. However, Dr. Chollet said that before that can take place several questions must be answered first. He said that the researchers need to determine the length of time for optimal treatment; they also need to find out the long-term effects of the treatment on stroke patients; and what are the other possible effects on neuronal activity in general.
The participants of the study
118 subjects 5-10 days after ischemic stroke were randomized from 9 stroke centers in France. These stroke victims were between 18 and 85 years old and either had hemiplegia (paralysis on either the left or right side of the body) or hemiparesis (weakness on either the left or right side of the body) which are the most common deficits caused by a stroke, with a Fugl-Meyer motor scale of 55 or less. Patients with severe post stroke disabilities (NIHSS score > 20), clinically diagnosed with depression (MADRS > 19), pregnant or with other major diseases were excluded from the study.
Results: Fluoxetine vs. placebo
All of the stroke patients were randomly assigned into 2 groups of 59 members. One group was given 20 milligrams of fluoxetine while the other group was only given a placebo. The researchers started to administer fluoxetine or placebo 5-10 days after the onset of the stroke and they continued for a total of 3 months. All of the stroke victims were given standard post-stroke care and they also underwent physical rehab from physical therapists (PT) who were instructed to use conventional therapy according to the protocol of their medical centers. The PTs were also made to assess the motor functions of all the stroke victims starting from day 0 (the baseline), after 30 days and then 90 days after starting the program.
The result of the study shows that the group treated with fluoxetine recorded a 40% improvement on the Fugl-Meyer motor scale as compared to the placebo group (34 points in the fluoxetine group vs. 24.3 in the placebo group).
Fugl-Meyer Motor Assessment (FMA) is a clinical examination performed to assess the upper extremity and lower extremity motor and sensory impairments in post stroke patients. FMA is being increasingly being used for clinical assessment of motor recovery after a stroke. In a recent clinical trial from July 2011, FMA was used to evaluate safety and efficacy on motor recovery of NeuroAiD in 150 Caucasian subjects after stroke. Subjects on NeuroAiD achieved 27% higher recovery on their motor function as compared to the placebo group. Click here to learn more about the Fugl-Meyer Assessment after a stroke.
Limitations of the study
Although the results of this study shows the positive effect of fluoxetine in motor recovery on post ischemic stroke patients, we should not forget that there are some limitations to it. First, the number of patients included was small (118), also they were selected for motor deficit and do not represent the general population of stroke patients. Second, the treatment was performed for 90 days and it is not well known how the motor recovery evolves over time after the treatment has stopped. Third, a potential random error derived from the statistical analysis cannot be ignored, although this probability is remote (the change in FMA score at day 90 had a statistical relevance of p= 0.003, in other words, the odds that it is an error is 3 in 1000).
Benefits and side effects of SSRIs
Fluoxetine is relatively inexpensive and is commonly available. Fluoxetine, is not a new drug so its side effects are well known, generally mild and very infrequent. Other SSRIs aside from fluoxetine may have the same positive effects, as shown by a study published in 2010 which showed patients who are taking escitalopram (another type of SSRI) had a marked improvement in cognition, particularly memory, compared to patients who were given a placebo.
It is not unusual for post-stroke patient to experience depressive symptoms especially if they have disabilities arising from the stroke. Dr. Chollet‘s team noted that the placebo group had a higher number of stroke patients having significant deficits (7%) compared with the fluoxetine group (5%), there were more depressed stroke patients in the placebo. Approximately 30%-50% of post-stroke patients develop some form of depression and fluoxetine could serve as both mood and motor recovery enhancer. This in turn is a welcome combination of benefits to post-stroke patients.
Fluoxetine was given to the stroke patients as soon as possible after their stroke and that there was no “stroke window” during which it must have been delivered. On the contrary, tPAs must be given within 3.5 hours after the onset of the stroke symptoms because of the risk for bleeding. The earlier fluoxetine is administered, the better for the stroke patient. Dr. Chollet added that what healthcare providers know about the natural history of stroke is that patients recover mainly during the first three months. This period is the time where stroke patients experience the biggest improvements. However, it is still not clear what the optimal duration of treatment is. The long-term effects of fluoxetine and possible other benefits on neurologic functions of this new possible treatment for stroke patients needs to be elucidated.