Fluoxetine (Prozac) Boosts Motor Recovery After Stroke

Antidepressant drugs are being used for multiple non-depression indications including chronic pain, peripheral neuropathy, migraine prophylaxis, irritable bowel syndrome, hot flashes, premature ejaculation and insomnia (list not inclusive).   I had previously posted results of research looking at the effect of antidepressants after stroke on cognitive recovery.  This study from the University of Iowa College of Medicine, Department of Psychiatry found that escitalopram was linked to improved cognitive recovery following stroke compared to placebo.

Now on a related note, a study has been randomized placebo controlled study of fluoxetine has been published looking at recovery of motor function following acute ischemic stroke.   Here are the key elements of the design of this study:

• Subjects:  113 patients with acute ischemic stroke ages 18-85 suffering hemiplegia or hemiparesis
• Baseline motor deficit: Fugl-Meyer motor scale (FMMS) score of 55 or less
• Intervention: Fluoxetine 20 mg daily for 3 months or placebo
• Key outcome measure: FMMS score at day 90

The raters on the key outcome measure were blinded to the assigned treatment.  The findings from the study were impressive—mean (standard deviation) FMSS scores for the fluoxetine group was 54(28) compared to only 35.1 (22) in the placebo group.  As might be expected, rates of post-stroke depression were lower in the fluoxetine group (7% vs 29%).    Adverse events included nausea and diarrhea in the fluoxetine group—a typical selective serotonin reuptake inhibitor side effect.  One subject in each group died during the follow up period.  More patients in the fluoxetine group were more independent suggesting that motor recovery is an important contributor to global function after stroke.  The motor recovery effect appeared independent of lower depression rates in the fluoxetine group.

So why would a drug used typically for depression potentially have a role in post-stroke motor recovery?  The authors note animal studies have shown that drugs affecting brain neurotransmitters can modulate the rate and extent of recovery following brain injury.   Rats given fluoxetine after ischemic brain injury appear to have enhanced hippocampal neurogenesis.  These studies support a potential role for selective serotonin reuptake inhibitors like fluoxetine to have a neuroplasticity effect that may aid brain healing from a variety of insults.  This is not a magic bullet—it appears necessary to pair the drug treatment with active rehabilitation efforts.   But when used together, the combination appears to result in a better motor recovery after stroke.  I think we are likely to see more active research in this area and search for novel neuroprotective compounds that my provide better outcomes for stroke and other brain injury patients. 


Molecular model of fluoxetine molecule from Wikipedia Creative Commons, author Benjah-bmmj27.

Chollet F, Tardy J, Albucher JF, Thalamas C, Berard E, Lamy C, Bejot Y, Deltour S, Jaillard A, Niclot P, Guillon B, Moulin T, Marque P, Pariente J, Arnaud C, & Loubinoux I (2011). Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial. Lancet neurology, 10 (2), 123-30 PMID: 21216670