Cochrane systematic review of SSRIs for stroke recovery 9 %, p = 0.015) although there were not significant differences at other mRS cut-offs. Also, the frequency of independent patients was significantly higher in the fluoxetine group (26 % vs. At day 90, the improvement in the Fugl Meyer motor score from baseline was significantly greater in the fluoxetine group.
Citalopram 20 mg anti stroke trial#
In this double-blind, placebo-controlled, multicentre trial 118 patients with ischaemic stroke and unilateral motor weakness were randomised to receive fluoxetine 20 mg daily or placebo for 3 months. The FLAME trial results, presented in October 2010, ignited worldwide interest in the role of fluoxetine for motor recovery. Promising effect of fluoxetine on stroke recovery in the fluoxetine for motor recovery after acute ischaemic stroke (FLAME) trial In strokes resulting in motor deficits, fluoxetine can cause hyperactivation in the ipsi-lesional primary motor cortex during a motor task and a decrease of motor excitability over the unaffected hemisphere. In healthy humans, functional magnetic resonance imaging studies have demonstrated that fluoxetine can modulate cerebral motor activity.
Ī systematic review of SSRIs in animal models of stroke identified 21 experiments reporting the efficacy of fluoxetine in 252 animals neurobehavioural scores improved by 41 % (95 % CI 27–54 %) but there was insufficient evidence to determine the likely underlying mechanisms. SSRIs may also stimulate neuronal generation, secretion of growth factors that augment neuroplasticity, synaptic plasticity, expression of brain phosphorylated cyclic adenosine monophosphate response element binding protein and attenuate hypothalamic pituitary axis overactivity, thus reducing cortisol, which is associated with poorer outcomes post-stroke. Furthermore, animal studies have shown that fluoxetine may attenuate post-ischaemic brain injury by facilitating expression of neuro-protective and regenerative proteins, suppressing post-stroke hyperexcitability in unaffected brain and reducing inflammation. They are sometimes used to manage emotionalism after stroke. SSRIs have been used in clinical practice since 1988 to treat mood disorders, particularly depression. If fluoxetine is safe and effective in promoting functional recovery, it could be rapidly, widely and affordably implemented in routine clinical practice and reduce the burden of disability due to stroke. This is based on an ordinal analysis of mRS adjusted for baseline variables included in the minimisation algorithm. If FOCUS, AFFINITY and EFFECTS combined enrol 6000 participants as planned, they would have 90 % power (alpha 5 %) to detect a common odds ratio of 1.16, equivalent to a 3.7 % absolute difference in percentage with mRS 0–2 (44.0 % to 47.7 %). The methods of collecting these data are tailored to the national setting. Outcomes are collected at 6 and 12 months. Secondary outcomes include the Stroke Impact Scale, EuroQol (EQ5D-5 L), the vitality subscale of the Short-Form 36, diagnosis of depression, adherence to medication, adverse events and resource use. Our primary outcome measure is the modified Rankin scale (mRS) at 6 months. Patients are allocated fluoxetine 20 mg once daily or matching placebo capsules for 6 months. Patients are randomised centrally via web-based randomisation systems using a common minimisation algorithm. The trials include patients ≥18 years old with a clinical diagnosis of stroke, persisting focal neurological deficits at randomisation between 2 and 15 days after stroke onset. A prospectively planned individual patient data meta-analysis of all three trials will subsequently provide the most precise estimate of the overall effect of fluoxetine after stroke and establish whether any effects differ between trials and subgroups of patients. Each trial is run and funded independently and will report its own results. Minor variations have been tailored to the national setting in the UK (FOCUS), Australia and New Zealand (AFFINITY) and Sweden (EFFECTS). The three trial investigator teams have collaboratively developed a core protocol.
FOCUS, AFFINITY and EFFECTS are a family of investigator-led, multicentre, parallel group, randomised, placebo-controlled trials that aim to determine whether routine administration of fluoxetine (20 mg daily) for 6 months after acute stroke improves patients’ functional outcome. Several small trials have suggested that fluoxetine improves neurological recovery from stroke.