AT ECTRIMS 2016
LONDON (FRONTLINE MEDICAL NEWS) – Contrary to expectation of a neuroprotective benefit, fluoxetine does not slow down the progressive phase of multiple sclerosis, according to the results of a randomized, double-blind, multicenter trial.
The first results of the FLUOX-PMS trial, reported by Melissa Cambron, MD, of University Hospital Brussels (Belgium), showed no statistically significant difference between fluoxetine and placebo for improving the primary endpoint of the time to confirmed disease progression.
This had been defined as the proportion of patients without a sustained 20% increase in the Timed 25-Foot Walk or the 9-Hole Peg Test from the 12th week of treatment to the final follow-up assessment at just over 2 years. Results showed around 58% of patients treated with fluoxetine were without progression, compared with 66% of placebo-treated patients (P = .07) at week 120.
“The progressive phase of MS remains an ill-understood part of the disease and it is a holy grail to find a drug that can stop this progression,” Dr. Cambron said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
The rationale for looking at whether fluoxetine, a well-studied antidepressant drug, could be such a drug, was that it had several neuroprotective features – it has been shown to stimulate the release of brain-derived neurotrophic factor, stimulate metabolism in astrocytes, and lower glutamatergic toxicity, she said. All of these could potentially help prevent axonal degeneration.
The FLUOX-PMS (Fluoxetine in Progressive Multiple Sclerosis) trial ( Trials. 2014;15:37 ) ran from 2012 to June 2016 and enrolled patients with primary progressive MS (PPMS) or secondary progressive MS (SPMS), as defined by the 2010 McDonald criteria. A total of 137 patients were enrolled, and 69 were randomized to treatment with fluoxetine 40 mg/day and 68 were randomized to placebo. Fluoxetine treatment was started at a dose of 20 mg and titrated to the full 40-mg dose by 12 weeks.
Patient demographics were mostly similar between the groups. Around 44% of patients in the fluoxetine and placebo groups were female; roughly 40% had PPMS and 60% had SPMS in both groups; the mean Expanded Disability Status Scale score was 5.2 in both groups; the mean age was 54 and 51 years, respectively; and the disease duration was between 18 and 20 years.
Dr. Cambron also reported that the trials’ secondary endpoints showed no advantage of using fluoxetine over placebo. The proportion of patients without sustained progression during the trial was similar among the fluoxetine- and placebo-treated patients, at a respective 69.6% and 61.8% (P = .434). The proportion of patients with a stable Hauser Ambulation Index was also similar (P = .371).
The primary and secondary endpoints were assessed every 3 months in the trial. Patients also underwent cognitive testing, completed the Beck Depression Inventory-II, and Modified Fatigue Impact Scale before treatment and at 48 and 108 weeks after treatment with fluoxetine or placebo. Brain MRI was also performed at baseline and at week 108. The results of these measurements have yet to be analyzed.
Although patients in the fluoxetine group versus the placebo arm experienced more side effects, there was no evidence of an excess of severe adverse events.
“Unfortunately, our study was inconclusive because we failed to show a statistical significant difference between the placebo arm and the fluoxetine group, although I’m convinced that there’s a trend that can certainly not be ignored,” Dr. Cambron maintained. “Probably there was not enough progression in the study and possibly the study duration was too short, she suggested, “but it remains challenging to study these patients for a long period of time, especially with a placebo-controlled design.”
The trial was funded by IWT, the Government Agency for Innovation by Science and Technology in Flanders (Belgium). Dr. Cambron had no relevant financial disclosures.
