Cambron M, Mostert J, D’Hooghe M, Nagels G, Willekens B, Debruyne J, Algoed L, Verhagen W, Hupperts R, Heersema D, De Keyser J; FLUOX-PMS Study Group. Mult Scler. 2019 Jun 20:1352458519843051.
BACKGROUND: Preclinical studies suggest that fluoxetine has neuroprotective properties that might reduce axonal degeneration in multiple sclerosis (MS).
OBJECTIVE:To determine whether fluoxetine slows accumulation of disability in progressive MS.
METHODS: In a double-blind multicenter phase 2 trial, patients with primary or secondary progressive MS were randomized to fluoxetine 40 mg/day or placebo for a period of 108 weeks. Clinical assessments were performed every 12 weeks by trained study nurses who visited the patients at their home. The primary outcome was the time to a 12-week confirmed 20% increase in the Timed 25 Foot Walk or 9-Hole Peg test. Secondary outcomes included the Hauser ambulation index, cognitive tests, fatigue, and brain magnetic resonance imaging (MRI).
RESULTS: In the efficacy analysis, 69 patients received fluoxetine and 68 patients received placebo. Using the log-rank test (p = 0.258) and Cox regression analysis (p = 0.253), we found no significant difference in the primary outcome between the two groups. Due to an unexpected slow rate of progression in the placebo group, there was insufficient statistical power to detect a potential benefit of fluoxetine. We found no differences between the two groups for secondary outcomes.
CONCLUSION:The trial failed to demonstrate a neuroprotective effect of fluoxetine in patients with progressive MS.
We have heard of this study already because the design was already published. But just like Buses when you have been waiting for one to come along you get two one after the other. This is the first one that was presented at ECTRIMS about 2 years ago and the take home message is it failed…..But did it ?
Fluoxetine in progressive multiple sclerosis (FLUOX-PMS): study protocol for a randomized controlled trial. Cambron M, Mostert J, Haentjens P, D’Hooghe M, Nagels G, Willekens B, Heersema D, Debruyne J, Van Hecke W, Algoed L, De Klippel N, Fosselle E, Laureys G, Merckx H, Van Wijmeersch B, Vanopdenbosch L, Verhagen W, Hupperts R, Hengstman G, Michiels V, Van Merhaegen-Wieleman A, De Keyser J. Trials. 2014 Jan 25;15:37. doi: 10.1186/1745-6215-15-37.
The effect of fluoxetine on progression in progressive multiple sclerosis: a double-blind, randomized, placebo-controlled trial. Mostert J, Heersema T, Mahajan M, Van Der Grond J, Van Buchem MA, De Keyser J. ISRN Neurol. 2013 Jul 29;2013:370943.
We will never know because the second one came along at ECTRIMS last year and that failed too..
So prozac (fluoxitine) is not going to be of value, probably. That is a shame, but if we don’t try we can’t succeed.
However, people with progressive MS have been waiting for studies for so long that there was a great placebo effect by going into a trial. As a consequence people did not progresess as fast expected and so there was no conclusion to be made……So we learn little except that academic trials are often horribly underpowered to get an answer. people did not progress as quickly as thought and years of effort wasted. Maybe if they had kept recruting until they had enough events to make an informative choice…this would not have been wasted effort. But these studies have cost mplications
So effective trial design is key for finding agents that work. This study could never work because there was not enough people in the trial. I have been saying this for so long that I look like a SMURF.
Don’t understand?. I have said this so many times that I am “blue in the face” because of not breathing whilst talking.
MS_SMART came along , three drugs against placebo, all failed. Were they all rubbish? or was the trial design wrong?
What do we do next…..a pertinent question…Same again but with a different drug choice? or Target Biology and get rid of what you know you can get rid of and then try control the unknown.
Have a DMT on the bottom rung.