Fluoxetine in progressive multiple sclerosis: The FLUOX-PMS trial

Melissa Cambron, Jop Mostert, Marie D'Hooghe, Guy Nagels, Barbara Willkens, Jan Debruyne, Luc Algoed, Winn Verhagen, Raymond Hupperts, Dorothea Heersema, Jacques De Keyser*, Liesbeth De Groot, Erwin Foselle, Daniel Guillaume, Henri Merckx, Ludo Vanopdenbosch, Mathieu Vokaer, Nina De Klippel, Dirk Nuytten, Ann Van RemoortelAnoek Symons, Miguel D'haeseleer, Veronique Bissay, Annick Van Merhaegen-Wieleman, Michel Van Lint, Veronique Michiels, Patrick Haentjens, Bart Van Wijmeersch, Bart Tillemans, Wim Van Hecke, Gerald Hengstman, FLUOX-PMS Study Group

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

17 Citations (Web of Science)


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.

Original languageEnglish
Pages (from-to)1728-1735
Number of pages8
JournalMultiple Sclerosis Journal
Issue number13
Publication statusPublished - Nov 2019


  • Multiple sclerosis
  • progressive multiple sclerosis
  • clinical trial
  • fluoxetine
  • outcome
  • neuroprotection

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