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Fluoxetine as disease modifying treatment in multiple sclerosis : rationale, evaluation of the use of MRI to monitor treatment, and preliminary findings

(2009) Mostert, Jop Pieter

Patients with multiple sclerosis (MS) lack astrocytic β2-adrenergic receptors and this may contribute to the focal inflammatory demyelinating lesions and axonal degeneration that characterize this disease. We hypothesized that the antidepressant fluoxetine might be able to compensate for the loss of the β2-adrenergic receptors. In this thesis we evaluated the use of cerebral MRI scans to monitor disease activity and we performed several exploratory studies to evaluate effects of fluoxetine on patients with MS.
A convenient way to find out whether a drug is able to reduce disease activity in MS is by measuring the development of new focal lesions on serial MRI scans of the brain.
MS patients who received fluoxetine during 6 months had a trend towards the development of less new focal lesions compared to patients receiving placebo. To assess whether preventing new lesions formation reduces disability on the long term, we studied the relationship between the focal (T2) lesions and disease progression. The number of focal lesions predicted progression of disability and conversion to a progressive disease course in patients with relapsing remitting MS. However, once patients had entered the progressive phase, T2 lesions were no longer predictive for further progression of disability. In another study, we found that 2 weeks use of fluoxetine resulted in an increase in NAA/Cr (a marker of axonal function) in the white matter of MS patients.
These preliminary studies suggest that fluoxetine reduces new focal lesion formation and may improve axonal metabolism in MS patients.

	Title and contents
	Chapter 1
	Chapter 2
	Chapter 3
	Chapter 4
	Chapter 5
	Chapter 6
	Chapter 7
	Chapter 8
	Chapter 9
	Summary
	Samenvatting
	Dankwoord
	List of publications
	Curriculum vitae
	Complete thesis