October 14, 2007 (Prague, Czech Republic) --
Fluoxetine (Prozac) may help reduce the number of
new brain lesions in patients with multiple
sclerosis (MS), according to a study presented
here at the 23rd Congress of the European
Committee for the Treatment and Research in
Multiple Sclerosis (ECTRIMS). The study, which was
performed by Jop P. Mostert, MD, and colleagues at
the University of Groningen, the Netherlands,
assessed the efficacy of fluoxetine in patients
with relapsing-remitting or relapsing secondary
progressive multiple sclerosis.
Why Fluoxetine?
Fluoxetine, a selective serotonin reuptake
inhibitor (SSRI), was approved by the U.S. Food
and Drug Administration (FDA) in 1987, and is
frequently prescribed for the treatment of various
psychiatric disorders, including major depression.
However, fluoxetine also has a number of
immunomodulatory effects, and previous studies
have indicated that it might be beneficial for
patients with MS, Dr. Mostert said in his
presentation.
One
of these earlier studies, which was first
presented at the 1997 Annual Meeting of the
American Association of Neurology (AAN), showed
that fluoxetine reduced disease activity in
experimental autoimmune encephalomyelitis (EAE),
the animal model of MS, Dr. Mostert noted.
“Furthermore, psychiatrists already reported in
1991 reduced MS in patients using fluoxetine,” he
added.
Previous research has also found that astrocytes
in MS patients lack beta 2 adrenergic receptors,
and this leads to decreased cyclic adenosine
monophosphate (cAMP) production, which in turn
contributes to the initiation of the inflammatory
cascade that eventually results in demyelination,
Dr. Mostert explained. Because fluoxetine is able
to increase the amount of cAMP in the astrocyte,
the researchers hypothesized that the drug could
help compensate for the loss of beta 2 adrenergic
receptors, and thus reduce the amount of
inflammation in MS.
Fewer New Lesions
To test their hypothesis, Dr.
Mostert’s team enrolled 40 patients (age 18 to 65
years) with relapsing-remitting or relapsing
secondary progressive multiple sclerosis in a
randomized, double-blind, placebo-controlled
trial, with a duration of 24 weeks. Half of the
patients were given fluoxetine (20 mg per day),
while the remaining subjects received placebo.
The
primary end point was the cumulative number of new
gadolinium-enhancing lesions on T1-weighted
magnetic resonance imaging (MRI) of the brain
performed on weeks 4, 8, 16 and 24. Secondary
outcome measures included changes in the Expanded
Disability Status Scale (EDSS) and in the Multiple
Sclerosis Self-Efficacy Scale (MSSE)
from baseline to week 24.
The
investigators found that the study drug was
generally well tolerated, with only one patient
dropping out due to side effects (nausea) in the
treatment group. One patient also dropped out from
the placebo arm, leaving 19 completers in each
group.
Regarding the primary end point, the results
showed that there was a trend towards a reduction
in the number of new enhancing lesions in patients
treated with fluoxetine. The mean (SD) cumulative
number of new enhancing lesions during the 24
weeks of treatment was 1.84 (2.9) in the
fluoxetine treated patients and 5.16 (8.6) in the
control subjects (p = 0.15).
At
week 4, the cumulative number of new enhancing
lesions was “quite comparable” in the two groups,
pointed out Dr. Mostert. He emphasized, however,
that in the latter part of the trial, there was a
steady increase in new lesions in the placebo
group, while the number of lesions in the
fluoxetine-treated patients remained relatively
stable. Restricting the analysis to the last 16
weeks showed a “nearly significant” reduction in
the cumulative number of new enhancing lesions and
a higher number of patients without new enhancing
lesions (63% vs. 26%; p = 0.02).
Commenting on the study, session co-chair Ronald
Liblau, MD, PhD, noted that the researchers used
“a very interesting approach,” because fluoxetine
has a very good safety profile. “It has been used
in hundreds of thousands of patients, so we know
it’s safe,” he told Medscape. “The possibility
that it has even a slight effect in multiple
sclerosis would be very interesting,” he added.
“The data showed a trend toward efficacy in MS,
and I would strongly encourage further trials
involving more patients.”
This study was an
investigator-initiated trial, with no
pharmaceutical industry funding.
23rd Congress of the European
Committee for the Treatment and Research in
Multiple Sclerosis: Parallel Session 7 (86).
Presented October 13, 2007.
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