Fluoxetine Shows Promise in Multiple Sclerosis

News Author: Thomas S. May
CME Author: Laurie Barclay, MD

October 16, 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 ECTRIMS 2007: 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis.

The study, which was conducted by Jop P. Mostert, MD, and colleagues at the University of Groningen, the Netherlands, shows a trend toward a reduction in new enhancing lesions with fluoxetine treatment in patients with relapsing-remitting or relapsing secondary progressive MS.

Why Fluoxetine?

Fluoxetine, a selective serotonin reuptake inhibitor, was approved by the US Food and Drug Administration 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, showed that fluoxetine reduced disease activity in experimental autoimmune encephalomyelitis, 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 patients with MS 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 - 65 years) with relapsing-remitting or relapsing secondary progressive MS in a randomized, double-blind, placebo-controlled trial, with a duration of 24 weeks. Half of the patients were given fluoxetine (20 mg/day), whereas 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 at 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 1 patient dropping out because of adverse effects (nausea) in the treatment group. One patient also dropped out from the placebo group, leaving 19 completers in each group.

Regarding the primary end point, the results show that there was a trend toward 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 = .15).

At week 4, the cumulative number of new enhancing lesions was "quite comparable" in the two 2 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 = .02).

Commenting on the study, session cochair Roland Liblau, MD, PhD, from Toulouse University Hospital in France, 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 Neurology and Neurosurgery. "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.

Medscape Medical News 2007. ©2007 Medscape


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Antidepressants Appear Ineffective in Relieving Depression in MS

Jacquelyn K. Beals

June 6, 2007 (Washington, DC) — A study of multiple sclerosis (MS) patients diagnosed with major depressive disorder (MDD) and/or dysthymia shows no relation between antidepressant use and improved outcomes.

A poster presentation here at the 21st annual meeting of the Consortium of Multiple Sclerosis Centers reported the results of a University of Washington study involving 96 MS patients enrolled in a trial investigating the value of exercise as a treatment for depression. Inclusion criteria for the study were a diagnosis of MDD and/or dysthymia based on the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, 4th ed (DSM-IV).

Investigators became aware that some subjects in the primary study were being treated with antidepressants and some were not. This offshoot study investigated the proportion of people with MS and MDD and/or dysthymia taking antidepressants and assessed behavioral variables associated with antidepressant use.

Celeste Hunter, from the Multiple Sclerosis Rehabilitation Research and Training Center, University of Washington, in Seattle, and an author of the poster, explained to Medscape that 1 of her colleagues noticed that although all patients in the study suffered from clinical depression, there appeared to be no discernible difference in terms of affect between patients who took antidepressants and those who did not.

"Depression is harder to pin down in patients with MS," Ms. Hunter said. "I see the MS patients as being more emotionally reactive in a given situation than if they didn't have MS. The unpredictability factor is so important — they don't know, if they have a really bad exacerbation, whether they'll get the same function back as before."

Almost half of the patients in this group (44%) were not taking antidepressants. Those on treatment were receiving various agents.

Patient-Reported Antidepressant Use

Treatment (%)
None 44.0
Fluoxetine 5.0
Citalopram 6.0
Bupropion 14.0
Venlafaxine 11.0
Sertraline 6.0
Other 14.0

Subjects were 85% female, 42.7% employed, and 91.7% white. Their Expanded Disability Status Scale scores were 4 or less in 52.1%, 4.5 to 6.0 in 45.8%, and 6.5 or more in 2.1%.

The researchers compared patients taking antidepressants (n = 54) with those not taking antidepressants (n = 42) — using the Hamilton Rating Scale for Depression, the Hopkins Symptom Checklist, the Modified Fatigue Impact Scale, item 8 of the Brief Pain Inventory, and the Expanded Disability Status Scale — and found no significant difference between the outcome scores of the 2 groups on any of these scales.

The authors concluded, "Because the study did not include people who were on antidepressants and not suffering from current MDD, our results may have been biased against finding improved outcomes associated with antidepressant use." Further studies in this area of MS treatment are needed, they added.

Kurt Johnson, PhD, a professor in the department of rehabilitation medicine at the University of Washington, but not an author of this study, commented to Medscape that there has not been much evidence in the MS literature that antidepressants are useful in treating depression. "We found the same thing in another study with a larger group of people. A lot of people in our sample were taking antidepressants when they weren't depressed, and a lot were depressed but were not taking antidepressants."

Higher Incidence of Depression

Medscape also talked with Stephen Kirzinger, MD, from the Multiple Sclerosis Care Center Program, Department of Neurology, University of Louisville, in Kentucky, about this poster. "Certainly we feel that patients who have a chronic disease can develop a reactive depression, but in the MS population the incidence is much greater than what you would expect, comparing it with other chronic-disease processes," said Dr. Kirzinger. "So we feel it is a manifestation of the disease that our patients, because of their MS activity, actually have a chemical change that leads to depression."

The antidepressants listed by patients participating in this study are serotonin reuptake inhibitors. Dr. Kirzinger noted that some preliminary data have indicated that serotonin itself has a beneficial effect on the immune system. "I think the present study flies in the face of most of our clinical experience [in which] the patients who have depression seem to respond to antidepressants. The fact that they did not see a dramatic difference between those on antidepressants and those not taking antidepressants is a little surprising."

This study was funded by the National Rehabilitation Research and Training Center on Multiple Sclerosis from the US Department of Education, National Institute on Disability and Rehabilitation Research.

Consortium of Multiple Sclerosis Centers 21st annual meeting: Abstract S110. Presented June 1, 2007.



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