麻豆传媒

LONDON – A small trial failed to show that treating progressive multiple sclerosis patients with the antidepressant fluoxetine (Prozac) could improve physical function lost during the course of the disease, researchers said here.

After 120 weeks of treatment, about 70% of the patients taking fluoxetine had not experienced disease progression as assessed by standard walking and coordination tests compared to around 60% of patients who were on placebo (P=0.07), saida neurologist at Vrije Universiteit, Brussels.

Cambron, in her oral late-breaker presentation at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis, said that in the secondary endpoint – the proportion of patients without progression – the results were similar.

She said 69.6% or 48 of 69 patients on fluoxetine did not have signs of progression based on the timed 25-foot test or the 9-hole peg test while 61.8% or 42 of 68 patients on placebo did not have signs of disease progression (P=0.434).

In another secondary endpoint -- the proportion of patients who exhibited stability on the Hauser Ambulatory Index -- the differences were not statistically significant (P=0.371), Cambron said.

The patients receiving fluoxetine, however, did pay a price for the treatment in an added side effect profile which included more gastrointestinal complaints, more psychiatric disorders, more nervous system disorders and more musculoskeletal and connective tissue disorders than were experienced by patients in the placebo arm of the study.

Cambron noted that the proportion of placebo patients showing no progression was relatively high, which made it harder to show an advantage for fluoxetine. She also acknowledged that both the study duration and the number of patients enrolled may have been too small.

The study included patients with primary or secondary progressive MS who were age 25-65 and had an Expanded Disability Status Scale (EDSS) score of 3.0-to-6.5, indicating moderate to severe disability. For entry into the study, the patients had to have confirmed evidence of disease progression independent of clinical relapses over the past year. They also were required to practice reliable contraception, and, hence, pregnancy made women ineligible for the study.

The multicenter, randomized, double-blind study was conducted from February 2012 to June 2016 in clinics in the Netherlands and in Belgium. Patients began treatment with 20 mg/day of fluoxetine or placebo for 4 weeks, with doses doubled thereafter.

During the course of the trial they underwent numerous tests with the timed 25-foot walk, the 9-hole peg test and the Hauser test being performed every 12 weeks. The patients were tested for cognitive functioning, fatigue status and depression at baseline, at 60 weeks and at 108 weeks. A brain MRI was performed at week 12 and at week 108, Cambron reported.

Cambron said mean age for the fluoxetine patients was somewhat older – 54 years compared with 51 for the placebo patients. She said that difference was statistically significant but unlikely to have been clinically meaningful. About 55% of the patients in both arms of the study were men. About 42% of the patients had primary progressive MS; most of the rest had secondary progressive disease. The patients has been diagnosed for about 20 years with multiple sclerosis. Mean baseline EDSS score was 5.2.

In commenting on the study,a neurologist in private practice in Coconut Creek, Fla., and past president of the Florida Society of Neurology, told 麻豆传媒, "The trend was interesting, but the sample size probably was much too small for this to have been a positive trial. They did show a trend, and the p-value (P=0.07) wasn't terrible, so it means that the story is not over. If you had doubled the number of people in that trial, it might have been a positive result.

"I think it is a worthwhile discussion to have with my patients," Kantor said. "There are now emerging things that you can bring up to patients with progressive multiple sclerosis. We have to say that we don't have full data on fluoxetine and people have to make their own decisions," he said.

"There are potential other benefits with fluoxetine such as improvements in mood, but there are also potential side effects," he said. "These people are already on a lot of medicines so there is the problem of poly-pharmacy, and even though fluoxetine is still generic, there is a factor of costs as well."