Fluoxetine for acute myelitis flaccid?

The fluoxetine antidepressant (Prozac) has not improved muscle strength in children with acute flaccid myelitis associated with enterovirus (EV) D68, a rare disease resembling polio, an open study not randomized found.

Children with acute flaccid myelitis who received fluoxetine had worse neurologic outcomes than untreated children, said Kevin Messacar, MD, of the Colorado Children's Hospital at Aurora and his colleagues at Neurology.

"Although it has been demonstrated that fluoxetine had an activity against EV-D68 in laboratory, dosing and timing of administration clinically administered to patients with acute flaccid myelitis in 2016, it does not have a positive effect. has not demonstrated any sign of effectiveness, "Messacar said. MedPage today. "The lack of efficacy signal underscores the need to develop and prospectively study better treatments and preventive strategies for acute flaccid myelitis."

Since 2014, several clusters of acute flaccid myelitis have been reported alongside epidemics of EV-D68, an enterovirus associated with mild respiratory disease, noted Katja Wolthers, MD, Ph.D., clinical virologist at Amsterdam University. Medical Centers in the Netherlands. did not participate in the study.

"Since then, the relationship between EV-D68 and acute flaccid myelitis has been proven, not only by epidemiological association, but also by showing that the newly circulating strains of EV-D68, 2014, could induce paralysis in mice, while older virus variants, "said Wolthers MedPage today.

In the United States, the CDC reported a total of 404 confirmed cases of flaccid acute myelitis, mainly in children, from August 2014 to October 2018. At present, there is no evidence treatment, but efforts to find compounds that can inhibit enteroviruses in vitro have led to several possible candidates.

"Fluoxetine is one of those compounds that has shown an antiviral effect against enteroviruses in vitro," said Wolthers. "Since this drug is already registered for clinical use – but for different indications – there is a safety experience, which makes it a candidate candidate to use in a different indication, such as acute flaccid myelitis. "

In this study, Messacar and colleagues studied 56 children aged 3.8 years on average with acute flaccid myelitis in 12 US medical centers in 2015 and 2016, comparing 28 children who received> 1 dose of fluoxetine with 26 children. Not having received the drug. . (Two children who received only one dose were considered part of the untreated group.) Patients treated with more than one dose of fluoxetine were more likely to have EV-D68 identified from samples (57.1% vs. 14.3%). P<0.001).

The researchers identified a prodromal disease in 51 out of 56 patients – most often with fever and respiratory symptoms. The neurological onset of weakness began an average of 8.5 days after the onset of prodromal disease. Fluoxetine was started 5 days after the onset of neurological signs, 37% before nadir and 60% after nadir. The median time from neurologic onset to last follow-up was 210 days.

The research team used the Summative Strength Member Score (SLSS), the sum of the strength of the Medical Research Council for the four members, ranging from 20 (normal strength) to 0 (full quadriparesis), to determine the effectiveness of the drug.

In the initial review, the mean ESSSS was similar (treated at 12.9 vs. 14.3 untreated). P= 0.31) but lower in nadir-treated patients (9.25 vs. 12.82, P= 0.02) and at the last follow-up (12.5 vs. 16.4, P= 0.005). No serious adverse events have been reported.

In the propensity-adjusted analysis, the SLSS between the first and last follow-up decreased from 0.2 (95% CI -1.8 to 1.4) in treated patients and increased by 2.5 (95% CI 0.7 to 4.4) in untreated patients (P= 0.015).

"In such a retrospective observational study, it is difficult not to have differences between treated and untreated groups, and indeed, patients with more severe paralysis were treated more often, as well as patients with EV-positive D68 ", observed Wolthers. The treatment was often started several days after the onset of initial weaknesses, which might be too late for a clinical benefit, she noted.

A retrospective study of non-randomized clinical treatments for an uncommon disease with cases scattered across the country has inherent limitations, Messacar noted, and prospective comparative trials are routinely required to evaluate treatments. "Although acute flaccid myelitis is rare, the biennial upsurge of potentially long-term polio-like paralysis since 2014 suggests that this should be a public health priority that deserves increased attention and funding," he said. declared.

• Reviewed by
  Robert Jasmer, MD Associate Professor of Clinical Medicine at the University of California at San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

2018-11-09T17: 00: 00-0500