The antidepressant fluoxetine (Prozac) did not improve muscle strength in children with enterovirus (EV) D68-associated acute flaccid myelitis, a rare polio-like disease, a non-randomized, open-label study found.
Children with acute flaccid myelitis who received fluoxetine had poorer neurological outcomes than untreated children, reported Kevin Messacar, MD, of Children’s Hospital Colorado in Aurora and colleagues in
Neurology.
“Though fluoxetine has been shown to have
activity against EV-D68 in the laboratory, at the dosage and timing administered clinically to patients with acute flaccid myelitis in 2016, it did not demonstrate a signal of efficacy,” Messacar told
MedPage Today. “The lack of an efficacy signal emphasizes the need to develop and prospectively investigate better therapeutics and preventative strategies for acute flaccid myelitis.”
Since 2014, several clusters of acute flaccid myelitis have been reported in parallel with outbreaks of EV-D68, an enterovirus associated with mild respiratory disease, noted Katja Wolthers, MD, PhD, a clinical virologist at Amsterdam University Medical Centers in the Netherlands, who was not involved in the study.
“Since then, the relation between EV-D68 and acute flaccid myelitis has been proven, not only by epidemiological association but also by showing that the newly circulating 2014 strains of EV-D68 could induce paralysis in mice, while the older virus variants could not,” Wolthers told MedPage Today.
In the U.S., the CDC has reported a total of
404 confirmed cases of acute flaccid myelitis, mostly in children, from August 2014 to October 2018. Currently, there is no 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 antiviral effect against enteroviruses in vitro,” Wolthers noted. “Since this drug is already registered for use in the clinic — but for different indications — there is experience with safety, which makes it an appealing candidate drug to use for a different indication, such as acute flaccid myelitis.”
In this research, Messacar and colleagues studied 56 children, median age of 3.8, who had acute flaccid myelitis in 12 U.S. medical centers in 2015 and 2016, comparing 28 children who received >1 dose of fluoxetine with 26 children who did not receive the drug. (Two children who had one dose only were considered part of the untreated group.) Patients treated with >1 dose of fluoxetine were more likely to have EV-D68 identified from specimens (57.1% versus 14.3%, P<0.001).
The researchers identified a prodromal illness in 51 of 56 patients — most commonly with fever and respiratory symptoms. Neurologic onset of weakness began a median of 8.5 days after prodromal illness onset. Fluoxetine was initiated a median of 5 days after neurologic onset, prior to nadir in 37% of cases and following nadir in 60%. The median time from neurologic onset to latest follow-up was 210 days.
The research team used the summative limb strength score (SLSS), the sum of Medical Research Council strength in all four limbs that ranges from 20 (normal strength) to 0 (complete quadriparesis), to determine the drug’s effectiveness.
At initial exam, mean SLSS was similar (treated 12.9 versus untreated 14.3, P=0.31) but lower in treated patients at nadir (9.25 versus 12.82, P=0.02) and at latest follow-up (12.5 versus 16.4, P=0.005). No serious adverse events were reported.
In propensity-adjusted analysis, SLSS from initial exam to latest follow-up decreased by 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 treatment versus non-treatment groups, and indeed, patients with more severe paralysis were treated more often, as well as EV-D68 positive patients,” observed Wolthers. Treatment often was started days after initial weaknesses manifested, which could be too late for clinical benefit, she noted.
A retrospective study of non-randomized clinical treatments for an uncommon condition with cases scattered across the country has inherent limitations, Messacar noted, and prospective, controlled trials to evaluate treatments systematically are needed. “Though acute flaccid myelitis is uncommon, the biennial surge in cases of potentially long-term, polio-like paralysis since 2014 suggests this should be a public health priority warranting increased attention and funding,” he said.
This study was supported by the National Institutes of Health.
The researchers reported no relationships relevant to the manuscript.
- Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner
