Safety, tolerability, and efficacy of fluoxetine as an antiviral for acute flaccid myelitis

Kevin Messacar; Stefan Sillau; Sarah E Hopkins; Catherine Otten; Molly Wilson-Murphy; Brian Wong; Jonathan D Santoro; Andrew Treister; Harlori K Bains; Alcy Torres; Luke Zabrocki; Julia R Glanternik; Amanda L Hurst; Jan A Martin; Teri Schreiner; Naila Makhani; Roberta L DeBiasi; Michael C Kruer; Adriana H Tremoulet; Keith Van Haren; Jay Desai; Leslie A Benson; Mark P Gorman; Mark J Abzug; Kenneth L Tyler; Samuel R Dominguez

doi:10.1212/WNL.0000000000006670

Safety, tolerability, and efficacy of fluoxetine as an antiviral for acute flaccid myelitis

Neurology. 2019 Apr 30;92(18):e2118-e2126. doi: 10.1212/WNL.0000000000006670. Epub 2018 Nov 9.

Authors

Kevin Messacar¹, Stefan Sillau², Sarah E Hopkins², Catherine Otten², Molly Wilson-Murphy², Brian Wong², Jonathan D Santoro², Andrew Treister², Harlori K Bains², Alcy Torres², Luke Zabrocki², Julia R Glanternik², Amanda L Hurst², Jan A Martin², Teri Schreiner², Naila Makhani², Roberta L DeBiasi², Michael C Kruer², Adriana H Tremoulet², Keith Van Haren², Jay Desai², Leslie A Benson², Mark P Gorman², Mark J Abzug², Kenneth L Tyler², Samuel R Dominguez²

Affiliations

¹ From the Departments of Pediatrics (K.M., J.A.M., T.S., M.J.A., S.R.D.) and Neurology (K.M., S.S., J.A.M., T.S., K.L.T.), University of Colorado School of Medicine; Children's Hospital Colorado (K.M., A.L.H., J.A.M., T.S., M.J.A., S.R.D.), Aurora; Children's Hospital of Philadelphia (S.E.H.), PA; Seattle Children's Hospital (C.O.), University of Washington; Boston Children's Hospital (M.W.-M., L.A.B., M.P.G.), MA; Children's Hospital of Los Angeles (B.W., J.D.), CA; Stanford University (J.D.S., K.V.H.), Palo Alto, CA; University of California San Diego (A.T., A.H.T.); Phoenix Children's Hospital (H.K.B., M.C.K.), AZ; Boston Medical Center (A.T.), MA; Naval Medical Center of San Diego (L.Z.), CA; Departments of Pediatrics (J.R.G., N.M.) and Neurology (N.M.), Yale School of Medicine, New Haven, CT; and Children's National Medical Center (R.L.D.), Washington, DC. kevin.messacar@childrenscolorado.org.
² From the Departments of Pediatrics (K.M., J.A.M., T.S., M.J.A., S.R.D.) and Neurology (K.M., S.S., J.A.M., T.S., K.L.T.), University of Colorado School of Medicine; Children's Hospital Colorado (K.M., A.L.H., J.A.M., T.S., M.J.A., S.R.D.), Aurora; Children's Hospital of Philadelphia (S.E.H.), PA; Seattle Children's Hospital (C.O.), University of Washington; Boston Children's Hospital (M.W.-M., L.A.B., M.P.G.), MA; Children's Hospital of Los Angeles (B.W., J.D.), CA; Stanford University (J.D.S., K.V.H.), Palo Alto, CA; University of California San Diego (A.T., A.H.T.); Phoenix Children's Hospital (H.K.B., M.C.K.), AZ; Boston Medical Center (A.T.), MA; Naval Medical Center of San Diego (L.Z.), CA; Departments of Pediatrics (J.R.G., N.M.) and Neurology (N.M.), Yale School of Medicine, New Haven, CT; and Children's National Medical Center (R.L.D.), Washington, DC.

Abstract

Objective: To determine the safety, tolerability, and efficacy of fluoxetine for proven or presumptive enterovirus (EV) D68-associated acute flaccid myelitis (AFM).

Methods: A multicenter cohort study of US patients with AFM in 2015-2016 compared serious adverse events (SAEs), adverse effects, and outcomes between fluoxetine-treated patients and untreated controls. Fluoxetine was administered at the discretion of treating providers with data gathered retrospectively. The primary outcome was change in summative limb strength score (SLSS; sum of Medical Research Council strength in all 4 limbs, ranging from 20 [normal strength] to 0 [complete quadriparesis]) between initial examination and latest follow-up, with increased SLSS reflecting improvement and decreased SLSS reflecting worsened strength.

Results: Fifty-six patients with AFM from 12 centers met study criteria. Among 30 patients exposed to fluoxetine, no SAEs were reported and adverse effect rates were similar to unexposed patients (47% vs 65%, p = 0.16). The 28 patients treated with >1 dose of fluoxetine were more likely to have EV-D68 identified (57.1% vs 14.3%, p < 0.001). Their SLSS was similar at initial examination (mean SLSS 12.9 vs 14.3, p = 0.31) but lower at nadir (mean SLSS 9.25 vs 12.82, p = 0.02) and latest follow-up (mean SLSS 12.5 vs 16.4, p = 0.005) compared with the 28 patients receiving 1 (n = 2) or no (n = 26) doses. In propensity-adjusted analysis, SLSS from initial examination to latest follow-up decreased by 0.2 (95% confidence interval [CI] -1.8 to +1.4) in fluoxetine-treated patients and increased by 2.5 (95% CI +0.7 to +4.4) in untreated patients (p = 0.015).

Conclusion: Fluoxetine was well-tolerated. Fluoxetine was preferentially given to patients with AFM with EV-D68 identified and more severe paralysis at nadir, who ultimately had poorer long-term outcomes.

Classification of evidence: This study provides Class IV evidence that for patients with EV-D68-associated AFM, fluoxetine is well-tolerated and not associated with improved neurologic outcomes.

Publication types

Multicenter Study
Observational Study
Research Support, N.I.H., Extramural

MeSH terms

Antiviral Agents / therapeutic use*
Central Nervous System Viral Diseases / drug therapy*
Child
Child, Preschool
Female
Fluoxetine / administration & dosage
Fluoxetine / therapeutic use*
Humans
Male
Myelitis / drug therapy*
Neuromuscular Diseases / drug therapy*
Retrospective Studies
Treatment Outcome

Safety, tolerability, and efficacy of fluoxetine as an antiviral for acute flaccid myelitis

Authors

Affiliations

Abstract

Publication types

MeSH terms

Substances

Supplementary concepts

Grants and funding