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

• Published in: Neurology Vol. 92; no. 18; pp. e2118 - e2126
• Main Authors: Messacar, Kevin, Sillau, Stefan, Hopkins, Sarah E, Otten, Catherine, Wilson-Murphy, Molly, Wong, Brian, Santoro, Jonathan D, Treister, Andrew, Bains, Harlori K, Torres, Alcy, Zabrocki, Luke, Glanternik, Julia R, Hurst, Amanda L, Martin, Jan A, Schreiner, Teri, Makhani, Naila, DeBiasi, Roberta L, Kruer, Michael C, Tremoulet, Adriana H, Van Haren, Keith, Desai, Jay, Benson, Leslie A, Gorman, Mark P, Abzug, Mark J, Tyler, Kenneth L, Dominguez, Samuel R
• Format: Journal Article
• Language: English
• Published: United States American Academy of Neurology 30-04-2019; Lippincott Williams & Wilkins
• Subjects: 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; Null Hypothesis; Retrospective Studies; Treatment Outcome
• ISSN: 0028-3878; 1526-632X
• DOI: 10.1212/WNL.0000000000006670

OBJECTIVETo determine the safety, tolerability, and efficacy of fluoxetine for proven or presumptive enterovirus (EV) D68–associated acute flaccid myelitis (AFM).
METHODSA 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.
RESULTSFifty-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).
CONCLUSIONFluoxetine 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 EVIDENCEThis study provides Class IV evidence that for patients with EV-D68-associated AFM, fluoxetine is well-tolerated and not associated with improved neurologic outcomes.