TY - JOUR
T1 - Safety, tolerability, and efficacy of fluoxetine as an antiviral for acute flaccid myelitis
AU - Messacar, Kevin
AU - Sillau, Stefan
AU - Hopkins, Sarah E.
AU - Otten, Catherine
AU - Wilson-Murphy, Molly
AU - Wong, Brian
AU - Santoro, Jonathan D.
AU - Treister, Andrew
AU - Bains, Harlori K.
AU - Torres, Alcy
AU - Zabrocki, Luke
AU - Glanternik, Julia R.
AU - Hurst, Amanda L.
AU - Martin, Jan A.
AU - Schreiner, Teri
AU - Makhani, Naila
AU - DeBiasi, Roberta L.
AU - Kruer, Michael C.
AU - Tremoulet, Adriana H.
AU - Van Haren, Keith
AU - Desai, Jay
AU - Benson, Leslie A.
AU - Gorman, Mark P.
AU - Abzug, Mark J.
AU - Tyler, Kenneth L.
AU - Dominguez, Samuel R.
N1 - Funding Information:
Supported by NIH (K23AI28069, T32AI007210, R01NS101208, UL1TR002535). K. Messacar received support from the NIH: National Institute of Allergy and Infectious Diseases (K23AI28069) and National Center for Advancing Translational Sciences Colorado Clinical Translational Sciences Award (UL1TR002535). S. Sillau, S. Hopkins, C. Otten, M. Wilson-Murphy, B. Wong, J. Santoro, A. Treister, H. Bains, A. Torres, and L. Zabrocki report no disclosures relevant to the manuscript. J. Glanternik received support from the NIH: National Institute of Allergy and Infectious Diseases (T32AI007210). A. Hurst, J. Martin, T. Schreiner, N. Makhani, R. DeBiasi, M. Kruer, A. Tremoulet, K. Van Haren, J. Desai, L. Benson, M. Gorman, and M. Abzug report no disclosures relevant to the manuscript. K. Tyler received support from the NIH: National Institute of Neurologic Diseases and Stroke (R01NS101208). S. Dominguez reports no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures.
Funding Information:
AFM = acute flaccid myelitis; CI = confidence interval; EC50 = % effective concentration; EV = enterovirus; FDA = Food and Drug Administration; IQR = interquartile range; IVIg = IV immunoglobulin; MRC = Medical Research Council; QTc = corrected QT interval; SAE = serious adverse events; SLSS = summative limb strength score; WLSS = weakest limb strength score.
Funding Information:
K. Messacar received support from the NIH: National Institute of Allergy and Infectious Diseases (K23AI28069) and National Center for Advancing Translational Sciences Colorado Clinical Translational Sciences Award (UL1TR002535). S. Sillau, S. Hopkins, C. Otten, M. Wilson-Murphy, B. Wong, J. Santoro, A. Treister, H. Bains, A. Torres, and L. Zabrocki report no disclosures relevant to the manuscript. J. Glanternik received support from the NIH: National Institute of Allergy and Infectious Diseases (T32AI007210). A. Hurst, J. Martin, T. Schreiner, N. Makhani, R. DeBiasi, M. Kruer, A. Trem-oulet, K. Van Haren, J. Desai, L. Benson, M. Gorman, and M. Abzug report no disclosures relevant to the manuscript. K. Tyler received support from the NIH: National Institute of Neurologic Diseases and Stroke (R01NS101208). S. Dominguez reports no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures.
Funding Information:
Supported by NIH (K23AI28069, T32AI007210, R01NS101208, UL1TR002535).
Publisher Copyright:
Copyright © 2018 American Academy of Neurology.
PY - 2019/4/30
Y1 - 2019/4/30
N2 - 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.
AB - 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.
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U2 - 10.1212/WNL.0000000000006670
DO - 10.1212/WNL.0000000000006670
M3 - Article
C2 - 30413631
AN - SCOPUS:85061068865
VL - 92
SP - E2118-E2126
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 18
ER -