Safety, tolerability, and efficacy of fluoxetine as an antiviral for acute flaccid myelitis. (30th April 2019)

• Record Type: Journal Article
• 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.
• Is Part Of: Neurology. Volume 92:Number 18(2019)
• Publication Date: 2019-04-30
• Subjects: Neurology -- Periodicals; Neurology -- Periodicals; Neurologie -- Périodiques; 616.8
• DOI: 10.1212/WNL.0000000000006670
• Languages: English
• ISSNs: 0028-3878

Abstract

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.