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

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.

Report on the 2018 Acute Flaccid Myelitis Outbreaks in the USA

“…The antiviral Fluoxetine has been trailed as treatment for presumptive EV-D68 associated AFM. However, it was not associated with improved outcomes (35).…”

Acute Flaccid Myelitis: Characteristics and Outcomes of 2014 and 2016 Cases at a Single Center

“…Pain was also a common complaint at diagnosis in our case series, which may be underestimated given the young age of our patients. 11,12 There is increasing evidence of an association between AFM and EV infection, but whether this association is related to direct viral invasion of the spinal cord, para-infectious autoimmune response to infection, or a combination of the two, remains unclear. 3,13,14 We did not find EV by PCR testing in cerebrospinal fluid from the 13 children that underwent lumbar puncture.…”

“…13 Fluoxetine treatment was implemented in 2016 based on in vitro data that it inhibited the replication of EV D68, but there was no clear treatment effect in retrospective analysis so this agent has since been removed from our institutional treatment protocol. 11,18,19 This highlights the observation that adding new therapies at the leading edge of knowledge is not always successful, and rational use must be constantly reassessed clinically to streamline treatment protocols.…”

“…Weakness in AFM is rapidly progressive, with a median of 4 days between symptom onset and nadir of symptoms. 11 Proximal weakness, in particular, can be easy to miss on a screening general medical examination. The presence of a recent or current febrile illness with asymmetry in motor function, even if initially attributed to pain, should prompt a thorough neurologic examination and consideration of AFM.…”

Acute Flaccid Myelitis: A Clinical Overview for 2019

“…However, this intervention was not associated with improved neurologic outcomes. 24 The convalescent phase of AFM lasts months to years with lingering or residual weakness. The long-term prognosis of AFM is unknown.…”