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.

Figure 1. Study inclusion flowchart

Flowchart of study site and study population inclusion with intention-to-treat analysis of safety and tolerability conducted comparing 30 fluoxetine-exposed patients to 26 fluoxetine-unexposed patients and per protocol analysis of patient characteristics and efficacy comparing 28 fluoxetine-treated patients (receiving >1 dose) to 28 fluoxetine-untreated patients.

Figure 2. Fluoxetine efficacy on limb strength outcomes

Unadjusted mean summative limb strength score with SE is depicted at the time of initial examination, nadir, and latest follow-up examination for the fluoxetine-treated group (n = 28, black line) and the fluoxetine-untreated group (n = 28, gray line). ^aFluoxetine was initiated prior to nadir in 11 of 30 (37%) treated patients and on or after nadir in 18 of 30 (60%) treated patients; fluoxetine timing was unknown for one patient.