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Open Access 28-02-2023 | Epilepsy | ORIGINAL RESEARCH

Efficacy and Safety of Fenfluramine in Epilepsy: A Systematic Review and Meta-analysis

Authors: Payam Tabaee Damavandi, Natalia Fabin, Riccardo Giossi, Sara Matricardi, Cinzia Del Giovane, Pasquale Striano, Stefano Meletti, Francesco Brigo, Eugen Trinka, Simona Lattanzi

Published in: Neurology and Therapy | Issue 2/2023

Abstract

Introduction

Fenfluramine (FFA) is an amphetamine derivative that promotes the release and blocks the neuronal reuptake of serotonin. Initially introduced as an appetite suppressant, FFA also showed antiseizure properties. This systematic review aimed to assess the efficacy and safety of FFA for the treatment of seizures in patients with epilepsy.

Methods

We systematically searched (in week 3 of June 2022) MEDLINE, the Cochrane Central Register of Controlled Trials, and the US National Institutes of Health Clinical Trials Registry. Randomized, double- or single-blinded, placebo-controlled studies of FFA in patients with epilepsy and uncontrolled seizures were identified. Efficacy outcomes included the proportions of patients with ≥ 50% and 100% reductions in baseline seizure frequency during the treatment period. Tolerability outcomes included the proportions of patients who withdrew from treatment for any reason and suffered adverse events (AEs). The risk of bias in the included studies was assessed according to the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions. The risk ratio (RR) along with the 95% confidence interval (CI) were estimated for each outcome.

Results

Three trials were identified and a total of 469 Dravet syndrome (DS) and Lennox–Gastaut syndrome (LGS) subjects were randomized. All three trials were judged to be at low risk of biases. In patients with DS, the RRs for ≥ 50% and 100% reductions in convulsive seizure frequency for the FFA group compared to placebo were 5.61 (95% CI 2.73–11.54) and 4.71 (95% CI 0.57–39.30), respectively. In patients with LGS, the corresponding RRs for ≥ 50% and 100% reductions in drop seizure frequency were 2.58 (95% CI 1.33–5.02) and 0.50 (95% CI 0.031–7.81), respectively. The drug was withdrawn for any reason in 10.1% and 5.8% of patients receiving FFA and placebo, respectively (RR 1.79, 95% CI 0.89–3.59). Treatment discontinuation due to AEs occurred in 5.4% and 1.2% of FFA- and placebo-treated patients, respectively (RR 3.63, 95% CI 0.93–14.16). Decreased appetite, diarrhoea, fatigue, and weight loss were AEs associated with FFA treatment.

Conclusion

Fenfluramine reduces the frequency of seizures in patients with DS and LGS. Decreased appetite, diarrhoea, fatigue, and weight loss are non-cardiovascular AEs associated with FFA.

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Title: Efficacy and Safety of Fenfluramine in Epilepsy: A Systematic Review and Meta-analysis
Authors: Payam Tabaee Damavandi
Natalia Fabin
Riccardo Giossi
Sara Matricardi
Cinzia Del Giovane
Pasquale Striano
Stefano Meletti
Francesco Brigo
Eugen Trinka
Simona Lattanzi
Publication date: 28-02-2023
Publisher: Springer Healthcare
Keywords: Epilepsy
Dravet Syndrome
Lennox Gastaut Syndrome
Published in: Neurology and Therapy / Issue 2/2023
Print ISSN: 2193-8253
Electronic ISSN: 2193-6536
DOI: https://doi.org/10.1007/s40120-023-00452-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Efficacy and Safety of Fenfluramine in Epilepsy: A Systematic Review and Meta-analysis

Abstract

Introduction

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusion

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