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

Tabaee Damavandi, Payam; Fabin, Natalia; Giossi, Riccardo; Matricardi, Sara; Del Giovane, Cinzia; Striano, Pasquale; Meletti, Stefano; Brigo, Francesco; Trinka, Eugen; Lattanzi, Simona (2023). Efficacy and Safety of Fenfluramine in Epilepsy: A Systematic Review and Meta-analysis. Neurology and therapy, 12(2), pp. 669-686. Springer 10.1007/s40120-023-00452-1

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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.


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.


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 The drug was withdrawn for any reason in 10.1% and 5.8% of patients receiving FFA and placebo, respectively (RR 1.79, 95% CI 0.89-3.59).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.


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.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Medical Education > Institute of General Practice and Primary Care (BIHAM)

UniBE Contributor:

Del Giovane, Cinzia


600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services








Pubmed Import

Date Deposited:

06 Mar 2023 07:48

Last Modified:

28 Mar 2023 15:45

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

Dravet syndrome Epilepsy Fenfluramine Lennox–Gastaut syndrome Seizures





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