Impact of Antiseizure Medications on Appetite and Weight in Children

Buraniqi, Ersida; Dabaja, Hicham; Wirrell, Elaine

doi:10.1007/s40272-022-00505-2

Cited by 13 publications

(10 citation statements)

References 200 publications

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“…In clinical practice, adjustments are made in these medications to reduce side effects, minimize drug–drug interactions, and optimize efficacy. 26 , 27 , 28 , 29 , 30 …”

Section: Discussionmentioning

confidence: 99%

“…In our study, recurrent ASM dose adjustments were mostly dosage decreases in the ASMs valproate, clobazam, lamotrigine, rufinamide, topiramate, levetiracetam, and felbamate; cannabidiol was the most common addition after 6 months. In clinical practice, adjustments are made in these medications to reduce side effects, minimize drug–drug interactions, and optimize efficacy 26–30 …”

Section: Discussionmentioning

confidence: 99%

“…Our study results also suggest that the dynamics of weight loss are discontinuous in some patients and may stabilize over time. Managing short‐term (discontinuous, stabilizing) and long‐term (continuous) weight loss and decreased appetite can be accomplished with standard approaches used in clinical practice (e.g., dietary interventions, adjustments in concomitant ASM dose) 27,34 . Furthermore, children with LGS require continuous caregiver support, thereby allowing for identification and timely intervention to manage weight should issues arise.…”

Section: Discussionmentioning

confidence: 99%

“…In clinical practice, adjustments are made in these medications to reduce side effects, minimize drug-drug interactions, and optimize efficacy. [26][27][28][29][30] Fenfluramine was originally developed as an anorexigenic agent, making weight loss a TEAE of interest in long-term studies. As in the OLEs with Dravet syndrome, 31 weight loss stabilized over time in our study.…”

Section: Discussionmentioning

confidence: 99%

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Fenfluramine provides clinically meaningful reduction in frequency of drop seizures in patients with Lennox–Gastaut syndrome: Interim analysis of an open‐label extension study

et al. 2022

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Objective: This study was undertaken to evaluate the long-term safety and effectiveness of fenfluramine in patients with Lennox-Gastaut syndrome (LGS). Methods: Eligible patients withLGS who completed a 14-week phase 3 randomized clinical trial enrolled in an open-label extension (OLE; NCT03355209).All patients were initially started on .2 mg/kg/day fenfluramine and after 1 month were titrated by effectiveness and tolerability, which were assessed atThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

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“…In clinical practice, adjustments are made in these medications to reduce side effects, minimize drug–drug interactions, and optimize efficacy. 26 , 27 , 28 , 29 , 30 …”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Fenfluramine provides clinically meaningful reduction in frequency of drop seizures in patients with Lennox–Gastaut syndrome: Interim analysis of an open‐label extension study

et al. 2022

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“…Chronic administration of vigabatrin (75–300 mg/kg/day for 14 d) dose-dependently decreased rat weight (up to 20% of the original body weight) by decreasing appetite 71 , 72 . Clinically, vigabatrin ranks as an antiepileptic drug with minimal effects on weight loss 73 . Based on these clinical findings, ABAT suppression by vigabatrin does not seem to be a promising target for reducing antipsychotic-induced weight gain and metabolic complications originating from hypothalamic AMPK signalling activation.…”

Section: Discussionmentioning

confidence: 99%

Opposing effects of clozapine and brexpiprazole on β-aminoisobutyric acid: Pathophysiology of antipsychotics-induced weight gain

2023

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Clozapine is one of the most effective antipsychotics and has the highest risk of weight gain and metabolic complications; however, the detailed pathophysiology of its clinical action and adverse reactions remains to be clarified. Therefore, the present study determined the chronic effects of clozapine (high risk of weight gain) and brexpiprazole (relatively low risk of weight gain) on intracellular and extracellular levels of β-aminoisobutyric acid (BAIBA) enantiomers, which are endogenous activators of AMP-activated protein kinase (AMPK). L-BAIBA is the dominant BAIBA enantiomer in the rat hypothalamus and cultured astrocytes, whereas L-BAIBA accounts for only approximately 5% of the total plasma BAIBA enantiomers. L-BAIBA displayed GABAB receptor agonistic action in the extracellular space and was released through activated astroglial hemichannels, whereas in the intracellular space, L-BAIBA activated AMPK signalling. Chronic administration of the effective doses of clozapine increased intracellular and extracellular levels of L-BAIBA in the hypothalamus and cultured astrocytes, whereas that of brexpiprazole decreased them. These results suggest that enhancing hypothalamic AMPK signalling by increasing intracellular L-BAIBA levels is, at least partially, involved in the pathophysiology of clozapine-induced weight gain and metabolic complications.

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Practical considerations for the use of fenfluramine to manage patients with Dravet syndrome or Lennox–Gastaut syndrome in clinical practice

Wirrell,

Lagae,

Scheffer

et al. 2024

Epilepsia Open

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Fenfluramine (FFA), an antiseizure medication (ASM) with serotonergic and sigma‐1 receptor activity, is used to manage patients with developmental and epileptic encephalopathies (DEEs). It is approved in the US for treating seizures associated with Dravet syndrome (DS) and Lennox–Gastaut syndrome (LGS) in patients ≥2 years old and as add‐on therapy for seizures associated with DS and LGS in the EU, UK, and Japan in similarly aged patients. Consensus guidelines for treatment of DS have recommended FFA to be an early‐line ASM, and it has also shown efficacy in managing seizures associated with LGS. DS and LGS are DEEs associated with a range of seizure types, developmental impairments, and multiple comorbidities. Here we provide case vignettes describing 4 patients (3 DS and 1 LGS) aged 4–29 years old in whom up to 14 ASMs had previously failed, to illustrate real‐world practice issues encountered by neurologists. This review provides guidance on the use of FFA in the context of ASM polytherapy and drug–drug interactions (DDIs), behavioral issues, dose titration, and adverse events. Along with data from the clinical trial program, these case vignettes emphasize the low risk of DDIs, a generally well‐tolerated safety profile, and other seizure and nonseizure benefits (eg, improved cognition and sleep) associated with the use of FFA in DS or LGS.Plain Language SummaryFenfluramine is used to treat seizures in individuals with Dravet syndrome and Lennox–Gastaut syndrome, but there are a range of issues that clinicians may face when treating patients. This review highlights four patients from the authors’ everyday clinical work and offers guidance and practical considerations by neurologists with expertise in managing these complex conditions related to drug interactions, dosing, and side effects associated with fenfluramine.

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Impact of Antiseizure Medications on Appetite and Weight in Children

Cited by 13 publications

References 200 publications

Fenfluramine provides clinically meaningful reduction in frequency of drop seizures in patients with Lennox–Gastaut syndrome: Interim analysis of an open‐label extension study

Fenfluramine provides clinically meaningful reduction in frequency of drop seizures in patients with Lennox–Gastaut syndrome: Interim analysis of an open‐label extension study

Opposing effects of clozapine and brexpiprazole on β-aminoisobutyric acid: Pathophysiology of antipsychotics-induced weight gain

Practical considerations for the use of fenfluramine to manage patients with Dravet syndrome or Lennox–Gastaut syndrome in clinical practice

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