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Randomized Controlled Trial
. 2024 Apr;9(2):582-591.
doi: 10.1002/epi4.12892. Epub 2024 Jan 25.

Phosphatidylserine enriched with polyunsaturated n-3 fatty acid supplementation for attention-deficit hyperactivity disorder in children and adolescents with epilepsy: A randomized placebo-controlled trial

Sylvain Rheims  1   2   3 , Vania Herbillon  2   4 , Ségolène Gaillard  5 , Catherine Mercier  6 , Nathalie Villeuve  7 , Frédéric Villéga  8 , Claude Cances  9 , Pierre Castelnau  10 , Silvia Napuri  11 , Anne de Saint-Martin  12 , Stéphane Auvin  13   14   15 , Sylvie Nguyen The Tich  16 , Patrick Berquin  17 , Julitta de Bellecize  4 , Mathieu Milh  7 , Pascal Roy  6 , Alexis Arzimanoglou  2   4 , Jacques Bodennec  2   3 , Laurent Bezin  2   3 , Behrouz Kassai  5   18 ; investigators of the AGPI study group
Affiliations
Randomized Controlled Trial

Phosphatidylserine enriched with polyunsaturated n-3 fatty acid supplementation for attention-deficit hyperactivity disorder in children and adolescents with epilepsy: A randomized placebo-controlled trial

Sylvain Rheims et al. Epilepsia Open. 2024 Apr.

Abstract

Background: Attention-deficit hyperactivity disorder (ADHD) is a frequent comorbidity in children with epilepsy, which management mostly relies on the usual treatments of ADHD, especially methylphenidate. Supplementation with polyunsaturated n-3 Fatty Acid (PUFA) has been proposed as an alternative therapeutic approach in ADHD without epilepsy but has never been evaluated in epilepsy-associated ADHD.

Methods: A multicenter double blind randomized placebo-controlled trial evaluating supplementation with PUFA, in eicosapentaenoic- and docosahexaenoic-acid form, conjugated to a phospholipid vector (PS-Omega3) in children aged >6 and <16-years old, and suffering from any type of epilepsy and ADHD (inattentive or combined type) according to DSM-V. After a 4-week baseline period, patients were allocated (1:1) either to placebo group or to PS-Omega 3 group and entered a 12 week-double-blind treatment period which was followed by a 12 week-open-label treatment period. The primary outcome was the reduction of the ADHD-rating scale IV attention-deficit subscore after 12 weeks of treatment.

Results: The study was stopped early because of lack of eligible participants and the expected sample size was not reached. Seventy-four patients were randomized, 44 in PS-Omega3, and 30 in the placebo group. The reduction after 12 weeks of treatment in the inattention subscore of the ADHD-IV scale was -1.57 in the PS-Omega3 group, and -2.90 in the placebo group (p = 0.33, α = 5%). Results were similar after 24 weeks of treatment and for all other ADHD-related secondary outcomes, with no difference between placebo and PS-Omega3.

Conclusion: Our study remaining underpowered, no formal conclusion about the effect of Ps-Omega3 could be drawn. However, our data strongly suggested that the PS-Omega 3 formulation used in the current study did not improve ADHD symptoms in children with epilepsy.

Plain language summary: Supplementation with polyunsaturated n-3 Fatty Acid (PUFA) has been proposed in ADHD but has never been evaluated in patients with both epilepsy and ADHD. To address this issue, we conducted a multicenter double blind randomized placebo-controlled trial evaluating supplementation with PUFA in children with epilepsy and ADHD. The study was stopped early because of lack of eligible participants, hampering formal conclusion. However, the evolution of the ADHD symptoms at 12 and 24 weeks did not differ between placebo and PUFA supplementation, strongly suggesting that PUFA did not improve ADHD symptoms in children with epilepsy.

Keywords: ADHD; epilepsy; omega 3; polyunsaturated n‐3 fatty acid.

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Conflict of interest statement

SR received speaker and/or consulting fees from UCB Pharma, Angelini Pharma, EISAI, Livanova, JAZZ Pharma, Medtronic, Zogenix. AA, in agreement with his Institution, has served as principal investigator or member of DMCs in clinical trials for Eisai, UCB, GW Pharma; received consulting fees from Jazz, Zogenix, Eisai, Takeda, Biocodex, Encoded Therapeutics; unrestricted research grants from, UCB, Caixa Foundation and Jazz and academic research grants from EJP‐RD and the EU. We confirm that we have read the journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Figures

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FIGURE 1
Flow diagram of participants.
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