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Switching from VPA to other medications in women with idiopathic generalized epilepsy

Valproic acid showed great efficacy in patients with generalized idiopathic epilepsy, but many women of child-bearing age need to switch from VPA due to its risks and side effects, creating a dilemma between managing these side effects and the risk of persistent seizures. A multicenter retrospective study identified predictors of seizure relapse after discontinuing VPA, such as higher VPA doses and shorter seizure-freedom duration, to aid physicians in making safer transitions to less teratogenic ASMs. Women switching to LEV had a lower risk of breakthrough seizures compared to those switching to LTG: clinicians may wish to consider LEV over LTG when discontinuing VPA.

Valproic acid (VPA) is highly effective for managing idiopathic generalized epilepsy (IGE), as showed in the randomized, unblinded SANAD and SANAD II trials, where time to seizure control was superior for VPA compared with Lamotrigine (LTG) and Levetiracetam (LEV) (1). Nevertheless, it poses substantial side effects, significant teratogenicity and neurodevelopmental risks during pregnancy.
Regulatory agencies thus advise against its use in pregnant women; hence physicians must face the difficult choice between the side effects of VPA and the risk of uncontrolled seizures.
In order to determine which women can safely transition to less teratogenic and better-tolerated ASMs, a multicenter retrospective study conducted by Cerulli Irelli et al. (2) aimed to identify the predictors of seizure recurrence or worsening in women who discontinued VPA and switched to other medications.
The Authors found 4 independent factors associated with increased frequency of seizures: higher VPA doses, shorter seizure-freedom duration before the switch, multiple seizure types, and catamenial seizure exacerbations.
LTG and LEV were the safer alternatives of choice because of their favorable side effect profiles and the reassuring evidence for favorable pregnancy outcomes. Women switching to LEV had a lower risk of breakthrough seizures compared to those switching to LTG. Clinicians may, therefore, consider using LEV over LTG in people with difficult-to-control idiopathic generalized epilepsy switching away from VPA.
This study helps informing clinical decisions for women of childbearing age with epilepsy, highlighting the need for personalized treatment plans based on individual epilepsy characteristics. (3)

Key Points:

• Predictors of seizure recurrence after discontinuing VPA: higher doses of VPA, shorter seizure-free duration before switching, multiple seizure types, and catamenial seizure exacerbations
• Lamotrigine (LTG) and levetiracetam (LEV) are safer alternatives during pregnancy, with LEV associated with a lower risk of breakthrough seizures compared to LTG
• Personalized treatment plans based on individual epilepsy characteristics are essential

References:

  1. Marson AG, Al-Kharusi AM, Alwaidh M, Appleton R, Baker GA, Chadwick DW, Cramp C, Cockerell OC, Cooper PN, Doughty J, Eaton B, Gamble C, Goulding PJ, Howell SJ, Hughes A, Jackson M, Jacoby A, Kellett M, Lawson GR, Leach JP, Nicolaides P, Roberts R, Shackley P, Shen J, Smith DF, Smith PE, Smith CT, Vanoli A, Williamson PR; SANAD Study group. The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial. Lancet. 2007 Mar 24;369(9566):1016-26. doi: 10.1016/S0140-6736(07)60461-9.
  2. Cerulli Irelli E, Cocchi E, Morano A, et al.; Women with Epilepsy Treatment Options and Research (WETOR) study group. Predictors of seizure recurrence in women with idiopathic generalized. Neurology. 2024 May;102(9):e209222. doi: 10.1212/WNL.0000000000209222.
  3. Johnson EL. Valproate: Weighing the Unique Risks. Neurology. 2024 May;102(9):e209325. doi: 10.1212/WNL.0000000000209325. Epub 2024 Apr 3. PMID: 38569129.

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