Lamotrigine versus Valproic Acid as First‐line Monotherapy in Newly Diagnosed Typical Absence Seizures: An Open‐label, Randomized, Parallel‐group Study

Abstract

Summary: Purpose:To compare the efficacy of lamotrigine (LTG) and valproic acid (VPA) in newly diagnosed children and adolescents with typical absence seizures.Methods: A randomized, open-label parallel-group design was used. After undergoing an awake video-EEG recording, which included one to two trials of 3 min of hyperventilation and intermittent photic stimulation, eligible patients were randomized to receive LTG or VPA. LTG was initiated at a daily dose of 0.5 mg/kg for 2 weeks in two divided doses, followed by 1.0 mg/kg/day for an additional 2 weeks. Thereafter, doses were increased in 1-mg/kg/day increments every 5 days until seizures were controlled, intolerable adverse effects occurred, or a maximum dose of 12 mg/kg/day had been reached. VPA was equally uptitrated according to clinical response, starting at 10 mg/kg and increasing by 5 mg/kg/24 h every 3 days, if required, to a maximum of 30 mg/kg/day in three divided doses. Patients were seen in the clinic every month for ≤12 months.The primary efficacy end point at each visit was seizure freedom, defined as lack of clinically observed seizures since the previous visit and lack of electroclinical seizures during ambulatory 24-h EEG testing and a video-EEG session with hyperventilation.Results: Thirty-eight children (17 boys, 21 girls), aged from 3 to 13 years (mean, 7.5 years), all newly diagnosed with childhood or juvenile typical absence seizures, were enrolled. After 1 month of treatment, 10 (52.6%) of 19 children taking VPA and one (5.3%) of 19 taking LTG were seizure free (p = 0.004). By the 3-month follow-up, 12 (63.1%) children taking VPA and seven (36.8%) taking LTG were controlled (p = 0.19). After 12 months, 13 children taking VPA (dose range, 20-30 mg/kg/day; mean serum level, 76.8 mg/L; range, 51.4-91 mg/L) and 10 taking LTG (dose range, 2-11 mg/kg/day; mean serum level, 8.1 mg/L; range, 1.1-18 mg/L) were seizure free (p = 0.51). Side effects were mostly mild and transient and were recorded in two (10.6%) children treated with VPA and in six (31.8%) treated with LTG.Conclusions: Both VPA and LTG can be efficacious against absence seizures, although VPA shows a much faster onset of action, at least in part because of its shorter titration schedule.

Antiepileptic drug treatment in children

“…In addition, a doubleblind, placebo-controlled study suggested that LTG is effective for children with newly diagnosed absence seizures [56]. One open-label, randomized trial revealed that LTG was equivalent to VPA for the initial treatment of CAE, although equivalent seizure control was not seen for a year after beginning treatment, which was attributed to the very slow dose titration of LTG [57]. It is not uncommon for the slow titration to be a limiting factor for the use of LTG, particularly when fast seizure control is required; this may necessitate the use of a bridge medication, such as clonazepam, until a therapeutic dose is achieved.…”

Epigenetic Downregulation of Scn3a Expression by Valproate: a Possible Role in Its Anticonvulsant Activity

“…Valproate (VPA) is one of the most commonly used drugs for the treatment of various types of seizures, chronic neuropathic pain, bipolar disorder, and migraine headaches [13][14][15][16][17]. The antiepileptic action of VPA is believed to achieve through inhibiting the firing frequencies of high-excitable neurons by its multiple effects on GABAergic system, enzymes related to the metabolic pathways, and the activities of ion channels [18][19][20].…”

Lamotrigine Adjunctive Therapy Among Children and Adolescents With Primary Generalized Tonic-Clonic Seizures

“…These results support the hypotheses developed from open-label reports suggesting that lamotrigine might be effective in PGTC seizures. 9,10,15 Previous clinical trials have shown that lamotrigine is effective in the treatment of primarily generalized absence seizures 6,7 and in partial seizures in childhood. 5 Lamotrigine is also effective in the treatment of generalized seizures associated with the Lennox-Gastaut syndrome.…”

“…Lamotrigine has demonstrated efficacy from published randomized clinical trials (RCTs) for childhood partial seizures, 5 absence seizures, 6,7 and for the generalized seizures associated with Lennox-Gastaut syndrome. 8 Lamotrigine has been reported in open-label studies 9,10 and in double-blind, active-comparator RCTs to be effective in patients with newly diagnosed, previously untreated primary or secondary generalized seizures.…”