Lacosamide effectiveness and tolerability in patients with drug-resistant epilepsy and severe disability under polytherapy: Therapy optimization as emerging from an observational study.
Epilepsy Behav
; 128: 108598, 2022 03.
Article
en En
| MEDLINE
| ID: mdl-35151192
ABSTRACT
OBJECTIVE:
We explored the efficacy and safety of lacosamide combined with inhibitors of fast-inactivated sodium channels or with other antiepileptic drugs, in patients with drug refractory focal epilepsy associated with intellectual or psychiatric disability.METHODS:
Observational study of lacosamide including the monitoring of lacosamide trough plasma levels and of electroencephalograms.RESULTS:
We followed up 44 patients from the start of lacosamide therapy for up to 3â¯years, with a clinical, electroencephalogram (EEG), and pharmacological follow-up. Median patients' age was 32.7â¯years, median age at epilepsy onset was 3.5â¯years. Intellectual disability was severe in 55.4% of the cohort and drug refractoriness was diagnosed in 88.6% of patients, who had predominantly focal seizures (80%). The severity of their epilepsy was suggested by the use of combined therapies with non-sodium blockers and sodium blockers in 75% of patients. Lacosamide was added to previous therapies and up-titrated to a median of 300â¯mg/d. Lacosamide add-on led to simplification of the previous drug regimen with a dose reduction in 87.9% of users of sodium blockers and in 66.7% of users of non-sodium blockers, and to withdrawal of previously administered sodium blockers in 48.5% users and non-sodium blockers in 47.6% users. Lacosamide was prescribed at lower doses in the presence of oxcarbazepine (pâ¯=â¯0.029), lamotrigine (pâ¯=â¯0.015), and topiramate (pâ¯<â¯0.001). Mean lacosamide plasma levels were 6.0⯱â¯2.4â¯mg/L; they were in linear correlation with the administered dose (R2â¯=â¯0.38, pâ¯<â¯0.001) and were influenced by the association with lamotrigine (pâ¯=â¯0.008), zonisamide (pâ¯=â¯0.012), and clobazam (pâ¯=â¯0.028). Lacosamide combination regimens led to an average reduction of 42% in baseline seizure frequency, with 50% patients reporting ≥50% seizure frequency reduction. Efficacy was directly correlated with lacosamide dose (R2â¯=â¯0.47, pâ¯<â¯0.001, Bâ¯=â¯0.53) and trough plasma levels (R2â¯=â¯0.31, pâ¯<â¯0.001, Bâ¯=â¯0.16). Electroencephalogram profiles were improved in 40.9% of patients and EEG improvement was not significantly correlated with seizure frequency reduction. Lacosamide safety was good, with 37 adverse reactions in 30 patients, of which 50% were attributed to lacosamide and led to lacosamide withdrawal in 18% of cases. The retention rate of lacosamide was of 88.6% at 1â¯year, 86.4% at 2â¯years, and 72.7% after three years. The severity of intellectual disability was directly correlated with increased possibility of lacosamide retention (ORâ¯=â¯0.46 per severity tier, pâ¯=â¯0.016).CONCLUSION:
Lacosamide add-on allowed dose reduction of previous therapies and reduced the frequency of seizures, showing good tolerability even at high doses, without exceeding reference plasma levels.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Epilepsia
/
Epilepsia Refractaria
Tipo de estudio:
Observational_studies
Límite:
Adult
/
Humans
Idioma:
En
Revista:
Epilepsy Behav
Asunto de la revista:
CIENCIAS DO COMPORTAMENTO
/
NEUROLOGIA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Italia