Side Effects of Sodium Valproate in Monotherapy Controlled by Plasma Levels: A Study in 88 Pediatric Patients

Abstract

The incidence of toxicity associated with the use of valproic acid (VPA) is considered remarkably low compared to other antiepileptic drugs. This study reports the toxicity of VPA administered as a single drug to 88 children in relation to the daily dose and drug plasma level. The frequency of side effects observed clinically was 42.0%, but it increased to 80.7% when a questionnaire was introduced. In spite of the limitations of this method, the results show the need to perform systematic surveillance for side effects of all antiepileptic drugs, similar to those made to assess their clinical effectiveness. Anorexia, vomiting, and sleep alterations were the most common side effects detected in the clinical record; patients who showed anorexia, hyperactivity, lassitude, sleep disturbances, and sadness had received daily doses significantly higher than patients not showing side effects. Similarly, the children who needed to reduce or discontinue the treatment were receiving the highest doses. No relations, however, could be established between the incidence of side effects and plasma levels of VPA except for lassitude and drowsiness. Severe or fatal toxicity was not detected.

Valproate Induced Agitation and Irritability in a Patient With Mania: Case Report

“…Coulter et al used valproic acid in children with uncontrolled seizures and reported that valproic acid therapy adversely affected 8 children out of 100, causing belligerent behavior or hallucinations (9). A study that examined 88 pediatric patients with seizure disorders who were on valproate monotherapy reported behavioral alterations in 42% of patients, including irritability, hyperactivity, and aggressiveness (10). Another study noted that 25% of children with complex partial seizures treated with valproate developed hyperactivity, irritability, and aggression, that were severe enough to discontinue or decrease valproate (11).…”

Measuring side effects of psychopharmacologic medication in individuals with mental retardation and developmental disabilities

“…''), systematic assessment through a checklist of signs and symptoms (e.g., rating scale), and spontaneous reporting (by the client) [Corso et al, 1992]. Compared to spontaneous reporting alone, side effect detection approximately doubles when systematic inquiry methods such as rating scales are used with spontaneous reporting [Corso et al, 1992;Herranz et al, 1982]. Although spontaneous reporting by nonverbal clients is problematic, Lingjaerde et al [1987] note that even verbal clients do not always report or complain about even important side effects.…”

Study of adverse drug effects of antiepileptic drugs used in pediatric patients in a tertiary care rural hospital – a Pharmacovigilance study

“…29 Increased thirst has been demons trated in several other studies with VPA. 30 As it can be a manifestation of seizure itself and hence change of therapy or further investigations may be required.…”