Valproate‐induced enuresis: a prospective study

Abstract

AIM The aim of this study was to determine the frequency and characteristics of secondary enuresis in children initiated on valproate treatment.METHOD This was a prospective study conducted in children aged 5 to 12 years with suspected newly diagnosed epilepsy and maintained on valproate for at least 1 month. Adverse events spontaneously reported by parents were recorded at each follow-up visit. In addition, we specifically asked about enuresis and other side effects known to occur with valproate treatment. We assessed the frequency of enuresis and its association with a number of variables.RESULTS Seventy-two children (43 males and 29 females) with a mean age of 8 years 7 months (range 5-12y) were included in this study. Secondary enuresis developed in 17 (24%) of these children after, on average, 19.8 days of exposure to valproate. The data obtained from a multivariate analysis indicate that age was the only significant factor in predicting the development of enuresis. Enuresis ceased in all children after discontinuation of valproate use, and in 10 out of 11 children still on the drug.INTERPRETATION Secondary enuresis is a common adverse event associated with valproate use in children, which is not usually spontaneously reported and is reversible in most cases.Valproate is a broad-spectrum antiepileptic drug approved as monotherapy and adjunctive therapy for the treatment of simple and complex partial seizures in adults and children 10 years or older; as adjunctive therapy for the treatment of multiple seizure types, including absence seizures; for the treatment of acute manic episodes in those with bipolar disorder older than 18 years of age; and as a prophylactic agent for migraine headaches in adults and children older than 16 years.1 Adverse events associated with valproate include idiosyncratic reactions, such as hepatotoxicity and pancreatitis, and dose-related adverse events including weight gain, hair thinning, tremor, drowsiness, nausea, vomiting, ataxia, and thrombocytopenia. [2][3][4] Primary and secondary nocturnal enuresis is common in children, with a peak prevalence of 15% to 25% at age 5 years.5 Although enuresis typically disappears as the child matures, it can be distressing for children and their families and can prompt treatment with desmopressin or imipramine, or behavioural interventions. 5,6 An association between the emergence of enuresis and treatment with valproate has been suggested but is not well characterized in the literature.7-11 A recently published review, which comprehensively described the adverse events of valproate, failed to mention enuresis as a side effect of this drug. 12In this study, we prospectively assessed the frequency of enuresis in children with suspected newly diagnosed epilepsy, naive to antiepileptic drug treatment, and initiated on valproate. We also attempted to elucidate the characteristics of and the risk factors for the development of valproate-induced enuresis. METHODChildren eligible for this study were identified from those already enrolled in an on...

The Effect of Sodium Valproate on Urinary Frequency and Enuresis Compared to Carbamazepine in Children with Epilepsy

“…In 2015, Yamak et al performed a perspective study on 72 epileptic children aged 8 years and 7 months (range 5 -12 years) consuming sodium valproate (as monotherapy). The enuresis caused by sodium valproate was present in 24% of their cases in a mean time period of 19.8 days after exposure (13). This study, which is more similar to results from the current study, showed a higher range of enuresis rate that might be due to different factors such as genetic and/or epigenetic variations.…”

“…According to the literature, these side effects are more likely to occur in patients who require dosage increase. Despite these reports, there is a lack of solid evidences on association of urinary complications with sodium valproate and thus these complications are not known as side effects of this drug (11,13,14). Egger and Brett performed a retrospective study on the side effects of sodium valproate on epileptic children focusing on weight gain, they showed that among 100 cases, only 7% exhibited enuresis as a side effect (15).…”

Sleep Architecture in Valproate-Induced Nocturnal Enuresis in Primary School and Preschool Children

“…25 Previous research studies assessing the side effects of valproic acid found that nocturnal enuresis was a potential reaction to this medication, with a documented frequency of 7% to 24%. 12,26,27 The frequency of nocturnal enuresis in our study was 10.7% (28 patients), which was similar to prior studies. Nocturnal enuresis was reported by the parents in only 12 of the 260 cases (4.6%) in our study; the remaining 16 cases were detected by specifically asking about nocturnal enuresis, because this side effect is usually under-reported by parents.…”

“…10 However, more recent studies reported a variable incidence of valproic acid-induced nocturnal enuresis of 2.2% to 24%. 11,12 Three major factors hypothesized to be behind enuresis are increased nocturnal urine production, detrusor hyperactivity, and impaired arousal process. Both the arousal process and the micturition reflex are mediated by nuclei in the brain stem.…”

Analytical Method Development for Sodium Valproate through Chemical Derivatization

“…Valproic acid is considered a safer alternative to phenytoin for the treatment of adult onset epilepsy [5][6][7][8]. Side effects including anorexia, vomiting, and sleep alterations were the most commonly reported in clinical records [9][10][11][12][13][14].…”