Secondary Nocturnal Enuresis Associated with Valproic Acid

Zaiem, Ahmed; Aouinti, Imen; Lakhoua, Ghozlane; Kastalli, Sarrah; Daghfous, Riadh; Lakhal, Mohamed; Aidli, Sihem El

doi:10.2515/therapie/2013004

Cited by 8 publications

(9 citation statements)

References 3 publications

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“…Some previous studies and case reports evaluating the adverse events associated with valproate mentioned enuresis as a possible side effect of this drug with a frequency, when reported, ranging between 2% and 7%. [7][8][9][10][11]14,15 In a retrospective study of 100 children, which evaluated the frequency and amount of weight gain after exposure to valproate, nocturnal enuresis was reported in 7% of participants; however, further details, other than the fact that enuresis spontaneously abated after a few months, were not provided. 7 In a prospective comparative trial of phenobarbital, primidone, and valproate for the prevention of febrile seizures, 1 child out of 48 children (2%) exposed to valproate was reported to have developed enuresis.…”

Section: Discussionmentioning

confidence: 99%

“…An association between the emergence of enuresis and treatment with valproate has been suggested but is not well characterized in the literature . A recently published review, which comprehensively described the adverse events of valproate, failed to mention enuresis as a side effect of this drug …”

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confidence: 99%

“…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][8][9][10][11] A recently published review, which comprehensively described the adverse events of valproate, failed to mention enuresis as a side effect of this drug. 12 In 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.…”

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confidence: 99%

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Valproate‐induced enuresis: a prospective study

Yamak

Hmaimess

Makke

et al. 2015

Develop Med Child Neuro

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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...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Valproate‐induced enuresis: a prospective study

Yamak

Hmaimess

Makke

et al. 2015

Develop Med Child Neuro

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“…6 A search of the literature concerning VPA revealed that this adverse effect has been rarely reported. 7 However, enuresis is a common problem that can be troubling for children and their families; therefore, this adverse effect requires the special attention of pediatricians or epileptologists, as it can potentially interfere with the further treatment of epilepsy.…”

Section: Introductionmentioning

confidence: 99%

“…It has been suggested that some AEDs can occasionally cause renal tubular impairment. [6][7][8][9] The degree of renal damage can be detected by an increase in either enzymes or proteins present in urine. Among the many urinary enzymes studied, N-acetyl-β-glucosaminidase (NAG) is considered a sensitive and reliable measure for detecting renal tubular damage.…”

Section: Introductionmentioning

confidence: 99%

The Relationship between Nocturnal Enuresis and Sequential Changes of NAG/Morning Urine Gravity in Epileptic Children Treated with Valproate Sodium

et al. 2015

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The aim of this study was to examine the presence of enuresis as an adverse effect of valproate sodium (VPA) and to prospectively evaluate renal tubular function in children receiving VPA as monotherapy and polytherapy. The study was conducted in 226 children. The patients were subdivided into the following four groups according to their therapy: VPA monotherapy as A; combination of VPA with other conventional antiepileptic drug (AED) therapy as B; and new AED administration after VPA therapy as C. To assess renal tubular function of all patient groups, urinary N-acetyl-?-glucosaminidase (NAG) levels and morning urine gravity were measured at baseline and after 2 weeks, 3 months, 6 months, and 1?year of treatment. Five (2.2%, A:B:C?=?1:4:0) of 226 children presented with enuresis. Enuresis appeared at a median of 19 days after the beginning of therapy. All patients showed normal results on the urinary excretion of NAG through the study period; however, urinary NAG activity in the patients with enuresis was significantly higher than those without enuresis at 2 weeks (p?=?0.0092), 3 months (p?=?0.0097), and 6 months (p?=?0.0021) of treatment with VPA. In contrast, morning urine gravity presenting with enuresis was significantly lower than that in the patients without enuresis after only 2 weeks of treatment (p?=?0.035). The results of this study also revealed that VPA therapy does not always increase NAG excretion or decrease morning urine gravity. However, urinary NAG levels of reflected tubular function in the patients with enuresis were significantly higher than those in patients without enuresis. This change may have some effects on the development of enuresis.

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Valproic acid

2013

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Secondary Nocturnal Enuresis Associated with Valproic Acid

Cited by 8 publications

References 3 publications

Valproate‐induced enuresis: a prospective study

Valproate‐induced enuresis: a prospective study

The Relationship between Nocturnal Enuresis and Sequential Changes of NAG/Morning Urine Gravity in Epileptic Children Treated with Valproate Sodium

Valproic acid

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