Tolerability, Safety, and Benefits of Risperidone in Children and Adolescents with Autism: 21-Month Follow-up After 8-Week Placebo-Controlled Trial.

OBJECTIVE: Risperidone has demonstrated efficacy for acute (8 week) and intermediate length (6 month) management of severe irritability and aggression in children and adolescents with autism. Less is known about the long-term effects of risperidone exposure in this population. We examined the tolerability, safety, and therapeutic benefit of risperidone exposure over a 1-2 year follow-up period. METHODS: In a naturalistic study, 84 children and adolescents 5-17 years of age (from an original sample of 101) were assessed an average of 21.4 months after initial entry into a placebo-controlled 8 week trial of risperidone for children and adolescents with autism and severe irritability. They were assessed at baseline and at follow-up on safety and tolerability measures (blood, urinalysis, electrocardiogram [ECG], medical history, vital signs, neurological symptoms, other adverse events), developmental measures (adaptive behavior, intelligence quotient [IQ]), and standardized rating instruments. Treatment over the follow-up period, after completion of protocol participation, was uncontrolled. Statistical analyses assessed outcome over time with or without prolonged risperidone therapy. RESULTS: Two-thirds of the 84 subjects continued to receive risperidone (mean 2.47 mg/day, S.D. 1.29 mg). At follow-up, risperidone was associated with more enuresis, more excessive appetite, and more weight gain, but not more adverse neurological effects. No clinically significant events were noted on blood counts, chemistries, urinalysis, ECG, or interim medical history. Regardless of drug condition at follow-up, there was considerable improvement in maladaptive behavior compared with baseline, including core symptoms associated with autism. Height and weight gains were elevated with risperidone. Social skills on Vineland Adaptive Behavior Scale (VABS) improved with risperidone. Parent-rated Aberrant Behavior Checklist (ABC) Irritability subscale scores were reduced in those taking risperidone at follow-up. Several other measures of maladaptive behavior (some related to socialization) also showed improved functioning in association with risperidone on the ABC or on the Modified Real Life Rating Scale. CONCLUSIONS: Increased appetite, weight gain, and enuresis are risks associated with long-term risperidone. Our data suggest that these risks were balanced by longer-term behavioral and social benefits for many children over 1.8 years of ongoing treatment.

Valproate-induced enuresis: a prospective study.

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.

Sodium valproate induced increased frequency of micturition and enuresis.

Sodium valproate is a commonly used antiepileptic drug (AED) for control of a broad range of seizures. Adverse drug reactions (ADR) due to sodium valproate range from sedation to nausea, vomiting, weight gain, idiosyncratic adverse effects like hepatotoxicity and life threatening conditions like pancreatitis. We present a case of sodium valproate induced enuresis in child. This ADR of valproate is an underreported ADR and requires special attention of pediatricians as it can interfere with the further treatment of the disease.

Secondary enuresis & body dysmorphic disorder in a caucasian male with catatonic schizophrenia: a case report.

We describe a patient with Schizophrenia and secondary enuresis. The enuresis settled with resolution of his psychotic symptoms but later remerged after starting Clozapine. We explore the mechanisms of incontinence in Schizophrenia and those due to Clozapine. This case highlights the need to inquire about incontinence in patients with schizophrenia prior to prescribing clozapine.

Use of aripiprazole in clozapine induced enuresis: report of two cases.

This report describes the efficacy of combined use of aripiprazole in the treatment of a patient with clozapine induced enuresis. Aripiprazole acts as a potential dopamine partial agonist and the dopamine blockade in the basal ganglia might be one of the causes of urinary incontinence and enuresis. We speculate that aripiprazole functioned as a D2 agonist in hypodopaminergic state of basal ganglia caused by clozapine and maintained dopamine level that would improve enuresis ultimately.

Unusual side-effects due to clobazam: a case report with genetic study of CYP2C19.

We describe the case of a 10-year-old girl with two epileptic seizures and subcontinuous spike-waves during sleep, who presented unusual side-effects related to clobazam (CLB) monotherapy. High plasma levels of N-desmethyl-clobazam (N-CLB), the major metabolite of CLB were detected. The patient and her parents underwent molecular analysis of the CYP2C19 gene, which may be implicated in the metabolism of this drug. Our patient presents one copy of the most common mutation (CYP2C19*2) affecting the activity of the isoenzyme and probably another rare or private mutation. CLB and N-CLB plasma level dosages and molecular analysis may be useful when a poor metabolic condition is suspected.

Failure of tolterodine to treat clozapine-induced nocturnal enuresis.

OBJECTIVE: To report the use and subsequent failure of the bladder-selective agent tolterodine, to treat clozapine-induced nocturnal enuresis in an adolescent patient with psychotic illness. CASE SUMMARY: A 16-year-old Hispanic girl was admitted to the state psychiatric hospital with a diagnosis of bipolar disorder with psychotic features. Clozapine therapy was initiated, and after three months of treatment the patient began experiencing episodes of nocturnal enuresis. The bladder-selective agent tolterodine was tried and subsequently failed to resolve the enuresis episodes. Desmopressin was initiated, which resulted in amelioration of symptoms. DISCUSSION: This is the first published report of using tolterodine to treat clozapine-induced nocturnal enuresis. Several methods to decrease clozapine-induced urinary incontinence have been used and typically include the addition of agents with high anticholinergic properties. Tolterodine is a bladder-selective anticholinergic agent indicated for the treatment of urinary urge incontinence and may be employed as a treatment for antipsychotic-induced incontinence. CONCLUSIONS: Nocturnal enuresis is an adverse effect that infrequently occurs with use of clozapine therapy. Although tolterodine was ineffective in our patient to treat clozapine-induced nocturnal enuresis, further trials are required to appropriately evaluate the effectiveness of tolterodine to treat this adverse drug reaction.