deamino-arginine-vasopressin and Attention-Deficit-Disorder-with-Hyperactivity

ADHD is common among children with comorbidity of enuresis. Findings concerning prepulse inhibition (PPI) of startle reflexes are controversial. Although PPI is improved through desamino-arginine vasopressin (dDAVP) in enuresis, some patients also improve concomitant ADHD through dDAVP. This study aims to evaluate whether methylphenidate (MPH) also improves PPI in ADHD.. Nineteen ADHD patients were investigated in a prospective, double-blind, crossover study with MPH versus placebo. PPI was measured as a reduction of acoustic startle reflexes. Subgroups of gender, ADHD subtype, and baseline PPI were analyzed.. Median baseline PPI of ADHD patients (51.7%) was below the value of age-matched normal controls (73%, p = .090). MPH showed no improvement in the whole group, or the subgroups gender or subtype. Reduced baseline PPI was significantly improved (22.5%-39.3%, p = .039).. Heterogeneity of ADHD is confirmed with a wide range of baseline PPI. The improvement of reduced baseline PPI through MPH suggests impaired sensorimotor gating in this subgroup.

Topics: Acoustic Stimulation; Adolescent; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Cross-Over Studies; Deamino Arginine Vasopressin; Double-Blind Method; Enuresis; Female; Humans; Male; Methylphenidate; Prospective Studies; Reactive Inhibition; Reflex, Startle; Treatment Outcome

Children with attention deficit hyperactivity disorder disproportionately experience voiding dysfunction and persistent nocturnal enuresis due to a combination of sphincter and detrusor overactivity and nocturnal polyuria. The different treatment approaches to nocturnal enuresis often fail in these patients. Therefore, we performed a prospective study to compare the efficacy of combination therapy with desmopressin and oxybutynin vs the tricyclic antidepressant imipramine in patients with attention deficit hyperactivity disorder who have nocturnal enuresis.. A total of 54 patients with attention deficit hyperactivity disorder and nocturnal enuresis were randomly stratified into 2 groups. Demographic data on patient age and gender were identical in the 2 groups. Functional bladder symptoms were judged using the dysfunctional voiding symptoms survey. The initial dysfunctional voiding symptoms survey score was similar in the 2 groups. The total survey score was compared between the 2 groups in aggregate as well as specifically regarding the incidence of nocturnal enuresis following treatment.. The first group consisted of 27 patients who received desmopressin and oxybutynin, and the second group of 27 was treated with imipramine. Of the 27 children in each group 23 (85%) received methylphenidate for attention deficit hyperactivity disorder. The mean +/- SD initial dysfunctional voiding symptoms survey score in groups 1 and 2 was 20.5 +/- 3.3 and 20.9 +/- 4.1, respectively. Following treatment the mean survey score decreased significantly in groups 1 and 2 (6.5 +/- 2.5 and 9.4 +/- 2.1, respectively, p <0.001). However, between groups analysis showed that the dysfunctional voiding symptoms survey score was significantly lower in group 1 than in group 2 (mean 6.5 +/- 0.5 vs 9.6 +/- 0.4, p <0.001). There was also a statistically significant decrease in the incidence of nocturnal enuresis in group 1 (survey question 2 score 0.9 +/- 0.2 vs 2.9 +/- 0.2).. Our data show that there is a high incidence of voiding dysfunction in children with attention deficit hyperactivity disorder. Combination therapy with desmopressin and oxybutynin is a feasible, safe and effective treatment for nocturnal enuresis in these children.

Topics: Antidepressive Agents, Tricyclic; Antidiuretic Agents; Attention Deficit Disorder with Hyperactivity; Child; Deamino Arginine Vasopressin; Drug Therapy, Combination; Enuresis; Female; Humans; Imipramine; Male; Mandelic Acids; Parasympatholytics; Prospective Studies; Treatment Outcome

Nocturnal enuresis (bedwetting) is a common disorder affecting 10-16% of 7-year-old children globally. Nocturnal enuresis is highly heritable, but its genetic determinants remain unknown. We aimed to identify genetic variants associated with nocturnal enuresis and explore its genetic architecture and underlying biology.. We did a genome-wide association study (GWAS) of nocturnal enuresis. Nocturnal enuresis cases were identified in iPSYCH2012, a large Danish population-based case cohort established to investigate mental disorders, on the basis of 10th revision of the International Statistical Classification of Diseases (ICD-10) diagnoses and redeemed desmopressin prescriptions in Danish registers. The GWAS was done in a genetically homogeneous sample of unrelated individuals using logistic regression with relevant covariates. All genome-wide significant variants were analysed for their association with nocturnal enuresis in an independent Icelandic sample from deCODE genetics. Standardised polygenic risk scores for attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder were constructed from summary statistics of large GWASs and analysed for association with nocturnal enuresis.. The GWAS included 3882 nocturnal enuresis cases and 31 073 controls. We found two loci at chromosome 6 and chromosome 13 significantly associated with nocturnal enuresis. Six genetic variants at the two loci (five variants at chromosome 6q16.2 and one variant at chromosome 13q22.3) surpassed the threshold for genome-wide significance (p<5 × 10. This study shows that common genetic variants contribute considerably to nocturnal enuresis, and it identifies potential nocturnal enuresis risk genes with roles in sleep, urine production, and bladder function. Given that available treatments target these mechanisms, any of the identified genes and their functional gene networks are potential drug targets.. The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Stanley Foundation.

Topics: Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Child; Chromosomes, Human, Pair 13; Chromosomes, Human, Pair 6; Deamino Arginine Vasopressin; Female; Genetic Loci; Genetic Variation; Genome-Wide Association Study; Humans; Male; Nocturnal Enuresis; Phenotype

The aim of this study was to evaluate the effectiveness of treatment with methylphenidate or desmopressin (dDAVP) in patients with comorbid attention-deficit/hyperactivity disorder (ADHD) and enuresis.. We enrolled 103 patients affected by ADHD and 125 patients with monosymptomatic nocturnal enuresis (NE). Data were collected between January 2014 and December 2015. The study was carried out in compliance with the Helsinki Declaration.. About children with ADHD, 9/103 (8.7%) were also suffering from NE; of those 8/9 followed treatment with methylphenidate and cognitive behavioral therapy. After 3 months 2/8 (25%, CI 95%: 8-65%) showed improvements, remaining 75% has been increased dosage of methylphenidate. After 6 months a response was achieved in 6/8 (75%, CI 95%: 35-96%) children and 1/8 was lost to follow-up. Furthermore the drug withdrawal showed a recurrence of symptoms both ADHD and NE in 1/7 (14.3%, CI 95%: 0.3-57%) vs. 6/7 (85.7%, CI 95%: 42-99%) that not presented recurrences. About children with NE enrolled at Campus Bio-Medico University it was found that 4/125 (3.8%) children were also suffering from ADHD; 3/4 (75%) treated with dDAVP and motivational therapy, of those 2/3 (66.7%, CI 95%: 9-99%) showed no improvements of symptoms vs. 1/3 (33.3%, CI 95%: 0.8-90%) that showed partial response with a reduction of wet-nights.. It is important the service of recruitment of patients with NE. In fact considering NE in a Child Neuropsychiatry Service where patients belong to a diagnosis of ADHD and NE is an incidental finding, this one is not considered as the addressee of treatment, but the therapy is directed to the neuro-behavioral problem using specific drugs and therapies, which are resolutive in the enuretic disorder.

Topics: Adolescent; Antidiuretic Agents; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Child, Preschool; Deamino Arginine Vasopressin; Female; Follow-Up Studies; Humans; Male; Methylphenidate; Nocturnal Enuresis; Prospective Studies; Retrospective Studies; Treatment Outcome

Nocturnal enuresis is a common pediatric condition with limited treatment options. In older children, pharmacologic therapy is often the preferred treatment. Pharmacologic therapies including desmopressin (DDAVP) or imipramine are effective in 40-50% of children. However, imipramine has serious safety concerns. Desmopressin in combination with a fixed dose anticholinergic has been shown to be useful in individuals who fail desmopressin monotherapy, but still fails to achieve success rates greater than 60%.. The goal was to explore the efficacy and safety of using combination therapy desmopressin plus oxybutynin with increasing dose of oxybutynin in patients refractory to standard combination therapy.. This was a single institution, IRB-approved, retrospective chart review of 61 patients (ages 7-18 years) including those with monosymptomatic primary nocturnal enuresis and non-monosymptomatic enuresis with controlled daytime voiding symptoms (CDVS) treated initially with desmopressin. All patients who failed initial therapy with desmopressin were started on combination therapy desmopressin (0.6 mg) plus standard dose (5 mg) oxybutynin. In patients who failed standard combination therapy, the dose of oxybutynin was titrated upwards until a response or the maximum dose of 10 mg was achieved. Demographic and medical history data were evaluated to determine predictive factors associated with response/failure to different therapy groups.. The use of escalating doses of oxybutynin in combination with desmopressin achieved an overall response rate of 96.7% defined as a 2-week period without any enuretic events following initiation of treatment. Low-dose combination therapy (LDCT) (0.6 mg of desmopressin+5 mg of oxybutynin) had a response rate of 68% (Table). Advanced dose combination therapy (ADCT) (0.6 mg of desmopressin+7.5-10 mg of oxybutynin) had a response rate of 75.0%. A statistically significant relationship was found correlating both attention deficit disorder/attention-deficit hyperactivity disorder(ADD/ADHD) and CDVS with failure on monotherapy. No patients in the study reported any adverse events or side effects from the medications.. The overall success rate of 96.7% with titrated doses of oxybutynin in combination with desmopressin is considerably higher than the response rates on fixed dose combination therapy quoted in the literature and supports the need for further evaluation in larger studies. Additionally, we found a statistically significant association between monotherapy failure and children with either ADD/ADHD or controlled daytime voiding symptoms. Our study is limited by small numbers and larger studies are needed to confirm these results.. Our results suggest that ADCT is a safe and effective treatment option for primary nocturnal enuresis refractory to standard and low-dose combination therapy.

Topics: Adolescent; Antidiuretic Agents; Attention Deficit Disorder with Hyperactivity; Child; Deamino Arginine Vasopressin; Drug Therapy, Combination; Female; Humans; Male; Mandelic Acids; Muscarinic Antagonists; Nocturnal Enuresis; Retrospective Studies

To evaluate the effectiveness of presence of desmopressin in treating primary enuresis (PE) for children with attention deficit-hyperactivity disorder (ADHD) symptoms.. Children aged from 5 to 12 years with the chief complaint of PE treated with desmopressin were enrolled in pediatric urology clinics. The parent-reported SNAP-IV questionnaire was used to evaluate ADHD symptoms (cut-off value: 90th percentile). Voiding symptoms were assessed by the Dysfunctional Voiding Scoring System (DVSS) questionnaire. The responses to desmopressin were analyzed in children with and without ADHD symptoms.. The study sample comprised 68 children; 27 (39.7%) presented with ADHD symptoms and 41 (60.3%) with non-ADHD symptoms. The children collected from a tertiary referral center may explain the high prevalence of ADHD symptoms in the present study. The total DVSS score in the ADHD symptoms group was significantly higher than in the non-ADHD symptoms group (7.72 versus 5.65, P=0.05). In the ADHD symptoms group, there were significantly higher score in the "pee 1-2 times/day" and "can't wait" subscales of DVSS and lower sleep quality based on the Pediatric Sleep Quality questionnaire, as well as significantly lower peak flow rate and voided volume. The responses to desmopressin for enuresis were comparable between children with ADHD and non-ADHD symptoms.. Approximately 39.7% of PE children presented with ADHD symptoms at urologic clinics. PE children with ADHD symptoms had higher risk of daytime LUTS and comparable response to desmopressin treatment for PE. To evaluate ADHD symptoms and daytime voiding symptoms is important in children with PE.

Topics: Adolescent; Antidiuretic Agents; Attention Deficit Disorder with Hyperactivity; Child; Deamino Arginine Vasopressin; Enuresis; Female; Humans; Male; Urination

Topics: Adolescent; Arginine Vasopressin; Attention Deficit Disorder with Hyperactivity; Child; Deamino Arginine Vasopressin; Female; Humans; Learning Disabilities; Male; Mental Recall; Paired-Associate Learning; Serial Learning; Verbal Learning