Sleep Problems in Children with Anxiety and Attention Deficit Hyperactivity Disorders

Objective: The aim of this thesis is to examine sleep problems in a clinical sample of children with anxiety and attention deficit/hyperactivity disorder (ADHD). The more specific aims are to investigate the frequency, the associations with behavioral and attentional functioning, and the persistence of sleep problems (both overall sleep problems and types of sleep problems). The sleep problems of children in the clinical sample are compared to those of a group of nonreferred children. The thesis also examines the influence of comorbidity on the frequency of sleep problems and explores possible predictors of persistence of sleep problems in the group of referred children. Methods: The total sample consisted of 141 children aged 7–13 years, 51 girls and 90 boys, comprising 105 children referred to two child and adolescent outpatient clinics and 36 nonreferred children recruited as controls. The clinical sample was recruited from 421 consecutive referrals to the clinics, and the children were eligible for inclusion if they met diagnostic criteria for an anxiety disorder and/or ADHD after diagnostic interview with the parents, given no exclusion criteria applied. The clinical sample was grouped as follows: anxiety disorders without comorbid ADHD (ANX, n = 41), ADHD and no comorbid anxiety disorder (n = 39), anxiety disorders and ADHD (ANX+ADHD, n = 25). Of the 141 children participating at the initial assessment (T1), 76 referred and 31 nonreferred children were retained at the follow-up assessment after about 18 months (T2), giving an overall attrition rate of 24.1%. Diagnoses were assessed at T1 with parental interviews using the Kaufman Schedule for Affective Disorders and Schizophrenia present and lifetime version (Kiddie-SADS-PL). Sleep problems were assessed with mother reports on the Children’s Sleep Habit Questionnaire (CSHQ) at both T1 and T2. Attention was assessed at T1 by the Attention Network Test for children (ANT). Emotional and behavioral problems were assessed at T1 by teacher reports on the Achenbach System of Empirically Based Assessment, Teacher Report Form (ASEBA TRF). Results: Referred children were reported to have more total sleep problems compared to nonreferred controls, and children in the ANX and ANX+ADHD groups more than children in the ADHD group. As to types of sleep problems, children in the ANX and ANX+ADHD groups had more bedtime resistance, sleep duration problems, sleep anxiety, parasomnias, and more daytime sleepiness compared to controls. Children in the ADHD group had more sleep disordered breathing problems and more daytime sleepiness compared to the controls. Children in the ANX group had more bedtime resistance problems than children in the ADHD group, and children in the ANX+ADHD group more night waking than the other groups of children. Comorbidity with other axis I disorders did not influence the frequency of total sleep problems among the referred children. A higher reported frequency of overall sleep problems was associated with reduced efficiency of attentional functioning for both referred and nonreferred children, and daytime sleepiness predicted internalizing problems as rated by the teacher in children in the ANX group. No association was found between the sleep problems and teacher ratings of internalizing or externalizing problems in children in the ADHD or the ANX+ADHD groups, or between the sleep problems and teacher ratings of externalizing problems for any group of children. The persistence rate from T1 to T2 of having sleep problems in a clinical range (total CSHQ score above 41) was 72.4% in the group of referred children. The persistence rates of having a total sleep problem in a clinical range did not differ significantly between children in the ANX group (76.0%), the ADHD group (70.6%), or in the ANX+ADHD group (68.8%). Persistence rates for types of sleep problems varied from 56.3% (bedtime resistance problems) to 86.0% (parasomnias) in the group of referred children. The total CSHQ score at T1 significantly predicted the CSHQ score at T2 in the group of referred children. Conclusion: The results demonstrate a high frequency of sleep problems as reported by the mother in a clinical sample children with anxiety disorders and/or ADHD. Children with anxiety disorders have more sleep problems than children with ADHD. The sleep problems are associated with impairments in attentional function for both referred and nonreferred children, and with more internalizing problems reported by the teacher in the subgroup of children with anxiety disorders and no comorbid ADHD. The sleep problems are persistent in the majority of children in the clinical sample. Clinicians in child and adolescent mental health service (CAMHS) need to be aware of sleep problems and include assessment and targeted intervention towards sleep problems when treating children with anxiety disorders and/or ADHD

Association Between Prescribed Hypnotics in Infants and Toddlers

As previously indicated an association may exist between early sleep problems in infants and toddlers, and a diagnosis of attention deficit hyperactivity disorder (ADHD). The aim of this study was to study if this association could be replicated in a complete nationwide cohort of children. Prospective cohort study using national registries. All children born in Norway from January 2004 to December 2010 were included (N = 410,555). Information on hypnotic drugs dispensed to children 0–3 years of age outside of institutions was collected from the Norwegian Prescription Database and used as a proxy for sleep problems. The outcome ADHD (ICD-10), as diagnosed by specialists in the Child Mental Health Service, was obtained from the Norwegian Patient Registry. Data were analysed using weighted estimation in Cox regression. The unadjusted weighted hazard ratio (wHR) for a later diagnosis of ADHD in children dispensed two or more prescriptions for any hypnotic drug, compared to zero prescriptions, was 2.30 [95% confidence interval (CI) 1.63–3.23] for girls and 1.75 (95% CI 1.48–2.07) for boys. For the sedative antihistamine trimeprazine the corresponding wHR was 3.71 (95% CI 1.83–7.52) for girls and 2.78 (95% CI 2.04–3.80) for boys. After adjusting for parental ADHD and parental education the wHR for trimeprazine users was 2.81 (95% CI 1.34–5.88) for girls and 2.33 (95% CI 1.70–3.20) for boys. Infants and toddlers who were dispensed hypnotics had an increased risk of ADHD at school age. This association was most pronounced with the use of trimeprazine, a drug traditionally prescribed to toddlers for sleep problems in Norway. After adjusting for parental ADHD and educational level the risk for ADHD among the trimeprazine users was still more than twice the risk among controls

Association Between Prescribed Hypnotics in Infants and Toddlers

As previously indicated an association may exist between early sleep problems in infants and toddlers, and a diagnosis of attention deficit hyperactivity disorder (ADHD). The aim of this study was to study if this association could be replicated in a complete nationwide cohort of children. Prospective cohort study using national registries. All children born in Norway from January 2004 to December 2010 were included (N = 410,555). Information on hypnotic drugs dispensed to children 0-3 years of age outside of institutions was collected from the Norwegian Prescription Database and used as a proxy for sleep problems. The outcome ADHD (ICD-10), as diagnosed by specialists in the Child Mental Health Service, was obtained from the Norwegian Patient Registry. Data were analysed using weighted estimation in Cox regression. The unadjusted weighted hazard ratio (wHR) for a later diagnosis of ADHD in children dispensed two or more prescriptions for any hypnotic drug, compared to zero prescriptions, was 2.30 [95% confidence interval (CI) 1.63-3.23] for girls and 1.75 (95% CI 1.48-2.07) for boys. For the sedative antihistamine trimeprazine the corresponding wHR was 3.71 (95% CI 1.83-7.52) for girls and 2.78 (95% CI 2.04-3.80) for boys. After adjusting for parental ADHD and parental education the wHR for trimeprazine users was 2.81 (95% CI 1.34-5.88) for girls and 2.33 (95% CI 1.70-3.20) for boys. Infants and toddlers who were dispensed hypnotics had an increased risk of ADHD at school age. This association was most pronounced with the use of trimeprazine, a drug traditionally prescribed to toddlers for sleep problems in Norway. After adjusting for parental ADHD and educational level the risk for ADHD among the trimeprazine users was still more than twice the risk among controls

The use of sleep medication in youth residential care

Objectives: To investigate the use of sleep medication and concomitant psychotropic medication in children and adolescents placed under residential care (RC). Methods: Participants were youth 0–20 years of age placed in RC institutions at least once during 2016. Data on filled prescriptions were taken from the Norwegian Prescription Database to compare the use of sleep medication in RC with the general child population (GenPop) and how it covaried with gender, age, reasons for RC placement, and concomitant use of other psychotropic medications (antidepressants, anxiolytics, antipsychotics, and psychostimulants). Results: A total of 2171 youths were identified in RC at mean age 14 years (82% ‡ 13 years). Seventeen percent (371/2171) used sleep medications (melatonin 11%, alimemazine 7%, and benzodiazepines/z-hypnotics 2%) significantly more than the 2.3% who used in GenPop. The girl/boy ratio for medication use in RC was 1.8 (95% confidence interval [CI] = 1.5–2.2), not significantly different from the corresponding ratio in GenPop (1.4; 95% CI = 1.3–1.5). The use of sleep medication increased with age. When comparing reasons for placement in RC, medication use was particularly low among unaccompanied minor asylumseekers (2%). About half of the youths used concomitant psychotropic medication, with clear gender differences; Girls used about twice as much antidepressants, anxiolytics, and antipsychotics, whereas boys used 1.3 times more psychostimulants. Conclusion: Youths in RC used more sleep medication and concomitant psychotropic medication than the GenPop, most likely reflecting the increased psychosocial strain and mental disorders reported in this population. Further studies of prevalence, assessment, and treatment of sleep problems in RC populations are warranted

High prevalence of ADHD symptoms in unmedicated youths with post-H1N1 narcolepsy type 1

Objectives To characterize attention deficit-hyperactivity disorder (ADHD) symptoms in unmedicated post-H1N1 narcolepsy type 1 (NT1) youths, and explore associations between ADHD symptoms and the narcolepsy phenotype. Methods A total of 50 consecutively enrolled post-H1N1 NT1 youths (7–20 years, 62% females, 98% HLA-DQB1∗06:02-positive, 98% CSF hypocretin-1 deficient, 88% vaccinated) were assessed after two weeks off medication for ADHD (ADHD diagnosis pre/post-narcolepsy, parent-rated ADHD symptoms) and narcolepsy-phenotyped (semi-structured interview, Stanford Sleep Questionnaire, Epworth Sleepiness Scale, polysomnography (PSG), Multiple Sleep Latency Test (MSLT)). Results In sum, 26 (52%) and 15 (30%) of participants had ADHD symptoms above and below the clinical significant cut-off, respectively, while 9 (18%) had no ADHD symptoms. High values were found for ADHD total score (mean (SD), 17.9 (9.5)) and ADHD subscores (inattentive score, 11.0 (6.3); hyperactive/impulsivity score, 6.9 (4.7)). These were significantly higher than previously reported in a mainly medicated narcolepsy cohort (p < 0.0001). Age, gender and disease duration did not influence scores. Two participants (4%) had ADHD diagnosis prior to narcolepsy onset. ADHD symptoms were correlated with parent-rated, but not with patient rated ESS scores, objective sleepiness (mean sleep latency), sleep fragmentation (sleep stage shift index, awakening index), or CSF hypocretin-1 level. Conclusion Comorbid ADHD symptoms were more prevalent in unmedicated post-H1N1 NT1 youths than previously reported in mainly medicated pediatric narcolepsy cohorts. The high prevalence was not due to pre-existing ADHD and generally not correlated with core narcolepsy sleep/wake phenotype characteristics, indicating that the ADHD symptoms were not a direct consequence of disturbed sleep or daytime sleepiness