Melatonin use in managing insomnia in children with autism and other neurogenetic disorders - An assessment by the international pediatric sleep association (IPSA).

Though it is widely prescribed for improving sleep of children with autism and other neurogenetic disorders, there is a need for practical guidance to clinicians on the use of melatonin for managing insomnia in this population. Because data were either lacking or inconclusive, a task force was established by the International Pediatric Sleep Association (IPSA) to examine the literature based on clinical trials from 2012 onwards. A summary of evidence pertaining to melatonin's utility and potential side effects, practice-related caveats, and insights for use are published herewith.

Sertraline for anxiety in adults with a diagnosis of autism (STRATA): study protocol for a pragmatic, multicentre, double-blind, placebo-controlled randomised controlled trial.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed to manage anxiety in adults with an autism diagnosis. However, their effectiveness and adverse effect profile in the autistic population are not well known. This trial aims to determine the effectiveness and cost-effectiveness of the SSRI sertraline in reducing symptoms of anxiety and improving quality of life in adults with a diagnosis of autism compared with placebo and to quantify any adverse effects. METHODS: STRATA is a two-parallel group, multi-centre, pragmatic, double-blind, randomised placebo-controlled trial with allocation at the level of the individual. It will be delivered through recruiting sites with autism services in 4 regional centres in the United Kingdom (UK) and 1 in Australia. Adults with an autism diagnosis and a Generalised Anxiety Disorder Assessment (GAD-7) score ≥ 10 at screening will be randomised 1:1 to either 25 mg sertraline or placebo, with subsequent flexible dose titration up to 200 mg. The primary outcome is GAD-7 scores at 16 weeks post-randomisation. Secondary outcomes include adverse effects, proportionate change in GAD-7 scores including 50% reduction, social anxiety, obsessive-compulsive symptoms, panic attacks, repetitive behaviours, meltdowns, depressive symptoms, composite depression and anxiety, functioning and disability and quality of life. Carer burden will be assessed in a linked carer sub-study. Outcome data will be collected using online/paper methods via video call, face-to-face or telephone according to participant preference at 16, 24 and 52 weeks post-randomisation, with brief safety checks and data collection at 1-2, 4, 8, 12 and 36 weeks. An economic evaluation to study the cost-effectiveness of sertraline vs placebo and a QuinteT Recruitment Intervention (QRI) to optimise recruitment and informed consent are embedded within the trial. Qualitative interviews at various times during the study will explore experiences of participating and taking the trial medication. DISCUSSION: Results from this study should help autistic adults and their clinicians make evidence-based decisions on the use of sertraline for managing anxiety in this population. TRIAL REGISTRATION: ISRCTN, ISRCTN15984604 . Registered on 08 February 2021. EudraCT 2019-004312-66. ANZCTR ACTRN12621000801819. Registered on 07 April 2021.

Psychotropic Medication Prescribing for Youth at a Regional Autism Center.

Objectives: The Seattle Children's Autism Center (SCAC) serves youth throughout Washington state (WA). The authors examined (1) whether the ethnicity and race of patients seen at the SCAC aligned with the demographics reported in the WA census, and (2) whether psychotropic medication prescriptions were associated with patient factors, including age, sex, ethnicity, race, insurance, visit number, and diagnoses. Methods: The authors extracted demographic and prescription data from electronic medical records for all patients (3-21 years) seen at the SCAC in 2018 for psychiatric medication evaluation in the context of autism spectrum disorder (ASD) and/or other related neurodevelopmental disorder (n = 1112), and used binary logistic regression to ascertain the effects of patient factors on psychotropic prescriptions. Results: The SCAC study sample appeared to align well with the WA census. Older age and higher visit number were among the most significant factors associated with psychotropic prescriptions. Psychotropic prescriptions increased with age, across all categories, except attention-deficit/hyperactivity disorder medications. There were no sex differences in prescribing rates. There were differences in prescribing rates by ethnicity and race. There were also increased prescription rates among those with Medicaid insurance. Conclusion: These demographic differences in prescribing for youth with ASD provide more specificity than prior studies about sex, ethnic, racial, and insurance-related differences, and can serve as an impetus to examine the reasons for variance.

Epilepsy in adulthood: Prevalence, incidence, and associated antiepileptic drug use in autistic adults in a state Medicaid system.

LAY ABSTRACT: Epilepsy is more common in autistic children compared to children without autism, but we do not have good estimates of how many autistic adults have epilepsy. We used data from a full population of 7513 autistic adults who received Medicaid in Wisconsin to figure out the proportion of autistic adults who have epilepsy, as compared to 18,429 adults with intellectual disability. We also wanted to assess how often epilepsy is first diagnosed in adulthood. Finally, we wanted to see whether antiepileptic drugs are being used to treat epilepsy in autistic adults. We found that 34.6% of autistic adults with intellectual disability and 11.1% of autistic adults without intellectual disability had epilepsy, compared to 27.0% of adults with intellectual disability alone. Autistic women and autistic adults with intellectual disability were more likely than autistic men and autistic adults without intellectual disability to have both previous and new diagnoses of epilepsy. Finally, we found that antiepileptic medications are commonly prescribed to autistic people who do not have epilepsy potentially to treat mental health conditions or behavior problems, and that antiepileptic medications are not always prescribed to autistic people with epilepsy even though they are indicated as a first-line epilepsy treatment. The findings of this study highlight the need to effectively treat and prevent epilepsy in autistic adults.

Spillover effects of state medicaid antipsychotic prior authorization policies in US commercially insured youth.

PURPOSE: To evaluate spillover effects of Medicaid antipsychotic prior authorization (PA) policies among commercially insured youth. METHODS: Commercially insured youth residing in nine US states that implemented PA exclusively for antipsychotics in 2011 or 2012 were identified using a 10% random sample of enrollees in the IQVIA PharMetrics Plus database spanning 2007 to 2015. Youth were included if they were ≤18 years, met the age criteria of the PA at the time of dispensing, and had at least 1 month of prescription drug coverage from 2007 to 2015. The primary outcome of interest was the monthly prevalence of antipsychotics. We implemented segmented regression of interrupted time series analysis to estimate changes in the monthly prevalence of targeted medications, overall and stratified by age. Trends were compared in the 4-year period before and the 3-year period after implementation of PA policies. RESULTS: Antipsychotics prescribing significantly decreased 6.74/10 000 (95% CI, -9.04 to -4.44) enrollees per month immediately after PA implementation. However, PA was not associated with significant long-term trend changes (-0.06; 95% CI, -0.16 to 0.03). Antipsychotic prescribing in children <12 years-old significantly decreased 0.14/10 000 (95% CI, -0.21 to -0.07) enrollees per month after PA implementation, while prescribing in adolescents 12 to 18 years-old significantly increased 0.32/10 000 (95% CI, 0.16 to 0.47) enrollees per month. CONCLUSION: While Medicaid PA polices for antipsychotic oversight did not affect overall prescribing, there were spillover effects in U.S. commercially insured children <12 years-old. This suggests that state-level Medicaid policies intended to improve the quality of care and safe use of antipsychotics can have broad reach.

Treatment for Sleep Problems in Children with Autism and Caregiver Spillover Effects.

Sleep problems in children with autism spectrum disorders (ASD) are under-recognized and under-treated. Identifying treatment value accounting for health effects on family members (spillovers) could improve the perceived cost-effectiveness of interventions to improve child sleep habits. A prospective cohort study (N = 224) was conducted with registry and postal survey data completed by the primary caregiver. We calculated quality of life outcomes for the child and the primary caregiver associated with treatments to improve sleep in the child based on prior clinical trials. Predicted treatment effects for melatonin and behavioral interventions were similar in magnitude for the child and for the caregiver. Accounting for caregiver spillover effects associated with treatments for the child with ASD increases treatment benefits and improves cost-effectiveness profiles.

The relationship between mental health diagnosis and treatment with second-generation antipsychotics over time: a national study of U.S. Medicaid-enrolled children.

OBJECTIVE: To describe the relationship between mental health diagnosis and treatment with antipsychotics among U.S. Medicaid-enrolled children over time. DATA SOURCES/STUDY SETTING: Medicaid Analytic Extract (MAX) files for 50 states and the District of Columbia from 2002 to 2007. STUDY DESIGN: Repeated cross-sectional design. Using logistic regression, outcomes of mental health diagnosis and filled prescriptions for antipsychotics were standardized across demographic and service use characteristics and reported as probabilities across age groups over time. DATA COLLECTION: Center for Medicaid Services data extracted by means of age, ICD-9 codes, service use intensity, and National Drug Classification codes. PRINCIPAL FINDINGS: Antipsychotic use increased by 62 percent, reaching 354,000 youth by 2007 (2.4 percent). Although youth with bipolar disorder, schizophrenia, and autism proportionally were more likely to receive antipsychotics, youth with attention deficit hyperactivity disorder (ADHD) and those with three or more mental health diagnoses were the largest consumers of antipsychotics over time; by 2007, youth with ADHD accounted for 50 percent of total antipsychotic use; 1 in 7 antipsychotic users were youth with ADHD as their only diagnosis. CONCLUSIONS: In the context of safety concerns, disproportionate antipsychotic use among youth with nonapproved indications illustrates the need for more generalized efficacy data in pediatric populations.

State variation in psychotropic medication use by foster care children with autism spectrum disorder.

OBJECTIVE: The objective of this study was to compare on a national cohort of children with autism spectrum disorder (ASD) the concurrent use of >or=3 psychotropic medications between children in foster care and children who have disabilities and receive Supplemental Security Income, and to describe variation among states in the use of these medications by children in foster care. METHODS: Studied was the concurrent use of >or=3 classes of psychotropic medications, identified from the 2001 Medicaid claims of 43406 children who were aged 3 to 18 years and had >or=1 annual claim for ASD. Medicaid enrollment as a child in foster care versus a child with disabilities was compared. Multilevel logistic regression, clustered at the state level and controlling for demographics and comorbidities, yielded standardized (adjusted) estimates of concurrent use of >or=3 medications and estimated variation in medication use within states that exceeded 1 and 2 SDs from the average across states. RESULTS: Among children in foster care, 20.8% used >or=3 classes of medication concurrently, compared with 10.1% of children who were classified as having a disability. Differences grew in relationship to overall use of medications within a state; for every 5% increase in concurrent use of >or=3 medication classes by a state's population with disabilities, such use by children in a state's foster care population increased by 8.3%. Forty-three percent (22) of states were >1 SD from the adjusted mean for children who were using >or=3 medications concurrently, and 14% (7) of the states exceeded 2 SDs. CONCLUSIONS: Among children with ASD, children in foster care were more likely to use >or=3 medications concurrently than children with disabilities. State-level differences underscore policy or programmatic differences that might affect the receipt of medications in this population.

Assessment and pharmacologic treatment of sleep disturbance in autism.

Like children with other developmental disabilities, children with autism spectrum disorders suffer with sleep problems at a higher rate than do typically developing children. There is a growing recognition that addressing these sleep problems may improve daytime functioning and decrease family stress. Presented here is a discussion of the sleep problems experienced by children with autism spectrum disorders, focusing on appropriate assessment and pharmacologic treatment.

Psychotropic medication use among Medicaid-enrolled children with autism spectrum disorders.

OBJECTIVE: The objective of this study was to provide national estimates of psychotropic medication use among Medicaid-enrolled children with autism spectrum disorders and to examine child and health system characteristics associated with psychotropic medication use. METHODS: This cross-sectional study used Medicaid claims for calendar year 2001 from all 50 states and Washington, DC, to examine 60,641 children with an autism spectrum disorder diagnosis. Logistic regression with random effects was used to examine the child, county, and state factors associated with psychotropic medication use. RESULTS: Of the sample, 56% used at least 1 psychotropic medication, 20% of whom were prescribed > or = 3 medications concurrently. Use was common even in children aged 0 to 2 years (18%) and 3 to 5 years (32%). Neuroleptic drugs were the most common psychotropic class (31%), followed by antidepressants (25%) and stimulants (22%). In adjusted analyses, male, older, and white children; those who were in foster care or in the Medicaid disability category; those who received additional psychiatric diagnoses; and those who used more autism spectrum disorder services were more likely to have used psychotropic drugs. Children who had a diagnosis of autistic disorder or who lived in counties with a lower percentage of white residents or greater urban density were less likely to use such medications. CONCLUSIONS: Psychotropic medication use is common among even very young children with autism spectrum disorders. Factors unrelated to clinical presentation seem highly associated with prescribing practices. Given the limited evidence base, there is an urgent need to assess the risks, benefits, and costs of medication use and understand the local and national policies that affect medication use.

An evaluation of positive behavioural support for people with very severe challenging behaviours in community-based settings.

This study employs a multiple baseline across individual design to describe positive behaviour support for five people in community settings. The individuals represent all people with intellectual disability residing in one county with long-standing challenging behaviour resulting in serious physical injury. Five types of outcome are presented: rates of behaviour, rates of medication, psychiatric symptomatology, quality of life and revenue costs. The systems of support required to maintain outcomes and develop real lifestyles include behaviour support planning, mental health review, on-call intensive support and emergency respite care. Behaviours reduced to near-zero levels following implementation of positive behaviour support and improvements were sustained over 24 months. The use of psychotropic medications reduced by 66 percent over the same period. Quality of Life Questionnaire scores improved significantly for three of the five participants. The results are discussed in the context of a framework for supporting people with severe challenging behaviours in the community.

Medication use among children with autism spectrum disorders.

The study characterizes the use of psychoactive medications among children and youth with autism-spectrum disorders over the course of a calendar year. Eighty-three percent of the sample had at least one drug claim during the year. Prescribed drugs came from 125 different therapeutic classes. The seven most frequently prescribed classes of psychoactive drugs were antidepressants, stimulants, tranquilizers/antipsychotics, anticonvulsants, hypotensive agents, anxiolytic/sedative/hypnotics, and benzodiazepines. The data on other relevant diagnoses indicate that children and youth are frequently treated with medication under an autism-spectrum diagnosis, even though the target symptoms may be commonly associated with other mental disorders. Age data indicate that about 70% of children with autism-spectrum disorders age 8 yr and up receive some form of psychoactive medication in a given year.

Behaviour management problems as predictors of psychotropic medication and use of psychiatric services in adults with autism.

We examined behaviour management problems as predictors of psychotropic medication, use of psychiatric consultation and in-patient admission in a group of 66 adults with pervasive developmental disorder (PDD) and intellectual disability (ID) and 99 controls matched in age, gender and level of ID. Overall, people with PDD had higher rates of most DAS behaviour problems and more frequent use of anti-psychotics than matched controls. Logistic regression analyses showed that physical aggression and problems such as pestering staff independently predicted use of anti-psychotics. Physical aggression and overactivity predicted further involvement of psychiatric services. PDD diagnosis predicted admission to an in-patient unit. The results suggest that externalizing problem behaviours in adults with autism can predict type of treatment intervention.

Spironolactone might be a desirable immunologic and hormonal intervention in autism spectrum disorders.

Multiple studies now demonstrate that autism is medically characterized, in part, by immune system dysregulation, including evidence of neuroglial activation and gastrointestinal inflammation. This neuroglial process has further been characterized as neuroinflammation. In addition, a subset of autistic children exhibit higher than average levels of androgens. Spironolactone is an aldosterone antagonist and potassium-sparing diuretic with a desirable safety profile. It possesses potent anti-inflammatory and immune modifying properties that might make it an excellent medical intervention for autism spectrum disorders. Furthermore, spironolactone demonstrates substantial anti-androgen properties that might further enhance its appeal in autism, particularly in a definable subset of hyperandrogenic autistic children. One case report is briefly reviewed demonstrating objective clinical improvements in an autistic child after spironolactone administration. Additional research in controlled trials is now needed to further define the risks and benefits of spironolactone use in children with autism.

Deaths resulting from hypocalcemia after administration of edetate disodium: 2003-2005.

From 2003 to 2005, deaths of 3 individuals as a result of cardiac arrest caused by hypocalcemia during chelation therapy were reported to the Centers for Disease Control and Prevention. Two were children, both of whom were treated with edetate disodium. At the time of this writing, the adult case was still under investigation. No previous cases of death resulting from hypocalcemia during chelation have been reported. From our experience and review of the literature, we suggest that health care providers who are unfamiliar with chelation consult an expert before undertaking treatment and that hospital formularies evaluate whether stocking edetate disodium is necessary, given the risk for hypocalcemia and the availability of less toxic alternatives.