Practice Pearls for Stimulant Treatment of Attention-Deficit/Hyperactivity Disorder in Youth.

Over half of youth with attention-deficit/hyperactivity disorder (ADHD) have co-occurring psychiatric or medical conditions that present treatment challenges. Stimulants are the most effective pharmacologic treatment of ADHD for preschoolers to adults but questions about safety with co-occurring conditions frequently arise. In addition, stigma surrounding diagnosis and treatment can negatively impact care. This manuscript presents evidence-based practice pearls to guide treatment decisions for youth with ADHD and common coexisting psychiatric and medical conditions. Recommendations address specific stimulant adverse effects (i.e., anxiety, cardiac, growth, mania, psychosis) along with management strategies. Pearls were developed for the most common clinical questions, controversial topics, or therapeutic issues that may not be widely known. The goals of this manuscript are to: 1) provide a detailed resource for interprofessional teams regarding stimulant use in youth with ADHD, 2) improve therapeutic outcomes for youth with ADHD and co-occurring psychiatric and/or medical conditions through evidence-based recommendations, and 3) decrease stigma associated with stimulant use through education.

Impact of Pharmacogenomics on Pediatric Psychotropic Medication Prescribing in an Ambulatory Care Setting.

Objective: Evidence for pharmacogenomic (PGx) guided treatment in child and adolescent psychiatry is growing. This study evaluated the impact of PGx testing on psychotropic medication prescribing in an ambulatory child and adolescent psychiatry and a developmental pediatrics clinic. Methods: This was a single-center, retrospective, descriptive analysis of patients who underwent PGx testing between January 2015 and October 2022 at a child and adolescent psychiatry clinic or developmental pediatrics clinic. The primary outcome was the proportion of patients with at least one psychotropic medication modification made 6-month posttesting that could be attributed to CYP2C19, CYP2D6, HLA-B*15:02, or HLA-A*31:01. Secondary outcomes included reason for testing, types of therapeutic modifications made, and whether the therapeutic modifications concorded with PGx guidelines. Results: A total of 193 patients were analyzed. The average age was 10 ± 4 years old, 60% were male, 78% were Caucasian. Sixty-eight percent had a primary diagnosis of a neurodevelopmental disorder, namely autism spectrum disorder (51%), and attention-deficit/hyperactivity disorder (14%). The reasons for PGx testing included medication inefficacy (34%), medication intolerance (20%), and family request (19%). At the time of PGx testing, 37% of patients were taking ≥1 psychotropic medication with PGx annotation. Overall, 35 PGx-related therapeutic modifications were made in 32 (17%) patients. These included continuing current PGx medication (6.2%) and starting PGx medication (5.2%). These modifications mainly involved antidepressants. Out of these 35 PGx-related therapeutic modifications, 94% were concordant with PGx guidelines. Among 29 patients who were prescribed at least one CYP2D6 inhibitor, 25 (86%) underwent CYP2D6 phenoconversion. Conclusions: It is critical to apply pediatric age-specific considerations when utilizing PGx testing in child and adolescent psychiatry. PGx testing stewardship could provide a framework to guide the clinical utility of PGx in a pediatric population with mental health conditions, including neurodevelopmental disorders.

Long-term use of antidepressants, mood stabilizers, and antipsychotics in pediatric patients with a focus on appropriate deprescribing.

It is estimated that 8% to 12% of youth are prescribed psychotropic medications. Those in foster care, juvenile justice systems, residential treatment facilities, and with developmental or intellectual disabilities are more likely to be prescribed high-risk regimens. The use of psychotropic medications in this age group is often off-label and can be associated with significant risk, warranting critical evaluation of their role. Landmark trials, pediatric-specific guidelines, and state-driven initiatives play critical roles in supporting evidence-based use of psychotropic medications in children. Overall, there is a lack of literature describing the long-term use of psychotropic medications in youth-particularly with regard to neurobiological, physical, and social changes that occur throughout development. Deprescribing is an important practice in child and adolescent psychiatry, given concerns for over-prescribing, inappropriate polytherapy, and the importance of reevaluating the role of psychotropic medications as children develop.

The Utility of Pharmacogenetic-Guided Psychotropic Medication Selection for Pediatric Patients: A Retrospective Study.

BACKGROUND: To describe trends and clinical experiences in applying commercial pharmacogenetic testing among pediatric patients with neuropsychiatric disorders. METHODS: Demographic and clinical data of patients receiving GeneSight® testing from January 2015 to November 2016 at an urban pediatric hospital were retrospectively extracted from medical charts. Outcome data included pharmacogenetic test results and medication prescriptions before and after the test. RESULTS: A total of 450 patients (12.1 ± 4.3 years) diagnosed with anxiety disorder, attention deficit hyperactivity disorder, developmental disorders including autism, and/or a mood disorder received testing, and 435 of them were prescribed medications. Comparing data before and after testing, the total number of psychotropic prescriptions were reduced by 27.2% and the number of prescribed medications with severe gene-drug interactions decreased from 165 to 95 (11.4% to 8.9% of total medications prescribed). Approximately 40% of actionable genetic annotation were related to CYP2CD6 and CYP2C19. Patients of Asian descent had significantly higher likelihood than other races of being classified as poor to intermediate metabolizers of antidepressants, mood stabilizers, and antipsychotics (p = 0.008, 0.007, and 0.001, respectively). Diagnoses, including autism spectrum disorder, were not associated with increased risks of severe gene-drug interactions. CONCLUSIONS: Pharmacogenetic testing in child and adolescent psychiatry is currently based on few clinically actionable genes validated by CPIC and/or FDA. Although this approach can be moderately utilized to guide psychotropic medication prescribing for pediatric patients with psychiatric disorders, clinicians should cautiously interpret test results while still relying on clinical experience and judgment to direct the final selection of medication.

Pitolisant in an Adolescent with Prader-Willi Syndrome.

This case report evaluates the potential benefit of pitolisant in a 15-year-old female with Prader-Willi syndrome, obsessive-compulsive disorder, autism spectrum disorder, and mild intellectual disability. Due to its action on the H3 receptor, it enhances central activity of histaminergic neurons resulting in increased alertness, irrespective of the loss of orexin neurons seen in narcolepsy. Additionally, it is thought to modulate various other neurotransmitter systems including acetylcholine, norepinephrine, and dopamine. Pitolisant has the potential to improve many symptoms in patients with Prader-Willi syndrome and it appears to be well tolerated with minimal side effects observed. Therefore, the use of pitolisant should be considered in patients with Prader-Willi syndrome who fail a psychostimulant trial.

Providers' perspectives on the clinical utility of pharmacogenomic testing in pediatric patients.

Aim: To assess providers' knowledge, attitudes, perceptions, and experiences related to pharmacogenomic (PGx) testing in pediatric patients. Materials & methods: An electronic survey was sent to multidisciplinary healthcare providers at a pediatric hospital. Results: Of 261 respondents, 71.3% were slightly or not at all familiar with PGx, despite 50.2% reporting prior PGx education or training. Most providers, apart from psychiatry, perceived PGx to be at least moderately useful to inform clinical decisions. However, only 26.4% of providers had recent PGx testing experience. Unfamiliarity with PGx and uncertainty about the clinical value of testing were common perceived challenges. Conclusion: Low PGx familiarity among pediatric providers suggests additional education and electronic resources are needed for PGx examples in which data support testing in children.

Olanzapine-Induced Withdrawal Oculogyric Crisis in an Adolescent With a Neurodevelopmental Disorder.

This case report describes an adolescent female with a complex psychiatric history and Fragile X syndrome who developed an antipsychotic-withdrawal emergent oculogyric crisis (OGC) in approximately 12 hours following reduction in olanzapine dose from 20 mg total daily dose to 5 mg twice daily. The team concluded that the OGC was likely related to olanzapine withdrawal based on the following clinical factors: 1) prior treatment with olanzapine 20 mg for 4 to 5 days/week for several months, without such reaction; 2) proximity of the OGC to the olanzapine dose reduction (within 12 hours); and 3) lack of recurrence with olanzapine dose increase. Additionally, her neurodevelopmental disorder and age were identified as risk factors for an acute dystonic reaction. Published case reports describe withdrawal emergent dystonia, including OGC, following abrupt discontinuation of clozapine in adults. Given structural similarities of clozapine and olanzapine it can be postulated that this phenomenon is based in muscarinic receptor function-specifically, super-sensitized muscarinic receptors may react to excessive acetylcholine upon antipsychotic discontinuation, resulting in muscle motor end plate hyperactivity. Providers caring for pediatric patients with neurodevelopmental disorders should carefully consider risks for withdrawal emergent dystonia, obtain clear medication histories, and consider slow, conservative tapers when discontinuing antipsychotics.

The Use of N-acetylcysteine Supplementation to Decrease Irritability in Four Youths With Autism Spectrum Disorders.

Children and adolescents with autism spectrum disorder (ASD) often experience high levels of irritability, which adversely affects their functioning and behaviors. N-acetylcysteine (NAC), an antioxidant precursor to glutathione, has recently been studied for a variety of neuropsychiatric disorders. There is growing evidence to support its use to decrease irritability and self-injurious behaviors in youth with ASD. However, previous studies were limited to outpatient youth with mild symptoms of irritability, maintained on stable medication regimens, who do not meet criteria for higher levels of care. We describe the use of NAC among 4 youths (14-17 years) with ASD who had Aberrant Behavior Checklist-Irritability (ABC-I) scores of ≥ 20 and other psychotropic medication trials prior to treatment with NAC. In all of the cases, NAC appeared to be well tolerated. There was a reduction of symptoms of irritability and/or antipsychotic medication dosages in these cases; despite this, the authors cannot know whether use of NAC or other medication or behavioral strategies were responsible for such changes because this study was not a controlled trial.

L-methylfolate Augmentation to Antidepressants for Adolescents with Treatment-Resistant Depression: A Case Series.

Despite antidepressant treatment, some patients continue to experience significant symptoms of depression. Literature has demonstrated modest benefit of folate supplementation in treatment-resistant depression among adults, though evidence is lacking in the pediatric population. This case series describes 10 adolescents (mean age 14.4 ± 2.8 years) with treatment-resistant depression prescribed adjunctive l-methylfolate (LM). The patient population was predominantly female (80%), Caucasian (90%), with an average of three comorbid psychiatric diagnoses, and failures of three psychotropic medications before starting LM. The majority of patients (80%) had a single mutation among the two methylene tetrahydrofolate reductase (MTHFR) gene variants evaluated (50% A1298 AC; 30% C677 CT), indicating reduced MTHFR activity. Eighty percent of patients demonstrated improvement in depression, anxiety, and irritability. Overall, LM was well tolerated. These cases suggest that LM as an adjunct to antidepressant treatment may be a safe and effective strategy for managing treatment-resistant depression in pediatric patients.

Acetylcysteine for treatment of autism spectrum disorder symptoms.

PURPOSE: Successful use of acetylcysteine to control irritability and aggressive behaviors in a hospitalized adolescent patient with autism spectrum disorder (ASD) is described. SUMMARY: A 17-year-old Hispanic male with ASD and intellectual disability was hospitalized for inpatient psychiatric treatment due to impulsive and violent behavior. Despite receiving various medications in the initial weeks of hospitalization, including intramuscular lorazepam and diphenhydramine injections (four days a week on average), the patient continued to exhibit aggressive and unpredictable behaviors. Treatment with 20% acetylcysteine oral solution was initiated at a dosage of 600 mg twice daily as an adjunct to quetiapine therapy. Over the next six weeks, reductions in the patient's aggressive behavior, tantrums, and irritability were noted. The use of as-needed medications to control aggression was decreased, and the dosage of quetiapine was lowered from 700 to 400 mg daily over the course of the hospitalization. Acetylcysteine was well tolerated, with no observed or reported adverse effects. Unlike clonidine or guanfacine (other medications used for ASD-related behavioral symptoms), acetylcysteine is not sedating; moreover, it lacks the metabolic, extrapyramidal, and endocrine adverse effects of atypical antipsychotics. Published data from small controlled trials and case reports suggest that acetylcysteine use is associated with improvements in irritability and aggression in prepubertal children with ASD; these therapeutic benefits may be associated with acetylcysteine's glutamatergic, dopaminergic, antioxidant, and anti-inflammatory properties. CONCLUSION: Treatment with acetylcysteine improved ASD symptoms, including irritability and aggression, in a teenage patient.