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American Academy of Child and Adolescent Psychiatry 2019
The 66th Annual Meeting of the American Academy of Child and Adolescent Psychiatry (AACAP) was held from October 14 through October 19 in Chicago, Illinois. We review selected sessions below.
Allowing insurers to use prior authorization and step therapy to limit children’s use of powerful antipsychotic medications may seem controversial. But based on several presentations at the AACAP’s 2019 meeting, it may not be such a bad idea.
“We know that rates of psychotropic medication use in children are high, but in many cases we can take a system of care approach and identify gaps in care. We can look at patients and their families in a holistic way; they may be getting medicated because gaps and difficulties in the system make it difficult to treat them otherwise,” said David Lohr, MD, Associate Professor of Child and Adolescent Psychiatry at the University of Louisville School of Medicine.
Dr. Lohr chaired “When the Meds Aren’t Working: Rethinking Medication Regimens for Youth With a Focus on Deprescribing,” an AACAP clinical perspectives session. “There needs to be research on the safety and efficacy of deprescribing,” Dr. Lohr said. He was echoed by W. Peter Metz, MD, Professor of Psychiatry and Pediatrics at the University of Massachusetts Medical School in Worcester, who served as discussant at the session. “For example, we need research about how long might you need to gradually reduce the dose for a particular medication,” Dr. Metz said. “Antipsychotics and mood stabilizers are not felt to be addictive in a traditional sense, but withdrawal can be difficult. Antidepressants can have a certain period of withdrawal, but I’m not aware of any good studies of the phenomenon,” Dr. Metz noted.
Cohort Analysis of Antipsychotic Treatment in ADHD
- Ryan Sultan, MD, Psychiatrist, Columbia University Medical Center, New York, New York
Almost half of young patients who are prescribed an antipsychotic medication following a new diagnosis of attention-deficit/hyperactivity disorder (ADHD) are not first tried on a stimulant—despite guidelines from AACAP and the American Psychiatric Association that encourage the reduction of off-label prescription of antipsychotics in these patients.
“With untreated ADHD, the ability of someone to control themselves is three to five times lower. The take-home message is that if someone has ADHD and it isn’t treated, their risk of getting in a car accident or failing out of school goes up. But if you’re going to go to pharmacologic treatment, trying a stimulant first is evidence-based,” said Dr. Sultan, lead author of this poster presentation. “In fact, treatment recommendations call for trying both kinds of stimulants before going to an antipsychotic. Doing otherwise is really premature.”
In the study, researchers retrieved data from the MarketScan Commercial Database for 187,563 patients between the ages of 3 and 24 years who were newly diagnosed with ADHD from 2010 to 2015. Of those patients, only 2.6% (4,869) were prescribed an antipsychotic, but within that group, 47.9% did not receive a stimulant prescription first. “The number is small, but the finding is of concern, because they’re not getting another treatment,” Dr. Sultan said.
Between 1999 and 2014, prescriptions of antipsychotics for children and adolescents in the U.S. increased by 50%. But antipsychotics are associated with significant adverse effects: “most commonly metabolic issues, such as weight gain and diabetes, and if there is a history of cardiac death in the family,” that could be an issue too, Dr. Sultan said.
Joining other societies that have issued guidelines, the American Academy of Pediatrics this year issued “Guidance on Strategies to Promote Best Practice in Antipsychotic Prescribing for Children and Adolescents,” which calls for prior authorization or mandatory peer review.
Long-Acting Injectable Antipsychotics in Children, Adolescents, and Young Adults: A Retrospective Follow-up
- Victor Pereira-Sanchez, MD, Psychiatrist, New York University Langone Child Study Center, New York, New York
A retrospective analysis of patient charts from a hospital in Spain found that when long-acting injectable antipsychotics were prescribed in children, the most common reason was for impulse control in patients diagnosed with ADHD or oppositional defiant disorder, according to a poster presentation.
In 27.5% of cases, the treatment was stopped for medical reasons. In 28.9% of those cases, metabolic changes were the reason for stopping the treatment.
The drugs are approved by the Food and Drug Administration and European Medicines Agency for adults with either bipolar disorder or schizophrenia. The long-acting medicines have not been approved for use in children, although oral versions of some have been approved for once-monthly treatment of psychosis in children and some have been approved for children with autism spectrum disorder (ASD), according to Dr. Pereira-Sanchez. “But the long-acting forms are still not in the official guidelines, so we are pioneers,” he added.
In the study, the researchers examined charts from patients 30 years of age and younger at the Clinica Universidad de Navarra in Pamplona, Spain. There were 133 patients (including 71 children and adolescents) prescribed long-acting injectable antipsychotics (risperidone, paliperidone palmitate, and aripiprazole) no later than spring 2018.
“This option would be kind of a last resort, because they are especially trying to help those adolescents and young adults for whom it is easy to forget about taking their medications every day,” Dr. Pereira-Sanchez said. “What we would do is to start with a low dose of the drugs’ oral counterparts on a daily basis. Then if we see they are well tolerated and effective, we might think of switching to the long-acting formulations.
“They are pretty convenient for children so they don’t have to worry about having to take pills every morning, and also for parents. They are especially convenient for adolescents who may have more difficulties complying,” he added. “Another advantage is that they provide more stable dosing, because if you take them orally every day, your blood levels will shrink a lot, but if you’re on the intramuscular medication during the month, it will be releasing slowly and the blood levels will be more steady.”
A Systematic Review and Network Meta-Analysis of the Efficacy and Safety of Antipsychotics for Depression Associated With Bipolar Disorder in Youth
- Melissa DelBello, MD, Professor, Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, Ohio
A meta-analysis of three drugs was described in a poster presentation that attempted to make up for the absence of head-to-head trials in antipsychotics used to treat depression. Both olanzapine/fluoxetine and lurasidone showed efficacy in the analysis, unlike standard-release quetiapine, according to the presentation—one of several that looked at lurasidone at AACAP 2019.
Remission was higher among patients taking olanzapine/fluoxetine compared with lurasidone (mean odds ratio, 0.88), but lurasidone was associated with a 3.6 kg reduction in weight and reductions from baseline in cholesterol, low-density lipoprotein-cholesterol, and triglycerides.
“In the last placebo-controlled bipolar studies in kids, placebo was just as good as quetiapine,” Dr. DelBello said. “We know that depression responds to therapy, which has a huge placebo effect in these trials. So we need to do some kind of placebo lead-in, in which people who respond to placebo would not be randomized.”
The FDA approved lurasidone in 2010 for the treatment of schizophrenia and in 2013 for the treatment of bipolar disorder in adults. In 2018, the agency approved lurasidone for use in children and adolescents with bipolar disorder. The combination of olanzapine and fluoxetine is the only drug approved in the U.S. for the treatment of bipolar depression. Quetiapine was approved by the FDA for the treatment of schizophrenia in 2007 and is sometimes used as a sleep aid. However, that same year, the FDA approved an extended-release formulation of quetiapine, which was not used in this study.
In the meta-analysis, Dr. DelBello and colleagues searched for literature describing any pediatric randomized controlled trials of atypical antipsychotics for the treatment of bipolar depression. At least 50% of the study population had to be diagnosed with bipolar I depression to be included in the meta-analysis. The researchers found only four trials.
No significant differences were observed for tolerability between lurasidone and the other interventions, the poster showed. However, some researchers have expressed concern that lurasidone may be associated with movement disorders, such as tardive dystonia, tardive akathisia, and drug‐induced parkinsonism, as well as anemia.
Escitalopram in Adolescents With Generalized Anxiety Disorder: A Double-Blind, Randomized, Placebo-Controlled Trial
- Jeffrey Strawn, MD, Associate Professor of Psychiatry and Pediatrics, University of Cincinnati, Cincinnati, Ohio
Biomarkers may hold important information that could guide doctors in prescribing drugs for anxiety.
Researchers looked at three genes (CYP2C19, HTR2A, and SLC6A4) and found that patients having certain characteristics of those genes experienced greater benefits from the drug escitalopram. The significance of the findings was shown by P values ranging from less than 0.001 to less than 0.016.
“This was one of the first studies looking at psychiatric biomarkers in children,” said Dr. Strawn, the lead author. “We recognized when using [selective serotonin reuptake inhibitor (SSRI)] medications for folks that some respond very robustly whereas others have a much more tepid response.”
In the NIH-sponsored study, the researchers enrolled 51 patients with generalized anxiety disorder; 25 were randomized to placebo. A greater reduction in the Pediatric Anxiety Rating Scale score was associated with changes in SLC6A4 (a serotonin transporter), HTR2A (a serotonin receptor), and CYP2C19 (which encodes one of the enzymes that breaks down escitalopram) in patients who received escitalopram.
However, slower CYP2C19 metabolism was associated with greater exposure and more adverse events, according to a companion poster, “CYP2C19 Metabolizer Status Predicts Escitalopram Pharmacokinetics in Adolescents With Generalized Anxiety Disorder.”
In Dr. Strawn’s research, patients in the treatment arm, compared with the placebo group, experienced more fatigue (34.6% versus 20%), weight gain (3.8% versus 0%), dizziness (7.7% versus 0%), and dysmenorrhea (15% versus 8%).
Assessment of ADHD Medication Use and Associations With Serious Cardiovascular Events in Children and Adolescents With ASD in the United States
- Richard Houghton, MSC, Principal Data Scientist, Roche PD Personalized Healthcare, Basel, Switzerland
The use of ADHD medications in children with autism spectrum disorder (ASD) is not associated with serious, adverse cardiovascular events, according to a large study.
“Out of 480 patients that did not have an event, 106 were taking a stimulant, while out of the 48 patients that did have an event, only six were taking a stimulant,” Houghton said. “It probably comes down to physician choice if somebody has a perceived risk.”
The researchers used the MarketScan insurance claims database to create a cohort of 326,221 patients with two or more claims for ASD. Of those, 48 (0.01%) had a serious cardiovascular event over a mean 2.62 years, including 25 strokes and one myocardial infarction, in patients ranging in age from 3 to 18 years.
However, the study was not designed to compare the number of events in patients on ADHD drugs to the number of events in patients who did not receive ADHD drugs. Instead, the researchers compared the number of patients who were on medications among patients who had an event to the number of patients who were on medications among those who did not have an event.
The study did not produce a P value but has a confidence interval of 0.14, according to Houghton.
Simplifying Somatization: Reducing Healthcare Utilization With a Clinical Pathway for Pediatric Somatic Symptom and Related Disorders
- Edwin Klein, MS, Medical Student, University of Michigan, Ann Arbor, Michigan
Hospitals can implement a clinical pathway for patients with functional neurological symptom disorder and somatic symptom and related disorders (SSRD), reducing unnecessary expenditure.
Researchers from the University of Michigan (UM) presented data from the first two years of that institution’s pathway, which was created in 2015. That pathway significantly reduced total costs, which were $60,000 per patient in the control group (composed of patients presenting before the pathway) and less than $10,000 for patients in the pathway.
“The median length of stay for kids on the pathway was about a day and a half, compared with a little over three days before we started the protocol, which is a pretty significant decrease,” said Kristin Kullgren, PhD, a UM Associate Professor of Pediatrics. “One of the outcomes on the poster is the 30-day readmission rate [9% to 12%], which is commonly reported to look at bounce-backs. That did not change over the course of the pathway.”
Klein was the lead author on the poster. “The goal of the pathway was to keep care in the hands of the primary care doctor and not include high-cost specialists in the care,” he said.
Psychopharmacologic Therapy in 4- and 5-Year-Old Preschoolers With Diagnoses of ADHD and ASD
- Cesar Ochoa-Lubinoff, MD, Developmental Behavioral Pediatrician, Rush University Medical Center Developmental-Behavioral Pediatrics Clinic, Chicago, Illinois
Guanfacine and methylphenidate may be about equally effective for treating ADHD in patients 4 and 5 years of age, but when the children have comorbid autism spectrum disorder (ASD), guanfacine may be more effective than methylphenidate. And when treated with methylphenidate, 4- and 5-year-old patients with ADHD and comorbid ASD experience greater irritability (50%) than when treated with guanfacine (7%).
By contrast, patients with both disorders who took guanfacine experienced no greater side effects than patients in a general ADHD database, according to the poster presentation. But when patients with both disorders took methylphenidate, they had greater irritability than patients in the general ADHD database (50% compared with 14%). Emotional lability was also higher (13% versus 4%).
Researchers compared data for all patients ages 4 and 5 who met criteria for ADHD and ASD diagnoses using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, who were seen at the clinic from 2012 to 2018. Children were offered guanfacine or methylphenidate, and the results compared to a database of preschoolers diagnosed generally with ADHD.
ADHD with comorbid ASD has not been studied. Two-thirds of the patients need medication. In those patients, guanfacine is more effective than methylphenidate (67% versus 44%), explained Dr. Ochoa-Lubinoff, the lead author.
“Autism is a risk factor for irritability in ADHD patients treated with methylphenidate,” he said. “These are both very benign drugs, which one can stop, the better to balance risks.”
Time Until Clinical Response in the Treatment of Early-Onset Schizophrenia Spectrum Disorders Study (TEOSS)
- Jerome Taylor, MD, Child and Adolescent Psychiatrist, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
Time to clinical response for patients with early-onset schizophrenia spectrum disorder did not vary significantly according to which of several antipsychotics the children took, according to a secondary analysis of data from an important 2008 trial.
By week 6, 97% of patients showed at least a 5% reduction in symptoms, according to Dr. Taylor’s poster presentation. “If there is no change in symptoms by week 4, there is an 80% likelihood that the patient is not going to respond to that medicine at all,” he said. If a patient fails a first medication, the response rate with a second medication is about the same.
Described as the largest randomized controlled trial in the field in 2008, the original TEOSS study randomized 119 patients between 8 and 19 years of age with early-onset schizophrenia or schizoaffective disorder to treatment with one of three antipsychotics: molindone, risperidone, or olanzapine. The original trial found that while efficacy doesn’t vary among drugs, side effects do.
The analysis found that 21 patients responded to molindone by week 6, 20 to risperidone by week 4.5, and 15 to olanzapine by week 4.
Formularies have gone through changes since the original TEOSS trial. “Molindone was associated with motor effects such as akathisia, where you feel like you have to move all the time. However, it usually goes away in time,” Dr. Taylor noted. “Molindone wasn’t making a profit, so it was taken off the market. Then they brought it back three years ago.”
In the original study, there was more weight gain with olanzapine and more hyperprolactinemia with risperidone. The 2019 poster also found that older patient age predicted slightly reduced likelihood of clinical response (hazard ratio, 0.90, P = 0.04).
Note: An abbreviated version of our coverage of the American Academy of Children and Adolescent Psychiatry meeting ran in the print edition of the December issue.