'No Identifiable Reason' for 50% of Antipsychotic Use in ADHD

Michael Vlessides

November 04, 2019

CHICAGO ― Only about 50% of antipsychotic prescriptions for children and youth who have been newly diagnosed with attention-deficit/hyperactivity disorder (ADHD) have an identifiable clinical indication. Furthermore, fewer than half of these patients receive initial treatment with stimulants ― the recommended first-line pharmacologic therapy ― results of a national analysis show.

Dr Ryan S. Sultan

"Overall, we found that 2.6% of kids with a new diagnosis of ADHD were treated with an antipsychotic medication despite no FDA [US Food and Drug Administration–approved] indication," study investigator Ryan S. Sultan, MD, assistant professor of clinical psychiatry, Columbia University, New York City, told Medscape Medical News.

"Among these, 52.7% had a potential clinical explanation for the administration of an antipsychotic, such as evidence of treatment-resistant ADHD. That still leaves approximately half of them who have no identifiable reason for receiving an antipsychotic. But they did nonetheless," he added.

The findings were presented here at the American Academy of Child & Adolescent Psychiatry (AACAP) 66th Annual Meeting.

Increased Risk for Death

There is significant concern over the use of antipsychotics to treat ADHD in children and youth. Nevertheless, during the past decade, the prescribing of these agents in this population has increased by 50%.

Although some of this rise may be attributable to prescribing for clinical indications approved by the FDA, including schizophrenia, bipolar disorder, irritability associated with autism spectrum disorder, and Tourette syndrome, much of it is associated with off-label prescribing for ADHD. Sultan noted there's not much known about the factors driving antipsychotic prescribing in this population.

The investigators also note that antipsychotic prescribing in youth is associated with adverse metabolic effects, including rapid weight gain, hyperlipidemia, and increased risk for type 2 diabetes. More recently, as reported by Medscape Medical News, antipsychotics have been linked to an increased risk for unexpected death in this patient population.

"There's been a lot of discussion about poor pharmacologic treatment in children and youth with ADHD. We were concerned. Why is such a significant proportion of children getting an antipsychotic? So we wanted to do a deeper dive," said Sultan.

To determine the percentage of youth for whom antipsychotic prescriptions were filled in the year following an initial diagnosis of ADHD, the investigators examined clinical and demographic factors associated with antipsychotic prescribing in children and youth with ADHD.

With coinvestigator Mark Olfson, MD, MPH, Sultan obtained data from the Truven Health MarketScan Commercial Database for January 1, 2010, to December 31, 2015. This database includes a host of medical and prescription drug data for more than 110 million patients.

The retrospective, longitudinal cohort analysis included 187,563 children and youth (aged 3 years to 24 years) who were newly diagnosed with ADHD but who did not have FDA-approved or evidence-based indications for antipsychotic treatment.

The researchers examined several outcome measures, including the percentage of patients who were prescribed an antipsychotic in the first year following a new diagnosis of ADHD and the percentage for whom an antipsychotic prescription was filled before a prescription for a stimulant was filled.

"Deeply Concerning"

They also examined a subset of youth who were prescribed antipsychotic medications. They assessed the percentage of those who received a diagnosis of conduct disorder, oppositional defiant disorder, or a disorder that was an FDA-approved indication with respect to at least one antipsychotic medication.

The mean age of the children and youth included in the study was 13.74 ± 5.61 years; 114,305 (60.9%) were male. The investigators found that within 1 year of their being newly diagnosed with ADHD, antipsychotics were initiated in 4869 patients (2.6%; 95% confidence interval [CI], 2.5% – 2.7%).

The investigators found that there was a potential clinical diagnostic rationale for treatment with antipsychotic medications for only 52.7% of patients who received them.

"I would understand these results if these children had complicated cases with aggression, and the stimulant was tried and didn't work. But that was not the case, because half of the antipsychotic-treated youth with ADHD never got a stimulant medication before they got an antipsychotic. It's deeply concerning. These youth have no clear indication for an antipsychotic, and stimulants are bread-and-butter treatment for ADHD," said Sultan.

"Assuming they aren't very young or only have mild symptoms, the treatment recommendations for ADHD are that you give adequate treatment trials for each psychostimulant class first; you don't jump right to an antipsychotic," he said.

Patients who received antipsychotics were more likely to be male, to be aged 13 to 18 years, to have been recently diagnosed with comorbid mental health conditions, or to have recently been admitted for inpatient mental health treatment.

Antipsychotic initiation was associated with self-harm or suicidal ideation (adjusted odds ratio [aOR], 7.5; 95% CI, 5.9 – 9.6), oppositional defiant disorder diagnosis (aOR, 4.4; 95% CI, 3.9 – 4.9), substance use disorder (aOR, 4.0; 95% CI, 3.6 – 4.5), and inpatient mental health care (aOR, 7.9; 95% CI, 6.7 – 9.3) in the preceding 6 months.

The analysis also showed that initial treatment with stimulants was not as common among ADHD patients who received antipsychotics. Indeed, 47.9% (95% CI, 46.5% – 49.3%) received no initial stimulant therapy before initiation of antipsychotics.

Similarly, 43.8% (95% CI, 42.4% – 45.1%) received a drug of one stimulant class, and only 8.4% of patients (95% CI, 7.6% – 9.1%) received methylphenidate or a methylphenidate derivative and an amphetamine derivative.

Going forward, the investigators plan to use electronic health and medical records to further analyze the findings in order to identify the specific reasons young patients were initially treated with antipsychotics.

"Is it that the parent refused the stimulant and now the child is in the emergency room with severe aggressive behavior and someone has reactively started giving an antipsychotic?"

"Major Tranquilizers"

Commenting on the findings for Medscape Medical News, Lily Hechtman, MD, McGill University, Montreal, Canada, noted that antipsychotics have traditionally been prescribed for children with ADHD with comorbid aggression.

"However, these types of medications also have many serious side effects, and it is generally believed that a comprehensive behavioral approach for parents and the child is best to treat these children. More recently, guanfacine ― which is not an antipsychotic and has fewer negative side effects ― has been shown to be effective for aggressive outbursts," she said.

"Antipsychotics are really major tranquilizers," Hechtman added, "so it's important not to assume that we are dealing with a psychotic process when we are really just observing a tranquilizing effect. Children with ADHD have many comorbidities, but psychosis is really very rare."

Sultan recognized that antipsychotic therapy does play a role in ADHD treatment for a small subset of children and youth.

"I'll be the first to admit that there may be occasions where antipsychotics may be the right thing to do," he explained. "But for me, that's only after you've used two stimulants, have done behavioral training and parent-management training, and still have severe symptoms. Alternatively, they can be prescribed on a short-term basis if there is evidence of aggression causing acute danger. But they should not be first line, which is essentially what this analysis suggests."

The study was funded by an AACAP Pilot Research Award for Attention Disorders. Sultan and Hechtman have disclosed no relevant financial relationships.

American Academy of Child & Adolescent Psychiatry (AACAP) 66th Annual Meeting: Abstract 2.3, presented October 16, 2019.

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