Psychotropic polypharmacy in youth: Increasing complexity calls for more safety

Loren Bonner

From 2001 to 2020, the overall use of psychotropic medications increased from 5% to 8% for individuals aged 6 years to 34 years, according to a study published in the Journal of the American Academy of Child & Adolescent Psychiatry.

“The rise was especially notable among children and young adults and was driven largely by stimulant use,” said lead author Lin-Chieh Meng, BSPharm, MS, from the Perelman School of Medicine at the University of Pennsylvania.

At the same time, the research team found that psychotropic polypharmacy increased, particularly among young adults. The prescribing of more than one medication rose from 1.8% to 3.3%, according to the findings, which were published online on December 19, 2025. About one in four patients taking a psychotropic had a potential contraindication or major drug–drug interaction as well.

However, the reality of how polypharmacy may play out for children taking psychotropic medications should not be oversimplified.

“I would attribute much of the very real increase in psychotropic utilization to our better understanding of comorbid but distinct pathologies in pediatric patients and young adults,” said Kari Allan, PharmD, BCPS, BCPPS, a pharmacist specialist at Children’s Hospital Colorado.

Neurocognitive and behavioral disorders in children are often comorbid and require multiple medications to successfully manage.

Children with developmental or intellectual disabilities as well as those in foster care, the juvenile
justice system, and residential treatment facilities are more likely to be prescribed high-risk antipsychotic regimens.

“While using multiple meds might be flagged in a generic interaction checker, these are often dose-dependent interactions and safely managed under medical supervision,” said Allan.

The best-case scenario is when patients can have a medical home with a pharmacist on the team—where careful monitoring and deprescribing could take place.

“These findings should not be interpreted to mean that psychotropic prescribing in youth is inherently inappropriate or excessive. The larger message is that increasing treatment complexity should be matched by increasing attention to safety, follow up, and coordination of care,” said Meng. “For pharmacists, clinicians, families, and policymakers alike, this is an opportunity to think about how to support safer and more thoughtful psychotropic use in children and young adults.”

Results of studies like this and others make the case for a stronger focus on psychotropic stewardship in young people.

In practice

Because psychotropic medications often require cross titrating, and some degree of trial and error over time to find the best regimen for a patient, Lauren Leiby, PharmD, BCPP, said it’s common to see psychotropic polypharmacy in practice.

“Patients may get ‘stuck’ in the midst of a cross titration, for example, from one antipsychotic medication to another. This may occur if a cross-titration schedule needs to occur over several weeks to months, but during the process, behaviors seem to improve, so instead of completing the transition, both medications are continued at sub-optimal doses,” said Leiby, a behavioral health patient care pharmacist at Nationwide Children’s Hospital in Columbus, OH.

Leiby sees patients admitted to the inpatient pediatric psychiatry unit who typically have had many medication trials in the past, leading them to the point of psychotropic polypharmacy.

“When assessing each patient, a thorough medication history is essential,” she said. “It is vital to understand as much as possible about medication classes tried in the past, their indications, titration achieved, duration of therapy, clinical outcomes, adverse effects, cost, and access concerns, [etc.]”

Another piece—and equally important—is the patient and caregiver’s perspective on the successes and shortcomings of previous medications. Bringing to light the how and why psychotropic polypharmacy occurred in addition to the current clinical picture helps clarify what adjustments could be made to a medication regimen in order to improve outcomes and safety going forward, Leiby said.

“This process is psychotropic stewardship at its core—decreasing polypharmacy, increasing medication safety, ensuring patient and prescriber satisfaction, and reducing adverse events as well as health care costs,” she said.

In the pediatric specialty care clinic at Children’s Hospital Colorado, Allan sees medically complex patients in the medical home practice setting. Roughly 75% of the patients there have at least one psychological or neurological diagnosis, and the vast majority are on some degree of psychotropic medication plus other medications.

“Polypharmacy is our specialty,” said Allan.

In an ideal scenario, noted Allan, a pediatrician or primary care provider will examine any drug–drug interactions in a methodical way and preferably with a pharmacist involved.

“We have to be thoughtful about what else the patient is on—that’s where we [pharmacists] have real opportunity to do a full review, to see the medication list. The specialists are weighing the risk and benefit,” said Allan.

They also have to be thoughtful about monitoring. In her practice at Children’s Hospital Colorado, Danielle Stutzman, PharmD, BCPP, sees pediatric patients prescribed one or two atypical antipsychotics.

“The big issue there are the cardiometabolic side effects,” she said. “These kids need to be monitored with lipid panels and more,” she said.

Unfortunately, less than 30% receive those panels.

“When pharmacists are involved in that process, rates are better,” Stutzman said.

The reality is that many children taking multiple drug combinations do not have a medical home. These more vulnerable patients, like children in foster care, are the ones switching providers constantly. Deprescribing could be necessary, in addition to intensive monitoring.

In the American Academy of Child & Adolescent Psychiatry study, Meng said she was struck by their finding that about one in four pediatric patients taking a psychotropic medication had a potential contraindicated or major drug–drug interaction, with even higher proportions of patients taking antipsychotics and antidepressants.

“While many clinicians are aware of these potential interactions, our findings highlight how common these complex prescribing situations may be in real-world practice,” she said.

For a major drug–drug interaction, one example researchers observed was the combination of fluoxetine, an SSRI antidepressant, and naproxen, an NSAID, commonly used for pain relief.

“This combination is not contraindicated, but it is considered a major interaction because SSRIs can impair platelet aggregation, and when used together with NSAIDs like naproxen, they can increase the risk of bleeding,” said Meng, who is a PhD student in epidemiology at the University of Pennsylvania.

She noted that although this combination may be more commonly discussed in adults, both medications can also be used in children and adolescents.

She would like to see more research to better understand the extent to which these interactions affect safety.

From research to practice

Considerations for deprescribing in children and adolescents

Proposed steps (should involve multidisciplinary team): Discuss benefits and risks of current medications, importance of reevaluating the need for psychotropic medications with patient and/or caregiver(s). Identify medication. Introduce idea of deprescribing to patient/caregiver and gain buy-in. Choose the right time (e.g., school break/days off). Develop specific plan, including start date, rate of taper, and monitoring. Monitor, adapt, and provide frequent follow up/support.

Indications: Changing benefit-to-risk ratio. Unclear rationale for use/role. Lack of evidence to support medication use. Completion of typical or expected treatment course. Nonadherence. Treatment alliance. Inappropriate polytherapy.

Risk assessment: Four or more psychotropic medications. Two or more concomitant medications from a single class (exception: short-and long-acting stimulant). Medication prescribed does not match presentation and/or diagnoses. Medication exceeds usual recommended dose. Prescribed at a very young age (e.g., younger than 4 years old).

Source: Stutzman DL. Long-term use of antidepressants, mood stabilizers, and antipsychotics in pediatric patients with a focus on appropriate deprescribing. Ment Health Clin. 2021;11(6):320–333.

Meng said they conducted the research study because of the increasing use of psychotropic medications among youth; the need for a more contemporary, nationally representative picture of how psychotropic medication use has changed over time; and the question of whether increasing treatment complexity may be raising safety concerns.

Current literature on overall prescribing patterns, polypharmacy, and potential drug–drug interactions, she said, is limited or outdated.

For the study, the research team began by examining prevalence trends as a first step toward characterizing patterns of psychotropic medication use among youth in the United States.

“Pediatric populations are often excluded from clinical trials, which means we frequently have more limited evidence to guide treatment decisions than we would like,” Meng said. “That makes real-world data especially important for understanding how these medications are actually being used in practice.”

The study used national representative data from the U.S. National Health and Nutrition Examination Survey across nearly two decades. Meng said this allowed them to examine long-term trends with children, adolescents, and young adults in the U.S. population.

However, a main limitation of the national survey data was that it captured medication use only over the past 30 days.

“Our measure of concurrent use may include short-term overlap rather than sustained combination treatment,” Meng said.

The survey data also did not provide detailed information on dose, duration, medication switching, or actual adverse events, meaning researchers could not determine the clinical severity of each potential interaction.

Another downside is that the interaction classifications came from Micromedex, which is useful for identifying potential risks but does not incorporate all patient-specific clinical context.

Meng said psychiatric pharmacists can play a major role in psychotropic stewardship by helping to identify high-risk combinations, reviewing medication lists for potential interaction risks, supporting dose optimization, and assisting clinicians and families during treatment changes or transitions of care.

“This is particularly important because many of the potential interactions we identified involved predictable pharmacologic mechanisms, such as QT prolongation, serotonin toxicity, and additive sedation,” she said.

For Stutzman, a bigger focus on psychotropic stewardship has created opportunities for psychiatric pharmacists and established a clear role in which they can have positive impacts.

The biggest growth is identifying kids on high-risk psychotropic medications—or high-risk patients for various reasons—through a tool in the EHR and making sure a psychiatric pharmacist sees those patients with the providers.

“Maybe we are getting them on less meds,” said Stutzman. ■

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What’s psychotropic stewardship?

Similar to antimicrobial stewardship, psychotropic stewardship promotes the safe and appropriate use of psychotropics, minimizes unintended consequences, and improves patient outcomes.

As an emerging model, psychotropic stewardship promotes board-certified psychiatric pharmacists playing an essential role in medication management on interdisciplinary psychiatry teams.

The American Association of Psychiatric Pharmacists (AAPP) is promoting the development of psychotropic stewardship programs. In a 2023 paper, published in Mental Health Clinician, researchers define what psychotropic stewardship is—and its ultimate purpose.

“AAPP envisions every patient with a psychiatric diagnosis will have their medication treatment plan reviewed, optimized, and managed by a psychotropic stewardship team with a psychiatric pharmacist as a co-leader,” researchers wrote.

AAPP and others want psychotropic stewardship to be officially recognized by regulatory agencies as a standard of care for patients who receive a diagnosis of a psychiatric disorder or SUD.  ■

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HHS includes pharmacists in deprescribing initiative for psychiatric medications

On May 4, 2026, HHS announced a plan to curb psychiatric medication overprescribing, especially in children and young adults. Within the plan, CMS issued guidance emphasizing the importance of deprescribing.

CMS released an FAQ that specifically calls out pharmacists as being able to submit claims under “incident to” for deprescribing.

The FAQ document illustrates some of the ways in which ongoing, medically necessary clinical management related to tapering or discontinuing medication may be included in various care management service codes for payment under the Medicare Physician Fee Schedule (PFS).

However, CMS has historically limited the codes pharmacists can bill incident-to physicians and non-physician practitioners, prohibiting service delivery for many patients. As such, APhA has been collaborating with the American Society of Health-System Pharmacists (ASHP) to fix the larger issue to allow pharmacists to submit codes through “incident to” mechanisms that reflect the complexity of care pharmacists are providing. More recently, APhA with ASHP and the American Association of Psychiatric Pharmacists asked CMS to discuss this latest development in billing opportunities for pharmacists.

CMS noted in the FAQ that practitioners have reported uncertainty about whether existing physician care management service codes encompass this work and can be used to bill for aspects of deprescribing furnished in-between office visits.

The FAQ states that pharmacists must be working within their scope of practice and in accordance with applicable state law, and the services cannot also be covered under Medicare Part D or paid under other Part B services.

“CMS encourages team-based care models that leverage the expertise of clinical pharmacists in medication management and deprescribing,” they state.

The multifaceted HHS action plan, which targets overprescription of psychiatric medications, has an end goal of ensuring that psychiatric drugs are being prescribed appropriately, especially in the pediatric population, and that they are being safely tapered or discontinued in anyone not receiving adequate clinical benefit from their use.

HHS said its various agencies will work together to accomplish the objectives of the plan through education and outreach, program and policy work, and research-to-practice efforts.

Pharmacists can visit apha.us/DeprescribingPsychotropics to read the FAQs. ■