Risky combinations of psychiatric drugs prescribed to young patients

A new study finds that young patients being treated with psychiatric drugs are being given potentially dangerous combinations of drugs with alarming frequency.

Researchers from Rutgers Health and other institutions recently analyzed New York State Medicaid records for more than 141,000 patients on psychiatric medications. Nearly 400 of them had been given at least one potentially dangerous combination for a month or longer. Doctors call these serious drug-drug interactions, and their use is typically considered “contraindicated” (recommended against).

Lead study author Lawrence Kleinman, a professor of pediatrics at Rutgers Robert Wood Johnson Medical School, cautioned that while some children whose disease is resistant to usual treatments may have more benefits than risks from the combination, “good practice requires that patients and caregivers be informed of and agree to the risks and benefits, including being informed that the proposed combination of drugs is usually contraindicated.”

The studypublished in BMC Primary Careanalyzed 2014 prescription data for New York Medicaid enrollees under 21. While the overall rate of these potentially dangerous combinations is small — about 3 in 1,000 children who received a prescription for a mental health medication had at least one month of prescription overlap, and 5 in 1,000 had some overlap — these cases represent a significant potential for harm or death. Kleinman noted that New York State Medicaid had previously implemented a program to reduce harmful drug interactions, suggesting that the rates may be higher in other populations.

Polypharmacy (the use of multiple medications) is common: nearly 38% of patients in the study were taking two or more medications with at least one month of overlap, resulting in more than 11,000 different drug combinations.

The study offered some reassurance: The most commonly used mental health medications were stimulants, typically used for conditions such as attention-deficit/hyperactivity disorder, and these were never combined with other medications to create serious interaction risks. The most contraindicated combinations included the antipsychotic drug ziprasidone, which can increase the risk of potentially fatal heart rhythm problems such as QT interval prolongation or serotonin syndrome when combined with certain medications. Kleinman noted, “Because of this risk, the FDA has warned that ziprasidone should not be prescribed with other medications that have been shown to cause QT prolongation.”

Approximately 32% (364) of the 1,121 patients prescribed ziprasidone were also taking a contraindicated partner drug for at least 30 days. This increased to 54% when overlapping prescriptions of any duration were taken into account.

Other common risky combinations include antidepressants such as fluoxetine (Prozac) and trazodone in combination with various antipsychotic medications, with the risk of life-threatening QT prolongation and serotonin syndrome.

Researchers analyzed prescription claims data for all New York State Medicaid enrollees under age 21 in 2014, identifying 84 different behavioral and mental health medications. They flagged combinations with serious interactions according to established drug interaction databases.

The team examined different durations for overlapping prescriptions: one day, 15 days or 30 days. Even at the 30-day threshold, 392 young patients received contraindicated combinations, rising to 651 for some overlap.

Contraindicated pairings were more common in adolescents and young adults than in younger children, with no children under 6 receiving risky pairings. Although boys were more likely to receive mental health medications, there was no gender difference in potentially dangerous pairing use.

Of the more than 20,000 clinicians who prescribed psychiatric medications, 386 prescribed at least one contraindicated pair. Most were psychiatrists rather than pediatricians, which Kleinman says is because psychiatrists are more likely to see patients with more serious mental illnesses.

Kleinman added that insufficient research into the treatment of mental illness in children often leaves doctors and families “flying blind.”

One limitation of the study was the age of the data. Prescribing patterns may have changed, especially after COVID-19. Researchers also couldn’t determine whether patients were taking all medications as prescribed or whether prescribers and parents were making informed, well-considered decisions about risky combinations.

Nevertheless, Kleinman stressed the need for continued monitoring of prescribing patterns to prevent potential harm. He suggested that health systems and insurers implement systems to flag these rare but concerning cases for review.

“We believe our data and this methodology can serve as the beginning of such efforts,” Kleinman said. “Ultimately, such ongoing monitoring could reduce harmful prescription combinations and drug-related adverse events.”