Adolescents and young adults with attention deficit hyperactivity disorder (ADHD) who are treated with stimulant medications have a small risk of developing psychosis — something that drug labels already warn about.
Adding to this, a new study found that this risk is higher in 13- to 25-year-olds prescribed amphetamines such as Vyvanse and Adderall, compared to those who received methylphenidates such as Ritalin or Concerta.
Experts stress people taking the medication and parents should not be alarmed by the findings. The overall risk was low, occurring in approximately 1 in 660 patients, according the study published this week in the New England Journal of Medicine.
“Although the risk of psychosis in association with ADHD treatment with stimulant medication may worry patients, it must be remembered that this was a very rare side effect,” said Dr. Andrew Adesman, chief of developmental and behavioral pediatrics at the Steven & Alexandra Cohen Children’s Medical Center of New York in New Hyde Park, New York.
Researchers used two national insurance claim databases to follow 221,846 adolescents and young adults with ADHD who began taking a stimulant medication between 2004 and 2015.
Half were prescribed amphetamines by their doctor, and the other half received methylphenidates.
Patients who received an amphetamine had a 0.21 percent chance of having a psychotic episode in the few months after starting the drug. For those who received methylphenidate, it was 0.1 percent.
“Among the stimulant medications, methylphenidate appears less likely to be associated with subsequent new psychosis than amphetamine,” said Dr. Michael Brodsky, medical director of behavioral health at L.A. Care Health Plan.
For the study, researchers considered a psychotic episode to be a new diagnosis for psychosis and a prescription for an antipsychotic medication.
The researchers followed patients for several months after they started the ADHD medication.
But Adesman said, “It is unclear to what extent there is a continued risk of developing psychosis if a patient has been on stimulant medications for several years without any problems.”
The condition is often treated with a combination of behavior therapy and medication.
Brodsky said, “Stimulant medications are the most effective treatment for ADHD,” although they do “come with a small risk of increasing the likelihood of psychosis.”
Adesman pointed out that the study focused only on psychosis. This involves disruptions to a person’s thoughts and perceptions that make it hard for them to know what is real.
He said a more common side effect of stimulant ADHD drugs is “transient hallucinations,” which the researchers didn’t look at.
Dr. James Lewis, a professor of pediatrics at the Joan C. Edwards School of Medicine at Marshall University in Huntington, West Virginia, said children who have this side effect may “cry uncontrollably, see spiders or bugs on their skin, become anxious about cars driving by, or see a large green frog in their closet.”
He added, “But this is a very rare experience, and the symptoms resolved when the medication was discontinued.”
Lewis, who is the author of “Making Sense of ADHD: Overcoming the Challenges of Coexisting Conditions,” also pointed out that the study didn’t include children under 13 or people with public insurance or no insurance. So the results may not apply to those groups.
The authors write in the paper that the differences between the rates of psychosis may be due to differences in how the drugs work in the brain.
Both drugs stimulate the release of the brain chemical dopamine from neurons. They also block dopamine from being removed from the synapses, the spaces between the ends of the neurons.
Amphetamine causes more dopamine to be released, resulting in a surge. Methylphenidate is better at blocking the removal of dopamine, which causes it to stick around longer.
Changes in the how the neurons transmit signals during psychosis are more similar to what happens after use of amphetamine, write the researchers.
Some experts worry that this study may alarm parents and deter them from opting to use medication to treat their child’s ADHD.
Many medical decisions are a matter of balancing the risks and benefits, however.
Children whose ADHD is left untreated may continue to have academic, social, and emotional difficulties throughout childhood and even as adults.
There is also a balancing of the risks associated with different drugs.
Adesman said, “Given these findings, some patients may feel more comfortable going forward being treated with a methylphenidate formulation instead of amphetamines.”
“The reality is that some patients may get greater benefits from an amphetamine formulation than from a methylphenidate formulation,” he added.
Lewis stressed that the rate of psychosis is extremely low, even though there is an increased risk for people taking amphetamines.
“Parents, however, should be given this information so that they are aware of the possibility and determine which medication they would prefer,” Lewis said.