Stimulant Medications Don't Cause Psychosis, New Study Finds

Medscape

14-05-2025

Prescription stimulants taken during childhood for attention-deficit/hyperactivity disorder (ADHD) do not cause psychosis, according to a new study published on Monday in Pediatrics, contradicting what some observational studies had suggested.
Instead, the new study found children with more severe attention and hyperactivity issues or other mental health conditions such as anxiety were more likely to be medicated for ADHD. These children were also more likely to experience psychotic episodes, suggesting stimulants such as Adderall were not the cause.
'These results provide reassurance both to families and to prescribers that routine ADHD medication treatment is unlikely to cause psychotic experiences,' said Ian Kelleher, PhD, chair of child and adolescent psychiatry in the Centre for Clinical Brain Sciences at The University of Edinburgh in Edinburgh, Scotland, who led the trial.
Kelleher and his colleagues used data from the Adolescent Brain Cognitive Development Study, a longitudinal study tracking brain development and child health in the United States. The study included more than 8300 children and teens who were between 9 years and 14 years of age from 2016 to 2020.
At the beginning of the study, none of the children were taking a prescription stimulant. In the first year, 460 kids were prescribed a drug for ADHD, which included methylphenidate, dexmethylphenidate, amphetamine, dextroamphetamine, and lisdexamfetamine. They did not have information on the dose of medication. Researchers then compared rates of psychosis among these children with approximately 7900 children who were not on one of these medications.
The researchers analyzed self-reported questionnaires from each child, which they filled out at baseline and again 1 year into the study. The screener for psychosis risk asked 21 questions about whether they had experienced hallucinations or delusions, and if so, how distressed they were by these experiences.
Among the population taking stimulants, the drugs were not associated with psychosis after adjusting for confounding factors that can predispose a person to psychosis, including mental illness, parental income, and race (odds ratio [OR], 1.09; 95% CI, 0.71-1.56).
In the unweighted analysis, children prescribed ADHD medications were about 1.5 times more likely to have had a psychotic episode than those not taking a stimulant (OR, 1.46; 95% CI, 1.15-1.84).
Those who had more severe ADHD symptoms, like hyperactivity or impulsiveness, and those who had other, co-occurring mental health symptoms like anxiety and depression, were most likely to report psychotic episodes. This group, as well as boys generally, were also more likely to have been prescribed stimulants.
'It's important to recognize that any difference in risk may not be due to stimulant treatment,' Kelleher said. 'If you take children with ADHD and you divide them into two groups, kids treated with medication and kids not treated with medication, those two groups are not the same.'
Kelleher said previous research linking stimulants with episodes of psychosis had not done a thorough job of factoring in a person's mental health or severity of ADHD.
One observational study published in 2024 suggested higher doses of prescription amphetamines were associated with more than a fivefold increase in the risk of developing psychosis.
A 2023 meta-analysis also cited studies suggesting taking higher doses of stimulants than typically prescribed for ADHD could cause psychosis. An observational study published in 2024, in the Journal of the American Academy of Child & Adolescent Psychiatry , concluded that while risk for psychosis was low, taking amphetamines and atomoxetine for longer periods of time may increase a person's risk for psychosis. However, the authors of the meta-analysis did note that clinicians may have misidentified a child's symptoms as ADHD instead of signs of psychosis.
In addition to factors like race and age, researchers should consider that hallucinations and delusions are 'quite common' during childhood, said Melissa Batt, MD, MPH, an assistant professor of psychiatry at the University of Colorado Anschutz Medical Campus, Aurora, Colorado, who was not involved with the trial. They should take this knowledge into account when looking into potential causes of psychotic episodes in kids.
'They are usually fleeting and usually go away,' Batt said, adding that only a small number of young people who report having a psychotic episode are eventually diagnosed with a psychotic disorder. 'Upwards of 90% do not go on to have a diagnosis,' she said.
Batt said one limitation of the study was the 9- to 14-year-old age range.
'They are missing a pretty critical range of folks, especially older teens and people in their 20s. Those are the ages that we see who develop psychosis or mania,' she said.
Batt agreed observational studies left out a lot of factors that could connect psychotic episodes to influences other than stimulant medications. Family history, she said, is a huge influence in whether a person develops a psychotic disorder.
Future trials should build on these new findings and take different patient characteristics into account, she said.
'We should be looking at family history, other medications they are taking, they could be using other substances such as cannabis, which they didn't control for,' she said. 'That is a huge variable we should be looking at.'.
This study was funded in part by an International Secondment Award to J.F.B. from the Royal College of Surgeons in Ireland University of Medicine and Health Sciences. The study authors reported receiving financial support from the St John of God Research Foundation and the Health Research Board, among others.