ADHD News & Research

Study: ADHD Amphetamines Linked to Higher Risk of Psychosis

The first extensive study on the risk of psychosis in adolescents and young adults with ADHD revealed that, although low overall, patients newly prescribed amphetamines have twice the risk of developing psychosis when compared to patients using methylphenidate.

March 22, 2019

A study published in The New England Journal of Medicine1 finds that young patients with attention deficit disorder (ADHD or ADD) beginning a first-time amphetamine, like Adderall or Vyvanse, are more likely to develop psychosis than are similar patients starting methylphenidate, like Ritalin or Concerta. Though the chance of developing psychosis — including depressive disorder or bipolar disorder with psychotic features, schizophrenia spectrum disorders, delusional disorder, hallucinations, and unspecified psychosis — is low overall, patients taking amphetamine are twice as likely as patients taking methylphenidate to merit a diagnosis.

The studied population included 221,846 adolescents and young adults ages 13-25 who received a stimulant prescription for ADHD. The participants were evenly split between those who had started taking amphetamine and those who took methylphenidate for the first time between January 1, 2004, and September 30, 2015.

Among this population, there were 343 new diagnoses of psychosis that merited a prescription for an antipsychotic medication within the first four to five months of stimulant-medication treatment. Among those, 237 psychosis diagnoses came from the group taking amphetamine and 106 came from the group taking methylphenidate. In other words, psychosis occurred in 1 out of every 660 patients, and the risk for psychosis was nearly twice as high among patients taking amphetamine for the first time compared to those taking methylphenidate for the first time.

“This study reminds us that we need to keep a close watch on our patients and follow up on any suspicious changes in mood, thinking or behavior,” says Dr. Anthony Rostain, professor of psychiatry and pediatrics at the Perelman School of Medicine at the University of Pennsylvania, and attending and supervising psychiatrist at the Children’s Hospital of Pennsylvania and the University of Pennsylvania Health System. “Additionally, we should always educate patients about the potential risks of side effects. One possible contributor to the onset of psychosis is misuse/abuse of stimulant medication including snorting and IV use; immediate release preparations are more likely to be misused.”

Researchers stressed that these new findings do not apply to those who have taken either ADHD stimulant and tolerated it well — only to those who have recently began treatment with an amphetamine. This study was not a randomized, controlled trial.

Researchers also stressed that physicians must exercise an abundance of caution when prescribing a stimulant medication for the first time to a patient, particularly an adolescent or young adult. Specifically, doctors should screen for potential risk factors including:

  • History of a mood disorder or other psychiatric disorder
  • Family history of psychiatric illness
  • Use of cannabis or other non-prescription drug

In August 2018, researchers from the UK undertook a systemic review and network meta-analysis of 133 double-blind, randomized, controlled trials designed to compare the drug effectiveness and tolerability of amphetamines and methylphenidate — plus atomoxetine, bupropion, clonidine, guanfacine, and modafinil. For children and adolescents, the research found that methylphenidate and modafinil produced the best results.

For children diagnosed with ADHD before age 6, the American Academy of Pediatrics (AAP) recommends methylphenidate if the first-line treatment of behavior therapy alone does not produce significant results. For children ages 6 to 11, the AAP recommends stimulant medication paired with behavior therapy but it does not stipulate a preference for methylphenidate or amphetamine. The same is true for teen-aged patients. Still, amphetamines are prescribed more often — and at a faster growing rate — than are methylphenidates in the United States today.

In 2007, the Food and Drug Administration mandated that ADHD medication labels warn about potential psychiatric risks. To date, the risk of psychosis among adolescents taking a new amphetamine vs. methylphenidate has not been rigorously studied.


Lauren V. Moran, M.D., Dost Ongur, M.D., Ph.D., John Hsu, M.D., M.S.C.E., Victor M. Castro, M.S., Roy H. Perlis, M.D., Sebastian Schneeweiss, M.D., Sc.D. Psychosis with Methylphenidate or Amphetamine in Patients with ADHD. The New England Journal of Medicine (Mar. 2019).