People who take more than 40 milligrams of Adderall may be at increased risk of incident psychosis or mania, according to a new study.

Moran LV, Skinner JP, Shinn AK, et al. Risk of Incident Psychosis and Mania With Prescription Amphetamines. The American Journal of Psychiatry. 2024.

The study adds to research showing a link between prescription amphetamines and psychosis risks, now suggesting that the dose of amphetamines a person takes may correlate with their level of risk. The latest conclusion: the higher the dose you prescribe, the higher a patient’s risk for incident psychosis or mania.

“The current study highlights a greater understanding of the risk, particularly at higher doses,” says David Merrill, MD, PhD, a board-certified geriatric psychiatrist at Providence Saint John’s Health Center in Santa Monica, CA, and the Singleton Endowed Chair in Integrative Brain Health. “The extent of risk at specific dosage thresholds is becoming clearer.”

Dr. Merill adds that the study is a reminder for doctors to prioritize “careful patient selection, dose titration, and close monitoring” when prescribing—or working with patients who use—prescription amphetamines. 

“This study prompts an immediate reconsideration of risk-benefit analysis in the prescribing process, particularly for patients with a history of mental health issues or those at high risk for psychosis,” he says.

Use and misuse of prescription amphetamines

Prescription amphetamines include drugs like Adderall, Dexedrine, and Vyvanse. They are commonly prescribed to treat conditions like attention-deficit hyperactivity disorder (ADHD), but can also be used illicitly as party drugs or as a “study drug” by people without ADHD.

In the study, researchers defined a high dose as more than 40 milligrams of Adderall, 100 milligrams of Vyvanse, and 30 milligrams of dextroamphetamine.  psychosis or mania

Caron C. Adderall in Higher Doses May Raise Psychosis Risk, Study Says. The New York Times. September 12, 2024.

. Taking any of these drugs at high doses could increase the risk of developing psychosis or mania by five times compared with those who aren’t taking the stimulants.

However high doses can still be recommended to treat a person’s ADHD. 

“Patients on 40 milligrams or higher doses of Adderall are typically those with severe ADHD symptoms that have not responded to lower doses,” Dr. Merill says.

If increasing a patient’s Adderall dose to 40 milligrams, doctors should prioritize mental health check-ins to look out for side effects and risks, he advises.

“Doctors should regularly reassess the need for such high doses and monitor for any signs of emerging psychosis,” Dr. Merill adds. Looking into alternative treatments, “like non-stimulant medications or combining lower doses with behavioural therapies along with regular mental health checkups,” may also help some patients stay on lower doses, he says.

When it comes to potential illegal uses of the drugs, Dr. Merill expresses additional concern. “Students who use Adderall without a prescription face significant risks, including psychosis, particularly at high doses or when combined with other substances,” he says.