A new study released Thursday in the American Journal of Psychiatry links high doses of ADHD medications to more than five times greater risk of psychosis or mania.
Among the earliest studies to establish a link between rising drug dosages—amphetamines especially—and a higher risk of psychotic symptoms is this one.
Among the pharmaceuticals are Adderall, Vyvanse, generic amphetamines like dextroamphetamine.
Amphetamines and psychosis have an old relationship. Amphetamines raise brain levels of dopamine. Although the neurotransmitter is involved in memory, motivation and mood as well as in other physiological functions, it is also linked to psychosis.
According to psychiatrist and co-director of the INSPIRE Clinic at Stanford Medicine, a facility dedicated to patients with psychosis, the medications “can flood the brain with dopamine and when you flood the brain with dopamine you potentially can cause psychosis.”
High doses of ADHD medications connected to increased risk of psychosis
A phenomenon known as a “dose-response relationship,” what had not been demonstrated was that greater dosages increased the likelihood of psychosis.
“That’s what this study offers,” Northwestern Medicine’s vice chair for clinical affairs in psychiatry, Dr. Will Cronenwett said.
“Right now, The United States is experiencing sort of an amphetamine moment,” Cronenwett remarked. “Popularity and use of amphetamines is high and getting higher.”
Especially among adults, stimulant use in the United States has surged recently. Prescription rates for amphetamines for attention-deficit hyperactivity disorder had increased 30% from 2018 to 2022 among persons ages 20 to 39, according a study published this year in JAMA Psychiatry. Rates climbed 17% among those between the ages of 40 and 59.
Takeda Pharmaceuticals, the manufacturer of Vyvanze, said in a statement to NBC News, “Takeda believes it is important for patients to take our medicines in accordance with U.S. Food and Drug Administration (FDA)-approved labelling guidance and in consultation with their prescribing health care provider.”
Adderall’s manufacturer, Teva Pharmaceuticals, turned down a request for comment.
High doses
According to lead study author Dr. Lauren Moran, a psychiatrist and researcher at McLean Hospital, a teaching hospital affiliated with Mass General Brigham in Boston, psychosis connected with amphetamines is not unusual.
“We have seen plenty of this,” Moran remarked. “We are seeing college students coming in prescribed stimulants who lacked much of a psychiatric history developing new onset psychosis.”
Focusing on teens and adults between the ages of 16 and 35, the usual age range for the onset of psychosis or schizophrenia, Moran and her associates examined electronic health records from Mass General Brigham from 2005 through 2019 in the current study. Compared with 2,648 individuals hospitalised for other mental diseases, such sadness or anxiety, they found 1,474 cases of patients hospitalised with initial bouts of psychosis or mania.
They also inquired about whether the patients had received stimulant prescriptions in the past month and, if so, what amounts.
Patients taking the highest dosages—more than 40 milligrammes of Adderall, 100 mg of Vyvanse or 30 mg of dextroamphetamine—were 5.3 times more likely to experience psychosis than those not using any stimulants.
Linked to a 3.5 times increased risk was the medium dosage, 20 mg to 40 mg of Adderall, 50 mg to 100 mg of Vyvanse, or 15 mg to 30 mg of dextroamphetamine. Less than 20 mg of Adderall, 50 mg of Vyvanse, or 15 mg of dextroamphetamine does not clearly correlate with an elevated risk of psychosis, Moran said.
Another ADHD medication, Ritalin, not an amphetamine, did not raise any risk of psychosis.
Based on a review of national insurance claim data, Moran said, approximately 6% of amphetamine users are prescribed the highest dosages and approximately 22% are assigned the medium dosages.
According to Cronenwett, about 1 in 1,000 people run the unusual chance of experiencing psychosis from an amphetamine. High dosage users should still be cautious of the hazards, though.
“I would counsel patients who have a personal or family psychiatric history of significant mental illness, including things like bipolar disorder with mania or schizophrenia,” he remarked. “If these kinds of diseases run in the family tree, then that’s someone who might want to be quite careful about how much of these drugs they use and in what doses.”
