A new study published Thursday in the American Journal of Psychiatry has found a significant association between high doses of ADHD medications and an increased risk of developing psychosis or mania. This research is among the first to establish a clear “dose-response relationship” between escalating doses of amphetamine-based drugs and the likelihood of psychotic symptoms.
The study highlights that medications such as Adderall, Vyvanse, and generic amphetamines like dextroamphetamine may substantially elevate the risk of psychosis when taken in high doses. Amphetamines are known to increase dopamine levels in the brain, a neurotransmitter involved in mood, memory, and motivation, but also linked to psychosis when present in excessive amounts.
Dr. Jacob Ballon, a psychiatrist and co-director of the INSPIRE Clinic at Stanford Medicine, explained, “When the brain is flooded with dopamine, it can potentially lead to psychosis.” However, the study introduces a new dimension by demonstrating that this risk intensifies with higher doses of the drugs.
Dr. Will Cronenwett, vice chair for clinical affairs in psychiatry at Northwestern Medicine, remarked on the growing prevalence of amphetamine use in the U.S. “The popularity and usage of amphetamines are increasing significantly,” he noted. Recent data from JAMA Psychiatry reveals a 30% rise in prescription rates for amphetamines among individuals aged 20 to 39 from 2018 to 2022, with a 17% increase among those aged 40 to 59.
In response to the study, a spokesperson for Takeda Pharmaceuticals, which manufactures Vyvanse, emphasized the importance of adhering to FDA-approved guidelines and consulting with healthcare providers. Teva Pharmaceuticals, the producer of Adderall, did not respond to requests for comment.
The study, led by Dr. Lauren Moran of McLean Hospital, analyzed electronic health records from Mass General Brigham spanning from 2005 to 2019. The research focused on patients aged 16 to 35, a demographic typical for the onset of psychosis or schizophrenia. The study identified 1,374 cases of first episodes of psychosis or mania, compared to 2,748 cases of other psychiatric conditions.
Participants who received the highest doses of ADHD medications—exceeding 40 mg of Adderall, 100 mg of Vyvanse, or 30 mg of dextroamphetamine—were found to be 5.3 times more likely to develop psychosis compared to those not using stimulants. Medium doses, defined as 20-40 mg of Adderall, 50-100 mg of Vyvanse, or 15-30 mg of dextroamphetamine, were associated with a 3.5 times higher risk. The study did not establish a clear risk for lower doses.
No increased risk of psychosis was observed with Ritalin, a non-amphetamine ADHD medication.
According to Dr. Moran, about 6% of patients on amphetamines are prescribed the highest doses, while 22% receive medium doses. Dr. Cronenwett noted that while the overall risk of psychosis remains relatively low—around 1 in 1,000—patients on high doses should be informed of the potential risks.
He advised, “Patients with a personal or family history of severe mental illnesses, such as bipolar disorder or schizophrenia, should be particularly cautious with high doses of these medications.”
Dr. Ballon added, “For some patients, high doses may be pursued in an attempt to achieve better effectiveness, inadvertently increasing the risk of adverse effects.”
The study underscores the need for careful management of ADHD medication dosages to mitigate the risk of psychosis, highlighting the importance of ongoing research and patient education.
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