A recent study conducted by researchers from McLean Hospital in Massachusetts has found that high doses of prescription amphetamines can increase a person’s risk of developing psychosis or mania. This finding is concerning given the increasing trend in prescription amphetamine use in the United States, with a 70% increase from 2011 to 2021, and even higher rates during the COVID-19 pandemic. Amphetamines are commonly used to treat conditions such as attention deficit hyperactivity disorder (ADHD) and narcolepsy, but can also be misused as recreational drugs, leading to potential addiction.

The study analyzed medical data from adults treated at Mass General Brigham between 2005 and 2019, identifying about 1,300 individuals with a first-episode psychosis or mania and 2,700 people as a control group. The researchers found that study participants taking high doses of amphetamines, considered to be 30 milligrams or more, had a five-fold increased risk of developing psychosis or mania. This risk was not seen in individuals taking methylphenidate, a similar stimulant medication commonly known as Ritalin.

The lead study author, Lauren Moran, MD, emphasized that the dose of amphetamines plays a significant role in the risk of psychosis and mania, and should be carefully monitored by both patients and doctors when prescribing these medications. The findings suggest that up to 81% of psychosis or mania cases in individuals taking prescription amphetamines could have been avoided if they were not taking high doses. This highlights the importance of using the lowest effective dose and considering alternative medications for individuals at high risk for psychosis.

David Merrill, MD, PhD, a board-certified geriatric psychiatrist, noted the need for careful patient selection, dose titration, and close monitoring when prescribing amphetamines, especially for patients with a history of mental health issues or those at high risk for psychosis. He suggested using extended-release formulations and nonpharmacologic interventions as first-line treatments whenever possible. Regular mental health evaluations and more frequent follow-ups are also recommended, particularly during the initiation and titration phases of amphetamine therapy.

Stacy Doumas, MD, MBA, chairwoman of Psychiatry at Hackensack Meridian Jersey Shore University Medical Center, expressed concern over the study’s findings and emphasized the importance of understanding the potential mechanisms linking amphetamines with psychosis. Future research should focus on exploring the casual relationship between high-dose amphetamine prescriptions and the risk of psychosis and mania through longitudinal studies, pharmacovigilance studies, and mechanistic studies. This research could provide valuable insights into the risk associated with amphetamine use and inform prescribing practices to minimize harm to individuals.

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