High doses of amphetamine-based medications for ADHD, like Adderall, are linked to an over five times higher risk of psychosis or mania. The corresponding study was published in the American Journal of Psychiatry.
Amphetamines have been increasingly prescribed in the US in recent years. While earlier research has shown that prescription amphetamines increase risk of psychosis, until recently, little has been known on how dosage affects risk.
The impetus for the current study came from past observations of study author, Lauren Moran, MD, a pharmacoepidemiology researcher at McLean Hospital in the Boston area, who, as an inpatient psychiatrist, regularly saw patients experiencing first episodes of psychosis while being prescribed high doses of stimulants.
For the study, Moran and colleagues analyzed data from 1,374 patients aged 16-35 who had been hospitalized at McLean Hospital for incident psychosis or mania between 2005 and 2019. They also included 2 748 controls who had an initial psychiatric hospitalization for other reasons- predominantly depression and/ or anxiety.
Ultimately, the researchers found that the odds of psychosis and mania were higher among individuals with past-month prescription amphetamine use than those without.
They observed a dose-repsonse relationship, with high doses of dextroamphetamine- defined as those exceeding 30mg- being linked to a 5.28-fold increase in chances of developing psychosis or mania. Popular ADHD medication, Adderall, is a combination of amphetamine and dextroamphetamine.
The researchers found no link between past-month use of methylphenidate- sold as Ritalin, Concerta, and other names- and increased odds of mania or psychosis compared to no use.
The researchers further calculated that among people who take prescription amphetamines, 81% of cases of mania or psychosis could have been avoided if high doses were not taken.
Although the study did not prove casualty, the researchers noted that amphetamines increase levels of the neurotransmitter dopamine in a way that is similar to dopaminergic changes seen in psychosis.
There are limitations to the findings. Electronic health records may carry inconsistencies, and as the research took place in a psychiatric hospital in the Boston area, the results may not apply to other regions.
“This is a rare but serious side effect that should be monitored by both patients and their doctors whenever these medications are prescribed,” said Moran in a press release.
“There’s limited evidence that prescription amphetamines are more effective in high doses. Physicians should consider other medications our study found to be less risky, especially if a patient is at high risk for psychosis or mania,” she concluded.