High-Dose Prescription Amphetamines Increase Incident Psychosis, Mania Risk

High doses of prescription amphetamines over 30 mg dextroamphetamine equivalents are associated with substantially increased odds of incident psychosis and mania relative to non-use, according to study results published in the American Journal of Psychiatry.

Although stimulants are an effective pharmacotherapy option for individuals with attention-deficit/hyperactivity disorder (ADHD), they are also associated with an increased risk for psychosis and mania. However, the relationship between prescription amphetamine dosage and incident psychosis and/or mania risk remains uncertain.

To this aim, researchers conducted a case-control study to elucidate dose levels and other risk factors associated with incident psychosis and mania among individuals treated with prescription amphetamines. The researchers recruited individuals aged 16 to 35 years who were admitted to the McLean Hospital for an initial psychiatric hospitalization between January 1, 2005, and December 31, 2019. The exposure of interest was past-month prescription amphetamine use, obtained using electronic health records. The researchers converted amphetamine doses to dextroamphetamine equivalents, which were then were divided into terciles (ie, low-dose [≤15 mg], medium-dose [>15 mg to 30 mg], and high dose [>30 mg]).

A total of 1374 individuals with incident psychosis or mania and 2748 case-matched controls were included in the analysis. The researchers found that cases were more likely to be men, Black, and Hispanic, relative to controls (all P <.001). Additionally, cases had higher rates of ADHD, learning disabilities, cannabis use, tobacco use, opioid use, and hallucinogen use relative to controls (all P <.05).  Overall, 10.1% of individuals had past-month prescription amphetamine use.

In models adjusted for demographic and clinical variables, the researchers found that prescription amphetamine use in the past month was associated with significantly higher odds of incident psychosis and mania (adjusted odds ratio [aOR], 2.68; 95% CI, 1.90-3.77).

When stratified by amphetamine dosage, the researchers observed a dose-response relationship. The aOR for low doses of amphetamines was 1.79 (95% CI, 1.15-2.79), increasing to 5.28 (95% CI, 3.06-9.13) among individuals receiving high doses of amphetamines.

These findings indicate that prescription amphetamine use in the past month increases the odds of incident psychosis and mania in a dose-dependent manner. The researchers concluded, “The clinical utility of prescribing doses of amphetamines that exceed 30 mg dextroamphetamine equivalents is unproven; coupled with the elevated risk of inducing psychosis or mania, we recommend minimizing this practice.”

Study limitations include the potential selection bias via the use of hospitalized control subjects and the reliance on electronic health records, which are prone to inconsistencies in documentation and quality.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

This article originally appeared on Psychiatry Advisor