Prescription Stimulant Use Linked to Earlier Onset of Psychosis | Research

The takeaway

Patients with psychotic disorders who had previously used prescription stimulants developed psychosis an average of four years earlier than those who had not, even after controlling for cannabis use and family history.

Read this if you take stimulant medication and have concerns about psychosis risk, or have a family history of psychotic disorders.

4-year earlier psychosis onset in those exposed to prescription stimulants

What the researchers found

Among 205 patients recruited from an inpatient psychiatric unit, 40% reported using prescription stimulants (mostly for ADHD) before the onset of psychosis.

Those exposed to stimulants developed psychosis at an average age of 20.5 years compared to 24.6 years for unexposed patients. This 4-year difference remained significant after controlling for gender, IQ, education, cannabis use disorder, other drug abuse, and family history of psychosis.

There was a significant interaction with gender: stimulant exposure had a greater effect on age of onset in women, while the effect in men did not reach statistical significance.

Why it matters

ADHD is commonly diagnosed before psychosis onset, and stimulant medications are first-line treatment. If stimulants accelerate psychosis onset in vulnerable individuals, this has major implications for how ADHD is managed in people with psychosis risk factors.

The numbers in context

205 patients; 40% had prior stimulant exposure; age of onset: 20.5 vs. 24.6 years (p<0.001); effect remained significant after controlling for cannabis and family history; stronger effect in females

How the study worked

Cross-sectional study of 205 inpatients with psychotic disorders. Compared age of psychosis onset between those with and without prior prescription stimulant exposure. Multivariable analysis controlled for gender, IQ, education, cannabis use disorder, other substance abuse, and family history.

What this study cannot tell us

Cross-sectional design cannot prove stimulants caused earlier onset. Retrospective self-report of stimulant use. People with earlier psychosis onset may have had more severe childhood symptoms leading to more stimulant prescribing. Dose and duration of stimulant use not captured.

How to read the evidence

Cross-sectional study with appropriate statistical controls, but cannot establish causation and is subject to reverse causation bias.

When this study was published

Published in 2015. The relationship between stimulants and psychosis remains debated.

The bigger picture

This finding adds complexity to the substance-psychosis relationship. While cannabis has received most of the attention, prescription stimulants, which directly increase dopamine signaling, may also influence psychosis timing in vulnerable individuals.

Questions still open

Should stimulant prescribing for ADHD be modified in children with family history of psychosis? Is the effect dose-dependent? Do non-stimulant ADHD medications carry the same risk? Does this reflect a causal relationship or confounding by illness severity?

Common questions

Do ADHD medications cause psychosis?

This study found an association between prior stimulant use and earlier psychosis onset, but could not prove causation. It is possible that the underlying condition that led to stimulant prescribing (e.g., more severe childhood difficulties) also predisposed to earlier psychosis.

Was this about cannabis or stimulants?

The association between stimulants and earlier psychosis onset remained significant even after controlling for cannabis use disorder. This suggests the stimulant effect was independent of cannabis, though both may contribute to psychosis risk.

Read the original research

Prescription stimulant use is associated with earlier onset of psychosis.

Journal of psychiatric research, 71, 41-7

View on PubMed ↗Publisher’s paper ↗

Citation

Moran, Lauren V; Masters, Grace A; Pingali, Samira; Cohen, Bruce M; Liebson, Elizabeth; Rajarethinam, R P; Ongur, Dost. (2015). Prescription stimulant use is associated with earlier onset of psychosis.. Journal of psychiatric research, 71, 41-7. https://doi.org/10.1016/j.jpsychires.2015.09.012