# Risk Factors for Psychosis and Mania with Prescription Amphetamine Use

> **NIH NIH R01** · MCLEAN HOSPITAL · 2021 · $694,144

## Abstract

ABSTRACT: The use of prescription amphetamines for the treatment of attention-deficit hyperactivity disorder
(ADHD) has markedly increased in the last fifteen years, with the greatest increase in adolescents and young
adults. In 2007, the FDA mandated changes to stimulant labels to warn of increases in psychosis and mania in
patients without pre-existing conditions. Our multidisciplinary research team from Brigham and Women's
Hospital and McLean Hospital recently published a landmark cohort study demonstrating an increased risk of
psychotic episodes in new users of amphetamine compared to methylphenidate in adolescents and young
adults with ADHD. Alarmingly, the use of amphetamines increased four-fold over the study period (2004 –
2015). In addition, our data show that prescription amphetamine use has dramatically increased in patients
with pre-existing bipolar disorder. Thus, there is an urgent need to accelerate knowledge about prescriber-level
factors, patient-level factors and disease states that potentiate the risk of psychosis and mania with
prescription amphetamines. Large-scale studies using real-world data are the only option to study the risk of
infrequent and serious adverse outcomes. In Aim 1, using incident-user cohort study designs, we will utilize
data from two national administrative claims databases to identify prescriber dosing strategies that increase the
risk of first-episode psychosis in ~220,000 adolescents and adults with ADHD initiating amphetamines. We
hypothesize that there will be a dose-dependent increase in the risk of psychosis. The goal of Aim 2 is to
identify patient subgroups at heightened risk of psychosis/mania with prescription amphetamine use. To
accomplish this goal, we will perform a case control study using electronic medical records (EMR) from
McLean Hospital in ~1,650 patients hospitalized for an initial episode of psychosis or mania compared to
~3,300 controls with a first psychiatric hospitalization for reasons other than psychosis or mania. We will apply
natural language processing to unstructured narrative notes to capture detailed patient data not available in
claims data. We hypothesize that patients with a family history of psychiatric illness will have an increased risk
of psychosis/mania with amphetamines compared to patients without a family history. We also hypothesize
that patients with concurrent cannabis use will have an increased risk of psychosis/mania with amphetamines
compared to patients without cannabis use. Aim 3 compares the risk of treatment-emergent mania in ~52,000
new users of amphetamine versus methylphenidate in a cohort study of patients with pre-existing bipolar
disorder, an urgent issue given the known risk of mania with stimulant use. Combined, these studies will
provide actionable evidence to be incorporated into clinical practice guidelines with the goal of mitigating the
risk of psychosis and mania with prescription stimulants. The proposed research agenda aligns with NI...

## Key facts

- **NIH application ID:** 10188647
- **Project number:** 5R01MH122427-02
- **Recipient organization:** MCLEAN HOSPITAL
- **Principal Investigator:** LAUREN V MORAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $694,144
- **Award type:** 5
- **Project period:** 2020-06-10 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10188647

## Citation

> US National Institutes of Health, RePORTER application 10188647, Risk Factors for Psychosis and Mania with Prescription Amphetamine Use (5R01MH122427-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10188647. Licensed CC0.

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