# Antipsychotics and the Risk of Unexpected Death in Children and Youth

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2022 · $641,537

## Abstract

Each year an estimated 1.3 million persons ≤24 years of age receive 7 million antipsychotic
prescriptions in the U.S. Although the primary indications for antipsychotics are schizophrenia and related
psychoses, with no other treatment alternatives, an estimated 90% of antipsychotic prescriptions for
children and youth are for other, less serious conditions, including attention-deficit/hyperactivity disorder
(ADHD), disruptive or aggressive behaviors, affective disorders including bipolar disorder, and anxiety.
However, other recommended therapeutic interventions for children and youth with these disorders are
thought to have fewer adverse effects.
 Antipsychotics, which increase the risk of cardiovascular and all-cause mortality in adults, have serious
adverse cardiovascular, metabolic, respiratory, and neurologic effects in children and adolescents that
plausibly increase the risk of death in this population. We recently found that antipsychotic users of
doses>50mg chlorpromazine equivalents (median starting dose) had a greater than 3-fold increased risk of
unexpected death, leading to a 64% increase in total mortality (HR = 1.64 [1.03-2.63]). In contrast, the
adjusted risk of deaths from injuries or suicides did not increase nor was there increased risk of death from
any cause for lower doses of antipsychotics.
 Our data indicate antipsychotics increase risk of unexpected deaths, particularly cardiovascular deaths.
The increased risk is clinically meaningful: the incidence of unexpected death in higher-dose antipsychotic
users equaled that of injuries and suicides, which account for two-thirds of deaths in children and
adolescents. Thus, death should be considered as a potential harm when prescribing antipsychotics for
children and youth. However, to guide clinical practice, data are needed that define antipsychotic-related
mortality: 1) according to antipsychotic indication; and 2) according to important factors that practitioners
can control: a) individual drug, b) dose, and c) concurrent central nervous system (CNS) depressants.
 We will address these questions using the national Medicaid Analytical Extract (MAX) database, which
includes more than 15 years of longitudinal data that can be linked to death certificates for the estimated
39% of children in the U.S. who are Medicaid enrollees. There are two specific aims:
Aim 1: Test the hypothesis that the risk of unexpected deaths and total mortality in children and youth who
are antipsychotic new users with a) ADHD or disorders of behavior/conduct, b) unipolar depressive or
anxiety disorders, or c) bipolar disorders is greater than that for comparable patients starting alternative
medications.
Aim 2: Define how risk of unexpected deaths and total mortality in children and youth who are antipsychotic
new users varies with a) individual drug, b) dose, and c) concurrent CNS depressants.

## Key facts

- **NIH application ID:** 10328243
- **Project number:** 5R01HD097344-04
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** WAYNE A RAY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $641,537
- **Award type:** 5
- **Project period:** 2019-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10328243

## Citation

> US National Institutes of Health, RePORTER application 10328243, Antipsychotics and the Risk of Unexpected Death in Children and Youth (5R01HD097344-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10328243. Licensed CC0.

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