Dataset Information

Association of Antipsychotic Treatment With Risk of Unexpected Death Among Children and Youths.

ABSTRACT:

Importance

Children and youths who are prescribed antipsychotic medications have multiple, potentially fatal, dose-related cardiovascular, metabolic, and other adverse events, but whether or not these medications are associated with an increased risk of death is unknown.

Objective

To compare the risk of unexpected death among children and youths who are beginning treatment with antipsychotic or control medications.

Design, setting, and participants

This retrospective cohort study was conducted from 1999 through 2014 and included Medicaid enrollees aged 5 to 24 years in Tennessee who had no diagnosis of severe somatic illness, schizophrenia or related psychoses, or Tourette syndrome or chronic tic disorder. Data analysis was performed from January 1, 2017, to August 15, 2018.

Exposures

Current, new antipsychotic medication use at doses higher than 50 mg (higher-dose group) or 50 mg or lower chlorpromazine equivalents (lower-dose group) as well as control medications (ie, attention-deficit/hyperactivity disorder medications, antidepressants, or mood stabilizers) (control group).

Main outcomes and measures

Deaths during study follow-up while out of hospital or within 7 days after hospital admission, classified as either deaths due to injury or suicide or unexpected deaths. Secondary outcomes were unexpected deaths not due to overdose and death due to cardiovascular or metabolic causes.

Results

This study included 189 361 children and youths in the control group (mean [SD] age, 12.0 [5.1] years; 43.4% female), 28 377 in the lower-dose group (mean [SD] age, 11.7 [4.4] years; 32.3% female), and 30 120 in the higher-dose group (mean [SD] age, 14.5 [4.8] years; 39.2% female). The unadjusted incidence of death in the higher-dose group was 146.2 per 100 000 person-years (40 deaths per 27 354 person-years), which was significantly greater than that in the control group (54.5 per 100 000 population; 67 deaths per 123 005 person-years) (P < .001). The difference was primarily attributable to the increased incidence of unexpected deaths in the higher-dose group (21 deaths; 76.8 per 100 000 population) compared with the control group (22 deaths; 17.9 per 100 000 population). The propensity score-adjusted hazard ratios were as follows: all deaths (1.80; 95% CI, 1.06-3.07), deaths due to unintentional injury or suicide (1.03; 95% CI, 0.53-2.01), and unexpected deaths (3.51; 95% CI, 1.54-7.96). The hazard ratio was 3.50 (95% CI, 1.35-9.11) for unexpected deaths not due to overdose and 4.29 (95% CI, 1.33-13.89) for deaths due to cardiovascular or metabolic causes. Neither the unadjusted nor adjusted incidence of death in the lower-dose group differed significantly from that in the control group.

Conclusions and relevance

The findings suggest that antipsychotic use is associated with increased risk of unexpected death and appear to reinforce recommendations for careful prescribing and monitoring of antipsychotic treatment for children and youths and to underscore the need for larger antipsychotic treatment safety studies in this population.

SUBMITTER: Ray WA

PROVIDER: S-EPMC6440238 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceSignificant concern exists over treating youths with attention-deficit/hyperactivity disorder (ADHD) with antipsychotic medications, yet little is known about the factors associated with antipsychotic treatment.ObjectivesTo describe the percentage of youths who fill antipsychotic prescriptions in the year following a new diagnosis of ADHD and characterize the clinical and demographic factors associated with antipsychotic initiation.Design, setting, and participantsA retrospective longitudinal cohort analysis of antipsychotic treatment was performed in 187 563 youths, aged 3 to 24 years, with a new diagnosis of ADHD (without recent diagnosis of any US Food and Drug Administration [FDA]-indicated conditions for antipsychotic treatment). The sample was derived from the 2010 to 2015 MarketScan Commercial Database, with the analysis completed between November 1, 2018, and May 30, 2019.Main outcomes and measuresThe percentage of youths prescribed an antipsychotic in the first year following a new diagnosis of ADHD. Among those prescribed antipsychotic medications, the percentage who received a diagnosis of conduct disorder, oppositional defiant disorder, or a disorder for which 1 or more antipsychotic medication has received an indication for use in youths from the FDA (schizophrenia, bipolar disorder, and Tourette disorder) and the percentage that filled an antipsychotic prescription before filling a stimulant prescription (methylphenidate or amphetamine derivative).ResultsOf the 187 563 youths included in the study, 114 305 (60.9%) were male with a mean (SD) age of 13.74 (5.61) years. In the year following a new ADHD diagnosis, 4869 youths (2.6%; 95% CI, 2.5%-2.7%) with ADHD were prescribed an antipsychotic. Youths treated with antipsychotics with ADHD were more likely than their peers who were not receiving an antipsychotic to have recently received diagnoses of self-harm and/or suicidal ideation (adjusted odds ratio [aOR], 7.5; 95% CI, 5.9-9.6), oppositional defiant disorder (aOR, 4.4; 95% CI, 3.9-4.9), and substance use disorder (aOR, 4.0; 95% CI, 3.6-4.5). The youths who received antipsychotics were also more likely to have received inpatient treatment (aOR, 7.9; 95% CI, 6.7-9.3). During the year following the new ADHD diagnosis, 52.7% (95% CI, 51.3%-54.1%) of youths treated with antipsychotics received a diagnosis for which antipsychotics have either an FDA or evidence-supported indication for their use. Among youths who initiated antipsychotic medications, 47.9% (95% CI, 46.5%-49.3%) did not receive a stimulant prescription between their ADHD diagnosis and antipsychotic initiation. Antipsychotic prescribing was proportionally highest for preschool-aged children (4.3%) and associated with neurodevelopmental disorders (aOR, 3.9; 95% CI, 1.3-11.2) and recent inpatient mental health treatment (aOR, 8.9; 95% CI, 1.7-45.8).Conclusions and relevanceApproximately half of youths with a new ADHD diagnosis may have an evidence-supported indication for an antipsychotic medication. Less than half of these youths received a stimulant; the evidence-supported first line treatment for ADHD, before the antipsychotic was initiated. Use of antipsychotic prescribing appears to be associated with high levels of psychiatric comorbidity.

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