Wayne A Ray1, C Michael Stein2,3, Katherine T Murray3,4, D Catherine Fuchs5, Stephen W Patrick1,6,7, James Daugherty1, Kathi Hall1, William O Cooper6,7. 1. Department of Health Policy, Vanderbilt University School of Medicine, Nashville, Tennessee. 2. Division of Rheumatology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee. 3. Division of Clinical Pharmacology, Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee. 4. Division of Cardiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee. 5. Department of Psychiatry and Behavioral Science, Vanderbilt University School of Medicine, Nashville, Tennessee. 6. Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee. 7. Vanderbilt Center for Child Health Policy, Vanderbilt University School of Medicine, Nashville, Tennessee.
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.
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.
Authors: Aristotle N Voineskos; Benoit H Mulsant; Erin W Dickie; Nicholas H Neufeld; Anthony J Rothschild; Ellen M Whyte; Barnett S Meyers; George S Alexopoulos; Matthew J Hoptman; Jason P Lerch; Alastair J Flint Journal: JAMA Psychiatry Date: 2020-07-01 Impact factor: 21.596
Authors: Marco Solmi; Michele Fornaro; Edoardo G Ostinelli; Caroline Zangani; Giovanni Croatto; Francesco Monaco; Damir Krinitski; Paolo Fusar-Poli; Christoph U Correll Journal: World Psychiatry Date: 2020-06 Impact factor: 49.548
Authors: Joseph C Blader; Steven R Pliszka; Vivian Kafantaris; Carmel A Foley; Gabrielle A Carlson; Judith A Crowell; Brigitte Y Bailey; Colin Sauder; W Burleson Daviss; Christa Sinha; Thomas L Matthews; David M Margulies Journal: J Am Acad Child Adolesc Psychiatry Date: 2020-01-30 Impact factor: 8.829