Mortality risk of antipsychotic augmentation for adult depression
Importance Randomized controlled trials have demonstrated increased all-cause mortality in elderly patients with dementia treated with newer antipsychotics. It is unknown whether this risk generalizes to non-elderly adults using newer antipsychotics as augmentation treatment for depression. Objectiv...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2020-01-01
|
Series: | PLoS ONE |
Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526884/?tool=EBI |
_version_ | 1819171846811025408 |
---|---|
author | Tobias Gerhard T. Scott Stroup Christoph U. Correll Soko Setoguchi Brian L. Strom Cecilia Huang Zhiqiang Tan Stephen Crystal Mark Olfson James M. Wright |
author_facet | Tobias Gerhard T. Scott Stroup Christoph U. Correll Soko Setoguchi Brian L. Strom Cecilia Huang Zhiqiang Tan Stephen Crystal Mark Olfson James M. Wright |
author_sort | Tobias Gerhard |
collection | DOAJ |
description | Importance Randomized controlled trials have demonstrated increased all-cause mortality in elderly patients with dementia treated with newer antipsychotics. It is unknown whether this risk generalizes to non-elderly adults using newer antipsychotics as augmentation treatment for depression. Objective This study examined all-cause mortality risk of newer antipsychotic augmentation for adult depression. Design Population-based new-user/active comparator cohort study. Setting National healthcare claims data from the US Medicaid program from 2001–2010 linked to the National Death Index. Participants Non-elderly adults (25–64 years) diagnosed with depression who after ≥3 months of antidepressant monotherapy initiated either augmentation with a newer antipsychotic or with a second antidepressant. Patients with alternative indications for antipsychotic medications, such as schizophrenia, psychotic depression, or bipolar disorder, were excluded. Exposure Augmentation treatment for depression with a newer antipsychotic or with a second antidepressant. Main outcome All-cause mortality during study follow-up ascertained from the National Death Index. Results The analytic cohort included 39,582 patients (female = 78.5%, mean age = 44.5 years) who initiated augmentation with a newer antipsychotic (n = 22,410; 40% = quetiapine, 21% = risperidone, 17% = aripiprazole, 16% = olanzapine) or with a second antidepressant (n = 17,172). The median chlorpromazine equivalent starting dose for all newer antipsychotics was 68mg/d, increasing to 100 mg/d during follow-up. Altogether, 153 patients died during 13,328 person-years of follow-up (newer antipsychotic augmentation: n = 105, follow-up = 7,601 person-years, mortality rate = 138.1/10,000 person-years; antidepressant augmentation: n = 48, follow-up = 5,727 person-years, mortality rate = 83.8/10,000 person-years). An adjusted hazard ratio of 1.45 (95% confidence interval, 1.02 to 2.06) indicated increased all-cause mortality risk for newer antipsychotic augmentation compared to antidepressant augmentation (risk difference = 37.7 (95%CI, 1.7 to 88.8) per 10,000 person-years). Results were robust across several sensitivity analyses. Conclusion Augmentation with newer antipsychotics in non-elderly patients with depression was associated with increased mortality risk compared with adding a second antidepressant. Though these findings require replication and cannot prove causality, physicians managing adults with depression should be aware of this potential for increased mortality associated with newer antipsychotic augmentation. |
first_indexed | 2024-12-22T19:57:47Z |
format | Article |
id | doaj.art-edb702b8b8eb45c595e36bb9b81d03a9 |
institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-12-22T19:57:47Z |
publishDate | 2020-01-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS ONE |
spelling | doaj.art-edb702b8b8eb45c595e36bb9b81d03a92022-12-21T18:14:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01159Mortality risk of antipsychotic augmentation for adult depressionTobias GerhardT. Scott StroupChristoph U. CorrellSoko SetoguchiBrian L. StromCecilia HuangZhiqiang TanStephen CrystalMark OlfsonJames M. WrightImportance Randomized controlled trials have demonstrated increased all-cause mortality in elderly patients with dementia treated with newer antipsychotics. It is unknown whether this risk generalizes to non-elderly adults using newer antipsychotics as augmentation treatment for depression. Objective This study examined all-cause mortality risk of newer antipsychotic augmentation for adult depression. Design Population-based new-user/active comparator cohort study. Setting National healthcare claims data from the US Medicaid program from 2001–2010 linked to the National Death Index. Participants Non-elderly adults (25–64 years) diagnosed with depression who after ≥3 months of antidepressant monotherapy initiated either augmentation with a newer antipsychotic or with a second antidepressant. Patients with alternative indications for antipsychotic medications, such as schizophrenia, psychotic depression, or bipolar disorder, were excluded. Exposure Augmentation treatment for depression with a newer antipsychotic or with a second antidepressant. Main outcome All-cause mortality during study follow-up ascertained from the National Death Index. Results The analytic cohort included 39,582 patients (female = 78.5%, mean age = 44.5 years) who initiated augmentation with a newer antipsychotic (n = 22,410; 40% = quetiapine, 21% = risperidone, 17% = aripiprazole, 16% = olanzapine) or with a second antidepressant (n = 17,172). The median chlorpromazine equivalent starting dose for all newer antipsychotics was 68mg/d, increasing to 100 mg/d during follow-up. Altogether, 153 patients died during 13,328 person-years of follow-up (newer antipsychotic augmentation: n = 105, follow-up = 7,601 person-years, mortality rate = 138.1/10,000 person-years; antidepressant augmentation: n = 48, follow-up = 5,727 person-years, mortality rate = 83.8/10,000 person-years). An adjusted hazard ratio of 1.45 (95% confidence interval, 1.02 to 2.06) indicated increased all-cause mortality risk for newer antipsychotic augmentation compared to antidepressant augmentation (risk difference = 37.7 (95%CI, 1.7 to 88.8) per 10,000 person-years). Results were robust across several sensitivity analyses. Conclusion Augmentation with newer antipsychotics in non-elderly patients with depression was associated with increased mortality risk compared with adding a second antidepressant. Though these findings require replication and cannot prove causality, physicians managing adults with depression should be aware of this potential for increased mortality associated with newer antipsychotic augmentation.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526884/?tool=EBI |
spellingShingle | Tobias Gerhard T. Scott Stroup Christoph U. Correll Soko Setoguchi Brian L. Strom Cecilia Huang Zhiqiang Tan Stephen Crystal Mark Olfson James M. Wright Mortality risk of antipsychotic augmentation for adult depression PLoS ONE |
title | Mortality risk of antipsychotic augmentation for adult depression |
title_full | Mortality risk of antipsychotic augmentation for adult depression |
title_fullStr | Mortality risk of antipsychotic augmentation for adult depression |
title_full_unstemmed | Mortality risk of antipsychotic augmentation for adult depression |
title_short | Mortality risk of antipsychotic augmentation for adult depression |
title_sort | mortality risk of antipsychotic augmentation for adult depression |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526884/?tool=EBI |
work_keys_str_mv | AT tobiasgerhard mortalityriskofantipsychoticaugmentationforadultdepression AT tscottstroup mortalityriskofantipsychoticaugmentationforadultdepression AT christophucorrell mortalityriskofantipsychoticaugmentationforadultdepression AT sokosetoguchi mortalityriskofantipsychoticaugmentationforadultdepression AT brianlstrom mortalityriskofantipsychoticaugmentationforadultdepression AT ceciliahuang mortalityriskofantipsychoticaugmentationforadultdepression AT zhiqiangtan mortalityriskofantipsychoticaugmentationforadultdepression AT stephencrystal mortalityriskofantipsychoticaugmentationforadultdepression AT markolfson mortalityriskofantipsychoticaugmentationforadultdepression AT jamesmwright mortalityriskofantipsychoticaugmentationforadultdepression |