Mortality risk of antipsychotic augmentation for adult depression.
<h4>Importance</h4>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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0239206 |
| _version_ | 1819115087355445248 |
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| author | Tobias Gerhard T Scott Stroup Christoph U Correll Soko Setoguchi Brian L Strom Cecilia Huang Zhiqiang Tan Stephen Crystal Mark Olfson |
| author_facet | Tobias Gerhard T Scott Stroup Christoph U Correll Soko Setoguchi Brian L Strom Cecilia Huang Zhiqiang Tan Stephen Crystal Mark Olfson |
| author_sort | Tobias Gerhard |
| collection | DOAJ |
| description | <h4>Importance</h4>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.<h4>Objective</h4>This study examined all-cause mortality risk of newer antipsychotic augmentation for adult depression.<h4>Design</h4>Population-based new-user/active comparator cohort study.<h4>Setting</h4>National healthcare claims data from the US Medicaid program from 2001-2010 linked to the National Death Index.<h4>Participants</h4>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.<h4>Exposure</h4>Augmentation treatment for depression with a newer antipsychotic or with a second antidepressant.<h4>Main outcome</h4>All-cause mortality during study follow-up ascertained from the National Death Index.<h4>Results</h4>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.<h4>Conclusion</h4>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 | 2024-12-22T04:55:37Z |
| format | Article |
| id | doaj.art-fd150d19dd1246b3a8485d7a948c8635 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T04:55:37Z |
| publishDate | 2020-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-fd150d19dd1246b3a8485d7a948c86352022-12-21T18:38:23ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01159e023920610.1371/journal.pone.0239206Mortality risk of antipsychotic augmentation for adult depression.Tobias GerhardT Scott StroupChristoph U CorrellSoko SetoguchiBrian L StromCecilia HuangZhiqiang TanStephen CrystalMark Olfson<h4>Importance</h4>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.<h4>Objective</h4>This study examined all-cause mortality risk of newer antipsychotic augmentation for adult depression.<h4>Design</h4>Population-based new-user/active comparator cohort study.<h4>Setting</h4>National healthcare claims data from the US Medicaid program from 2001-2010 linked to the National Death Index.<h4>Participants</h4>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.<h4>Exposure</h4>Augmentation treatment for depression with a newer antipsychotic or with a second antidepressant.<h4>Main outcome</h4>All-cause mortality during study follow-up ascertained from the National Death Index.<h4>Results</h4>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.<h4>Conclusion</h4>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://doi.org/10.1371/journal.pone.0239206 |
| spellingShingle | Tobias Gerhard T Scott Stroup Christoph U Correll Soko Setoguchi Brian L Strom Cecilia Huang Zhiqiang Tan Stephen Crystal Mark Olfson 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://doi.org/10.1371/journal.pone.0239206 |
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