ArticlePloS one2020
Mortality risk of antipsychotic augmentation for adult depression.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Relative effectiveness of antidepressant treatments in treatment-resistant depression: a systematic review and network meta-analysis of randomized controlled trials.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Pooled it
- PRO-DEMET Randomized Controlled Trial on Probiotics in Depression-Pilot Study Results.Nutrients · 2023Trial
- Antidepressant therapeutic strategies and health care utilization in patients with depression.Journal of managed care & specialty pharmacy · 2024Article
- Association of Antipsychotic Polypharmacy and Two-Year All-Cause Mortality: A Population-Based Cohort Study of 33,221 Italian Continuous Users.Journal of clinical medicine · 2024Article
- Antipsychotics and the risk of diabetes and death among adults with serious mental illnesses.Psychological medicine · 2023Article
- The Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD): Changes in Preferred Treatment Strategies and Medications over 20 Years and Five Editions.Journal of clinical medicine · 2023Article
- An umbrella review on the use of antipsychotics in anxiety disorders: A registered report protocol.PloS one · 2022Article
- Probiotics as a Treatment for "Metabolic Depression"? A Rationale for Future Studies.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Use of antipsychotics in Denmark 1997-2018: a nation-wide drug utilisation study with focus on off-label use and associated diagnoses.Epidemiology and psychiatric sciences · 2021Article
- Adiposity in Depression or Depression in Adiposity? The Role of Immune-Inflammatory-Microbial Overlap.Life (Basel, Switzerland) · 2021Review
- Perspectives in Psychopharmacology.Focus (American Psychiatric Publishing) · 2021Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
importanceRandomized 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.
objectiveThis study examined all-cause mortality risk of newer antipsychotic augmentation for adult depression.
designPopulation-based new-user/active comparator cohort study.
settingNational healthcare claims data from the US Medicaid program from 2001-2010 linked to the National Death Index.
participantsNon-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.
resultsThe 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.
conclusionAugmentation 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.
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