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Mortality risk of antipsychotic augmentation for adult depression.

ABSTRACT: 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.

SUBMITTER: Gerhard T

PROVIDER: S-EPMC7526884 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Mortality risk of antipsychotic augmentation for adult depression.

Gerhard Tobias T Stroup T Scott TS Correll Christoph U CU Setoguchi Soko S Strom Brian L BL Huang Cecilia C Tan Zhiqiang Z Crystal Stephen S Olfson Mark M

PloS one 20200930 9

<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>Setti ...[more]

PMID: 32997687

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Project description:ObjectiveTo characterize the role of antipsychotic medications in the community treatment of adult depression.MethodsWe identified adults (aged 18-64 years) with new episodes of depression treatment (ICD-9-CM 296.2, 296.3, 300.4, or 311) in US national Medicaid data (2001-2010). Patients with alternative ICD-9-CM antipsychotic indications, such as schizophrenia or bipolar disorder, were excluded. Each patient was followed for at least 1 year to characterize antipsychotic and antidepressant treatment and emerging alternative antipsychotic indications. For patients without alternative indications through day 45 following start of antipsychotic treatment, antipsychotics were considered to be intended for treatment of depression. Among this group, we determined whether antipsychotic initiation was preceded by minimally adequate treatment with antidepressants, defined as active antidepressant treatment for ≥ 31 days prior to and including the day of antipsychotic initiation.ResultsWithin 1 year following onset, 14.0% of patients started an antipsychotic medication. A total of 41.3% of antipsychotic initiators developed an antipsychotic indication other than depression through day 45 following antipsychotic initiation, most often bipolar disorder or depression with psychotic features. The remaining 58.7% of antipsychotic initiators presumably started antipsychotics for nonpsychotic depression. Of these, 71.3% did not have minimally adequate antidepressant treatment prior to starting the antipsychotic medication.ConclusionAntipsychotic medications are used in approximately 1 in 7 patients with a new episode of depression. For 1 in 12 patients, the antipsychotic was considered to be intended for nonpsychotic depression. Almost three-quarters of these patients did not receive minimally adequate treatment with antidepressants prior to antipsychotic initiation. This pattern suggests potentially inappropriate and premature initiation of a drug class with substantial adverse effects and medical risks.

Project description:ImportanceAs many as 60% of patients with Parkinson disease (PD) experience psychosis, 80% develop dementia, and the use of antipsychotics (APs) in the population with PD is common. The use of APs by patients with dementia in the general population is associated with increased mortality, but whether this risk extends to patients with PD remains unknown.ObjectiveTo determine whether AP use in patients with PD is associated with increased mortality.Design, setting, and participantsThis retrospective matched-cohort study used data from a Veterans Health Administration database from fiscal years 1999 to 2010 to examine the risk associated with AP use in a cohort of patients with idiopathic PD and recent stable physical health. The rates of 180-day mortality were compared in 7877 patients initiating AP therapy and 7877 patients who did not initiate AP therapy (matched for age ±2.5 years, sex, race, index year, presence and duration of dementia, PD duration, delirium, hospitalization, Charlson Comorbidity Index, and new nonpsychiatric medications). Data were analyzed from October 19, 2012, to September 21, 2015.Main outcomes and measuresMortality rates at 180 days in those patients who initiated AP therapy compared with matched patients who did not use APs. Cox proportional hazards regression models were used with intent-to-treat (ITT) and exposure-only analyses.ResultsThe study population included 7877 matched pairs of patients with PD (65 women [0.8%] and 7812 men [99.2%] in each cohort; mean [SD] age, 76.3 [7.7] years for those who initiated AP therapy and 76.4 [7.6] years for those who did not). Antipsychotic use was associated with more than twice the hazard ratio (HR) of death compared with nonuse (ITT HR, 2.35; 95% CI, 2.08-2.66; P < .001). The HR was significantly higher for patients who used typical vs atypical APs (ITT HR, 1.54; 95% CI, 1.24-1.91; P < .001). Among the atypical APs used, HRs relative to nonuse of APs in descending order were 2.79 (95% CI, 1.97-3.96) for olanzapine, 2.46 (95% CI, 1.94-3.12) for risperidone, and 2.16 (95% CI, 1.88-2.48) for quetiapine fumarate.Conclusions and relevanceUse of APs is associated with a significantly increased mortality risk in patients with PD, after adjusting for measurable confounders. This finding highlights the need for cautious use of APs in patients with PD. Future studies should examine the role of nonpharmacologic strategies in managing psychosis in PD. In addition, new pharmacologic treatments that do not increase mortality in patients with neurodegenerative diseases need to be developed.

Project description:ContextDepression and diabetes mellitus have been associated with an increased risk of all-cause and cardiovascular disease (CVD) mortality. However, data evaluating the joint effects of these 2 conditions on mortality are sparse.ObjectivesTo evaluate the individual and joint effects of depression and diabetes on all-cause and CVD mortality rate.DesignProspective cohort study.SettingThe 11 states of the Nurses' Health Study.ParticipantsA total of 78 282 women who participated in the Nurses' Health Study aged 54 to 79 years at baseline in 2000 were followed up until 2006. Depression was defined as having self-reported diagnosed depression, treatment with antidepressant medications, or a score indicating severe depressive symptoms (ie, a 5-item Mental Health Index score ≤52). Self-reported type 2 diabetes was confirmed using a supplementary questionnaire.Main outcome measuresAll-cause and CVD-specific mortality rate.ResultsDuring 6 years of follow-up (433 066 person-years), 4654 deaths were documented, including 979 deaths from CVD. Compared with participants without either condition, the age-adjusted relative risks (RRs) (95% confidence interval) for all-cause mortality were 1.76 (1.64-1.89) for women with depression only, 1.71 (1.54-1.89) for individuals with diabetes only, and 3.11 (2.70-3.58) for women with both conditions. The corresponding age-adjusted RRs of CVD mortality were 1.81 (1.54-2.13), 2.67 (2.20-3.23), and 5.38 (4.19-6.91), respectively. These associations were attenuated after multivariate adjustment for other demographic variables, body mass index, smoking status, alcohol intake, physical activity, and major comorbidities (including hypertension, hypercholesterolemia, heart diseases, stroke, and cancer) but remained significant, with the highest RRs for all-cause and CVD mortality found in those with both conditions (2.07 [1.79-2.40] and 2.72 [2.09-3.54], respectively). Furthermore, the combination of depression with a long duration of diabetes mellitus (ie, >10 years) or insulin therapy was associated with a particularly higher risk of CVD mortality after multivariate adjustment (RRs, 3.22 and 4.90, respectively).ConclusionsDepression and diabetes are associated with a significantly increased risk of all-cause and CVD mortality rate. The coexistence of these conditions identifies women at particularly high risk.

Project description:BackgroundThe benefits and risks of augmenting or switching antidepressants in older adults with treatment-resistant depression have not been extensively studied.MethodsWe conducted a two-step, open-label trial involving adults 60 years of age or older with treatment-resistant depression. In step 1, patients were randomly assigned in a 1:1:1 ratio to augmentation of existing antidepressant medication with aripiprazole, augmentation with bupropion, or a switch from existing antidepressant medication to bupropion. Patients who did not benefit from or were ineligible for step 1 were randomly assigned in step 2 in a 1:1 ratio to augmentation with lithium or a switch to nortriptyline. Each step lasted approximately 10 weeks. The primary outcome was the change from baseline in psychological well-being, assessed with the National Institutes of Health Toolbox Positive Affect and General Life Satisfaction subscales (population mean, 50; higher scores indicate greater well-being). A secondary outcome was remission of depression.ResultsIn step 1, a total of 619 patients were enrolled; 211 were assigned to aripiprazole augmentation, 206 to bupropion augmentation, and 202 to a switch to bupropion. Well-being scores improved by 4.83 points, 4.33 points, and 2.04 points, respectively. The difference between the aripiprazole-augmentation group and the switch-to-bupropion group was 2.79 points (95% CI, 0.56 to 5.02; P = 0.014, with a prespecified threshold P value of 0.017); the between-group differences were not significant for aripiprazole augmentation versus bupropion augmentation or for bupropion augmentation versus a switch to bupropion. Remission occurred in 28.9% of patients in the aripiprazole-augmentation group, 28.2% in the bupropion-augmentation group, and 19.3% in the switch-to-bupropion group. The rate of falls was highest with bupropion augmentation. In step 2, a total of 248 patients were enrolled; 127 were assigned to lithium augmentation and 121 to a switch to nortriptyline. Well-being scores improved by 3.17 points and 2.18 points, respectively (difference, 0.99; 95% CI, -1.92 to 3.91). Remission occurred in 18.9% of patients in the lithium-augmentation group and 21.5% in the switch-to-nortriptyline group; rates of falling were similar in the two groups.ConclusionsIn older adults with treatment-resistant depression, augmentation of existing antidepressants with aripiprazole improved well-being significantly more over 10 weeks than a switch to bupropion and was associated with a numerically higher incidence of remission. Among patients in whom augmentation or a switch to bupropion failed, changes in well-being and the occurrence of remission with lithium augmentation or a switch to nortriptyline were similar. (Funded by the Patient-Centered Outcomes Research Institute; OPTIMUM ClinicalTrials.gov number, NCT02960763.).

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Mortality risk of antipsychotic augmentation for adult depression.

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Mortality risk of antipsychotic augmentation for adult depression.

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