BACKGROUND/RATIONALE:
Veterans have high rates of depression. In 2007, 15% of the VA patient population received depression treatment (759,888 Veterans). Annual VA expenditures for depression exceed $3 billion. In addition to high costs, depression negatively affects quality of life and health outcomes, with preliminary evidence that depression may reduce life expectancy in veterans. Although research on the general US population indicates that depression may increase mortality risks, associations are poorly understood, and there has been no research on large healthcare systems, where mortality risks associated with depression could be addressed. Research examining whether and to what extent depression may influence mortality among VA patients is critical for VA health system efforts to reduce mortality risks.

OBJECTIVE(S):
The objectives of this study are to 1) examine the risks and causes of mortality associated with depression among VA patients, 2) characterize the impact of specific modifiable health behaviors (smoking, drinking, and obesity) on the relationships between depression and all-cause mortality, mortality from cardiovascular disease, and mortality from cancer and 3) examine associations between receipt of depression treatment and mortality.

The extension of our original study Aim 3 will consist of a pharmacosurveillance study of sudden cardiac event risks associated with use of commonly prescribed antidepressants.

Aim 3a. To evaluate prevalence of ventricular arrhythmia associated with antidepressant use.
Aim 3b. To evaluate prevalence of cardiac-related mortality associated with antidepressant use.

METHODS:
To achieve our objectives, we will create a new panel dataset with health and sociodemographic information on all VA service users nationwide (N~4,700,000) from FY03 followed for up to five years. We will conduct analyses with merged secondary data from existing data sources. These sources will include the VA's National Patient Care Database (NPCD) for inpatient and outpatient clinical data, health care utilization, and prescription medications, Medicare data for eligible patients, National Death Index (NDI) for mortality data, and the 2003 Survey of Healthcare Experiences of Patients (SHEP) for additional sociodemographic and health behavior information. We will use survival analysis techniques, specifically Cox regression models, as well as logistic regression analysis to examine the impact of depression on timing and causes of death in our VA patient cohort. We will examine the independent association of depression with death, as well as the impact of potential confounding factors, including medical and psychiatric comorbidity, health behaviors, and sociodemographic characteristics. In analyses using statistical methods to control for possible treatment selection biases, we will examine the impact of depression treatment on mortality.

FINDINGS/RESULTS:
In our sample of over 5 million patients who met study criteria, 15.5% had depression, and 2.6% of the sample died within one year of follow-up. Depression was associated with an increased risk of one-year all-cause mortality, even when after adjusting for age, sex, race, number of medical comorbidities, inpatient and outpatient visits in the prior year, other psychiatric diagnoses, substance use disorders, nicotine use, and VA facility-level characteristics (HR: 1.15, 95% CI: 1.12, 1.17). Increased risk of mortality associated with baseline depression was very similar for two and three year mortality. We also assessed mortality due to multiple additional causes of death. 2.24 (95% CI, 1.95 to 2.57) from suicide, and 2.01 (95% CI, 1.72 to 2.35) for death from Parkinson's disease, 1.52 (95% CI, 1.35 to 1.72) for death from Alzheimer's disease, 1.43 (95% CI, 1.30 to 1.56) for death from cerebrovascular disease, 1.37 (95% CI, 1.26 to 1.49) for death from unintentional injuries, 1.30 (95% CI, 1.22 to 1.39) for death from respiratory illness, 1.21 (95% CI, 1.17 to 1.25) for death from heart disease, 1.23 (95% CI, 1.13 to 1.35) for death from diabetes, and 1.23 (95% CI, 1.11 to 1.37) for death from influenza. Depression was moderately positively associated with death from nephritis and septicemia, and moderately negatively associated with cancer and liver disease. Depression was not associated with death associated with hypertension or assault after covariate adjustment. Finally, depression was moderately positively associated with death from all other causes of death. A patient with depression died on average almost five years earlier than a patient without depression.

We have completed the paper focusing on Aim 1 and are in the process of revising and resubmitting it for publication. The paper demonstrates depression increases risk of mortality from most major causes of death. We have completed analyses for Aims 2 and 3 and are working to prepare them for publication. Specifically, we are finding that antidepressant use is protective against mortality among VA patients with depression, and have conducted subanalyses by type of antidepressant (all of which are protective). Psychotherapy is also protective against mortality.

IMPACT:
In addition to being associated with psychiatric-related and injury-related causes of death, depression is associated with increased risk of death from several medical causes, independent of several major risk factors.

Implications for policy, delivery, or practice: Patients treated for a range of disorders should also be assessed and treated for depression when applicable. These findings highlight the need to better understand and prevent the multisystem consequences of depression.

Antidepressants and psychotherapy may decrease risks of mortality among depressed patients, even when accounting for depression severity.

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External Links for this Project

NIH Reporter

Grant Number: I01HX000475-01
Link: https://reporter.nih.gov/project-details/8002832

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PUBLICATIONS:

Journal Articles

1. Saczynski JS, Rosen AB, McCammon RJ, Zivin K, Andrade SE, Langa KM, Vijan S, Pirraglia PA, Briesacher BA. Antidepressant Use and Cognitive Decline: The Health and Retirement Study. The American journal of medicine. 2015 Jul 1; 128(7):739-46. [view]
2. Zivin K, Yosef M, Miller EM, Valenstein M, Duffy S, Kales HC, Vijan S, Kim HM. Associations between depression and all-cause and cause-specific risk of death: a retrospective cohort study in the Veterans Health Administration. Journal of psychosomatic research. 2015 Apr 1; 78(4):324-31. [view]
3. Teo AR, Choi H, Andrea SB, Valenstein M, Newsom JT, Dobscha SK, Zivin K. Does Mode of Contact with Different Types of Social Relationships Predict Depression in Older Adults? Evidence from a Nationally Representative Survey. Journal of the American Geriatrics Society. 2015 Oct 1; 63(10):2014-22. [view]
4. Zivin K, Ilgen MA, Pfeiffer PN, Welsh DE, McCarthy J, Valenstein M, Miller EM, Islam K, Kales HC. Early mortality and years of potential life lost among Veterans Affairs patients with depression. Psychiatric services (Washington, D.C.). 2012 Aug 1; 63(8):823-6. [view]
5. Zivin K, Pfeiffer PN, Bohnert AS, Ganoczy D, Blow FC, Nallamothu BK, Kales HC. Evaluation of the FDA warning against prescribing citalopram at doses exceeding 40 mg. The American journal of psychiatry. 2013 Jun 1; 170(6):642-50. [view]
6. Pfeiffer PN, Bohnert KM, Zivin K, Yosef M, Valenstein M, Aikens JE, Piette JD. Mobile health monitoring to characterize depression symptom trajectories in primary care. Journal of affective disorders. 2015 Mar 15; 174:281-6. [view]
7. Johnson-Lawrence VD, Szymanski BR, Zivin K, McCarthy JF, Valenstein M, Pfeiffer PN. Primary care-mental health integration programs in the veterans affairs health system serve a different patient population than specialty mental health clinics. The primary care companion for CNS disorders. 2012 May 17; 14(3). [view]
8. Abraham KM, Ganoczy D, Yosef M, Resnick SG, Zivin K. Receipt of employment services among Veterans Health Administration users with psychiatric diagnoses. Journal of rehabilitation research and development. 2014 Jun 1; 51(3):401-14. [view]
9. Leggett A, Clarke P, Zivin K, McCammon RJ, Elliott MR, Langa KM. Recent Improvements in Cognitive Functioning Among Older U.S. Adults: How Much Does Increasing Educational Attainment Explain?. The journals of gerontology. Series B, Psychological sciences and social sciences. 2019 Feb 15; 74(3):536-545. [view]
10. Zivin K, Campbell DG, Lanto AB, Chaney EF, Bolkan C, Bonner LM, Miller EM, Valenstein M, Waltz TJ, Rubenstein LV. Relationships between mood and employment over time among depressed VA primary care patients. General hospital psychiatry. 2012 Sep 1; 34(5):468-77. [view]
11. Leggett A, Kavanagh J, Zivin K, Chiang C, Kim HM, Kales HC. The Association Between Benzodiazepine Use and Depression Outcomes in Older Veterans. Journal of geriatric psychiatry and neurology. 2015 Dec 1; 28(4):281-7. [view]
12. Ross EL, Vijan S, Miller EM, Valenstein M, Zivin K. The Cost-Effectiveness of Cognitive Behavioral Therapy Versus Second-Generation Antidepressants for Initial Treatment of Major Depressive Disorder in the United States: A Decision Analytic Model. Annals of internal medicine. 2019 Dec 3; 171(11):785-795. [view]
13. Pfeiffer PN, Kim HM, Ganoczy D, Zivin K, Valenstein M. Treatment-resistant depression and risk of suicide. Suicide & Life-Threatening Behavior. 2013 Aug 1; 43(4):356-65. [view]
14. Zivin K, Pirraglia PA, McCammon RJ, Langa KM, Vijan S. Trends in depressive symptom burden among older adults in the United States from 1998 to 2008. Journal of general internal medicine. 2013 Dec 1; 28(12):1611-9. [view]
15. Waltz TJ, Campbell DG, Kirchner JE, Lombardero A, Bolkan C, Zivin K, Lanto AB, Chaney EF, Rubenstein LV. Veterans with depression in primary care: provider preferences, matching, and care satisfaction. Families, systems & health : the journal of collaborative family healthcare. 2014 Dec 1; 32(4):367-77. [view]

Journal Other

1. Zivin K, Pfeiffer PN, Bohnert AS, Ganoczy D, Blow FC, Nallamothu BK, Kales HC. Safety of high-dosage citalopram. The American journal of psychiatry. 2014 Jan 1; 171(1):20-2. [view]

Conference Presentations

1. Zivin K. Depression treatment: warnings and outcomes. Examples from the VA health system. Paper presented at: Northwestern University Institute for Public Health and Medicine Grand Rounds; 2013 Feb 28; Chicago, IL. [view]
2. Zivin K. Depression, comorbidity, and mortality: perspectives from the VA health system. Paper presented at: University of California San Diego Grand Rounds; 2012 Jan 9; San Diego, CA. [view]
3. Zivin K. Methodological considerations associated with evaluating the relationship between depression and mortality. Paper presented at: University of Pennsylvania Perelman School of Medicine Center for Clinical Epidemiology and Biostatistics Seminar; 2012 Mar 15; Philadelphia, PA. [view]
4. Zivin K. Outpatient collaborative care for depression: Primary Care - Mental Health Integration in the VA Health System. Paper presented at: VA Philadelphia VAMC Grand Rounds; 2012 Mar 14; Philadelphia, PA. [view]
5. Zivin K. Psychopharmacological treatment of depression and anxiety. Paper presented at: American Psychiatric Association Annual Meeting; 2014 May 5; New York, NY. [view]
6. Zivin K, Pfeiffer PN, Ilgen MA, Welsh DE, McCarthy JF, Valenstein MT, Miller EM, Kales HC. Years of potential life lost associated with depression among Veterans. Poster session presented at: American Association for Geriatric Psychiatry Annual Meeting; 2012 Mar 16; Washington, DC. [view]

DRA: Mental, Cognitive and Behavioral Disorders
DRE: Treatment - Observational
Keywords: none
MeSH Terms: none