Major Depression and Varicella ZV

Varicella Zoster Virus–Specific Immune Responses to a Herpes Zoster Vaccine in Elderly Recipients With Major Depression and the Impact of Antidepressant Medications

1. Michael R. Irwin1, 
2. Myron J. Levin2, 
3. Mark L. Laudenslager2, 
4. Richard Olmstead1,
5. Anne Lucko3, 
6. Nancy Lang2, 
7. Carmen Carrillo1, 
8. Harold A. Stanley3,
9. Michael J. Caulfield4, 
10. Adriana Weinberg2, 
11. Ivan S. F. Chan4, 
12. Jim Clair4,
13. Jeff G. Smith4, 
14. R. D. Marchese4, 
15. Heather M. Williams3, 
16. Danielle J. Beck3,
17. Patricia T. McCook3, 
18. Jane H. Zhang5, 
19. Gary Johnson5, and 
20. Michael N. Oxman3,6

+Author Affiliations

1. ¹Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience, University of California, Los Angeles
2. ²University of Colorado Denver School of Medicine, Aurora
3. ³Department of Veterans Affairs San Diego Healthcare System, San Diego, California
4. ⁴Merck, Sharp, and Dohme Corp, Whitehouse Station, New Jersey
5. ⁵Veterans Affairs Cooperative Studies Program Coordinating Center, West Haven, Connecticut
6. ⁶Department of Medicine University of California, San Diego

1. Correspondence: Michael R. Irwin, MD, Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience, 300 UCLA Medical Plaza, Suite 3109, Los Angeles, CA 90095-7057 (mirwin1@ucla.edu).

Abstract

Background. The Depression Substudy of the Shingles Prevention Study (SPS) was designed to evaluate the association between major depression and immune responses to a high-titer live attenuated varicella zoster virus (VZV) vaccine (zoster vaccine), which boosts cell-mediated immunity (CMI) to VZV and decreases the incidence and severity of herpes zoster (HZ). The Depression Substudy was a 2-year longitudinal cohort study in 92 community-dwelling adults ≥60 years of age who were enrolled in the SPS, a large, double-blind, placebo-controlled Veterans Affairs Cooperative zoster vaccine efficacy study.

Methods. Forty subjects with major depressive disorder, stratified by use of antidepressant medications, and 52 age- and sex-matched controls with no history of depression or other mental illness had their VZV-CMI measured prior to vaccination with zoster vaccine or placebo and at 6 weeks, 1 year, and 2 years postvaccination.

Results. Depressed subjects who were not treated with antidepressant medications had lower levels of VZV-CMI following administration of zoster vaccine than nondepressed controls or depressed subjects receiving antidepressants even when antidepressant medications failed to alter depressive symptom severity (P < .005). Similar results were obtained taking into account the time-varying status of depression and use of antidepressant medications, as well as changes in depressive symptoms, during the postvaccination period.

Conclusions. Depressed patients have diminished VZV-CMI responses to zoster vaccine, and treatment with antidepressant medication is associated with normalization of these responses. Because higher levels of VZV-CMI correlate with lower risk and severity of HZ, untreated depression may increase the risk and severity of HZ and reduce the efficacy of zoster vaccine.