April 20, 2019
3 min read

ADT may increase depression risk among men with prostate cancer

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Men with prostate cancer who underwent androgen deprivation therapy with definitive radiation therapy demonstrated increased risk for depression and use of outpatient psychiatric services compared with men who received radiation therapy alone, according to study results published in Cancer.

This finding may support evidence regarding the long-term psychiatric health risks of ADT in the treatment of prostate cancer, according to researchers.

“There is conflicting evidence on the association of ADT with clinical depression. Although some studies have reported an association between ADT and depression, others have not,” Rishi Deka, PhD, postdoctoral researcher in the department of radiation oncology and applied sciences at University of California, San Diego School of Medicine, and colleagues wrote. “This inconsistency is likely due to methodological limitations that existed in many of these studies. This indicates a lack of appropriate control groups, small sample sizes, inadequate power and the use of cross-sectional study designs. In addition, these studies analyzed very heterogenous populations, including patients with localized metastatic disease, curative and palliative treatment intent, and ADT use in the upfront or recurrent setting.”

In the retrospective, observational cohort study, Deka and colleagues identified 39,965 veterans (median age, 66.8 years; 68.6% white) diagnosed with prostate cancer in the U.S. Department of Veterans Affairs health care system between Jan. 1, 2001 and Oct. 31, 2015. All the men received definitive radiation therapy, and 14,843 of them also initiated ADT within 1 year of prostate cancer diagnosis (median duration, 243 days; interquartile range, 90-570).

Men who underwent ADT were more likely to be older, nonwhite, from lower-income regions, and from the South or Northeast than men who received radiation therapy only.

They also had higher Gleason scores, clinical T stages and PSA levels and higher rates of antidepressant use and alcohol and substance abuse than non-ADT users.

New development of depression, from the date of the veteran’s prostate cancer diagnosis to his last health care encounter or the end of the study period, served as the study’s primary endpoint. Use of outpatient psychiatric service use of inpatient psychiatric services and suicide served as secondary endpoints.

Researchers followed the all the men for a median of 6.8 years, and 9,341 of them for a minimum of 10 years.

During follow-up, 934 men received a new diagnosis of depression, 7,825 used outpatient psychiatric services, 358 used inpatient psychiatric services and 54 committed suicide.

At 10 years, researchers observed cumulative incidence of 3.5% for depression (349 events for ADT users vs. 313 events for non-ADT users) and 27.5% for outpatient psychiatric use (4,429 events vs. 3,260 events; P < .05 for both). Cumulative incidence of inpatient psychiatric use at 10 years was 1.2%, but the difference between the cohorts was not statistically significant.


A multivariable competing risks regression model revealed correlations between ADT and the onset of depression (subdistribution HR [SHR] = 1.5; 95% CI, 1.32-1.71) and use of outpatient psychiatric services (SHR = 1.21; 95% CI, 1.16-1.27). Other predictors of outpatient psychiatric use included higher Charlson Comorbidity Index score, African-American race, use of a serotonin reuptake inhibitor, serotonin modulator or tricyclic antidepressants, atypical antidepressant use, substance abuse and cigarette use.

ADT did not appear associated with inpatient psychiatric use (SHR = 1.21; 95% CI, 0.98-1.51) or suicide (SHR = 0.93; 95% CI, 0.53-1.62).

The researchers acknowledged study limitations, noting that the results are most generalizable to patients treated with radiation therapy, the study population did not include patients with recurrent or metastatic disease, and that the determination of depression was made through ICD-9 codes.

ASCO offers a guideline for the screening, evaluation and treatment of depression in patients with cancer, which clinicians may use —along with other tools — to assess patients at diagnosis and regularly during treatment, Laura C. Polacek, BA, and Christian J. Nelson, PhD, of the department of psychiatry and behavioral services at Memorial Sloan Kettering Cancer Center, wrote in a related editorial.

“Although research surrounding depression, aging and cancer continues, there is no doubt that the phenomenology and diagnosis of depression in patients with cancer, and those with prostate cancer specifically, are complicated,” Polacek and Nelson wrote. “As research such as that of Deka [and colleagues] continues to provide robust support for the causal relationship between ADT use and depression in patients with prostate cancer, it is imperative that clinicians be vigilant in their screening for and treatment of depression in this population.” – by Jennifer Byrne

Disclosures: The researchers and editorial authors report no relevant financial disclosures.