An analysis of data from more than 30,000 men with prostate cancer revealed that those who took the second-generation drugs had more than twice the risk of developing depression, researchers report in JAMA Network Open.
"Men taking second-generation antiandrogens may be at a significantly increased risk of depression, in addition to that already associated with a cancer diagnosis, therefore patients and healthcare providers should be particularly proactive in identifying and treating depression in this patient population," said Dr. Kevin Nead, an assistant professor in the departments of epidemiology and radiology at the University of Texas MD Cancer Center in Houston.
That doesn't mean doctors should steer clear of these medications, Dr. Nead told Reuters Health by email.
"Second-generation antiandrogens are highly effective, life-extending medications, and we do not believe our findings suggest that they should be avoided in any patients with prostate cancer," he added. "The ideal patient population to utilize second-generation antiandrogens is a developing and active area of research. Traditionally they have been utilized in more-advanced cases of prostate cancer when first-line therapies are no longer effective. However, second-generation antiandrogens are highly effective and are increasingly being used as first-line therapy."
To take a closer look at the possibility that these medications might be tied to a higher risk of depression in prostate cancer patients, Dr. Nead and his team turned to data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER)-Medicare and the Texas Cancer Registry (TCR)-Medicare linked databases.
In their analysis, the researchers included men with a first primary prostate cancer diagnosis of localized, regional, or distant stage at age 66 or older from 2011 through 2015. None had a second cancer appear within 12 months. The patients all had continuous Medicare Parts A, B and D coverage, without HMO enrollment, from 12 months before until six months after diagnoses.
They excluded men from the study who received any form of hormone therapy before their prostate cancer diagnosis, those diagnosed with depression from 12 months before through six months after their cancer diagnosis, and those who did not survive at least six months after their cancer diagnosis.
The analysis was based on more than 30,000 patients (38% aged 66-70 years; 75% white), among whom, 17,710 received no hormone therapy, 11,311 who received traditional hormone therapy only, and 1,048 received a second-generation antiandrogen.
Patients who received a second-generation antiandrogen were more likely to be older and to present with advanced disease.
When the researchers performed a multivariable Cox proportional hazards analysis, they found men on a second-generation antiandrogen had 2.15 times the hazard of depression compared with men not on hormone therapy (P<0.001) and 2.26 times compared with those on traditional hormone therapy (P<0.001), including specifically among those with metastatic disease at diagnosis (hazard ratio, 2.40; P=0.002).
"Depression is common in patients with cancer and is associated with increased mortality in patients with prostate cancer," Dr. Nead said. "Patients being treated with second-generation antiandrogens have regular healthcare exposure, and early depression screening and treatment are feasible interventions that could greatly improve their quality of life and clinical outcomes."
"Depression has been found to be associated with worse outcomes in oncologic patients, increasing their risk of mortality," said Dr. Adriana Pedraza, a urologic oncology fellow at the Mount Sinai Health System in New York City. "Given the growing use of second-generation antiandrogen (AAs), especially in patients with metastatic prostate cancer, data on adverse effects in this setting are needed."
"This is a well-written paper that explores the association between the use of such medications and depression compared to the standard androgen-deprivation therapy (ADT), which is already known to be linked to an increased risk of depression and cognitive decline," Dr. Pedraza told Reuters Health by email. "Although patients included in the second-generation AA group were older and had more advanced stages of prostate cancer, this study showed a statistically significant association between the incidence of depression and the use of second-generation AA vs. standard ADT and no ADT."
There are limitations related to the retrospective nature of the analysis, as well as confounding factors in the baseline characteristics of each group, Dr. Pedraza said. "However, the study proposes an important hypothesis that warrants further investigation in prospective trials."
SOURCE: https://bit.ly/3sJcC3G JAMA Network Open, online December 23, 2021.
By Linda Carroll
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