Androgen deprivation therapy linked to depression



Men on androgen deprivation therapy for prostate cancer are at significantly increased risk for depression, a risk that increases with duration of therapy, investigators report.

A review of Surveillance, Epidemiology, and End Results (SEER) Medicare data on nearly 79,000 men older than 65 years with a diagnosis of prostate cancer showed that those who received androgen deprivation therapy (ADT) had a 23% increased risk for depression, compared with men who were not on ADT, reported Kathryn T. Dinh of Harvard Medical School, Boston, and her colleagues.

“We observed a significantly increased risk of depression and inpatient psychiatric treatment in men treated with ADT for prostate cancer, as well as a duration-response effect such that more ADT was linked to an increasing risk of depression and inpatient and outpatient psychiatric treatment. The possible psychiatric effects of ADT should be recognized by physicians and discussed with patients before initiating treatment,” they wrote (J Clin Oncol. 2016 Apr 11. doi: 10.1200/JCO.2015.64.1969).

Although ADT has been identified in some studies as a risk factor for clinical depression, evidence for such a relationship has been spotty, the investigators said, prompting them to conduct a population-based retrospective study to get a better handle on the issue.

They reviewed SEER Medicare data on 78,552 men older than 65 years with a diagnosis of stage I-III prostate cancer treated with ADT from 1992 through 2006, excluding from the sample those patients who had a psychiatric diagnosis within the past 12 months.

Ms. Dinh and her associates found that the 33,882 patients (43%) who received ADT had a significantly higher 3-year cumulative incidence of depression than patients who did not have ADT (7.1% vs. 5.2%, P less than .001), and a significantly higher proportion had either inpatient psychiatric treatment (2.8% vs. 1.9%, P less than .001) or outpatient psychiatric therapy (3.4% vs. 2.5%, P less than .001).

In proportional hazard models controlling for demographic and clinical factors, receipt of ADT was associated with adjusted hazard ratios of 1.23 for depression and 1.29 (P less than .001 for both) for inpatient psychiatric treatment. There was no significant increase in risk for outpatient psychiatric treatment in this analysis, however.

In addition, the longer patients that were on ADT, the greater the risk for depression. The risk of depression was 12% for patients treated for 6 months or less, 26% for those on ADT for 7-11 months, and 37% for those on ADT for at least 1 year.

“The impact of ADT on depression may plausibly occur via deregulation of neurochemicals, such as serotonin, in addition to the well-described physical effects,” Ms. Dinh and her associates wrote.

Side effects of ADT that can impair quality of life also may contribute to clinical depression, they noted.

The study was supported by charitable grants and internal institutional sources. One investigator reported consulting or advisory roles with Medivation, GenomeDx, and Ferring. Three of the other ten coauthors also reported financial disclosures.

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