Androgen deprivation therapy associated with increased risk of depression in elderly prostate cancer patients
Elderly patients on androgen deprivation therapy (ADT) as part of prostate cancer treatment may be at an increased risk of depression, a recent study states.
Men who received ADT had a higher 3-year cumulative incidence of depression (7.1 vs 5.2 percent), as well as a higher incidence of inpatient (2.8 vs 1.9 percent) and outpatient (3.4 vs 2.5 percent) psychiatric treatment (p<0.001 for all endpoints) compared to men who did not receive ADT. [J Clin Oncol 2016;doi:10.1200/JCO.2015.64.1969]
Men who received ADT also had elevated risks of depression (adjusted hazard ratio [aHR], 1.23, 95 percent CI, 1.15-1.31; p<0.001) and inpatient psychiatric treatment (aHR, 1.29, 95 percent CI, 1.17-1.43; p<0.001). The 7 percent increased risk of outpatient psychiatric treatment was insignificant (p=0.17).
The risk of depression also increased with duration of treatment (aHR, 1.12, 95 percent CI, 1.03-1.21 for ≤6 months of treatment; aHR, 1.26, 95 percent CI, 1.15-1.39 for 7 to 11 months of treatment; and aHR, 1.37, 95 percent CI, 1.26-1.49 for ≥12 months of treatment; p<0.001 for all).
The risk of inpatient psychiatric treatment also increased with treatment duration (aHR, 1.16, 95 percent CI, 1.02-1.32 for ≤6 months of treatment; aHR, 1.28, 95 percent CI, 1.10-1.50 for 7 to 11 months of treatment; and aHR, 1.47, 95 percent CI, 1.29-1.68 for ≥12 months of treatment; p<0.001 for all). The increase in risk of outpatient psychiatric treatment was more subtle with a 3 percent lower risk at ≤6 months of treatment to a 3 percent higher risk for 7 to 11 months treatment, and a 20 percent higher risk for ≥12 months of treatment (p=0.04).
“The association of ADT with psychiatric treatment provides further evidence that ADT may have a clinically significant effect on psychiatric health,” said the study authors.
Study participants were 78,552 men aged ≥66 years diagnosed with stage I to III prostate cancer from 1992-2006. Of these, 43 percent (n=33,882) had been administered ADT within 6 months of cancer diagnosis, 6 percent of whom underwent radical prostatectomy plus ADT, 64.9 percent radiation therapy plus ADT, and 29.1 percent ADT only.
“The potential benefits of ADT must be weighed against the potential harms, including increased depression risk,” said the authors, who advocated for the judicious use of ADT in order to avoid adverse effects.
As the subject pool was limited to older patients, the authors acknowledged that the results may not extend to younger men. They also recommended further research to identify which groups of patients would be most susceptible to ADT-related depression and interventions to mitigate this risk.
The results of this study add to previous ones that have demonstrated a link between ADT and depression. [Urol Oncol 2013;31:352-358; Psychooncology 2015;24:472-477] Studies have also demonstrated associations between ADT and low bone mineral density, increased insulin resistance, weight gain, decreased muscle mass and libido, and fatigue. [Eur Urol 2015;67:825-836]
“ADT is the first line of treatment for prostate cancer that has metastasized, ie, stage IV prostate cancer,” said Dr. Ronny Tan, director of andrology, Department of Urology, Tan Tock Seng Hospital.
“ADT makes a man hypogonadal. Hypogonadism is known to cause depression. The diagnosis of cancer by itself will make the man depressed and ADT can worsen that,” said Tan.
Family support is important for patients who are dealing with depression, and the main caregivers as well as the patient should be advised regarding these potential problems prior to the start of ADT, said Tan. “Cancer support group activities also give the patient both moral and emotional support,” he said.