Neuropsychiatric Impact of Androgen Deprivation Therapy in Patients with Prostate Cancer: Current Evidence and Recommendations for the Clinician

Abstract

Context: Although substantial literature examining the neuropsychiatric consequences of androgen deprivation therapy (ADT) exists, there are no clinical guidelines to inform providers about the specific risk of depression, suicide, and dementia for prostate cancer patients receiving chronic ADT.

Objective: To evaluate the strength of the evidence and interpret the literature describing the association between ADT and psychological outcomes in men with prostate cancer.

Evidence acquisition: NIH/NCBI PubMed database, EMBASE, and PsychINFO were searched for articles published indexed through December 16, 2019. Results from a total of 48 recent and highly relevant articles are summarized here.

Evidence synthesis: ADT increased the risk of depression (relative risk [RR] 1.51, p = 0.0002), which in turn magnifies the impact of ADT-related side effects on masculine identity. ADT may be associated with increased risk of cognitive impairment, including the risk of Alzheimer's dementia in American population-based cohorts and the risk of all-cause dementia in non-American cohorts (RR 1.45, p = 0.024). Statin use and higher levels of physical activity may be protective against ADT-associated dementia.

Conclusions: ADT increases the risk of worsening and incident depression, and may increase the risk of dementia in men with prostate cancer. Brief baseline mood and cognitive screening assessments, with re-evaluation at 6-12 mo is strongly recommended when initiating ADT. Patients exhibiting new or worsening symptoms of depression or dementia may benefit from referral for formal evaluation and possible treatment.

Patient summary: Patients initiating androgen deprivation therapy (ADT) should have brief baseline mood and cognitive screening assessments, with re-evaluation at least 6-12 mo after initiating therapy. All patients starting ADT should be counseled regarding possible neuropsychiatric side effects, and prescribers should counsel patients regarding the potential negative sexual side effects of antidepressant medications before prescribing them. Patients exhibiting new or worsening symptoms of depression or dementia may benefit from referral for formal evaluation and possible treatment.

Take home message: Androgen deprivation therapy (ADT) increases the risk of depression, which in turn magnifies the impact of ADT-related side effects on masculine identity and psychological distress in men with prostate cancer. ADT may be associated with an increased risk of cognitive impairment.

Keywords: Androgen deprivation therapy; Dementia; Depression; Neuropsychiatric; Prostate cancer.