Association of androgen deprivation therapy and depression in the treatment of prostate cancer: A systematic review and meta-analysis

Background: There is increasing evidence that androgen deprivation therapy (ADT) may be associated with depression. Existing studies have shown conflicting results.

Methods: PubMed, Web of Science, Embase, and PsycINFO were queried on April 5, 2017. Eligible studies were in English and reported depression among individuals with prostate cancer exposed to a course of ADT vs. a lesser-exposed group (e.g., any-ADT vs. no ADT and continuous ADT vs. intermittent ADT). We used the MOOSE statement guidelines and the Cochrane Review Group's data extraction template. Study quality was evaluated by Newcastle-Ottawa Scale criteria. We conducted a random-effects meta-analysis to calculate summary statistic risk ratios (RRs) and 95% CIs. Heterogeneity was quantified using the I² statistic and prespecified subgroup analysis. Small study effects were evaluated using Begg and Egger statistics.

Results: A total of 1,128 studies were initially identified and evaluated. A meta-analysis of 18 studies among 168,756 individuals found that ADT use conferred a 41% increased risk of depression (RR = 1.41; 95% CI: 1.18-1.70; P<0.001). We found a consistent strong statistically significant association when limiting our analysis to studies in localized disease (RR = 1.85; 95% CI: 1.20-2.85; P = 0.005) and those using a clinical diagnosis of depression (RR = 1.19; 95% CI: 1.08-1.32; P = 0.001). We did not find an association for continuous ADT with depression risk compared to intermittent ADT (RR = 1.00; 95% CI: 0.50-1.99; P = 0.992). There was no statistically significant evidence of small study effects. Statistically significant heterogeneity in the full analysis (I² = 80%; 95% CI: 69-87; P<0.001) resolved when examining studies using a clinical diagnosis of depression (I² = 16%; 95% CI: 0-60; P = 0.310).

Conclusion: The currently available evidence suggests that ADT in the treatment of prostate cancer is associated with an increased risk of depression.