Pharmacotherapy for the Prevention of Depression and Behavioral Side Effects in Hematopoietic Stem Cell Transplantation Patients

•Depression is a serious issue for HSCT patients before, during, and after transplantation.•Patients were randomized to sertraline or placebo plus 12 weeks of supportive psychotherapy.•At 12 weeks, the 2 treatment groups had equivalent mood, QoL, and survival.•Further research to evaluate antidepressants and psychotherapy treatments is needed.•Improvements in mood, QoL, and survival are critical supportive care goals for HSCT. Depression and decreased quality of life (QoL) develop in approximately 30% of nondepressed hematopoietic stem cell transplantation (HSCT) recipients early after transplantation. To potentially prevent this complication, we conducted a prospective randomized trial to assess whether prophylaxis of nondepressed HSCT patients with the antidepressant sertraline (SER) in addition to supportive psychotherapy starting at admission for transplantation decreases the risk of depression and improves QoL. The primary objective of the study was to evaluate whether there was an added benefit of SER versus placebo along with routine supportive psychotherapy on the development of depression in patients receiving HSCT. A secondary objective was to analyze the impact on patient-reported QoL and survival. The study was conducted at a single-site academic medical center. We randomized 123 nondepressed HSCT recipients (1:1) in a phase III double-blind study to receive SER starting at a dose of 50 mg/day, with possible dose escalations to 200 mg per day, or placebo beginning on admission for HSCT and continuing for 12 weeks. Supportive psychotherapy was provided for both groups. Depression (Beck Depression Inventory II [BDI-II]) and QoL (Functional Assessment of Cancer Therapy–Bone Marrow Transplantation [FACT-BMT]) were assessed prior to HSCT and then weekly to week 12 post-HSCT. A multivariable linear mixed-effects model was used to estimate the mean change in BDI-II scores as a function of elapsed time since baseline, treatment assignment, and their interaction. The same process was used to assess treatment effects on all QoL scores from the FACT-BMT assessment. A Kaplan-Meier curve was used to estimate the probability of survival for each group following initiation of treatment. A follow-up Cox proportional hazards model was used to estimate the mortality rate in the 2 groups. Our results do not indicate a benefit of SER in either a diminished risk of depression or improved QoL or survival outcomes. Based on our findings, we can only recommend early e