Sertraline Versus Placebo in Patients with Major Depressive Disorder Undergoing Hemodialysis: A Randomized, Controlled Feasibility Trial

Abstract

Background and objectives: Depression is common in patients on hemodialysis, but data on the benefits and risks of antidepressants in this setting are limited. We conducted a multicenter, randomized, double-blind, placebo-controlled trial of sertraline over 6 months in patients on hemodialysis with depression to determine study feasibility, safety, and effectiveness.

Design, setting, participants, & measurements: Patients on hemodialysis at five United Kingdom renal centers completed the Beck Depression Inventory II. Those scoring ≥16 and not already on treatment for depression were invited to undergo diagnostic interview to confirm major depressive disorder. Eligible patients with major depressive disorder were randomized to receive the study medication-either sertraline or placebo. Outcomes included recruitment and dropout rates, change in the Montgomery-Asberg Depression Rating Scale and Beck Depression Inventory II, and qualitative information to guide design of a large-scale trial.

Results: In total, 709 patients were screened and enrolled between April of 2013 and October of 2014; 231 (32.6%) had Beck Depression Inventory II scores ≥16, and 68 (29%) of these were already receiving treatment for depression. Sixty-three underwent diagnostic interview, 37 were diagnosed with major depressive disorder, and 30 were randomized; 21 completed the trial: eight of 15 on sertraline and 13 of 15 on placebo (P=0.05). Dropouts due to adverse and serious adverse events were greater in the sertraline group. All occurred in the first 3 months. Over 6 months, depression scores improved in both groups. Beck Depression Inventory II score fell from 29.1±8.4 to 17.3±12.4 (P<0.001), and Montgomery-Asberg Depression Rating Scale score fell from 24.5±4.1 to 10.3±5.8 (P<0.001). There were no differences between sertraline and placebo groups.

Conclusions: Although small, this is the largest randomized trial to date of antidepressant medication in patients on hemodialysis. Our results highlight recruitment issues. No benefit was observed, but trial size and the substantial dropout render consideration of benefit inconclusive. A definitive trial could use shorter follow-up and include depressed patients already taking antidepressants.

Keywords: Antidepressive Agents; Controlled Clinical Trials, Randomized; Depressive Disorder, Major; Double-Blind Method; Feasibility Studies; Follow-Up Studies; Humans; Personality Inventory; Placebos; Psychiatric Status Rating Scales; Risk Assessment; Sertraline; depression; hemodialysis; renal dialysis.

Figure 1.

Trial profile. BDI-II, Beck Depression Inventory II.

Figure 2.

Change in Montgomery–Asberg Depression Rating Scale (MADRS) scores in response to sertraline and placebo. The lines represent the MADRS scores for the sertraline (red) and placebo (blue) groups at baseline and 2, 4, and 6 months. The 95% confidence intervals are estimated at each time point for both groups. The confidence intervals for the sertraline group are larger at later time points due to the smaller group size.