Journal Article Annotations
2017, 1st Quarter

Psychonephrology

Annotations by Paula Zimbrean, MD, FAPM, and Marta Novak, MD, PhD
April 2017

Sertraline versus placebo in patients with major depressive disorder undergoing hemodialysis: A randomized, controlled feasibility trial

PUBLICATION #1 — Psychonephrology

Sertraline versus placebo in patients with major depressive disorder undergoing hemodialysis: A randomized, controlled feasibility trial

Friedli K, Guirguis A, Almond M, et al

Clin J Am Soc Nephrol 2017; 12(2):280-286

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.

On PubMed: Clin J Am Soc Nephrol 2017; 12(2):280-286

Annotation

The finding: Sertraline showed no benefit over placebo in a randomized controlled trial for treatment of depression in hemodialysis patients.

Strengths and weaknesses: This is a randomized placebo-controlled trial designed to evaluate the efficacy of sertraline for treatment of depression in patients on dialysis. The design was prospective, multicentered; over 700 patients were screened for eligibility. The number of subjects, however, was rather low and the drop-out rate was high. There were significant differences in the drop outs in the sertraline group versus placebo group.

Relevance: Antidepressants are frequently used to treat depression in patients with CKD, including those on hemodialysis; however, there is no systematic data about their efficacy and tolerability. This is the first placebo-controlled trial of an antidepressant in this population. Although the power of the study is not sufficient to draw final conclusions about the efficacy of sertraline in this population, drop outs and side effects were more common in the sertraline group. For the clinician, these results invite caution before starting antidepressants in hemodialysis patients, careful consideration of alternative interventions, and a realistic discussion with patients about risks and benefits of treatment in this situation.