Dataset Information

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.

SUBMITTER: Friedli K

PROVIDER: S-EPMC5293327 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Publications

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

Friedli Karin K Guirguis Ayman A Almond Michael M Day Clara C Chilcot Joseph J Da Silva-Gane Maria M Davenport Andrew A Fineberg Naomi A NA Spencer Benjamin B Wellsted David D Farrington Ken K

Clinical journal of the American Society of Nephrology : CJASN 20170126 2

<h4>Background and objectives</h4>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.<h4>Design, setting, participants, & measurements</h4>Patients on hemodialysis at five United Kingdom renal centers complete ...[more]

PMID: 28126706

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Project description:BackgroundMajor Depressive Disorder (MDD) has been associated with brain-related changes. However, biomarkers have yet to be defined that could "accurately" identify antidepressant-responsive patterns and reduce the trial-and-error process in treatment selection. Cerebral blood perfusion, as measured by Arterial Spin Labelling (ASL), has been used to understand resting-state brain function, detect abnormalities in MDD, and could serve as a marker for treatment selection. As part of a larger trial to identify predictors of treatment outcome, the current investigation aimed to identify perfusion predictors of treatment response in MDD.MethodsFor this secondary analysis, participants include 231 individuals with MDD from the EMBARC study, a randomised, placebo-controlled trial investigating clinical, behavioural, and biological predictors of antidepressant response. Participants received sertraline (n = 114) or placebo (n = 117) and response was monitored for 8 weeks. Pre-treatment neuroimaging was completed, including ASL. A whole-brain, voxel-wise linear mixed-effects model was conducted to identify brain regions in which perfusion levels differentially predict (moderate) treatment response. Clinical effectiveness of perfusion moderators was investigated by composite moderator analysis and remission rates. Composite moderator analysis combined the effect of individual perfusion moderators and identified which contribute to sertraline or placebo as the "preferred" treatment. Remission rates were calculated for participants "accurately" treated based on the composite moderator (lucky) versus "inaccurately" treated (unlucky).FindingsPerfusion levels in multiple brain regions differentially predicted improvement with sertraline over placebo. Of these regions, perfusion in the putamen and anterior insula, inferior temporal gyrus, fusiform, parahippocampus, inferior parietal lobule, and orbital frontal gyrus contributed to sertraline response. Remission rates increased from 37% for all those who received sertraline to 53% for those who were lucky to have received it and sertraline was their perfusion-preferred treatment.InterpretationThis large study showed that perfusion patterns in brain regions involved with reward, salience, affective, and default mode processing moderate treatment response favouring sertraline over placebo. Accurately matching patients with defined perfusion patterns could significantly increase remission rates.FundingNational Institute of Mental Health, the Hersh Foundation, and the Center for Depression Research and Clinical Care, Peter O'Donnell Brain Institute at UT Southwestern Medical Center.Trial Registration.Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMARC) Registration Number: NCT01407094 (https://clinicaltrials.gov/ct2/show/NCT01407094).

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Dataset Information

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

Background and objectives

Design, setting, participants, & measurements

Results

Conclusions

Publications

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

Similar Datasets

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