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Randomized Controlled Trial
. 2020 Apr 13;1(6):436-446.
doi: 10.34067/KID.0000062020. eCollection 2020 Jun 25.

Depression and the Effect of Sertraline on Inflammatory Biomarkers in Patients with Nondialysis CKD

L Parker Gregg  1   2 , Thomas Carmody  3   4 , Dustin Le  5 , Nina Bharadwaj  6 , Madhukar H Trivedi  4 , S Susan Hedayati  1
Affiliations
Randomized Controlled Trial

Depression and the Effect of Sertraline on Inflammatory Biomarkers in Patients with Nondialysis CKD

L Parker Gregg et al. Kidney360. .

Abstract

Background: Inflammatory biomarkers are elevated in patients with CKD and associated with poor outcomes. Major depressive disorder (MDD) is prevalent in CKD and associated with inflammation. No studies investigated the effect of MDD treatment on plasma inflammatory biomarkers in patients with nondialysis CKD.

Methods: In a prespecified analysis of the randomized, double-blind CKD Antidepressant Sertraline Trial, we investigated whether treatment with sertraline versus placebo or response to treatment would affect plasma levels of albumin, prealbumin, IL-6, and high-sensitivity C-reactive protein (hsCRP), measured at baseline and after 12 weeks of treatment. We also explored whether somatic versus nonsomatic depressive symptoms, measured using the Quick Inventory of Depressive Symptomatology, and quality-of-life subscales, measured using the Kidney Disease Quality of Life Short Form, were associated with baseline levels of these inflammatory biomarkers.

Results: Of the 193 participants, mean age was 58.4 (SD 13) years and 58% were black, 42% were white, and 18% were Hispanic. Higher baseline hsCRP correlated with somatic depressive symptoms (r=0.21; P=0.01), fatigue (r=0.22; P=0.005), and poorer physical functioning (r=-0.26; P=0.001). There was no change in hsCRP in the sertraline group. hsCRP increased in placebo nonresponders from baseline (median, 3.7 mg/L; interquartile range [IQR], 1.7-10.0 mg/L) to exit (median, 4.9 mg/L; IQR, 1.8-8.8 mg/L; P=0.01). The change from baseline to exit differed between placebo responders (median, -0.4 mg/L; IQR, -9.3 to 0.2 mg/L) and nonresponders (median, 0.8 mg/L; IQR, -0.1 to 3.9 mg/L; P=0.008). There were no differences in changes in albumin, prealbumin, or IL-6 from baseline in any group.

Conclusions: Among patients with CKD and MDD, hsCRP correlated with somatic symptoms of depression and fatigue, but not with nonsomatic symptoms. Sertraline treatment was not associated with a longitudinal change in hsCRP from baseline regardless of treatment effect on depressive symptoms, but those who failed to respond to placebo had an increase in hsCRP over time. This area deserves further investigation.

Clinical trial registry name and registration number: CKD Antidepressant Sertraline Trial (CAST), NCT00946998.

Keywords: C-reactive protein; Chronic Kidney Disease; Sertraline; biomarkers; chronic kidney disease; depression; fatigue; high-sensitivity C-reactive protein; inflammation; interleukin-6; major depressive disorder; medically unexplained symptoms; quality of life.

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Conflict of interest statement

M. Trivedi has served as an advisor or consultant to the following organizations: Allergan Sales LLC, Alkermes, Arcadia Pharmaceuticals Inc., AstraZeneca, Axon Advisors, Bristol-Myers Squibb Company, Eli Lilly & Company, Evotec, Johnson & Johnson, Lundbeck, MedAvante, Merck, MSI Methylation Sciences Inc., Nestle Health Science-PamLab Inc., Naurex, Neuronetics, One Carbon Therapeutics Ltd., Otsuka Pharmaceuticals, Roche Products Ltd., SHIRE Development, Takeda, and Tal Medical/Puretech Venture. M. Trivedi reports personal fees from Acadia, Akili Interactive (other), Alto Neuroscience Inc., Applied Clinical Intelligence LLC, Axome Therapeutics, Boehringer Ingelheim, Engage Health Media, GreenLight VitalSign6 Inc., Health Care Global Village, Janssen-Cilag, Janssen Research and Development LLC, Jazz Pharmaceuticals, Medscape LLC, Navitor Pharmaceuticals Inc, Otsuka Pharmaceutical Development & Commercialization Inc., Otsuka America Pharmaceutical Inc, Perception Neuroscience Holdings Inc., Pharmerit International LP, Policy Analysis Inc., Rexahn Pharmaceuticals Inc., Sage Therapeutics, Signant Health, SK Life Science Inc., and The Baldwin Group Inc. He also reports grants from the National Institute of Mental Health, Patient-Centered Outcomes Research Institute, Cancer Prevention Research Institute of Texas, other from Oxford University Press, and other from American Psychiatric Association (Deputy Editor for American Journal of Psychiatry), outside the submitted work. The coauthors have nothing to disclose.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Flow of participants through the study. MDD, major depressive disorder; QIDS-SR16, 16-Item Quick Inventory of Depressive Symptomatology-Self-Report.
Figure 2.
Figure 2.
Baseline hsCRP was higher in those with than without improvement in depressive symptoms, and hsCRP increased from baseline to exit in those without improvement in depressive symptoms. Comparison of hsCRP at baseline and study exit among (A) all participants, (B) the sertraline group, and (C) the placebo group, and (D) the change in hsCRP from baseline to study exit between those who achieved a three-point improvement in depressive symptoms (black) and those who did not (gray). *P<0.05 for the indicated between-groups comparison at baseline; **P<0.05 for the indicated within-group comparison from baseline to study exit. hsCRP, high-sensitivity C-reactive protein; IQR, interquartile range; QIDS-C, clinician-rated Quick Inventory of Depressive Symptomatology.
Figure 3.
Figure 3.
Baseline hsCRP was higher in sertraline responders than non-responders, and hsCRP increased from baseline to exit in those without placebo response. Comparison of at baseline and study exit among (A) all participants, (B) the sertraline group, and (C) the placebo group, and (D) the change in hsCRP from baseline to study exit between those who achieved depression treatment response (black) and those who did not (gray). *P<0.05 for the indicated between-groups comparison at baseline; **P<0.05 for the indicated within-group comparison from baseline to study exit; ***P<0.05 for the indicated between-groups comparison of the change in hsCRP from baseline to study exit.
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