Effect of Sertraline on Depressive Symptoms in Patients With Chronic Kidney Disease Without Dialysis Dependence

Abstract

IMPORTANCE Major depressive disorder (MDD) is prevalent among patients with chronic kidney disease (CKD) and is associated with morbidity and mortality. The efficacy and adverse events of selective serotonin reuptake inhibitors in these patients are unknown. OBJECTIVE To determine whether treatment with sertraline improves depressive symptoms in patients with CKD and MDD. DESIGN, SETTING, AND PARTICIPANTS The Chronic Kidney Disease Antidepressant Sertraline Trial (CAST) was a randomized, double-blind, placebo-controlled trial involving 201 patients with stage 3, 4, or 5 non–dialysis-dependent CKD, who were enrolled at 3 US medical centers. The Mini Neuropsychiatric Interview was used to establish MDD. The first participant was randomized in March 2010 and the last clinic visit occurred in November 2016. INTERVENTIONS After a 1-week placebo run-in, participants were randomized to sertraline (n = 102) for 12 weeks at an initial dose of 50 mg/d (escalated to a maximum dose of 200 mg/d based on tolerability and response) or matching placebo (n = 99). MAIN OUTCOMES AND MEASURES The primary outcome was improvement in depressive symptom severity from baseline to 12 weeks determined by the 16-item Quick Inventory of Depression Symptomatology–Clinician Rated (QIDS-C16) (score range, 0–27; minimal clinically important difference, 2 points). Secondary outcomes included improvement in quality of life (Kidney Disease Quality of Life Survey–Short Form; score range, 0–100; higher scores indicate more favorable quality of life) and adverse events. RESULTS There were 201 patients (mean [SD] age, 58.2 [13.2] years; 27%female) randomized. The primary analysis included 193 patients who had at least 1 outcome assessment after randomization. The mean (SD) baseline QIDS-C16 score was 14.0 (2.4) in the sertraline group (n = 97) and 14.1 (2.4) in the placebo group (n = 96). The median participation time was 12.0 weeks and the median achieved dose was 150 mg/d, which was not significantly different between the groups. The QIDS-C16 score changed by −4.1 in the sertraline group and by −4.2 in the placebo group (between-group difference, 0.1 [95%CI, −1.1 to 1.3]; P = .82). There was no significant between-group difference in change in patient-reported overall health on the Kidney Disease Quality of Life Survey (median score, 0 in the sertraline group vs 0 in the placebo group; between-group difference, 0 [95%CI, −10.0 to 0]; P = .61). Nausea or vomiting occurred more frequently in the sertraline vs placebo group (22.7%vs 10.4%, respectively; between-group difference, 12.3%[95%CI, 1.9%to 22.6%], P = .03), as well as diarrhea (13.4%vs 3.1%; between-group difference, 10.3%[95%CI, 2.7%to 17.9%], P = .02). CONCLUSIONS AND RELEVANCE Among patients with non–dialysis-dependent CKD and MDD, treatment with sertraline compared with placebo for 12 weeks did not significantly improve depressive symptoms. These findings do not support the use of sertraline to treat MDD in patients with non–dialysis-dependent CKD. TRIAL REGISTRATION clinica...

Is successful treatment of depression in dialysis patients an achievable goal?

“…There were no serious adverse events and side effect profiles for each drug were reportedly similar. 27 To date, there have only been three randomized placebo-controlled trials of an antidepressant agent in individuals with kidney disease, [28][29][30] of which two studies were in dialysis patients. The first, in 14 HD patients found no significant improvement in depression symptoms after an 8-week treatment with fluoxetine compared with placebo.…”

Different Approaches to Therapy of Depressive Disorders in Clinical Practice

“…Таковыми в первую очередь явля-ются препараты из группы селективных ингибиторов обратного захвата серотонина (СИОЗС), в частности сер-тралин (Золофт) [32][33][34][35][36][37], а также антидепрессанты двой-ного действия -венлафаксин [38] и препараты из группы норадренергических и специфических серотонинергиче-ских антидепрессантов -миртазапин 6 [39]. 5 Так, постинфарктная депрессия способствует повышению смертности в 2--2,5 раза [31].…”

“…Накоплено достаточно большое количество исследо-ваний, в которых доказана высокая эффективность, без-опасность и хорошая переносимость СИОЗС [32][33][34][35][36][37][45][46][47][48][49], в частности сертралина (Золофт), при терапии депрессий при хронических соматических заболеваниях, таких как сердечно-сосудистая патология [32,34,48], нервные болезни [36,38,44,49], хроническая болезнь почек [35], сахарный диабет [33], заболевания крови [37]. В приведенных работах продемонстрировано меньшее количество побочных эффектов у препаратов группы СИОЗС, их лучшая совместимость с соматотропной тера-и обоснованно.…”

Why don't SSRIs work in the medical subspecialty clinic?

“…During a recent supervision session with a resident, the question arose as to whether the diazepam being given to one of his clinic patients with chronic renal insufficiency should be replaced by a benzodiazepine that was either shorter‐acting or without active metabolites (the answer: probably unnecessary, since most of diazepam's metabolism is hepatic). Quite by coincidence, results of the Chronic Kidney Disease Antidepressant Sertraline Trial (CAST) had just been published by Hedayati et al, 1 allowing our supervision discussion to meander onto a related, and probably more important, topic: What is the best way to treat depression in the medically compromised?…”