Association of platelet function with depression and its treatment with sertraline in patients with chronic kidney disease: analysis of a randomized trial.
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ABSTRACT:
SUBMITTER: Jain N
PROVIDER: S-EPMC6819518 | biostudies-literature | 2019 Oct
REPOSITORIES: biostudies-literature
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Association of platelet function with depression and its treatment with sertraline in patients with chronic kidney disease: analysis of a randomized trial.
Jain Nishank N Wan Fei F Kothari Monica M Adelodun Anuoluwapo A Ware Jerry J Sarode Ravi R Hedayati S Susan SS
BMC nephrology 20191029 1
<h4>Background</h4>Major Depressive Disorder (MDD) can lead to adverse cardiovascular outcomes in patients with chronic kidney disease (CKD). Although one of the proposed mechanisms is heightened platelet activation, effects of MDD and its treatment with a selective serotonin reuptake inhibitor (SSRI) on platelet function in patients with CKD remain unclear.<h4>Methods</h4>In a pre-specified analysis, changes from baseline to 12 weeks in whole blood platelet aggregation (WBPA) and plasma levels ...[more]
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Project description:Major Depressive Disorder (MDD) affects one in five patients with Chronic Kidney Disease (CKD) and is an independent risk factor for hospitalization and death before and after dialysis initiation. However, it remains an under-recognized and under-treated problem, in part due to the lack of well-controlled studies that support or refute the efficacy and safety of antidepressant medications in CKD patients. Major trials of antidepressant treatment excluded patients with stages 3-5 CKD, precisely those at higher risk for both depression and increased mortality. The Chronic Kidney Disease Antidepressant Sertraline Trial (CAST) is a randomized, double-blinded, placebo-controlled trial of sertraline, a selective serotonin reuptake inhibitor (SSRI). It will enroll 200 adults with stages 3-5 CKD and MDD excluding kidney transplant and chronic dialysis patients. Sertraline will be administered at an initial dose of 50mg once daily or matching placebo followed by a dose escalation strategy consisting of 50mg increments at 2week intervals (as tolerated) to a maximum dose of 200mg. The primary outcome is improvement in depression symptom severity measured by the Quick Inventory of Depressive Symptomatology scale. Secondary outcomes include safety endpoints and improvement in quality of life. Changes in cognitive function, adherence to medications, nutritional status, inflammation, and platelet function will be explored as potential mechanisms by which depression may mediate poor outcomes. We discuss the rationale and design of the CAST study, the largest placebo-controlled trial aimed to establish safety and efficacy of a SSRI in the acute phase treatment of CKD patients with MDD.
| S-EPMC3525806 | biostudies-other
Project description:Depression is a proposed risk factor for heart failure based largely on epidemiological data; few experimental data addressing this hypothesis are available.Depression was evaluated in relation to cardiac structural and functional phenotypes assessed by transthoracic echocardiography in 42 adult female cynomolgus monkeys that consumed a Western-like diet for 3 years. Half of the monkeys were treated with sertraline HCl for 18 months, and depressive behavior was assessed for 12 months before echocardiography.Depressed monkeys (the 19/42 with depressive behavior rates above the mean rate) had higher heart rates (HRs; 171 [4.1[ versus 152 [6.1]) and smaller body surface area (0.13 [0.003] versus 0.15 [0.004]), left ventricular (LV) end-systolic dimension (0.75 [0.05] versus 0.89 [0.04]), LV systolic (0.76 [0.08] versus 1.2 [0.11]) and diastolic (2.4 [0.23] versus 3.4 [0.26]) volumes, and left atrial volumes (1.15 [0.14] versus 1.75 [0.12]; p values < .05). Doppler profiles of depressed monkeys indicated greater myocardial relaxation (higher e' and higher e'/a' ratio) and lower filling pressures (lower E/e') compared to nondepressed monkeys (p values < .05). Although sertraline treatment reduced HR (150 [5.8] versus 171 [4.8]) and modestly increased chamber dimensions (LV end-systolic dimension: 0.91 [0.05] versus 0.74 [0.03]; LV end-diastolic dimension, body surface area adjusted 1.69 [0.05] versus 1.47 [0.06]; p values < .05), it did not overtly affect systolic or diastolic function (p values > .10).These data suggest that behavioral depression in female primates is accompanied by differences in cardiac function, although not in ways classically associated with subclinical heart failure. Selective serotonin reuptakes show promise in supporting heart function by reducing HR and perhaps improving LV filling; however, further investigation is needed.
| S-EPMC3971435 | biostudies-literature
Project description:ImportanceMajor 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.ObjectiveTo determine whether treatment with sertraline improves depressive symptoms in patients with CKD and MDD.Design, setting, and participantsThe 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.InterventionsAfter 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 measuresThe 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.ResultsThere 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 relevanceAmong 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 registrationclinicaltrials.gov Identifier: NCT00946998.
| S-EPMC5710375 | biostudies-literature
Project description:The objective was to test the hypothesis that heart failure (HF) patients treated with sertraline will have lower depression scores and fewer cardiovascular events compared with placebo.Depression is common among HF patients. It is associated with increased hospitalization and mortality.The SADHART-CHF (Sertraline Against Depression and Heart Disease in Chronic Heart Failure) trial was a randomized, double-blind, placebo-controlled trial of sertraline 50 to 200 mg/day versus matching placebo for 12 weeks. All participants also received nurse-facilitated support. Eligible patients were age 45 years or older with HF (left ventricular ejection fraction < or =45%, New York Heart Association functional class II to IV) and clinical depression (Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria for current major depressive disorder). Those with significant cognitive impairment, psychosis, recent alcohol or drug dependence, bipolar or severe personality disorder, active suicidal ideation, and current antipsychotic or antidepressant medications were excluded. Primary end points were change in depression severity (Hamilton Depression Rating Scale total score) and composite cardiovascular status at 12 weeks.A total of 469 patients were randomized (n = 234 sertraline, n = 235 placebo). The mean +/- SE change from baseline to 12 weeks in the Hamilton Depression Rating Scale total score was -7.1 +/- 0.5 (sertraline) and -6.8 +/- 0.5 (placebo) (p < 0.001 from baseline, p = 0.89 between groups, mean change between groups -0.4; 95% confidence interval: -1.7 to 0.92). The proportions whose composite cardiovascular score worsened, improved, or was unchanged were 29.9%, 40.6%, and 29.5%, respectively, in the sertraline group and 31.1%, 43.8%, and 25.1%, respectively, in the placebo group (p = 0.78).Sertraline was safe in patients with significant HF. However, treatment with sertraline compared with placebo did not provide greater reduction in depression or improved cardiovascular status among patients with HF and depression. (Antidepressant Medication Treatment for Depression in Individuals With Chronic Heart Failure [SADHART-CHF]; NCT00078286).
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Project description:ObjectiveDepression is common in Alzheimer disease (AD), and antidepressants are commonly used for its treatment, however, evidence for antidepressant efficacy in this population is lacking. The authors conducted a multicenter, randomized, placebo-controlled trial titled "Depression in Alzheimer's Disease-2" to assess the efficacy and tolerability of sertraline for depression in AD.MethodsOne hundred thirty-one participants from five U.S. medical centers with mild-to-moderate AD (Mini-Mental State Examination scores 10-26) and depression of AD were randomized to double-blinded treatment with sertraline (N = 67) or placebo (N = 64), with a target dosage of 100 mg daily. Efficacy was assessed using logistic regressions and mixed effects models in an intention-to-treat analysis with imputation of missing data. Principal outcome measures were modified Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC), change in Cornell Scale for Depression in Dementia (CSDD) scores, and remission defined by both mADCS-CGIC score <or=2 and CSDD score <or=6.ResultsmADCS-CGIC ratings (odd ratio [OR = 1.01], 95% confidence interval [CI]: 0.52-1.97, p = 0.98), CSDD scores (median difference at 12 weeks 1.2, 95% CI: 1.65-4.05, p = 0.41), and remission at 12 weeks of follow-up (OR = 2.06, 95% CI: 0.84-5.04, p = 0.11) did not differ between sertraline (N = 67) and placebo (N = 64). Sertraline-treated patients experienced more adverse events, most notably gastrointestinal and respiratory, than placebo-treated patients.ConclusionSertraline did not demonstrate efficacy for the treatment depression symptoms in patients with AD. In addition, its use was associated with an increased incidence of adverse events. Thus, selective serotonin reuptake inhibitors may be of limited value for treating depression in patients with AD.
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Project description:Sertraline, a selective serotonin-reuptake inhibitor, has demonstrated substantial mood improvement in patients with post myocardial infarction or with unstable angina. The impact of sertraline on the prognosis and depression of patients with chronic heart failure (HF) and comorbid major depressive disorder (MDD) is unknown.This is a prospective, randomized, double-blind, placebo-controlled study designed to assess the safety and efficacy of sertraline in the treatment of MDD in patients with HF. The study is designed also to examine the effects of treating depression on cardiac events and morbidity/mortality in patients with HF. Approximately 500 men and women who are >or=45 years of age with current MDD and chronic systolic HF, characterized by left ventricular ejection fraction <or=45% and New York Heart Association class >or=II, comprise the study population. Eligible participants are randomized to either sertraline or placebo for a 12-week acute treatment phase. All patients, regardless of acute treatment phase completion, are followed routinely until the last subject completes 6-month follow-up. Quality of life and certain physiologic parameters, as well as pro-inflammatory and HF biomarkers, that may reflect the impact of sertraline in this particular population are measured at baseline and at the end of the acute treatment phase.Because of the high prevalence of depression and its significant adverse impact on prognosis of patients with ischemic heart disease (IHD) and HF, the Safety and Efficacy of Sertraline for Depression in Patients with Chronic Heart Failure (SADHART-CHF) trial aims to assess the effects of sertraline on response of depression as well as on the cardiac prognosis of patients with HF.
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Project description:Chronic kidney disease (CKD) increases the risk of cardiovascular disease and cognitive impairment. Curcumin is a polyphenol that improves vascular and cognitive function in older adults; however, its effects on vascular and cognitive function in patients with CKD are unknown. We hypothesized that curcumin supplementation would improve vascular and cognitive function in patients with CKD. Eighty-eight adults diagnosed with stage 3b or 4 CKD (aged 66 ± 8 years, 75% male) participated in a 12-month, randomized, double-blind, placebo-controlled study to test the effects of curcumin (Longvida®, 2000 mg/day) on vascular and cognitive function. Our primary outcome was brachial artery flow-mediated dilation (FMD). Our secondary outcomes were nitroglycerin-mediated dilation, carotid-femoral pulse wave velocity (cfPWV), and cognitive function assessed via the NIH Toolbox Cognition Battery. At baseline, the mean estimated glomerular filtration rate was 34.7 ± 10.8, and the median albumin/creatinine ratio was 81.9 (9.7, 417.3). A total of 44% of participants had diabetes. Compared with placebo, 12 months of curcumin did not improve FMD (median change from baseline was -0.7 (-2.1, 1.1) and -0.1 (-1.5, 1.5) for curcumin and placebo, respectively, with p = 0.69). Similarly, there were no changes in nitroglycerin-mediated dilation, cfPWV, or cognitive outcomes. These results do not support chronic curcumin supplementation to improve vascular and cognitive function in patients with CKD.
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Project description:Familial paroxysmal non-kinesigenic dyskinesia, which is a major form of paroxysmal dyskinesias, is characterized by intermittent attacks that include one side, subsequently spreading to the other side, involving the limbs and face, and is triggered by caffeine, alcohol, emotional stress, fatigue, and sleep deprivation, but not by sudden movement. A 26-year-old man had experienced dystonic movements and a choreiform right arm spreading to his arms, legs, and face since the age of one year. Oral dyskinesias and, rarely, dysarthria were also observed. Attacks lasting approximately five minutes occurred several times per day. Over three generations, his family members inherited a c.26C > T (p. Ala9Val) missense mutation in exon 1 of PNKD/MR-1 in an autosomal dominant manner and reported similar symptoms with clinical manifestations ranging from mild to severe. His scores on the Self-Rating Depression Scale, State-Trait Anxiety Inventory, and Profile of Mood States were high. This suggests that the patient also had comorbidities of anxiety and depression. The patient's attacks decreased from two times per week to once every two months, and his State-Trait Anxiety Inventory score decreased by 5-10 points on treatment with clonazepam and sertraline, allowing his condition to become stable enough that he was able to participate in society. Drug therapy with clonazepam and sertraline is the preferred treatment for reducing attacks in PNKD patients with strong anxiety and depression.
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Project description:BackgroundChronic and treatment-resistant depressions pose serious problems in mental health care. Mindfulness-based cognitive therapy (MBCT) is an effective treatment for remitted and currently depressed patients. It is, however, unknown whether MBCT is effective for chronic, treatment-resistant depressed patients.MethodA pragmatic, multicenter, randomized-controlled trial was conducted comparing treatment-as-usual (TAU) with MBCT + TAU in 106 chronically depressed outpatients who previously received pharmacotherapy (≥4 weeks) and psychological treatment (≥10 sessions).ResultsBased on the intention-to-treat (ITT) analysis, participants in the MBCT + TAU condition did not have significantly fewer depressive symptoms than those in the TAU condition (-3.23 [-6.99 to 0.54], d = 0.35, P = 0.09) at posttreatment. However, compared to TAU, the MBCT + TAU group reported significantly higher remission rates (χ2 (2) = 4.25, φ = 0.22, P = 0.04), lower levels of rumination (-3.85 [-7.55 to -0.15], d = 0.39, P = 0.04), a higher quality of life (4.42 [0.03-8.81], d = 0.42, P = 0.048), more mindfulness skills (11.25 [6.09-16.40], d = 0.73, P < 0.001), and more self-compassion (2.91 [1.17-4.65], d = 0.64, P = 0.001). The percentage of non-completers in the MBCT + TAU condition was relatively high (n = 12, 24.5%). Per-protocol analyses revealed that those who completed MBCT + TAU had significantly fewer depressive symptoms at posttreatment compared to participants receiving TAU (-4.24 [-8.38 to -0.11], d = 0.45, P = 0.04).ConclusionAlthough the ITT analysis did not reveal a significant reduction in depressive symptoms of MBCT + TAU over TAU, MBCT + TAU seems to have beneficial effects for chronic, treatment-resistant depressed patients in terms of remission rates, rumination, quality of life, mindfulness skills, and self-compassion. Additionally, patients who completed MBCT showed significant reductions in depressive symptoms. Reasons for non-completion should be further investigated.
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Project description:Serotonin reuptake inhibitors (SRIs) are efficacious treatments for premenstrual dysphoric disorder (PMDD) when given daily or for half of the menstrual cycle during the luteal phase. Preliminary studies suggest that SRI treatment can be shortened to the interval from symptom onset through the beginning of menses.To determine the efficacy of symptom-onset dosing with the SRI sertraline hydrochloride for treatment of PMDD.A double-blind, placebo-controlled, multisite, parallel-group randomized clinical trial conducted September 1, 2007, to February 29, 2012, at 3 university medical centers. In all, 252 women with PMDD started treatment at symptom onset and continued until the first few days of menses for 6 menstrual cycles. Intent-to-treat analyses were performed February 28, 2014, through April 21, 2015.Placebo or sertraline hydrochloride, 50 to 100 mg/d, during the symptomatic interval.Premenstrual Tension Scale (PMTS) score was the primary outcome measure (score range, 0-36; 36 indicates most severe score). Secondary outcome measures included the Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C) (score range, 0-84; 84 indicates most severe score), Daily Record of Severity of Problems (DRSP) (total and subscale scores; higher scores indicate most severe problems), Clinical Global Impression (CGI) scales (score range, 1-7; 7 indicates most severe symptoms and least improvement), and Michelson SSRI (Selective SRI) Withdrawal Symptoms Scale scores (range, 0-51; higher scores indicate more severe withdrawal symptoms).Among the participants, 125 with PMDD were randomized to sertraline, and 127 to placebo. At baseline the mean (SD) PMTS scores for sertaline and placebo were 22.3 (4.8) and 21.4 (4.5), respectively, which declined to 11.7 (6.8) and 12.0 (6.9), respectively; group mean difference, 1.88 (95% CI, 0.01-3.75; P?=?.06). The mean (SD) estimated difference in IDS-C scores between baseline (35.4 [10.7] for sertraline; 32.8 [10.4] for placebo) and the end point (15.3 [10.7] for sertraline; 17.8 [11.0] for placebo) favored the sertraline group by 5.14 (95% CI, 1.97-8.31) points (P?=?.02). Compared with the placebo group, those assigned to sertraline showed greater improvement on the total DRSP score (estimated mean difference, 1.09 [95% CI, 0.96-1.25] points; P?=?.02) and Anger/Irritability DRSP subscale score (1.22 [95% CI,?1.05-1.41] points; P?<?.01) and were more likely to respond to treatment (77 of 115 patients [67.0%] for sertraline and 65 of 124 [52.4%] for placebo; ?21?=?5.23; P?=?.02). The mean (SD) number of symptomatic days before treatment diminished over time (sertraline, -0.7 [3.4] days; placebo, -1.0 [3.2] days), with no group differences in symptomatic days or the Michelson SSRI Withdrawal Symptoms Scale.Depending on the symptom scale, women with PMDD may or may not benefit from SRI treatment during the interval from the onset of premenstrual symptoms through the first few days of menses. Abrupt treatment cessation was not associated with discontinuation symptoms.clinicaltrials.gov Identifier: NCT00536198.
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