fluvoxamine and Kidney-Failure--Chronic

Individuals receiving maintenance hemodialysis may be particularly susceptible to the lethal cardiac consequences of drug-induced QT prolongation because they have a substantial cardiovascular disease burden and high level of polypharmacy, as well as recurrent exposure to electrolyte shifts during dialysis. Electrophysiologic data indicate that among the selective serotonin reuptake inhibitors (SSRIs), citalopram and escitalopram prolong the QT interval to the greatest extent. However, the relative cardiac safety of SSRIs in the hemodialysis population is unknown.. In this retrospective cohort study, we used data from a cohort of Medicare beneficiaries receiving hemodialysis included in the US Renal Data System registry (2007-2014). We used a new-user design to compare the 1-year risk of sudden cardiac death among hemodialysis patients initiating SSRIs with a higher potential for prolonging the QT interval (citalopram, escitalopram) versus the risk among those initiating SSRIs with lower QT-prolonging potential (fluoxetine, fluvoxamine, paroxetine, sertraline). We estimated adjusted hazard ratios using inverse probability of treatment weighted survival models. Nonsudden cardiac death was treated as a competing event.. The study included 30,932 (47.1%) hemodialysis patients who initiated SSRIs with higher QT-prolonging potential and 34,722 (52.9%) who initiated SSRIs with lower QT-prolonging potential. Initiation of an SSRI with higher versus lower QT-prolonging potential was associated with higher risk of sudden cardiac death (adjusted hazard ratio, 1.18; 95% confidence interval, 1.05 to 1.31). This association was more pronounced among elderly individuals, females, patients with conduction disorders, and those treated with other non-SSRI QT-prolonging medications.. The heterogeneous QT-prolonging potential of SSRIs may differentially affect cardiac outcomes in the hemodialysis population.

Topics: Age Factors; Aged; Aged, 80 and over; Cardiac Conduction System Disease; Citalopram; Death, Sudden, Cardiac; Depression; Electrocardiography; Female; Fluoxetine; Fluvoxamine; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peroxidase; Registries; Renal Dialysis; Retrospective Studies; Risk Factors; Selective Serotonin Reuptake Inhibitors; Sertraline; Sex Factors; United States

Seven Japanese patients on maintenance hemodialysis who were comorbid with mild depression were medicated with 50 mg/day fluvoxamine maleate for 28 days. Effectiveness was obtained in four out of seven patients (57%). The plasma fluvoxamine concentrations were examined in three patients. The plasma fuvoxamine concentration decreased by 22% by hemodialysis. There is a tendency for the dialyzed rate of fluvoxamine to become lower if the plasma albumin concentration is higher. The half-life of fluvoxamine was possibly shortened more in the patient with hypoalbuminaemia. The plasma fluvoxamine concentration reached a steady state 8 days after the start of medication and thereafter. The time required to reach steady state was lengthened when compared with the results in normal Japanese volunteers.

Topics: Antidepressive Agents, Second-Generation; Biological Availability; Depressive Disorder; Diabetic Nephropathies; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluvoxamine; Half-Life; Humans; Japan; Kidney Failure, Chronic; Male; Metabolic Clearance Rate; Middle Aged; Personality Inventory; Renal Dialysis; Treatment Outcome