Cardiovascular mechanisms of SSRI drugs and their benefits and risks in ischemic heart disease and heart failure

Andrade, Chittaranjan; Kumar, C.B.; Surya, Sandarsh

doi:10.1097/yic.0b013e32835d735d

Cited by 39 publications

(23 citation statements)

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“…There already are clinically and translationally important data concerning paroxetine and HF. HF patients are often depressed, and trials have shown that paroxetine along with other SSRIs can be used effectively to treat depression in these patients (32)(33)(34). Although this therapy certainly improves mental outlook and data have shown improvement in patient outcomes and quality of life (32)(33)(34), specific improvements in cardiac function have not been evaluated.…”

Section: Discussionmentioning

confidence: 99%

Paroxetine-Mediated GRK2 Inhibition Reverses Cardiac Dysfunction and Remodeling After Myocardial Infarction

Schumacher

Gao

Zhu

et al. 2015

Journal of Cardiac Failure

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Section: Discussionmentioning

confidence: 99%

Paroxetine-Mediated GRK2 Inhibition Reverses Cardiac Dysfunction and Remodeling After Myocardial Infarction

Schumacher

Gao

Zhu

et al. 2015

Journal of Cardiac Failure

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“…There are several mechanisms through which SSRIs may improve heart function particularly in depression. For example they reduce heart rate, increase heart rate variability (55; 56; 58; this report), inhibit serotonin-mediated and collagen-mediated platelet aggregation, reduce inflammatory mediator levels, and improve endothelial function (59). …”

Section: Discussionmentioning

confidence: 99%

Effect of Depression and Sertraline Treatment on Cardiac Function in Female Nonhuman Primates

Groban

Kitzman²,

et al. 2014

Psychosomatic Medicine

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Objective Depression is a proposed risk factor for heart failure based largely on epidemiological data; little experimental data is available addressing this hypothesis. Methods 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 the SSRI sertraline HCl for 18 months and depressive behavior was assessed for 12 months prior to echocardiography. Results Depressed monkeys (the 19/42 with depressive behavior rates above the mean rate) had higher HRs (171±4.1 vs 152±6.1), and smaller BSA (0.13±0.003 vs 0.15±0.004). Cardiac measures showed lower LV end systolic dimension (0.75±0.05 vs 0.89±0.04), LV systolic (0.76±0.08 vs 1.2±0.11) and diastolic (2.4±0.23 vs 3.4±0.26) volumes, and left atrial volumes (1.15±0.14 vs 1.75±0.12) in depressed versus nondepressed monkeys (p’s <0.05). 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’s<0.05). Although treatment with sertraline reduced HR (150±5.8 vs 171±4.8) and modestly increased chamber dimensions (left ventricular end systolic dimension: 0.91±0.05 vs 0.74±0.03; left ventricular end diastolic dimension, BSA adjusted 1.69±0.05 vs 1.47±0.06) (p’s<0.05), it did not overtly affect systolic or diastolic function (p’s >0.10). Conclusions 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. SSRIs show promise in supporting heart function by reducing HR and perhaps improving LV filling, however further investigation is needed to confirm this hypothesis.

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“…SSRIs are the drug of choice for anxiety and depression, which may be ideally suited to hypercholesterolemic patients. These medicines may also decrease cardiovascular risks and improve clinical cardiovascular end points through several mechanisms 20. However, SSRIs are commonly associated with pharmacokinetic drug interactions, and many of these inhibit the metabolism of other drugs, thereby raising the blood levels of many coadministered drugs.…”

Section: Discussionmentioning

confidence: 99%

Simultaneous administration of fluoxetine and simvastatin ameliorates lipid profile, improves brain level of neurotransmitters, and increases bioavailability of simvastatin

Alasmari¹,

Ullah²,

Masoudi³

et al. 2017

JEP

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Simvastatin (STT), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, is widely prescribed for dyslipidemia, whereas fluoxetine (FLX) is the first-choice drug for the treatment of depression and anxiety. A recent report suggests that selective serotonin reuptake inhibitors can interact with the cytochrome P450 3A4 substrate, and another one suggests that STT enhances the antidepressant activity of FLX. However, the data are inconclusive. The present study was designed to explore the pharmacokinetic and pharmacodynamic consequences of coadministration of STT and FLX in experimental animals. For this, Wistar rats weighing 250±10 g were divided into four groups, including control, STT (40 mg/kg/day), FLX (20 mg/kg/day), and STT+FLX group, respectively. After the dosing period of 4 weeks, the animals were sacrificed, and the blood and brain samples were collected for the analysis of STT, simvastatin acid (STA), FLX, total cholesterol, triglyceride, high-density lipoprotein (HDL), 5-hydroxytryptamine, dopamine, and hydroxy indole acetic acid. It was found that the coadministration resulted in a significant increase in the bioavailability of STT in the plasma (41.8%) and brain (68.7%) compared to administration of STT alone (p<0.05). The maximum drug concentration (Cmax) of STT was also found to be increased significantly in the plasma and brain compared to that achieved after monotherapy (p<0.05). However, STT failed to improve the pharmacokinetics of FLX up to a significant level. The results of this study showed that the combined regimen significantly reduced the level of cholesterol and triglyceride and increased the level of HDL when compared to STT monotherapy. Furthermore, the coadministration of STT with FLX led to an elevated level of neurotransmitters in the brain (p<0.05). FLX increased the concentration of STT in the plasma and brain. The coadministration of these drugs also led to an improved lipid profile. However, in the long-term, this interaction may have a vital clinical importance because the increase in STT level may lead to life-threatening side effects associated with statins.

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Cardiovascular mechanisms of SSRI drugs and their benefits and risks in ischemic heart disease and heart failure

Cited by 39 publications

References 0 publications

Paroxetine-Mediated GRK2 Inhibition Reverses Cardiac Dysfunction and Remodeling After Myocardial Infarction

Paroxetine-Mediated GRK2 Inhibition Reverses Cardiac Dysfunction and Remodeling After Myocardial Infarction

Effect of Depression and Sertraline Treatment on Cardiac Function in Female Nonhuman Primates

Simultaneous administration of fluoxetine and simvastatin ameliorates lipid profile, improves brain level of neurotransmitters, and increases bioavailability of simvastatin

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