Sertraline Causes Strong Coronary Vasodilation: Possible Relevance for Cardioprotection by Selective Serotonin Reuptake Inhibitors

Melle, Joost P. van; Buikema, Hendrik; Berg, Maarten P. van den; Buiten, Azuwerus van; Veldhuisen, Dirk J. van; Boonstra, Piet W.; Gilst, Wiek H. van

doi:10.1007/s10557-004-6221-3

Cited by 19 publications

(16 citation statements)

References 26 publications

(30 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sertraline is an SSRI antidepressant capable of restoring the function of the hypothalamic–pituitary–adrenal axis, 25 of improving vascular vasodilatation through the stimulation of calcium mobilization/release in the vascular wall, 26 and of enhancing the production of nitric oxide 14 , 15 , 16 . A recent study showed that sertraline has vasoactive effects in preconstricted rat arteries (including the coronary vascular bed) and in rings of human internal mammary arteries 13 …”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of Selective Serotonin Reuptake Inhibitor Therapy on Endothelial Function and Inflammatory Markers in Patients With Coronary Heart Disease

Pizzi

Mancini

Angeloni

et al. 2009

Clin Pharmacol Ther

125

View full text Add to dashboard Cite

We investigated the effect of sertraline on inflammation and endothelial function in patients with coronary heart disease (CHD) and symptoms of depression. One hundred patients with CHD and depression were randomized in a double-blind fashion to receive sertraline or a placebo. We measured symptoms of depression (Beck Depression Inventory (BDI) score), levels of inflammatory markers (C-reactive protein (CRP) and interleukin-6 (IL-6)), and flow-dependent endothelium-mediated dilation (FMD) before and after 20 weeks of treatment. Sertraline treatment significantly reduced the BDI score as compared with both baseline and placebo. Levels of CRP and IL-6 also decreased after 20 weeks of sertraline treatment, whereas they did not significantly change in the placebo group. There was a significant improvement in FMD in patients on sertraline treatment, whereas there was no change in FMD in the placebo group. Sertraline improves endothelial function and reduces inflammatory markers in patients with CHD and symptoms of depression.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Antidepressant therapy involving selective serotonin reuptake inhibitors (SSRIs) has been shown to alleviate symptoms of depression, 10 improve quality of life, 11 regulate sympathetic and parasympathetic balance, 12 modulate vascular tone, 13 improve platelet function, and exhibit endothelium‐protective properties 14 …”

mentioning

confidence: 99%

Effects of Selective Serotonin Reuptake Inhibitor Therapy on Endothelial Function and Inflammatory Markers in Patients With Coronary Heart Disease

Pizzi

Mancini

Angeloni

et al. 2009

Clin Pharmacol Ther

125

View full text Add to dashboard Cite

show abstract

“…However, sertraline has multiple effects which could influence events in the artery wall. For example, sertraline is a potent vasodilator (58,59) and interferes with platelet function (60,61), although how these might adversely influence atherosclerosis is unclear. More research is needed to understand the effects of SSRIs on artery wall biology.…”

Section: Discussionmentioning

confidence: 99%

Effects of Long-Term Sertraline Treatment and Depression on Coronary Artery Atherosclerosis in Premenopausal Female Primates

Shively

Appt

et al. 2015

Psychosomatic Medicine

View full text Add to dashboard Cite

Objectives Major depressive disorder and coronary heart disease (CHD) often co-occur in the same individuals. Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed for depression and other disorders, but their effects on CHD risk remain unclear. We determined the effects of a SSRI on coronary artery atherosclerosis (CAA) in an established nonhuman primate model used to clarify the association between depression and CAA. Methods 42 adult female cynomolgus macaques consuming a Western diet were characterized during an 18-month pretreatment phase, and assigned to SSRI (sertraline HCl 20 mg/kg, po, once/day) or Placebo balanced on pretreatment depression, body weight (BW), and iliac artery atherosclerosis extent measured via biopsy. After 18 months CAA extent was measured using histomorphometry. Results Before and during treatment depressed monkeys had lower BW, body mass index (BMI), and plasma high density lipoprotein cholesterol, and higher heart rates during the pretreatment (p<0.01) but not the treatment phase (p=0.17). There were no pretreatment differences between the sertraline and placebo groups. Sertraline reduced anxious behavior but had no effect on BW, BMI, heart rate, plasma lipids, or depression. CAA, analyzed by a 2 (Depressed, Nondepressed) × 2 (Placebo, Sertraline) × 3 (coronary arteries) analysis of covariance adjusted for pretreatment iliac atherosclerosis, was greater in depressed than nondepressed monkeys (p<0.036), and in sertraline than placebo-treated monkeys (p=0.040). The observed CAA extent in depressed monkeys treated with sertraline was 4.9 times higher than in untreated depressed monkeys, and 6.5 times higher than in non-depressed monkeys, on average. Conclusions Depressed animals develop more CAA, and that longterm treatment with sertraline promotes CAA.

show abstract

“…Since the serotonin transporter is also expressed in platelets, there has been an active debate in the literature regarding the effects of SSRIs on the vascular system. Multiple studies suggest that SSRIs are generally safe in patients with vascular disease6 and have beneficial effects in such patients by decreasing platelet aggregation7 8 and by vasodilation 9 10. Other studies, however, have associated the use of SSRIs with increased incidence of vasospasm and poor clinical outcomes after subarachnoid haemorrhage11 as well as increased mortality and poor cardiovascular outcomes after coronary artery bypass grafting 12.…”

Section: Introductionmentioning

confidence: 99%

Incident user cohort study of risk for gastrointestinal bleed and stroke in individuals with major depressive disorder treated with antidepressants

et al. 2012

View full text Add to dashboard Cite

ObjectiveTo examine the association between exposure to newer antidepressants and risk of gastrointestinal (GI) and other bleeding complications among individuals with major depressive disorder (MDD).DesignThis study uses an incident user cohort design to compare associations between incidence of vascular/bleeding events and the relative affinity (low, moderate or high) of the antidepressant for the serotonin transporter during an exposure risk period for each patient.SettingNew England healthcare system electronic medical record database.Participants36 389 individuals with a diagnosis of MDD and monotherapy with a selective serotonin reuptake inhibitor, serotonin–norepinephrine reuptake inhibitor or other new-generation antidepressant were identified from among 3.1 million patients in a New England healthcare system.Primary and secondary outcome measuresRates of bleeding or other vascular complications, including acute liver failure, acute renal failure, asthma, breast cancer and hip fractures.Results601 GI bleeds were observed in the 21 462 subjects in the high-affinity group versus 333 among the 14 927 subjects in the lower affinity group (adjusted RR: 1.17, 95% CI 1.02 to 1.34). Similarly, 776 strokes were observed in the high-affinity group versus 434 in the lower affinity treatment group (adjusted RR: 1.18, 95% CI 1.06 to 1.32). No significant association with risk for a priori negative control outcomes, including acute liver failure, acute renal failure, asthma, breast cancer and hip fractures, was identified.ConclusionsUse of antidepressants with high affinity for the serotonin transporter may confer modestly elevated risk for GI and other bleeding complications. While multiple methodologic limitations must be considered, these results suggest that antidepressants with lower serotonin receptor affinity may be preferred in patients at greater risk for such complications.

show abstract

Sertraline Causes Strong Coronary Vasodilation: Possible Relevance for Cardioprotection by Selective Serotonin Reuptake Inhibitors

Abstract: One of the SSRIs, sertraline, showed marked vasodilatory effects in rat aorta and human IMAs. Sertraline elicited vasodilatation in coronary arteries during perfusion of rat hearts. These hemodynamic effects may explain

Cited by 19 publications

References 26 publications

Effects of Selective Serotonin Reuptake Inhibitor Therapy on Endothelial Function and Inflammatory Markers in Patients With Coronary Heart Disease

Effects of Selective Serotonin Reuptake Inhibitor Therapy on Endothelial Function and Inflammatory Markers in Patients With Coronary Heart Disease

Effects of Long-Term Sertraline Treatment and Depression on Coronary Artery Atherosclerosis in Premenopausal Female Primates

Incident user cohort study of risk for gastrointestinal bleed and stroke in individuals with major depressive disorder treated with antidepressants

Contact Info

Product

Resources

About