Can Zoloft Cause Heart Palpitations?

In the modern world, pills have become a symbol of medicine. They are able to help us even with psychological diseases. One of the pills commonly prescribed for some of the diseases of the psyche is Zoloft. However, with any interference with the normal processes in the body come certain risks. In this blog, we will look at the potential cardiovascular influence Zoloft can cause. We will focus on whether this drug can be the reason for heart palpitations.
Jakub Gwiazdecki

Jakub Gwiazdecki

Fifth year medical student at the Medical Faculty of Comenius University in Bratislava.

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Can Zoloft cause heart palpitations?

Zoloft, also known as sertraline, is generally well-tolerated, but it can cause a range of side effects. While heart palpitations are not officially mentioned among the side effects, they can occur as a result of a racing heart.

Zoloft was found to cause changes in the electrical activity of the heart. It prolongs the QT interval, which is the time needed for the heart to recharge between beats [1]. Longer QT intervals can potentially lead to irregular heart rhythms, which might be perceived as heart palpitations. There are some indications that the group of drugs to which sertraline belongs can both cause and protect against arrhythmia, a common source of palpitations [2]. That being said, heart palpitations are not a specific side effect of Zoloft. However, in some individuals, they can occur.

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What is Zoloft?

Zoloft is a selective serotonin reuptake inhibitor (SSRI). It is a medication used primarily in the treatment of depression in psychiatry. The active substance in Zoloft is sertraline hydrochloride. It works by influencing serotonin levels in the brain at neuronal connections. Serotonin is a naturally occurring neurotransmitter that produces a feeling of well-being. By increasing serotonin levels in the brain, Zoloft can improve mood, appetite, energy levels, and sleep quality [3, 4]. In psychiatry, Zoloft is prescribed for the treatment of major depressive disorder, obsessive-compulsive disorder (OCD), panic disorder, post-traumatic stress disorder (PTSD), social anxiety disorder, and bipolar disorder. It can be used alone or in combination with other drugs and therapies and is approved for use in children from 6 years old for OCD treatment [5, 3].

SSRIs can cause a life-threatening condition named serotonin syndrome

What is the physiology and the mechanism of action of Zoloft?

The primary mechanism of action of selective serotonin reuptake inhibitors is an increase in the extracellular levels of serotonin in the synaptic cleft. This is achieved by blocking and inhibiting the reuptake of serotonin, thus increasing its availability [6]. However, this is only a traditional description of the working mechanism. It was found that Zoloft can also inhibit different types of sodium and potassium channels, as well as glutamate uptake activity. The clearance of extracellular glutamate is essential to maintain the central nervous system in physiological conditions. The impairment of the Kir4.1 K+ channel activity, which Zoloft has been shown to inhibit, can result in an accumulation of extracellular glutamate [6]. Generally, an imbalance in glutamate distribution in the brain can potentially lead to disruption of neuronal metabolism. In addition, Zoloft has been found to have effects on intracellular vasculogenic membranes. These membranes contribute to the blood-brain barrier. In the absence of the serotonin/5-HT transporter, sertraline targets phospholipid membranes. This interaction with the membranes can lead to changes in their shape and function [7].

Furthermore, Zoloft has been shown to have acute functional effects on the nicotinic acetylcholine receptor (nAChR). The nAChRs impact many processes, such as anxiety responses. As they are also targeted by the drugs, they could play an additional role in their antidepressant effects [8].

How can Zoloft impact the cardiovascular system?

There is little in the medical literature about Zoloft’s impact on the cardiovascular system. Nevertheless, other SSRIs have been described from that perspective. As the mechanism of action of this class of medication is similar, it allows the drawing of some possible analogies. In general, SSRIs have a more benign cardiovascular safety profile compared to other antidepressants. For example, citalopram was found to have a small reduction in heart rate, with no significant effects on the electrical activity of the heart [9]. Another SSRI, fluoxetine, was found to induce a 6% decrease in heart rate, a 2% increase in systolic pressure, and a 7% increase in ejection fraction [10]. Two of these changes are beneficial for the heart and blood vessels, while the increase in systolic blood pressure is not. However, at certain concentrations, fluoxetine showed cardio-depressant and vasodilatory effects [11], both of which are favorable and lower cardiovascular risk. Escitalopram, another SSRI, was found to increase mean arterial pressure while decreasing heart rate. It also caused a reduction in the sympathetic component of heart rate variability and an elevation of the parasympathetic component [12]. A sedative effect on the heart is also a positive factor, as long as there is no physically exhausting chronic overload. All of the above are studies on other SSRIs. However, they indicate that this group of drugs can have a potentially good effect on the heart. Following this hypothetical thinking, Zoloft could similarly cause a decrease in heart rate. Obviously, this is just a theoretical statement, which needs evidence-based validation.

What are the cardiovascular risk factors for Zoloft?

Although Zoloft has a hypothetically positive impact on the heart, there are some risk factors associated with the cardiovascular system. One of the main cardiovascular risks is an increase in cholesterol levels. Katrine Kveli Fjukstad et al. found that SSRIs with an average range concentration were associated with an increase in total cholesterol by 14.56 mg/dL and in LDL cholesterol by 8.50 mg/dL. High levels of cholesterol are risk factors for atherosclerosis and coronary artery disease. Additionally, the levels of triglycerides were increased by 46.49 mg/dL [13]. SSRIs are also associated with metabolic syndrome. Therefore, the use of Zoloft increases the risk of heart disease, stroke, and type 2 diabetes. The occurrence of metabolic syndrome increases by a factor of 2.10 with an average of the recommended concentration of SSRIs [13].

Jakub Gwiazdecki

Jakub Gwiazdecki

Jakub is in his fifth year as a medical student at Comenius University in Bratislava, Slovakia. He has special interested in cardiology and in patient-centered medicine. His love for heart health isn't just book-smarts; he wants to know how it works, what it means for our feelings, and how key it is for health and happiness. Jakub thinks real good health care comes from always putting the patient at the centre, treating each person as a whole.