Is there a link between atrial fibrillation (A fib) and serotonin syndrome, particularly in individuals taking selective serotonin reuptake inhibitors (SSRIs)?

From the Guidelines

There is no established direct link between atrial fibrillation (A-fib) and serotonin syndrome in individuals taking selective serotonin reuptake inhibitors (SSRIs). While SSRIs like fluoxetine, sertraline, escitalopram, and paroxetine can potentially cause serotonin syndrome when taken in high doses or combined with other serotonergic medications, this syndrome typically manifests as neuromuscular abnormalities, autonomic hyperactivity, and mental status changes rather than cardiac arrhythmias like A-fib. Some SSRIs may cause minor QT interval prolongation, which theoretically could contribute to arrhythmias in susceptible individuals, but this is not directly related to serotonin syndrome.

Key Points to Consider

• Isolated cases of drug-induced atrial fibrillation have been reported with tricyclic and selective serotonin reuptake inhibitors antidepressants, as well as antipsychotics, in patients without previous heart diseases 1.
• The potential mechanisms of drug-induced atrial fibrillation are related to a direct effect on the heart, but the exact relationship between SSRIs and A-fib is not well established.
• Serotonin syndrome, on the other hand, is a condition caused by elevated brain serotonin levels, which can be triggered when serotonergic medications are combined, and its symptoms include mental status changes, neuromuscular hyperactivity, and autonomic hyperactivity 1.
• If you're taking SSRIs and develop symptoms like rapid heart rate, confusion, muscle rigidity, high fever, or sweating, seek immediate medical attention as these could indicate serotonin syndrome.
• Similarly, if you experience palpitations, shortness of breath, or chest discomfort while on SSRIs, consult your healthcare provider promptly as these could be signs of A-fib or other cardiac issues.

Important Considerations for Treatment

• Treatment for serotonin syndrome often involves discontinuing the precipitating agent and providing supportive care, which may include treatment of agitation, amelioration of hyperthermia, and management of autonomic instability 1.
• In severe cases of serotonin syndrome, emergency sedation, neuromuscular paralysis, and intubation may be considered.
• It's essential to monitor patients taking SSRIs for signs of serotonin syndrome and A-fib, and to seek medical attention immediately if any symptoms occur.

From the Research

Atrial Fibrillation and Serotonin Syndrome

• Atrial fibrillation (A fib) is a common heart rhythm disorder that can be influenced by various factors, including serotonin levels 2.
• Selective serotonin reuptake inhibitors (SSRIs) are known to affect cardiac conduction and may predispose individuals to A fib, although the relationship between SSRIs and A fib is complex and may be influenced by confounding factors 3.

Serotonin and Atrial Fibrillation

• Serotonin can cause arrhythmias in atrial trabeculae from patients with sinus rhythm, but this effect is reduced or abolished in patients with chronic A fib 2.
• SSRIs, such as fluoxetine, can have cardiodepressant and vasodilatory effects, which may contribute to the development of A fib 4.
• However, some studies suggest that SSRIs may actually reduce the incidence of A fib or decrease A fib burden in certain individuals 5.

Clinical Evidence

• A large register-based cohort study found that antidepressant use was associated with an increased risk of A fib during the first month following antidepressant initiation, but this risk diminished over time 3.
• A retrospective cohort study found that SSRI use was associated with reduced A fib burden in patients with cardiac implantable electronic devices 5.
• Another study found that fluoxetine, an SSRI, was not reported to affect the electrocardiogram (ECG) in chronic treatment, but dysrhythmia (atrial fibrillation and bradycardia) and syncope associated with fluoxetine treatment and overdose were reported 4.

Mechanisms and Interactions

• The mechanism by which SSRIs affect A fib is not fully understood, but it may involve the inhibition of the serotonin transporter and the potentiation of serotonin in the brain 6.
• The binding interactions between SSRIs and the serotonin transporter involve specific regions of the drug structures, which can influence the efficacy and side effects of these medications 6.
• Further research is needed to fully understand the relationship between SSRIs, serotonin, and A fib, as well as the potential benefits and risks of using SSRIs in individuals with A fib 3, 5.