Fluoxetine, more commonly known by its brand name Prozac, is an antidepressant medication belonging to the selective serotonin reuptake inhibitor (SSRI) drug class. By blocking the reuptake of the neurotransmitter serotonin, Prozac can reduce depression and induce feelings of happiness or well-being.1 Propofol is a widely used general anesthesia that exerts its effects by binding to gamma-aminobutyric acid (GABA) receptors in the brain, thereby amplifying the effect of GABA and inhibiting the transmission of electrical signals along neurons.2 Though fluoxetine and propofol may seem to share nothing in common, they can both lead to the same rare but serious side effect: irregular heart rhythms, or arrhythmias.
Arrhythmias occur via the prolongation of what is known as the QT interval, a measurement made on an electrocardiogram (ECG or EKG). An ECG measures the electrical activity of the heart by detecting electrical waves that propagate from the heart and can be picked up by electrodes attached to the skin. The readout of an ECG is a waveform comprised of three waves: P, QRS, and T. The P wave represents atrial depolarization, electrical signals that cause the atria, or upper chambers of the heart, to contract and push blood to the heart’s lower chambers, known as ventricles.3 The QRS wave complex represents ventricular depolarization, which causes the ventricles to contract and pump blood out to the body; atrial repolarization, or relaxation, is also represented by this wave. Finally, the T wave represents the start of ventricular repolarization, at which point the atria are also refilling with blood, restarting the cycle.
The QT interval, therefore, is the time it takes the ventricles to depolarize and repolarize: in other words, the amount of time for the heart to contract and pump blood and refill with blood before beating again.4 A long QT interval, which can be inherited congenitally or acquired via medication or treatment, sometimes does not manifest in symptoms, but there is a risk that it can disrupt the heart’s normal electrical signaling and produce arrythmias, which in turn can lead to fainting, seizures, and even cardiac arrest.
Both fluoxetine and propofol have been associated with rare instances of QT interval prolongation. In a 2017 study, researchers studied over 600,000 patients who received propofol over 17 years and found that the incidence of torsade de pointes—an arrythmia associated with long QT—was 1.93 per million.5 There have also been individual reports of patients acquiring long QT syndrome after taking fluoxetine.6 In theory, the concurrent use of two drugs that are implicated in long QT could lead to an increased risk of dangerous arrythmias.
An individual’s risk of developing drug-induced long QT syndrome, however, can be unpredictable. And many patients who develop the disorder have at least one risk factor, including congestive heart failure, potassium deficiency, and, interestingly, the female sex, in addition to exposure to a drug associated with long QT.7 Nevertheless, patients undergoing treatment with multiple such drugs, such as fluoxetine and propofol, should consult with care providers for proper risk management.
References
1. Sohel, A. J., Shutter, M. C., Patel, P. & Molla, M. Fluoxetine. in StatPearls (StatPearls Publishing, Treasure Island (FL), 2024).
2. Sahinovic, M. M., Struys, M. M. R. F. & Absalom, A. R. Clinical Pharmacokinetics and Pharmacodynamics of Propofol. Clin. Pharmacokinet. 57, 1539–1558 (2018), DOI: 10.1007/s40262-018-0672-3
3. Ashley, E. A. & Niebauer, J. Conquering the ECG. in Cardiology Explained (Remedica, 2004).
4. Cox, N. K. The QT interval: How long is too long? Nurs. Made Incred. Easy 9, 17 (2011).
5. Abrich, V. A., Ramakrishna, H., Mehta, A., Mookadam, F. & Srivathsan, K. The possible role of propofol in drug-induced torsades de pointes: A real-world single-center analysis. Int. J. Cardiol. 232, 243–246 (2017), DOI: 10.1016/j.ijcard.2017.01.011
6. Tiver, K. D. et al. Vomiting, electrolyte disturbance, and medications; the perfect storm for acquired long QT syndrome and cardiac arrest: a case report. J. Med. Case Reports 16, 9 (2022), DOI: 10.1186/s13256-021-03204-7
7. Roden, D. M., Woosley, R. L. & Primm, R. K. Incidence and clinical features of the quinidine-associated long QT syndrome: implications for patient care. Am. Heart J. 111, 1088–1093 (1986), DOI: 10.1016/0002-8703(86)90010-4