Atomoxetine × Escitalopram

Escitalopram prolongs the QT interval in a dose-dependent way (escitalopram summary of product characteristics, SmPC, Spanish Agency of Medicines and Medical Devices, AEMPS). According to its own SmPC, atomoxetine can also prolong QT, which is listed among its adverse reactions. In a dedicated study, the corrected QT interval (QTc) rose slightly as atomoxetine concentrations increased, although at the expected peak concentrations it did not differ from placebo (atomoxetine SmPC, AEMPS). The liver breaks down atomoxetine through the enzyme CYP2D6, which escitalopram inhibits. Escitalopram doubled the plasma concentrations of desipramine and metoprolol, two other substrates of this enzyme (SmPCs of both drugs, AEMPS). With the strong CYP2D6 inhibitors fluoxetine and paroxetine, atomoxetine exposure rose 6- to 8-fold. The US Food and Drug Administration (FDA) describes the effect of escitalopram on this enzyme as modest, and no study has tested this exact pair (atomoxetine and escitalopram FDA labels). The atomoxetine SmPC reports serotonin syndrome when atomoxetine was combined with selective serotonin reuptake inhibitors, the group escitalopram belongs to (atomoxetine SmPC, AEMPS).

QT interval prolongation itself causes no symptoms and shows only on the electrocardiogram (ECG). Torsade de pointes, a form of ventricular tachycardia, causes palpitations, dizziness and fainting. With escitalopram, such arrhythmias were reported mainly in women and in people with low potassium, a pre-existing long QT interval or other heart disease (escitalopram summary of product characteristics, SmPC). Higher atomoxetine concentrations raise the risk of its adverse reactions, with larger rises in heart rate and blood pressure (atomoxetine label, US Food and Drug Administration, FDA). Serotonin syndrome presents with agitation, tremor, muscle jerks and fever (escitalopram SmPC).

The combination is contraindicated. The escitalopram summary of product characteristics (SmPC) forbids its use with other drugs that prolong the QT interval (escitalopram SmPC, Spanish Agency of Medicines and Medical Devices, AEMPS). According to its own SmPC, atomoxetine can prolong QT (atomoxetine SmPC, AEMPS). The US Food and Drug Administration (FDA) labels are softer: they carry no QT contraindication and ask for caution when escitalopram is combined with drugs broken down by the enzyme CYP2D6 (escitalopram FDA label). Escitalopram is also contraindicated in people with a history of QT prolongation or congenital long QT syndrome (escitalopram SmPC, AEMPS). If both drugs are still taken, correct low potassium and magnesium before starting escitalopram. In stable heart disease, consider an electrocardiogram (ECG) before the start. If signs of arrhythmia appear, stop escitalopram and record an ECG (escitalopram SmPC, AEMPS). With CYP2D6 inhibitors, atomoxetine may need a slower titration and a lower final dose. If an inhibitor is started or stopped after the atomoxetine dose has been set, reassess response and tolerability (atomoxetine SmPC, AEMPS). Measure pulse and blood pressure before starting atomoxetine, after each dose change and at least every 6 months (atomoxetine SmPC, AEMPS). If serotonin syndrome appears, stop escitalopram and the serotonergic drug at once and start symptomatic treatment (escitalopram SmPC, AEMPS). In this case, the atomoxetine SmPC advises reducing the atomoxetine dose or stopping it, depending on severity (atomoxetine SmPC, AEMPS).