Escitalopram × Tramadol

This pair meets at three points. Tramadol inhibits serotonin reuptake, so with escitalopram the risk of serotonin syndrome rises. Both drugs lower the seizure threshold (both SmPCs). The third point is kinetic: most of the analgesia comes from a tramadol metabolite formed via CYP2D6, and escitalopram inhibits this enzyme (escitalopram SmPC). Less active metabolite is formed and more tramadol itself stays in the blood (FDA tramadol label).

Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia, sweating, diarrhoea, tachycardia, and in severe cases hyperthermia and rigidity. Seizures can occur on this combination, including without serotonin syndrome. When less active tramadol metabolite is formed, pain relief is weaker than expected.

The combination is allowed but needs monitoring. In a patient with depression, the FDA tramadol label advises considering a non-opioid analgesic first. If tramadol is still needed, keep the daily dose at or below 400 mg, because seizure risk rises above it (tramadol SmPC). Tramadol is contraindicated in epilepsy that is not controlled; in controlled epilepsy it is used only when the circumstances require it, with close observation (both SmPCs). Watch for signs of serotonin syndrome at the start of co-treatment and after each dose increase. If they appear, stop both drugs at once and start symptomatic treatment (escitalopram SmPC). If escitalopram is being started, correct potassium and magnesium first, and in stable heart disease consider an ECG before the first dose. Escitalopram is contraindicated with a prolonged QT interval. If signs of arrhythmia appear, such as palpitations, skipped beats or fainting, stop escitalopram and do an ECG (escitalopram SmPC).