Citalopram × Tramadol

Tramadol inhibits serotonin reuptake, and so does citalopram, so together they raise the risk of serotonin syndrome. Both drugs lower the seizure threshold. Pharmacokinetics play little part: citalopram is only a weak CYP2D6 inhibitor, the enzyme that forms tramadol's active metabolite.

Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia, sweating, diarrhoea, tachycardia, and in severe cases hyperthermia and rigidity. Symptoms usually appear within a day of adding the second drug or raising the dose. In patients with cardiac risk factors QTc is tracked separately.

The Spanish citalopram label states that citalopram should not be used with serotonergic drugs, opioids and tramadol included. For pain relief in a patient taking citalopram, choose paracetamol. If tramadol is still needed, warn the patient about serotonin syndrome and watch for agitation, tremor, myoclonus, sweating and fever during the first days and after each dose increase. Stop both drugs if serotonin syndrome is suspected. Keep tramadol at or below 400 mg a day per the label, and use it in patients with epilepsy only when the circumstances require it.