MAJOR — Use With Caution
DANGEROUS — potent CYP2D6 inhibition elevates TCA levels
Evidence level: STRONG
Paxil dramatically increases amitriptyline to dangerous levels.
Paroxetine is a potent CYP2D6 inhibitor, dramatically increasing TCA levels. Combined serotonergic effect.
Generally avoid. If necessary, major TCA dose reduction and level monitoring required.
Take Paroxetine at the same time each day — morning is most common to avoid sleep disruption. Amitriptyline follows its prescribed schedule. SSRIs have a long half-life, so consistency matters more than the exact hour.
Cardiac disease, elderly, CYP2D6 poor metabolizers
Cardiac arrhythmias, seizures, anticholinergic toxicity, serotonin syndrome
Discuss safer alternatives to combining these medications.
Discuss this combination with your prescriber. They may adjust timing, dosing, or switch to an alternative with fewer interaction risks. Never stop an antidepressant abruptly — taper under medical guidance.
Paxil dramatically increases amitriptyline to dangerous levels.
Take Paroxetine at the same time each day — morning is most common to avoid sleep disruption. Amitriptyline follows its prescribed schedule. SSRIs have a long half-life, so consistency matters more than the exact hour.
Cardiac arrhythmias, seizures, anticholinergic toxicity, serotonin syndrome
Discuss this combination with your prescriber. They may adjust timing, dosing, or switch to an alternative with fewer interaction risks. Never stop an antidepressant abruptly — taper under medical guidance.
Discuss safer alternatives to combining these medications.
Or browse the full interaction database (121,000+ pairs).