Amitriptyline × Selegiline

Selegiline selectively inhibits monoamine oxidase type B (MAO-B), the enzyme mainly responsible for dopamine breakdown in the brain (selegiline SmPC). The US Food and Drug Administration (FDA) label for selegiline in Parkinson's disease adds that this inhibition is irreversible, that selectivity for MAO-B may be incomplete even at the recommended dose, and that it is lost above it (selegiline SmPC: above 10 mg a day). Amitriptyline is a tricyclic antidepressant that blocks the reuptake of noradrenaline and serotonin at nerve endings (amitriptyline SmPC). With breakdown slowed and reuptake blocked, serotonin builds up in the synapse. The selegiline SmPC reports severe central nervous system toxicity, a serotonin syndrome, sometimes with hypertension, hypotension and sweating, in patients on tricyclic antidepressants plus selegiline. On that basis it contraindicates the combination. The FDA amitriptyline label reports hyperpyretic crises, severe convulsions and deaths in patients given a tricyclic antidepressant together with an MAO inhibitor.

Serotonin syndrome: agitation, confusion, hallucinations, delirium up to coma, tremor, myoclonus, muscle rigidity, hyperreflexia, incoordination, hyperthermia, tachycardia, labile blood pressure, sweating, nausea, vomiting, diarrhoea (amitriptyline and selegiline SmPCs). With tricyclic antidepressants the selegiline SmPC describes severe central nervous system toxicity with hypertension, hypotension and sweating. The US Food and Drug Administration (FDA) amitriptyline label warns of hyperpyretic crises, severe convulsions and deaths when a tricyclic antidepressant and a monoamine oxidase (MAO) inhibitor are taken together.

The combination is contraindicated. The selegiline SmPC bans selegiline with tricyclic antidepressants (sections 4.3 and 4.5). The amitriptyline SmPC bans amitriptyline with monoamine oxidase (MAO) inhibitors and names selegiline (sections 4.3 and 4.5). The US Food and Drug Administration (FDA) amitriptyline label bans MAO inhibitors as a class. The two drugs are not given together at any dose or for any length of time. When switching from selegiline to amitriptyline, allow at least 14 days after the last dose of selegiline (FDA amitriptyline label; FDA label for selegiline in Parkinson's disease). Start amitriptyline cautiously, with gradual dose increases (FDA amitriptyline label). When switching from amitriptyline to selegiline, allow 14 days after stopping amitriptyline (amitriptyline SmPC). If a patient is already taking both, stop both immediately at the first signs of serotonin syndrome and start supportive treatment (FDA amitriptyline label). When the syndrome is suspected, the amitriptyline SmPC asks for a dose reduction or interruption depending on severity. The FDA label for the selegiline patch names only clomipramine and imipramine among tricyclics, but the oral selegiline and amitriptyline documents ban the whole class.