Selegiline × Sertraline

Selegiline irreversibly inhibits monoamine oxidase (MAO), the enzyme that breaks down catecholamines and serotonin. At recommended doses it acts mainly on MAO type B (MAO-B) and loses this selectivity above 10 mg a day (selegiline SmPC; US Food and Drug Administration (FDA) selegiline label). Sertraline is a selective serotonin reuptake inhibitor: it stops nerve endings from taking serotonin back up. Selegiline slows serotonin breakdown, so serotonin builds up and serotonin syndrome can follow (sertraline SmPC, section 4.3; FDA sertraline label). Severe reactions have occurred even at the usual selegiline dose of 10 mg a day combined with sertraline, fluoxetine or paroxetine, and their mechanism is not fully understood (FDA selegiline label). Selegiline appears among the irreversible MAO inhibitors in the sertraline summary of product characteristics. The waiting times for this group therefore apply when switching between the two drugs (sertraline SmPC, section 4.5).

Combining selegiline with selective serotonin reuptake inhibitors, the class sertraline belongs to, can cause confusion, hypomania, hallucinations and manic episodes, agitation, myoclonus, hyperreflexia, incoordination, shivering, tremor, seizures, ataxia, sweating, diarrhoea, fever and hypertension, all of which can be part of serotonin syndrome (selegiline SmPC, section 4.5). Patients who started sertraline soon after stopping a monoamine oxidase inhibitor, or the other way round, have had tremor, myoclonus, sweating, nausea, vomiting, flushing, dizziness, hyperthermia resembling neuroleptic malignant syndrome and seizures, and some cases were fatal (sertraline SmPC, section 4.5). Tachycardia, labile blood pressure, muscle rigidity, delirium and coma can also occur (US Food and Drug Administration (FDA) sertraline label).

The combination is contraindicated (selegiline SmPC, sections 4.3 and 4.5; sertraline SmPC, sections 4.3 and 4.5, which give selegiline as an example; US Food and Drug Administration (FDA) sertraline label, section 4 and the table in section 7.1). Start sertraline no earlier than 14 days after stopping selegiline (sertraline SmPC, section 4.3; FDA sertraline and selegiline labels). When switching the other way, stop sertraline at least 7 days before the first dose of selegiline (sertraline SmPC, section 4.3). If a patient is already taking both, stop sertraline and selegiline immediately at the first signs of serotonin syndrome and start supportive symptomatic treatment (FDA sertraline label, section 5.2).