Amitriptyline and Selegiline interaction
Amitriptyline and Selegiline: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.
Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.
What the FDA labels say
From the Amitriptyline (Amitriptyline Hydrochloride) label · effective 2025-11-25
It should not be given concomitantly with monoamine oxidase inhibitors.
When it is desired to replace a monoamine oxidase inhibitor with amitriptyline hydrochloride, a minimum of 14 days should be allowed to elapse after the former is discontinued.
Monoamine oxidase inhibitors – see CONTRAINDICATIONS section.
From the Selegiline (ZELAPAR) label · effective 2021-06-01
John’s wort or cyclobenzaprine (a tricyclic muscle relaxant).
• May cause serotonin syndrome when used with antidepressants (5.2)
In the post-marketing period, fatal and non-fatal cases of serotonin syndrome have been reported in patients treated with antidepressants concomitantly with ZELAPAR [see Contraindications (4) and Drug Interactions ( 7.1 , 7.2 , 7.3 )] .
Because the mechanisms responsible for these reactions are not fully understood, avoid the combination of ZELAPAR with any antidepressant.
…allow concomitant use of any selective serotonin re-uptake inhibitor (e.g., fluoxetine-Prozac, fluvoxamine-Luvox, paroxetine-Paxil, sertraline, venlafaxine-Effexor, or nefazodone-Serzone) or any non-selective serotonin reuptake inhibiting antidepressant drug (except when taken at a low dose and only at night for the purpose of effective sleep) with ZELAPAR.
Taking more than these two? Interactions stack. Check your whole list at once; it stays in your browser.
Open in the checkerNot medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.