Amitriptyline and Milnacipran interaction
Amitriptyline and Milnacipran: the Milnacipran prescribing label flags 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 Milnacipran (Milnacipran Hydrochloride) label · effective 2026-03-19
• Serotonin Syndrome : Increased risk when co-administered with other serotonergic agents, but also when taken alone.
If concomitant use of milnacipran hydrochloride with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms.
The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, tramadol, meperidine, methadone, lithium, tryptophan, buspirone, amphetamines, and St.
If it occurs, discontinue milnacipran hydrochloride and any other serotonergic agents, and initiate supportive treatment ( 5.2 ).
The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients.
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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.