Amitriptyline and Paroxetine interaction
Amitriptyline and Paroxetine: 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
Anyone considering the use of amitriptyline hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need.
Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other.
The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide).
While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition.
The extent to which SSRITCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved.
From the Paroxetine (BRISDELLE) label · effective 2025-04-28
Serotonin Syndrome: BRISDELLE can cause serotonin syndrome with increased risk when co-administered with other serotonergic agents, but also when taken alone.
If concomitant use of BRISDELLE with other serotonergic drugs (besides MAOIs) is clinically warranted, consider the increased risk of serotonin syndrome and carefully observe the patient, particularly during BRISDELLE initiation [see Contraindications ( 4.1 )
Use caution with concomitant use of BRISDELLE with other drugs that are metabolized by CYP2D6, including nortriptyline, amitriptyline, imipramine, desipramine, fluoxetine, phenothiazines, risperidone, and Type 1C antiarrhythmics (e.g., propafenone, flecainide, and encainide).
The risk is increased with concomitant use of other serotonergic agents (including triptans, tricyclic antidepressants, fentanyl, tramadol, meperidine, methadone, lithium, tryptophan, buspirone, amphetamines, and St.
Tricyclic Antidepressants (TCA) (e.g., Desipramine) Increased plasma concentrations and elimination half-life Plasma TCA concentrations may need to be monitored and the TCA dosage may need to be reduced if a TCA is used concomitantly with BRISDELLE.
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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.