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What the FDA labels say about taking them together

Amitriptyline and paroxetine

Amitriptyline's FDA label of September 8, 2026 names paroxetine in its drug interactions section, and paroxetine's label names amitriptyline too. The amitriptyline label: “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.”

Check it at the source: the amitriptyline FDA label on DailyMed (effective September 8, 2026, Sun Pharmaceutical Industries, Inc.); the paroxetine FDA label on DailyMed (effective February 12, 2026, Mylan Pharmaceuticals Inc.).

What does the amitriptyline label say about paroxetine?

Amitriptyline label, drug interactions

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.

Source: FDA drug label (Amitriptyline Hydrochloride), Sun Pharmaceutical Industries, Inc., effective September 8, 2026 (SPL set 4e520c63-1cf6-40f6-a51c-3f9b0e181342), via openFDA; the full label on DailyMed

What does the paroxetine label say about amitriptyline?

Brisdelle label (Legacy Pharma USA, Inc., April 28, 2025), drug interactions

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).

Source: FDA drug label (Brisdelle, NDA204516), Legacy Pharma USA, Inc., effective April 28, 2025 (SPL set 502311b3-b617-4cbd-a3ab-a60f2c62880a), via openFDA

Source: FDA drug label (Paroxetine), Mylan Pharmaceuticals Inc., effective February 12, 2026 (SPL set 89dd7e24-85fc-4152-89ea-47ec2b48a1ed), via openFDA; the full label on DailyMed

These are the labels' own sentences. PlainMeds does not grade interactions; a pharmacist or prescriber can say what they mean for one person's medicines.

Both medicines on the record

34Amitriptyline generic labelers
45Paroxetine generic labelers
AmitriptylineParoxetine
Labeled forDepressionDepression, Anxiety, Menopause symptoms
Boxed warningYesYes
Pharmacy cost (NADAC)$0.03 per tablet 10 mg tablet$0.0611 per tablet 20 mg tablet
Shortage nowNo current entryNo current entry

Source: FDA NDC Directory, CMS NADAC of October 7, 2026 and the FDA Drug Shortage Database (FDA files October 8, 2026)

What next?