Protriptyline and Sertraline interaction
Protriptyline and Sertraline: 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 Protriptyline (Protriptyline Hydrochloride) label · effective 2023-07-25
Anyone considering the use of protriptyline hydrochloride or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need.
Tachycardia and postural hypotension may occur more frequently with protriptyline than with other antidepressant drugs.
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.
From the Sertraline (sertraline hydrochloride) label · effective 2025-08-06
Serotonin Syndrome: Increased risk when co-administered with other serotonergic agents, but also when taken alone.
If concomitant use of sertraline hydrochloride capsules with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms.
If serotonin syndrome occurs, consider discontinuation of sertraline hydrochloride capsules and/or concomitant serotonergic drugs [see Warnings and Precautions ( 5.2 )] .
The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, meperidine, methadone, tryptophan, buspirone, amphetamines, and St.
If it occurs, discontinue sertraline hydrochloride capsules and serotonergic agents and initiate supportive treatment ( 4 , 5.2 , 7.1 )
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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.