Nefazodone and Paroxetine interaction
Nefazodone 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 Nefazodone (Nefazodone Hydrochloride) label · effective 2025-07-31
Anyone considering the use of nefazodone hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need.
Nefazodone hydrochloride tablets are also contraindicated in patients who have demonstrated hypersensitivity to nefazodone hydrochloride, its inactive ingredients, or other phenylpiperazine antidepressants.
…nefazodone and its major metabolites are not altered in these “poor metabolizers.” Plasma concentrations of one minor metabolite (mCPP) are increased in this population; the adjustment of nefazodone dosage is not required when administered to “poor metabolizers.” Nefazodone and its metabolites have been shown in vitro to be extremely weak inhibitors of CYP2D6.
Hyponatremia : Hyponatremia may occur as a result of treatment with SNRIs and SSRIs, including nefazodone.
For a selective serotonin reuptake inhibitor (SSRI), these reactions have included hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma.
From the Paroxetine (PAROXETINE HYDROCHLORIDE) label · effective 2026-09-16
Serotonin Syndrome: Increased risk when co-administered with other serotonergic agents, but also when taken alone.
If concomitant use of Paroxetine HCL CR 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, lithium, tramadol, meperidine, methadone, tryptophan, buspirone, amphetamines, and St.
Other Serotonergic Drugs Clinical Impact The concomitant use of serotonergic drugs with Paroxetine HCL CR increases the risk of serotonin syndrome.
Activation of Mania or Hypomania In patients with bipolar disorder, treating a depressive episode with Paroxetine HCL CR or another antidepressant may precipitate a mixed/manic episode.
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.