Drug interactions
Paroxetine + Trazodone
Severity: Major
Paroxetine and Trazodone: major interaction.
Last updated
For healthcare professionals — reference only. This page is a brief summary, not medical advice and not a substitute for official labeling or clinical judgement. Always verify before prescribing or dispensing.
Summary
Both drugs enhance serotonergic neurotransmission, so combined use raises the risk of serotonin syndrome, with agitation, tremor, hyperthermia, and neuromuscular hyperactivity. Paroxetine also inhibits CYP2D6 and may raise exposure to trazodone's active metabolite, adding to sedation and serotonergic effects.
What this interaction means in plain words
Paroxetine and Trazodone can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for.
Paroxetine belongs to Central Nervous System; Trazodone belongs to Central Nervous System.
Why it happens
Additive serotonergic effects (SSRI reuptake inhibition plus trazodone serotonin modulation), with possible CYP2D6 inhibition by paroxetine.
What to do
Avoid the combination where possible; if low-dose trazodone is used for insomnia with paroxetine, start at the lowest dose and monitor for serotonin toxicity signs. Stop both drugs and give supportive care if serotonin syndrome develops.
What to ask your pharmacist
- Does the benefit of taking both outweigh the risk in my case?
- Do I need any blood test, ECG or other check while on both?
- What early warning signs should I watch for, and what should I do if they appear?
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Other interactions of Paroxetine
- Isocarboxazid + Paroxetine Contraindicated
- Methylene blue + Paroxetine Contraindicated
- Paroxetine + Phenelzine Contraindicated
- Paroxetine + Pimozide Contraindicated
- Paroxetine + Procarbazine Contraindicated
- Paroxetine + Selegiline Contraindicated
Other interactions of Trazodone
- Arsenic trioxide + Trazodone Contraindicated
- Ibutilide + Trazodone Contraindicated
- Isocarboxazid + Trazodone Contraindicated
- Levoketoconazole + Trazodone Contraindicated
- Methylene blue + Trazodone Contraindicated
- Phenelzine + Trazodone Contraindicated
Frequently asked questions
Can I take Paroxetine with Trazodone?
MediHelp rates the interaction as major. Paroxetine and Trazodone can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for. Both drugs enhance serotonergic neurotransmission, so combined use raises the risk of serotonin syndrome, with agitation, tremor, hyperthermia, and neuromuscular hyperactivity. Paroxetine also inhibits CYP2D6 and may raise exposure to trazodone's active metabolite, adding to sedation and serotonergic effects.
How serious is the interaction between Paroxetine and Trazodone?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Avoid the combination where possible; if low-dose trazodone is used for insomnia with paroxetine, start at the lowest dose and monitor for serotonin toxicity signs. Stop both drugs and give supportive care if serotonin syndrome develops.
What other medicines interact with Paroxetine?
MediHelp also lists interactions of Paroxetine with, for example, Isocarboxazid, Methylene blue, Phenelzine. The full list is on the Paroxetine page.
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