Amitriptyline and Fluvoxamine: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Amitriptyline
Fluvoxamine
No brand names on record
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
Both of these medicines raise serotonin in your body, and one can also slow how you break down the other. Fluvoxamine can push up the level of amitriptyline in your blood, which can make amitriptyline's side effects stronger (like drowsiness, dizziness, dry mouth, or a faster heartbeat). Together they can also raise your risk of a reaction called serotonin syndrome.
Watch for warning signs like shakiness, agitation, sweating, fever, a racing heart, confusion, or nausea and diarrhea, especially in the first weeks or after any dose increase. This combination is used carefully, and your care team can manage it by checking levels, adjusting your dose, and watching you closely. If you feel any of those symptoms, contact your doctor or pharmacist right away.
Direction: Fluvoxamine increases amitriptyline exposure via CYP inhibition (notably CYP2C19 and CYP1A2, which contribute to TCA metabolism), plus additive serotonergic (PD) effects. Neither agent is a prodrug, so effect and toxicity risk rise.
- Effect: Elevated TCA plasma levels; increased risk of serotonin syndrome.
- Onset: Unspecified; risk highest at initiation and dose escalation.
- Evidence: Probable. Severity: major.
- Management: Use caution; monitor plasma TCA concentrations and reduce TCA dose as needed. Monitor for serotonin syndrome (mental status changes, autonomic instability, neuromuscular signs, GI symptoms). If it occurs, consider discontinuing fluvoxamine and/or the serotonergic agent.
What happens
Increased tricyclic antidepressant exposure and an increased risk of serotonin syndrome
Interaction Deep Dive
When fluvoxaMINE is given together with serotonergic agents like tricyclic antidepressants (TCAs), plasma TCA levels may rise and the likelihood of serotonin syndrome may increase. Combining fluvoxaMINE with TCAs therefore warrants caution. Check plasma TCA concentrations and lower the TCA dose when necessary. In addition, watch patients for indications of serotonin syndrome, especially at the start of therapy and when the dose is being raised. The clinical picture of serotonin syndrome can involve altered mental status (for instance, agitation, hallucinations, delirium, and coma), autonomic instability (such as tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular findings (such as tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal manifestations (for example, nausea, vomiting, diarrhea). Surveillance for the onset of serotonin syndrome is advised. Should serotonin syndrome develop, discontinuing fluvoxaMINE and/or the accompanying serotonergic drugs should be considered1.
Why it happens (mechanism)
Additive serotonergic effects
How to manage this interaction
This combination can be managed with monitoring and dose tailoring. Keep taking both medicines as prescribed unless your prescriber tells you otherwise.
- Your team may check your amitriptyline blood levels and adjust (often lower) the amitriptyline dose to fit you.
- Expect closer monitoring, especially when starting either drug or increasing a dose.
- Learn the warning signs of serotonin syndrome: agitation, confusion, tremor, muscle stiffness or twitching, fever, sweating, fast or irregular heartbeat, and nausea, vomiting, or diarrhea.
- Contact your pharmacist or prescriber if these appear, and seek urgent care for severe or fast-worsening symptoms.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
5 reports — tap to read
a) The impact of fluvoxaMINE on the pharmacokinetics of imipramine and desipramine was examined in 12 healthy volunteers. When given together with fluvoxaMINE, imipramine half-life rose significantly (from 23 to 41 hours) and its clearance fell (from 1.02 to 0.28 L/h/kg). No meaningful changes in the pharmacokinetics of desipramine were observed 2.
b) In four patients, adding fluvoxaMINE to imipramine or desipramine was reported to cause markedly elevated tricyclic antidepressant plasma concentrations. Three of these four patients displayed indications of tricyclic toxicity 3.
c) The influence of fluvoxaMINE, 100 mg/day for 10 days, on tricyclic antidepressant plasma concentrations was investigated in 15 depressed patients receiving maintenance treatment with imipramine (7 patients) or desipramine (8 patients). When fluvoxaMINE was added to desipramine therapy, a small but insignificant rise in desipramine concentrations occurred after 10 days. Imipramine plasma levels were three to four times higher while fluvoxaMINE was coadministered. One patient reported anticholinergic effects, together with tremor and confusion. The basis of this drug interaction was inhibition of the demethylation of imipramine 4.
d) FluvoxaMINE has been demonstrated to significantly raise plasma concentrations of amitriptyline and clomiPRAMINE and to mildly raise levels of their respective metabolites nortriptyline and desmethylclomiPRAMINE. This may result from competitive inhibition of oxidative metabolism in the liver 5.
e) The metabolism of tricyclic antidepressants given alongside fluvoxaMINE was studied in eight depressed patients (one patient received amitriptyline). FluvoxaMINE was found to interfere with the N-demethylation of amitriptyline. Combining fluvoxaMINE with amitriptyline produced increased amitriptyline plasma levels and decreased concentrations of amitriptyline's N-demethylated metabolite, nortriptyline. Additionally, fluvoxaMINE plasma levels were increased 6.
Common questions
Can I take Amitriptyline and Fluvoxamine together?
Fluvoxamine can raise amitriptyline levels and add to serotonin effects, increasing the risk of serotonin syndrome, so your care team will likely lower the amitriptyline dose and monitor you, especially early on. Watch for agitation, tremor, fever, sweating, or a racing heart and report them promptly. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amitriptyline and Fluvoxamine interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Amitriptyline and Fluvoxamine interaction managed?
This combination can be managed with monitoring and dose tailoring. Keep taking both medicines as prescribed unless your prescriber tells you otherwise. Your team may check your amitriptyline blood levels and adjust (often lower) the amitriptyline dose to fit you. Expect closer monitoring, especially when starting either drug or increasing a dose. Learn the warning signs of serotonin syndrome: agi… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Amitriptyline or Fluvoxamine need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (6)
- Product Information: Fluvoxamine maleate oral tablets, fluvoxamine maleate oral tablets. ANI Pharmaceuticals Inc (per FDA), Baudette, MN, 2023. DailyMed
- Spina E, Pollicino AM, Avenoso A, et al: Effect of fluvoxamine on the pharmacokinetics of imipramine and desipramine in healthy subjects. Ther Drug Monit 1993; 15:243-246. PubMed
- Spina E, Campo GM, Avenoso A, et al: Interaction between fluvoxamine and imipramine/desipramine in four patients. Ther Drug Monit 1992; 14:194-196. PubMed
- Spina E, Pollicino AM, Avenoso A, et al: Fluvoxamine-induced alterations in plasma concentrations of imipramine and desipramine in depressed patients. Int J Clin Pharmacol Res 1993a; 13:167-171.
- Bertschy G, Vandel S, Vandel G, et al: Fluvoxamine-tricyclic antidepressant interaction: an accidental finding. Eur J Clin Pharmacol 1991; 40:119-120. PubMed
- Hartter S, Wetzel H, Hammes E, et al: Inhibition of antidepressant demethylation and hydroxylation by fluvoxamine in depressed patients. Psychopharmacology 1993; 110:302-308. PubMed
Keep reading about Amitriptyline
Keep reading about Fluvoxamine
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