Lower Strength Tricyclics; Trazodone/Fluoxetine; Paroxetine Interactions

This information is generalized and not intended as specific medical advice. Consult your healthcare professional before taking or discontinuing any drug or commencing any course of treatment.

Medical warning:

Moderate. These medicines may cause some risk when taken together. Contact your healthcare professional (e.g. doctor or pharmacist) for more information.

How the interaction occurs:

When these two medicines are taken together, your body may not process your tricyclic medicine or trazodone properly.

What might happen:

The blood levels of your tricyclic medicine or trazodone may increase and cause adverse effects.

What you should do about this interaction:

Contact your healthcare professionals (e.g. doctor of pharmacist) about taking these medicines together. If your doctor prescribed these medicines together and one of your medicines is a tricyclic antidepressant, you may need have your your blood level checked to be sure you are on an effective and safe dose.If you experience heart palpitations or fainting episodes; new onset shivering, muscle tremors or stiffness; blurred vision, urinary retention, confusion, agitation, restlessness, or seizures contact your healthcare professional (e.g. doctor or pharmacist) right away.Your healthcare professionals may already be aware of this interaction and may be monitoring you for it. Do not start, stop, or change the dosage of any medicine before checking with them first.

View Reference
  • 1.This information is based on an extract from the Certara Drug Interaction Database (DIDB) Platform, Copyright Certara 1999-2023..
  • 2.US Food and Drug Administration (FDA). Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers. Available at: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and- drug-interactions-table-substrates-inhibitors-and-inducers. Updated 11/14/2017.
  • 3.USDepartment of Health and Human Services Food and Drug Administration. ICH E14 Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs. Available at: https://www.fda.gov/media/71372/download October, 2005.
  • 4.Preskorn SH, Beber JH, Faul JC, Hirschfeld RM. Serious adverse effects of combining fluoxetine and tricyclic antidepressants. Am J Psychiatry 1990 Apr;147(4):532.
  • 5.Kahn DG. Increased plasma nortriptyline concentration in a patient cotreated with fluoxetine. J Clin Psychiatry 1990 Jan;51(1):36.
  • 6.Ciraulo DA, Shader RI. Fluoxetine drug-drug interactions: I. Antidepressants and antipsychotics. J Clin Psychopharmacol 1990 Feb; 10(1):48-50.
  • 7.Vaughan DA. Interaction of fluoxetine with tricyclic antidepressants. Am J Psychiatry 1988 Nov;145(11):1478.
  • 8.Bell IR, Cole JO. Fluoxetine induces elevation of desipramine level and exacerbation of geriatric nonpsychotic depression. J Clin Psychopharmacol 1988 Dec;8(6):447-8.
  • 9.Aranow AB, Hudson JI, Pope HG Jr, Grady TA, Laage TA, Bell IR, Cole JO. Elevated antidepressant plasma levels after addition of fluoxetine. Am J Psychiatry 1989 Jul;146(7):911-3.
  • 10.Goodnick PJ. Influence of fluoxetine on plasma levels of desipramine. Am J Psychiatry 1989 Apr;146(4):552.
  • 11.Schraml F, Benedetti G, Hoyle K, Clayton A. Fluoxetine and nortriptyline combination therapy. Am J Psychiatry 1989 Dec;146(12):1636-7.
  • 12.Downs JM, Downs AD, Rosenthal TL, Deal N, Akiskal HS. Increased plasma tricyclic antidepressant concentrations in two patients concurrently treated with fluoxetine. J Clin Psychiatry 1989 Jun;50(6):226-7.
  • 13.Downs JM, Dahmer SK. Fluoxetine and elevated plasma levels of tricyclic antidepressants. Am J Psychiatry 1990 Sep;147(9):1251.
  • 14.Westermeyer J. Fluoxetine-induced tricyclic toxicity: extent and duration. J Clin Pharmacol 1991 Apr;31(4):388-92.
  • 15.Rosenstein DL, Takeshita J, Nelson JC. Fluoxetine-induced elevation and prolongation of tricyclic levels in overdose. Am J Psychiatry 1991 Jun; 148(6):807.
  • 16.Bergstrom RF, Peyton AL, Lemberger L. Quantification and mechanism of the fluoxetine and tricyclic antidepressant interaction. Clin Pharmacol Ther 1992 Mar;51(3):239-48.
  • 17.Skjelbo E, Brosen K. Inhibitors of imipramine metabolism by human liver microsomes. Br J Clin Pharmacol 1992 Sep;34(3):256-61.
  • 18.Preskorn SH, Alderman J, Chung M, Harrison W, Messig M, Harris S. Pharmacokinetics of desipramine coadministered with sertraline or fluoxetine. J Clin Psychopharmacol 1994 Apr;14(2):90-8.
  • 19.Drew BJ, Ackerman MJ, Funk M, Gibler WB, Kligfield P, Menon V, Philippides GJ, Roden DM, Zareba W. Prevention of torsade de pointes in hospital settings: a scientific statement from the American Heart Association and the American College of Cardiology Foundation. J Am Coll Cardiol 2010 Mar 2;55(9):934-47.
  • 20.Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med 2005 Mar 17; 352(11):1112-20.
  • 21.American Geriatrics Society 2023 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc 2023 Jul;71(7):2052-2081.
  • 22.Balant-Gorgia AE, Ries C, Balant LP. Metabolic interaction between fluoxetine and clomipramine: a case report. Pharmacopsychiatry 1996 Jan; 29(1):38-41.
  • 23.Amrix (cyclobenzaprine extended release) US prescribing information. Teva Pharmaceuticals Ltd. May, 2016.
  • 24.Reeves RR, Bullen JA. Serotonin syndrome produced by paroxetine and low-dose trazodone. Psychosomatics 1995 Mar-Apr;36(2):159-60.
  • 25.Amin R. Fluoxetine and Trazodone Combination Pharmacotherapy Resulting in Severe Irritability, Anger, Anxiety, and Anorexia: Probable Adverse Drug Interaction. Prim Care Companion CNS Disord 2016 Aug 11;18(4):.
  • 26.Paul KL, Bhatara VS. Anticholinergic delirium possibly associated with protriptyline and fluoxetine. Ann Pharmacother 1997 Oct;31(10):1260-1.
  • 27.Maes M, Westenberg H, Vandoolaeghe E, Demedts P, Wauters A, Neels H, Meltzer HY. Effects of trazodone and fluoxetine in the treatment of major depression: therapeutic pharmacokinetic and pharmacodynamic interactions through formation of meta-chlorophenylpiperazine. J Clin Psychopharmacol 1997 Oct;17(5):358-64.
  • 28.George TP, Godleski LS. Possible serotonin syndrome with trazodone addition to fluoxetine. Biol Psychiatry 1996 Mar 1;39(5):384-5.
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CONDITIONS OF USE: The information in this database is intended to supplement, not substitute for, the expertise and judgment of healthcare professionals. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for you or anyone else. A healthcare professional should be consulted before taking any drug, changing any diet or commencing or discontinuing any course of treatment.