Tricyclic; Tetracyclic Compounds/MAOIs 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:

Very Serious. These medicines may interact and cause very harmful effects and are usually not taken together. Contact your healthcare professional (e.g. doctor or pharmacist) for more information.

How the interaction occurs:

Both of these medicines can increase the level of serotonin in your body.

What might happen:

High serotonin levels may cause changes in body temperature, blood pressure and behavior, leading to a medical condition called Serotonin Syndrome. Serotonin Syndrome may be life threatening.

What you should do about this interaction:

Make sure your healthcare professionals (e.g. doctor or pharmacist) know that you are taking these medicines together.If you experience muscle twitching, tremors, shivering or stiffness, fever, heavy sweating, heart palpitations, restlessness, confusion, agitation, trouble with coordination, or severe diarrhea contact your doctor 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.

  • 1.Manerix (moclobemide) Canadian prescribing information. Hoffmann-La Roche Limited May 9, 1995.
  • 2.Blier P, de Montigny C, Chaput Y. A role for the serotonin system in the mechanism of action of antidepressant treatments: preclinical evidence. J Clin Psychiatry 1990 Apr;51 Suppl:14-20; discussion 21.
  • 3.Amitriptyline hydrochloride, US prescribing information. Sandoz Inc. January, 2010.
  • 4.Anafranil (clompiramine hydrochloride) US prescribing information. Mallinckrodt Inc. May 10, 2019.
  • 5.Pamelor (nortriptyline hydrochloride) US prescribing information. Mallinckrodt Inc. October, 2012.
  • 6.Amrix (cyclobenzaprine extended release) US prescribing information. Teva Pharmaceuticals Ltd. May, 2016.
  • 7.Remeron (mirtazapine) US prescribing information. Organon Inc. November, 2021.
  • 8.Nardil (phenelzine sulfate) US prescribing information. Parke-Davis May, 2007.
  • 9.Zelapar (selegiline hydrochloride) US prescribing information. Valeant Pharmaceuticals June, 2021.
  • 10.Parnate (tranylcypromine sulfate) US prescribing information. GlaxoSmithKline January 4, 2018.
  • 11.Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med 2005 Mar 17; 352(11):1112-20.
  • 12.USFood and Drug Administration. FDA Drug Safety Communication: Serious CNS reactions possible when methylene blue is given to patients taking certain psychiatric medications. available at: gs/DrugSafety/ucm263190.htm July 26, 2011.
  • 13.USFood and Drug Administration. FDA Drug Safety Communication: Updated information about the drug interaction between methylene blue (methylthioninium chloride) and serotonergic psychiatric medications. available at: October 21, 2011.
  • 14.Ramsay RR, Dunford C, Gillman PK. Methylene blue and serotonin toxicity: inhibition of monoamine oxidase A (MAO A) confirms a theoretical prediction. Br J Pharmacol 2007 Nov;152(6):946-51.
  • 15.Peter C, Hongwan D, Kupfer A, Lauterburg BH. Pharmacokinetics and organ distribution of intravenous and oral methylene blue. Eur J Clin Pharmacol 2000 Jun;56(3):247-50.
  • 16.Brachfeld J, Wirtshafter A, Wolfe S. Imipramine-tranylcypromine incompatibility. Near-fatal toxic reaction. JAMA 1963 Dec 28; 186(13):1172-3.
  • 17.Young JP, Lader MH, Hughes WC. Controlled trial of trimipramine, monoamine oxidase inhibitors, and combined treatment in depressed outpatients. Br Med J 1979 Nov 24;2(6201):1315-7.
  • 18.Pentel P, Olson KR, Becker CE, Benowitz N. Late complications of tricyclic antidepressant overdose. West J Med 1983 Mar;138(3):423-4.
  • la Fuente JR, Berlanga C, Leon-Andrade C. Mania induced by tricyclic-MAOI combination therapy in bipolar treatment-resistant disorder: case reports. J Clin Psychiatry 1986 Jan;47(1):40-1.
  • 20.Pascual J, Combarros O, Berciano J. Partial status epilepticus following single low dose of chlorimipramine in a patient on MAO-inhibitor treatment. Clin Neuropharmacol 1987 Dec;10(6):565-7.
  • 21.Richards GA, Fritz VU, Pincus P, Reyneke J. Unusual drug interactions between monoamine oxidase inhibitors and tricyclic antidepressants. J Neurol Neurosurg Psychiatry 1987 Sep;50(9):1240-1.
  • 22.Tackley RM, Tregaskis B. Fatal disseminated intravascular coagulation following a monoamine oxidase inhibitor/tricyclic interaction. Anaesthesia 1987 Jul;42(7):760-3.
  • 23.O'Brien S, McKeon P, O'Regan M, O'Flaherty A, Patel R. Blood pressure effects of tranylcypromine when prescribed singly and in combination with amitriptyline. J Clin Psychopharmacol 1992 Apr;12(2):104-9.
  • 24.Schuckit M, Robins E, Feighner J. Tricyclic antidepressants and monoamine oxidase inhibitors. Arch Gen Psychiatry 1971 Jun;24(6):509-14.
  • 25.Graham PM, Potter JM, Paterson J. Combination monoamine oxidase inhibitor/tricyclic antidepressants interaction. Lancet 1982 Aug 21; 2(8295):440.
  • 26.White K, Simpson G. The combined use of MAOIs and tricyclics. J Clin Psychiatry 1984 Jul;45(7 Pt 2):67-9.
  • 27.Ponto LB, Perry PJ, Liskow BI, Seaba HH. Drug therapy reviews: tricyclic antidepressant and monoamine oxidase inhibitor combination therapy. Am J Hosp Pharm 1977 Sep;34(9):954-61.
  • 28.Manshadi MS, Lippmann SB. Combined treatment of refractory depression with an MAO inhibitor and a tricyclic. Psychosomatics 1984 Dec; 25(12):929-31.
  • 29.Spigset O, Mjorndal T, Lovheim O. Serotonin syndrome caused by a moclobemide-clomipramine interaction. BMJ 1993 Jan 23;306(6872):248.
  • 30.Neuvonen PJ, Pohjola-Sintonen S, Tacke U, Vuori E. Five fatal cases of serotonin syndrome after moclobemide-citalopram or moclobemide-clomipramine overdoses. Lancet 1993 Dec 4;342(8884):1419.
  • 31.Sjoqvist F. Psychotropic drugs (2). Interaction between monoamine oxidase (MAO) inhibitors and other substances. Proc R Soc Med 1965 Nov;58(11 Part 2):967-78.
  • 32.Stern SL, Mendels J. Drug combinations in the treatment of refractory depression: a review. J Clin Psychiatry 1981 Oct;42(10):368-73.
  • 33.White K, Simpson G. Combined MAOI-tricyclic antidepressant treatment: a reevaluation. J Clin Psychopharmacol 1981 Sep;1(5):264-82.
  • 34.Surmaitis RM, Nappe TM, Cook MD. Serotonin syndrome associated with therapeutic metaxalone in a patient with cirrhosis. Am J Emerg Med 2016 Feb;34(2):346.e5-6.
  • 35.Skelaxin (metaxalone) US prescribing information. Pfizer Laboratories Div Pfizer Inc. January, 2024.
  • 36.Phansalkar S, Desai AA, Bell D, Yoshida E, Doole J, Czochanski M, Middleton B, Bates DW. High-priority drug-drug interactions for use in electronic health records. J Am Med Inform Assoc 2012 Sep-Oct; 19(5):735-43.

Selected from data included with permission and copyrighted by First Databank, Inc. This copyrighted material has been downloaded from a licensed data provider and is not for distribution, except as may be authorized by the applicable terms of use.

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.