Basic Information
ID DDInter2064 and DDInter1948
Interaction By inhibiting serotonin metabolism, monoamine oxidase inhibitors (MAOIs) may potentiate the pharmacologic activity of selective serotonin reuptake inhibitors (SSRIs) and increase the risk of serotonin syndrome, which is a rare but serious and potentially fatal condition thought to result from hyperstimulation of brainstem 5-HT1A and 2A receptors.
Management In general, SSRIs should not be used concurrently with MAOIs or other agents that possess MAOI activity (e.g., furazolidone, procarbazine). At least 14 days should elapse between discontinuation of MAOI therapy and initiation of treatment with SSRIs, and vice versa. Due to the long half-life of fluoxetine and its active metabolite, norfluoxetine, a washout period of 5 weeks minimum is recommended when switching from fluoxetine to an MAOI. Similarly, a washout period of 3 weeks is recommended when switching from vortioxetine to an MAOI.
References [1] Pettinger WA, Soyangco FG, Oates JA "Inhibition of monoamine oxidase in man by furazolidone." Clin Pharmacol Ther 9 (1968): 442-7 [2] Schulz R, Antonin KH, Hoffmann E, et al. "Tyramine kinetics and pressor sensitivity during monoamine oxidase inhibition by selegiline." Clin Pharmacol Ther 46 (1989): 528-36 [3] Kline SS, Mauro LS, Scala-Bennett DM, Zick D "Serotonin syndrome versus neuroleptic malignant death syndrome as a cause of death." Clin Pharm 8 (1989): 510-4 [4] Sternbach H "Danger of MAOI therapy after fluoxetine withdrawal." Lancet 2 (1988): 850-1 [5] Nierenberg DW, Semprebon M "The central nervous system serotonin syndrome." Clin Pharmacol Ther 53 (1993): 84-8 [6] Sternbach H "The serotonin syndrome." Am J Psychiatry 148 (1991): 705-13 [7] Feighner JP, Boyer WF, Tyler DL, Neborsky RJ "Adverse consequences of fluoxetine-MAOI combination therapy." J Clin Psychiatry 51 (1990): 222-5 [8] Suchowersky O, deVries J "Possible interactions between deprenyl and prozac." Can J Neurol Sci 17 (1990): 352-3 [9] Ciraulo DA, Shader RI "Fluoxetine drug-drug interactions. II." J Clin Psychopharmacol 10 (1990): 213-7 [10] Ciraulo DA, Shader RI "Fluoxetine drug-drug interactions: I. Antidepressants and antipsychotics." J Clin Psychopharmacol 10 (1990): 48-50 [11] Graham PM, Ilett KF "Danger of MAOI therapy after fluoxetine withdrawal." Lancet 2 (1988): 1255-6 [12] Bhatara VS, Bandettini FC "Possible interaction between sertraline and tranylcypromine." Clin Pharm 12 (1993): 222-5 [13] "Product Information. Zoloft (sertraline)." Roerig Division (2001): [14] Suchowersky O, deVries JD "Interaction of fluoxetine and selegiline." Can J Psychiatry 35 (1990): 571-2 [15] "Product Information. Prozac (fluoxetine)." Dista Products Company (2001): [16] "Product Information. Paxil (paroxetine)." GlaxoSmithKline (2001): [17] Brannan SK, Talley BJ, Bowden CL "Sertraline and isocarboxazid cause a serotonin syndrome." J Clin Psychopharmacol 14 (1994): 144-5 [18] Graber MA, Hoehns TB, Perry PJ "Sertraline-phenelzine drug interaction: a serotonin syndrome reaction." Ann Pharmacother 28 (1994): 732-5 [19] Ruiz F "Fluoxetine and the serotonin syndrome." Ann Emerg Med 24 (1994): 983-5 [20] "Product Information. Luvox (fluvoxamine)." Solvay Pharmaceuticals Inc (2001): [21] Phillips SD, Ringo P "Phenelzine and venlafaxine interaction." Am J Psychiatry 152 (1995): 1400-1 [22] Darcy PF, Griffin JP "Interactions with drugs used in the treatment of depressive illness." Adverse Drug React Toxicol Rev 14 (1995): 211-31 [23] De Vita VT, Hahn MA, Oliverio VT "Monoamine oxidase inhibition by a new carcinostatic agent, n-isopropyl-a-(2-methylhydrazino)-p-toluamide (MIH). (30590)." Proc Soc Exp Biol Med 120 (1965): 561-5 [24] Fischer P "Serotonin syndrome in the elderly after antidepressive monotherapy." J Clin Psychopharmacol 15 (1995): 440-2 [25] Corkeron MA "Serotonin syndrome - a potentially fatal complication of antidepressant therapy." Med J Aust 163 (1995): 481-2 [26] Beasley CM Jr, Masica DN, Heiligenstein JH, Wheadon DE, Zerbe RL "Possible monoamine oxidase inhibitor-serotonin uptake inhibitor interaction: fluoxetine clinical data and preclinical findings." J Clin Psychopharmacol 13 (1993): 312-20 [27] Mills KC "Serotonin syndrome: A clinical update." Crit Care Clin 13 (1997): 763 [28] "Product Information. Celexa (citalopram)." Forest Pharmaceuticals (2001): [29] Chan BSH, Graudins A, Whyte IM, Dawson AH, Braitberg G, Duggin GG "Serotonin syndrome resulting from drug interactions." Med J Aust 169 (1998): 523-5 [30] "Product Information. Lexapro (escitalopram)." Forest Pharmaceuticals (2002): [31] Martin TG "Serotonin syndrome." Ann Emerg Med 28 (1996): 520-6 [32] Gillman PK "Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity." Br J Anaesth (2005): [33] Paruchuri P, Godkar D, Anandacoomarswamy D, Sheth K, Niranjan S "Rare case of serotonin syndrome with therapeutic doses of paroxetine." Am J Ther 13 (2006): 550-552 [34] Jimenez-Genchi A "Immediate switching from moclobemide to duloxetine may induce serotonin syndrome." J Clin Psychiatry 67 (2006): 1821-1822 [35] "Product Information. Brintellix (vortioxetine)." Takeda Pharmaceuticals America (2013):
Alternative for Furazolidone G01A
Chloramphenicol Brinzolamide Ketoconazole Darunavir Sulfadiazine Probenecid
Sulfadoxine Ascorbic acid Econazole Nystatin Tioconazole
More
Alternative for Vortioxetine N06A
Esketamine
Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.