Basic Information
ID DDInter1653 and DDInter504
Interaction Coadministration of monoamine oxidase inhibitors (MAOIs) and dibenzazepine derivatives (e.g., tricyclic and tetracyclic antidepressants, cyclobenzaprine, carbamazepine) may produce significant adverse reactions including nausea, vomiting, flushing, dizziness, tremor, myoclonus, rigidity, diaphoresis, hyperthermia, autonomic instability, hypertensive crises, disseminated intravascular coagulation, severe convulsive seizures, coma, and death. The exact mechanism of interaction is unknown, but may involve excessive serotonergic activity in the central nervous system (i.e., serotonin syndrome).
Management In general, dibenzazepine derivatives should not be used concurrently with MAOIs or other agents that possess MAOI activity (e.g., furazolidone, methylene blue, procarbazine). At least 14 days should elapse between discontinuation of MAOI therapy and initiation of treatment with tricyclic antidepressants, and vice versa.
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Ann Emerg Med 28 (1996): 520-6 [25] Keegan MT, Brown DR, Rabinstein AA "Serotonin syndrome from the interaction of cyclobenzaprine with other serotoninergic drugs." Anesth Analg 103 (2006): 1466-8 [26] Dardennes RM, Even C, Ballon N, Bange F "Serotonin syndrome caused by a clomipramine-moclobemide interaction." J Clin Psychiatry 59 (1998): 382-3 [27] 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 [28] Hardman JG, Gilman AG, Limbird LE eds. "Goodman and Gilman's the Pharmacological Basis of Therapeutics. 9th ed." New York, NY: McGraw-Hill (1995): [29] Graham PM, Potter JM, Paterson J "Combination monoamine oxidase inhibitor/tricyclic antidepressants interaction." Lancet 2 (1982): 440 [30] Nierenberg DW, Semprebon M "The central nervous system serotonin syndrome." Clin Pharmacol Ther 53 (1993): 84-8 [31] White K, Pistole T, Boyd JL "Combined monoamine oxidase inhibitor-tricyclic antidepressant treatment: a pilot study." Am J Psychiatry 137 (1980): 1422-5 [32] Pascual J, Combarros O, Berciano J "Partial status epilepticus following single low dose of chlorimipramine in a patient on MAO-inhibitor treatment." Clin Neuropharmacol 10 (1987): 565-7 [33] "Product Information. Methylene Blue (methylene blue)." American Regent Laboratories Inc, Shirley, NY. [34] Ketter TA, Post RM, Parekh PI, Worthington K "Addition of monoamine oxidase inhibitors to carbamazepine: preliminary evidence of safety and antidepressant efficacy in treatment-resistant depression." J Clin Psychiatry 56 (1995): 471-5 [35] "Product Information. Marplan (isocarboxazid)" Roche Laboratories, Nutley, NJ. [36] "Product Information. Nardil (phenelzine)." Parke-Dvis, Morris Plains, NJ. [37] Lefebvre H, Noblet C, Morre N, Wolf LM "Pseudo-phaeochromocytoma after multiple drug interactions involving the selective monoamine oxidase inhibitor selegiline." Clin Endocrinol (Oxf) 42 (1995): 95-8 [38] Spiker DG, Pugh DD "Combining tricyclic and monoamine oxidase inhibitor antidepressants." Arch Gen Psychiatry 33 (1976): 828-30 [39] "Product Information. Eldepryl (selegiline)." Somerset Pharmaceuticals Inc, Tampa, FL. [40] Kay DW, Garside RF, Fahy TJ "A double-blind trial of phenelzine and amitriptyline in depressed out- patients. A possible differential effect of the drugs on symptoms." Br J Psychiatry 123 (1973): 63-7 [41] Pettinger WA, Soyangco FG, Oates JA "Inhibition of monoamine oxidase in man by furazolidone." Clin Pharmacol Ther 9 (1968): 442-7 [42] Feighner JP, Herbstein J, Damlouji N "Combined MAOI, TCA, and direct stimulant therapy of treatment- resistant depression." 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Ann Emerg Med 28 (1996): 520-6 [51] Tailor SA, Shulman KI, Walker SE, Moss J, Gardner D "Hypertensive episode associated with phenelzine and tap beer--a reanalysis of the role of pressor amines in beer." J Clin Psychopharmacol 14 (1994): 5-14 [52] Sweet RA, Liebowitz MR, Holt CS, Heimberg RG "Potential interactions between monoamine oxidase inhibitors and prescribed dietary supplements." J Clin Psychopharmacol 11 (1991): 331-2 [53] "Product Information. Furoxone (furazolidone)." Roberts Pharmaceutical Corporation, Eatontown, NJ. [54] Domino EF, Selden EM "Red wine and reactions." J Clin Psychopharmacol 4 (1984): 173-4 [55] Pettinger WA, Soyangco FG, Oates JA "Inhibition of monoamine oxidase in man by furazolidone." Clin Pharmacol Ther 9 (1968): 442-7 [56] "Product Information. Nardil (phenelzine)." Parke-Dvis, Morris Plains, NJ. [57] Ban TA "Drug interactions with psychoactive drugs." Dis Nerv Syst 36 (1975): 164-6 [58] 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 [59] Maxwell MB "Reexamining the dietary restrictions with procarbazine (an MAOI)." Cancer Nurs 3 (1980): 451-7 [60] Darcy PF, Griffin JP "Interactions with drugs used in the treatment of depressive illness." Adverse Drug React Toxicol Rev 14 (1995): 211-31 [61] Nuessle WF, Norman FC, Miller HE "Pickled herring and tranylcypromine reaction." JAMA 192 (1965): 142-3 [62] Goldberg LI "Monoamine oxidase inhibitors: adverse reactions and possible mechanisms." JAMA 190 (1964): 456-62 [63] Walker JI, Davidson J, Zung WWK "Patient compliance with MAO Inhibitor therapy." J Clin Psychiatry 45 (1984): 78-80
Alternative for Selegiline N04B
Cabergoline
Alternative for Desipramine -
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.