Withdrawal and Discontinuation Phenomena Associated with Tranylcypromine: A Systematic Review

Abstract

Tranylcypromine (TCP) is an effective antidepressant with a complex pharmacological profile and a relevant risk of abuse and dependence. Withdrawal phenomena (WP, in the case of TCP-abuse/dependence) or discontinuation phenomena (DP, in the case of absent TCP-abuse/dependence) subsequent to abrupt termination of TCP are a potentially severe clinical syndrome. We conducted a systematic review of all previously published WP/DP cases following abrupt termination of TCP in order to identify typical clinical presentations and risk factors of WP/DP and frequency of TCP abuse or dependence within these patients. By searching the Medline and Scopus databases we identified n=25 cases (cohort WP: n=18, cohort DP: n=7). Delirium was found in n=13 patients (cohort WP: 10/55.6%; cohort DP: 3/42.9%), n=6 demonstrated WP/DP without delirium (WP: 6/33.3%; DP: 0/0%) and n=5 rapid relapse in depression (WP: 1/5.6%; DP: 4/57.1%). Mean time until development of WP/DP was 1.9 (WP) and 2.2 (DP) days. Mean duration of WP/DP was 5.7 (WP) and 11.3 (DP) days. All patients of cohort WP were described to feature TCP-abuse/dependence. Patients with delirium were on average older (41.8 years vs. 37.8 years) and featured higher mean prescribed (71.0 mg vs. 38.3 mg) and actually taken daily TCP dosages (285.8 mg vs. 187.7 mg). In conclusion, even termination of lower daily dosages of TCP may result in delirium. Thrombocytopenia features diagnostic value in patients with deliria of unknown etiology. TCP should be administered with great care, especially in dependence-prone patients.·

Key words

antidepressants - delirium - Jatrosom - Parnate - monoamine oxidase ­inhibitors - psychopharmacotherapy

• References

• 1 Parker G, Wilhelm K, Mitchell P. Assessing the comparative effectiveness of antidepressant therapies: a prospective clinical practice study. J Clin Psychiatry 2001; 62: 17-25
• 2 Stewart J, Thase M. Treating DSM-IV depression with atypical features. J Clin Psychiatry 2007; 68: e10
• 3 Pae C, Tharwani H, Marks D et al. Atypical depression: a comprehensive review. CNS Drugs 2009; 23: 1023-1037
• 4 Amsterdam J, Shults J. MAOI efficacy and safety in advanced stage treatment-resistant depression – a retrospective study. J Affect Disord 2005; 89: 183-188
• 5 Baker G, Coutts R, McKenna K et al. Insights into the mechanisms of action of the MAO inhibitors phenelzine and tranylcypromine: a review. J Psychiatr Neurosci 1992; 17: 206-214
• 6 Shih J, Chen K. Regulation of MAO-A and MAO-B gene expression. Curr Med Chem 2004; 11: 1995-2005
• 7 Billett E. Monoamine oxidase (MAO) in human peripheral tissues. Neurotoxicology 2004; 25: 139-148
• 8 Kalgutkar A, Dalvie D, Castagnoli N et al. Interactions of nitrogen-containing xenobiotics with monoamine oxidase (MAO) isoenzymes A and B: SAR studies on MAO substrates and inhibitors. Chem Res Toxicol. 2001. 14. 1139-1162
• 9 Philips S, Boulton M. The effects of monoamine oxidase inhibitors on some arylalkylamines in rat striatum. J Neurochem 1979; 33: 159-167
• 10 Boulton M, Juorio A. Brain trace amines. In: Lajtha A. ed. Handbook of Neurochemistry. New York: Plenum Press; 1982: 189-222
• 11 Baker G, Martin I, Mitchel P. The effects of some indolalkylamines on the uptake and release of 5-hydroxytryptamine in rat striatum. Br J Pharmacol 1977; 61: 151P-152P
• 12 Raiteri M, Del Carmine R, Bertollini A et al. Effect of sympathomimetic amines on the synaptosomal transport of noradrenaline, dopamine and 5-hydroxytryptamine. Eur J Pharmacol 1977; 41: 133-142
• 13 Paterson I, Boulton M. Beta-phenylethylamine enhances single cortical neurone responses to noradrenaline in the rat. Brain Ress Bull 1988; 20: 173-177
• 14 Paterson I, Iurio A, Boulton M. 2-Phenylethylamine: a modulator of catecholamine transmission in the mammalian central nervous system?. J Neurochem 1990; 55: 1827-1837
• 15 Jones R. Tryptamine: a neuromodulator or neurotransmitter in mammalian brain?. Prog Neurobiol 1982; 19: 117-139
• 16 Jones R. Trace biogenic amines: a possible functional role in the CNS. Trends Pharmacol Sci 1983; 4: 426-429
• 17 Beavan T. The cheese reaction. Lancet 1964; 1: 540
• 18 Blackwell B. Hypertensive crisis due to monoamine-oxidase inhibitors. Lancet 1963; 2: 849-850
• 19 Asatoor A, Levi A, Milne M. Tranylcypromine and cheese. Lancet 1963; 54: 733-734
• 20 Graham W. Hypertension caused by tranylcypromine and cheese. JAMA 1964; 188: 782
• 21 Cuthill J, Griffiths A, Powell D. Death associated with tranylcypromine and cheese. Lancet 1964; 1: 1076-1077
• 22 Bethune N, Burrell R, Culpan R. Headache associated with monoamine oxidase inhibitors. Lancet 1963; 2: 1233-1234
• 23 Horwitz D, Lovenberg W, Engelman K et al. Monoamine oxidase inhibitors, tyramine, and cheese. JAMA 1964; 188: 1108-1110
• 24 Adli M, Philhatsch M, Bauer M et al. Safety of high-intensity treatment with the irreversible monoamine oxidase inhibitor tranylcypromine in patients with treatment-resistent depression. Pharmacopsychiatry 2008; 41: 252-257
• 25 McGrath P, Stewart J, Fava M et al. Tranylcypromine versus venlafaxine plus mirtazapine following three failed antidepressant medication trials for depression: a STAR*D report. Am J Psychiatry 2006; 163: 1531-1541 quiz 1666
• 26 Amsterdam J, Berwish N. High dose tranylcypromine therapy for refractory depression. Pharmacopsychiatry 1989; 22: 21-25
• 27 Glaxo-Smith-Kline. Parnate. Prescribing information 2010
• 28 Aristo-Pharma. Jatrosom N. Prescribing information 2010
• 29 Degner D, Porzig J, Ruther E et al. Serotonin syndrome with severe hyperthermia after ingestion of tranylcypromine combined with serotinin reuptake inhibitors and tyramine-rich food in a case of suicide. Pharmacopsychiatry 2010; 43: 284-285
• 30 Gillman P. A review of serotonin toxicity data: implications for the mechanisms of antidepressant drug action. Biol Psychiatry 2006; 59: 1046-1051
• 31 Gillman P. CNS toxicity involving methylene blue: the exemplar for understanding and predicting drug interactions that precipitate serotonin toxicity. J Psychopharmacol (Oxf) 2011; 25: 423-429
• 32 Tuomisto J, Tuomisto L, Smissman E. Conformation study of the inhibition of monoamine uptake in rat brain synaptosomes. Ann Med Exp Biol Fenn 1973; 51: 51-58
• 33 Tuomisto J, Smith D. Effects of tranylcypromine enantiomers on monoamine uptake and release and imipramine binding. J Neural Transm 1986; 65: 135-145
• 34 Frieling H, Bleich S. Tranylcypromine: new perpectives of an “old” drug. Eur Arch Psychiatry Clin Neurosci 2006; 256: 268-273
• 35 Le Gassicke J, Ashcroft G, Eccleston D et al. The clinical state, sleep and amine metabolism of a tranylcypromine ("Parnate") addict. Br J Psychiatry 1965; 111: 357-364
• 36 Le Gassicke J. Trancylcypromine. Lancet 1963; 281: 269-270
• 37 Mielczarek J, Johnson J. Tranylcypromine. Lancet 1963; 281: 388-389
• 38 Morgan D. Tranylcypromine. Lancet 1963; 281: 389
• 39 Szelényi A, Albrecht J. Tranylcypromine abuse associated with an isolated thrombocytopenia. Pharmacopsychiatry 1998; 31: 238-240
• 40 Vartzopoulos D, Krull F. Dependence on monoamine oxidase inhibitors in high dose. Br J Psychiatry 1991; 158: 856-857
• 41 Griffin N, Draper R, Webb M. Addiction to tranylcypromine. Br Med J (Clin Res Ed) 1981; 283: 346
• 42 Briggs N, Jefferson J, Koenecke F. Tranylcypromine addiction: a case report and review. J Clin Psychiatry 1990; 51: 426-429
• 43 Bellon A, Coverdale J. Delirium, thrombocytopenia, insomnia, and mild liver damage associated with MAOI withdrawal. Eur J Clin Pharmacol 2009; 65: 1269-1270
• 44 Halle M, Dilsaver S. Tranylcypromine withdrawal phenomena. J Psychiatr Neurosci 1993; 18: 49-50
• 45 Chatterjee A, Tosyali M. Thrombocytopenia and delirium associated with tranylcypromine overdose. J Clin Psychopharmacol 1995; 15: 143-144
• 46 Pennings E, Verkes R, de Koning J et al. Tranylcypromine intoxication with malignant hyperthermia, delirium, and thrombocytopenia. J Clin Psychopharmacol 1997; 17: 430-432
• 47 Davids E, Röschke J, Klawe C et al. Tranylcypromine abuse associated with delirium and thrombocytopenia. J Clin Psychopharmacol 2000; 20: 270-271
• 48 Dilsaver S. Heterocyclic antidepressant, monoamine oxidase inhibitor and neuroleptic withdrawal phenomena. Prog Neurpsychopharmacol Biol Psychiatry 1990; 14: 137-161
• 49 Haddad P. Newer antidepressants and the discontinuation syndrome. J Clin Psychiatry 1997; Suppl 7: 17-21 discussion 22
• 50 Charney D, Heninger G, Sternberg D et al. Abrupt discontinuation of tricyclic antidepressant drugs: evidence for noradrenergic hyperactivity. Br J Psychiatry 1982; 141: 377-386
• 51 Schatzberg AF, Blier P, Delgado PL et al. Antidepressant discontinuation syndrome: consensus panel recommendations for clinical management and additional research. J Clin Psychiatry 2006; 67 (Suppl. 04) 27-30
• 52 Dilsaver S. Monoamine oxidase inhibitor withdrawal phenomena: symptoms and pathophysiology. Acta Psychiatr Scand 1988; 78: 1-7
• 53 APA . Diagnostical and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. 4^th ed. Washington, DC: American Psychiatric Association; 2000
• 54 Eyer F, Jetzinger E, Pfab R et al. Withdrawal from high-dose tranylcypromine. Clin Toxicol (Phila) 2008; 46: 261-263
• 55 Brady K, Lydiard R, Kellner C. Tranylcypromine abuse. Am J Psychiatry 1991; 148: 1268-1269
• 56 Abdi S, Fishman S. Acute exacerbation of depression after discontinuation of monoamine oxidase inhibitor prior to cardiac surgery. Anesth Analg 1996; 83: 656-657
• 57 Absher J, Black D. Tranylcypromine withdrawal delirium. J Clin Psychopharmacol 1988; 8: 379-380
• 58 Ben-Arie O, George G. A case of tranylcypromine (‘Parnate’) addiction. Br J Psychiatry 1979; 135: 273-274
• 59 Cramer H, Ohlmeier D. Ein Fall von Tranycypromine- und Trifluoperazin-(Jatrosom)-Sucht: Psychopathologische, schlafphysiologische und biochemische Untersuchungen. Arch Psych ges Neurol 1967; 210: 182-197
• 60 Shaikh W, Fuls K. Tranylcypromine dependence and withdrawal. Aust N Z J Psychiatry 2009; 43: 580-581
• 61 Shopsin B, Kline N. Monoamine oxidase inhibitors: potential for drug abuse. Biol Psychiatry 1976; 11: 451-456
• 62 Westermeyer J. Addiction to tranylcypromine (Parnate): a case report. Am J Drug Alcohol Abuse 1989; 15: 345-350
• 63 Thorp M, Toombs D, Harmon B. Monoamine oxidase inhibitor overdose. West J Med 1997; 166: 275-277
• 64 Boyer E, Shannon M. The serotonin syndrome. N Engl J Med 2005; 352: 1112-1120
• 65 Brubacher J, Hoffmann R, Lurin M. Serotonin syndrome from venlafaxine-tranylcypromine interaction. Vet Hum Toxicol 1996; 38: 358-361
• 66 Silverstone T, Turner P. Drug Treatment in Psychiatry. In. 5^th ed. London: Rutledge; 1995: 140-189
• 67 Robinson D. High-dose monoamine-oxidase inhibitor therapy JAMA 1983; 250: 2212
• 68 Youdim M, Aronson J, Blau K et al. Tranylcypromine (“Parnate”) overdose: measurement of tranylcypromine concentrations and MAO inhibitory activity and identification of amphetamines in plasma. Psychol Med 1979; 9: 377-382
• 69 Keck PJ, Carter W, Nierenberg A et al. Acute cardiovascular effects of tranylcypromine: correlation with plasma drug, metabolite, norepinephrine, and MHPG levels. J Clin Psychiatry 1991; 52: 250-254
• 70 Mutschler E, Möhrke W. Kinetics of MAO inhibitors. Mod Probl Pharmacopsychiatry 1983; 19: 126-134
• 71 Sherry R, Rauw G, McKenna K et al. Failure to detect amphetamine or 1-amino-3-phenylpropane in humans or rats receiving the MAO inhibitor tranylcypromine. J Affect Disord 2000; 61: 23-29
• 72 Jefferson J. Is tranylcypromine really metabolized to amphetamine?. J Clin Psychiatry 1992; 53: 450-451
• 73 Baker G, Urichuk L, McKenna K et al. Metabolism of monoamine oxidase inhibitors. Cell Mol Neurobiol 1999; 19: 411-426
• 74 Cohen R, Campbell I, Dauphin M et al. Changes in alpha- and beta-receptor densities in rat brain as a result of treatment with monoamine oxidase inhibiting antidepressants. Neuropharmacology 1982; 21: 293-298
• 75 Siever L, Uhde T, Murphy DL. Possible subsensitization of alpha 2-adrenergic receptors by chronic monoamine oxidase inhibitor treatment in psychiatric patients. Psychiatry Res 1982; 293-302
• 76 Casillas A, Clark L. Dependency, impulsivity, and self-harm: traits hypothesized to underline the association between cluster B personality disorder and substance abuse disorders. J Pers Disord 2002; 16: 424-436
• 77 Cohen P, Chen H, Crawford T et al. Personality disorders in early adolescence and the development of later substance use disorders in the general population. Drug Alcohol Depend 2007; 88 (Suppl. 01) S71-S84
• 78 Calverley D, Baker G, Coutts R et al. A method for measurement of tranylcypromine in rat brain regions using gas chromatography with electron capture detection. Biochem Pharmacol 1981; 30: 861-867
• 79 Kang G, Chung S. Identification of N-acetyl and hydroxylated N-acetyltranylcypromine from tranylcypromine-dosed rat urine. Arch Pharm Res (Korea) 1984; 7: 65-68
• 80 Baker G, Hampson D, Coutts R et al. Detection and quantification of a ring-hydroxylated metabolite of the antidepressant drug tranylcypromine. J Neural Transm 1986; 65: 233-243
• 81 Alleva J. Metabolism of tranylcypromine-C¹⁴ and d, 1-amphetamine-C¹⁴ in the rat. J Med Chem 1965; 6: 621-624
• 82 Gillman P. Advances pertaining to the pharmacology and interactions of irreversible nonselective monoamine oxidase inhibitors. J Clin Psychopharmacol 2011; 31
• 83 Yun C, Shimada T, Guengerich F. Purification and characterization of human liver microsomal cytochrome P450 2A6. Mol Pharmacol 1991; 40: 679-685
• 84 Mallinger A, Edwards D, Himmelhoch J et al. Pharmacokinetics of tranylcypromine in patients who are depressed: relationship to cardiovascular effects. Clin Pharmacol Ther 1986; 40: 444-450
• 85 Bieck P, Antonin K. Tyramine potentiation during treatment with MAO inhibitors: brofaromine and moclobemide vs irreversible inhibitors. J Neural Transm Suppl 1989; 28: 21-31
• 86 Mawdsley J. “Parstelin”. A case of fatal overdose. Med J Austr 1968; 2: 292