Download PDF
Pharmacopsychiatry 2013; 46(04): 123-129
DOI: 10.1055/s-0032-1333265
Review
© Georg Thieme Verlag KG Stuttgart · New York

Withdrawal and Discontinuation Phenomena Associated with Tranylcypromine: A Systematic Review

M. Gahr
1   Department of Psychiatry and Psychotherapy III, University of Ulm, Ulm, Germany
,
C. Schönfeldt-Lecuona
1   Department of Psychiatry and Psychotherapy III, University of Ulm, Ulm, Germany
,
M. A. Kölle
1   Department of Psychiatry and Psychotherapy III, University of Ulm, Ulm, Germany
,
R. W. Freudenmann
1   Department of Psychiatry and Psychotherapy III, University of Ulm, Ulm, Germany
› Author Affiliations
Further Information

Publication History

received 10 October 2012
revised17 December 2012

accepted 18 December 2012

Publication Date:
28 January 2013 (online)

Also available at
    Permissions and Reprints

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

Supporting information:

 

  • 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
    PubMedGoogle Scholar
  • 2 Stewart J, Thase M. Treating DSM-IV depression with atypical features. J Clin Psychiatry 2007; 68: e10
    CrossrefPubMedGoogle Scholar
  • 3 Pae C, Tharwani H, Marks D et al. Atypical depression: a comprehensive review. CNS Drugs 2009; 23: 1023-1037
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 6 Shih J, Chen K. Regulation of MAO-A and MAO-B gene expression. Curr Med Chem 2004; 11: 1995-2005
    CrossrefPubMedGoogle Scholar
  • 7 Billett E. Monoamine oxidase (MAO) in human peripheral tissues. Neurotoxicology 2004; 25: 139-148
    CrossrefPubMedGoogle Scholar
  • 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
    Google Scholar
  • 9 Philips S, Boulton M. The effects of monoamine oxidase inhibitors on some arylalkylamines in rat striatum. J Neurochem 1979; 33: 159-167
    CrossrefPubMedGoogle Scholar
  • 10 Boulton M, Juorio A. Brain trace amines. In: Lajtha A. ed. Handbook of Neurochemistry. New York: Plenum Press; 1982: 189-222
    Google Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 13 Paterson I, Boulton M. Beta-phenylethylamine enhances single cortical neurone responses to noradrenaline in the rat. Brain Ress Bull 1988; 20: 173-177
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 15 Jones R. Tryptamine: a neuromodulator or neurotransmitter in mammalian brain?. Prog Neurobiol 1982; 19: 117-139
    CrossrefPubMedGoogle Scholar
  • 16 Jones R. Trace biogenic amines: a possible functional role in the CNS. Trends Pharmacol Sci 1983; 4: 426-429
    CrossrefPubMedGoogle Scholar
  • 17 Beavan T. The cheese reaction. Lancet 1964; 1: 540
    PubMedGoogle Scholar
  • 18 Blackwell B. Hypertensive crisis due to monoamine-oxidase inhibitors. Lancet 1963; 2: 849-850
    PubMedGoogle Scholar
  • 19 Asatoor A, Levi A, Milne M. Tranylcypromine and cheese. Lancet 1963; 54: 733-734
    PubMedGoogle Scholar
  • 20 Graham W. Hypertension caused by tranylcypromine and cheese. JAMA 1964; 188: 782
    PubMedGoogle Scholar
  • 21 Cuthill J, Griffiths A, Powell D. Death associated with tranylcypromine and cheese. Lancet 1964; 1: 1076-1077
    PubMedGoogle Scholar
  • 22 Bethune N, Burrell R, Culpan R. Headache associated with monoamine oxidase inhibitors. Lancet 1963; 2: 1233-1234
    PubMedGoogle Scholar
  • 23 Horwitz D, Lovenberg W, Engelman K et al. Monoamine oxidase inhibitors, tyramine, and cheese. JAMA 1964; 188: 1108-1110
    CrossrefPubMedGoogle Scholar
  • 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 26 Amsterdam J, Berwish N. High dose tranylcypromine therapy for refractory depression. Pharmacopsychiatry 1989; 22: 21-25
    Article in Thieme ConnectPubMedGoogle Scholar
  • 27 Glaxo-Smith-Kline. Parnate. Prescribing information 2010
    PubMed
  • 28 Aristo-Pharma. Jatrosom N. Prescribing information 2010
    PubMed
  • 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 30 Gillman P. A review of serotonin toxicity data: implications for the mechanisms of antidepressant drug action. Biol Psychiatry 2006; 59: 1046-1051
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 33 Tuomisto J, Smith D. Effects of tranylcypromine enantiomers on monoamine uptake and release and imipramine binding. J Neural Transm 1986; 65: 135-145
    CrossrefPubMedGoogle Scholar
  • 34 Frieling H, Bleich S. Tranylcypromine: new perpectives of an “old” drug. Eur Arch Psychiatry Clin Neurosci 2006; 256: 268-273
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 36 Le Gassicke J. Trancylcypromine. Lancet 1963; 281: 269-270
    PubMedGoogle Scholar
  • 37 Mielczarek J, Johnson J. Tranylcypromine. Lancet 1963; 281: 388-389
    PubMedGoogle Scholar
  • 38 Morgan D. Tranylcypromine. Lancet 1963; 281: 389
    CrossrefPubMedGoogle Scholar
  • 39 Szelényi A, Albrecht J. Tranylcypromine abuse associated with an isolated thrombocytopenia. Pharmacopsychiatry 1998; 31: 238-240
    Article in Thieme ConnectPubMedGoogle Scholar
  • 40 Vartzopoulos D, Krull F. Dependence on monoamine oxidase inhibitors in high dose. Br J Psychiatry 1991; 158: 856-857
    CrossrefPubMedGoogle Scholar
  • 41 Griffin N, Draper R, Webb M. Addiction to tranylcypromine. Br Med J (Clin Res Ed) 1981; 283: 346
    PubMedGoogle Scholar
  • 42 Briggs N, Jefferson J, Koenecke F. Tranylcypromine addiction: a case report and review. J Clin Psychiatry 1990; 51: 426-429
    PubMedGoogle Scholar
  • 43 Bellon A, Coverdale J. Delirium, thrombocytopenia, insomnia, and mild liver damage associated with MAOI withdrawal. Eur J Clin Pharmacol 2009; 65: 1269-1270
    CrossrefPubMedGoogle Scholar
  • 44 Halle M, Dilsaver S. Tranylcypromine withdrawal phenomena. J Psychiatr Neurosci 1993; 18: 49-50
    PubMedGoogle Scholar
  • 45 Chatterjee A, Tosyali M. Thrombocytopenia and delirium associated with tranylcypromine overdose. J Clin Psychopharmacol 1995; 15: 143-144
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 47 Davids E, Röschke J, Klawe C et al. Tranylcypromine abuse associated with delirium and thrombocytopenia. J Clin Psychopharmacol 2000; 20: 270-271
    CrossrefPubMedGoogle Scholar
  • 48 Dilsaver S. Heterocyclic antidepressant, monoamine oxidase inhibitor and neuroleptic withdrawal phenomena. Prog Neurpsychopharmacol Biol Psychiatry 1990; 14: 137-161
    PubMedGoogle Scholar
  • 49 Haddad P. Newer antidepressants and the discontinuation syndrome. J Clin Psychiatry 1997; Suppl 7: 17-21 discussion 22
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 52 Dilsaver S. Monoamine oxidase inhibitor withdrawal phenomena: symptoms and pathophysiology. Acta Psychiatr Scand 1988; 78: 1-7
    PubMedGoogle Scholar
  • 53 APA . Diagnostical and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. 4th ed. Washington, DC: American Psychiatric Association; 2000
    Google Scholar
  • 54 Eyer F, Jetzinger E, Pfab R et al. Withdrawal from high-dose tranylcypromine. Clin Toxicol (Phila) 2008; 46: 261-263
    CrossrefPubMedGoogle Scholar
  • 55 Brady K, Lydiard R, Kellner C. Tranylcypromine abuse. Am J Psychiatry 1991; 148: 1268-1269
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 57 Absher J, Black D. Tranylcypromine withdrawal delirium. J Clin Psychopharmacol 1988; 8: 379-380
    PubMedGoogle Scholar
  • 58 Ben-Arie O, George G. A case of tranylcypromine (‘Parnate’) addiction. Br J Psychiatry 1979; 135: 273-274
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 60 Shaikh W, Fuls K. Tranylcypromine dependence and withdrawal. Aust N Z J Psychiatry 2009; 43: 580-581
    PubMedGoogle Scholar
  • 61 Shopsin B, Kline N. Monoamine oxidase inhibitors: potential for drug abuse. Biol Psychiatry 1976; 11: 451-456
    PubMedGoogle Scholar
  • 62 Westermeyer J. Addiction to tranylcypromine (Parnate): a case report. Am J Drug Alcohol Abuse 1989; 15: 345-350
    CrossrefPubMedGoogle Scholar
  • 63 Thorp M, Toombs D, Harmon B. Monoamine oxidase inhibitor overdose. West J Med 1997; 166: 275-277
    PubMedGoogle Scholar
  • 64 Boyer E, Shannon M. The serotonin syndrome. N Engl J Med 2005; 352: 1112-1120
    CrossrefPubMedGoogle Scholar
  • 65 Brubacher J, Hoffmann R, Lurin M. Serotonin syndrome from venlafaxine-tranylcypromine interaction. Vet Hum Toxicol 1996; 38: 358-361
    PubMedGoogle Scholar
  • 66 Silverstone T, Turner P. Drug Treatment in Psychiatry. In. 5th ed. London: Rutledge; 1995: 140-189
    Google Scholar
  • 67 Robinson D. High-dose monoamine-oxidase inhibitor therapy JAMA 1983; 250: 2212
    PubMed
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 70 Mutschler E, Möhrke W. Kinetics of MAO inhibitors. Mod Probl Pharmacopsychiatry 1983; 19: 126-134
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 72 Jefferson J. Is tranylcypromine really metabolized to amphetamine?. J Clin Psychiatry 1992; 53: 450-451
    PubMedGoogle Scholar
  • 73 Baker G, Urichuk L, McKenna K et al. Metabolism of monoamine oxidase inhibitors. Cell Mol Neurobiol 1999; 19: 411-426
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 81 Alleva J. Metabolism of tranylcypromine-C14 and d, 1-amphetamine-C14 in the rat. J Med Chem 1965; 6: 621-624
    PubMedGoogle Scholar
  • 82 Gillman P. Advances pertaining to the pharmacology and interactions of irreversible nonselective monoamine oxidase inhibitors. J Clin Psychopharmacol 2011; 31
    PubMedGoogle Scholar
  • 83 Yun C, Shimada T, Guengerich F. Purification and characterization of human liver microsomal cytochrome P450 2A6. Mol Pharmacol 1991; 40: 679-685
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 86 Mawdsley J. “Parstelin”. A case of fatal overdose. Med J Austr 1968; 2: 292
    PubMedGoogle Scholar