Safety of High-intensity Treatment with the Irreversible Monoamine Oxidase Inhibitor Tranylcypromine in Patients with Treatment-resistant Depression

Abstract

Introduction: Because the irreversible monoamine oxidase inhibitor tranylcypromine (TCP) was introduced nearly 50 years ago, only few studies exist on today's clinical prescribing practice together with 2nd and 3rd generation psychotropic drugs.

Methods: We performed a practice-based observational study of patients with depression treated with TCP in two psychiatric departments in Berlin to assess side effects, effectiveness, comedication and acceptance of the low-tyramine diet.

Results: We identified thirty-two patients treated with TCP at a mean dose of 51.9 mg/day after an average of 3.3 pre-treatments in the current episode. Dosing of TCP and the use of multiple psychotropic comedications indicate a high-intensity treatment. The most frequent side effects resulted from arterial hypotonia (28%). Dietary restrictions were mainly rated as moderate. 59% of patients remitted (HAMD-₂₁<9 or CGI-I=1) and 22% responded (HAMD-₂₁ reduction >50% or CGI-I=2).

Discussion: A high-intensity treatment of inpatients with TCP is clinically feasible, i.e., the use of high doses and multiple comedications with a good benefit-risk-ratio. Prospective data aiming at comparisons with modern antidepressants and clarifying further safety issues are warranted.

References

• 1 Adli M, Baethge C, Heinz A. et al . Is dose escalation of antidepressants a rational strategy after a medium-dose treatment has failed? A systematic review.  Eur Arch Psychiat Clin Neurosci. 2005;  255 387-400
• 2 Adli M, Berghofer A, Linden M. et al . Effectiveness and feasibility of a standardized stepwise drug treatment regimen algorithm for inpatients with depressive disorders: results of a 2-year observational algorithm study.  J Clin Psychiat. 2002;  63 782-790
• 3 Adli M, Rush AJ, Moller HJ. et al . Algorithms for optimizing the treatment of depression: making the right decision at the right time.  Pharmacopsychiatry. 2003;  36 ((Suppl 3)) 222-229
• 4 Amsterdam JD, Berwish NJ. High dose tranylcypromine therapy for refractory depression.  Pharmacopsychiat. 1989;  22 21-25
• 5 Bauer M, Whybrow PC, Angst J. et al . World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 1: Acute and continuation treatment of major depressive disorder.  World J Biol Psychiat. 2002;  3 5-43
• 6 Beasley Jr CM, Masica DN, Heiligenstein JH. et al . Possible monoamine oxidase inhibitor-serotonin uptake inhibitor interaction: fluoxetine clinical data and preclinical findings.  J Clin Psychopharmacol. 1993;  13 312-320
• 7 Berlin I, Zimmer R, Cournot A. et al . Determination and comparison of the pressor effect of tyramine during long-term moclobemide and tranylcypromine treatment in healthy volunteers.  Clin Pharmacol Ther. 1989;  46 344-351
• 8 Birkenhäger TK, Broek WW van den, Mulder PG. et al . Efficacy and tolerability of tranylcypromine versus phenelzine: a double-blind study in antidepressant-refractory depressed inpatients.  J Clin Psychiat. 2004;  65 1505-1510
• 9 Bucci L. The negative symptoms of schizophrenia and the monoamine oxidase inhibitors.  Psychopharmacology (Berl). 1987;  91 104-108
• 10 Fava M. Diagnosis and definition of treatment-resistant depression.  Biol Psychiat. 2003;  53 649-659
• 11 Gardner DM, Shulman KI, Walker SE. et al . The making of a user friendly MAOI diet.  J Clin Psychiat. 1996;  57 99-104
• 12 Gillman PK. Tricyclic antidepressant pharmacology and therapeutic drug interactions updated.  Br J Pharmacol. 2007;  151 737-748
• 13 Goforth HW, Carroll BT. Aripiprazole augmentation of tranylcypromine in treatment-resistant major depression.  J Clin Psychopharmacol. 2007;  27 216-217
• 14 Guy W, Bonato RR. Manual for the ECDEU Assessment Battery. 2nd Rev edn. Chevy Chase, Md: National Institute of Mental Health 1970
• 15 Hamilton M. A rating scale for depression.  J Neurol Neurosurg Psychiat. 1960;  23 56-62
• 16 Heinze G, Rossel L, Gabelic I. et al . Double-blind comparison of moclobemide and tranylcypromine in depression.  Pharmacopsychiatry. 1993;  26 240-245
• 17 Jacobsen FM. Low-dose trazodone as a hypnotic in patients treated with MAOIs and other psychotropics: a pilot study.  J Clin Psychiat. 1990;  51 298-302
• 18 Jenike MA. The use of monoamine oxidase inhibitors in the treatment of elderly, depressed patients.  J Am Geriatr Soc. 1984;  32 571-575
• 19 Kahn D, Silver JM, Opler LA. The safety of switching rapidly from tricyclic antidepressants to monoamine oxidase inhibitors.  J Clin Psychopharmacol. 1989;  9 198-202
• 20 Kuss HJ, Ackenheil M. No change of amitriptyline concentration by comedication of tranylcypromine.  Pharmacopsychiatry. 2005;  38 S55
• 21 Lesse S. Tranylcypromine – A study of 1000 patients with severe agitated depressions.  Am J Psychother. 1978;  32 220-242
• 22 López-Muñoz F, Álamo C, Rubio G. et al . Reboxetine combination in treatment-resistant depression to selective serotonin reuptake inhibitors.  Pharmacopsychiatry. 2007;  40 14-19
• 23 MacGrath PJ, Stewart JW, Fava M. et al . Tranylcypromine versus venlafaxine plus mirtazapine following three failed antidepressant medication trials for depression: a STAR*D report.  Am J Psychiat. 2006;  16 1531-1541
• 24 Mittmann N, Herrmann N, Shulman KI. et al . The effectiveness of antidepressants in elderly depressed outpatients: a prospective case series study.  J Clin Psychiat. 1999;  60 690-697
• 25 Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990–2020: Global Burden of Disease Study.  Lancet. 1997;  349 1498-1504
• 26 Nolen WA, Putte JJ van de, Dijken WA. et al . Treatment strategy in depression. II. MAO inhibitors in depression resistant to cyclic antidepressants: two controlled crossover studies with tranylcypromine versus L-5-hydroxytryptophan and nomifensine.  Acta Psychiat Scand. 1988;  78 676-683
• 27 Nolen WA, Broek WW van den, Birkenhager TK. Treatment with low doses of tranylcypromine resulted in a disappointing remission rate.  Am J Psychiat. 2007;  164 524
• 28 Parker G, Mitchell P, Wilhelm K. et al . Are the newer antidepressant drugs as effective as established physical treatments? Results from an Australasian clinical panel review.  Aust N Z J Psychiat. 1999;  33 874-881
• 29 Parker G, Roy K, Wilhelm K. et al . Assessing the comparative effectiveness of antidepressant therapies: a prospective clinical practice study.  J Clin Psychiat. 2001;  62 117-125
• 30 Pilhatsch MK, Burghardt R, Wandinger K-P. et al . Augmentation with atomoxetine in treatment-resistant depression with psychotic features. A case report.  Pharmacopsychiatry. 2006;  39 79-80
• 31 Rabkin J, Quitkin F, Harrison W. et al . Adverse reactions to monoamine oxidase inhibitors. Part I: a comparative study.  J Clin Psychopharmacol. 1984;  4 270-278
• 32 Razani J, White KL, White J. et al . The safety and efficacy of combined amitriptyline and tranylcypromine antidepressant treatment. A controlled trial.  Arch Gen Psychiat. 1983;  40 657-661
• 33 Remick RA, Froese C, Keller FD. Common side effects associated with monoamine oxidase inhibitors.  Prog Neuropsychopharmacol Biol Psychiat. 1989;  13 497-504
• 34 Salsali M, Holt A, Baker GB. Inhibitory effects of the monoamine oxidase inhibitor tranylcypromine on the cytochrome P450 enzymes CYP2C19, CYP2C9, and CYP2D6.  Cell Mol Neurobiol. 2004;  24 63-76
• 35 Schmauss M. High dosage tranylcypromine treatment of “therapy refractory” depressions.  Nervenarzt. 1996;  67 390-393
• 36 Schmauss M, Kapfhammer HP, Meyr P. et al . Combined MAO-inhibitor and tri- (tetra) cyclic antidepressant treatment in therapy resistant depression.  Progr Neuropsychopharmacol Biol Psychiat. 1988;  12 523-532
• 37 Stoll AL, Haura G. Tranylcypromine plus risperidone for treatment-refractory major depression.  J Clin Psychopharmacol. 2000;  20 495-496
• 38 Tariot PN, Murphy DL, Sunderland T. et al . Rapid antidepressant effect of addition of lithium to tranylcypromine.  J Clin Psychopharmacol. 1986;  6 165-167
• 39 Thase ME, Mallinger AG, MacKnight D. et al . Treatment of imipramine-resistant recurrent depression, IV: A double-blind crossover study of tranylcypromine for anergic bipolar depression.  Am J Psychiat. 1992;  149 195-198
• 40 Thase ME, Rush AJ. When at first you don't succeed: sequential strategies for antidepressant nonresponders.  J Clin Psychiat. 1997;  58 ((S13)) 23-29
• 41 Thase ME, Trivedi MH, Rush AJ. MAOIs in the contemporary treatment of depression.  Neuropsychopharmacology. 1995;  12 185-219
• 42 Volz HP, Heimann H, Bellaire J. et al . Brofaromine in non-endogenous major depressed inpatients – results of a preliminary dose-finding trial versus tranylcypromine.  Pharmacopsychiatry. 1994;  27 152-158
• 43 White K, Razani J, Cadow B. et al . Tranylcypromine vs nortriptyline vs placebo in depressed outpatients: a controlled trial.  Psychopharmacology (Berl). 1984;  82 258-262

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