To The Editor: The article by Patrick J. McGrath, M.D., et al. from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study team (1) reported that treatment with the monoamine oxidase inhibitor (MAOI) tranylcypromine resulted in a 6.9% remission and 12.1% response rate for patients who had not achieved remission in three prior medication trials. These rates are not in accordance with most previous controlled studies on tranylcypromine in refractory depression (some also with patients who failed three prior medication trials), in which response rates up to 50% were found (1–3).
As acknowledged by the authors, tranylcypromine treatment was probably not optimal, since patients received rather low daily doses of tranylcypromine (mean=36.9 mg, maximum: 60 mg). In most other trials in refractory depression, dosages up to 100 mg (or even higher) were used.
One of the first randomized placebo-controlled trials in depression, by the Medical Research Council (MRC), evaluated the effect of another MAOI: phenelzine (4). In this study, both electroconvulsive therapy and imipramine (maximum: 150 mg/day) were more effective than both phenelzine (maximum: 45 mg/day) and placebo. Together with the risks associated with the use of MAOIs (e.g., tyramine effect) this led to almost complete disappearance of the MAOIs from the therapeutic arsenal. Nevertheless, phenelzine in doses up to 90 mg/day was found to be an effective treatment for patients who had not responded to previous antidepressants (3).
One of the conclusions by the authors is that the combination of venlafaxine and mirtazapine “may be preferred over tranylcypromine for patients with highly treatment-resistant depression who have not benefited adequately from several prior treatments” (1, pp. 1538–1539). In order to prevent that something may now happen with tranylcypromine as the result of the STAR*D trial similar to what occurred with phenelzine after the MRC trial, we would like to add that this only appears true for low doses of tranylcypromine, but that tranylcypromine (and phenelzine) at higher doses are still valid treatment options for refractory depression.
1.McGrath PJ, Stewart JW, Fava M, Trivedi MH, Wisniewski SR, Nierenberg AA, Thase ME, Davis L, Biggs MM, Shores-Wilson K, Luther JF, Niederehe G, Warden D, Rush AJ, STAR*D Study Team: Tranylcypromine versus venlafaxine plus mirtazapine following three failed antidepressant medication trials for depression: a STAR*D report. Am J Psychiatry 2006; 163:1531–1541
2.Nolen WA, Van de Putte JJ, Dijken WA, Kamp JS, Blansjaar BA, Kramer HJ, Haffmans J: 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 Psychiatr Scand 1988; 78:676–683
3.Birkenhäger TK, Van den Broek WW, Mulder PG, Bruijn JA, Moleman P: Efficacy and tolerability of tranylcypromine versus phenelzine: a double-blind study in antidepressant-refractory depressed inpatients. J Clin Psychiatry 2004; 65:1505–1510
4.Medical Research Council Clinical Psychiatry Committee: Medical Research Council trial of the treatment of depressive illness. BMJ 1965; 1:881–886
Dr. Nolen reports the following: grants from the Netherlands Organisation for Health Research and Development, Netherlands Organisation for Scientific Research, Stanley Medical Research Institute, Astra Zeneca, Eli Lilly, GlaxoSmithKline, and Wyeth; honoraria/speaker’s fees from Astra Zeneca, Eli Lilly, Johnson & Johnson, Servier, Pfizer, and Wyeth; and advisory board service with Astra Zeneca, Cyberonics, Eli Lilly, GlaxoSmithKline, Johnson & Johnson, Pfizer, and Servier. Drs. van den Broek and Birkenhäger report no competing interests.