To The Editor: We agree with the important point raised by Drs. Nolen et al. Their landmark studies, cited in our paper, clearly suggest that doses of tranylcypromine higher than those approved by the Food and Drug Administration (FDA) in the United States show substantial efficacy in treatment-resistant depression. Because STAR*D decided to use dosages only up to the FDA recommended maximum, STAR*D was unable to test the effectiveness of the doses Nolen et al. and others have used for treatment-resistant depression. As indicated in our article, even the maximum allowable dose was infrequently used. The low likelihood of remission in STAR*D patients treated with tranylcypromine, together with its low dosing and poor tolerance, support our conclusion that tranylcypromine is not a treatment clinicians in most practice settings are likely to use optimally or successfully. Nevertheless, we fully agree with Nolen et al. that a vigorous trial of an MAOI should be considered for depressed patients not responsive to multiple other antidepressant trials. However, the experience of STAR*D suggests that tranylcypromine and other MAOI treatment may be better handled by a psychopharmacology specialist who is knowledgeable about these agents, and who is aware that higher than recommended doses of tranylcypromine may be very effective for select patients.