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More on STAR*D’s Trials (and Tribulations)

Little new light from the latest STAR*D reports

Two more reports have emerged from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, which concerns the treatment of "real-world" patients with major depression, including many with comorbidities. In Wave 1, 4041 patients received open-label citalopram. In Wave 2, those who failed to respond to, or were intolerant of, citalopram were randomized to sertraline, sustained-release bupropion, or extended-release venlafaxine or to citalopram augmentation with bupropion SR or buspirone (Journal Watch Psychiatry Apr 5 2006). Of those with drug intolerance or with no remission in Wave 2, 235 were randomized in Wave 3 to mirtazapine or nortriptyline; no differences were seen in tolerability or in remission rates (mirtazapine, 12.3%; nortriptyline, 19.8%) (Journal Watch Psychiatry Jul 17 2006).

The two latest reports from STAR*D are informative but, unfortunately, not much more enlightening.

Researchers followed a separate cohort of 142 patients who showed drug intolerance or no remission in Wave 2. These patients continued treatment with citalopram, sertraline, bupropion SR, or venlafaxine XR and were randomized to augmentation with triiodothyronine (T₃; initial dosage, 25 µg/day; maximum, 50 µg/day) or lithium (initial dosage, 450 mg/day; maximum, 900 mg/day). Duration of augmentation treatment averaged 9.6 weeks. The T₃ and lithium groups had statistically similar remission rates (T₃, 24.7%; lithium, 15.9%), but lithium recipients had more frequent adverse effects.

In a Wave 4 study, 109 patients whose depression had failed to remit in Wave 3 were randomized to tranylcypromine (average dosage at exit, 36.9 mg/day) or to mirtazapine plus venlafaxine XR (average exit dosages, 210.3 mg/day and 35.7 mg/day, respectively). Again, remission rates were not different between groups (e.g., remission on Hamilton Rating Scale for Depression: mirtazapine plus venlafaxine, 13.7%; tranylcypromine, 6.9%). The tranylcypromine group showed less symptom reduction and more dropouts due to adverse effects.

Comment: The STAR*D data point to no "home runs" for particular treatments but to a number of as-yet-unpredictable "infield singles." The lack of placebo arms in these studies limits interpretation of these data. Overall, they offer little guidance to clinicians as to specific medications or strategies for patients with treatment-resistant depression, but they do indicate the general rates of remission that might be expected from the various combination and augmentation strategies included in the STAR*D algorithm. This large-scale study proscribed mood stabilizers, atypical antipsychotics, stimulants, ECT, and other common strategies; thus, we await other large-scale "real-world" studies to examine these augmentation and combination strategies. We hope that biologic, perhaps allelic, markers will enable us at some point to predict which strategies best suit which patients, sparing them the burden of enduring three or four sequential trials.

— Joel Yager, MD

Published in Journal Watch Psychiatry October 16, 2006

Citation(s):

Nierenberg AA et al. A comparison of lithium and T₃ augmentation following two failed medication treatments for depression: A STAR*D report. Am J Psychiatry 2006 Sep; 163:1519-30.

• Original article (Subscription may be required)
• Medline abstract (Free)

McGrath PJ et al. Tranylcypromine versus venlafaxine plus mirtazapine following three failed antidepressant medication trials for depression: A STAR*D report. Am J Psychiatry 2006 Sep; 163:1531-41.

• Original article (Subscription may be required)
• Medline abstract (Free)