The STAR*D study: Treating depression in the real world
ABSTRACTThe Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study evaluated feasible treatment strategies to improve clinical outcomes for real-world patients with treatment-resistant depression. Although the study found no clear-cut "winner," it does provide guidance on how to start therapy and how to proceed if initial treatment fails.
KEY POINTS
- Remission (ie, complete relief from a depressive episode) rather than response (merely substantial improvement) should be the goal of treatment, as it is associated with a better prognosis and better function.
- Should the first treatment fail, either switching treat mentor augmenting the current treatment is reasonable.
- For most patients, remission will require repeated trials of sufficiently sustained, vigorously dosed antidepressant medication. Physicians should give maximal but tolerable doses for at least 8 weeks before deciding that an intervention has failed.
- After two well-delivered medication trials, the likelihood of remission substantially decreases. Such patients likely require more complicated regimens. Given the thin existing database, these patients are best referred to a psychiatrist for more complex treatments.
- With persistent and vigorous treatment, most patients will enter remission: about 33% after one step, 50% after two steps, 60% after three steps, and 70% after four steps (assuming patients stay in treatment).
Measurement-based care
We used a systematic approach to treatment called “measurement-based care,”24 which involves routinely measuring symptoms23 and side effects22 and using this information to modify the medication doses at critical decision points. This algorithmic approach provided flexible treatment recommendations to ensure that the dosage and duration of antidepressant drug treatment were adequate.25
The severity of depression was assessed by the clinician-rated, 16-item Quick Inventory of Depressive Symptomatology (QIDS-C16). The QIDS-SR16 (the self-report version) can substitute for the QIDS-C1623 to make this approach more feasible. Both tools are available at www.ids-qids.org.
This approach was easily worked into busy primary care and specialty care office workflows (clinic physicians, most with limited research experience, provided the treatment), and could be translated into primary care practice in the community as well.
Four-step protocol
A unique feature of the study design was that the patients, in consultation with their physicians, had some choice in the treatments they received. In this “equipoise-stratified randomized design,”26 at levels 2 and 3 the patient could choose either to switch therapies (stop the current drug and be randomized to receive one of several different treatments) or to augment their current therapy (by adding one of several treatments in a randomized fashion). Patients could decline certain strategies as long as there were at least two possible options to which one might be randomized.
At level 2, one of the options for both switching and augmentation was cognitive therapy, although patients could decline that option. Conversely, if they definitely wanted cognitive therapy, they could choose to be randomized to either cognitive therapy alone or to cognitive therapy added to citalopram. Also, anyone who received cognitive therapy in level 2 and failed to enter remission was additionally randomized to either bupropion or venlafaxine (level 2a) to ensure that all patients had failed trials on two medications before entering level 3.
When switching to medications other than a monoamine oxidase inhibitor (MAOI), the clinician could choose either to stop the current medication and immediately begin the next one, or to decrease the current medication while starting the new one at a low dose and then tapering and titrating over 1 week. (Switching to an MAOI, used only in the final level of treatment, required a 7- to 10-day washout period.)
Outcomes measured
Remission (complete recovery from the depressive episode), the primary study outcome, was defined as a HAM-D17 score of 7 or less, as assessed by treatment-blinded raters.A secondary remission outcome was a QIDS-SR16 score of 5 or less. Of note, the HAM-D17 remission rates were slightly lower than the rates based on the QIDS-SR16, since patients who did not have a HAM-D17 score measured at exit were defined as not being in remission a priori. Thus, the QIDS-SR16 rates might have been a slightly better reflection of actual remission rates.
Response, a secondary outcome, was defined as a reduction of at least 50% in the QIDS-SR16 score from baseline at the last assessment.
FEW DIFFERENCES BETWEEN PSYCHIATRIC, PRIMARY CARE PATIENTS
The patients seen in primary care clinics were surprisingly similar to those seen in psychiatric clinics.27,28 The two groups did not differ in severity of depression, distribution of severity scores, the likelihood of presenting with any of the nine core criteria of a major depressive episode, or the likelihood of having a concomitant axis I psychiatric disorder in addition to depression (about half of participants in each setting had an anxiety disorder).
Recurrent major depressive disorders were common in both groups, though more so in psychiatric patients (78% vs 69%, P < .001), while chronic depression was more common in primary care than in psychiatric patients (30% vs 21%, P < .001). Having either a chronic index episode (ie, lasting > 2 years) or a recurrent major depressive disorder was common in both groups (86% vs 83%, P = .0067).
That said, primary care patients were older (44 years vs 39 years, P < .001), more of them were Hispanic (18% vs 9%, P < .001), and more of them had public insurance (23% vs 9%, P < .001). Fewer of the primary care patients had completed college (20% vs 28%, P < .001), and the primary care patients tended to have greater medical comorbidity. Psychiatric patients were more likely to have attempted suicide in the past and to have had their first depressive illness before age 18.
