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).
RESULTS FROM LONG-TERM FOLLOW-UP AFTER REMISSION OR RESPONSE
Patients with a clinically meaningful response or, preferably, remission at any level could enter into a 12-month observational follow-up phase. Those who had required more treatment levels had higher relapse rates during this phase.41 Further, if a patient achieved remission rather than just response to treatment, regardless of the treatment level, the prognosis at follow-up was better, confirming the importance of remission as the goal of treatment.
Results also provided a warning—the greater the number of treatment levels that a patient required, the more likely that patient and physician would settle for response. Whether the greater relapse rates reflect a harder-to-treat depression or the naturalistic design of the follow-up phase (with less control over dosing) is unclear.
WHAT DO THESE RESULTS MEAN FOR PRIMARY CARE PHYSICIANS?
- Measurement-based care is feasible in primary care. Primary care doctors can ensure vigorous but tolerable dosing using a self-report depression scale to monitor response, a side-effects tool to monitor tolerability, and medication adjustments at critical decision points guided by these two measures.
- Remission, ie, complete recovery from a depressive episode, rather than merely substantial improvement, is associated with a better prognosis and is the preferred goal of treatment.
- Pharmacologic differences between psychotropic medications did not translate into substantial clinical differences, although tolerability differed. These findings are consistent with a large-scale systematic evidence review recently completed by the Agency for Healthcare Research and Quality that compared the effectiveness of antidepressants.42 Given the difficulty in predicting what medication will be both efficacious for and tolerated by an individual patient, familiarity with a broad spectrum of antidepressants is prudent.
- Remission of depressive episodes will most likely require repeated trials of sufficiently sustained,vigorously dosed antidepressant medication. From treatment initiation, physicians should ensure maximal but tolerable doses for at least 8 weeks before deciding that an intervention has failed.
- If a first treatment doesn’t work, either switching or augmenting it is a reasonable choice. Augmentation may be preferred if the patient is tolerating and receiving partial benefit from the initial medication choice. While bupropion SR and buspirone were not different as augmenters by the primary remission outcome measure, secondary measures (eg, tolerability, depressive symptom change over the course of treatment, clinician-rated Quick Inventory of Depressive Symptomatology) recommended bupropion-SR over buspirone.
- If physicians switch, either a within-class switch (eg, citalopram to sertraline) or an out-of-class switch (eg, citalopram to bupropion SR) is effective, as is a switch to a dual-action agent (eg, venlafaxine XR).
- The likelihood of improvement after two aggressive medication trials is very low and likely requires more complicated medication regimens, and the existing evidence base is quite thin. These primary care patients should likely be referred to psychiatrists for more aggressive and intensive treatment.
- For patients who present with major depressive disorder, STAR*D suggests that with persistence and aggressive yet feasible care, there is hope: after one round, approximately 30% will have a remission; after two rounds, 50%; after three rounds, 60%; and after four rounds, 70%.
- While STAR*D excluded depressed patients with bipolar disorder, a depressive episode in a patient with bipolar disorder can be difficult to distinguish from a depressive episode in a patient with major depressive disorder. Primary care physicians need to consider bipolar disorder both in patients presenting with a depressive episode and in those who fail an adequate trial.43
FUTURE CONSIDERATIONS
Subsequent STAR*D analyses will compare in greater depth outcomes in primary care vs psychiatric settings at each level of treatment. Given the greater risk of depression persistence associated with more successive levels of treatment, subsequent research will focus on ways to more successfully treat depression in the earlier stages, possibly through medication combinations earlier in treatment (somewhat analogous to a “broad-spectrum antibiotic” approach for infections).
