Delivery of care
An important and implicit aspect of the STAR*D trial, according to Insel, was the diligent delivery of care.
“People who entered this very large trial received a management of care approach that is really quite different from what many people in the United States receive when they see a primary care physician or even a psychiatrist for depression,” Insel said. “This trial included a depression care specialist who was, in some ways, a coordinator of how care was delivered and who would make sure there was very careful monitoring of side effects. There was also a relentless attempt to optimize the dose. This is really an important part of this treatment. . . . It is changing the way in which people with depression get care in a very proactive way.”
When discussing the quality of care delivered, Rush said the investigators came to a “Goldilocks' decision—not too hot, not too cold, just right.” They didn’t want to use standard, routine care, because too often it involves relatively infrequent treatment visits and does not include assessment using careful interviewing and rating scales. In addition, there is widespread variability among clinicians as to when to raise medication doses and by how much, he said.
In the STAR*D trial, the depression care specialist guided clinicians in the application of measurement-based care, including the measurement of symptoms and side effects at each treatment visit and the use of a treatment manual that described when and how to modify medication doses based on the measures.3
Take-home messages
There are 3 take-home messages from STAR*D that are relevant to clinical practice, according to Rush. First, the duration of a trial of a medication to determine whether it is going to be effective must exceed 4 weeks.
“Do not make that judgment until you have hit 6 to 8 weeks,” he said. Second, in making the judgment about the efficacy of a particular medication, it “is extremely wise to use tools, not just a quick interview where you ask the patient, 'Are you feeling a little or a lot better?’”
Many of those tools are available on the STAR*D Web site, including the QIDS-SR-16, in both English and Spanish; the Frequency, Intensity, and Burden of Side Effects Rating (FIBSER) in both English and Spanish; and the Patient-Rated Inventory of Side Effects, which is used in combination with the FIBSER.7
The tools are self-report ratings done by the patient, so they take no time away from the physician. They make measurements much more precise and make the choices to proceed, stop, or switch the medication much clearer, Rush said.
The third take-home message, according to Rush, is that physicians can now say to patients, “If you stay in treatment for 2 steps, you have a greater than 50% chance of not just getting better but getting rid of the depression.” Since depression sucks the life-force out of patients and can even cause them to avoid getting into or staying in treatment if they encounter some challenge, the assurance of possible remission can be motivating.
Much of what was learned in the STAR*D trial will need to be considered in any revision of clinical practice guidelines, Rush told Psychiatric Times.
The future
In an editorial accompanying the Level 2 reports in the New England Journal of Medicine, David Rubinow, MD, Assad Meymandi professor and chair of the department of psychiatry at the University of North Carolina, Chapel Hill, said, “Much of the promise of the STAR*D trials may be found in the identification of predictors of response to antidepressant therapies—the differences among patients that should permit the design of more specific, individualized treatment.”8
On the other hand, he noted, the carefully performed trials were discouraging, in part because the “results suggest that at least half of patients with depression do not have a remission.”
In a response to Rubinow’s statement, Insel said, “The glass is half empty in the sense that we need to come up with yet better treatments in the future that increase remission to 100% and do it more quickly.”
The challenge, Insel said, is to “come up with new classes of medications. That is going to require a better understanding of the pathophysiology of depression. . . . That understanding will enable us to go after new targets. There are some on the horizon; a whole series of compounds are being tried out in our intramural programs, with the hope of finding a response in hours rather than weeks.”
