Remission in Patients with Depression is Possible, But Hard to Sustain


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Patients who recover from a major depressive episode are at high of a relapse according to a study released by the National Institute of Mental Health. This is why it is critical for patients to not only sustain the response, but to be vigilant about staying well by strictly following the doctor's long term treatment plan.

Findings from the latest phase of the National Institute of Mental Health's STAR*D (Sequenced Treatment Alternatives to Relieve Depression) study indicate that patients who require multiple antidepressant drug trials to reach remission not only have significantly higher rates of relapse but also relapse sooner, compared with patients who require only one or two drug trials. Nonetheless, with persistence, about two-thirds of people with depression can reach remission if they are willing to try different medications.

I fully appreciated and understood the ramifications of this five year study. This latest report, which appeared in the November American Journal of Psychiatry, is the 38th article on STAR*D published in peer-reviewed journals. It details the outcomes of the series of acute treatment steps that patients took to be well enough to progress to follow-up or maintenance treatment. Because the report connects acute treatment outcomes to longer-term prognosis in a well-characterized patient population of more than 3,600 patients, it may end up being one of the most important ever published on the treatment of major depression.

The study was conducted at 41 clinical sites; 18 provided primary care, while 23 provide psychiatric care. The results of the successive treatment steps have been reported previously (Psychiatric News, January 20, April 21, July 7, September 15).

In the latest report, researchers consolidated an enormous amount of data on 3,671 patients who entered the protocol at the first step and their subsequent quest for remission through the four potential treatment steps.

Here are a few details about this landmark national study. All of the study patients started the study in step 1, taking citalopram (Celexa). Those who did not do well on citalopram could progress to step 2, which involved either switching to a different antidepressant or augmenting citalopram with a second drug. For those who still were not well enough to enter follow-up, step 3 again offered a switch to a different antidepressant or augmentation of the patients’ step 2 drug regimen. Step 4 offered a final opportunity to switch medications or augment a patients’ step 3 regimen. Each of the individual steps in the protocol lasted for up to 14 weeks, and the follow-up phase of the study lasted for 12 months.

Sicker Patients Need More Steps

Patients with more severe depression, greater general medical or psychiatric comorbidity, and chronicity made up the group that needed more treatment steps" to reach follow-up—either by achieving remission or at least a meaningful improvement with acceptable tolerability. So, the more problems you enter treatment with, the more steps you'll likely need.

The bottom line of the study is that over the four acute treatment steps, 67 percent of the patients achieved remission. The lead study investigator commented that it was a pretty good overall outcome, but it assumed that everyone stays in treatment as long as it takes to reach remission—it assumed no dropouts.

Long-Term Outlook: Remission Elusive

The most important finding from the follow-up phase of the study, is that the more steps a patient has to take to be well enough to go into follow-up, the worse the longer-term prognosis is.

For example, he said, after six months of follow-up, about 65 percent of patients who entered follow-up from step 1 remained well (while about 35 percent had relapsed). In contrast, at the six-month follow-up, only about 53 percent of patients from step 2 remained well, compared with less than 40 percent of those from either step 3 or step 4.

The study investigators remarked that this was very discouraging. After working hard through multiple steps, the patient is finally well enough to enter follow-up, then the medication that got them well enough to begin with doesn't keep them well over the longer-term. Now there is a second issue—of not being able to keep the patient well.

So, the take-home message, is that a positive longer-term prognosis for patients with depression is dependent on achieving and sustaining full remission, regardless of how many treatment steps it takes to get there.

It also told the investigators that psychiatrists must be more vigilant with patients who are in follow-up, especially [with] those who have required several steps to get there.

For me personally, I was rescued from the grips of depression, thanks to a new FDA approved procedure called vagus nerve stimulation. It is a ninety-minute out-patient procedure and I continue to “enjoy" the benefits of this remarkable, medical breakthrough treatment. For more information visit

Charles Donovan was a patient in the FDA investigational trial of vagus nerve stimulation as a treatment for chronic or recurrent treatment-resistant depression. He was implanted with the vagus nerve stimulator in April of 2001. He chronicles his journey from the grips of depression thanks to vagus nerve stimulation therapy in his book:

Out of the Black Hole: The Patient's Guide to Vagus Nerve Stimulation and Depression

His all inclusive book prepares depression sufferers to make an informed decision about this ninety-minute out-patient procedure. It is a “must read" before you discuss this treatment with your psychiatrist. A prescription for the procedure is required from an M. D. and it is covered by most insurance plans.

He is the founder of the Web Site and Bulletin.


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