Major Depression: An Interview with Dr. Eric M. Plakun page 2

For instance?
To understand the problem, you have to go back to the way that studies get conducted. Most treatment trials begin by screening out people who have more than one disorder. Our whole diagnostic system in psychiatry — and the whole effort to determine what’s effective in treatment — has been constructed around single disorders. But in doing that we may send away half or three quarters — or more — of the people who would present to be candidates in the study of a disorder, say with depression. Our experience at Austen Riggs, and we hear this from other psychiatrists, too, is that the people who get excluded from studies are a lot like the people who come into clinicians’ offices. They have multiple disorders on top of depression, whether it’s substance use disorders, anxiety disorders, or personality disorders. Having multiple disorders is called “comorbidity.” Our patients at Riggs have an average of 6 comorbid disorders if we use careful research level diagnosis.

So the trials of a treatment, say for depression, start out with a skewed sample, and then treat them with one or another form of psychotherapy or, more typically, a course of medication. There’s often a statistically significant improvement. So, to take a hypothetical depression inventory that goes from 0 to 20, with non-depressed people scoring below 8, you may see someone’s score dip from an 18 to a 13 with a high degree of statistical significance. But someone who has a score of 13 is still pretty depressed. So we need to ask, how much better do they get? Wouldn’t they still deserve and want treatment with a score of 13 if non-depressed people score below 8?

And then there is the placebo effect. Often half to 2/3 of the effect of a drug for depression is its placebo effect. You also have to consider the “file drawer” phenomenon. When drug companies do research, they’ve tended to offer for publication the studies that show benefit. They’ve tended not to reveal the studies that don’t. And journals aren’t necessarily as interested in studies that fail to show a benefit from a treatment, too. They have wanted to publish exciting new developments, not evidence of lack of benefit from a tested treatment When we add all this up, how does that revise our sense of the efficacy of anti-depressant medications? A recent study found that when we considered the issues we’ve been discussing that confound the research, we are overestimating the efficacy of antidepressant drugs by about a third.

So there’s growing recognition of what we call treatment resistant depression. In plain terms, this refers to patients who have tried over and over again to get help for their depression, but remain troubled and symptomatic. It is not about patients intentionally resisting treatment. And the problem is not just treatment resistant depression. We are discovering the limits of treatment for most disorders. My colleague Dr. David Mintz did a survey of citations of treatment resistant disorders in publications, and found an 800 percent increase in them in the last decade. The field seems to be noticing the problem.

Treatment resistance isn’t only a clinical problem, but it’s also a financial one. Your average patient with a relatively uncomplicated treatment responsive depression costs nineteen times less to treat than a patient with a more complicated treatment resistant — we also call it “treatment refractory” — depression.

The typical picture of a Riggs patient is somebody with just this sort of treatment refractory mood disorder. Most of them, perhaps as many as 80 percent, have unipolar major depression, among other diagnoses. And others come with a depression that meets criteria for a major depressive episode, but is actually part of a bipolar disorder. So we know that the vast majority of our patients are people with treatment refractory depression of one kind or another—along with several other problems, including, much of the time, a personality disorder.

No one gets to Riggs without substantial treatment elsewhere? Why do other treatments fail them?
In some ways it is the treatments rather than the patients that are failing in treatment resistance. If you survey the field, you find that many good psychiatrists tend to have biological blinders on because of how they’ve been trained. The algorithms that psychiatrists are using for treatment refractory depression — the ones you find in the American Psychiatric Association practice guidelines, for example — are almost exclusively biological: They essentially say, “Try this or that medication. If that doesn’t work, switch medications. If that doesn’t work, augment with this pill. If that doesn’t work, try ECT.” The notion of intensive psychotherapy, much less residential treatment, of refractory depression scarcely occurs to many clinicians. If it isn’t about molecules, it isn’t in their minds.

There are missing steps in this narrow view of treatment resistance. Most glaringly, these treatments tend to neglect a psychosocial portrait of the patient: How are they doing in relationships? How are they doing at work? Have they needed one or more hospitalizations? Is suicide an issue? It’s quite striking that this gets left out, as though psychiatrists are only looking at humans as brain cell receptor sites for drugs.

Continued - page 3