Posts Tagged ‘personalized medicine’

The Best Laid Plans

April 8th, 2011

During the decades I have spent in academic medicine and psychiatry, I have read countless inspired theories and hypotheses concerning diseases and their treatments. Unfortunately, few have panned out. Scientists were going to cure schizophrenia with renal dialysis. Personally, I was going to alleviate tardive dyskinesia and depression with the dietary neurotransmitter precursors lecithin and tyrosine.

Fortunately, medical science is not a religious faith. The nature of empiricism allows for hypotheses to be proved—or more commonly, disproved. That’s been the story of my career and, sadly, most psychiatric science of the last century. But in our healing arts, it’s better to face the truth.

Doesn’t it stand to reason that if we inhibit both the norepinephrine and serotonin reuptake pumps, we should heal more depressed people than if we block only the serotonin transporter? A study called PREVENT showed that not to be the case.

And if we administer long-acting injectable antipsychotic medicines to patients with schizophrenia, shouldn’t we lower the relapse rate more than if we depend on their taking oral tablets? Again, no. An upcoming article in Biological Therapies in Psychiatry—“Does LAIR Beat Oral Antipsychotics?”—bursts this very logical bubble.

Someday, we’ll reach “personalized medicine” in psychiatry. Someday, more good theories will prove true than not. We’re not there yet.

-Alan J. Gelenberg, M.D.
Editor, Biological Therapies in Psychiatry
Shively/Tan Professor and Chair, Psychiatry, Penn State University
Editor-in-Chief, Journal of Clinical Psychiatry


 

Do You Believe In Magic?

March 18th, 2011

Psychiatrists often treat patients who have magical thinking. But I’ve also observed magical thinking in psychiatrists and other physicians.

I recently spoke at a conference about treating depression. I presented data from several large recent studies (STAR*D, REVAMP, PREVENT), all of which refuted hypotheses about how to tailor depression treatment to individual cases. I spoke of what Gary Sachs calls a “menu of reasonable options.” I endorsed algorithm- and measurement-based care, recommending TMAP as a reasonable and easily accessed algorithm. I cited numerous articles I’ve reviewed in the pages of BTP.

When it was time for questions, someone asked if I could please provide guidance on how to choose the right antidepressant for a given patient. For example, the questioner went on, could the agitated/retarded dimension be used to select the optimal drug? I could give an answer, I responded, but it would be free of science or evidence—since there is none. There have been many theories on this, going back to the 1950s—using behavioral symptoms, urinary metabolites, and more. But they’ve all come a cropper.

I’ve heard speakers endorse hypotheses as if they were facts. Some “experts” were well compensated by companies, who hoped their products would gain competitive market advantage from doctors believing groundless theories. Other speakers promoting magical solutions to unanswered questions appeared simply to relish the celebrity status pseudoscience provided.

I do not like to be ignorant. I yearn for the day when personalized medicine will be a reality in all specialties, psychiatry included. But for our patients, it is better to be candid, to acknowledge the boundaries of medical knowledge. Today the best treatment for a patient is the one the patient will adhere to. And the best doctor is the one who knows what he or she does not know.

- Alan J. Gelenberg, M.D.
Editor,
Biological Therapies in Psychiatry
Professor and Chair, Psychiatry, Penn State University
Editor-in-Chief,
Journal of Clinical Psychiatry

When mechanism matters

December 13th, 2010

Maprotiline (Ludiomil) is a tetracyclic antidepressant introduced in the early 1980s. It is a norepinephrine reuptake inhibitor, which is believed to be its primary mechanism of antidepressant action. It had a particularly high incidence of seizures, which the manufacturer initially minimized. Today maprotiline is seldom prescribed.

Initial advertising for maprotiline featured the headline, “When Mechanism Matters.” Perhaps the people who wrote the ad copy were banking on the Emperor’s-New-Clothes phenomenon: doctors would be too embarrassed to admit we didn’t know when mechanism mattered in selecting an antidepressant for a depressed patient. We still don’t.

We make assumptions. SSRIs work by enhancing serotonin. SNRIs work via both serotonin and norepinephrine. MAOIs work by inhibiting MAO. Perhaps these theories are valid; perhaps not. In theory, a patient who fails to respond to one SSRI should do better with a drug with a different mechanism of action, rather than a different SSRI. But the data say otherwise.

I am convinced that, ultimately, mechanism matters. And psychiatric patients are different one from the other. Someday we will understand the unique pathophysiology that underlies abnormal thinking, feeling, and behavior. Someday we will elucidate the various etiologies that distort normal brain function in these ways. And when that time comes, we will tailor treatments to the abnormalities: targeted treatments; personalized medicine.

But until that time, let’s not become gullible to those who peddle expensive new products with thinly veiled promises that understanding the receptor or other properties of a compound translates into real-life advantages. And remember that sales people are not only the companies’ marketers and representatives, but also some of our colleagues who write and lecture. A professor of mine admonished his students to be “therapeutic skeptics—but not nihilists.” Amen.

- Alan J. Gelenberg, M.D.
Editor,
Biological Therapies in Psychiatry
Professor and Chair, Psychiatry, Penn State University
Editor-in-Chief,
Journal of Clinical Psychiatry