Talk Therapy or Pill? A Brain Scan May Tell What’s Best

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Figure 2. Potential treatment-specific biomarker candidates. Mean regional activity values for remitters and nonresponders segregated by treatment arm are plotted for the 6 regions showing a significant treatment × outcome analysis of variance interaction effect. Regional metabolic activity values are displayed as region/whole-brain metabolism converted to z scores. Regions match those shown in Table 2. Escitalopram was given as escitalopram oxalate. CBT indicates cognitive behavior therapy. Figure courtesy the authors and the JAMA Psychiatry.

In a new paper out yesterday in JAMA Psychiatry, a team led by Emory University neurologist Helen Mayberg, whom I’ve written about several times, identifies a possible biomarker for predicting whether a depressed patient will respond better to an antidepressant or a type of talk therapy called cognitive behavioral therapy, or CBT. As the paper says, “if confirmed with prospective testing, this putative TSB [treatment-specific biomarker] has both clinical and pathophysiological implications” — that is, it might help improve and speed treatment while revealing physiological differences between two different strains of depression.

The 63 patients in the trial were all pretty sick, with depression scores averaging about 19 on the 26-point Hamilton depression scale. (1 to 7 is normal; 8 to 13 is moderately depressed, and if you’re at 20 you’re in a very dark place.) Each patients underwent a 40-minute session in a brain-activity scanner called PET (for positron emission tomography) scanner during which they lay awake, eyes closed, and were asked to not ruminate on any one subject the whole time. The scanner tracked the blood glucose levels in their different brain areas during that time — a type of study assumed to be a proxy for significant brain activity. After that, roughly half the patients took a 12-week course of standard doses of the antidepressant Lexapro, while the other half got 16 sessions, roughly weekly, of cognitive behavioral therapy — a talk therapy aimed at learning to rework negative loops of thought, and the talk therapy with the best-documented and highest rates of effectiveness.

When all this was over, the researchers went back and analyzed the pre-therapy brain scans to see if they could find anything distinguishing the patients who responded to Lexapro from those who responded to CBT.

They did. A brain area called the anterior insula, which is involved in many brain functions, was busier than normal in the patients who later responded to Lexapro and less active than normal in the patients who responded to CBT. To put it another way: patients with high insula activity tended to respond better than most depression patients to Lexapro but worse to CBT, while low-insula-activity patients responded better than most depression patients to CBT but worse to Lexapro. (Alas, no particular pattern in the insula or elsewhere marked the patients who didn’t respond to whichever treatment they got.)

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Figure 1. Study design and outcomes. Outcome groups defined by Hamilton Depression Rating Scale (HDRS) scores. Remission was defined as an HDRS score of 7 or less; partial response, as an HDRS score decrease of more than 30% but not achieving remission; and nonresponse, as an HDRS score decrease of 30% or less. Escitalopram was given as escitalopram oxalate. CBT indicates cognitive behavior therapy and PET, positron emission tomography. Courtesy the authors and JAMA Psychiatry.

If this holds up — if PET scans can reliably predict which patients will respond at high rates to different therapies — then it will save patients much suffering and time, including time that is often critical and especially frustrating, even dangerous, as clinicians try different treatments to ease a depressed patient’s despair. This is hardly unusual; clinicians treating depression must often try several different therapies, often for weeks or months, before finding one that works (if indeed any work at all). A PET scan that helped shortcut this could save much grief, as well as substantial time and money.

This study, as Mayberg is quick to note, needs to be replicated by larger studies if it’s to be useful. Mayberg herself wants to run a study that treats half the patients at random with either CBT or Lexapro and half according to which type of insula activity they show — that is, within that second half of the study, low-insula-activity patients would get Lexapro while high-insula-activity patients would get CBT. That would directly test the predictive power of these scans: If they’re actually useful, these targeted-treatment patient groups in the study’s second half would get better results than the first-half control group that got assigned a therapy at random. So  70% of them might recover instead of the usual 50-ish that most therapies struggle to reach.

That, she says, might open the door to more precise treatment. “We’d finally have a way to discriminate the biology. You’d know you should use treatment A instead of B.” She’s waiting to hear whether her grant application to do such a study will get approved.

I’ll probably write more on this later, for there are layers and layers to this story, and many implications; this finding arises not from a whim, but from a couple decades of work by Mayberg and others trying to characterize the brain dynamics of depression — a body of work that shows both the potential and the difficulties of creating a brain-based psychiatry.

PS 6/14/13: Wanted to add a +1 to this note from Neurocritic in Neurocritic’s sharp, smart write-up of this study:

With the newly prominent nattering nabobs of neuroimaging negativity, it’s important to remember that it’s not all neuroprattle and bunk. Some of this research is trying to alleviate human suffering.

Second that. In the years I’ve reported on and written about Mayberg, keeping up with her work frequently (see below), I’ve always been impressed with the fierceness of her focus on helping patients, and in particular on relieving the strange torturous pain of depression.

Other coverage:

The Neurocritic: A New Biomarker for Treatment Response in Major Depression? Not Yet.

Brain scan predicts best therapy for depression : Nature News & Comment

No dishonour in depression : Nature News & Comment

Study Helps Predict Response to Depression Drug –

and some of my earlier work on Mayberg and/or the neurology of depression here:

A Depression Switch? – New York Times

Depression’s wiring diagram

Optogenetics Relieves Depression in a Mouse Trial 

Is Psychology Stuck In a Paradigm Shaft?

The Hole in My Brain: Amnesia’s Lessons About Memory, Depression, and Love

Rachel Maddow Gets Depressed

*Standard competing interest info: Some of the several authors report consulting relationships with pharmaceutical companies; other authors practice CBT. Mayberg declares a consulting relationship with a maker of neuromodulation instruments, for deep-brain stimulation treatments that she has experimented with in other studies. See the COI disclaimers in the study for details. I’ve written about Mayberg several other times, as noted above.

Photo appearing on homepage: Self-portrait by ndanger, licenseAttributionShare Alike Some rights reserved.