To Treat Depression, Drugs or Therapy? ( Check How).

You’re feeling down, and your doctor or therapist has confirmed it: You have depression. Now what?

Until recently, many experts thought that your clinician could literally pick any antidepressant or type of psychotherapy at random because, with a few clinical exceptions, there was little evidence to favor one treatment over another for a given patient.

In fact, I used to delight in tormenting the drug company representatives when they asked me how I picked an antidepressant. I would take a quarter out of my pocket, flip the coin and say I’d let chance decide because their drug was no better or worse than their competitors’.

Although the holy grail of personalized therapy — be it with psychotropic drugs or psychotherapy — has proved elusive, we’ve learned a lot recently about individual factors that might predict a better response to one type of treatment over another.

Dr. Helen Mayberg, a professor of psychiatry at Emory University, recently published a study in JAMA Psychiatry that identified a potential biomarker in the brain that could predict whether a depressed patient would respond better to psychotherapy or antidepressant medication.

Using PET scans, she randomized a group of depressed patients to either 12 weeks of treatment with the S.S.R.I. antidepressant Lexapro or to cognitive behavior therapy, which teaches patients to correct their negative and distorted thinking.

Over all, about 40 percent of the depressed subjects responded to either treatment. But Dr. Mayberg found striking brain differences between patients who did well with Lexapro compared with cognitive behavior therapy, and vice versa. Patients who had low activity in a brain region called the anterior insula measured before treatment responded quite well to C.B.T. but poorly to Lexapro; conversely, those with high activity in this region had an excellent response to Lexapro, but did poorly with C.B.T.

What might explain these different responses?

We know that the insula is centrally involved in the capacity for emotional self-awareness, cognitive control and decision making, all of which are impaired by depression. Perhaps cognitive behavior therapy has a more powerful effect than an antidepressant in patients with an underactive insula because it teaches patients to control their emotionally disturbing thoughts in a way that an antidepressant cannot.

This finding fits with what we’ve learned from previous brain imaging studies, which show that antidepressants and psychotherapy share some common effects, but also have different effects in distinct brain regions.

These neurobiological differences may also have important implications for treatment, because for most forms of depression, there is little evidence to support one form of treatment over another. (The exceptions are psychotic depression, a severe form marked by delusions in addition to depressive symptoms, which is best treated with either a combination of antidepressant and antipsychotic drugs, or electroconvulsive therapy; and atypical depression, characterized by hypersomnia, increased appetite and highly reactive mood, which may respond best to an older class of antidepressants called monoamine oxidase inhibitors.)

Currently, doctors typically prescribe antidepressants on a trial-and-error basis, selecting or adding one antidepressant after another when a patient fails to respond to the first treatment. Rarely does a clinician switch to an empirically proven psychotherapy like cognitive behavior therapy after a patient fails to respond to medication, although these data suggest this might be just the right strategy. One day soon, we may be able to quickly scan a patient with an M.R.I. or PET, check the brain activity “fingerprint” and select an antidepressant or psychotherapy accordingly.

It turns out that other clinical factors may also help patients get the best treatment. For example, there is intriguing evidence that depressed patients who have a history of childhood trauma, such as the early loss of a parent or sexual or physical abuse, do not respond as well to an antidepressant as they do to psychotherapy.

In a large, multicenter study, Dr. Charles Nemeroff, then a professor of psychiatry at Emory and now at the University of Miami, found that for depressed adults without a history of abuse, there was a clear ranking order of treatment efficacy: Combined psychotherapy (using a form of cognitive behavior therapy) and an antidepressant (in this case, Serzone) was superior to either treatment alone. But for those who had a history of childhood trauma, the results were strikingly different: 48 percent of these patients achieved remission with psychotherapy alone, but only 33 percent of these patients responded to an antidepressant alone. The combination of psychotherapy and a drug was not significantly better than psychotherapy alone.

One explanation for the varying response is that a history of trauma early in life is strongly correlated with shrinkage of the hippocampus, a brain region critical to memory and learning. Perhaps if you are depressed with a compromised hippocampus, you need the active learning that comes with psychotherapy to beat your depression. Antidepressants alone may not suffice.

Considering the high rate of early trauma in chronically depressed patients — in Dr. Nemeroff’s study, about a third experienced parental loss, and 45 percent suffered physical abuse — this should be an important factor in selecting the right treatment.

Because some patients respond better to psychotherapy than medication — and vice versa — or prefer one type of treatment over another, we need to learn much more about how various types of psychotherapy compare with medications clinically as well as at the level of the brain.

Is the nonspecific nature of talk therapy — feeling understood and cared for by another human being — responsible for its therapeutic effect? Or will specific types of therapy — like C.B.T. or interpersonal or psychodynamic therapy — show distinctly different clinical and neurobiological effects for various psychiatric disorders?

Right now we don’t have a clue, in part because of the current research funding priorities of the National Institute of Mental Health, which strongly favors brain science over psychosocial treatments. But these are important questions, and we owe it to our patients to try to answer them.