The Frontal Cortex

I’ve written before about the the failure of basic neuroscience research to advance neuropharmacology (at least, it’s been a failure so far), but it’s nice to see Eric Kandel, my old mentor (and one of my scientific heroes), make the same argument. Kandel began his scientific career as a Freudian psychiatrist – he was soon turned off by the blatant the lack of empiricism – so his recent interest in the biological benefits of talk therapy, and ways of rigorously measuring those benefits, provides an interesting snapshot on the state of neuroscience.

On the one hand, it’s sobering that talk therapy remains the most effective treatment for a wide variety of illness, from chronic back pain to depression. Alas, this says more about the failure of pharmacology than it does about the therapeutic value of talk therapy. On the other hand, science is finally beginning to understand the anatomical mechanisms that allow talk therapy to work. We can see how mere words and conversation profoundly influence the activity of the brain. Here’s Kandel, writing for the Dana Foundation:

The other thing that has impressed me is that in the last 20 years we’ve had no advances in pharmacotherapy. We started off with interesting antipsychotic agents, interesting antidepressants, but they really have progressed very modestly. Selective serotonin [re]-uptake inhibitors–each company’s copying from the other using exactly the same assays to develop it. Twenty years, and there’s general agreement that there is no difference between most of the selective serotonin [re]-uptake inhibitors and no improvement either. A drug sells not because it’s any better than any other but because there are major names associated with it.

In schizophrenia, the issue is even worse, because for 45 years there probably hasn’t been a better drug. There are drugs that have better side effects, but there have not been major developments in drugs.

The one thing that has become better is the legitimacy of psychotherapy. There are several behavioral therapies out there–interpersonal therapy, cognitive behavioral therapy–that have been shown in rigorous control studies, in depression, for example, to be at least as good as selective serotonin [re]-uptake inhibitors for mild and moderate depression and to be synergistic with drugs in severe depression.

Moreover, we’ve beginning to identify–particularly in depression–certain areas of the brain that function abnormally. For example, [Emory University psychiatry professor] Helen Mayberg showed that [Brodmann] area 25–the subgenual cingulate cortex–is hyperactive in depression. This area connects to the amygdala; the amygdala also is hyperactive in depression. When patients respond to psychotherapy, those abnormalities reverse. So for the first time we not only have a psychotherapy that works but we have an independent, biological measure, an assay, and we can see to what degree this works.

Thanks Ted!

Comments

#1 Howard
December 30, 2008

From the clinical trials point of view, each SSRI helps about 2/3 of patients taking each drug. That doesn’t equate to no differences among them. As patients and clinicians will attest, there can be profound differences in efficacy and in tolerabiity for individuals, which is all that matters for the patient.

For the scientist and the psychopharmacologist, mechanisms of action matter more, as each new type of compound reveals something new about the brain. As much as I am loathe to disagree with Dr. Kandel, the locus of “better” is the patient, and not the pharma company or researcher’s name. Prozac, Paxil, and Effexor sell, while Serzone was taken off the market.
#2 OftenWrongTed
December 30, 2008

Virginia Woolf wrote about the absence of successful treatment for her life-long, mental illness:
“One could wish the psycho-analysts would go into the question of diary keeping. For often it is the one mysterious fact in a life otherwise as clear as the sky and as candid as the dawn.”
LIFE ITSELF by Virginia Woolf
#3 Gray Gaffer
December 30, 2008

And then there is Dr Jeffrey M. Schwartz at the UCLA School of Medicine. He has focused on the role of the amygdala in OCD, and developed psychotherapy techniques for modifying the pathological operation that results in OCD. With MRI etc goodness validating the claim of modified neurological operation. I happen to also think smoking is related to OCD in its behavioral aspects, and used that idea in conjunction with what I read in Jeffrey’s books to successfully quit smoking. After twenty years and thousands of dollars ineffectively spent on pharmacological quitting techniques.
#4 Peter Reiner
December 30, 2008

As it turns out, just today I posted a piece over at the Neuroethics & Law Blog that riffs off of this same theme:

“The most important question that the Angell piece raises is whether the field of neurosciences (writ large) is at least partly cupable for this incursion into psychiatric disease by promulgating the notion that all diseases of the brain are due to disordered chemistry. Don’t get me wrong: I am a dyed-in-the-wool neurobiologist who is fully convinced that, on some level, all diseases of the brain are due to disordered chemistry. But it is one thing to say that a disease is caused by altered chemistry and something else entirely to know what that altered chemistry is. I can think of no disease of the brain for which we have developed a mature and robust understanding of the underlying pathophysiology (suggestions welcome). Absent that, all that the pharmaceutical industry can offer are chemical band-aids. The problem is that the general public wants – no, expects cure-alls. And the marketing arms of the pharmaceutical industry are all too eager to depict their latest offerings as such.”
#5 Seks
December 30, 2008

Thanks
#6 Greg
December 30, 2008

The brain disease we understand best at the cellular (if not molecular) level is epilepsy.
#7 Neuroskeptic
January 1, 2009

“On the one hand, it’s sobering that talk therapy remains the most effective treatment for a wide variety of illness, from chronic back pain to depression.”

That’s very controversial (at least in the case of depression.) Psychotherapy trials are often methdologically weak.

Also, Kandel is wrong about schizophrenia drugs – clozapine is better than all the earlier drugs. Unfortunately, it can occasionally kill you. But apart from that it’s a brilliant drug. (Seriously).
#8 Texas Reader
January 1, 2009

I think the SSRIs are significantly different in side effects. For me, Prozac made me unable to eat enough and I dropped to just under 100 pounds, Paxil made me nauseous, Zoloft made me feel like I was watching things go around around me, and not part of them. Remeron made me obsessed with eating. I’m now taking Lexapro and I struggle with my weight but not to the extent that I did with Remeron where “what can I eat next?” was always on my mind.
#9 WotWot
January 2, 2009

Psychotherapy trials are often methdologically weak.

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