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!
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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.
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
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.
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."
Thanks
The brain disease we understand best at the cellular (if not molecular) level is epilepsy.
"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).
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.
Psychotherapy trials are often methdologically weak.
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The name Pentium (meaning five) refers to the act that it is the fifth microprocessor in their 80x86 series.
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... one of the main causes of the fall of the Roman Empire was that, lacking zero, they had no way to indicate successful termination of their C programs.
God gave men both a penis and a brain, but unfortunately not enough blood supply to run both at the same time.
I find that the harder I work, the more luck I seem to have.
Before the war is ended, the war party assumes the divine right to denounce and silence all opposition to war as unpatriotic and cowardly.
So I rang up a local building firm, I said 'I want a skip outside my house.' He said 'I'm not stopping you.'
Far too many development shops are run by fools who succeed despite their many failings.
Programming is one of the most difficult branches of applied mathematics; the poorer mathematicians had better remain pure mathematicians.
If the United Nations once admits that international disputes can be settled by using force, then we will have destroyed the foundation of the organization and our best hope of establishing a world order.
The surest way to corrupt a youth is to instruct him to hold in higher esteem those who think alike than those who think differently
When you have to kill a man, it costs nothing to be polite.
Sometimes a scream is better than a thesis.
God gave men both a penis and a brain, but unfortunately not enough blood supply to run both at the same time.
The difference between fiction and reality? Fiction has to make sense.
Death does not concern us, because as long as we exist, death is not here. And when it does come, we no longer exist.
A fast word about oral contraception. I asked a girl to go to bed with me, she said 'no'.
A fast word about oral contraception. I asked a girl to go to bed with me, she said 'no'.
A fast word about oral contraception. I asked a girl to go to bed with me, she said 'no'.
I don't approve of political jokes... I've seen too many of them get elected.
The true measure of a man is how he treats someone who can do him absolutely no good.
It is practically imposible to teach good programming to students that have had a prior exposure to BASIC: as potential programmers they are mentally mutilated beyond hope of regeneration.
One of the symptoms of an approaching nervous breakdown is the belief that one's work is terribly important.
One of the symptoms of an approaching nervous breakdown is the belief that one's work is terribly important.
Sex is like a Chinese dinner. It isn't over until everyone gets their cookies.
If people can judge me on the company I keep, they would judge me with keeping really good company with Laura.
If people can judge me on the company I keep, they would judge me with keeping really good company with Laura.
In science one tries to tell people, in such a way as to be understood by everyone, something that no one ever knew before. But in poetry, it's the exact opposite.
The Bible was a consolation to a fellow alone in the old cell. The lovely thin paper with a bit of matress stuffing in it, if you could get a match, was as good a smoke as I ever tasted.
The Bible was a consolation to a fellow alone in the old cell. The lovely thin paper with a bit of matress stuffing in it, if you could get a match, was as good a smoke as I ever tasted.
A state of war only serves as an excuse for domestic tyranny.
If absolute power corrupts absolutely, where does that leave God?
Tact is the ability to tell a man he has an open mind when he has a hole in his head.
Tact is the ability to tell a man he has an open mind when he has a hole in his head.
Tact is the ability to tell a man he has an open mind when he has a hole in his head.
Build a man a fire, and he'll be warm for a day. Set a man on fire, and he'll be warm for the rest of his life.
Emulate your heros, but don't carry it too far. Especially if they are dead.
Emulate your heros, but don't carry it too far. Especially if they are dead.
God gave men both a penis and a brain, but unfortunately not enough blood supply to run both at the same time.
In science one tries to tell people, in such a way as to be understood by everyone, something that no one ever knew before. But in poetry, it's the exact opposite.
It's not the size of the dog in the fight, it's the size of the fight in the dog.
Pascal /n./ A programming language named after a man who would turn over in his grave if he knew about it.
When you have to kill a man, it costs nothing to be polite.
When you have to kill a man, it costs nothing to be polite.
One out of every three Americans is suffering from some form of mental illness. Think of two of your best friends. If they are OK, then it must be you.
I wouldn't mind dying - it's the business of having to stay dead that scares the shit out of me.
Many journalists have fallen for the conspiracy theory of government. I do assure you that they would produce more accurate work if they adhered to the cock-up theory.
Many journalists have fallen for the conspiracy theory of government. I do assure you that they would produce more accurate work if they adhered to the cock-up theory.
Always go to other people's funerals, otherwise they won't come to yours.
I've had a wonderful time, but this wasn't it.
First they ignore you, then they laugh at you, then they fight you, then you win.
Go on, get out. Last words are for fools who haven't said enough.
Death does not concern us, because as long as we exist, death is not here. And when it does come, we no longer exist.
God is a comedian playing to an audience too afraid to laugh.
Science is like sex: sometimes something useful comes out, but that is not the reason we are doing it
How wrong it is for a woman to expect the man to build the world she wants, rather than to create it herself.
Every day I get up and look through the Forbes list of the richest people in America. If I'm not there, I go to work.
Every day I get up and look through the Forbes list of the richest people in America. If I'm not there, I go to work.
Before the war is ended, the war party assumes the divine right to denounce and silence all opposition to war as unpatriotic and cowardly.
Humor is always based on a modicum of truth. Have you ever heard a joke about a father-in-law?
Early to rise and early to bed. Makes a male healthy, wealthy and dead.
Men are not disturbed by things, but the view they take of things.
People who think they know everything greatly annoy those of us who do.
Any man who is under 30, and is not a liberal, has not heart; and any man who is over 30, and is not a conservative, has no brains.
There are some experiences in life which should not be demanded twice from any man, and one of them is listening to the Brahms Requiem.
Conservatives are not necessarily stupid, but most stupid people are conservatives
If you're sick and tired of the politics of cynicism and polls and principles, come and join this campaign.
If the automobile had followed the same development cycle as the computer, a Rolls-Royce would today cost $100, get a million miles per gallon, and explode once a year, killing everyone inside.
It's the liberal bias. The press is liberally biased to the right.
I'm all in favor of keeping dangerous weapons out of the hands of fools. Let's start with typewriters.
First they ignore you, then they laugh at you, then they fight you, then you win.
As the post said, 'Only God can make a tree,' probably because it's so hard to figure out how to get the bark on.
The backbone of surprise is fusing speed with secrecy.
Conservatives are not necessarily stupid, but most stupid people are conservatives
The shepherd always tries to persuade the sheep that their interests and his own are the same.
Devlin's First Law - Buyer beware: in the hands of a charlatan, mathematics can be used to make a vacuous argument look impressive. Devlin's Second Law - So can PowerPoint.
Computers can figure out all kinds of problems, except the things in the world that just don't add up.
It's not the size of the dog in the fight, it's the size of the fight in the dog.