Study Faults How Mental Disorders Are Classified

Main Category: Depression
Article Date: 20 Jul 2003 - 0:00 PST

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But expert says system, though flawed, is best available.

Serious flaws in the way doctors classify psychiatric disorders have sent drug development way off track, two scientists assert.

Specifically, the researchers, writing in the July 19 issue of the British Medical Journal, attack the Diagnostic and Statistical Manual of Mental Disorders (DSM) -- the bible for psychiatric diagnoses -- for failing to reflect the biology of different conditions.

'We need to take all of our copies of the DSM and throw them into the sea,' cries Edward Shorter, lead author of the article and a professor of the history of medicine at the University of Toronto in Canada.

'There are such fundamental flaws that the whole thing needs to be rethought. We need to have indications that correspond to natural, underlying disease processes.'

Other experts feel there may be a valid point in these assertions, albeit not a new one, but this point is lost in a pool of rhetoric and even incorrect statements.

'There was a great deal of cacophony for many years around psychiatric disorders,' says Dr. Jerrold Rosenbaum, a professor of psychiatry at Harvard Medical School and chief of psychiatry at Massachusetts General Hospital.

'The DSM was an attempt to create a vocabulary so that, when I say major depression or schizophrenia, I'm meaning roughly the same thing as what somebody else is saying.'

The system is far from perfect but it has been helpful in some ways, Rosenbaum contends. 'We're stuck with these categories until there's new data,' he says. 'This is a limited dictionary that helps us in some ways but limits us in others.'

Most people would agree that a fundamental problem in psychiatry concerns categories that are descriptive, arrived at by consensus among experts and not through evidence. The simple reason is that experts don't have the kind of pathophysiological evidence required to create and sustain clear-cut categories.

'They are the consensus of scientists and clinical experts as to what they thought the actual disorders were and then they become the language,' Rosenbaum says.

'The problem is that if you start studying populations based on these categories, the categories may not cleave nature at its joints. It's a taxonomy and it doesn't reflect the biology.'

Shorter alleges that depression and anxiety, which constitute the lion's share of psychiatric disorders, were wrongfully separated from each other in the 1980 revision of the DSM.

'Anxiety and depression are a single disease for the most part and, by separating them, the disease designers of DSM have forced companies to develop drugs for what really are artifacts,' he says.

This, Shorter claims, is what has led to the drug development shortfall we are experiencing now. 'You have regulators insisting that DSM diagnoses be used as indications for drug trials,' Shorter says.

But the DSM classifications, he adds, have wrongly divided disorders into small, artificial categories. 'One of the things that has happened is the splitting up of microfragments like social anxiety disorder and panic disorder,' he says. 'It's just like drawing lines in a bucket of water. It all flows together.'

This reasoning is patently wrong, Rosenbaum counters. 'All the drugs that are for depression are [also] for anxiety,' he says. 'Quite clearly, the two disorders have substantial overlap and may even be an expression of the same vulnerability and that's reflected in the fact that the FDA [U.S. Food and Drug Administration] indicates drugs for both. It's not either/or. It's both.'

The problem with trying to come up with drugs for broad categories is that huge samples of people are needed even to see small effects. 'It ends up making drug development enormously costly,' Rosenbaum says. 'You have to be successful in large, heterogeneous groups.'

The flip side of the coin is that industry sometimes comes up with molecules that might be helpful for a symptom or symptoms, but they don't correspond to a specific DSM target and so they flounder, Rosenbaum adds.

Ultimately, the same original problem returns: deficits in the understanding of the basic science of psychiatric disorders. Both the DSM and drug developers are hampered by the same deficiency.

'It's like the lost wallet and the streetlight,' Rosenbaum says. 'This is the only place we have light, even though we all know the answer lies somewhere downstream.'

Rosenbaum also believes there's a light at the end of the tunnel, thanks to new tools like neuroimaging and phenotyping.

'We're able to look intracellularly, and we're now able to look at gene expression. That makes us think we're going to have new treatments in a decade. It's not the FDA that's holding us back,' he says. 'It's a little like beating a dead horse to say that the DSM is a problem for drug development. There's no news here. It's hard to argue that the DSM isn't a problem, but it's not like they discovered that.'