Blind alley in psychopharmacology and classification of disease:
“No new drugs for mood and anxiety disorders have reached the market for over a decade. Why is there so little innovation in a sector that accounts for the largest proportion by far of sales of psychiatric drugs?
The current division between anxiety and depression is increasingly recognised as inadequate. In the community, most mood disorders present as a combination of depression and anxiety. Yet the Food and Drug Administration in the United States, which has become the world bellwether of drug approval, indicates drugs either for major depression or for the various forms of anxiety recognised by the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM). As a result, the pharmaceutical industry is compelled to develop drugs for diagnoses that are of questionable clinical relevance. This is one reason for the big slowdown in drug discovery in psychiatric drugs. A return to the former unitary classification of mood and anxiety disorders as nervousness or cothymia might represent a way out of this blind alley.” British Medical Journal, Shorter and Tyrer, 327 (7407): 158
This is an exceedingly important article which demands close attention. It in essence fires a shot across the bow of some very important vested interests in psychiatry, both financial and, more significantly, conceptual, and, if it attracts any attention, will surely provoke a backlash. I will be looking in the letters section of the British Medical Journal over the coming weeks for the fallout.
The authors proceed from three principles with which my own clinical experience agrees:
# The concept of “major depression” is far too heterogeneous to be useful
# The subdivision of anxiety into separate micro-diagnoses of panic, social anxiety disorder, etc, is questionable
# The firewall between anxiety and depression ignores the fact that the commonest form of affective disorder is mixed anxiety-depression.
There is a constant tension between the “lumpers” and the “splitters” in psychiatric classification (“nosology”), which readers of FmH know is one of my preoccupations in my field. As you can see from the points the authors make, the answer is not simply coming down on the side of one of those camps; some “lumping” causes problems and some “splitting” causes problems. Then, as the authors point out, if psychiatric drug approval by the FDA is tied to the current scheme of diagnoses, there will be important conceptual failings in new drug development. I have long taught that calling the antidepressants “antidepressants” is a conceptual misnomer, and I have seen the way this language constrains practice. Many other MDs as well as patients are aghast at my claim that the “antidepressants” are better choices for treating anxiety than the “anti-anxiety” medications (diazepam [Valium] and its derivatives).
But as long as drugs vie to win FDA approval as indicated for specific diagnoses, there is market pressure to proliferate diagnoses as, essentially, marketing niches for the pharmaceutical industry. The authors make a good case that the interpenetration of academic psychiatry and the drug industry is the devil’s bargain in this sense. This is not just a problem along the dividing line between depression and anxiety either. Other classes of psychiatric distress, such as psychosis, aggression, irritability, impulsivity, and mood lability, are artificially carved out as separate domains requiring separate diagnoses and different medications — “mood stabilizers”, “antipsychotics.” A welter of diagnoses devolve on our patients, and they arrive at my doorstep with a shopping bag full of medications which interact additively and often destructively, if not merely redundantly.
But it is good business:
Industry has been busy behind the scenes in this handy convergence of eccentric new diagnoses and the market nicheing of compounds. For example, in May 1984, Robert Spitzer, the chief disease designer of DSM-III and DSM-III-R, convoked a meeting of the anxiety working group, cosponsored by “the Psychopharmacology Unit of the Division of Medical Affairs of the Upjohn Company.” At the end of the discussion of the relation between panic and agoraphobia, Spitzer announced, “Consensus favors the Upjohn model.”14 It is now routine for psychopharmacologists, such as Brown University’s Martin Keller, to receive as much as $500 000 (£320 000) in consulting fees from industry in a given year.15 USA Today has calculated that at 55% of the meetings of the various advisory committees of the FDA, “half or more of the FDA advisers had a conflict of interest.”
Sometimes the relation between academic psychiatrists and industry veers over the line of acceptability in the form of ghost writing—academics lending their names to articles drafted by industry hacks. This has been a problem in psychopharmacology since the 1950s.17 But only last year, Vienna psychiatry professor Siegfried Kasper was identified in the Austrian press as signing an industry ghostwritten article about an antidepressant.18 Under normal circumstances, the interpenetration of industry and academe can be fruitful, as talent and ideas wash back and forth. Yet when drugs start earning the kind of money usually associated with the oil industry, there is potential for trouble.
The authors conclude, eloquently and aptly:
We believe that the failure to advance the treatment of anxiety and depression is related to wrong classification. If you don’t have natural disease categories, you can’t develop drugs for them. If the Food and Drug Administration will accept only drugs that are effective for DSM diagnoses, and if the diagnoses are artefacts, the drugs are bound to be less valuable, even if in the short term they increase their market share. Companies must start developing drugs for mixed anxiety and depression and forget about dividing this giant illness segment into salami slices. Doctors could encourage this change by being more cynical about pitches from drug representatives claiming to have “the latest” in anxiolytic medication. Ask instead for the latest in nervousness.
And, I would add, consumers should ask the same of their prescribing doctors.
