{"id":25389,"date":"2012-07-28T12:56:46","date_gmt":"2012-07-28T16:56:46","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=25389"},"modified":"2012-07-28T12:56:46","modified_gmt":"2012-07-28T16:56:46","slug":"fresh-air","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2012\/07\/28\/fresh-air\/","title":{"rendered":"fresh air…"},"content":{"rendered":"
The record amounts of the recent GSK<\/font><\/strong> settlement [Biggest Deal Ever: Glaxo Pays $3B For Bad Behavior<\/font><\/strong><\/u><\/a>] and the one pending for Johnson and Johnson<\/font><\/strong> [J&J Penalty May Total $2.2 Billion<\/font><\/strong><\/u> <\/a>] for false advertising may not satisfy those who point to the billions made from these drugs and the damage done. And the failure to bring the human perpetrators in industry and medicine itself to justice may be equally frustrating. I’m among the ranks of the dissatisfied. But there are a couple of things to note about all of this. People want to feel better, and so they took these drugs. The doctors that gave them wanted to help people feel better too, so they prescribed them. The drugs weren’t that good, but they were handed out and taken like candy, yet the truth is that they are only really effective for a specific, selected subgroup of patients. Here’s the thing. If they had been as effective as advertised, there wouldn’t have been a need to advertise them in the first place. A few years back, Dr. Bernard Carroll made this analogy on the Healthcare Renewal<\/font><\/strong><\/u><\/a> blog:<\/div>\n
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… As for the charge that psychiatrists and primary care physicians just throw drugs at mental health problems, that is nothing new. It is a reflection of the professional pragmatism that permeates medical practice. Think back to the 1950s when the new wonder drugs called antibiotics were handed out like Pez, mostly for people who did not really need them and who would not benefit from them. The working principle was misguided simplicity and pragmatism, which minimized and discounted the risks. Even today the over-use of antibiotics remains a public health concern. Just as in the 1950s patients with nonspecific upper respiratory symptoms were “given the benefit of the doubt” and were prescribed an antibiotic on the reasoning that it might help them while probably not hurting them, so today patients with nondescript depressive or anxiety symptoms are prescribed an SSRI drug on the same reasoning. The cost of this approach in wasted money, in unnecessary side effects, and in unproductive clinical management is non-trivial.<\/sup><\/div>\n<\/blockquote>\n
And as for the state of the art… <\/div>\n
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Psychiatry, The Pharmaceutical Industry, and The Road to Better Therapeutics<\/font><\/strong><\/u><\/a>
by H. Christian Fibiger<\/sup>
Schizophrenia Bulletin<\/font><\/strong>. 2012 38(4):649–650.<\/div>\n

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Psychopharmacology is in crisis. The data are in, and it is clear that a massive experiment has failed: despite decades of research and billions of dollars invested, not a single mechanistically novel drug has reached the psychiatric market in more than 30 years. Indeed, despite enormous effort, the field has not been able to escape the “me too\/me [questionably] better” straightjacket. In recent years, the appreciation of this reality has had profound consequences for innovation in psychopharmacology because nearly every major pharmaceutical company has either reduced greatly or abandoned research and development of mechanistically novel psychiatric drugs. This decision is understandable because pharmaceutical and biotechnology executives see less risky opportunities in other therapeutic areas, cancer and immunology being the current pipeline favorites. Indeed, in retrospect, one can wonder why it took so long for industry to abandon psychiatry therapeutics. So how did we get here and more importantly, what do we need to do to find a way forward?<\/sup><\/div>\n<\/blockquote>\n
How refreshing to read such an honest assessment of the current era! particularly from someone who has been involved in industry himself: <\/div>\n
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Department of Psychiatry, University of British Columbia Vancouver, B.C., Canada. Subsequent to his academic career, Dr Fibiger was Vice President of Neuroscience at Eli Lilly and Company, Vice President of Neuroscience at Amgen, and Senior Vice President and Chief Scientific Officer at Biovail Laboratories International.<\/sup><\/em><\/div>\n<\/blockquote>\n
I would, however, quibble with his priorities in "So how did we get here and more importantly<\/font><\/strong>, what do we need to do to find a way forward?"<\/em>. I don’t think "a way forward<\/em>" trumps "how did we get here?<\/em>". "a way forward<\/em>" sounds too much like NIMH Director Tom Insel’s recurrent schemes to keep the ball rolling [just plain crazy!…<\/font><\/a><\/strong><\/u>], more Myth of Sisyphus<\/font><\/strong> than scientific progress to my mind. In fact, Dr. Fibiger goes on to make the point himself:<\/div>\n
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The discovery of all three major classes of psychiatric drugs, antidepressants, antipsychotics, and anxiolytics, came about on the basis of serendipitous clinical observation. At the time of their discoveries, the mechanisms by which these molecules produce their effects were unknown, and it was only later that antipsychotics were shown to be D2 receptor antagonists, antidepressants monoamine reuptake inhibitors, and anxiolytics GABA receptor modulators. It is interesting and perhaps instructive to consider whether any of these classes of drugs could have been discovered by current drug discovery strategies. For example, what genetic or preclinical data exist that point to the D2 dopamine receptor as a likely target for antipsychotic activity? Presently there are no genetic data that suggest that this receptor is expressed or functions abnormally in psychotic disorders. And without the benefit of the prior clinical validation, it is difficult to see how preclinical data alone would point to the D2 receptor as an interesting potential target for the treatment of psychotic disorders. The same can be said for monoamine transporters with respect to depression where, like psychosis, there are no animal models based on disease pathophysiology and no compelling preclinical data pointing to these as potential targets for antidepressant drugs. This raises a troubling question: if in retrospect the three major classes of currently prescribed psychiatric drugs would likely never have been discovered using current drug discovery strategies, why should we believe that such strategies are likely to bear fruit now or in the future? <\/sup><\/div>\n<\/blockquote>\n
Like the old gestalt book title said, Don’t push the river. It flows by itself<\/font><\/strong>. We don’t need a driver for human curiosity – "serendipitous clinical observation<\/em>" is the stuff of good science. What we have to offer is the scientific methods of proof, the Hippocratic Oath to do no harm, and the integrity to put these things before all others. I agree that "a massive experiment has failed<\/em>," but again I’d quibble. The real "massive experiment<\/em>" that failed was allowing therapeutic zeal and entrepreneurism to gain an unprecedented upper hand. And I don’t "wonder why it took so long for industry to abandon psychiatry therapeutics<\/em>". I think it’s abundantly clear why. But none of these criticisms are aimed at Dr. Fibiger. I found these comments generally on the mark, and a welcome breath of fresh air.<\/div>\n","protected":false},"excerpt":{"rendered":"

The record amounts of the recent GSK settlement [Biggest Deal Ever: Glaxo Pays $3B For Bad Behavior] and the one pending for Johnson and Johnson [J&J Penalty May Total $2.2 Billion ] for false advertising may not satisfy those who point to the billions made from these drugs and the damage done. And the failure […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_bbp_topic_count":0,"_bbp_reply_count":0,"_bbp_total_topic_count":0,"_bbp_total_reply_count":0,"_bbp_voice_count":0,"_bbp_anonymous_reply_count":0,"_bbp_forum_subforum_count":0,"footnotes":""},"categories":[2],"tags":[],"class_list":["post-25389","post","type-post","status-publish","format-standard","hentry","category-politics"],"_links":{"self":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/25389","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/comments?post=25389"}],"version-history":[{"count":20,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/25389\/revisions"}],"predecessor-version":[{"id":25409,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/25389\/revisions\/25409"}],"wp:attachment":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/media?parent=25389"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/categories?post=25389"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/tags?post=25389"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}