if [and only if]…

Posted on Thursday 22 August 2013

    There’s more than one answer to these questions,
    Pointing me in a crooked line…
          Closer to Fine, Indigo Girls 1989

New York Times
Perspective
By RICHARD A. FRIEDMAN, M.D.
August 19, 2013

Fully 1 in 5 Americans take at least one psychiatric medication. Yet when it comes to mental health, we are facing a crisis in drug innovation. Sure, we have many antidepressants, antipsychotics, hypnotic medications and the like. But their popularity masks two serious problems. First, each of these drug classes is filled with “me too” drugs, which are essentially just copies of one another; we have six S.S.R.I. antidepressants that essentially do the same thing, and likewise for the 10 new atypical antipsychotic drugs. Second, the available drugs leave a lot to be desired: patients with illnesses like schizophrenia, major depression and bipolar disorder often fail to respond adequately to these medications or cannot tolerate their side effects. Yet even though 25 percent of Americans suffer from a diagnosable mental illness in any year, there are few signs of innovation from the major drug makers.

After a series of failed clinical trials in which novel antidepressants and antipsychotics did little or no better than placebos, the companies seem to have concluded that developing new psychiatric drugs is too risky and too expensive. This trend was obvious at the 2011 meeting of the American Society for Clinical Pharmacology and Therapeutics, where only 13 of 300 abstracts related to psychopharmacology and none related to novel drugs. Instead, they are spending most of their research dollars on illnesses like cancer, heart disease and diabetes, which have well-defined biological markers and are easier to study than mental disorders. To understand this predicament, it helps to know how we got here.

All of our current antidepressants, antipsychotics and anti-anxiety drugs share the same molecular targets in the brain as their prototypes from the 1950s. For example, the new antipsychotic drugs block dopamine receptors in critical brain regions, just like the first antipsychotic, Thorazine, synthesized in 1950. And all of our current antidepressants increase the levels of one or more of the neurotransmitters serotonin, dopamine or norepinephrine, just like the early tricyclic antidepressants. With rare exceptions, it is hard to think of a single truly novel psychotropic drug that has emerged in the last 30 years. True, the new psychotropic drugs are generally safer and more tolerable than older prototypes, but they are no more effective. So why has the pharmaceutical industry churned out so many copycat drugs? The simple answer is that we don’t yet understand the fundamental cause of most psychiatric disorders, in part because the brain is uniquely difficult to study; you can’t just biopsy the brain and analyze it. That is why scientists have had great trouble identifying new targets for psychiatric drugs.
Reading the highlighted question, I thought of the line from that song up there. Some other answers to these questions? because they work for some; because doctors prescribed them; because patients kept taking them; because they were incredibly profitable; because hope springs eternal. And it’s almost impossible to think about the answer to these questions without blaming somebody [else]. We’ve all done our share of that, myself included. And to be accurate, the song is actually about the singer’s journey and her therapy:
    I’m trying to tell you something about my life
    maybe give me insight between black and white
    and the best thing you’ve ever done for me
    is to help me take my life less seriously
    it’s only life after all
    well darkness has a hunger that’s insatiable
    and lightness has a call that’s hard to hear
    I wrap my fear around me like a blanket
    I sailed my ship of safety till I sank it
    I’m crawling on your shores
      I went to the doctor,
      I went to the mountains
      I looked to the children,
      I drank from the fountains
    there’s more than one answer to these questions
    pointing me in a crooked line
    and the less I seek my source for some definitive
    the closer I am to fine…
Sometimes our poets in frayed jeans hit the bulls-eye. But that’s not why I picked the song or flagged this article:
Also, knowing how a drug works in the brain doesn’t necessarily reveal the cause of the illness. For example, just because an S.S.R.I. antidepressant increases serotonin in the brain and improves mood, that does not mean that serotonin deficiency is the cause of the disease; many depressed patients get better with medications that have no effect on serotonin. Until very recently, scientists have relied on the same animal models to screen for potential psychotropic drugs that had been used for decades, which predictably yielded a raft of “me too” medications that shared the same mode of action as the old drugs. Sure, this old method of drug development has produced commercially successful blockbuster drugs, like the antipsychotics Seroquel and Abilify. But soon the patents on these medicines will expire, and there is little new in the pipeline
I flagged the article because of that sentence in red. What in the hell does the patent life of the drugs have to do with anything that really matters? We all know it has had a huge impact on psycho·economics and pharmaco·economics, but what in the hell does it have to do with patient care? ["nothing" is the answer I’m looking for here]. It doesn’t even have anything to do with Dr. Friedman’s sentence. The sentence "there is little new in the pipeline" would’ve sufficed on its own. I think its inclusion says something about Dr. Friedman’s perspective that he even sees the expiring of patents as relevant to his point. He’s in a PHARMA frame of mind.

And as long as I’m on the topic of that sentence, the metaphor of the pipeline has outlived its symbology [and its usefulness, in my humble opinion]. It’s a pharmaceutical industry buzz-word used to catalog the drugs they have in development to replace the ones they lose exclusive rights on due to expiring patents. Maybe it’s useful to them as a way to conceptualize their business plans, but it has taken on a different meaning as the pundits talk about psychiatric drugs. I never even heard the term, the pipeline, until a few years ago when people started talking about it going empty. I said talking, but maybe I should have said wailing – maybe thrown in something like with great gnashing of teeth. They talked [and still talk] like the pipeline is [or should be] something real, like there are un-found drugs that will be better [stronger, more efficacious, less toxic, more specific, etc.] than the ones we have now [and we need to get cracking to find them]. Well, the pipeline isn’t a real thing. We don’t know if there are these hypothesized drugs up ahead. The majority of the people now taking them don’t have the probably biological mental illnesses the drugs were developed for [Schizophrenia, Manic Depressive Illness, Melancholia, etc.]. They have other kinds of problems with emotional symptoms. Actually, Dr. Friedmans’ article raises the question, "Was there ever a pipeline in the first place?" ["With rare exceptions, it is hard to think of a single truly novel psychotropic drug that has emerged in the last 30 years."]. Probably not.

And the reason I picked that song/poem is obvious. There really are more than one answers to these questions on the way to  closer I am to fine. Dr. Friedman’s article goes on to talk about ketamine, and brings up that academic researchers are less bound by commercial interests, can be more creative, think out of the box, maybe make some novel discoveries. He ends with:

…These discoveries, in turn, may entice the drug makers to reinvest in psychiatric drug development. As consumers desire new treatments, they have to recognize that innovation carries risks. Drugs are approved by the Food and Drug Administration on the basis of short-term studies, so there is always limited knowledge about the long-term safety of new medications. This is particularly true for drugs that act on new targets in the brain about which relatively less is known. But if we are to find better medical solutions for the mental illnesses that disrupt and destroy so many lives, we need to acknowledge a simple truth: there can be no innovation without financial — and medical — risk.
As I read this, he’s admonishing doctors and patients [AKA consumers] that they may have to tolerate more risk to get what they want. The glaring point he doesn’t address is that we may or may not know that already, but what we’re complaining about is that we already had to deal with more risk than we knew about! Maybe some are complaining about the efficacy and the toxicity of the drugs. I’m not. The drugs are what they are. It’s just chemistry. My complaint is that their efficacy was misreported – falsely inflated – and that the toxicity was misreported – hidden – and they knew it at the time. Doctors and patients are perfectly capable of making the kinds of decisions Dr. Friedman is talking about, if [and only if] they know the truth about the drugs presented to them…
  1.  
    Bernard Carroll
    August 22, 2013 | 1:14 PM
     

    You’re right… ‘pipeline’ is an empty trope. Besides, what use is a pipeline if it contains just me-too drugs? As for new approaches like ketamine being developed in academic centers, the academics have already filed for patents on them before anything useful has emerged. Thank you Bayh-Dole Act 1980. Commercialism has seeped into the very pores of academic psychiatry. Just look at the Stanford spinoff company Corcept Therapeutics – search on the term here http://hcrenewal.blogspot.com/

  2.  
    wiley
    August 22, 2013 | 3:43 PM
     

    “Pipeline” is a very commercial term filled with a tough of hysteria. Massive amounts of new drugs are required to satisfy “consumers” in a society in which one out of four people suffers from a “mental illness”. Hogwash. It’s obscene.

  3.  
    wiley
    August 22, 2013 | 3:44 PM
     

    touch of hysteria

    I’d sacrifice a small electronic object for an edit option.

  4.  
    August 22, 2013 | 4:15 PM
     

    The term “pipeline” was originally used in financial analysis, to identify which pharmaceutical companies might have profitable futures in new on-patent drugs.

    “Pipeline” is linked to projected profits. It’s a way of handicapping pharma companies.

    Odd factoid: Robert Whitaker (“Anatomy of an Epidemic”) made his first fortune providing investors analysis of clinical trials and their real-life implications for the $$$ pipeline.

    I was also struck by Lieberman’s reference to drugs going off patent. My guess is he was alluding to pharma not having any additional incentive, or maybe the means, to conduct new psychiatric drug development — something his crowd regards as an immense tragedy.

    By crying wolf about burgeoning mental illness, Lieberman is also saying we need new drugs to get MORE than 20% of the population on at least one psychiatric medication.

  5.  
    a-non
    August 22, 2013 | 4:51 PM
     

    “The commodity must flow: there can be no innovation without financial — and medical — risk.”
    https://upload.wikimedia.org/wikipedia/commons/f/fa/Discharge_pipe.jpg
    (wastewater discharge pipe wikimedia)
    “Culture jamming is a form of subvertising.[6] Many culture jams are intended to expose apparently questionable political assumptions behind commercial culture. Common tactics include re-figuring logos, fashion statements, and product images as a means to challenge the idea of “what’s cool” along with assumptions about the personal freedoms of consumption.[7]”
    https://en.wikipedia.org/wiki/Culture_jamming

  6.  
    TinCanRobot
    August 22, 2013 | 5:27 PM
     

    “we are facing a crisis in drug innovation”

    Friedman: “Quick, pour gas on the fire, we’ll burn it out!”

  7.  
    a-non
    August 22, 2013 | 5:51 PM
     

    “We’re gonna need a new pipeline but what about damage control and public perception management?”

    “US brain project puts focus on ethics” * Helen Shen 14 August 2013 Nature
    http://www.nature.com/news/us-brain-project-puts-focus-on-ethics-1.13549

  8.  
    August 23, 2013 | 3:19 PM
     

    And don’t forget the rebranding: Discredited “chemical imbalance” biopsychiatry becomes shiny new eminently fundable neuroscience.

  9.  
    a-non
    August 23, 2013 | 10:59 PM
     

    With new fundamental problems that need to be addressed as well. The last paragraph in that Nature article details this:
    “Thomas Murray, one of the architects of ELSI and president emeritus of the Hastings Center, a bioethics research institute in Garrison, New York, is among the speakers invited to the commission meeting. He considers the BRAIN Initiative a timely opportunity to develop an ELSI programme for neuroscience. “There will be wonderful questions about human responsibility, human agency,” he says. “It’s never too soon to begin.”
    http://www.nature.com/news/us-brain-project-puts-focus-on-ethics-1.13549
    Watch for James Giordano for more about neuroethics. What has happened to Big Pharma might just happen to “Big Neuro” in the future.

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