no mo’ mojo…

Posted on Thursday 12 January 2017

By Kate Kelland
January 11, 2017

LONDON — It is likely to be at least 10 years before any new generation of antidepressants comes to market, despite evidence that depression and anxiety rates are increasing across the world, specialists said on Wednesday. The depression drug pipeline has run dry partly due to a "failure of science" they said, but also due to big pharma pulling investment out of research and development in the neuroscience field because the profit potential is uncertain. "I’d be very surprised if we were to see any new drugs for depression in the next decade. The pharmaceutical industry is simply not investing in the research because it can’t make money from these drugs," Guy Goodwin, a professor of psychiatry at the University of Oxford, told reporters at a London briefing.

Andrea Cipriani, a consultant psychiatrist at Oxford, said such risk aversion was understandable given uncertain returns and the approximately billion dollar cost of developing and bringing a new drug to market. "It’s a lot of money to spend, and there’s a high rate of failure," Cipriani said. Treatment for depression usually involves either medication, some form of psychotherapy, or a combination of both. But up to half of all people treated fail to get better with first-line antidepressants, and around a third of patients are resistant to relevant medications.
It’s now been three decades since Prozac® was added to our pharmacopeia. Psychiatry as a specialty had rededicated itself to its medical roots, and this new drug class was a welcomed addition. While no more effective than the older tricyclic antidepressants, it was better tolerated [even though it had some side effects of its own]. After a few years, a progression of competitors came to market, and that came to be called the pipeline, and psychiatry settled into a rhythm of discussing their various differences. With the focus on the future, what’s coming next?

There were many attempts to enhance efficacy – sequencing, combining, augmenting with a variety of other drugs. Non-responders were said to have Treatment Resistant Depression, discussed almost as if it represented a unique entity. Multiple markers were queried looking for something that would predict the right drug – called Personalized Medicine. Practitioners and patients alike kept their eyes on the future – what’s coming down the pipeline. And there was a vague sense that the newer drugs were improvements over the earlier offerings, though that’s hard to justify in retrospect. Somewhere in there, the notion developed that the incidence of depression was rising rapidly, although that was hard to put together with the predominant view that depression was a biological-?-genetic entity. And the scientific basis for that escalating prevalence is hard to pin down.

And then in the summer of 2012, the Pharmaceutical companies threw in the towel and began to shut down their R&D programs for CNS drugs. They’d run out of candidates ["me too drugs"]. A great wail was heard throughout the land. There were conferences and task forces – much rhetoric and blaming. The NIMH seemed to have a new idea about how to jump-start drug development  every month. Multiple schemes were proposed to lure PHARMA back into the game. And all eyes turned to the search for something "novel" to keep things alive [eg Ketamine and its derivatives].


The experts said that since the current generation of SSRI [selective serotonin reuptake inhibitors] antidepressants – including Pfizer’s blockbuster Prozac [fluoxetine] – are widely available as cheap generics, there is reluctance among health services to fund expensive new drugs that may not be much better. That is partly because existing medications, while by no means perfect, are quite effective in more than half of patients, the specialists said, and partly because in this condition in particular, placebo can have a massive impact. That makes it difficult, they explained, to show that a new drug is working above and beyond a positive placebo response and an already effective generation of available drugs.
Looking at the pipeline graphic and the decades of industry introducing new versions of SSRIs, this explanation doesn’t make much sense. Maybe most prescrbng physicians [and their patients] have caught on to the fact that there’s no more mojo to be harvested from the SSRI antidepressants. Also, maybe what the drug companies say might well be true – that they’ve run out of candidate molecules [SSRIs] to even try. In other words, the SSRI paradigm has been exhausted, and there’s not another class of drugs to put in its place.
Depression is already one of the most common forms of mental illness, affecting more than 350 million people worldwide and ranking as the leading cause of disability globally, according to the World Health Organization. And rates are rising. Glyn Lewis, a professor of psychiatric epidemiology at University College London, cited data for England showing a doubling in prescriptions for antidepressants in a decade, to 61 million in 2015 from 31 million in 2005.
Here, we are asked to believe that the doubling of antidepressant prescriptions over that ten year span justifies the heading above [DEPRESSION RATES RISING]. A much more reasonable heading would be SSRI PRESCRIPTION RATES RISING. Why? Marketing. Primary Care Physicians prescribing SSRIs. Waiting Room screening. Patients taking them longer thinking they’re staving off something or correcting somethng [or inertia]. Knock yourself out here. I’ve just scratched the surface.
In the United States too, more people than ever are taking antidepressants. A study in the Journal of the American Medical Association [JAMA] in 2015 found that prevalence almost doubled from 1999 to 2012, rising to 13 from 6.9 percent. Yet several major drug companies including GlaxoSmithKline and AstraZeneca have scaled right back on neuroscience R&D in recent years, citing unfavorable risk-reward prospects.
Rejecting the [far-fetched] idea that the doubling of prescriptions equals a doubling of the disease prevalence, the drug companies have accepted another [more palatable] explanation – that the market is saturated. The likely reason they think that is that the market is saturated.
Goodwin said the absence of a drug development pipeline was also due to lagging scientific research into what is really happening in the brains of those who do and do not respond to current antidepressants. "It’s partly a failure of science, to be frank," said Goodwin. "Scientists have to … get more of an understanding about how these things actually work before we can then propose ways to improve them."

With all due respect to Dr. Goodwin, his pronouncement might’ve worked in the 90s [the Decade of the Brain] or the 2000s [the Research Agenda for the DSM-V]. But after thirty years, this argument itself has run out of mojo too. The scientists have scienced themselves silly trying to do what he suggests without much success. They’ve certainly gone through a small fortune in the process. The marketeers have had more success, raking in a beyond-modest fortune in the process. But this train is pulling into the station, its journey’s almost done. 

A supernova is a stellar explosion that briefly outshines an entire galaxy, radiating as much energy as the Sun or any ordinary star might emit over its lifespan. This astronomical event occurs during the last stages of a massive star’s life, whose dramatic and catastrophic destruction is marked by one final titanic explosion concentrated in a few seconds, creating a "new" bright star that gradually fades from sight over several weeks or months.

[click image for info]

Will the SSRIs have the same kind of fate as SN2014J? evaporating into the ether? I doubt it. At least not any time soon. They’re still useful in clinical practice when used carefully and in moderation. I expect the short acting ones will gradually disappear because of their heightened withdrawal profiles. And hopefully the others will be used in a more time limited way. And then, maybe we can get around to reworking our diagnostic system to bring it closer to clinical reality.

We’ll see… and speaking of shiny objects:

ASASSN-15lh [supernova designation SN 2015L] is a bright astronomical object. Initially thought to be a superluminous supernova, it was detected by the All Sky Automated Survey for SuperNovae [ASAS-SN] in 2015 in the southern constellation Indus. The discovery, confirmed by ASAS-SN group with several other telescopes, was formally described and published in a Science article led by Subo Dong at the Kavli Institute of Astronomy and Astrophysics [Peking University, China] on January 15, 2016. In December 2016, another group of scientists raised a hypothesis that ASASSN-15lh might not be a supernova. Based on observations from several stations on the ground and in space [including Hubble], these scientists proposed that this bright object might have been "caused by a rapidly spinning supermassive black hole as it destroyed a low-mass star". ASASSN-15lh, if a supernova, would be the most luminous ever detected; at its brightest, it was approximately 50 times more luminous than the whole Milky Way galaxy with an energy flux 570 billion times greater than the Sun….

[click image for info]
    January 12, 2017 | 9:55 PM

    Maybe there isn’t a new class of medication to treat depression and anxiety because the fraud that chemicals alone or primarily aren’t the ticket to effectively stabilizing mood and thought struggles.

    Perhaps Einstein was beyond right, he was painfully obvious and aware that doing the same thing over and over to allegedly fix a problem or issue is really insanity. But, it doesn’t take an Einstein to figure that out in the end, eh?!

    What is both really insane and pathetic is how so many psychiatrists continue to embrace this failed notion that illness is just a chemical imbalance to such a degree it sucks the soul out of the treatment process these days.

    New year, same fecal impaction, and now more ludicrous leadership and failed representation, what does the song by The Who, “Won’t get fooled Again” end with? “Meet the new boss, same as the old boss…”

    Fascinating how the personality disorder of our Presidents just gets more entrenched and disturbing, but, it is what the public not only wants, but deserves. So to tie it in here in the end, yeah, more depression and anxiety abounds, because we can’t find sanity in those who lead and influence us.

    But, we can’t medicate personality disorder, can we, folks!?!?

    January 13, 2017 | 12:05 AM

    I ran across this article that may explain the rising incidence of depression.
    The authors did a meta-analyses of 49 studies where depressed people were randomized either to receive placebo at all times, and others who got pills, and then were randomly assigned to placebo.
    The relapse rate for people who only got placebo for their depression was 24.7 %. The relapse rate for people who got pills, and then discontinued pills, was 48% across all drug types.
    This has staggering implications. The pills that are called antidepressants are actually prodepressants!! The relapse rate is double, compared to those who receive only placebo. Even if one assumes that pills are more effective than placebo in treating depression (although this difference is marginal at best) the doubling of the relapse rate means that more people wind up with depression in the long run than if they had taken nothing at all.

    James OBrien, M.D.
    January 13, 2017 | 11:45 AM

    Trimonoamine-fetish is well past its expiration date.

    I think there will be in the next ten years new generations of AMPA mediated drugs and therapy-facilitating drugs. Ketamine or MDMA may not be the eventual solution, but I do think research in this area is turning up some interesting findings.

    berit bryn jensen
    January 14, 2017 | 8:48 AM

    Rates of depression and suicides are steeply on the rise in some European countries, Greece, UK… the US too? I believe what my eyes see and what people tell about loss of opportunity for decent jobs and wages, loss of hope and decent into despair. More professionals ought to raise their voices publicly on the awful consequences of neoliberal laissez faire politics depriving whole populations of the means for an ordinary, decent life, and continuing wars sending millions into homelessness and mortal danger. Depression should be seen, most often, as natural, healthy reactions to too much adversity and trauma, telling us that external living conditions need change, that is personal and political work for change. I remember the huge hope engendered by the outgoing, constantly warring and dronekilling POTUS, deeply disappointing and dishonoring more of us than a gullible Nobel Peace Prize committee. Doctors cannot heal most depression. Responsible social politics can. And now the Donald. Good grief… Yes, grief is on the rise. I could lie myself down to die, but as I have children and grandchildren, friends and neighbors, some from Somalia, Afghanistan and the Middle East, a better choice is to go forth with political activism to uphold our once vibrant social democracy, instead of voting for our conservative, extremely stupidly US-loyal government’s road to perdition. My heartfelt thanks from me in outback Norway for your most diligent work to keep your readers informed!

    James OBrien, M.D.
    January 14, 2017 | 10:59 AM

    Terrible politicians are pretty much a constant in life, but are not the independent variable. If that were the case, MDD would have been at its peak in 1940. Increasing lack of resiliency from broken families is far more likely to be the independent variable. One’s personal happiness depends very little on who wins elections.

    So many terrible articles in the psychiatric throwaway journals treating election results as the foundation of a PTSD diagnosis or trauma psychology. I wonder what Victor Frankl or Audie Murphy would have had to say about that.

    Here’s Martha Washington anticipating Anna Freud by about 150 years:

    The greater part of our happiness or misery depends on our dispositions and not on our circumstances. We carry the seeds of the one or the other about with us in our minds wherever we go.

    January 15, 2017 | 12:10 PM

    “One’s personal happiness depends very little on who wins elections.”
    Working heavily with Hispanic immigrant and LGBT populations I don’t know that I would entirely concur.

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