Revitalizing Psychiatric Therapeutics?

In January of this year, Steven Hyman MD, former Director of NIMH and currently a leading psychiatric researcher at MIT and Harvard, published Revitalizing Psychiatric Therapeutics in Neuropsychopharmacology.  The article is in the journal’s commentary section and is essentially an opinion piece.  Here’s Dr. Hyman’s summary:

“Despite high prevalence and enormous unmet medical need, the pharmaceutical industry has recently de-emphasized neuropsychiatric disorders as ‘too difficult’ a challenge to warrant major investment.  Here I describe major obstacles to drug discovery and development including a lack of new molecular targets, shortcomings of current animal models, and the lack of biomarkers for clinical trials.  My major focus, however, is on new technologies and scientific approaches to neuropsychiatric disorders that give promise for revitalizing therapeutics and may thus answer industry’s concerns.”

Dr. Hyman is a key figure in the promotion of bio-psychiatry.  His opinions carry weight, and I thought it might be useful to examine what he has written.

Dr. Hyman begins with a brief look at the psychopharmacological “revolution” of 1949-1957, during which lithium, chlorpromazine, iproniazid and imipramine were introduced.

“These serendipitously recognized drugs gave rise to a large number of related compounds in each therapeutic class that in aggregate produced enormous benefit to patients while fundamentally changing the scientific and clinical landscape of psychiatry.”

and

“Later, beginning with clomipramine, serotonin-selective antidepressants were found to exhibit a degree of efficacy for obsessive-compulsive disorder.  These discoveries not only improved many lives but also motivated significant advances in both basic science and clinical investigation.”

Dr. Hyman’s enthusiasm for the drug revolution in psychiatry is clearly evident, and there’s little or no recognition that the drugs he mentions may have done, on balance, more harm than good.  He does concede some toxicity concerns but assures us that the drugs developed in the last 50 years are less toxic than their forerunners.  He acknowledges, however, that they are no more effective.

“What has not happened for five decades across the range of psychiatric drug classes is any significant improvement in efficacy.”

Dr. Hyman attributes this lack of improvement in efficacy to the fact that

“…the molecular targets of all of today’s widely used psychiatric medications are the same as the targets of their 1950s prototypes.”

Dr. Hyman notes that

“…the past 4 years have seen the industry significantly decreasing its investment in psychiatric disorders while investing in other areas.”

He attributes this reduction in investment to pharma’s perception that the “scientific underpinnings” of psychiatry are “less mature” than in other medical fields.

This, he tells us, has “enormous negative consequences for patients with psychiatric disorders and their families” because “…discoveries that may come from academic labs in the near term…” will not result in marketable products without pharmaceutical funding.

So, according to Dr. Hyman, pharma is distancing itself from psychiatry because psychiatry’s scientific underpinnings are less mature than other fields.  Specifically, Dr. Hyman mentions:

1.  “poor understanding of disease mechanisms”
2.  “significant disillusionment with animal models”
3.  “a phenomenological diagnostic system and a lack of biomarkers for diagnosis or ascertainment of treatment response”

With regards to the third item, Dr. Hyman is fairly blunt about psychiatry’s current diagnostic categories.

“Newer technologies combined with growing momentum for a ‘cognitive jailbreak’ from the fictive DSM categories that have captured grant making, journal editing, and regulatory decisions for the past several decades suggest that progress may be in the offing for biomarkers as well.” 

The general theme of the rest of the article is that great breakthroughs are at hand – maybe.

“Because of advances in genomic technologies, psychiatry is at the threshold of gaining information about molecular mechanisms of disease.  That said, putting genetic findings to work in the service of understanding the pathogenesis on psychiatric disorders and revitalizing therapeutics poses very difficult challenges.”

SUMMARY

Dr. Hyman’s article is interesting from a number of perspectives.

Firstly, he is clearly wedded to the bio-psychiatric approach and to the notion that psychiatric “patients” have gene-linked neural defects, the identification and remediation of which should be the primary focus of research.

Secondly, he is optimistic that breakthroughs in this area will occur, and that the pharma industry will resume its financial support of psychiatric research.

“The pace of technology development seems only to be accelerating, and should thus give us hope.  Despite the challenges, there is a substantial opportunity to win back industry and to revitalize psychiatric therapeutics by embracing clear thinking and by putting technologies to work.”

But of greatest interest is Dr. Hyman’s claim that pharma is abandoning psychiatric research because the latter has failed to identify precise “disease mechanisms” or biomarkers.

Pharma had been a staunch supporter of psychiatric research for five decades, during which time there were no identified disease mechanisms or biomarkers.  There were hypotheses, of course (e.g. the biogenic amine theory of depression, the serotonin theory of depression, the dopamine theory of schizophrenia, etc.), and these theories were promoted, both by psychiatry and by pharma, with more enthusiasm and vigor than their merits warranted.

It is also the case that psychiatry’s relationship with pharma was riddled with corruption at all levels of the profession, but especially among its leadership.

One facet of this corruption was the routine over-statement of psychiatry’s effectiveness, and, equally routine, under-statement of adverse effects.

And through all of this, psychiatry and pharma remained blissfully hand in glove.

What has changed in recent years is simply that the bubble of deception and profiteering has burst.  The spurious concepts and the destructive practices have been exposed; there is an active, growing, and outspoken survivor movement; and we’re seeing an increasing number of successful lawsuits.

In addition, there is a growing sense that it is only a matter of time before a definite link between psycho-pharma products and the school shootings will be established.

Pharma’s decision to hitch its wagon to psychiatry was never driven by science.  It was driven by business considerations.  Likewise, the decision to unhitch has nothing to do with science.  It’s because the cost of doing business with psychiatry has become unacceptably high.

  • Francesca Allan

    Phil, this quote “psychiatry is at the threshold of gaining information about molecular mechanisms of disease ….” is eerily familiar. It is my understanding that we have been at this threshold for years. Perhaps we’re not dealing with a threshold that needs to be overcome, but rather an insurmountable barrier that needs to be acknowledged.

  • Phil_Hickey

    Francesca,

    Yes. We’ve been at this threshold for decades. And each new brain-imaging and brain-stimulating technology gives the search a new impetus. Now it’s the genome and its related technology.

  • Francesca Allan

    Yeah, but let’s let them waste their time with this kind of research. The more money and other resources poured into that, the less available to torture people like me. You know, I have no doubt that eventually there will be found a consistent particular genetic recipe that correlates with an increased risk of mental illness although clearly it won’t be as simple as, say, the genetics of blue eyes. The problem is that finding such a correlation still won’t address what mental illness actually is. Finding the “silly” gene or the “irritable” gene would be just as beneficial. My answer would be: So what?

  • cannotsay

    I think that the real reason big pharma companies are retreating from the development of new psychotropic drugs is a justifiable concern by some of its executives that they might end up in jail.

    Psychotropic drugs are among the most profitable drugs because they need to be “taken for life”. Developing “me too” drugs that prolong patents is not that difficult.

    The problem is that the largest fines that Big Pharma companies have received relate to the illegal promotion of psychotropic drugs. It is one thing to pay with shareholders’ money fines that still make the drug hugely profitable, quite another to risk jail time.

  • Phil_Hickey

    Francesca,

    Interesting timing. I have just completed a post on schizophrenia and genetics. It’s scheduled to go up Wednesday morning. And, indeed, the point is: so what?

  • Phil_Hickey

    cannotsay,

    I hadn’t really thought about the jail time aspect – but you’re right. This will have special significance if we ever get definitive proof of the link to the school shootings and there is evidence that this information was suppressed.