The Unfulfilled Promises of Psychotropics

I remember thinking over 40 years ago when I began my clinical career, that with the rapid advances made in psychotropic agents, psychotherapy would become a venture of the past. A recent editorial published in Schizophrenia Bulletin dispels my myth of becoming unemployed.

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?

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 (emphasis added). 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?

Given that there cannot be a coherent biology for syndromes as heterogeneous as schizophrenia, it is not surprising that the field has failed to validate distinct molecular targets for the purpose of developing mechanistically novel therapeutics. Although it has taken our field too long to gain this insight, we seem to be getting there. For example, at the 2011 meeting of the American College of Neuropsychopharmacology, the need for change and the need for new strategies were predominant themes.

In summation the excitement in the past two decades about the “Decades of the Brain” are fading to realism. Our human genome is much more complex than we can imagine. Half of our genes are devoted to brain form and function. The interaction between geneotype and phenotype is also more complex that we realize. Thus, we are approaching this science with more skepticism and realism.


Fibiger HC (2012). Psychiatry, the pharmaceutical industry, and the road to better therapeutics. Schizophrenia bulletin, 38 (4), 649-50 PMID: 22837348

Image via Kuzmin Andrey / Shutterstock.

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  • I completely agree – “better living through chemistry” is a myth!

    Thanks for getting the word out about the shortcomings of psychotropic medication.

    • Dear David-
      A close reading of the article reveals that the author did not bemoan the shortcomings of psychotropics, but only the fact that even more, newer, better, improved psych drugs aren’t coming out soon enough.
      I do not think this author, or this organization, shares the critical.perspective that you and I have, about psych drugs. Just a thought.
      Joan Priestley, M.D.
      Executive Director,
      Alliance for Addiction Solutions

      • baba yaga

        Dear Joan,

        Although I share your critical perspective to a large extent, I don’t dismiss psychotropics: I believe they help when used appropriately. One of the problems is that all too often they are NOT used appropriately. I have personal experience of this.

        One of my concerns is the mis- (or dis-) information given to doctors and patients by the pharmaceutical industry, in order to sell product even where it is not going to do the job. Another is the exaggerated focus on what per cent of patients get “better” according to some arbitrary measure, at the expense of listening to people’s actual lived experience.

        As someone currently struggling to reduce my consumption of psychotorpics, I would appreciate more information about the Alliance for Addiction Solutions. I assume you have a website in that name?

        Baba yaga

  • baba yaga

    This is the sort of discussion I have been looking for. I am a long term user of antidepressant medication, and I also work in mental health, as a service user consultant. I have a long standing interest in the pros and cons of psychotropics, and I need to find a more intelligent conversation about this than “keep taking the tablets dear”!!

    I recently joined a service-user-led research project in the UK. I have submitted a research proposal for a qualitative study of the experiences of people who have been long term users of SSRIs. The object is to set some parameters for a larger scale study of how users actually experience using the drugs: what is helpful, unhelpful, problematic and so on from a consumer oersoective, and what else may correlate with these experiences. I am particularly interested in so called discontinuation syndrome — who is affected by it, how badly, what else might be a factor.

    If you, Richard, or any of your readers know of other relevant research, I would be most grateful for the references!

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  • Paul

    What do you mean by mechanistically. Is it that drugs that were specifically designed to counteract scientifically founded biological causations of mental illness. Its hard to believe that a drug of this type has not entered the market in 30 years. It does confirm that science is still not up to solving this problem , especially in the case of antipsychotics. I can attest to the fact that these drugs can tangibly reduce the minds racing thoughts. I can say that this is independent of sedation. But the side effects Depression , Sedation and hopelessness are intolerable. People should only take these drugs in crisis situations or at very low dosage levels. In those situations I can see their merit. If a person is living their life doped out , that is much more intolerable than living a life where a person is intelligently using these drugs. The goal should be stability not surrender or turning yourself into something as inanimate as a chair. What makes a person a person its their character , their gusto , their spirit , if a person finds themselves lifeless its time to start again.

    • baba yaga

      It is good to hear from someone like Paul who has “been there”. I have not taken antipsychotics (except a very brief spell on a low dose of Melleril, but I have heard a lot of people say similar things about them (though not always so articulately).

      What Paul says connects to what I wrote about medical research using arbitrary measures of getting “better” (i.e the patient does what the nurse tells them instead of shouting or crawling on the floor) and not listening to how the person FEELS. I think (I hope!) things are better now than in the old days of Chlorpromazine, but there is still a long way to go.

      As far as I understand it, the “scientifically founded biological causations” are pretty thin on the ground, and that’s part of the problem. It’s clear that dopamine receptors are by no means the whole story of how psychosis works, and science doesn’t yet know about all the other things that are going on, therefore
      doesn’t know what else to target.

      Scientists genuinely want to help sick people (and also stop them causing big problems for others), so in desperation they try out things out that MIGHT work. I guess that’s what Richard means by “serendipitous clinical observation”. That’s how ECT and lobotomy started out; modern drugs were developed a little bit more scientifically but still based on hunches. We have much stricter ethics rules now so the hunch thing doesn’t work so well –but there are also easier ways to make money than trying to tailor chemical substances to the complexity of human experience.

      “Stability not surrender” — I like that.

  • MMC

    “Psychotropics” in the real world are glorified street drugs that don’t fix any mythical “chemical imbalance” but rather CAUSE chemical imbalance as well as iotregenic damage, systemic functional brain damage and chemically lobotomize a person’s brain. If the psychiatric industry wants to see real world data on these drugs, check out the numerous online groups of people trying to survive their effects. These drugs destroy lives and inflict the nine circles of hell on people. Don’t believe me? Then feel free to try them yourself and play Russian Roulette with your sanity and soul. Google “Benzo withdrawal”, Google “Anti-depressant withdrawal”, Google “Anti-psychotic withdrawl”…millions of human lab rats are screaming in horror at the evil that has been done to them…unimaginable suffering, horror, death and destruction in their lives…ALL due to “psychotropics”. The answer to mental distress isn’t a nuerotoxin, it’s finding the true source which can be anything: hormone issues, sugar, thyroid, virus, bacterial, horrid diet, major nutritional deficencies, addictions, not knowing God, trauma, swallowing lies etc. These drugs take a camp fire and turn it into World War III on the brain. You want proof? Come see with your own eyes the truth about these drugs: God bless~

    • baba yaga

      Hello MMC and others

      I was not expecting any more responses to this thread, as there have not been any for a year!

      I don’t really agree with you — I think it’s about using chemicals responsibly and not just peddling them to get rich — but interested to pursue the conversation, as I’m not having much luck finding people to discuss this with on the forums I subscribe to.

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  • baba yaga

    I just looked at the quotes from Russell Barkley’s “D2 receptors and Executive Function” book, referenced on this site. I intend to follow this book up, because what he is saying resonates with me, even though I don’t believe I have ever had ADHD.

    My experience of trying to withdraw from antidepressants, after using them for many years, seems to relate in certain ways to what is being described — impairment of executive function. I don’t know much about ADHD, but I assume it doesn’t necessarily involve low mood or anxiety. In which case the problems I am experiencing are not a form of ADHD.

    However, my guess would be that someof the neural mechanisms involved in ADHD are the same as those affected in my own case, when I try to withdraw from antidepressants. I have used TCAs/SSRIs for many years, but have not yet met anyone else who has had this kind of withdrawal problem. It has also proved virtually impossible to have conversations with doctors about this, because the problem isn’t supposed to exist.

    This is giving me a lot to think about. I am rather hoping it might trigger someone else’s thoughts too.

Richard Kensinger, MSW

Richard Kensinger, MSW, has over forty years of clinical experience in behavioral healthcare as a psychotherapist, trainer, consultant, and faculty member in the Psychology Department, Mount Aloysius College. He has also taught at Penn State, University of Pittsburgh, and Temple University.
He is also a lover of “football”, known in the USA as soccer. He is currently associated for over 30 years with youth “football”, 26 as a referee.

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