On Medscape yesterday they ran an article/video by a Dr Jeffrey Leiberman, lamenting the failure of three psychotropic drugs –one for the treatment of schizophrenia, and the others for Alzheimer’s — to pass beyond either phase 3 or phase 2 clinical trials. This is part of what Leiberman had to say (please note that the emphasis is decidedly mine…)
“The brain is an organ that is orders of magnitude more complex than any other organ in the body. The brain has 100 billion cells. Each of the areas of the brain is organized cytoarchitecturally differently, and the cells connect via over 30 trillion synapses. Compare this to the heart, the liver, the gastrointestinal system, or the lungs, and there is no comparison in terms of complexity and intricacy. In addition, given the fact that we are developing treatments for brain disorders that affect mental function and behavior, the animal models that are an essential component of biomedical research and drug development are limited, because how can lower species like rodents model the complexity of human behaviors and mental disorders that we are trying to correct pharmacologically?
“In addition, the biomarkers we use to signal the effect of the treatment or prove the target engagement of a molecule at the desired location in the brain or protein in the brain are still in development and not fully validated. Thus, the complexity of the brain and the limitations of existing tools make the prospects of certainty in drug development [for brain disorders] more questionable than in other organ systems and disease areas. “Certainly the research community and the National Institutes of Health (NIH) understand the importance of redoubling our efforts to develop treatments for this important group of disorders. The NIH has recently established a new Institute, NCATS, or National Center for Advancing Translational Science, which has as part of its core mission drug discovery and development. In addition, various other Institutes have put out RFAs [request for applications]; this includes the National Institute of Mental Health, which has initiated a series of what are called the “fast programs” to identify drugs that exist within the pharmaceutical industry and may no longer be under development, but can be repurposed for study for specific disorders. A quick, rigorous study using a fast-fail strategy can determine whether these agents have the potential for further development.
“New efforts are coming from the biomedical research community as well as the NIH to spur drug development. I hope this will act as a catalyst for the pharmaceutical and biotech industries to not despair or back away from the risk of developing drugs in these areas, but rather to find the resources to support drug-development programs for these disorders.
“What is the benefit? Anyone who works with psychiatric patients knows that there are tremendous unmet clinical needs, whether in schizophrenia, depression, bipolar disorder, autism, or Alzheimer disease. With these needs come tremendous market potential, so for those who stay the course and persevere, there will be very lucrative rewards .To me, this seems like a great opportunity, and I think our partners in the private sector should appreciate this. I look forward to partnering with them to try and work in a way that uses their precious resources most efficiently but still serves our scientific goals and the needs of our patients. Thank you for listening.”
Yes, I noted the last statement, that he wants to serve science and his patients, but i could not help but feel great dismay at the other statements, including the first, that largely states what I already suspected: using animals to prove anything about human brain disorders or states of mind is downright ridiculous. All you can say about a rat’s “schizophrenia” is that it appears to “behave” in some fashion that looks similar to someone who is psychotic…but how would you know if a rat is psychotic, or hallucinating or thinking in a delusional fashion?
Come on? How would you know if a rat had negative symptoms of schizophrenia, or was depressed, or simply felt lethargic because it was hungry or drugged or sleepy or some other physiological reason. Well, you likely could not! Using animals that can not communicate with us to model human mental functioning is downright silly, and yet it seems to have only just occurred to Dr Leiberman, perhaps in his own disappointment with the glutamate-dampening anti-schizophrenia drug that just went bust…I dunno.
Once again, having read about how they are using Ketamine to treat 6-12 years olds with bipolar illness (mind you, I am not convinced that the children are actually Bipolar, only that more and more kids are being diagnosed because conveniently shrinks are allowed to drug them with Abilify and Seroquel and other adult antipsychotics and the drug companies push it on them, pay them for using it etc)
I believe that the use of psychoactive drugs and the rampant use of them is more often inappropriate than not. Truly. The very idea that Abilify and Seroquel are prescribed willy nilly for everything from insomnia to mild anxiety is just plain SCARY. Has anyone out there taking these drugs even bothered to read the side effects, or do they no longer care what they are taking? Obesity no longer scares anyone, but what about diabetes and high blood pressure, nope, I guess not, since those are epidemic too.
It truly astounds me how both those drugs, not to mention a whole host of other powerful drugs are being pushed on the American public, but we are a public that LOVES to take drugs rather than deal with problems by, well, looking at ourselves and thinking about what our responsibilites are and how we might change things…and doing some hard work and hard thinking about things…No, god forbid, why not just take a pill and forget about everything else, and if the pill doesn’t do anything, well, then, probably we are incurably ill and need to take those useless pills for the rest of our lives, because if we didn’t take them we might might might be even worse than we are taking them, right?
Not! Why do we take drugs that don’t help us, or that we do not notice any benefit from (though the shrinks are always willing to point out to us how much better “you are feeling”), drugs that might even make us feel worse in other ways.
Some people who are depressed lose all sexual enjoyment and functioning from their antidepressants, but refuse to stop the drugs because they are afraid…even though the drugs themselves make little difference in their mood, but their lack of sexual pleasure and responsiveness surely has…in a negative way. Why do they continue taking the pills? Hope? Obedience? Uncertainty? Perhaps all three…They may hope that if they take the antidepressant just a little longer, the side effects will “go away” as their doctor likely assured them, and they naturally want to be an aobedient and good patient, so they keep complying. And of course, depressed as they still are, uncertainty about the future plays a huge role, since how do they know that things wouldn’t get even worse, should they cease taking these pills that the doctor says not only will help them but somehow noticeably is helping them, whether they feel it or not.
Argh. I am reading a book, Rethinking Madness, by Paris Williams, PhD. and it is a very interesting take on psychosis and the treatment of it. He suggests that it is NOT always a lifelong condition, or that one breakdown means that one needs to be on medication for life, or in fact that even with repeated psychotic episodes, one can be on intermittent medication and at low doses. I have difficulty reading, myself, so I have not read far along, but the first case study discussed a man who became psychotic suddenly in the late 60s or early 70s when he was threatened with the draft. After that he was ill for a long period of time, in and out of madness until he met the “right doctor” at age 28 or so. I believe it was then that he made the slow transition off all medication and since he was 35 or so has been off meds altogether. And has been well. Recovered, in every sense that matters, completely.
Everything about his history would today dictate that he never be taken off meds, and would mitigate against his ever dreaming of working in the mental health system, let alone as a worker in a state hospital. Yet this is where he has been employed for many years…(I may misremember some details, but that is the gist of it.) I could scarcely wrap my mind around such an outcome…it seemed that amazing.
Yet, I cannot be envious, because I know how often I tried to get off my medications, and because I did not know how, I likely induced a recrudescence of psychosis without even understanding that was what was happening. And naturally, they put me back on the drugs again…It was not my fault, just how it was in those days. I didn’t know, and they still don’t! Even now, though, I do not know if I could get off the meds.
But in my case, I am not sure I want to, largely because I function so well on them. I write, I do art, I sleep well, I am not obese, I have no chronic physical health problems because of them…So I have no pressing need to get off the antipsychotics, nor the anti-seizure meds, which I may need due to temporal lobe epilepsy anyhow. I would like to get off the sertraline, yes, and we are working on that. But why fix what ain’t broke at this particular time? I mean, I only got out of the danged hospital a month ago, and it would seem a little, er, crazy to fiddle with things this soon, much as I wish I could. On the other hand, I don’t mind taking these meds, because by and large, I believe, frankly, that my body has re-established some kind of homeostasis and has adapted to the lowered dopamine…so it has ramped up production to a different balance, meaning that I am fine where I am, but would risk a massive overload should I stop cold turkey.
OTOH, I do not yet understand the absolutely immediate improvement in all my mental capabilities when I take Zyprexa. Yes, I eat and eat and eat. But I can read and pay attention to people telling me things to movies and the TV and just “intake” in a way that I cannot now and have not in years…And it is literally within 2 doses. That cannot be a matter of homeostasis so what is it? Can Zyprexa be the ONLY drug that actually has some beneficial effects? I doubt it. So what is it? Anyhow, any comments on these points would be appreciated. I don’t mind if you want to argue to the contrary, if you feel it strongly. I am here to hear different points of view as well. Though you know of course that I may “argue” with you back! All in friendship and good cheer.