New York TimesPerspectiveBy RICHARD A. FRIEDMAN, M.D.August 19, 2013
Fully 1 in 5 Americans take at least one psychiatric medication. Yet when it comes to, we are facing a crisis in drug innovation. Sure, we have many , 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 , and 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.
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
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 mountains
I looked to the children,
I drank from the fountains
pointing me in a crooked line
and the less I seek my source for some definitive
the closer I am to fine…
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…
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.