Psychiatric Drug Development: Why So Slow?

Jeffrey A. Lieberman, MD


May 14, 2010

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Jeffrey A. Lieberman, MD: Hello. This is Dr. Jeffrey Lieberman of Columbia University talking to you today for Medscape. I wanted to talk about a series of developments that have occurred that are likely to affect the pace of new drug development, particularly in the area of psychotropic drugs.

I think everybody who practices clinical psychiatry knows that the rate of real mechanistic innovation for drugs in all the major drug classes -- whether they are antipsychotics, anticonvulsant mood stabilizers, antidepressants, or anxiolytics --has been painfully slow. In fact, currently in this 21st century we are still using drugs that work by essentially the same mechanisms of action [MOA] as those developed as original prototypes for these classes of medications back in the 50s and the 60s. For antipsychotic drugs the MOA is still D2 antagonists. For mood stabilizers we have lithium and the anticonvulsant medications. For antidepressants we have drugs that inhibit the uptake of catecholamine and indolamine neurotransmitters. For anxiolytics we have essentially antidepressant medications and benzodiazepine receptor agonists.

Now, it hasn't been for lack of effort, because the pharmaceutical industry and the psychiatric research community have been intensively and furiously laboring to find new drugs with mechanistically novel actions. However, it has just been very difficult. In this way, we are not dissimilar to many of the disorders that are treated by our sibling disciplines in medicine and neurology. For example, Parkinson's disease, where there has not been a major breakthrough since the breakthrough of L-dopa. Or Huntington's disease; though we know the gene which causes the illness, there still hasn't been an effective treatment developed. Even Alzheimer's disease -- we have a series of at least 4 genes that identify either the cause of early-onset Alzheimer or risk factors for later-onset Alzheimer's, [and] we have some effective palliative treatments. But we still don't have any real effective disease-modifying treatment. These are hard disorders in which it is hard to find an effective treatment, particularly with a new mechanism of action, even when you have a substantial knowledge about the cause and the pathology associated with the illness.

In addition to this difficult task facing us -- along with our partners in the private sector in the pharmaceutical and biotechnology industries -- comes a series of what I regard as very worrisome developments. Specifically, a number of major pharmaceutical companies in the throes of this current financial recession that we are experiencing have undergone a retrenchment where they are cutting back on their programs in drug discovery and development. That is understandable given the cutbacks one sees in economic downturns throughout all of the private sector and in private companies, but this retrenchment has occurred selectively in the areas of CNS [central nervous system] drug development and particularly in areas affecting psychotropic drugs.

Recently, GlaxoSmithKline eliminated its drug discovery unit in 2 of its major centers in Europe. AstraZeneca also had a major reduction in their scope of drug discovery efforts in CNS and psychotropic drugs. Pfizer and Wyeth's merging has also reduced their discovery effort, particularly in CNS. Other companies as well. This is of concern because whatever you might say about the pharmaceutical industry in terms of [them] pursuing the more conservative development strategy -- with an emphasis on "me-too" drugs that will be definitely effective and can be marketed profitably -- they are essential partners in the development of therapeutics, both for pharmaceuticals as well as for devices. We need the private sector.

Why has there been the selective reduction in efforts to develop drugs in the CNS, particularly in the mental illness/psychiatric psychotropic drug area? I think that although there is a huge unmet need in terms of treating people with mental illnesses that are currently not getting treatments, and therefore a great potential upside in terms of marketability, it is perceived that this is an area of great risk -- and that the difficulty in finding a treatment that doesn't just work by a conventional or identified mechanism of action, but by a novel mechanism of action, has been extremely difficult. There have been many trials at doing this and hundreds of millions of dollars spent, but there has been little to show for it in terms of mechanistically novel therapeutic agents.

As a result of this, companies are steering away from what they view as risky and potentially expensive development avenues. What this means is that we are going to have to do more with our current treatments rather than hoping for the big breakthrough on a new mechanistically novel and potentially vastly superior agent. There is, to be sure, much we can improve upon in the way we use existing treatments and how we deliver services. This reduction in emphasis on CNS drug discovery and development will assuredly slow down the pace for new and novel drugs developing, and that is unfortunate. I do feel that there will be a return to an emphasis on drug development in brain-directed drugs, specifically for purposes of developing therapeutic indications for mental illnesses, but this is going to take a while to return. In the meantime, we are going to have to use our existing treatments more effectively than ever and to provide services in which these can be provided in a more effective and cost-effective way. Those are my comments for today. This is Dr. Jeffrey Lieberman from Columbia University wishing you a good day. See you again on Medscape. Thank you.


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