Little hope for further innovations in psychopharmacology?

Modern psychotropic drugs were discovered serendipitously in the 1950s. By the end of this decade, the prototypes of the main classes of psychotropic drugs had been identified and introduced into psychiatric practice. At that time, there was considerable optimism regarding the future of psychotropic drug development. Unfortunately, today, optimism has not been realized in spite of the considerable investment in drug development by the pharmaceutical industry. Although there are undoubtedly many reasons for this, the ever increasing concentration of the pharmaceutical industry into conglomerates, and the negative impact of the regulatory authorities on the regulation and use of novel drugs, has played a part. Of at least similar importance is the usage of unsuitable diagnostic systems for defining the indications for psychotropic drugs. The purpose of this commentary is to highlight the concerns that the authors have in the future of psychotropic drug development and to present possible solutions to the problem. The globalization of world trade has stimulated the concentration of pharmaceutical companies particularly in Western Europe and North America, and this change has been associated with a reduction in psychotropic drug research. This has been due to the closure of research laboratories in companies that were previously devoted to psychotropic drug research with an inevitable result in the reduction in novel drugs. In the past two decades, approximately 15 new psychotropic drugs have been marketed in Europe and, with the current situation in the pharmaceutical industry, the future outlook is bleak! The European College of Neuropsychopharmacology has expressed its deep concern at the recent decision of many international pharmaceutical companies (such as AstraZeneca, GSK, Pfizer, Merck, Sanofi, and Novartis) to reduce their investment in neuroscience research. This decision is particularly unacceptable when it is known that over one third of Europeans experience some form of mental disorder annually at a total cost of some Euro 800 billion. This amounts to almost 25% of the total healthcare costs of the European Union. Clearly, this demonstrates the need for more investment in psychotropic drugs research, not less! Another serious consequence of the reduction in central nervous system (CNS) research by international pharmaceutical companies has been the negative impact on the employment of neuroscience researchers in Europe. The loss of hundreds of research positions in the pharmaceutical industry, at a time of major retractions in employment by research institutions and universities throughout Europe, will have a profound effect on the future of neuroscience research here. However, it is evident that the major pharmaceutical companies are aware of these problems and still have proceeded to cut investment in many vital areas of CNS drug research (Schoepp, 2011). A further significant impediment to the development of novel drugs is linked to the harmonization of regulatory guidelines particularly with regard to the design and monitoring of clinical trials. This has inevitably increased the cost of developing and manufacturing novel drugs. An even larger problem concerns the restrictions for defining the indications for use of psychotropic drugs (Loonen and Stahl, 2010; Van Praag, 2010). The harmonization of regulatory guidelines has led to the universal adoption of Diagnostic and Statistical Manual (DSM) of Mental Disorders of the American Psychiatric Association (APA Task Force, 1980) as the criterion for the registration of psychotropic drugs. The DSM categories are, however, heterogeneous, and the pathological targets upon which psychotropic drugs act often contribute to several diagnostic categories. DSM categories are based on Kraepelin’s concept of psychic disorders, such as “schizophrenia” and “depression”, being nosological entities. “Packages” each with its own etiology, symptomatology and course; each with its own specific pathophysiology. Nosology, according to Kraepelin, should be the principle guideline in exploring the biological roots of mental pathology (Van Praag, 2008). However, the DSM categories are bogus nosological entities, and this renders them unsuitable as targets for the development of new and innovative drugs.