Medication development for mental disorders has stalled over the past three decades. After the serendipitous discovery of antipsychotic and antidepressant medications in the 1950’s and 1960’s, and the development of more selective and better tolerated compounds in the 1970’s and 1980’s, the field has come to rely on “me-too” compounds and aggressive marketing. This approach has led to robust sales of medication but little evidence of greater efficacy. One exception is the development of clozapine, an antipsychotic that appears more effective than other compounds but is under-prescribed because of rare adverse hematologic events. Recently, many major pharmaceutical companies have all but abandoned drug discovery efforts for mental illness. We may have left behind the era of blockbuster drugs designed to treat large segments of the population. We now need to identify new drug targets and refocus our drug discovery efforts to search -- as Munos [2009] put it -- for breakthroughs rather than blockbusters.
