January 9, 2015
Despite great need, pool of new, innovative psychotropic drugs is running dry
Even though antidepressants are estimated to be ineffective for nearly half of those treated, and as many as one-third of schizophrenia patients do not respond well to current medications, a new study by researchers at Brandeis University’s Heller School for Social Policy and Management and Truven Health Analytics finds there is a serious blockage in the pipeline of new drugs that differ dramatically from what is already available.
The study’s authors wanted to know why, despite the fact that mental illness and substance use disorders are so prevalent in the U.S. (for instance, an estimated 16 million adults in the U.S. suffer from major depression), psychotropic drug development lags well behind the development of other medications. In 2011 the Pharmaceutical Research and Manufacturers Association of America (PhRMA) reported that just 240 drugs to treat psychiatric disorders were in development, compared with more than 3,000 for cancer and 750 for infectious disease.
The researchers consulted pre-existing academic literature, conducted interviews with experts in the fields of psychiatry and substance abuse treatment, and analyzed drugs in phase III clinical trials. They cited incentives that encourage firms to focus on incremental innovation rather than take risks on radically new approaches; human brain complexity; and great uncertainty as to ultimate approval, as three major roadblocks to the creation of innovative medications.
“Our interviews with experts indicated that the costs to manufacturers and the benefits of incremental improvements of drugs already on the market, which may improve tolerability, are considerably more favorable for manufacturers than the estimated $2 billion dollars it takes to bring a new drug to market given the uncertainty of approval,” says the Heller School’s Cindy Parks Thomas. “There are additional challenges in the area of mental health. The complex nature of human brain function and chemical pathways creates a challenge for psychotropic drug development, with a failure of animal trials in this area to translate well to human trials.”
According to PhRMA, for every 5,000 compounds that begin development, an average of just five enter phase I testing, and the FDA ultimately approves only one.
Given those figures, lead researcher Peggy O’Brien, PhD'14, of Truven Health Analytics says the team expected there would be little in the way of truly innovative psychotropic drugs in the development pipeline. “The degree to which this is true, however, was astonishing,” she says.
In their analysis of 99 psychotropic drugs that were currently in late stage development, O’Brien and her colleagues found the large majority of trials were of existing drugs being tested for new uses or in combinations with other drugs, that most of the remaining drugs were similar to existing medications, and only three were new drugs that represented substantial departures from existing treatment.
According to O’Brien, the small number of innovative drugs in phase III is made more significant by the fact that, even at such a late stage of development, ultimate success and approval is not guaranteed.
“I hope that our findings will spur discussion and trigger consideration of options to improve the psychotropic drug pipeline and drug development, as well as research that considers other behavioral health interventions, with and without pharmacotherapy,” O’Brien said. “There are many stakeholders, but those with the largest stake are patients who need access to safe and effective medications and other treatments.”
The study, which is published in Psychiatric Services, was funded by the Substance Abuse and Mental Health Services Administration.