Developing new drugs for schizophrenia is becoming increasingly difficult as more patients are responding to placebos given in clinical trials, according to researchers at the Food and Drug Administration (FDA).
Recent clinical trials of second-generation anti-psychotics have been showing smaller “treatment effects” compared to trials from the early 1990s. A treatment effect refers to the difference in symptoms between patients given the real drug in a study and those given a placebo for comparison.
For the study, FDA researchers looked at 32 clinical trials that were submitted to the agency between 1991 and 2008. The trials were all included as part of various companies’ applications to the FDA for approval of their new schizophrenia drugs.
The researchers discovered that North American trials done in more recent years resulted in smaller treatment effects than older studies.
But it was not because drugs in the newer studies were less effective, said Dr. Thomas P. Laughren, head of the FDA’s division of psychiatry products and one of the researchers on the study. The difference is that study patients have been receiving placebo pills and have been showing a greater response to them.
Exactly why is unclear. One possibility, Laughren said, is that schizophrenia patients in clinical trials might be less sick than in the past — and those patients may be more likely to improve even if they are on a placebo. Another possibility is that earlier research was biased in support of the medication, while newer trials are more balanced.
But Laughren said more research is needed to figure out what’s really going on.
The trend is concerning, according to the FDA researchers, because clinical trials with big placebo responses are more likely to fail because they don’t show a statistically clear difference between the treated group and the placebo group.
The more often trials fail, the less interested drug companies will be in even trying to develop new schizophrenia drugs, Laughren said. And new treatments are needed, he added.
“We haven’t changed the standards for approving drugs,” Laughren said.
But it will be important to figure out why placebo responses are rising, he added. The FDA researchers are going to further investigate data on individual patients involved in these trials, to see if there are clues.
From there, Laughren said, it might be possible to design better studies. That could lead to changes in how studies measure symptoms to how long they follow patients, he noted.
Source: Journal of Clinical Psychiatry