Studies of drugs that treat schizophrenia, what are also known as antipsychotics, are having fewer effects over time β€” and it's not because these drugs are becoming any less effective. Rather it's because patients are responding better to placebos – and it's not immediately obvious why this is happening.

Antipsychotics have been helping schizophrenics manage their symptoms β€” such as hallucinations and delusional thinking β€” for decades. For many people, these drugs have been indispensable, allowing schizophrenics to live a relatively normal life. But a strange thing has been happening since the introduction of second generation antipsychotics nearly 20 years ago: clinical trials of these drugs have been finding less dramatic effects, compared with trials from the early 1990s.


What this means is that the impacts of the drugs are narrowing over time, when you compare patients who are taking the real thing to people who are given a placebo.

The discovery was recently made by the Food and Drug Administration, which recently concluded a meta-analysis of 32 clinical trials that were submitted to the agency between 1991 and 2008. The trials, which involved 11,567 patients, showed a tendency towards decreased effects, compared to older studies.


But the FDA says this wasn't because the new drugs were ineffective β€” it was because patients given placebo pills were starting to show more significant responses. The researchers are stumped.

Dr. Thomas P. Laughren, head of the FDA's division of psychiatry products and one of the researchers on the study, speculates that schizophrenics may be less severely affected by the condition than they were a few decades ago. Consequently, they may be more likely to improve, even if they are on a placebo.


But on the face of it, that sounds like a very unsatisfactory answer. There's no reason to believe that schizophrenics are exhibiting weaker symptoms, or that they would respond differently to placebos more or less than anyone else.

PalMD at White Coat Underground offers a different explanation, what he refers to as the "decline effect":

The early studies of the new drug may have captured a less random moment in time. As more and more people are treated, there is a "regression toward the mean", with more studies giving us more accurate (and less impressive) numbers. There may also have been some publication bias, in which studies with interesting positive results were more likely to be submitted and published.

What is less likely is that something about placebos has changed. While placebo [effects] increased, there may be many explanations for this. Study design can affect placebo response considerably, as can measurement biases. But since placebos don't change, they're not to blame.


Which are all excellent points β€” we clearly need to start asking smarter questions about what exactly is going on.

That said, the news of drugs' declining effectiveness is clearly not good. If the trend continues, the FDA worries that pharmaceutical companies will stop trying to develop these drugs β€” the more often their trials fail, the less inclined they will be to spend the money on new research projects.


To deal with the situation, Laughren has said that FDA researchers need to take a closer look at data on individual patients involved in these trials, to find some clues as to why this is happening.

The FDA study can be access here.

Via Reuters. Image via Ten Eyck (JTeffects).