A recent study by researchers at Stanford and the University of Chicago found that a significant proportion of prescriptions for atypical antipsychotics, currently the top-selling class of drugs in the United States, lack sufficient evidence for their effectiveness.

Atypical antipsychotics are a newer generation of antipsychotic medications introduced to the market in 1989. While their “typical” first-generation predecessors target dopamine pathways in the brain thought to be the origins of psychotic symptoms, atypical drugs address a variety of other neurotransmitters whose influences are less obvious but equally significant.

“What we were interested was, first of all, the shift from the older generation to the newer generation,” said Randall Stafford, senior author of the study and associate professor of medicine. “And then also among all of the uses, to what extent were antipsychotic medications being used for conditions that were not part of their FDA approval for the drug.”

The study tracked prescriptions of both typical and atypical antipsychotics between 1995 and 2008 using data from a physicians’ survey by private health-care information company IMS Health.

“Basically what we found was that there was a substantial use–actually more than half of the uses for the newer-generation antipsychotics did not have strong evidence behind them,” Stafford said. “Not only were these uses not approved by the FDA, they didn’t even have the sort of evidence that we expect of drugs that are going to be widely used.”

Physicians frequently prescribe atypical antipsychotics to address illnesses for which their effectiveness has yet to be proved by the FDA. These illnesses include other psychoses, autism, bipolar disorder, delirium, dementia, depression and personality disorders. Side effects range from weight gain to diabetes to heart disease.

“When drugs are approved, it’s not a blanket approval. It’s approval for a very specific use,” he said. “For instance, although antipsychotics could be used for a whole range of psychiatric conditions, many of them were first approved for schizophrenia and over time have gradually been used for many other psychiatric conditions.”

The study determined that prescriptions for atypical antipsychotics nearly tripled to 16.7 million in 2008 from 6.2 million in 1995, and Stafford estimates that in recent years, $15 billion per year has been spent on the drugs. Of the $6 billion spent in 2008 for off-label uses, $5.4 billion was for uses with “uncertain evidence.”

“At best, what we have here is practice getting ahead of the evidence,” he said. “At worst, what we have is practice being influenced by the substantial marketing that went on for these drugs.”

Stafford suggests that the major solution to preventing unfounded prescriptions lies in curbing the advertising done by pharmaceutical companies in order to provide consumers–both patients and physicians–with “objective information about the drugs.” Although consumers have won hundreds of millions of dollars from the companies in what is the single largest class of litigation filed under the federal False Claims Act, this remains an insignificant financial blow to the industry.

“For physicians, part of the message here is that we need to be careful about the medications we’re using, particularly if those medications have serious side effects,” Stafford said. “From the consumer point of view, I think it’s always worth asking physicians, ‘What’s the evidence that leads you to believe that this drug will be helpful for me?’”

However, Stafford remains hopeful about the future of atypical antipsychotics and their ability to effectively aid most patients. For example, the study found a decrease in prescriptions between 2006 and 2008 after the FDA issued a “black box” warning against in the drugs in 2005 because of their role in increasing the risk of death for patients with dementia.

“My hope is that they will be some recalibration of the use of these medications, and that their use will be more appropriate in the future,” Stafford said. “There’s greater attention on these drugs. And in all likelihood that will result in better practices and more evidence-based practice.”

Contact Ellora Israni at [email protected].