Downer for SSRI Makers

The multi-billion-dollar SSRI market has for years been a source of joy for drug makers working in the space. But these popular antidepressants may not be as effective as once thought, leaving SSRI patients wondering if they're on the right meds--and pharma companies clambering for a stake in a different reuptake-inhibitor market.

The potential blow came last week in the form of a Journal of the American Medical Association study, which suggests that about half of patients currently treated with selective serotonin reuptake inhibitors (SSRIs) would be better off on another antidepressant.

"SSRIs are the most widely used first-line drugs," said study author Bernard Carroll, scientific director at the Pacific Behavioral Research Foundation. "The trade-off is that while they're somewhat effective, they're not barn burners."

The JAMA study, which followed 241 Korean patients over five years, found a link between gene polymorphisms and a patient's response to different classes of drugs for late-life depression.

If clinicians treated patients based on these polymorphisms, the most commonly used drugs would be norepinephrine reuptake inhibitors (NRIs) rather than the more popular SSRIs. Of the 189,500 antidepressant prescriptions dispensed last year, more than 100,000 were for SSRIs, according to information from Verispan and IMS. The total category of antidepressants, of which SSRIs make up more than half, is valued at $12.5 billion.

NRIs, which were first introduced in the 1950s, fell out of favor as a primary treatment because of undesirable side effects. Carroll points out, though, that if clinicians evaluated patients for the presence of gene polymorphisms, the benefit of using an NRI could outweigh the side effects--thereby reducing SSRI use by as much as 50 percent. The JAMA paper could also lead to research on new targets for drugs that work like NRIs, but have a more acceptable side-effect profile, Carroll noted.

In the JAMA study, about 56 percent of Koreans and 45 percent of Caucasians had the GG genotype, which was associated with higher response rates to an NRI (83 percent) rather than an SSRI (59 percent).

Although prescriptions for SSRIs have been falling fast--four percent between 2004 and 2005--because of concerns about suicide risks, they remain one of the top-five most commonly prescribed drugs, according to Verispan. Last year's top-selling antidepressant, Pfizer's Zoloft (sertaline), which went off patent in June, is an SSRI. So is the third-most successful antidepressant, Forest Labs' Lexapro (escitalopram), which brought in $1.87 billion in the last fiscal year.

But companies that make SSRIs shouldn't panic yet.

"We all sort of knew [that genes play a role in treatment outcomes], but we didn't know what to do about it," Andrew Farah, chief of psychiatry and medical director at High Point Regional Health Systems in North Carolina, said about the findings. With no way to test patients for these polymorphisms in a clinical setting, "we've had only crude ways of pointing us in the right direction," he said.

"This study confirms what we know," Farah said, "but it's still too research-based at this point."