The rise and fall of the blockbuster antipsychotic Seroquel

The advent of direct-to-consumer advertising made billion dollar blockbuster drugs possible for the first time. Often the drugs were rushed to market before their side effects were fully known or admitted like the cardiac side effects with COX-2 inhibitors like Vioxx and osteonecrosis of the jaw (ONJ) side effects with bone drugs like Fosamax and Boniva.

AstraZeneca’s popular antipsychotic Seroquel (quetiapine), approved in 1997 for schizophrenia, is a case in point. Even before Seroquel hit pharmacy shelves, its team leader at the FDA, Thomas Laughren, noted that “there were 16 additional deaths” and “16 additional overdoses with quetiapine” since the original database was compiled.

Soon afterward, an article in the South Dakota Journal of Medicine questioned Seroquel’s long-term safety and its safety when combined with eleven other drugs. And three years after Seroquel’s approval, researchers began questioning Seroquel’s effect on the heart, a risk that was not acknowledged by the FDA until years later.

Seroquel was nevertheless heavily marketed, often for the off-label indications of dementia, insomnia and Alzheimer’s disease in elderly patients despite clear label warnings about increased risk of death in that population. The British Medical Journal found that Seroquel was ineffective in reducing agitation among Alzheimer’s patients and actually made cognitive functioning worse.

In 2008, an AstraZeneca sales rep “made an unsolicited sales call to a physician at his office” and “stated that Seroquel was approved for treatment of Major Depressive Disorder (MDD),” charges a letter sent to James L. Gaskil, Director of AstraZeneca’s Promotional Regulatory Affairs from FDA Regulatory Review Officer Amy Toscano. AstraZeneca reps were even coached to sell Seroquel using the Winnie the Pooh figures like Tigger, for bipolar disorder, and Eeyore, for depression. When Seroquel was approved for bipolar disorder, ads sought to convince people they suffered from it in what is sometimes termed “disease mongering.”

Serious Seroquel side effects were seen in the military where its use increased 700 percent during the Iraq and Afghanistan wars. In a short period of time, Pfc. Derek Johnson, 22, of Hurricane, West Virginia; Cpl. Andrew White, 23, of Cross Lanes, West Virginia; Cpl. Chad Oligschlaeger, 21, of Roundrock, Texas; Cpl. Nicholas Endicott, 24, of Pecks Mill, West Virginia; and Spc. Ken Jacobs, 21, of Walworth, New York all died suddenly while taking Seroquel cocktails. Families of the five men, who had been previously healthy, and medical professionals suspected lethal heart effects from Seroquel. At the time of the military deaths, at least 99 articles in the U.S. National Library of Medicine linked Seroquel to “sudden death,” “QT prolongation” (a heart disturbance that can led to death), “cardiac arrest” and “death.”

Still, an investigation by the VA’s Office of Inspector General into the possible Seroquel-related deaths of two soldiers found “no apparent signal to indicate increased mortality” from Seroquel and/or its interaction with the other drugs.

Yet three years later, with little fanfare and as Seroquel’s patent was about to expire, the FDA changed its mind. It warned doctors and patients that Seroquel and Seroquel XR was indeed dangerous and “should be avoided” in combination with at least 12 other medications, including methadone, other antipsychotics, some antibiotics and heart rhythm drugs. The reason was heart risks. In fact, said the FDA, Seroquel should not be used at all by the elderly or by people with heart disease.

The rise and fall of Seroquel parallels that of other expensive blockbuster drugs marketed as “better” than existing drugs. Atypical antipsychotics like Seroquel were marketed as lacking the side effects of rigidity and tremor associated with older antipsychotics like Haldol and Thorazinem but a 2005 New England Journal of Medicine article found no advantages whatsoever. (Unless you consider price.)

Drug companies, as they price new drugs in the thousands of dollars and seek to dodge US taxes by incorporating overseas, are currently under the ethical microscope. Their march to Wall Street before their drugs’ risks are known or acknowledged should be thoroughly investigated.

This is an excerpt from Drug Injury: Liability, Analysis, and Prevention, 4th Ed. by James O’Donnell to be available from Lawyers & Judges Publishing Company, Inc. March 2016.

Martha Rosenberg is a freelance journalist and the author of the highly acclaimed “Born With A Junk Food Deficiency: How Flaks, Quacks and Hacks Pimp The Public Health,” published by Prometheus Books. Check her Facebook page.