Concerned about "suspicions" of overprescribing antipsychotic drugs, the Pentagon took steps in the last few weeks to limit the use of those powerful medicines to treat the growing legion of war fighters suffering from post-traumatic stress disorder.
For Stan and Shirley White, the limits can't go into effect soon enough because, in their case, it's already too late.
The retired educators' youngest son, Andrew, was an Eagle scout, a baseball player, and an honor student in high school near the family home in Cross Lanes, W.Va.
Following his brothers into the military, Andrew joined the Marine Corps Reserve. His unit went to Iraq in January 2005.
During about 300 missions, Andrew had a steady diet of death and destruction.
A combat engineer, Andrew cleared mines and improvised explosive devices from roads before they blew up his fellow Marines, soldiers, and civilians. After nine months, White was sent home and eventually received a medical discharge for PTSD.
"It changed him," Stan White said of combat. "He became a recluse. In the last four months of his life, he ate two meals with the family. He would take his food to his room."
On Feb. 12, 2008, when Andrew had failed to meet her for a planned lunch at a restaurant, Shirley White went home. She found him dead in his bed. He was 23.
The problem, Stan White said, is that Andrew had been taking what the father called a "lethal cocktail" of Paxil, Klonopin, and Seroquel, prescribed by the doctor treating Andrew at a nearby Veterans Administration hospital. Paxil is an antidepressant. Klonopin, generally prescribed for panic disorder, is in a group of drugs that military officials now discourage using.
Seroquel, an antipsychotic, is made by AstraZeneca P.L.C., a global drugmaker with U.S. headquarters in Wilmington. After initially taking 25 milligrams of Seroquel per day, Andrew was taking 1,600 mg per day when he died, his father said.
Andrew had episodes of problem drinking, but the coroner found no alcohol in his system and attributed his death to an accidental intoxication of drugs, Stan White said.
The 40 pounds that Andrew gained is one of the known side effects of antipsychotic drugs like Seroquel.
"We don't think they should be given to troops in the field," Stan White said. "It's worth asking whether they should be given to anybody anytime, civilian or military."
The Whites, who have testified before the U.S. Food and Drug Administration, were in Philadelphia last week during the American Psychiatric Association convention. The Whites spoke off-site to a gathering of the Citizens Commission on Human Rights, which was founded in 1969 by a psychiatrist and the Church of Scientology to fight the use of antipsychotic drugs.
The Whites are not members of the group. Stan was calm and composed in describing his son's situation, which is what you'd want from a retired assistant principal. But you could excuse the Whites if they were angry and bitter from the moment they get out of bed each day.
Five days after Andrew came home from Iraq, the family learned that their middle son, Robert, was killed by a rocket-propelled grenade while serving with the 82d Airborne Division in Afghanistan. Their oldest son, William, retired in July from the Navy after 26 years in the service. Daughter Christina is attending law school.
The Whites are advocating more money and greater emphasis on counseling for veterans. They said that Andrew seemed to benefit from peer-group meetings, but that the social worker he saw at the V.A. center had been laid off in the months before his death.
Too late for Andrew White, the V.A. said last month that it would hire 1,900 more psychiatrists, psychologists, social workers, and support staff to help veterans.
Beyond that, Stan White said, veterans and family members, even doctors, need to speak up.
"We all need to question the medications we're given," White said. "We didn't do that."
The Pentagon is doing more of that now.
On Feb. 22, Assistant Secretary of Defense Jonathan Woodson sent a memo to all branches of the military regarding PTSD with the message: "The greatest concern is the suspicion of the overprescription of antipsychotic medications for PTSD."
Pharmaceutical companies are prohibited from marketing drugs beyond uses approved by the FDA and included on label, all of which happens after clinical trials. Doctors can legally prescribe off-label as they see fit. Though they can't legally say it, drug companies hope doctors pick their products.
Several of the more-prominent antipsychotic drugs, in addition to Seroquel, are Abilify, Zyprexa, and risperidone, which is the generic version of Johnson & Johnson's Risperdal.
Some antipsychotic drugs are FDA-approved only for use in patients with schizophrenia and bipolar disorder. Depression is a less serious, but more widely diagnosed, mental illness than schizophrenia and bipolar disorder. Hoping for greater profit from a wider market, drug companies have sought FDA approval to add depression and other ailments to acceptable uses on the label. Seroquel XR, among others, have been approved for limited use with antidepressants, but they are not FDA approved for anxiety disorders or difficulty sleeping.
Only two antidepressants, and their generic equivalents, are FDA approved for PTSD: GlaxoSmithKline's Paxil (paroxetine) and Pfizer's Zoloft (sertraline).
Woodson noted that, militarywide, antidepressant use had changed little between 2002 and 2009, but that prescription rates for atypical antipsychotics increased during that period from 0.1 percent to 1 percent. In fiscal 2010, Seroquel was prescribed to 1.4 percent of Army personnel and 0.7 percent of Marines.
As of March 27, a service member taking any antipsychotic was disqualified from deploying to Iraq or Afghanistan without explicit permission from the Central Command surgeon, according to Army Lt. Col. Patrick Seiber, a spokesman for the Joint Chiefs of Staff.
"Seroquel was previously 'approved' as a sleep aid without any oversight — and that's the very thing that just changed," Seiber said via e-mail. "Seroquel is in the formulary, but prescribers must now request permission from the U.S. CENTCOM surgeon."
On April 10, the Army's Office of the Surgeon General issued a guidance memo for PTSD, including caution about antipsychotic drugs. "There are numerous concerns with potential long-term adverse health effects," the memo said, "and these medications have shown disappointing results in clinical trials in the treatment of PTSD."
Versions of Seroquel brought AstraZeneca nearly $6 billion in revenue last year.
An AstraZeneca spokesman said in a statement, "Seroquel is not approved for the treatment of PTSD or indicated for use as a sleep aid. Atypical antipsychotics, like many other medications, are often prescribed by mental-health professionals for indications beyond those set forth in the FDA-approved label. Like patients, we trust doctors to use their medical judgment to determine when it is appropriate to prescribe medications. Patient safety is a core priority for AstraZeneca, and we believe that Seroquel is a safe and effective medication when used as recommended in the prescribing information."
The psychiatrist convention's product-exhibition hall served to illustrate the challenging and, perhaps conflicting, situation of mixing the military and antipsychotic drugs.
Like other companies, AstraZeneca had a big display for Seroquel, hoping visiting psychiatrists would remember it when they wrote prescriptions.
Down the aisle was a much smaller display for the U.S. Navy, manned by Joseph Rawson, chief petty officer and medical recruiter, who is from Northeast Philadelphia.
"The Navy," Rawson said, "is trying to rebuild its mental-health capabilities."
Contact David Sell at 215-854-4506 or firstname.lastname@example.org, or follow on Twitter @PhillyPharma. Read his PhillyPharma blog on philly.com.