(Martha Rosenberg)
After two days of hearings, the FDA Psychopharmacologic Drugs Advisory Committee voted to recommend approval of the following: AstraZeneca’s Seroquel (quetiapine) for the acute treatment of schizophrenia in adolescents 13 to 17, acute treatment of bipolar mania in children 10 to 12 and adolescents 13 to 17; Pfizer’s Geodon (ziprasidone) for the acute treatment of manic or mixed episodes associated with bipolar disorder, with or without psychotic features, in children and adolescents ages 10 to 17; and Eli Lilly’s Zyprexa (olanzapine) for the acute treatment of manic or mixed episodes associated with bipolar I disorder and acute treatment of schizophrenia in adolescents.
Most people know pharma’s blockbuster atypical antipsychotics Seroquel, Zyprexa, and Geodon, off-label marketed to kids, the elderly, and the suggestible correlate with weight gain, diabetes, and metabolic derangement.
But who knew until the hearings that Seroquel also causes an extra seven or eight heart beats a minute in children—possibly for as long as they take it—with no studies to show the long-term effect or the safety of drugs to treat the effect? And no theory as to why.
Who knew Seroquel could cause cataracts?
Who knew Geodon could cause a prolonged QT interval [heart electrical conduction problem], which predisposes to “sudden death”?
Who knew that the atypicals, along with tremor and muscle rigidity, could cause the permanent and stigmatizing tardive dyskinesia they were developed to prevent?
Of course AstraZeneca doctor Liza O’Dowd, M.D., did her best during her presentation to sail through the negatives—assuring the panel that Seroquel’s blood pressure, weight, glucose, and prolactin issues could be “controlled and monitored” and that they “didn’t lead to discontinuation of the study.” (Let’s hope not when the trial was for only three weeks.)
But she was less forthcoming when discussing the five child suicides seen during trials, a slide she only produced in response to panel questions.
AstraZeneca’s Ihor Rak, M.D., did his best to dismiss cataract problems as “poor hygiene, nutrition, and accidents” seen with schizophrenics but had no ready answer when panelist member Benedetto Vitiello, M.D., asked, then why not remove instructions to examine patient lenses from the prescribing information?
AstraZeneca presenter Lili Kopala, M.D., was certain the study suicides stemmed from patients who were “still on the recovery curve,” but when panelist Christopher Granger, M.D., challenged her, she changed her mind and said, “They may be random.”
And panelists had other questions.
Not being trained psychiatrists, how did you make the differential diagnosis of bipolar for your studies, asked panelist Kenneth Towbin, M.D.? How do you know irritability, anxiety, or aggression don’t denote other disorders? How could a Seroquel study in which children with mania are kept on stimulants be scientifically valid or ethical?
Children are often on “cocktails of seven or eight medications” agreed Rochelle Caplan, M.D., and “once we get them off,” they might just have a learning disability.
Panelist Nitin Gogtay, M.D., said that 3,000 suspected childhood schizophrenia cases yielded only 110 actual cases, according to one study. Worse than problems diagnosing pediatric bipolar or schizophrenia and worse than the lack of “real world” and mixed-medicine “cocktail” studies was the brevity of the studies themselves, panelists said.
How can three- and six-week studies suggest safety for maintenance treatment of schizophrenia and bipolar disorders, which last decades? “We know they won’t stop [using the medications] at the acute phase,” said Towbin.
Panelist Granger confessed to “real discomfort” approving drugs that “generate metabolic syndrome in adolescents in a very short period of time” for “indefinite use” on the basis of three or six week trials. “Hopefully we’re not exposing someone for decades,” agreed fellow cardiologist Edward Pritchett, M.D.
But Thomas Laughren, M.D., FDA’s director of psychiatric drugs was more upbeat. Not only was he sure pediatric safety could be extrapolated from adult studies—promising to include the clinical leap on labels—he didn’t want to be derailed over the two children who perversely died from stroke and cardiopulmonary failure in Geodon studies either.
There’s “hazard in drawing too much from subsetting the data,” said Laughren. Phillip Chappell, M.D., of Pfizer thanked him.
Frank Greenway, M.D., an endocrine specialist on the panel, was also upbeat; observing prolactin elevation from the atypicals was less than a “prolactin-secreting tumor.” Whew!
Still the elephant in the room at the proceedings was why drugs that are already available off-label need FDA approval at all—and why it’s urgent that kids showing symptoms be treated now.
One pharma doctor claimed gray matter shrinks every time someone is “psychotic,” but others admitted early treatment has no effect on the course of the diseases.
The answer of course was in the other elephant in the room—the wall of 40 pharma-funded doctors sitting at attention, outnumbering FDA representatives two to one and unabashedly referred to as “sponsors.” (Though their Medicaid streams imply that’s backwards.)
It’s the sponsors who exhort doctors—and parents—to subject kids to increased heart beat, sudden death, metabolic syndrome, tardive dyskinesia, cataracts, stroke, and suicidal side effects for diseases they may not even have.
Certainly that’s how two mothers who testified during the open public hearings felt.
Liza Ortiz of Austin, Texas, lost her 13-year-old son to Seroquel toxicity earlier this year. “His hands twisted in ways I never thought possible in the I.C.U., “ she said.
Mary Kitchens of Bandera, Texas, said her son suffers from crossed eyes, nightmares, trembling, neutropenia, hypothyroidism, tachycardia, dyskinesia, and cogwheeling since Seroquel treatment.
“AstraZeneca marketed this to my child in 2003,” she said, holding the original Seroquel package for the panel to see. “And now they want your seal of approval.”
Martha Rosenberg is a freelance writer living in Chicago.
