Even as a US District Court prepares 6,000 Seroquel lawsuits for trial, Eli Lilly pays $1.42 billion for illegal Zyrexa marketing and 30 states sue over heisted Medicaid funds for atypical antipsychotics, an FDA advisory panel has recommended approval of Seroquel, Zyrexa and Geodon for children.
After two days of hearings, the FDA Psychopharmacologic Drugs Advisory Committee voted to recommend approval of AstraZeneca's Seroquel (quetiapine) for the acute treatment of schizophrenia in adolescents 13-17, acute treatment of bipolar mania in children 10-12 and adolescents 13-17; 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 10-17; 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, the uncategorizable and the suggestible --are you sure you don't have racing thoughts ask ads?--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 also known as "sudden death."
Who knew the atypicals, along with tremor and muscle rigidity, could cause the permanent and stigmatizing tardive dyskinesia they were developed to prevent? Hello?
Of course AstraZeneca doctor Liza O'Dowd 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 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, MD 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, MD asked why not, then, remove instructions to examine patient lenses from the prescribing information.
AstraZeneca presenter Lili Kopala, MD was certain the study suicides stemmed from patients who were "still on the recovery curve," but when panelist Christopher Granger, MD 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, MD? 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, MD, and "once we get them off," they might just have a learning disability.
Worse than problems diagnosing pediatric bipolar or schizophrenia--3,000 suspected childhood schizophrenia cases yielded only 110 actual cases in one study said panelist Nitin Gogtay, MD--and worse than the lack of "real world" and mixed medicine "cocktail" studies was the brevity of the studies themselves said panelists.
How can three and six week studies suggest safety for maintenance treatment of schizophrenia and bipolar disorders which lasts decades? "We know they won't stop [using the medications] at the acute phase," said Towbin.
Panelist Granger confessed to "real discomfort" approving drugs which "generat[e] 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, MD.
But Thomas Laughren, MD, 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, MD of Pfizer thanked him.
Frank Greenway, MD, 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 ever 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 unabashed referred 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, TX 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, TX 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."