AS THE TMAP PANEL MEMBERS worked on the protocols, drug companies aggressively promoted the new antipsychotics across the psychiatric landscape. Their key selling point: that they were more effective and caused fewer serious side effects than the older antipsychotics, especially Haldol, the most widely used. Though it did approve six atypicals, the FDA was dubious of some of these claims. "We would consider any advertisement or promotional labeling for Risperdal false, misleading or lacking fair balance… if there is a presentation of data that conveys the impression that [Risperdal] is superior to [Haldol] or any other marketed antipsychotic drug product with regard to safety or effectiveness," an FDA official wrote in a 1993 letter to Janssen Pharmaceutica. But the letter was only made public years later, when journalist Robert Whitaker quoted it in his 2002 book, Mad in America. Most prescribing doctors were left in the dark. (For more on how drug companies manipulated clinical trials for atypicals see motherjones.com/spinningdoctors.)

The largest study to date, a review of 52 clinical trials including more than 12,000 patients published in the British Medical Journal in 2000, found "no clear evidence that atypical antipsychotics are more effective or better tolerated than conventional antipsychotics." A 2003 study comparing Zyprexa, the top-selling atypical antipsychotic, and Haldol, published in the Journal of the American Medical Association, found the new drug "does not demonstrate advantages compared with [Haldol]… in compliance, symptoms… or overall quality of life."

The new drugs now appear to be associated with higher suicide rates and to cause tardive dyskinesia, too, though perhaps at lower rates than the first-generation drugs. They can cause rapid weight gain and thus an increased risk of diabetes. In September 2003, the FDA required the makers of all atypicals to add to their labels a warning that the drugs can cause hyperglycemia, diabetes, and even death. Janssen was also made to send doctors a letter conceding it had misled them when it said that Risperdal does not increase the risk of diabetes. In fact, the company had to admit, it probably does.

When TMAP's schizophrenia algorithm was finalized in 1997, however, it did exactly what industry representatives must have hoped for: It called for the newest, most expensive drugs—five atypicals—to be used first. If a patient does not respond well to one of those drugs, a second member of this group should be tried. If that drug also fails, a third drug should be tried, this time either another atypical or an older antipsychotic. The guidelines for major depression and bipolar disorder similarly favor new drugs.

"When [the drug companies] saw the newer medications were there, they liked that, of course," says Shon. "I know that has raised questions in people's minds: 'Why are the newest, most expensive first?' Well, the newest, most expensive are either the most efficacious and/or the safest."

But that assertion is increasingly disputed. "When atypicals came out, they looked a little better in effectiveness and a lot better in terms of side effects," says Mike Hogan, Ohio's mental health director and former chairman of President Bush's New Freedom Commission on Mental Health. "These days, they look perhaps a tiny bit better in terms of effectiveness, but increasingly it's not clear whether the side-effect profile is better or just different."

Ohio adopted a TMAP-like algorithm in 2001 but with a critical difference. According to Hogan, it's merely a guideline for prescribing doctors to consider. But in Texas, state officials put far more pressure on its physicians to follow the protocols. Under regulations codified by the legislature in 1999, doctors in state-owned and state-funded mental health entities must follow the algorithm, or justify a different course with a note in a patient's file—a hurdle that sends the message that such deviation should be the rare exception.

As the TMAP guidelines began to be adopted in 1997, Texas Medicaid spending on the five atypical antipsychotics skyrocketed from $28 million to $177 million in 2004.

MANY DOSES OF THESE DRUGS went to patients like Aliah Gleason. She was one of 19,404 Texas teenagers prescribed an antipsychotic in July or August of 2004 through a publicly funded program, according to ACS-Heritage, a medical consulting firm hired by Texas to investigate the use of psychotropic drugs on children. Nearly 98 percent were atypical antipsychotics—unapproved for children and prescribed "off-label," a controversial practice in which doctors legally prescribe FDA-cleared drugs to patients, such as children, or for conditions, such as depression, for which they are not approved. The report found that more than half of the doses for antipsychotics appeared inappropriately high, that almost half did not appear to have valid diagnoses warranting their use, and that one-third of child patients were on two or more medications.

When she was transferred from Austin State Hospital to a residential facility on March 18, 2004, Aliah was on five different medications, putting her on the extreme end of a growing practice known as polypharmacy that worries many doctors. "This is a complicated regimen using powerful psychotropic medications in a barely adolescent girl, so I would be quite concerned about it," says Dr. Joseph Woolston, a Yale University professor and chief of child psychiatry at Yale-New Haven Hospital. "It isn't grossly, acutely dangerous, but it is sedating and would make it difficult for a child to experience the world in a normal way. If you or I were on that regimen we would have a lot of trouble attending to work or school. We don't have any idea what that combination of medications does to a developing child. It may have a number of long-term side effects." He also suspects that the drugs may have been used as much to control the angry reactions of a girl who was hospitalized against her will as to treat any mental and emotional problems.

Dr. Clifford Moy, clinical director of Austin State Hospital, says that while the hospital's philosophy is to avoid using more than one member of any particular class of psychiatric medication, using multiple drugs from different classes is often the best way to treat a patient with multiple symptoms. While declining, for privacy reasons, to discuss Aliah's treatment, he said medication and restraint would never be used for punitive purposes or merely to promote compliance with hospital rules, but only in the case of a "significant emergency behavioral situation." He added that forced injection of an antipsychotic—which happened to Aliah several times—might be used "if there were a legal consent for an oral antipsychotic medication, which the patient refused." Such consent was apparently provided, in Aliah's case, by the Department of Protective and Regulatory Services.

The 46-bed child and adolescent wing where Aliah stayed was not, like the rest of Austin State Hospital, obligated to follow TMAP. Its treatment regimens were influenced more by CMAP, the children's algorithm not yet mandated by the legislature. CMAP steers clear of providing protocols for schizophrenia and bipolar disorder—the disorders that atypicals were designed to address—in part, says DSHS's Doug McBride, because there's "little scientific evidence" as to what the appropriate regimen for kids would be. CMAP does, however, call for combining atypicals with antidepressants for children diagnosed—as Aliah was—as suffering from depression "with psychotic features." McBride defends such off-label use of prescription drugs, saying that the FDA approval process "is not the end of clinical and other scientific evidence on the use of that medication."

Beyond their technical dictates, the algorithms established a culture that affected which medications were prescribed. Steven Shon, who, along with his colleagues, had led training sessions for the staff of Austin State Hospital, argues that the algorithms were designed to prevent irrational and excessive medication. Yale's Woolston agrees with the goal, though not necessarily the reality. "Algorithms are supposed to cut down on people using medications inappropriately and to take into account medication interaction," he says. "Where they become a problem is when people use them as a mandate, forget their own clinical judgment, and believe that when you're in doubt, you're supposed to move forward in the algorithm and add more medication."

Medications can be invaluable, and some patients say their lives have been transformed by atypicals. But algorithms reinforce the perception in both psychiatry and popular culture that mental problems always require drug treatment. "An algorithm may put blinders on a psychiatrist and create the presumption that the only clinical approach to problems is to use medications," Woolston says. If a patient doesn't respond to a particular medication, a doctor relying on an algorithm may think they need to use or add a different medication, he says. "But sometimes, the best approach is to say, 'Medication isn't working; let's try something else.'"

ONCE THE DEVELOPMENT of the algorithms was largely complete, Shon began hitting the road, making about one trip a month—often at the expense of drug companies—to spread the TMAP gospel to officials in other states. This close relationship between TMAP and the pharmaceutical industry raises disturbing questions about whether the drug companies were wielding undue influence or profiting at the expense of patients. But no one raised these questions until 2002, when Allen Jones, an investigator for the state of Pennsylvania's Office of Inspector General (OIG) began to look into a complaint that mental health officials had set up an unorthodox bank account to collect money from drug companies.

Jones, a lanky, 50-year-old chain-smoker, had spent several years with the OIG in the late '80s and early '90s, but left to pursue real estate investing to pay for his daughters' college tuition. He had only just rejoined the agency in the summer of 2002 when he began investigating this case. Over several months, he interviewed state officials, traveled to New York and New Jersey to question pharmaceutical company executives, and learned all he could about TMAP. He soon felt that something inappropriate, and possibly illegal, was going on. "It just did not pass the smell test," he says.

Jones learned that in early 2000, Dr. Steven Karp, who was then medical director of the state's Office of Mental Health, had become interested in implementing a Pennsylvania version of TMAP. Karp discussed his interest with executives of Janssen Pharmaceutica, Jones found, and the company paid for Shon to come to Pennsylvania in late 2000 to meet with Karp and Steven Fiorello, the state's chief pharmacist. Shon returned in March 2001 to train state medical personnel, according to records Jones obtained and provided to Mother Jones. To cover Shon's travel expenses, Janssen made an "educational grant" of $1,765.75. A Janssen funding request form notes that the grant was to support the "TMAP initiative to expand atypical usage and drive Steve Shon's expenses." A box marked "Risperdal" is checked on the form. Janssen's check was sent to Fiorello and placed in the account where other donations from pharmaceutical companies were deposited.

Two months later, Janssen provided $4,000 for Fiorello and a state psychiatrist to travel to New Orleans for meetings with Dr. Madhukar Trivedi, a UT-Southwestern psychiatrist and TMAP project team director. The funding request form for this payment listed the "deliverable" as the "successful implementation of PennMAP." A Janssen representative also attended and paid for $80-per-person dinners for the Pennsylvania and Texas officials. Fiorello and the psychiatrist made another trip to New Orleans later that year, also paid for by Janssen, according to Jones. Such perks, while of no great consequence to a company the size of Janssen, did forge a friendly relationship with Pennsylvania officials whose decisions carried enormous financial stakes for the company.

Fiorello told Jones he was the state's "point man" for selecting drugs for the state formulary—those used in state hospitals—and that industry representatives visit him often "to ensure access of their drugs to the state system," Jones wrote in a file memo as he pursued his investigation. In April 2002, Fiorello and Dr. Frederick Maue, clinical director for the state's Department of Corrections, spoke at a Janssen-sponsored symposium for prison doctors and nurses on treating mentally ill offenders. They were paid $2,000 by Comprehensive NeuroScience, a marketing firm working for Janssen that helped shape their presentation. Another marketing company hired by Janssen appointed Karp to its advisory board, flying him to meetings in Seattle and Tampa. Pfizer put Fiorello on an advisory council and twice paid his expenses to come to New York.

Jones became convinced that, as he puts it, "the pharmaceutical companies were buying influence with key decision makers in state government, trying to turn their drugs into blockbusters." But as he brought these findings to his boss, Daniel Sattele, he was told to stop pushing so hard. After he was barred from investigating whether state officials had received inappropriate payments from drug companies, Jones sued in federal court, alleging that "major public corruption investigations were being delayed, obstructed, or otherwise hindered by officials in the OIG." Sattele subsequently conceded in a deposition taken in 2003 that he asked Jones if he were "a salmon," telling him, "go with the flow, don't swim against the current." Sattele also said that after Jones came to him with his concerns for the fourth or fifth time, he reminded Jones of the industry's power and influence. "I said, 'Allen, pharmaceutical companies are very aggressive in their marketing…. They probably donate to both sides of the aisle,'" he recalled in the deposition.

When Jones continued to pursue the case he was removed as lead investigator, then pulled off altogether, he says. Nonetheless, over the coming months, he quietly copied documents and, on his own time, gathered more information.

In February 2004, Jones laid out his charges for the New York Times and the British Medical Journal. In April he was suspended. In May he again sued in federal court, charging that his superiors were harassing him to "cover up, discourage, and limit any investigations or oversight into the corrupt practices of large drug companies and corrupt public officials who have acted with them." He was then fired. He is now working as a bricklayer; both his actions are pending.

A spokeswoman for the Pennsylvania Office of Inspector General declined to comment on Jones' allegations or his termination. A representative of the Department of Corrections told Mother Jones that Maue donated the honorarium he was given by Comprehensive NeuroScience to the state's general fund. And Stacey Ward, a spokeswoman for the Department of Public Welfare, said that the state "did not receive contributions of any kind from any pharmaceutical company to study or support the implementation of PennMAP." [Ed note: After the print edition of this story went to press, the Pennsylvania State Ethics Commission fined Steven Fiorello, the state’s chief pharmacist, $27,000 for using his position to earn extra income from sources that included Pfizer.]

Meanwhile, another Pennsylvania official was becoming increasingly alarmed with how drugs being pushed by the pharmaceutical industry were actually affecting patients. Dr. Stefan Kruszewski, a Harvard-trained psychiatrist working for the state's Department of Public Welfare, was charged with reviewing psychiatric care provided by state-funded agencies to identify cases of waste, fraud, and abuse. In the summer of 2001, he began documenting examples of what he calls "insane polypharmacy" and widespread use of drugs for reasons not approved by the FDA. Most shocking to him were the cases of children placed in state-funded residential treatment facilities, sometimes for years, and heavily drugged on the new antipsychotics and anticonvulsants, including some of the same medications given, off-label, to Aliah Gleason.

"These kids were on multiple medications without the clinical diagnoses to support the medications," Kruszewski says. One drug, Neurontin, approved for controlling seizures, "was being massively prescribed for anxiety, social phobia, PTSD, social anxiety, mood instability, sleep, oppositional defiant behavior, attention deficit disorder. Yet there's almost no evidence to support these uses in adults and no evidence for kids whatsoever."

Last year a Pfizer subsidiary pleaded guilty to criminal fraud and agreed to pay $430 million in fines for promoting off-label prescribing of Neurontin, which racked up $2.8 billion in U.S. sales in 2004. Officials estimate that off-label uses account for some 90 percent of its sales. New York attorney Andrew Finkelstein says he's been enlisted by the relatives of 425 people who committed suicide while on Neurontin, and thus far has filed 46 lawsuits against Pfizer.

Kruszewski sent memos to his bosses about dangerous off-label uses of these medications but says they were ignored. He also looked into the deaths of four children in residential programs and submitted a report on an Oklahoma facility, where Pennsylvania children were sometimes sent. He found that many of the kids "were severely overmedicated" with atypical antipsychotics, antidepressants, and anticonvulsants, and he theorized that the death of at least one child could be attributed to a culture that combined polypharmacy and neglect.

His report earned him no plaudits. The day after submitting it, he says, he was yelled at for "trying to dig up dirt." The next day he was fired and escorted to the street. He has since filed suit in federal court against the state officials who fired him, along with several drug companies that, he charges, have "distorted statistics, violated regulations… and misrepresented the effects of the use of their psychotropic drugs… simply to make money." (The Pennsylvania Department of Public Welfare declined to comment on Kruszewski's charges because of his pending lawsuit.) Months after he was fired, Kruszewski alternates between anger and sorrow as he thumbs through documents piled in the dining room of his Harrisburg home. "I get very emotional about these reports," he says. "The people who were paid to protect consumers did exactly the wrong thing."

UNLIKE SOME OTHER HEAVILY medicated children, Aliah Gleason survived. In June 2004, more than five months after she was taken from school, Calvin and Anaka Gleason saw their daughter for the first time—in a courtroom. "I was so excited," Aliah recalls. "I hid under the table so I could surprise them. I started crying when I saw them. I thought I would never see them again."

It would take another four months of legal wrangling with the state before a district court judge ordered Aliah released into her parents' custody. Finally, the Gleasons were allowed to choose the people who would treat their daughter. They selected Austin psychologist John Breeding, a well-known critic of the overuse of psychiatric medications, and soon the whole family began meeting with him.

The first priority, Breeding said, "was to get her off the medication." Working with the family's doctor, he helped design a program for tapering her off her final drugs, Risperdal and Depakote, a process that was completed by the end of last year. He says the goal now is to help her recover from the emotional wounds she suffered as a result of her time under the state's care. She also needs to lose all the weight she gained while on the atypicals.

The good news, he says, is that "the family is reunited, she's doing well in school, and is even participating in extracurricular activities." Like her sisters, Aliah plays in the school band and also takes part in a drill team. "She's coming back, starting to get that gleam in her eye," Breeding says.

Aliah found herself at the intersection of a capricious child-protection system and a health care system that's all too ready to medicate. As doctors dispense ever-greater quantities of potent psychiatric drugs, and the industry spends ever-greater amounts of money promoting them, how can consumers be confident that decisions about their care are truly informed and in their interest? Whatever the stakes for the drug companies, the stakes for patients are infinitely higher.

Rob Waters has written extensively on the use of psychiatric medication by children. Last year he revealed in the San Francisco Chronicle that the FDA suppressed an internal report linking antidepressants to an increased risk of suicide among children, a story that led to congressional hearings and warnings being issued for the drugs.