Making Drugs, Shaping the Rules
Melody Petersen, New York Times- 2/1/2004

The drug industry has created vast markets for products like Viagra, Celebrex and Vioxx by spending billions of dollars on consumer advertising. But to sell medicines that treat schizophrenia, the companies focus on a much smaller group of customers: state officials who oversee treatment for many people with serious mental illness. Those patients -- in mental hospitals, at mental health clinics and on Medicaid -- make states among the largest buyers of antipsychotic drugs. For Big Pharma, success in the halls of government has required a different set of marketing tactics. Since the mid-1990's, a group of drug companies, led by Johnson & Johnson, has campaigned to convince state officials that a new generation of drugs -- with names like Risperdal, Zyprexa and Seroquel -- is superior to older and much cheaper antipsychotics like Haldol. The campaign has led a dozen states to adopt guidelines for treating schizophrenia that make it hard for doctors to prescribe anything but the new drugs. That, in turn, has helped transform the new medicines into blockbusters.
     Ten drug companies chipped in to help underwrite the initial effort by Texas state officials to develop the guidelines. Then, to spread the word, Johnson & Johnson, Pfizer and possibly other companies paid for meetings around the country at which officials from various states were urged to follow the lead of Texas, according to documents and interviews that are part of a lawsuit and an investigation in Pennsylvania.
     How did this play out? In May 2001, as Pennsylvania was weighing whether to adopt the Texas guidelines, Janssen Pharmaceutica, a Johnson & Johnson subsidiary that sells Risperdal, paid $4,000 to fly two state mental health officials to New Orleans, where they dined at an elegant Creole restaurant in the French Quarter, visited the aquarium and met with company executives and Texas officials, according to documents. Janssen also paid two Pennsylvania officials $2,000 each for giving speeches at company-sponsored educational seminars for doctors and nurses working in the state's prisons.
     The payments were discovered a little more than a year ago by Allen L. Jones, an investigator in the inspector general's office in Pennsylvania, who stumbled upon them when he was looking into why state officials had set up a bank account to collect grants from pharmaceutical companies. With the help of his congressman in Pennsylvania, Mr. Jones, who is 49 and a former parole officer, brought the information to the attention of federal health officials -- after, he says, his superiors removed him from the investigation, citing the political influence of the drug industry. The Department of Health and Human Services has asked the health care fraud unit of the Federal Bureau of Investigation to determine whether any laws were broken, according to letters Mr. Jones has received from federal officials.
     Details of the drug companies' efforts, recorded in Mr. Jones's investigative files and confirmed in part by drug companies and state officials, offer a glimpse inside the drug industry's behind-the-scenes efforts to promote the new-generation antipsychotics, called atypicals because their action in the body is unlike that of earlier drugs.
     There is no proof that drug-industry money changed any state official's opinion about the drugs. And compared with the billions of dollars spent marketing to doctors from their first days as medical students -- or the billions spent to underwrite and publish research -- the dollar amounts are small.
But questions have multiplied about the many ways that the drug industry tries to influence the medical information that determines its products' success or failure. Last month, for example, some senators sharply criticized the National Institutes of Health for allowing its scientists to accept consulting fees and stock options from drug and biotechnology companies. Officials of the agency said that its top-level scientists were no longer accepting such compensation.
     Sales of the new antipsychotics totaled $6.5 billion last year, according to an estimate by Richard T. Evans, an analyst at Sanford C. Bernstein & Company. About a third of those sales were to state Medicaid programs, whose costs have ballooned with their adoption of the new medications. Texas, for example, says it spends about $3,000 a year, on average, for each patient on the new drugs, versus the $250 it spent on older medications. The escalating costs have prompted a few states to try to limit access to the new antipsychotics -- efforts that drug makers have opposed vigorously.

Report on Smoking Is Broken Down by Ethnicity
Reuters News Service, 2/1/2004

WASHINGTON - American Indians and Alaska natives are more likely to smoke than any other group in the United States, with 40 percent of adults defined as smokers, the Centers for Disease Control and Prevention said this week. People of Chinese descent were the least likely to smoke, with just 12 percent reporting that they had smoked a cigarette in the past month, said the agency survey, which was released on Thursday.
     The survey of 74,000 youths ages 12 to 17 and 133,000 adults is the agency's first detailed statistical breakdown by ethnicity of who smokes and who does not, said a spokesman, Joel London. "This gives us a good snapshot of some information that we and other tobacco control communities have been looking for," Mr. London said in a telephone interview.
     Among adults, 25 percent of blacks said they were smokers, compared with nearly 26 percent of whites and 26.5 percent of the population overall. Among youths, 16 percent of whites and 7 percent of blacks said they smoked, compared with 13.8 percent overall. "That's a good thing," Mr. London said. In the past, blacks in the United States have been much more likely than whites to smoke. He said perhaps antismoking messages that had been aimed at blacks could now be aimed at Native Americans and other groups.
     The report, noted that smoking "remains the foremost preventable cause of death in the United States." Each year about 440,000 persons die from illnesses attributed to smoking, the report said.



FDA to Hear Views on Drugs' Suicide Link
Carey Goldberg, Boston Globe- 2/2/2004

After her 11-year-old son began taking the antidepressant Lexapro this summer, Yvette Prayor of Worcester found herself pacing the floors at night. As a nurse, she said, she had heard that such drugs could raise the risk of suicide in young people, and her son already suffered from low self-esteem. But the psychiatrist had said Lexapro could do some good. So she paced, "for fear that if I go to sleep, he's not going to be awake when I wake up."
     Confusion and concern about whether Paxil and other Prozac-generation antidepressants increase suicidal tendencies in some children and teenagers have become so widespread among parents, doctors, and researchers that the Food and Drug Administration will convene a public hearing tomorrow to take testimony and review the evidence. The agency is not expected to reach a conclusion until this summer about whether the drugs increase the risk of suicide among children and teenagers.
     Estimates vary, but perhaps as many as 1 million American young people take the drugs, known as selective serotonin reuptake inhibitors or SSRIs. In Massachusetts, about 1.3 percent, more than 5,000 in all, of children and teens on Medicaid take them, according to the only state records on prescriptions.
     Concerns that Prozac might make some adults suicidal were first raised publicly in 1990 but were set aside a year later when the FDA found the drug safe. Now, events and disclosures in the last few months have infused the suicide debate with new urgency. Last summer, reports emerged that in clinical trials, Paxil and another drug, Effexor, were linked to heightened suicidal tendencies in youngsters. British authorities warned against Paxil's use in young people, citing new data indicating that among 1,100 children given Paxil, those on the drug were up to three times more likely to have suicidal thoughts as those on a placebo. Then in December, British authorities warned doctors not to prescribe SSRIs -- except Prozac -- for children, saying the risks outweighed the benefits.
     In the United States last fall, the FDA warned doctors to use caution and carefully monitor young patients on SSRIs. Prozac is the only SSRI the FDA has approved for treating depression in children, but doctors are free to prescribe the others as well. Children are particularly difficult to treat, psychiatrists say, because it is harder to diagnose them and determine the right dosages for medication.
     Meanwhile, those who question the suicide connection have also been gaining impetus. On Jan, 21, a task force of psychiatric pharmacologists convened by the American College of Neuropsychopharmacology issued a report concluding that SSRIs do not appear to increase the risk of suicide in teens and children. They based their conclusion on a review of the data on about 2,000 young people who had enrolled in clinical trials of the drugs. The American Psychiatric Association has reached a similar conclusion, said Dr. David Fassler, a Burlington, Vt., psychiatrist and specialist on child depression who is scheduled to speak on behalf of the association at the FDA hearing. Based on the association's review of the available literature on SSRIs, he said, "There is not a clear and convincing association with an increased risk of suicidal thinking or behavior."
     The FDA now faces a serious dilemma. A memo it issued in advance of tomorrow's hearing defines the issue in stark terms: If, as it sorts through the data, the agency overlooks a pattern of increased risk of suicidal tendencies, then doctors treating pediatric depression could feel "greater comfort than is warranted in the safety of these drugs." But if the agency decides prematurely that there is increased risk, the drugs could be used too conservatively or become unavailable altogether, and patients with serious and even life-threatening cases of depression would have fewer treatment options.
     Many psychiatrists sound a similar note. They worry that they could lose a drug that has often proven effective in fighting depression in their young patients. "I'm somewhat concerned that all the attention around this issue may frighten some parents away from getting help for their kids, and that would be a tragedy because we really can help most of these kids," said Fassler.
     Psychiatrists also argue that suicidal tendencies tend to be relatively common among teenagers and that in 15 countries, the advent of SSRIs has coincided with a drop in the rate of suicide among young people. In the United States, the suicide rate among young people ages 15 to 24 has dropped since the mid-1990s from about 13 to 10 per 100,000 people.
     On the other hand, anecdotal evidence abounds that the SSRIs can trigger agitation that can turn suicidal. Leah Harris, a 28-year-old Washington, D.C., writer who was put on Prozac when she was 12, plans to offer herself as an example at today's hearing. She had been introverted as a child but never suicidal, she said. But, "as soon as I went on the drugs -- bam! -- I started having suicidal thoughts," thoughts like, "killing yourself might be a good idea." She also began cutting herself and suffering from anxiety and insomnia. When she told psychiatrists of her turmoil, she said, "They would say, `Oh, you're getting worse, let's give you more.' " At 18, she said, she went off the drugs and has been fine ever since. "You get enough anecdotes, and it starts to add up," said Harris, who is working on a memoir.
     A spate of lawsuits in recent years has revolved around the argument that Prozac and other antidepressants can trigger suicide. Patient advocacy groups also have entered the fray, arguing that the drug companies that make the antidepressants have purposely hidden clinical trial results that indicate that the drugs are ineffective or that they can induce suicidal tendencies. The FDA has failed in its duty to warn the public of the drugs' dangers, said Vera H. Sharav, president of the Alliance for Human Research Protection. Doubts also remain as to whether today's panel will correct that, she said, because it may be stacked with researchers "who have huge financial interlocking interests with the drug companies that manufacture these drugs."
     The drug companies acknowledge that they have not published all their results, but that is not the only problem. The methodology in many of the trials has been flawed, said Dr. Martin Teicher, head of the Developmental Biopsychiatry Research Program at McLean Hospital in Belmont. It was not designed to catch suicidal tendencies, and the trials may not have been big enough to catch a relatively rare side effect. The FDA is now trying to reanalyze the data from 20 trials of nine SSRI drugs, totaling more than 4,000 patients, to try to catch subjects whose suicidal tendencies increased.
     If there is anything close to a consensus on the topic, all sides agree that more research would help. Meanwhile, psychiatrists say, no one should abruptly drop taking an SSRI; it should always be done under medical supervision. The key in prescribing SSRIs to young people is to start with a low dose, go slowly and carefully, and treat them at the same time with a sedative or psychotherapy, said Dr. Alexander Bodkin, chief of clinical psychopharmacology research at McLean. "If you're doing all these things then they're great," he said. "But if you're prescribing to 100 people a day that you don't even know, and just handing the stuff out -- and kids are more impulsive anyway -- then you would expect more of these kinds of `surprises.' "

Prozac Nation Under Fire
Joanna Schaffhausen, ABC News- 2/1/2004

Renewed concerns about the safety of the antidepressants have prompted the Food and Drug Administration to convene hearings today to determine whether antidepressants like Paxil and Zoloft are unsafe for use in children under 18. Last summer, the British drug authorities announced findings of an associated risk of increased suicidal behavior. On trial is a class of drugs called specific serotonin reuptake inhibitors (SSRIs), which include Prozac, Paxil and Zoloft. Currently only Prozac is approved by the FDA for use in children.
For parents whose children have had terrible experiences while taking antidepressants, the FDA hearing is long overdue. Teenager Corey Baadgaard was taking Effexor when he walked into his honors English class with a rifle and held his classmates hostage. One of the antidepressant's actions is to increase serotonin like Prozac and Paxil. "I've never been in a fight before, never done anything like that, never wanted to hurt somebody," Corey told World News Tonight correspondent Lisa Stark.
     But doctors who have seen the drugs work "miracles" in children worry one of their best weapons for treating depression in kids might be taken away without any hard science to support a ban. "The British decision to ban all SSRIs but Prozac for use in children was not based on science," says adolescent psychiatrist Chris Okiishi of the University of Iowa Hospitals and Clinics. "These are the only effective medications we have for children."

Benefits Outweigh Risks?
Among the evidence the FDA will consider is a report from the American College of Neuropsychopharmacology, or ACNP, which convened a task force in September 2003 to study the data linking antidepressants to suicide in teenagers. The ACNP examined a total of 15 clinical trials of SSRI -- totaling more than 2,000 kids and teens -- including those reviewed in Great Britain last year. It concluded there is no reliable evidence linking antidepressants to increased suicide in teenagers. Instead, ACNP said there is good reason to believe antidepressants help prevent adolescent suicide. The review of over 2,000 children on antidepressants found not one suicide. The report also notes the British study found only slight increases in suicidal thinking in kids who were taking antidepressants.
     The ACNP considered other evidence as well. They reviewed a recent study on 49 teenagers who had committed suicide, 24 percent of whom had been prescribed antidepressants. However, none of the kids tested positive for the SSRIs at the time of their death. This suggests the teenagers may have been less suicidal on the medication than off of it.
     Finally, the report examined suicide rates in countries where the antidepressants are prescribed. They found teen suicide has dropped about 33 percent among populations using SSRI anti-depressants over the past 14 years. The reduction followed several decades of increases in youth suicide.

Suicide a Risk with Depression
Doctors admit there is always a risk of suicide when treating a severely depressed patient. As patients start to feel better, energy and motivation sometimes return before the suicidal thinking has faded. "You get patients who are too depressed to commit suicide," says Dr. David Fassler, a trustee of the American Psychiatric Association who is testifying about the antidepressant safety at the FDA hearing. "Patients start treatment and then they feel just better enough to go through with it."
     Others question whether the antidepressants might have more of a "rebound effect" in children. The kids feel better when the drugs are in their system, but may feel even worse as the drugs wear off. We know kids metabolize drugs faster," Okiishi explains. "One possibility is that we may not be giving them enough."
     Doctors agree it is important to watch a person starting antidepressants very carefully. Jay Reeve, senior psychologist at Bradley Hospital in Providence, R.I., explains, "We often admit severely depressed kids to the hospital. We watch them very closely for at least three to four days. After that, we make sure we have a lot of parental education about possible side effects." But with increased suicidal thinking as a possible side effect, some feel you can't be too careful. Dr. Thomas J. Moore of George Washington University told World News Tonight, "I believe there is not enough evidence that these drugs are safe."
     The ACNP report notes safety evidence in adults is much better. "More than 20,000 adults have been studied in clinical trials of SSRIs and other antidepressants … Analysis of the database found no relationship between SSRIs and suicidal attempts or actual suicides in adults."
     Experts hope the FDA hearing will provide more answers to the question of effectiveness and safety of antidepressants in children."We need large scale multi-site studies," Fassler says."A hearing to evaluate what we know and what we don't know is a good thing."

Verdict Not Likely to Come Soon
For the millions of people taking SSRIs for depression, a definitive answer is not immediately in sight. Dr. Russell Katz of the FDA explains: "We don't believe we have the information at the moment to be able to make that decision, and we think it is very, very important to get this correct, because a mistake in either direction can have very significant health consequences."
     Meanwhile, some question whether the FDA panel may be overly biased in favor of the drug companies. The Center for Science in the Public Interest, for instance, has urged the FDA to remove three of 11 scientists on one of its advisory boards evaluating the link between antidepressants and suicide in youths because they have been paid consultants for the companies that make the drugs under investigation.
     The FDA says they are just beginning the review process and may not have an answer until next summer. In the meantime, they have urged doctors to be especially careful when prescribing antidepressants to children. All doctors emphasize parents should not stop their children's antidepressant medications without first talking to a physician. "Drugs are not the whole answer," acknowledges Fassler. "But there is a high risk of not treating kids." Okiishi explains, "I have 15-20 patients with a parent overseas in the Gulf. The parents heard the British report on the BBC about SSRIs and suicide and wrote home to have their kids taken off the medications without consulting me. I ended up with some pretty sick kids." Okiishi says his young patients are back on their medications and doing fine.

Some Data Link Use of Antidepressants, Suicidal Thoughts
Shankar Vedantam, Washington Post- 2/2/2004

A government panel of doctors will meet today to weigh disturbing but ambiguous evidence that widely used antidepressants may make some children suicidal, concerns that peaked in December when British authorities warned doctors not to prescribe the drugs to children. Clinical trials conducted by the drug industry in recent years have produced a steady drumbeat of data suggesting that suicidal thoughts and behavior are slightly more likely to develop in depressed children who take antidepressants such as Paxil, Zoloft and Effexor than in children who get dummy pills, according to several scientists who have analyzed many of the studies. The Food and Drug Administration, after concluding that the numbers in each trial were too small to settle the question, has mounted its own detailed review of the studies and convened the expert panel to advise it on how to evaluate the data.
     If the danger is real, thousands of American children are potentially at risk. About 1 percent of children in the United States are diagnosed with depression each year, according to a recent review, and more than half of those diagnosed are prescribed antidepressants.
     Last month, a panel convened by the American College of Neuropsychopharmacology (ACNP) reported that in drug company-sponsored trials involving 1,921 children on Prozac, Paxil, Zoloft and Celexa, 47 children developed suicidal thoughts or harmed themselves. Only 32 children taking dummy pills, or placebos, showed suicidal behavior. The panel of psychiatrists said the difference was not statistically significant. The doctors, who reflect the prevailing view of U.S. psychiatrists, said they believe the medicines significantly reduce the risk of suicide among depressed children.
     Others who have seen the same data strongly disagree. "Across all of these drugs, the rate of children who become suicidal is 2.5 times higher than on placebo," said David Healy, a Welsh psychiatrist who has reviewed several unpublished industry studies, including those analyzed by the ACNP panel. Healy is an expert witness in several lawsuits against pharmaceutical companies.
In an interview, Healy said that overall, "4 to 5 percent of the kids are becoming suicidal" among those taking the drugs. "It's probably a shade less than 2 percent in the placebo arm."
     Psychiatrists and regulators in the United States have been much more hesitant than their British counterparts to find fault with the drugs. The issue has resurrected charges by patient advocates and some physicians that widespread ties to the pharmaceutical industry have biased U.S. doctors toward drug therapy. Most doctors deny this and say they believe in the drugs. They say many more children would commit suicide if the medicines were banned. "Most people who commit suicide with depression are not being treated," said John Mann, who co-chaired the ACNP panel that studied the issue. Mann, who heads the Department of Neuroscience at the New York State Psychiatric Institute and is a professor of psychiatry at Columbia University, noted that 1,883 children and teenagers in the United States committed suicide last year. The only one of these drugs specifically approved for use in children with depression is Prozac, the first of the selective serotonin reuptake inhibitors (SSRIs), after Eli Lilly and Co. met FDA requirements for approval by submitting two studies showing it to be safe and effective in children. Doctors, however, are free to prescribe any drug approved for adults to children.
     Although the FDA says none of the other antidepressants has been approved to treat children's depression, Russell Katz, director of the agency's neuropharmacology division, said this was not sufficient to rule out their usefulness. "For all I know, if they did two more studies, they might be positive," Katz said. "We are not prepared to say they don't work. As of now, all we can say is that the evidence doesn't show they work. On the risk side, we can't say anything definitive." By contrast, he said, the British "are saying there is no evidence they work, and there is a risk, so you shouldn't use the drugs," Katz said.
     FDA staff members are reviewing 20 trials involving about 4,000 children; the analysis may not be complete until the summer. Katz said the agency had asked the makers of eight drugs to resubmit their data in a format that would allow comparisons. In the original reports, the companies classified different behaviors as suicidal or used different terminologies, making comparisons problematic. "It's not simple to decide whether an action by a child or adolescent is a suicide attempt," Katz said. "There are adolescents who cut themselves with razor blades -- that is not a suicidal gesture."
     Even as U.S. regulators and psychiatrists have played down the risks, three major manufacturers have warned doctors not to prescribe their products. Wyeth Pharmaceuticals issued a warning last year against prescribing Effexor to depressed children. "Despite the fact that these products are not approved, they are being prescribed," Wyeth spokesman Douglas Petkus said in a recent interview. "We do not encourage that, we do not recommend the use of these products in this patient population." GlaxoSmithKline, the maker of Paxil, issued a similar warning last year in Britain. Compared with children who got dummy pills, the company said, youths getting the drug, called Seroxat in Britain, had double the rate of hostility, agitation, suicidal thoughts and attempted suicide.
Eli Lilly, which makes Prozac, also told British doctors in December that for children, the drug was "not recommended." The makers of Prozac and Paxil said the warnings issued in Britain reflected that country's regulatory position on the drugs.
     Other manufacturers have not issued warnings. Cathryn Clary, vice president of psychiatry and neurology for U.S. Medical at Pfizer Inc., which makes Zoloft, said the company was appealing the British ban. Although studies had not yet shown the medicine was effective in children, the company believes there is not enough data to rule it ineffective, she said. "The risk of this kind of warning is that people who are really benefiting from these SSRI drugs may be encouraged to stop inappropriately or prematurely," said Steven Hyman, former director of the National Institute of Mental Health and now provost at Harvard University. "To publicly suggest there is a substantial suicide risk based on these numbers creates another risk."
     Graham Emslie, a professor of psychiatry at the University of Texas Southwestern Medical Center, who has conducted many trials for the industry, said the "safety concerns have been vastly overblown." No child had actually committed suicide in any industry-sponsored trial, he said.
Some children who became suicidal may have been misdiagnosed as depressed when they were actually manic-depressive and therefore more likely to become hostile or self-injurious on an antidepressant, several doctors said. Critics such as Healy, however, point out that the trials systematically excluded children who were already suicidal, so the studies are little help to doctors deciding whether to prescribe antidepressants for children at risk for suicide. The current director of the National Institute of Mental Health, Thomas Insel, said a government-funded study nearing completion may answer such questions because it included "real-world patients."
     The disagreements about the proper use of the drugs are about more than just data, some doctors say. Lawrence Diller, a Walnut Creek, Calif., pediatrician who prescribes the drugs but is cautious about their usefulness, said, "The difference between the British and American takes on the data reflect cultural differences. American doctors have used psychiatric medicines on children at 10 to 20 times the rate of European doctors."

Stronger Warning Urged on Antidepressants for Teenagers
Erica Goode, New York Times- 2/3/2004

BETHESDA, Md.— A scientific advisory panel urged the Food and Drug Administration on Monday to issue stronger warnings to doctors now about the possible risks to children of a newer generation of antidepressant drugs, rather than wait until the agency's review of the drugs was completed. "Our sense is that we would like in the interim for the F.D.A. to go ahead and issue stronger warning indications to clinicians" about the chance that the antidepressants might be linked to suicidal thinking and behavior, hostility or other forms of violent behavior, said Dr. Matthew Rudorfer, a scientist at the National Institute of Mental Health and the chairman of the F.D.A. advisory committee. Dr. Rudorfer said such a warning would not discourage doctors from using the antidepressants but would alert them to warning signs that a drug might be having harmful effects. The recommendation came at the end of an emotional daylong public hearing on the issue. Most of the antidepressants belong to the class known as selective serotonin reuptake inhibitors, or S.S.R.I's. Dr. Thomas Laughren, the team leader for the F.D.A.'s division of neuropharmacological drug products, said that the agency took the panel's recommendation "very seriously" and that it would probably issue such a warning "sooner rather later."
      Along with experts who testified at the hearing, the panel listened to parent after parent, and children, who stepped up to the microphone to tell stories of suffering and loss. A father spoke of his 13-year-old son who hanged himself from a closet hook after starting on an antidepressant. A teenager said that after a few weeks on the drugs he took a hunting rifle to school and threatened his classmates. He had no memory of his actions, he said, and woke up afterward in a juvenile detention center. One mother asked, "How many more people have to die before a warning gets issued?" Other parents said the antidepressants had helped their children enormously and saved many other children's lives. "I shudder to think of their plight if these medications were not available," said a mother whose son suffers from manic-depression.
      Dr. Rudorfer said the committee was struck by the fact that in some cases described at the hearing doctors had seemingly prescribed antidepressants casually and failed to monitor the children closely while they were taking them. "We were all concerned about the stories we heard," Dr. Rudorfer said, noting that the drugs were "very powerful but also potentially very effective."
      In December, British drug regulators told doctors to stop writing new prescriptions for children under 18 for six newer antidepressants because the potential risks outweighed benefits. Use of the drugs might still be warranted in some cases, the regulators said, and they exempted Prozac from the order. The F.D.A. has been conducting its own review of the safety and effectiveness of the antidepressants, but has not yet taken action to stiffen warning labels or restrict use of the drugs. Officials from the agency said the investigation would probably not be completed until summer and that another public hearing would be held before then.
      Dr. Laughren told the advisory committee on Monday that the agency was reviewing 25 studies of nine antidepressants, involving more than 4,000 patients. The drugs under review include Prozac, which is made by Eli Lilly; Zoloft, by Pfizer; Paxil, by GlaxoSmithKline; Luvox, by Solvay; Celexa, by Forest Laboratories; Wellbutrin, by GlaxoSmithKline; Effexor, by Wyeth; Serzone, by Bristol-Myers Squibb, and Remeron, by Akzo Nobel. He said there was "a suggestion from that data that there is a signal of something, there is an excess of something occurring." But trying to figure out what that "something" is, Dr. Laughren said, is enormously complicated. At the hearing, Dr. Laughren and other F.D.A. officials asked the panel to advise them on several questions, including whether their plans for analyzing the existing studies of the antidepressants are adequate.
      The F.D.A. has asked researchers at Columbia University to trace the data used in the drugs' clinical trials to make sure that behaviors coded in the trials as suicidal in fact represent suicidal thoughts or actions. Parents and some psychiatrists have been critical of the F.D.A. for taking so long to investigate. "I don't think much is going to come of this," said Jay Baadsgaard, of Yelm, Wash., whose son took the hunting rifle to school. Some parents also say the F.D.A. is too heavily influenced by the drug industry, which heavily promotes antidepressants for a variety of psychiatric problems including depression, social phobia, anxiety disorders and obsessive-compulsive disorder. About 11 million prescriptions for a group of newer antidepressants were written for American children under 18 in 2002, according to the F.D.A.
      Some parents at the hearing, who had two minutes each to tell their stories, described how their children seemed to change abruptly after starting the drugs, becoming aggressive, suicidal or violent toward others. But Dr. David Shaffer, a professor of psychiatry at Columbia, told the advisory panel that suicide rates among children and adolescents had declined in recent years and that the growing use of antidepressants was a possible explanation for the drop.

Parents Blame Medicines for Suicides
Elizabeth Shogren, Los Angeles Times- 2/3/2004

BETHESDA, Md. — Dozens of relatives of children who either committed or attempted suicide told a panel convened Monday by the Food and Drug Administration that the youngsters' actions were prompted by the antidepressant drugs that were supposed to help them. The FDA is assessing whether there is a link between suicide in children and drugs such as Zoloft and Paxil, which are in a class of pharmaceuticals known as selective serotonin reuptake inhibitors, or SSRIs. The British government announced in December that the drugs should not be taken by children because of the possible increased risk of suicide.
      The FDA has taken a milder approach, alerting doctors in October about the reports of suicidal thoughts and suicide attempts among children in clinical tests of the antidepressants. The agency plans to analyze the data from 15 clinical studies of the drugs before deciding whether to prohibit doctors from prescribing them for children or to require that drug companies warn doctors of possible links to increased suicide. "To err in either direction has significant consequences," said Thomas Laughren, leader of the FDA's psychiatric drug products team.
      The FDA has approved only one SSRI for treating children and adolescents — Prozac, which came on the market in the United States in 1988. Despite that, many doctors prescribe other SSRIs for their young patients. About 2.7 million children younger than 12 and 8.1 million adolescents between 12 and 17 took antidepressants in 2002, according to the FDA.
      Banning the drugs, if they do not present extra suicide risks, could rob children of medications that could help them. However, failing to ascertain that the drugs increase the risk of suicide could give parents false comfort that these drugs were safe. But many of the parents and patients who testified Monday said that the FDA already had made a significant error by failing to warn parents that suicide was a risk.
     "We are 100% convinced that Zoloft killed our daughter," said Tom Woodward of North Wales, Pa. Woodward said his teenage daughter had hanged herself in July, seven days after starting the drug. She had never shown any violent or suicidal tendencies before taking the drug and had just scored 1,300 on the SAT, her father said. "Instead of picking out colleges with our daughter, my wife and I were picking out a cemetery," Woodward said. "The FDA should be a zealous advocate of the public," he said. But instead, it protects drug companies, he added.
      Lorraine Slater said her 14-year-old daughter, Dominique, went from being a sightly depressed honor student to a suicidal young woman after their family doctor prescribed one of these drugs. Dominique was taking the antidepressant Effexor when she drowned herself last February in the Delta Mendota Canal near Patterson, in California's Central Valley. Slater said she was unaware of the possible link between the drug and suicide until after her daughter's death. "Dominique's life was taken from her as a result of a drug-induced psychosis," said Slater, 38. "If we had known" about the reported risks, Slater said, "I don't believe we would have let her be on Effexor. It's too late for us; we hope it's not too late for other families."
      But some parents urged the panel not to ban these drugs for children, saying that the medications have been very helpful. Suzanne Vogel-Scibilia, a psychiatrist, has two children who take antidepressants. "I shudder to think of their plight if these medications were not available," said Vogel-Scibilia, who was speaking for the National Alliance for the Mentally Ill.
      Some doctors who testified at the daylong meeting Monday stressed that the benefits to children who take the drugs do not outweigh the risks, because clinical tests have not shown them to be much more effective than placebos. "The meager benefits don't justify putting a child at risk," said David Antonuccio, a professor in the department of psychiatry and behavioral sciences at the University of Nevada School of Medicine. But Russell Katz, director of FDA's division of neuropharmacological drug products, stressed that while tests have not shown clear benefits of the drugs over placebos, that is "not the same thing as showing them to be ineffective."
      The FDA has contracted with Columbia University to analyze the data on the suicidal behavior from the drug companies' clinical trials. The agency plans to convene another meeting in August to address the issue, but Katz said that even then, the FDA still may not have a definitive answer about the risks of the antidepressants for children and teenagers.
      It has been part of medical lore for decades that taking antidepressants may give a person the energy to follow through on suicidal impulses before there is a chance for the drugs to improve the patient's mood. But both patients and parents on Monday told the FDA that, months after starting the drugs, children had become extremely hostile and experienced other forms of severely altered behavior. In some cases, that behavior led to suicide or suicide attempts. In others it led to violent outbursts toward others, including homicidal tendencies. Wyeth, the manufacturer of Effexor, warned doctors in September that tests showed its antidepressant caused an increased risk of suicidal behavior in children. Other companies have not sent out warnings.

Memo Left Out Key Psychologist's Report on Jackson
Chuck Philips, Los Angeles Times- 2/3/2004

A private psychologist told Los Angeles County child-welfare officials in June that he believed a 12-year-old boy he was treating had been molested by Michael Jackson, documents show. But child-welfare officials made no mention of the psychologist's report in a highly publicized memo that described as "unfounded" allegations that Jackson abused the boy.
      The county Department of Children and Family Services interviewed the boy, his two siblings and his mother in February 2003, after a TV documentary about Jackson sparked a complaint to the agency's hotline. On the broadcast, Jackson was seen holding hands with the boy, then 12, and saying that he saw no harm in sharing his bed with children. Social workers reported finding no evidence of abuse. In November, after Santa Barbara County authorities had arrested Jackson and charged him with molesting the same 12-year-old boy, an official of the child-welfare agency asked a subordinate for a report on the earlier investigation.
      In a memo dated Nov. 26, Jennifer Hottenroth, the department's assistant regional administrator, wrote that the boy, when questioned by social workers, had "denied any form of sexual abuse," and that his mother had said Jackson was "like a father" to her children. The confidential one-page memo appeared in December on a website called thesmoking gun.com and was widely reported by media outlets around the world. Jackson's attorneys trumpeted the memo as evidence of the pop star's innocence, and legal experts predicted that it would bolster the entertainer's defense in court.
      But documents obtained by The Times show that a child psychologist who had been treating the boy met with David Sanders, the head of the child-welfare department, and two social workers on June 12 and told them that he believed Jackson had molested the child. Larry R. Feldman, a Century City lawyer who was representing the boy, attended the meeting. In a subsequent letter to Sanders, Feldman wrote: "The child psychologist told your social workers that he believed that my young client had been sexually abused by the same entertainer who allegedly abused a young boy in 1993." The reference was to a case in which Jackson was accused of molesting a 13-year-old boy. The singer paid more than $15 million to settle those allegations in 1994, and he was never criminally charged. Feldman represented the complainant in that case.
      When Sanders wrote back, he did not dispute the lawyer's description of the meeting. Instead, he focused on what he said was the paramount issue for child-welfare authorities: whether Jackson's latest alleged victim was in "imminent danger." "You and the psychologist … indicated that the mother was taking action to protect the child from harm and was not allowing him to have any access" to Jackson, Sanders wrote. "Thus, based upon the facts you and the psychologist presented … there was no basis for the department to intervene." Sanders wrote that his staff members had explained that if the boy was not in immediate danger, the allegation was a police matter. Feldman and the psychologist had been told to report the allegation to law enforcement officials in Santa Barbara, Sanders wrote. The psychologist later made such a report.
      Sources close to the case said that Hottenroth, author of the Nov. 26 memo, attended the meeting with the psychologist and Feldman. She did not return phone calls seeking a comment. Sanders and Charles Sophy, a department official to whom Hottenroth's memo was addressed, declined to comment. A spokesman for the agency issued a statement saying: "As in every case of abuse and neglect that we handle, this matter was taken seriously and investigated with the utmost professionalism and sensitivity."
      The leak of the memo sparked an exchange of heated letters between Feldman and Sanders. "It is extremely hard to understand why the Nov. 26 report was created in the first place, let alone leaked to the press," Feldman wrote on Dec. 11. "Moreover, if someone took the time, in good faith, to write such a report, why did this report not contain the entire reporting history of the case?" Feldman would not comment on the correspondence. Sanders, in a letter dated Jan. 12, defended Hottenroth's memo as accurate and complete, and said he had ordered an investigation into the leak.
      The memo and the correspondence shed light on the origins of the latest child-abuse allegations against Jackson. Last Feb. 6, ABC-TV's "20/20" program aired "Living with Michael Jackson," a British documentary. The show included footage of the 12-year-old boy holding hands with Jackson and leaning against his shoulder. Jackson said on camera that he saw nothing wrong in sharing his bed with children, and described it as "the most loving thing to do." The memo says that after the show aired, an unnamed Los Angeles school official called a child-abuse hotline to report allegations of abuse against Jackson, described in the memo as "the entertainer." The investigation began Feb. 14 and was completed Feb. 27, the memo states.
      Before interviewing the boy, investigators discovered that the agency had investigated allegations of domestic violence between his parents in 2001. That information was included in the memo. The memo also said that the boy, his mother, and his brother and sister had told investigators that Jackson never did anything improper during their visits to his Neverland Ranch in Santa Barbara County. Circumstances surrounding the investigation made the family reluctant to speak freely about Jackson at that time, sources close to the family said. A Jackson employee escorted the boy and his family to their interviews with county investigators, the sources said. The employee waited outside as the family members were questioned, then chauffeured them back home, the sources said. In addition, Jackson employees had arranged hotel accommodations for the boy and his family and helped them obtain passports for travel to Brazil, the family sources said. Jackson had also hired a British attorney so the family could sue the producers of the documentary for invasion of privacy, the sources said.
      But by April, the boy's family had distanced themselves from Jackson. The mother had hired her own attorney to pursue a possible suit against the producers and to force Jackson to return various family belongings from Neverland, the sources said. In May, the family's lawyer referred the mother to Feldman, who met several times with the boy and the mother and in turn referred them to the psychologist. In one of his letters, Feldman said he called Sanders to alert him to the latest allegations against Jackson and to remind him that the psychologist, if he determined that the boy had been abused, would be obliged by law to report the allegation to the child-welfare agency. Feldman wrote that he had warned Sanders to prevent any leak of "sensitive material," which the lawyer said had occurred with the 1993 allegations against Jackson.

Lies, Secrets Undermine Relationships
Michele M. Melendez, Newhouse News Service- 2/3/2004

Charlie Nelson couldn't lie to his wife anymore. He sat her down at the breakfast table and told her he'd been secretly hitting the slot machines, gambling away thousands. "I lied, because I was so deeply embarrassed by my failure as a man," said Nelson, 67, of Des Moines, Iowa. "It's a natural human condition, I guess, to cover your faults."
     Nelson and his wife have been working through his addiction, but secrets and lies can break couples. Marriage counselors hear from spouses who lie to each other about almost anything. Generally, experts say, spouses should come clean in the most direct way --just as Nelson did.
"Why do we lie to begin with? It's a defensive posture," said Pamela Brill, psychologist and author of the upcoming book, "Winner's Way: A Proven. Method for Achieving Your Personal Best in Any Situation." "We lie because we cover things up, even to ourselves," Brill said. "Or, we're protecting our self-image." Lying spares us shame, hurt and conflict.
     "Lying starts very early in life, when children are around 4" and begin to understand rules and consequences, said Meri Wallace, therapist and director of the Heights Center for Adult and Child Development in Brooklyn, N.Y. "They'll be caught with chocolate all over their hands, and they'll say, `I didn't do it."' A parent's reaction to a child's mistakes and dishonesty can affect how the youngster will use lying in adulthood, Wallace said. If the parent reacts harshly, the child might feel discouraged to be truthful. But fibbing during childhood does not excuse a lying spouse, Wallace said. In marriage, lying "undermines the relationship."
     On some level, Nelson knew that danger. But he said he couldn't help lying about his trips to the casino until something told him to stop. "It was a special moment," he said. "I thought I heard God speaking to me, although that could have been my conscience, or a shred of common sense I had left." After he told his wife, he felt better. "She loves me deeply, and she did everything to make it easier for me," Nelson said.
     Like Nelson, Julie Ann Barnhill of Prairie Hill, Ill., thought it best to confess to her husband outright when her deception about a hidden credit card became over-whelming. "You have to get to the mail before he does," and answer the phone before he does, she said. "You feel bad, but the main thing is you don't want to get caught." Barnhill's husband, Rick, was the sole income-earner, but she handled the money. She had been charging restaurant dinners, electric and phone bills, gifts for herself and cash advances. In a year and a half, she accumulated more than $3,000 in debt and couldn't make the card's minimum payment. Rick Barnhill said he felt betrayed: "It hurt me. I thought we were supposed to talk about all these things." The Barnhills, both 38, said the disclosure actually made her more honest and him more involved with the cash flow, inspiring Julie Ann Barnhill to write the 2002 book, "'Til Debt Do Us Part: Real Help for Couples Dealing with Finances."
     While the Barnhills resolved their money problem, experts say financial dishonesty can lead to divorce. "Both husband and wife should know at all times everything about the family income and expenses," said Elinor Verville, of Tulsa, Okla., a clinical psychologist and author of "For the Sake of the Marriage: What You Give -- What You Get."
     Next to money, an affair ranks among the top marriagebreakers, experts say. Estimates on infidelity vary dramatically, suggesting that a fourth to three-fourths of spouses in the United States either have had or will have an affair. When a person is unfaithful, experts say, the spouse often finds out. So, said ethicist Bruce Weinstein, a person should consider: "Do I want my spouse to find out from me, or my Visa bill? Or the perfume on my necktie?"
     Experts say deciding whether to reveal an affair should include deep self-reflection and consideration of the marital relationship, although the honesty ideally should precede the adultery.
Brill said a person could tell his or her partner: "I have a need for this type of intimacy or this kind of conversation. How can we fulfill this need, so I don't have to look elsewhere?" Much depends on the nature of the affair, including the level of involvement -- whether it was an emotionally and physically intimate relationship or a one-time fling, said Weinstein, New Yorkbased author of "What Should I Do?: 4 Simple Steps to Making Better Decisions in Everyday Life." "One might very well be justified in not mentioning it," he said, particularly if it won't happen again and the revelation would crush a family. Ultimately, Weinstein said, the best solution to any moral problem is one that allows us to respect our moral obligations. Those responsibilities depend on the person. One individual's beliefs might make lying always wrong. To another, some lies seem insignificant.
     Jane Miller and her husband, Rick, of Avalon, Pa., both 48, had made a ritual of prepping their flower garden. One fall, when their work schedules threatened to keep them both occupied during planting season, Miller's husband cultivated the irises himself. She thought he had done it all wrong. She replanted half the bulbs, she recalled, thinking that she would tell him after her flowers bloomed and his didn't. But the opposite happened. His grew lush. He couldn't figure out why half were scrawny, and Miller told him she didn't know. "It didn't become a lie until several months later, when I realized that I should have trusted both him and Mother Nature," Miller said. "It was really such a little moment, but it stayed in my heart as a reminder to believe in and stay behind the people we love -- spouses, children, friends -- even when we think that they should have (or) could have done better."
     Some argue that "little white lies" can actually do good. "When a woman asks her guy, `Do I look fat in this?' and he secretly thinks she does, the guy would probably do best to tell her no ... to suggest another outfit he likes better," said Gilda Carle, a New York-based therapist and advice columnist. "In other words, if delicate lying will prevent lowered selfesteem, I'd suggest that that is the better choice."