PSYCHIATRISTS, CHILDREN AND DRUG INDUSTRY¹S ROLE

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PSYCHIATRISTS, CHILDREN AND DRUG INDUSTRY¹S ROLEBy Gardiner Harris, Benedict Carey and Janet RobertsNew York TimesMay 10, 2007http://www.nytimes.com/2007/05/10/health/10psyche.htmlWhen Anya Bailey developed an eating disorder after her 12th birthday, hermother took her to a psychiatrist at the University of Minnesota whoprescribed a powerful antipsychotic drug called Risperdal.Created for schizophrenia, Risperdal is not approved to treat eatingdisorders, but increased appetite is a common side effect and doctors mayprescribe drugs as they see fit. Anya gained weight but within two yearsdeveloped a crippling knot in her back. She now receives regular injectionsof Botox to unclench her back muscles. She often awakens crying in pain.Isabella Bailey, Anya¹s mother, said she had no idea that children might beespecially susceptible to Risperdal¹s side effects. Nor did she know thatRisperdal and similar medicines were not approved at the time to treatchildren, or that medical trials often cited to justify the use of suchdrugs had as few as eight children taking the drug by the end.Just as surprising, Ms. Bailey said, was learning that the universitypsychiatrist who supervised Anya¹s care received more than $7,000 from 2003to 2004 from Johnson & Johnson, Risperdal¹s maker, in return for lecturesabout one of the company¹s drugs.Doctors, including Anya Bailey¹s, maintain that payments from drug companiesdo not influence what they prescribe for patients.But the intersection of money and medicine, and its effect on the well-beingof patients, has become one of the most contentious issues in health care.Nowhere is that more true than in psychiatry, where increasing payments todoctors have coincided with the growing use in children of a relatively newclass of drugs known as atypical antipsychotics.These best-selling drugs, including Risperdal, Seroquel, Zyprexa, Abilifyand Geodon, are now being prescribed to more than half a million children inthe United States to help parents deal with behavior problems despiteprofound risks and almost no approved uses for minors.A New York Times analysis of records in Minnesota, the only state thatrequires public reports of all drug company marketing payments to doctors,provides rare documentation of how financial relationships between doctorsand drug makers correspond to the growing use of atypicals in children.From 2000 to 2005, drug maker payments to Minnesota psychiatrists rose morethan sixfold, to $1.6 million. During those same years, prescriptions ofantipsychotics for children in Minnesota¹s Medicaid program rose more thanninefold.Those who took the most money from makers of atypicals tended to prescribethe drugs to children the most often, the data suggest. On average,Minnesota psychiatrists who received at least $5,000 from atypical makersfrom 2000 to 2005 appear to have written three times as many atypicalprescriptions for children as psychiatrists who received less or no money.The Times analysis focused on prescriptions written for about one-third ofMinnesota¹s Medicaid population, almost all of whom are disabled. Somedoctors were misidentified by pharmacists, but the information provides arough guide to prescribing patterns in the state.Drug makers underwrite decision makers at every level of care. They paydoctors who prescribe and recommend drugs, teach about the underlyingdiseases, perform studies and write guidelines that other doctors often feelbound to follow.But studies present strong evidence that financial interests can affectdecisions, often without people knowing it.In Minnesota, psychiatrists collected more money from drug makers from 2000to 2005 than doctors in any other specialty. Total payments to individualpsychiatrists ranged from $51 to more than $689,000, with a median of$1,750. Since the records are incomplete, these figures probablyunderestimate doctors¹ actual incomes.Such payments could encourage psychiatrists to use drugs in ways thatendanger patients¹ physical health, said Dr. Steven E. Hyman, the provost ofHarvard University and former director of the National Institute of MentalHealth. The growing use of atypicals in children is the most troublingexample of this, Dr. Hyman said.³There¹s an irony that psychiatrists ask patients to have insights intothemselves, but we don¹t connect the wires in our own lives about how moneyis affecting our profession and putting our patients at risk,² he said.The PrescriptionAnya Bailey is a 15-year-old high school freshman from East Grand Forks,Minn., with pictures of the actor Chad Michael Murray on her bedroom wall.She has constant discomfort in her neck that leads her to twist it in abirdlike fashion. Last year, a boy mimicked her in the lunch room.³The first time, I laughed it off,² Anya said. ³I said: ŒThat¹s so funny. Ithink I¹ll laugh with you.¹ Then it got annoying, and I decided to hide it.I don¹t want to be made fun of.²Now she slumps when seated at school to pressure her clenched muscles, shesaid.It all began in 2003 when Anya became dangerously thin. ³Nothing tasted goodto her,² Ms. Bailey said.Psychiatrists at the University of Minnesota, overseen by Dr. George M.Realmuto, settled on Risperdal, not for its calming effects but for itsnormally unwelcome side effect of increasing appetite and weight gain, Ms.Bailey said. Anya had other issues that may have recommended Risperdal todoctors, including occasional angry outbursts and having twice heard voicesover the previous five years, Ms. Bailey said.Dr. Realmuto said he did not remember Anya¹s case, but speaking generally hedefended his unapproved use of Risperdal to counter an eating disorderdespite the drug¹s risks. ³When things are dangerous, you use extraordinarymeasures,² he said.Ten years ago, Dr. Realmuto helped conduct a study of Concerta, an attentiondeficit hyperactivity disorder drug marketed by Johnson & Johnson, whichalso makes Risperdal. When Concerta was approved, the company hired him tolecture about it.He said he gives marketing lectures for several reasons.³To the extent that a drug is useful, I want to be seen as a leader in myspecialty and that I was involved in a scientific study,² he said.The money is nice, too, he said. Dr. Realmuto¹s university salary is$196,310.³Academics don¹t get paid very much,² he said. ³If I was an entertainer, Ithink I would certainly do a lot better.²In 2003, the year Anya came to his clinic, Dr. Realmuto earned $5,000 fromJohnson & Johnson for giving three talks about Concerta. Dr. Realmuto saidhe could understand someone¹s worrying that his Concerta lecture fees wouldinfluence him to prescribe Concerta but not a different drug from the samecompany, like Risperdal.In general, he conceded, his relationship with a drug company might prompthim to try a drug. Whether he continued to use it, though, would dependentirely on the results.As the interview continued, Dr. Realmuto said that upon reflection hispayments from drug companies had probably opened his door to useless visitsfrom a drug salesman, and he said he would stop giving sponsored lectures inthe future.Kara Russell, a Johnson & Johnson spokeswoman, said that the company selectsspeakers who have used the drug in patients and have either undertakenresearch or are aware of the studies. ³Dr. Realmuto met these criteria,² Ms.Russell said.When asked whether these payments may influence doctors¹ prescribing habits,Ms. Russell said that the talks ³provide an educational opportunity forphysicians.²No one has proved that psychiatrists prescribe atypicals to children becauseof drug company payments. Indeed, some who frequently prescribe the drugs tochildren earn no drug industry money. And nearly all psychiatrists whoaccept payments say they remain independent. Some say they prescribed andextolled the benefits of such drugs before ever receiving payments to speakto other doctors about them.³If someone takes the point of view that your doctor can be bought, whywould you go to an E. R. with your injured child and say, ŒCan you helpme?¹² said Dr. Suzanne A. Albrecht, a psychiatrist from Edina, Minn., whoearned more than $188,000 from 2002 to 2005 giving drug marketing talks.The Industry CampaignIt is illegal for drug makers to pay doctors directly to prescribe specificproducts. Federal rules also bar manufacturers from promoting unapproved, oroff-label, uses for drugs.But doctors are free to prescribe as they see fit, and drug companies cansidestep marketing prohibitions by paying doctors to give lectures in which,if asked, they may discuss unapproved uses.The drug industry and many doctors say that these promotional lecturesprovide the field with invaluable education. Critics say the payments andlectures, often at expensive restaurants, are disguised kickbacks thatencourage potentially dangerous drug uses. The issue is particularlyimportant in psychiatry, because mental problems are not well understood,treatment often involves trial and error, and off-label prescribing iscommon.The analysis of Minnesota records shows that from 1997 through 2005, morethan a third of Minnesota¹s licensed psychiatrists took money from drugmakers, including the last eight presidents of the Minnesota PsychiatricSociety.The psychiatrist receiving the most from drug companies was Dr. Annette M.Smick, who lives outside Rochester, Minn., and was paid more than $689,000by drug makers from 1998 to 2004. At one point Dr. Smick was doing so manysponsored talks that ³it was hard for me to find time to see patients in myclinical practice,² she said.³I was providing an educational benefit, and I like teaching,² Dr. Smicksaid.Dr. Steven S. Sharfstein, immediate past president of the AmericanPsychiatric Association, said psychiatrists have become too cozy with drugmakers. One example of this, he said, involves Lexapro, made by ForestLaboratories, which is now the most widely used antidepressant in thecountry even though there are cheaper alternatives, including genericversions of Prozac.³Prozac is just as good if not better, and yet we are migrating to theexpensive drug instead of the generics,² Dr. Sharfstein said. ³I think it¹sthe marketing.²Atypicals have become popular because they can settle almost any extremebehavior, often in minutes, and doctors have few other answers for desperatefamilies.Their growing use in children is closely tied to the increasingly common andcontroversial diagnosis of pediatric bipolar disorder, a mood problem markedby aggravation, euphoria, depression and, in some cases, violent outbursts.The drugs, sometimes called major tranquilizers, act by numbing brain cellsto surges of dopamine, a chemical that has been linked to euphoria andpsychotic delusions.Suzette Scheele of Burnsville, Minn., said her 17-year-old son, Matt, wasgiven a diagnosis of bipolar disorder four years ago because of intense moodswings, and now takes Seroquel and Abilify, which have caused substantialweight gain.³But I don¹t have to worry about his rages; he¹s appropriate; he¹s pleasantto be around,² Ms. Scheele said.The sudden popularity of pediatric bipolar diagnosis has coincided with ashift from antidepressants like Prozac to far more expensive atypicals. In2000, Minnesota spent more than $521,000 buying antipsychotic drugs, most ofit on atypicals, for children on Medicaid. In 2005, the cost was more than$7.1 million, a 14-fold increase.The drugs, which can cost $1,000 to $8,000 for a year¹s supply, are hugesellers worldwide. In 2006, Zyprexa, made by Eli Lilly, had $4.36 billion insales, Risperdal $4.18 billion and Seroquel, made by AstraZeneca, $3.42billion.Many Minnesota doctors, including the president of the Minnesota PsychiatricSociety, said drug makers and their intermediaries are now paying themalmost exclusively to talk about bipolar disorder.The DiagnosesYet childhood bipolar disorder is an increasingly controversial diagnosis.Even doctors who believe it is common disagree about its telltale symptoms.Others suspect it is a fad. And the scientific evidence that atypicalsimprove these children¹s lives is scarce.One of the first and perhaps most influential studies was financed byAstraZeneca and performed by Dr. Melissa DelBello, a child and adultpsychiatrist at the University of Cincinnati.Dr. DelBello led a research team that tracked for six weeks the moods of 30adolescents who had received diagnoses of bipolar disorder. Half of theteenagers took Depakote, an antiseizure drug used to treat epilepsy andbipolar disorder in adults. The other half took Seroquel and Depakote.The two groups did about equally well until the last few days of the study,when those in the Seroquel group scored lower on a standard measure ofmania. By then, almost half of the teenagers getting Seroquel had droppedout because they missed appointments or the drugs did not work. Just eightof them completed the trial.In an interview, Dr. DelBello acknowledged that the study was notconclusive. In the 2002 published paper, however, she and her co-authorsreported that Seroquel in combination with Depakote ³is more effective forthe treatment of adolescent bipolar mania² than Depakote alone.In 2005, a committee of prominent experts from across the country examinedall of the studies of treatment for pediatric bipolar disorder and decidedthat Dr. DelBello¹s was the only study involving atypicals in bipolarchildren that deserved its highest rating for scientific rigor. The panelconcluded that doctors should consider atypicals as a first-line treatmentfor some children. The guidelines were published in The Journal of theAmerican Academy of Child and Adolescent Psychiatry.Three of the four doctors on the panel served as speakers or consultants tomakers of atypicals, according to disclosures in the guidelines. In aninterview, Dr. Robert A. Kowatch, a psychiatrist at Cincinnati Children¹sHospital and the lead author of the guidelines, said the drug makers¹support had no influence on the conclusions.AstraZeneca hired Dr. DelBello and Dr. Kowatch to give sponsored talks. Theylater undertook another study comparing Seroquel and Depakote in bipolarchildren and found no difference. Dr. DelBello, who earns $183,500 annuallyfrom the University of Cincinnati, would not discuss how much she is paid byAstraZeneca.³Trust me, I don¹t make much,² she said. Drug company payments did notaffect her study or her talks, she said. In a recent disclosure, Dr.DelBello said that she received marketing or consulting income from eightdrug companies, including all five makers of atypicals.Dr. Realmuto has heard Dr. DelBello speak several times, and her talkspersuaded him to use combinations of Depakote and atypicals in bipolarchildren, he said. ³She¹s the leader in terms of doing studies on bipolar,²Dr. Realmuto said.Some psychiatrists who advocate use of atypicals in children acknowledgethat the evidence supporting this use is thin. But they say children shouldnot go untreated simply because scientists have failed to confirm whatclinicians already know.³We don¹t have time to wait for them to prove us right,² said Dr. Kent G.Brockmann, a psychiatrist from the Twin Cities who made more than $16,000from 2003 to 2005 doing drug talks and one-on-one sales meetings, and lastyear was a leading prescriber of atypicals to Medicaid children.The ReactionFor Anya Bailey, treatment with an atypical helped her regain her appetiteand put on weight, but also heavily sedated her, her mother said. Shedeveloped the disabling knot in her back, the result of a nerve conditioncalled dystonia, in 2005.The reaction was rare but not unknown. Atypicals have side effects that arenot easy to predict in any one patient. These include rapid weight gain andblood sugar problems, both risk factors for diabetes; disfiguring tics,dystonia and in rare cases heart attacks and sudden death in the elderly.In 2006, the Food and Drug Administration received reports of at least 29children dying and at least 165 more suffering serious side effects in whichan antipsychotic was listed as the ³primary suspect.² That was a substantialjump from 2000, when there were at least 10 deaths and 85 serious sideeffects among children linked to the drugs. Since reporting of bad drugeffects is mostly voluntary, these numbers likely represent a fraction ofthe toll.Jim Minnick, a spokesman for AstraZeneca, said that the company carefullymonitors reported problems with Seroquel. ³AstraZeneca believes thatSeroquel is safe,² Mr. Minnick said.Other psychiatrists renewed Anya¹s prescriptions for Risperdal until Ms.Bailey took Anya last year to the Mayo Clinic, where a doctor insisted thatMs. Bailey stop the drug. Unlike most universities and hospitals, the MayoClinic restricts doctors from giving drug marketing lectures.Ms. Bailey said she wished she had waited to see whether counseling wouldhelp Anya before trying drugs. Anya¹s weight is now normal without the helpof drugs, and her counseling ended in March. An experimental drug, hermother said, has recently helped the pain in her back.