Proof is Scant on Psychiatric Drug Mix for Young
Source: The NY Times
Their rooms are a mess, their trophies line the walls, and both have profiles on. Stephen and Jacob Meszaros seem like typical teenagers until their mother offers a glimpse into the family’s medicine cabinet.
Bottles of psychiatric medications fill the shelves. Stephen, 15, takes the antidepressants Zoloft and Desyrel for,the anticonvulsant Lamictal to moderate his moods and the stimulantFocalin XR to improve concentration. Jacob, 14, takes Focalin XR forconcentration, the anticonvulsant Depakote to moderate his moods, theantipsychotic Risperdal to reduce anger and the antihypertensiveCatapres to induce sleep.
Over the last three years, each boy has been prescribed 28 different psychiatric drugs.
“Sometimes, when you look at all the drugs they’ve taken, youwonder, ‘Wow, did I really do this to my kids?’ ” said their mother,Tricia Kehoe of Sharpsville, Pa. “But I’ve seen them without the meds,and there’s a major difference.”
There is little doubt that some psychiatric medicines, taken bythemselves, work well in children. For example, dozens of studies haveshown that stimulants improve attentiveness. A handful of otherpsychiatric drugs have proven effective against childhood obsessivecompulsive disorder, among other problems.
But a growing number of children and teenagers in the United Statesare taking not just a single drug for discrete psychiatric difficultiesbut combinations of powerful and even life-threatening medications totreat a dizzying array of problems.
Last year in the United States, about 1.6 million children andteenagers — 280,000 of them under age 10 — were given at least twopsychiatric drugs in combination, according to an analysis performed byMedco Health Solutions at the request of The New York Times. More than500,000 were prescribed at least three psychiatric drugs. More than160,000 got at least four medications together, the analysis found.
Many psychiatrists and parents believe that such drug combinations,often referred to as drug cocktails, help. But there is virtually noscientific evidence to justify this multiplication of pills,researchers say. A few studies have shown that a combination of twodrugs can be helpful in adult patients, but the evidence in children isscant. And there is no evidence at all — “zero,” “zip,” “nil,” expertssaid — that combining three or more drugs is appropriate or eveneffective in children or adults.
“There are not any good scientific data to support the widespreaduse of these medicines in children, particularly in young childrenwhere the scientific data are even more scarce,” said Dr. Thomas R.Insel, director of the National Institute of Mental Health.
Psychiatrists who prescribe drug combinations say that the abilityto mix and match medications improves their chances of being able tohelp children who are seriously, even desperately, ill.
Dr. Joseph Biederman, a professor of psychiatry at Harvard, said that doctors commonly used multiple medicines to treat, , and .“Child psychiatry is not any different,” Dr. Biederman said. “Thesedrugs have revolutionized how we treat severe psychopathology inchildren.”
The controversy leaves parents in a terrible bind. Desperate to help, many agonize over whether to medicate their children.
Mothers and fathers sometimes disagree, with the dispute strainingor even ending marriages. Since some psychiatric drugs can causeworrisome physical effects, parents say that they must on occasion makea terrifying choice between their child’s physical health and his.
The parents interviewed for this article told their stories, theysaid, in hopes of gaining greater acceptance for their children andthemselves. Nearly all recalled being in a store when their child threwa tantrum and feeling that onlookers branded them as bad parents. Theyalso said they hoped to help others negotiate what many said wereunequal and often fraught relationships with psychiatrists.
“We struggled so much, made so many mistakes and felt sostigmatized, I hope our story can make it easier for others,” saidJacquie Erickson of Anchorage. Her daughter, Kaitlyn Johnston, 10, hastaken psychiatric drugs since she turned 5 for diagnoses that include.
On Shaky Ground
Stimulants like Ritalin are by far the most commonly prescribedpsychiatric medicines in children. But doctors routinely pairstimulants with antidepressants, antipsychotics and anticonvulsants,even though some of these medications can cause serious side effects,have few proven pediatric psychiatric benefits and lack clear evidenceabout how they interact or influence mental and physical development.
Last year, therequired drug makers to warn on their labels that antidepressants cancause suicidal thoughts and behavior in some children. Anticonvulsantdrugs carry warnings about liver and pancreas damage and fatal skinrashes. The side effects of antipsychotic medicines can include rapidweight gain, diabetes, irreversible tics and, in elderly patients withdementia, sudden death. When drugs are combined, these risks compound.
Ms. Kehoe, who receives government financial and child-careassistance because her children are considered mentally ill, said sheknew that there were risks to the drug cocktails. Both her sons areshort and underweight for their age — a common side effect ofstimulants — and she fears that the drugs have affected their healthand behavior in other ways.
“But I don’t think the insurance would pay for it if the F.D.A.didn’t decide that children should use it,” said Ms. Kehoe, who herselftakes psychiatric medication.
In fact, the drug agency has specifically warned against the use ofLamictal, one of the drugs Stephen takes, in children who, like him, donot suffer from seizures because in 8 out of 1,000 children the drugcauses life-threatening rashes.
Stephen and Jacob’s psychiatrist did not reply to telephone messagesleft with an office secretary on three different days. Ms. Kehoe saidthat she asked him to speak to this reporter but that he refused. Theboys have had 11 psychiatrists over the last three years, according toprescription records, and many more before that, Ms. Kehoe said.
In interviews, Stephen and Jacob said they hated taking their drug cocktails.
“Everybody hates meds,” Jacob said.
Ms. Kehoe said her youngest son, Lucas Keck, was showing signs ofattention deficit disorder and might soon need to start medication.
“I see the hyperness in him,” she said. “My pediatrician has said that he would venture to say that Lucas will be A.D.H.D.”
Stephen and Jacob were Lucas’s age — 6 — when they were given their first prescriptions.
The F.D.A. requires drug makers to prove that their drugs worksafely before the agency will approve them for sale in the UnitedStates. But doctors can prescribe and combine approved medicines asthey see fit. Such mixing is common in medicine but rarely studied bydrug makers.
Psychiatrists started mixing psychiatric medications because thedrugs were only moderately effective and often caused terrible sideeffects, said Dr. Steven E. Hyman, the provost ofand former director of the National Institute of Mental Health. “Noneof these drugs by themselves do an adequate job of controllingsymptoms,” Dr. Hyman said.
If one drug failed, many psychiatrists assumed that two or moredrugs used together might succeed. For decades, no one studied whetherthis was accurate. But in recent years, a trickle of studies haveexamined the question, with mixed results.
In studies in adults, some combinations of two drugs have been shownto work better than single medications to improve the symptoms ofdepression,and the mania associated with bipolar disorder. For example, a recentlarge government-financed study in adults, published in The ,found that two antidepressants worked a bit better than one for adultswho suffered from chronic, severe depression. But other studies havefound no benefit from commonly prescribed drug combinations.
The use of two-medicine combinations in children is on much shakierground. Even for single drugs, the effectiveness of some psychiatricmedications in younger patients is questionable: most trials ofantidepressants in depressed children, for instance, fail to show anybeneficial effect. But hardly any studies have examined the safety orthe effectiveness of medicine combinations in children. A 2003 reviewin The American Journal of Psychiatry found only six controlled trialsof two-drug combinations. Four of the six failed to show any benefit;in a fifth, the improvement was offset by greater side effects.
“No one has been able to show that the benefits of thesecombinations outweigh the risks in children,” said Dr. Daniel J. Safer,an associate professor of psychiatry atand an author of the 2003 review.
If the evidence for two-drug combinations is minimal, for three-drug combinations it is nonexistent, several top experts said.
“The data is zip,” Dr. Hyman said.
Many psychiatrists said that they turned to drug cocktails only indesperate circumstances. “If you’ve got a 15-year-old who is cutting upher arms, you’ve got a barn on fire and what are you supposed to do?”asked Dr. Alexander Lerman, a child and adolescent psychiatrist in NewYork, who said he rarely prescribed combinations.
Billy and Jackie Igafo-Te’o of Jackson, Mich., are among thedesperate. In the last seven years, their 12-year-old son, Michael,“has been on just about everything you can put a child on,” Mrs.Igafo-Te’o said. He is now taking four medications: an antipsychotic,an anticonvulsant, an antidepressant and a sleep medicine.
Despite the medications, Michael’s behavior has grown increasinglydisruptive. He has kicked and punched holes in almost every wall of theIgafo-Te’o home. He wrenched the sink off the wall in the upstairsbathroom and pulled two bedroom doors off their hinges, damaging theframes. The family no longer fixes the damage.
During a recent visit, Michael and Mr. Igafo-Te’o were sitting onthe living-room floor. Michael wanted the phone. His father held it outof reach to prevent Michael from playing with it. Michael becameincreasingly desperate. He cried. He cursed.
“That’s it, you have a timeout,” Mr. Igafo-Te’o said.
“No, no, no,” Michael answered. “You pimp!”
He slapped his father in the face, hard. Mr. Igafo-Te’o hustled Michael into the kitchen and forced him to sit for 20 minutes.
“What’s the purpose of all this medication if I still have to do that?” Mr. Igafo-Te’o asked.
He said he wanted to end Michael’s drug therapy. Among other side effects, the drugs have made Michael obese, which has led to.
Mrs. Igafo-Te’o quietly disagreed. “I’m afraid he wouldn’t be able to focus,” she said. “I’m afraid he would regress socially.”
“Regress socially? Look at him!” her husband responded, motioning to their son, crying uncontrollably on the kitchen floor.
“I have to believe in something,” his wife mumbled and walked out of the room.
Mr. Igafo-Te’o watched her go and then smiled apologetically.
“We always debate meds,” he said.
Most experts agree that some children are so violent or suicidalthat a combination of psychiatric drugs is worth trying. But recently,more psychiatrists have been asking whether in some cases drugs arebeing prescribed for children who do not need them, or for problemsthat fall within the spectrum of normal behavior. The doubters areespecially concerned with the growing use of drug combinations forpreschoolers.
Fate Riske, 3, of Fond du Lac, Wis., takes two antipsychotics and asleeping medicine to control what her mother, Elizabeth Klein-Riske,said were hours-long tantrums, a desire to watch the same moviesrepeatedly and an insistence on eating the meat, cheese and bread inher sandwiches separately.
On a recent visit, Fate played sweetly for four hours as herparents, who both have trouble walking, sat in front of a television.Sucking on a pacifier, Fate showed off her pink dress and matchingshoes.
Mrs. Klein-Riske credited the drugs for Fate’s cherubic behaviorduring the visit. But a few weeks on a different antipsychotic led Fateto become aggressive, talk rapidly and “run around wild, totally out ofcontrol,” said Mrs. Klein-Riske, who receives government financial andchild-care assistance because her daughter is considered mentally ill.
Fate’s weight ballooned in five months to 48 pounds from 30.
Dr. Gary Sachs, director of the Bipolar Clinic and Research Program atin Boston, estimated that half the children referred to his clinic forresearch in recent years — including many who took drug combinations —had the wrong diagnosis and often did well on fewer drugs. “Even amongproperly diagnosed bipolar patients, many come to our program alreadytaking medicines that interfered with each other,” Dr. Sachs said.
But Dr. Judith Rapoport, a senior investigator in child psychiatryat the National Institute of Mental Health, said that in herexperience, few children were overmedicated. Dr. Rapoport studieschildren with. Before entering her study, children must be drug-free for three weeks.
“We’ve had a handful of cases who are completely normal when theyget off drugs,” Dr. Rapoport said. “But most of these kids become very,very sick and unmanageable without drugs.”
The first psychiatric problem diagnosed in most children isattention deficit disorder, treated with stimulants — drugs thatimprove attentiveness. But when children’s problems persist, parents’relatively good experience with stimulants often convinces them toagree to try other medicines — in some cases drugs like theantipsychotic Risperdal or the anticonvulsant Depakote that have fewproven benefits in children and greater dangers, said Dr. RangaKrishnan, chairman of the department of psychiatry and behavioralscience at.
“After you get them on one drug, parents don’t seem to mind thesecond,” said Dr. Krishnan, who said that he had grave doubts about thegrowing use of psychiatric drug cocktails in children.
Antidepressants are commonly paired with stimulants, butantidepressant use has declined over the last year after the F.D.A.warning aboutrisk. In their place, physicians are prescribing combinations thatinclude antipsychotic and anticonvulsant drugs, according to Medco.From 2001 to 2005, the use of antipsychotic drugs in children andteenagers grew 73 percent, Medco found. Among girls, antipsychotic usemore than doubled.
On Again, Off Again
Andrew Darr of Caldwell, Idaho, whose sons took medications, saidthat he was opposed to it from the start. “When you come home from workand instead of getting them clawing at your feet and yelling, ‘Daddy,Daddy,’ you get a lethargic grunt, it just kills you,” Mr. Darr said.
His wife, Leslie Darr, eventually agreed to stop the medicines, but only after a family tragedy.
The Darrs have four children, Nicholas, 16, Nathan, 15, Becky, 12,and Benjamin, 9. At 3, Nicholas suffered a mild brain injury whenundiagnosedled him to suffer weeks of , Mrs. Darr said.
Mrs. Darr said that she was pressured by school officials to give Nicholas a stimulant at age 6. Nathan soon followed.
Three years later, the boys had a traumatic weekend away withrelatives. A month after that, Mrs. Darr said, both were hospitalizedfor a week and given a diagnosis of bipolar disorder and prescriptionsfor antipsychotic, antidepressant and sleeping medicines.
Over the next three years, Nicholas’s weight ballooned to 140 poundsfrom 52. Nathan went to 115 pounds from 48. Neither boy got muchtaller, Mrs. Darr said. They did poorly in school.
Then Becky developed a brain.A nurse practitioner gave Mrs. Darr free samples of an antipsychoticdrug to help her cope. After starting it, she said, she could not sleepor think straight. She realized that she had been giving similarmedicines to her sons for years and she decided to wean the boys offthe pills.
Their behavior immediately worsened. At one point, Nicholas left thehouse during a blizzard wearing only boxer shorts, Mrs. Darr said. Theyfound him in a tire swing saying, “Baaa.”
“There were several times that we almost gave up,” Mr. Darr said.
But after four months off medication, the boys’ behavior normalized,the Darrs said, and they were transferred out of special education andinto regular classes. The Darrs recently allowed the boys to spendtheir first evening at a mall without supervision, and in July theygave both boys their first bicycles. “They’ve come a long way,” Mrs.Darr said.
In an interview, Nicholas said the drugs “were not cool.”
“You go to school and everybody thinks, ‘Look at that retard,’ ” he said.
Still, most of the parents interviewed for this article said their children’s behavior deteriorated rapidly without medication.
Joanne Johnson of Hillsborough, N.J., described a psychiatrist’seffort to wean her 17-year-old son, Brad, off of all five of hispsychiatric medicines as “the biggest mistake of our lives.”
Brad, then 13, became suicidal and was hospitalized for weeks, Ms. Johnson said.
“He went into the hospital on five drugs and came out on fivedifferent ones, but he was unstable,” she said. “It took a little overtwo years to find the right match again.”
Brad is now taking lithium, an antipsychotic, an anticonvulsant, an antidepressant, a stimulant and a sleeping pill.
“He’ll probably be on these for the rest of his life,” Ms. Johnson said.
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