Proof Is Scant on Psychiatric Drug Mix for Young

Ms. Kehoe, who receives government financial and child-care assistance because her children are considered mentally ill, said she knew that there were risks to the drug cocktails. Both her sons are short and underweight for their age — a common side effect of stimulants — and she fears that the drugs have affected their health and 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 herself takes psychiatric medication.

In fact, the drug agency has specifically warned against the use of Lamictal, one of the drugs Stephen takes, in children who, like him, do not suffer from seizures because in 8 out of 1,000 children the drug causes life-threatening rashes.

Stephen and Jacob’s psychiatrist did not reply to telephone messages left with an office secretary on three different days. Ms. Kehoe said that she asked him to speak to this reporter but that he refused. The boys have had 11 psychiatrists over the last three years, according to prescription 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 of attention 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 work safely before the agency will approve them for sale in the United States. But doctors can prescribe and combine approved medicines as they see fit. Such mixing is common in medicine but rarely studied by drug makers.

Psychiatrists started mixing psychiatric medications because the drugs were only moderately effective and often caused terrible side effects, said Dr. Steven E. Hyman, the provost of Harvard University and former director of the National Institute of Mental Health. “None of these drugs by themselves do an adequate job of controlling symptoms,” Dr. Hyman said.

If one drug failed, many psychiatrists assumed that two or more drugs used together might succeed. For decades, no one studied whether this was accurate. But in recent years, a trickle of studies have examined the question, with mixed results.

In studies in adults, some combinations of two drugs have been shown to work better than single medications to improve the symptoms of depression, obsessive-compulsive disorder and the mania associated with bipolar disorder. For example, a recent large government-financed study in adults, published in The New England Journal of Medicine, found that two antidepressants worked a bit better than one for adults who suffered from chronic, severe depression. But other studies have found no benefit from commonly prescribed drug combinations.

The use of two-medicine combinations in children is on much shakier ground. Even for single drugs, the effectiveness of some psychiatric medications in younger patients is questionable: most trials of antidepressants in depressed children, for instance, fail to show any beneficial effect. But hardly any studies have examined the safety or the effectiveness of medicine combinations in children. A 2003 review in The American Journal of Psychiatry found only six controlled trials of 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 these combinations outweigh the risks in children,” said Dr. Daniel J. Safer, an associate professor of psychiatry at Johns Hopkins University and 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 in desperate circumstances. “If you’ve got a 15-year-old who is cutting up her 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 New York, who said he rarely prescribed combinations.

Billy and Jackie Igafo-Te’o of Jackson, Mich., are among the desperate. 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 increasingly disruptive. He has kicked and punched holes in almost every wall of the Igafo-Te’o home. He wrenched the sink off the wall in the upstairs bathroom and pulled two bedroom doors off their hinges, damaging the frames. The family no longer fixes the damage.

During a recent visit, Michael and Mr. Igafo-Te’o were sitting on the living-room floor. Michael wanted the phone. His father held it out of reach to prevent Michael from playing with it. Michael became increasingly 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 asthma.

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.

Divergent Views

Most experts agree that some children are so violent or suicidal that a combination of psychiatric drugs is worth trying. But recently, more psychiatrists have been asking whether in some cases drugs are being prescribed for children who do not need them, or for problems that fall within the spectrum of normal behavior. The doubters are especially concerned with the growing use of drug combinations for preschoolers.

Fate Riske, 3, of Fond du Lac, Wis., takes two antipsychotics and a sleeping medicine to control what her mother, Elizabeth Klein-Riske, said were hours-long tantrums, a desire to watch the same movies repeatedly and an insistence on eating the meat, cheese and bread in her sandwiches separately.

On a recent visit, Fate played sweetly for four hours as her parents, who both have trouble walking, sat in front of a television. Sucking on a pacifier, Fate showed off her pink dress and matching shoes.

Mrs. Klein-Riske credited the drugs for Fate’s cherubic behavior during the visit. But a few weeks on a different antipsychotic led Fate to become aggressive, talk rapidly and “run around wild, totally out of control,” said Mrs. Klein-Riske, who receives government financial and child-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 at Massachusetts General Hospital in Boston, estimated that half the children referred to his clinic for research in recent years — including many who took drug combinations — had the wrong diagnosis and often did well on fewer drugs. “Even among properly diagnosed bipolar patients, many come to our program already taking medicines that interfered with each other,” Dr. Sachs said.

But Dr. Judith Rapoport, a senior investigator in child psychiatry at the National Institute of Mental Health, said that in her experience, few children were overmedicated. Dr. Rapoport studies children with schizophrenia. Before entering her study, children must be drug-free for three weeks.

“We’ve had a handful of cases who are completely normal when they get 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 is attention deficit disorder, treated with stimulants — drugs that improve attentiveness. But when children’s problems persist, parents’ relatively good experience with stimulants often convinces them to agree to try other medicines — in some cases drugs like the antipsychotic Risperdal or the anticonvulsant Depakote that have few proven benefits in children and greater dangers, said Dr. Ranga Krishnan, chairman of the department of psychiatry and behavioral science at Duke University.

“After you get them on one drug, parents don’t seem to mind the second,” said Dr. Krishnan, who said that he had grave doubts about the growing use of psychiatric drug cocktails in children.

Antidepressants are commonly paired with stimulants, but antidepressant use has declined over the last year after the F.D.A. warning about suicide risk. In their place, physicians are prescribing combinations that include antipsychotic and anticonvulsant drugs, according to Medco. From 2001 to 2005, the use of antipsychotic drugs in children and teenagers grew 73 percent, Medco found. Among girls, antipsychotic use more than doubled.

On Again, Off Again

Andrew Darr of Caldwell, Idaho, whose sons took medications, said that he was opposed to it from the start. “When you come home from work and 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 when undiagnosed appendicitis led him to suffer weeks of high fever, 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 with relatives. A month after that, Mrs. Darr said, both were hospitalized for a week and given a diagnosis of bipolar disorder and prescriptions for antipsychotic, antidepressant and sleeping medicines.

Over the next three years, Nicholas’s weight ballooned to 140 pounds from 52. Nathan went to 115 pounds from 48. Neither boy got much taller, Mrs. Darr said. They did poorly in school.

Then Becky developed a brain tumor. A nurse practitioner gave Mrs. Darr free samples of an antipsychotic drug to help her cope. After starting it, she said, she could not sleep or think straight. She realized that she had been giving similar medicines to her sons for years and she decided to wean the boys off the pills.

Their behavior immediately worsened. At one point, Nicholas left the house during a blizzard wearing only boxer shorts, Mrs. Darr said. They found 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 and into regular classes. The Darrs recently allowed the boys to spend their first evening at a mall without supervision, and in July they gave 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’s effort to wean her 17-year-old son, Brad, off of all five of his psychiatric 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 five different ones, but he was unstable,” she said. “It took a little over two 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.