Questions Urged on Desipramine : Medicine: Prescribed for a variety of childhood ills, the drug has been linked to sudden, unexplained deaths.

Parents of children who take a medication called desipramine should discuss its use with the prescribing doctor, experts say.

The drug has been widely prescribed to children for hyperactivity, depression and bed-wetting at least since the early 1970s. But in the last few years it has been linked to several sudden, unexplained deaths in children.

Dr. Barbara Geller of the Washington University School of Medicine in St. Louis, who investigates use of psychiatric medicines in children, said psychiatrists have been concerned for several years about the possibility of sudden death in children taking desipramine.

She said caution should be exercised when children or adolescents take any drug of this class (called tricyclics), including imipramine, nortriptyline and chlomipramine. Imipramine is prescribed for bed-wetting more often than desipramine.

Desipramine is the tricyclic most commonly prescribed for children, which may explain why it has received more attention, she said.

But Dr. Mark Riddle, director of the division of child and adolescent psychiatry at Johns Hopkins University, said he is particularly concerned about desipramine because of the reports of children’s deaths in medical journals and the way the drug acts in the body.

The topic made the news again late last year. The Register-Guard of Eugene, Ore., reported that Food and Drug Administration records linked desipramine and imipramine to nearly 80 deaths in children since the early 1970s, and more deaths may have actually occurred. The reported number included at least a dozen suicides and a similar number of accidental overdoses.

But Dr. Sandra Kweder, acting director of FDA’s division of epidemiology and surveillance, told the Associated Press that she could not comment on the reported total of deaths without knowing more details.

Desipramine’s official prescribing guidelines include a warning about use in children. “Our position is that desipramine should not be used in children,” said Richard Johnson, spokesman for Marion Merrell Dow Inc., one of several makers of desipramine.

Doug Arbesfeld of Ciba-Geigy Corp., which makes imipramine, said the company was aware of 13 deaths since 1973 in children taking that drug. Ten were overdoses, two involved a child taking multiple drugs and one death was apparently due to injuries from child abuse, he said.

The company has not seen any reports of death from the drug’s use at recommended doses, he said.

Geller advised parents of children or adolescents who take any tricyclic to discuss it with the prescribing doctor so “they can make informed decision about continuing with this medication.”

Parents should make sure that every time the dose level is increased, the child’s blood levels are checked and an electrocardiogram is performed, she said. If that has not happened, parents should get a second opinion from another doctor, she said.

Similarly, before starting any tricyclic the child should have a thorough physical examination, including an electrocardiogram, and there should be no family history of sudden death in relatives younger than 40, she said.

The reasons for the deaths in children taking desipramine or imipramine are not always known, Geller said. Apart from suicides, accidental overdoses and interactions with other medications, they could include causes unrelated to the drugs, she said.

“We need a lot more research and investigation (into the reported deaths), and doctors need to be very careful in prescribing (the drugs) until there’s more information,” she said.

Concern over desipramine (pronounced day-ZIP-ra-meen) dates from June, 1990, when a medical publication reported three cases of children who died while taking the drug, Riddle said. He and colleagues reported a fourth death last July.

The children were two 8-year-old boys, a 9-year-old boy and a 12-year-old girl. None had taken an overdose, Riddle said.

Riddle said he thinks desipramine is still used fairly widely, but far less than it was before the 1990 report. “I think that many, many clinicians are concerned. Although this risk may be very small, sudden death of a child is obviously a big deal,” he said.

He and Geller said they think that psychiatrists who specialize in treating children and adolescents are generally informing parents of the risks of desipramine, because the topic has been stressed at professional meetings and in journals. Riddle said it is not clear whether that awareness campaign has reached other doctors who can prescribe the drug.

The federally regulated official guidelines for prescribing desipramine warn that the drug is not recommended for use in children, because safety and effectiveness in them has not been established. They also warn that there have been several reports of sudden death in children.

Doctors can still legally prescribe the drug in children in what is called “off-label” use.

Doctors who treat children often prescribe off-label because of a lack of information about many medications in children, Riddle said. “If I didn’t prescribe off-label, my ability to treat children effectively would be severely limited,” he said.

Some studies have shown desipramine to be safe and effective in children, but the research has not met the FDA’s criteria for changing the prescribing guidelines, Riddle said.

Desipramine “has been a big help to a lot of my patients” with depression or hyperactivity, Riddle said. But “I’m concerned about the drug and I don’t use it unless I need to. . . . I’m finding that most of the time I can provide quality care to my patients without using it.”

Geller said the decision whether to use desipramine can be complex, involving a weighing of risks and benefits.

While there are several drugs for treating hyperactivity, she said, some children respond best to desipramine. And since hyperactivity can lead to drug abuse and a tendency for minor and major accidents, withdrawing desipramine from one of those children would have its own risks, she said.

Similarly, for depressed children who respond particularly well to desipramine, “if you take it away, (they) may kill themselves. So again it’s a risk-benefit ratio that’s very complicated.”