The Food and Drug Administration's public health advisory on a potential increased risk of suicidal ideation in children and adolescents taking atomoxetine is a cautious move, given the paucity of data. But the data should not be ignored, several experts told CLINICAL PSYCHIATRY NEWS.
The FDA has instructed Eli Lilly & Co. to place a new black box warning on atomoxetine (Strattera) and to develop a medication guide that explains potential risks to patients and caregivers.
Previously, the FDA had instructed the company to search its databases for adverse psychiatric events associated with atomoxetine, including suicidal ideation or behavior. The agency identified a small but statistically significant increased risk of suicidal thinking with atomoxetine, compared with placebo.
Atomoxetine, marketed as the first nonstimulant for the treatment of attention-deficit hyperactivity disorder (ADHD) is not the only ADHD drug to come under FDA scrutiny. Manufacturers of other ADHD drugs, including methylphenidate and the stimulants, were recently asked to review their databases as well. Word on whether a similar increased risk of suicidal ideation and/or behavior exists is not expected until next year, according to an FDA spokesperson.
In the atomoxetine study, 6 children were identified in the Eli Lilly database and clinical trials—5 with suicidal ideation and 1 who attempted suicide—among 1,357 patients taking the drug, for a rate of 0.4%. There were no cases of suicidal ideation or behavior among 851 patients taking a placebo.
“In the FDA analysis, there was only one child who did anything, and it was a small overdose where the intention was not clear,” said Mina K. Dulcan, M.D., director of the division of child and adolescent psychiatry at Northwestern University, Chicago.
Dr. Dulcan, a member of the Lilly Straterra Global Advisory Board, said the black box warning is more severe than is warranted based on the data. “The signal is very weak, and the black box is very scary,” she said.
David Fassler, M.D., said any risk of potential suicide ideation or behavior should be taken seriously. But in the case of atomoxetine, the risk appears to be extremely low. “There were no actual suicides in the studies. We're talking about a small number of children, but we certainly shouldn't ignore it. We need to understand what it really means,” said Dr. Fassler, a child and adolescent psychiatrist practicing in Burlington, Vt.
“The FDA and the pharmaceutical companies are going out of their way to be extra cautious,” he added. “My concern is that, in an effort to get people as much information as quickly as possible, they can confuse the public.”
In October 2004, the FDA required black box warnings about possible increased risk of suicidal ideation on antidepressant agents, including selective serotonin reuptake inhibitors (SSRIs).
“It is important to note that here, as with the SSRIs, the increased rates are real, but not very much,” James Perrin, M.D., said.
“It is not an indication that we should discontinue a child on atomoxetine or not use it in the future. It tells us we need to at least assess for the possibility of suicidal ideation or behavior,” said Dr. Perrin, director of the division of general pediatrics at the MassGeneral Hospital for Children, Boston.
“As with the SSRIs, it's possible that the [ADHD] medications make someone more likely to report what they are thinking,” Dr. Fassler said. Because the atomoxetine data were based on spontaneous reports, he said that more research is needed, “but in the interim, physicians and parents need as much information as possible.”
Because of the black box warning, Dr. Perrin plans to ask patients or parents a few more questions when prescribing atomoxetine. Dr. Dulcan said the warning does not change how likely she is to prescribe atomoxetine, “but I will inform parents there is a warning.”
In a statement, the American Academy of Child and Adolescent Psychiatry expressed concern that the FDA's action might limit the number of patients who receive appropriate treatment for ADHD: “Though it is important for physicians to notify families of the benefits and risks associated with atomoxetine, the risks of not receiving appropriate treatment must be considered.” Possible school failure, substance abuse, and an increased likelihood of entrance to the juvenile justice system are possible risks cited by the academy.
Dr. Fassler does not expect significant changes in the practice pattern of child and adolescent psychiatrists based on these data. He also said that as additional studies and information become available, they would continue to be monitored.
FULL TEXT