Sept. 29, 2005 -- The FDA has issued a public health advisory about rare reports of suicidal thinking in children and adolescents taking Strattera, a drug approved to treat attention deficit hyperactivity disorder (ADHD) in adults and children.
The FDA has ordered Strattera's maker, Eli Lilly and Co., to revise this product to include a "black box" warning on Strattera's product label and additional warning statements that alert health care providers of the increased risk of suicidal thinking in children and adolescents.
"There were no suicides among children, adolescents, or adults on the medication during any Strattera clinical trials and there was no indication of an increased risk of suicidal thinking in the adult population," says Lilly.
A black box warning is the strongest type of warning that the FDA can require for a drug. It is generally reserved for warning prescription drug users about adverse drug reactions that can cause serious injury or death.
The FDA also determined that the company must prepare a medication guide about the risk associated with the drug, which will be distributed to patients when Strattera is dispensed.
Strattera's boxed warning will "communicate new information about uncommon reports of suicidal thoughts in children and adolescents," states a Lilly news release.
The drug company says it's working with the FDA to finalize the warning and with European and Australian regulatory agencies on label changes for Strattera in those countries.
Strattera is the first FDA-approved nonstimulant to treat ADHD and provide full-symptom relief, says Lilly. The company is a WebMD sponsor.
Strattera has been on the market since 2002 and has been used by more than 2 million patients, according to the FDA.
Monitoring Children Taking Strattera
The FDA is advising health care providers and caregivers that children and adolescents being treated with Strattera should be closely monitored for worsening of symptoms as well as agitation, irritability, suicidal thinking or behaviors, and unusual changes in behavior, especially during the initial few months of therapy or when the dose is changed (either increased or decreased).
This monitoring should include daily observation by families and caregivers and frequent contact with the physician, says the FDA.
Patients and caregivers who have concerns or questions about these symptoms should contact their health care provider, notes the FDA.
The advisory comes after a review and analysis of 12 studies conducted in children with ADHD and one trial in children with bedwetting that identified an increased risk of suicidal thinking for Strattera, says the FDA.
The FDA told Lilly to review its database and studies on the drug, which included more than 2,200 patients - 1,357 of whom had received Strattera and 851 of whom had received a fake drug (placebo).
The analysis showed that 0.4% of children treated with Strattera reported suicidal thinking (five children out of 1,357) compared with no cases in children treated with the placebo.
One patient taking Strattera in those trials attempted suicide, note the FDA and Lilly.
The increased risk of suicidal thinking with Strattera in the trials is "small but statistically significant," says Lilly.
What's on the Warning Label
Based on the data, the FDA has determined that the following points are appropriate for inclusion in the boxed warning:
- Strattera increases the risk of suicidal thinking in children and adolescents with ADHD.
- Anyone considering the use of Strattera in a child or adolescent for ADHD must balance the increased risk of suicidal thinking with the clinical need for the drug.
- Patients who are started on therapy should be observed closely for clinical worsening, suicidal thinking or behaviors, or unusual changes in behavior.
- Families and caregivers should be advised to closely observe the patient and to communicate changes or concerning behaviors with the prescriber.
"Lilly's top priority is to help doctors, patients, and their families make informed treatment decisions, so we are reaching out extensively to educate physicians and the public about this product label change," says Alan Breier, MD, vice president and chief medical officer at Lilly, in a news release.
"While suicidal thinking was uncommon in patients on the medication during clinical trials, it is important for parents to be aware it can occur, and to discuss any unusual symptoms with a physician," Breier continues.
"Also important for parents to know is that Lilly continues to view Strattera as a safe and effective treatment option, and those doing well on the medication should be able to continue their treatment with confidence," he says.
For perspective on the Strattera advisory, WebMD spoke with Eugenio Rothe, MD.
Rothe directs the child and adolescent psychiatry clinic at the University of Miami Jackson Memorial Hospital. He is also an associate professor of psychiatry at the University of Miami.
"We see hundreds and hundreds of kids with ADHD here at the clinic at Jackson Memorial. We're the largest child psychiatry clinic in the southeastern United States. And I have never seen anybody on Strattera get suicidal," says Rothe.
Be Aware, but Don't Panic
FDA warnings are generally "very positive and very necessary," says Rothe. However, he says those warnings often get blown out of proportion by the media and misunderstood by the public.
"Every time there's one of these warnings, the media presents this as, 'This is real high danger stay away from this.' The problem is that any medication is going to have side effects," says Rothe.
"The way it's presented to the public is that it it's some kind of catastrophic alarm that people should stay away from the medications. What it really means is that you just have to be careful and that people need to be treated carefully and by the right specialists and with enough frequency between visits so that the treatment can be conducted safely," says Rothe.
"The brain is the most complicated organ in the human body," he continues. "We've been to the moon and we still don't understand a lot of how the brain works. ... So this is all very new stuff," says Rothe.
"In adolescents, it's very common to be overwhelmed by a problem and think, 'Oh, just like Romeo and Juliet, I should commit suicide' or whatever, but that doesn't mean that the person's going to do it," says Rothe.
"That would be very interesting to hear how [the trials] defined suicidal thoughts or ideas. Did [the patients] really feel like they were going to do it?" Rothe asks.
"The follow-up [with patients taking Strattera] needs to be done much more carefully, and that would be my message," he says.
The FDA offers this contact information in its advisory:
Health care professionals are encouraged to report any unexpected adverse events associated with Strattera directly to Lilly at (800) LillyRx or to the FDA MedWatch program at (800) FDA-1088; by fax at (800) FDA-0178; by mail to MedWatch, Food and Drug Administration, HFD-410, 5600 Fishers Lane, Rockville, MD, 20857-9787; or online at www.fda.gov/medwatch/report.htm.