Evelyn Pringle February 15, 2006
A not yet released discussion paper written by the British Medicines and Healthcare Regulatory Agency, reveals that last fall, there were 130 reports of suicidality in a single month by patients treated with the attention deficit drug Strattera.
In addition, the paper reveals that there have also been more than 760 spontaneous reports of cardiac disorders, 172 reports of liver damage, and about 20 reports of completed suicides.
The large number of adverse event reports are exposed in a December 9, 2005, paper sent to the Swedish Medical Products Agency by the British agency. The information was obtained through FOIA-requests, and was released under a court order, according to Swedish investigative reporter Janne Larsson
A press release on the British discussion paper will be issued tomorrow morning, on February 16, 2006.
Drug making giant, Eli Lilly originally sought FDA approval of Strattera as an antidepressant and was unsuccessful. The drug has since been marketed as a treatment for ADHD. Strattera is approved for use with children and adult patients. However, the drug has not been tested in children less than 6 years of age or in geriatric patients, according Lilly.
Strattera is selective norepinephrine reuptake inhibitor, and the first non-stimulant drug approved to treat ADHD. Since Strattera is chemically similar to depression drugs linked to suicidal thoughts in children in 2004, last year the FDA ordered Lilly to analyze its data on Strattera.
The 12 short-term (6-18 weeks) trials reviewed involved more than 2200 patients, including 1357 receiving Strattera and 851 receiving placebo. The analysis found a greater risk of suicidal thinking during the first few months in those receiving Strattera. The average risk of suicidal thinking was about 4 per thousand with Strattera compared to no events in placebo-patients. There was 1 suicide attempt in a patient treated with Strattera.
Based on the above data, the FDA determined that the following points should be included in a boxed warning:
(1) Strattera increases the risk of suicidal thinking in children and adolescents with ADHD
(2) 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.
(3) Patients who are started on therapy should be observed closely for clinical worsening, suicidal thinking or behavior, or unusual changes in behavior
(4) Families and caregivers should be advised to closely observe the patient and to communicate changes or concerning behaviors with the prescriber
On September 29, 2005, the FDA announced that it had directed Lilly to revise Stattera labels to include black boxed statements to alert health care providers to an increased risk of suicidal thinking in children and adolescents treated with this drug.
The FDA also told Lilly to prepare a Patient Medication Guide, to advise patients of the risks and precautions that should be taken, to be distributed by pharmacists when Strattera is dispensed.
Once the media reported the new back box warnings and the risks became well-publicized, spontaneous reports of adverse events began to pour in. It was between September 23, 2005 and October 25, 2005, that the 130 cases of suicidal and self-injurious behavior were reported.
In the 3 year period prior to the warning, between November 2002 and September 2005, only about 300 cases had been reported between. "This means that 30 percent of all reports of suicidality were received in one month," Ms Larsson points out.
In 2004, Strattera was Lilly's 6-best-selling product, raking in over $665 million in global sales. However, when the FDA ordered the black box warning last fall, Friedman Billings Ramsey analyst, David Moskowitz, told Reuters News, he cut his 2006 sales forecast for Strattera to $518 million from $685 million.
Once the black box warning was announced, it apparently did not take long for sales to drop off. According to Dow Jones New Wire on January 26, 2006, sales of Strattera, fell 8% to $168 million for the last quarter of 2005.
On February 10, 2006, the FDA safety advisory committee recommended that attention deficit drugs carry a black box warning about heart-attack risks, because the panel members agreed that the public is largely unaware of the risks and may be overusing the drugs, to include Adderall, Concerta, Ritalin, and generic versions of Ritalin called methylphenidate. The committee also recommended that a medication guide for patients and parents be provided when the drugs are dispensed.
However, Strattera, is not classified as a stimulant and is therefore, not required to carry the new proposed black box warning. However, a Lilly warning on Strattera already states: "Patients with a history of high or low blood pressure, increased heart rate, or any heart or blood vessel disease should tell their doctor before taking Strattera."
It remains to be seen what will happen to Strattera once this latest devastating news about adverse reports reaches consumers.