US drugmaker Eli Lilly says it will update the label of its attention-deficit hyperactivity disorder drug, Strattera (atomoxetine), to carry a "black box" warning, the strongest required by US regulators, relating to the increased risk of suicidal thoughts in children and adolescents taking the product. Similar warnings will also appear in Europe and in Australia.

The US Food and Drug Administration is currently conducting a large-scale review of psychiatric drugs and their possible link to suicidal thoughts, under which it requested an analysis of adverse-event data from clinical trials with Strattera. This revealed a significant increase in the risk of suicidal ideation in patients treated with the drug.

Consequently, the agency FDA said in a statement that it is advising healthcare providers and caregivers that children and adolescents being treated with the should be closely monitored for clinical worsening, as well as agitation, irritability, suicidal thinking or behaviors, and unusual changes in behaviour.

However, Alan Breier, MD, vice president and chief medical officer at the firm, maintains that the drug is safe. He explained: “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. 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."

But this is not the first time the agent has been dogged by safety concerns. Earlier this year, the UK’s Medicines and Healthcare products Regulatory Agency issued a warning that Strattera, the only nonstimulant medicine approved for the treatment ADHD in children, had been associated with liver damage [[04/02/05a]], after Lilly cautioned that doctors should stop treatment in patients with jaundice [[20/12/04d]].

Strattera’s sales have already showed signs of struggle; second-quarter 2005 revenues tumbled 31% to $123.5 million compared to the year-earlier period. Furthermore, the firm says it expects this trend to continue for the rest of the year, as a fall in demand is coupled with greater-than-anticipated wholesaler de-stocking.

Shares in the drugmaker seemed relatively unaffected by the news, closing up 1.5% at $54.29, as Lilly backed its previous sales and earnings forecast for the full year, with earnings per share of $1.90-$1.96 on revenue growth of 6%-8%.

Meanwhile, data from a study reported in the September 29 edition of the New England Journal of Medicine indicate that Lilly’s Xigris (drotrecogin alfa activated), which is cleared in the USA for the treatment of sepsis, does not seem to provide any benefit to patients who are at low risk of death.

The trial revealed that the agent, which represents the first bioengineered therapy for this indication, did not show a superior efficacy to placebo in preventing death. The study authors concluded: “The absence of a beneficial treatment effect, coupled with an increased incidence of serious bleeding complications, indicates that DrotAA should not be used in patients with severe sepsis who are at low risk for death.”

Since its US approval in 2001 for the treatment of high-risk patients, Xigris has been subject to intense scrutiny, as the FDA’s decision to clear the drug was contingent on additional post-marketing trials [[21/11/01b]].