Assessment of the Safety and Efficacy Data for the Hypnotic Halcion^(R): Results of an Analysis by an Institute of Medicine Committee

Abstract

Recent estimates indicate a 10% prevalence of chronic insomnia in the adult population of the United States, with an associated annual cost of more than $90 billion. Since its approval in 1982 for use in the treatment of insomnia, an estimated 11 billion prescriptions for Halcion^(R) (triazolam) have been filled worldwide. Concerns about the safety of Halcion began to emerge when a Dutch psychiatrist reported a possible link between the drug and a syndrome that included depression, amnesia, hallucinations, and anxiety. Since that time, the United Kingdom, Brazil, Argentina, Norway, and Denmark removed Halcion from the market, and the manufacturer, Upjohn, withdrew Halcion from the market in The Netherlands. Other countries, including the United States and Canada, modified the labeling to reduce the recommended dose and duration of treatment and to heighten awareness regarding possible side effects affecting behavior and cognition. The labeling changes raised questions regarding the hypnotic effectiveness of these lower doses of Halcion. Based on a 1996 U.S. Food and Drug Administration (FDA) task force report, the Institute of Medicine (IOM) of the National Academy of Sciences assessed the adequacy, quality, and overall confidence in the data on the effectiveness and safety of Halcion at different doses and durations, including those specified in the current product labeling. This article provides a summary of the IOM report titled “Halcion: An Independent Assessment of Safety and Efficacy Data” and a more detailed overview of the statistical analysis that led to the committee's conclusions.

Key Words:

• Insomnia
• Institute of Medicine
• Mixed-effects regression models
• Ordinal probit regression
• Sedative-hypnotic medication
• Triazolam.