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 effect...

[1]  P. McCullagh.  Regression Models for Ordinal Data , 1980 .

[2]  C. Cox,et al.  Location-scale cumulative odds models for ordinal data: a generalized non-linear model approach. , 1995, Statistics in medicine.

[3]  D. Stram,et al.  Variance components testing in the longitudinal mixed effects model. , 1994, Biometrics.

[4]  C. V. D. Kroef.  REACTIONS TO TRIAZOLAM , 1979, The Lancet.

[5]  C. Morrell,et al.  Likelihood ratio testing of variance components in the linear mixed-effects model using restricted maximum likelihood. , 1998, Biometrics.

[6]  Robert W. Mee,et al.  A mixed-model procedure for analyzing ordered categorical data , 1984 .

[7]  Anthony S. Bryk,et al.  Hierarchical Linear Models: Applications and Data Analysis Methods , 1992 .

[8]  P. McCullagh,et al.  Generalized Linear Models , 1984 .

[9]  D. Hedeker,et al.  A Multilevel Thresholds of Change Model for Analysis of Stages of Change Data , 1998 .

[10]  F. Harrell,et al.  Partial Proportional Odds Models for Ordinal Response Variables , 1990 .

[11]  E. Uhlenhuth,et al.  New epidemiologic findings about insomnia and its treatment. , 1992, The Journal of clinical psychiatry.

[12]  A random effects model for ordinal responses from a crossover trial , 1991 .

[13]  Joseph V. Ierza.  Ordinal probit: A generalization , 1985 .

[14]  E. Uhlenhuth,et al.  Insomnia and its treatment. Prevalence and correlates. , 1985, Archives of general psychiatry.

[15]  Alan Agresti,et al.  A proportional odds model with subject-specific effects for repeated ordered categorical responses , 1993 .

[16]  S D Imber,et al.  Some conceptual and statistical issues in analysis of longitudinal psychiatric data. Application to the NIMH treatment of Depression Collaborative Research Program dataset. , 1993, Archives of general psychiatry.

[17]  D. Wysowski,et al.  Adverse behavioral reactions attributed to triazolam in the Food and Drug Administration's Spontaneous Reporting System. , 1991, Archives of internal medicine.

[18]  D. Bliwise.  Treating insomnia: pharmacological and nonpharmacological approaches. , 1991, Journal of psychoactive drugs.

[19]  M K Stoller,et al.  Economic effects of insomnia. , 1994, Clinical therapeutics.

[20]  D. Hedeker,et al.  MIXOR: a computer program for mixed-effects ordinal regression analysis. , 1996, Computer methods and programs in biomedicine.

[21]  K. Liang,et al.  Asymptotic Properties of Maximum Likelihood Estimators and Likelihood Ratio Tests under Nonstandard Conditions , 1987 .

[22]  D. Kupfer,et al.  Management of insomnia. , 1997, The New England journal of medicine.

[23]  Robert D. Gibbons,et al.  Trend in correlated proportions , 1987 .

[24]  J. Jansen,et al.  On the Statistical Analysis of Ordinal Data When Extravariation is Present , 1990 .

[25]  Barr Jb,et al.  HEALTH VISITING AND GENERAL PRACTICE. , 1964 .

[26]  D. Hedeker,et al.  A random-effects ordinal regression model for multilevel analysis. , 1994, Biometrics.