Disease-mongering through clinical trials.

Our goal in this paper is to articulate a precise concept of at least a certain kind of disease-mongering, showing how pharmaceutical marketing can commercially exploit certain diseases when their best definition is given through the success of a treatment in a clinical trial. We distinguish two types of disease-mongering according to the way they exploit the definition of the trial population for marketing purposes. We argue that behind these two forms of disease-mongering there are two well-known problems in the statistical methodology of clinical trials (the reference class problem and the distinction between statistical and clinical significance). Overcoming them is far from simple.

The impact of diazepam's discovery on the treatment and understanding of status epilepticus.

The fortuitous discovery of the benzodiazepines and the subsequent application of these agents to the treatment of status epilepticus (SE) heralds in the modern age of treating this neurologic emergency. More than 50 years after their discovery, the benzodiazepines remain the drugs of first choice in the treatment of SE. However, the benzodiazepines can be ineffective, especially in those patients whose seizures are the most prolonged. The benzodiazepines act by increasing the affinity of gamma-aminobutyric acid (GABA) for GABAA receptors. A receptor's subunit composition affects its functional and pharmacologic properties, trafficking, and cellular localization. The GABAA receptors that mediate synaptic inhibition typically contain a gamma2 subunit and are diazepam-sensitive. Among the GABAA receptors that mediate tonic inhibition are the benzodiazepine-insensitive delta subunit-containing receptors. The initial studies investigating the pathogenesis of SE demonstrated that a reduction in GABA-mediated inhibition within the hippocampus was important in maintenance of SE, and this reduction correlated with a rapid modification in the postsynaptic GABAA receptor population expressed on the surface of the hippocampal principal neurons. Subsequent studies found that this rapid modification is, in part, mediated by an activity-dependent, subunit-specific trafficking of the receptors that resulted in the reduction in the surface expression of the benzodiazepine-sensitive gamma2 subunit-containing receptors and the preserved surface expression of the benzodiazepine-insensitive delta subunit-containing receptors. This improved understanding of the changes in the trafficking of GABAA receptors during SE partially accounts for the development of benzodiazepine-pharmacoresistance and has implications for the current and future treatment of benzodiazepine-refractory SE.

Social reactions to Valium and Prozac: a cultural lag perspective of drug diffusion and adoption.

BACKGROUND: In the sociological context, the concept of cultural lag holds that material technologies advance more rapidly than social guidelines for their use. The result can be social conflict including liability accusations and product stigmatization that have characterized several new drugs which were widely accepted initially but then publicly criticized in the lay and scientific press. OBJECTIVES: The objective was to illustrate the utility of the concept of cultural lag to technology commercialization by applying cultural lag to the social and professional environments surrounding the diffusion of the "minor tranquilizers" Librium and Valium in the United States from the 1950s to the 1970s, and the antidepressant Prozac from 1987 to 2005. The intention is to develop a perspective from which to view patterns of social acceptance followed by critique that may occur when technological advances are introduced to the marketplace. METHODS: This study systematically reviews academic, medical, and lay literature regarding the diffusion of the "minor tranquilizers" Librium and Valium in the United States from the 1950s to the 1970s, and the antidepressant Prozac from 1987 to 2005. RESULTS: The minor tranquilizers and Prozac both reveal similar patterns of initial widespread public endorsement, followed by growing public criticism and recommendations for more restrictive usage guidelines. CONCLUSIONS: Cultural lag provides a perspective from which to anticipate, view, and avoid controversies that develop from new technologies in general and pharmaceutical technologies in particular. Market demands for rapid introduction must be balanced by public education. This requires proactive encouragement of lay and professional discussions and the establishment of marketing guidelines that aid development of social consensus regarding appropriate usage.