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.

[Nepenthe].

Iliad and Odyssey are two major literary sources on various phenomena related to human experience and knowledge. In the Odyssey we find references to the nepenthes, a mythical substance which can change the mood, causing sorrow and anger to be forgotten. We can not identify it with any of the well known substances that have these properties, such as opium from the opium poppy, the Egyptian kyfi or cannabis in the Scythians. Ancient Greeks used various anxiolytic, hypnotic and narcotic substances, but phenomena of addiction or withdrawal are not clearly described, with the exception of wine. Wine was used to lighten peoples minds and hearts, as well as a vehicle for drugs. Many ancient sources describe the negative effects of wine abuse. The study of ancient texts, from Homer's epics to Christian literature, allows a fundamental insight into the influence of psychotropic substances and alcohol on the human psyche.

The discovery of chlordiazepoxide and the clinical introduction of benzodiazepines: half a century of anxiolytic drugs.

The clinical introduction of chlordiazepoxide half a century ago was one of the major breakthroughs in the history of psychopharmacology, as it opened the door for the benzodiazepine saga, the pharmacological family par excellence in the treatment of anxiety disorders. This review analyses the discovery of this drug, which was filled with chance events, and numerous chemical and clinical errors of approach. Chlordiazepoxide, initially called methaminodiazepoxide, was patented in 1958 and introduced in clinical treatment in 1960 under the brand name Librium®. The benzodiazepines became the most widely prescribed drugs worldwide, provided truly effective treatment for "minor forms" (neuroses) of mental disorders for the first time, increased the quality of scientific methodology in clinical research, and enabled the development of new etiopathogenic theories for anxiety disorders, especially after the discovery in 1977 of their high-affinity receptor complex.

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.

[Leo Sternbach, an inventor of benzodiazepines].

A biography of Leo Sternbach, an inventor of benzodiazepine tranquillizers, is presented. It consists of (1) a societal desire for lifestyle pills, (2) Leo's birth in 1908 and youth, (3) education, (4) in Vienna, (5) in Zurich, (6) at Hoffmann-La Roche, Basel, (7) to the New World, (8) at Roche, Nutley NJ, (9) invention of the new drugs, (10) revolution of people's lifestyle, and (11) reward, retirement and obituary in 2005. This paper may be the first comprehensive biography of this remarkable chemist written in Japanese.

The role of serendipity in drug discovery.

Serendipity is one of the many factors that may contribute to drug discovery. It has played a role in the discovery of prototype psychotropic drugs that led to modern pharmacological treatment in psychiatry. It has also played a role in the discovery of several drugs that have had an impact on the development of psychiatry. "Serendipity" in drug discovery implies the finding of one thing while looking for something else. This was the case in six of the twelve serendipitous discoveries reviewed in this paper, i.e., aniline purple, penicillin, lysergic acid diethylamide, meprobamate, chlorpromazine, and imipramine. In the case of three drugs, i.e., potassium bromide, chloral hydrate, and lithium, the discovery was serendipitous because an utterly false rationale led to correct empirical results; and in case of two others, i.e., iproniazid and sildenafil, because valuable indications were found for these drugs which were not initially those sought The discovery of one of the twelve drugs, chlordiazepoxide, was sheer luck.

Meprobamate-tranquilizer or anxiolytic? A historical perspective.

Meprobamate was the first successful anti-anxiety drug of the modern era. On the 50th anniversary of its introduction, the authors trace the development of its synthesis, marketing and runaway success to understand the scientific and socio-political factors that may have shaped its use in clinical psychiatry. The relationship of this drug to the earlier development of chlorpromazine is explored to clarify the imperatives of drug classification in modern psychiatry.

Attitudes toward benzodiazepines over the years.

Benzodiazepines have been used extensively for the treatment of anxiety and related disorders since the 1960s. Although they have been proven to be effective as first-line treatment for anxiety disorders, during the 1980s public perception and concern for abuse liability and physical dependence with long-term use gave rise to a great deal of controversy. Negative perceptions toward the use of benzodiazepines for treating anxiety not only caused severely ill patients to go untreated or under-treated but also called into question whether the illness itself was worthy of treatment. Although new pharmacologic and psychological treatments for anxiety are available, psychopharmacologists continue to endorse benzodiazepines as primary or adjunct treatment for anxiety disorders. The intent of this article is to provide a historic overview of these issues and to offer some general clinical principles to help minimize the risk of abuse and dependence with benzodiazepine use.

[Pharmaceutical chemistry of sedato-hypnotics and anxiolytics]. / A szedato-hipnotikumok és anxiolitikumok gyógyszerészi kémiája.

The paper represents the 2nd part of a series about agents acting on the central nervous system. As previously, the material is divided into chapters of hystory, preparation; structure-properties-activity; therapeutical use; analysis.

Anxiolytics: past, present, and future agents.

Although anxiety disorders were classified as neurotic disorders and not systematically studied before DSM-III, researchers and clinicians have been searching for effective, safe agents to treat anxiety symptoms and disorders for over a century. In that time, barbiturates, benzodiazepines, and many classes of antidepressants have been used as anxiolytics, all with side effect profiles that made them less than optimal treatments for anxiety. The recognition of the role of GABA in anxiety disorders has led researchers to develop anxiolytics that target GABA. The long-sought-after class of anxiolytics that are both effective and safe may be found in the new research being conducted with agents that selectively target GABA receptors and their subtypes.

[Psychopharmacotherapy in the 20th century]. / Psychopharmakotherapie im 20. Jahrhundert.

Neuroleptics, antidepressants, mood stabilizers and anxiolytics are the most frequently prescribed drugs in psychiatric therapy. Their introduction came largely in the past five decades. This review summarizes the history that led to their discovery and introduction to the market in the 20th century.