The early history of the neuroscience of attention-deficit/hyperactivity disorder.

Research on the neurobiology and pharmacotherapy of attention-deficit/hyperactivity disorder (ADHD) has grown exponentially since 1980. A reasonable question is whether this research has improved our understanding and treatment of ADHD. This article describes relevant developments that took place roughly between 1900 and 1970. During this time, the efficacy of stimulant therapy for the disorder was established and the symptoms of ADHD were linked to many possible nervous system disorders including in the brain-stem, reticular formation, diencephalon, basal ganglia, frontal lobes, and cortex. In 1970, the catecholamine hypothesis of ADHD was proposed. It is concluded that early theories about the neurobiologic basis of ADHD anticipated core ideas of modern theory.

The end of drugging children: toward the genealogy of the ADHD subject.

This genealogy of the ADHD subject will demonstrate that over the course of the twentieth century a new relation between power, knowledge, the body, and ethical practices of self-formation emerged around the ADHD-type in ways that are not captured by the received critical perspective. By examining the history of knowledge and practices surrounding the ADHD-type, this work will argue that the deviant subject that was located relative to external institutional moral/juridical values or standards is replaced over the course of the century by a new intelligibility of rational self-management. A further analysis of this emergent intelligibility attempts to advance the critical understanding of the increasingly prevalent ADHD phenomenon by showing how novel drug and brain imaging technologies work to link behaviors to identity, establishing new relations of power to the subject not captured by the received medicalization perspective. This work will be of interest to anybody interested in the relations among knowledge, drugs, power, and the ADHD subject.

Case histories in pharmaceutical risk management.

The development and implementation of programs in the U.S. to minimize risks and assess unintended consequences of new medications has been increasingly required by the Food and Drug Administration (FDA) since the mid 1990s. This paper provides four case histories of risk management and post-marketing surveillance programs utilized recently to address problems associated with possible abuse, dependence and diversion. The pharmaceutical sponsors of each of these drugs were invited to present their programs and followed a similar template for their summaries that are included in this article. The drugs and presenting companies were OxyContin, an analgesic marketed by Purdue Pharma L.P., Daytrana and Vyvanse, ADHD medications marketed by Shire Pharmaceuticals, Xyrem for narcolepsy marketed by Jazz Pharmaceuticals, and Subutex and Suboxone for opioid dependence marketed by Reckitt Benckiser Pharmaceuticals Inc. These case histories and subsequent discussions provide invaluable real-world examples and illustrate both the promise of risk management programs in providing a path to market and/or for keeping on the market drugs with serious potential risks. They also illustrate the limitations of such programs in actually controlling unintended consequences, as well as the challenge of finding the right balance of reducing risks without posing undue barriers to patient access. These experiences are highly relevant as the FDA increasingly requires pharmaceutical sponsors to develop and implement the more formalized and enforceable versions of the risk management term Risk Evaluation and Mitigation Strategies (REMS).

Suffer the restless children: the evolution of ADHD and paediatric stimulant use, 1900-80.

This article traces the historical evolution of Attention Deficit/Hyperactivity Disorder (ADHD) and the controversial use of stimulants as a treatment for children diagnosed with the disorder in North America. While the children in question have exhibited similar behaviour over the last century, the diagnostic labels used to identify them have changed due largely to cultural, medical and scientific changes and discoveries. For decades, children's treatment with psychotropic drugs was sufficiently controversial that pharmaceutical companies would not finance research in the area. The only substantial source of research funding for paediatric psychopharmacology in the USA from the 1950s to the 1970s was the National Institute of Mental Health (NIMH). In 1970, the first in a long-running series of controversies erupted over children's treatment with stimulants.

Analeptic use in clinical toxicology: a historical appraisal.

BACKGROUND: The introduction and increasing popularity of the barbiturates during the first two decades of the 20th century was associated with a new life threatening toxicological problem: the barbiturate overdose. METHODS: This paper reviews the four major phases of analeptic use. As interest in the principles of physiologic antagonism between stimulants and depressants grew, analeptic agents were increasingly used to treat the obtundation and respiratory depression of barbiturate overdose. At first, naturally occurring stimulants such as camphor, strychnine, picrotoxin, and caffeine were used in desperate attempts to awaken patients. During the 1930s, and continuing at some centers into the 1960s, an increasing number of synthetic analeptics agents such as nikethamide, pentylenetetrazol, bemegride, amphetamine, and methylphenidate were enthusiastically recommended as barbiturate antidotes, often at very high doses. Unfortunately, utilizing generous amounts of multiple convulsants was not without its share of complications. Using this analeptic strategy the mortality rate after moderate to severe barbiturate overdose remained as high as 45%. Beginning in the mid-1940s a group of Scandinavian physicians pioneered a revolutionary approach to sedativehypnotic overdose that rejected the use of analeptics and relied on respiratory ventilation and supportive care. CONCLUSIONS: Although barbiturate overdose mortality decreased to less than 1% using this strategy, it would take another 20 years before this technique was universally adapted. While analeptic therapies for the treatment of drug overdose have now been abandoned, one of these analeptics, methylphenidate, currently enjoys wide use in the treatment of attention deficit hyperactivity disorder.