The Development and Use of Modern Psychotherapeutic Medications

April 15, 2008

The modern era of psychopharmacology is only 60 years old, having begun with the discovery of the psychotherapeutic benefits of reserpine, lithium, monoamine oxidase inhibitors, and chlorpromazine in the late 1940s and early 1950s, which was followed a few years later by the synthesis and testing of the tricyclic antidepressants and benzodiazepines.

The modern era of psychopharmacology is only 60 years old, having begun with the discovery of the psychotherapeutic benefits of reserpine, lithium, monoamine oxidase inhibitors, and chlorpromazine in the late 1940s and early 1950s, which was followed a few years later by the synthesis and testing of the tricyclic antidepressants and benzodiazepines.

The discovery of these drugs has had significance for the field of psychiatry in 3 distinct but related ways:

• They provided the first effective medications for patients who have serious psychiatric illnesses, such as schizophrenia, bipolar disorder, major depression, and anxiety disorders.
• In doing so, these drugs returned psychiatry to the field of medicine by showing that the medical model was applicable to the study and treatment of patients with serious psychiatric illnesses.
• While these outcomes were certainly important, the most important outcome was that these drugs served as tools that permitted the first steps to understanding brain mechanisms relevant to psychotherapeutic efficacy in these illnesses. The study of the effects of these drugs on the brain in the 1960s led to major discoveries of brain mechanisms that even today dominate the development of new psychiatric medications.

This issue provides a rich and diverse sampling of various aspects of the development and use of modern psychotherapeutic medications.

As discussed in 2 of the articles that follow-one on the vesicular monoamine transporter by Karley Y. Little, MD, and Anish V. Sharda, MD, MPH, and one on improving drug discovery in psychiatry by Carlos A. Zarate, Jr, MD, and Husseini K. Manji, MD-drugs such as reserpine and lithium are still useful tools to test brain mechanisms relevant to the discovery of new psychotherapeutics.

Two articles, the first by Thomas J. Raedler, MD, and the second by Holly A. Garriock, PhD, and Steven P. Hamilton, MD, PhD, illustrate how the current study of 2 older drug classes-muscarinic antagonists and opiates-holds promise for the development of new medications for schizophrenia and major depression, respectively.

Three additional articles in this issue move beyond drug discovery to the clinical management of existing medications for optimal patient outcomes. The first article is a discussion of a model psychopharmacology curriculum developed by Richard Balon, MD, and colleagues under the auspices of the American Society of Clinical Psychopharmacology. In their article, Eduardo J. Aguilar, MD, PhD, and his colleagues focus on the use of existing antipsychotics, beyond clozapine, to reduce the risk of suicide in patients with schizophrenia. Finally, Eugenio M. Rothe, MD, and his colleagues discuss genetic and cultural considerations in the use of pharmacological treatment for depression in minority and immigrant youth.

Over the coming decades, the Human Genome Project promises to provide greater insights into the mechanisms of normal and abnormal human emotion, perception, and cognition. The discovery of these mechanisms will provide new targets for the development of treatments well beyond those that we have today and in doing so will recapitulate the outcomes wrought by the medications discovered in the past century. They will revolutionize the field and improve outcomes for our patients.

The reader who is interested in the Human Genome Project and its implication for psychiatric drug development can find a series that I wrote on this subject on my Web site (http://www.preskorn.com/column4.html).

I trust that readers will enjoy the opportunity afforded by this special bonus edition of Psychiatric Times to glance into the near future of clinical psychopharmacology and see beyond what is to what will likely be.