by Neil B. Sandson, M.D. Arlington, Va, American Psychiatric Publishing, 2007, 408 pp., $59.00.
Neil Sandson’s previous publication, Drug Interactions Casebook: The Cytochrome P450 System and Beyond, is updated in this second edition, Drug-Drug Interaction Primer: A Compendium of Case Vignettes for the Practicing Clinician.
Learning the foundation of knowledge regarding the cytochrome P450 system is no small task. This book enlivens this task through a series of clinical vignettes. The author states that the text is not meant as a comprehensive guide to these metabolic interactions; for that purpose he recommends Cozza et al.’s Concise Guide to Drug Interaction Principles for Medical Practice(1). However, Sandson provides a detailed index of case titles for each interaction, as well as for general subjects. The reader can quiz himself and go on an adventure by browsing through the case title index and imagining each story before turning to the page and comparing details with the author’s version. For example, did you know orange juice is an inhibitor of P-Glycoprotein?
Six sections of the book are dedicated to drug interaction by specialty. Additional sections contain various formats for presenting the basics of drug-drug interactions, including a reprint of one of Sandson’s articles entitled “An Overview of Psychotropic Drug-Drug Interactions” (2), several straightforward and comprehensive tables, and lists of P450 interactions, along with glucuronidation interactions, P-Glycoprotein interactions, and the aforementioned detailed indices. The schematic breakdown of information is laid out in the first section, entitled “Core Concepts.” It details each system in an efficient manner, defines foundational terms (including “substrate,” “inhibitor,” and “inducer”), and produces approachable definitions for such complex metabolic systems as the P450 system, P-Glycoprotein transporters, and UDP-glucuronosyltransferase’s phase II conjugative metabolic glucuronidation. The major players in the P450 system are defined: 3A4, 1A2, 2D6, 2C9, 2C19, 2B6, and 2E1. They contribute recurrently to the many vignettes that follow.
The six basic patterns of drug-drug interactions are then laid out in the text. Understanding this information is essential for any hope in moving forward with developing an easier understanding of and working with drug-drug interactions. Inducers or inhibitors acting independently on substrates seem to have some degree of predictability. Multiple and complex interactions consisting of multiple simultaneous inducers and inhibitors become more difficult to predict. However, the importance of having and accessing knowledge regarding the multitude of potential interactions can help guide patient monitoring and evolving treatment decisions, enhancing the probability of avoiding disastrous outcomes related to inadvertent toxic overdoses.
Substrate medications that are added to a situation of enzymatic inhibition can produce rapid and dramatic results. There is nowhere for the active compound to go—it simply accumulates, potentially overwhelming the system. Substrate medication that is added to an induced state produces a less dramatic reaction, but it can be difficult for physicians to find a therapeutic dose of the medication without adequate knowledge of drug-drug interactions. Complicating factors could range from ongoing seizures or unexpected pregnancy to suboptimal treatment of chronic disorders and diseases.
The sections detailing drug-drug interactions by specialty, beginning with and maintaining a concerted focus on psychotropic medications, provide a nice basis for the categories of clinical vignettes. There is a definite mindset necessary when preparing to read chapter upon chapter of drug-drug interactions; there is undoubtedly a meditative quality to such exercises. For me it recalls a personal reading of the Vajracchedika Prajnaparamita Sutra(3) and the process of discovering wisdom through repetition. The wisdom entrained through repetitious retellings of drug-drug interactions can impact patient care and safety.
Whether seeking an initial foundation in drug-drug interactions or preparing for recertification, the variance of the case descriptions accompanied by the comprehensive indices make a desirable combination for broad audiences. This book is likely to be the most accessible point for establishing the foundation of this important information.
1.Cozza KL, Armstrong SC, Oesterheld JR: Concise Guide to Drug Interaction Principles for Medical Practice: Cytochrome P450s, UGTs, P-Glycoproteins, Second Edition. Washington, DC, American Psychiatric Publishing, 2003
2.Sandson NB, Armstrong SC, Cozza KL: An overview of psychotropic drug-drug interactions. Psychosomatics 2005; 46:464–494
3.Hahn TN: The Diamond That Cuts Through Illusion: Commentaries on the Prajnaparamita Diamond Sutra. Berkeley, Calif, Parallax Press, 1992
Book review accepted for publication December 2007 (doi:10.1176/appi.ajp.2007.07121849).