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Book Review

Management of Treatment-Resistant Major Psychiatric Disorders

Henry A. Nasrallah, MD

Published: October 15, 2013

Management of Treatment-Resistant Major Psychiatric Disorders

edited by Charles B. Nemeroff, MD, PhD. Oxford University Press, New York, NY, 2012, 366 pages, $89.99 (hardcover).

Once in a while, a book arrives that fills a critical need for psychiatric practitioners whose waiting rooms are packed with patients who fail to respond to evidence-based therapies. This book, containing a state-of-the-art review of how to manage treatment resistance in 15 different psychiatric disorders, is a timely gift to clinicians who have to manage patients with unremitting mental disorders. It is an excellent resource that belongs on the bookshelf of not only psychiatrists and psychiatric nurse practitioners but also other mental health professionals because treatment-resistant patients almost universally need a combination of pharmacotherapy and psychotherapy.

The introductory chapter provides an outstanding broad overview of the notion of treatment resistance and the many factors that underlie it, ranging from enigmatic/heterogeneous pathophysiology to environmental factors, patient factors, and clinician factors. Obviously, despite many advances in psychiatric therapeutics, the current tools are limited in efficacy and appear to work well only in a subset of responsive patients but partially or not at all in others. Over 80% of DSM psychiatric disorders lack a single US Food and Drug Administration-approved medication,1 and therefore any pharmacotherapy for them is basically off-label, based on anecdotal or small, uncontrolled studies. (Surprisingly, there are no off-label psychotherapies!) Thus, treatment resistance may not necessarily be due to a more "severe" subtype of the psychiatric illness, but simply to patients who do not respond to the existing drugs and/or psychotherapies that are considered the evidence-based standard of care.

Most of the chapters provide an initial introduction of the usual treatments of the disorder before proceeding to reviewing the characteristics, staging, and off-label management approaches to treatment resistance. Most chapters are organized with subheadings except for the schizophrenia chapter, which provides a wealth of information but reads like a Virginia Woolf’s "stream of consciousness" with its lack of subheadings. Very few of the chapters are enriched by tables or figures, but a wonderful exception is the chapter on treatment-resistant insomnia, which is simply superb in both content and illustrations. The chapter on treatment-resistant bipolar disorder, a major challenge in clinical settings, is the shortest in the book, but is nevertheless informative and well-referenced. Actually, all the chapters are generously referenced with recent citations.

One unfortunate (and unavoidable) detraction for this extremely useful book is that it was published a few months before DSM-5 was launched. Thus, all of the authors use DSM-IV-TR for the diagnosis discussion in their respective chapters. The fact remains, however, that the substance of the management of treatment resistance is as relevant for DSM-5 as it is for DSM-IV-TR.

Especially useful is the scholarly discussion of ablative surgical approaches (a less charged term than psychosurgery) in the chapters on treatment-resistant refractory depression and obsessive-compulsive disorder. The expanding armamentarium of neuromodulation techniques from the oldest (electroconvulsive therapy) to the newest (deep-brain stimulation) and a dozen others in between are nicely discussed in the depression and schizophrenia chapters. Chapter 8, on treatment-resistant generalized anxiety disorder, includes an impressive list of new information on novel (ie, unapproved) options for both pharmacotherapies and psychotherapies.

It was surprising to see only half a paragraph on the emerging and highly promising new paradigm of using intravenous ketamine for chronic treatment-resistant unipolar or bipolar depression. This will certainly be expanded in the next edition. Other topics that I wish this very useful book covered are treatment-resistant suicidal or homicidal patients, who are the most urgent clinical priorities in psychiatry.

Finally, the editor is to be commended for having the authors list their disclosures at the end of each chapter. While this is now common practice in journals, very few books do that at this time. Perhaps this book will set the pace for others.

Overall, I urge every reader to own this book and use it as a practical reference for the many treatment-resistant or refractory patients in clinical practice. It will save hundreds of hours of browsing PubMed to access all of the data between the covers of this timely volume!


1. Devulapalli KK, Nasrallah HA. An analysis of the high psychotropic off-label use in psychiatric disorders: the majority of psychiatric diagnoses have no approved drug. Asian J Psychiatr. 2009;2(1):29-36. PubMed doi:10.1016/j.ajp.2009.01.005

Henry A. Nasrallah, MD

Author affiliation: Department of Psychiatry & Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, Ohio.

Potential conflicts of interest: None reported.

Volume: 74

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