Dean F. MacKinnon - Still Down

A Johns Hopkins Press Health Book

What to Do When
Antidepressants Fail

Dean F. MacKinnon, MD

Note to the Reader: This book is not meant to substitute for medical care of people with mental disorders, and treatment should not be based solely on its contents. Instead, treatment must be developed in a dialogue between the individual and his or her physician. This book has been written to help with that dialogue.

Drug dosage: The author and publisher have made reasonable efforts to determine that the selection of drugs discussed in this text conform to the practices of the general medical community. The medications described do not necessarily have specific approval by the US Food and Drug Administration for use in the diseases for which they are recommended. In view of ongoing research, changes in governmental regulation, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert of each drug for any change in indications and dosage and for warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently used drug.

2016 Johns Hopkins University Press
All rights reserved. Published 2016
Printed in the United States of America on acid-free paper
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Library of Congress Cataloging-in-Publication Data

Names: MacKinnon, Dean F., author.

Title: Still down : what to do when antidepressants fail / Dean F. MacKinnon.

Description: Baltimore : Johns Hopkins University Press, 2016. | Series: A johns hopkins press health book

Identifiers: LCCN 2016005166| ISBN 9781421421056 (hardcover) | ISBN 1421421054 (hardcover) | ISBN 9781421421063 (paperback) | ISBN 1421421062 (paperback) | ISBN 9781421421070 (electronic) | ISBN 1421421070 (electronic)

Subjects: LCSH: Depression, MentalTreatmentPopular works. | AntidepressantsPopular works. | BISAC: SELF-HELP / Depression. | PSYCHOLOGY / Psychopathology / Depression. | MEDICAL / Psychiatry / General.

Classification: LCC RC537 .M318 2016 | DDC 616.85/27dc23

LC record available at https://lccn.loc.gov/2016005166

A catalog record for this book is available from the British Library.

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Johns Hopkins University Press uses environmentally friendly book materials, including recycled text paper that is composed of at least 30 percent post-consumer waste, whenever possible.

I offer sincere gratitude to many friends, colleagues, and patients who encouraged me to write this book, and who read and commented on the text as I was writing it. In particular, I thank my wife, Dr. Catherine Washburn, Drs. Ray DePaulo and John Dougherty, along with Barbara Schweizer, Sunny Mendelsohn, and Dr. Eileen Epstein. Finally, the book owes its existence to the many patients who have shared not only their symptoms but also their life stories with me.

Major depressive disorder is among the most common and debilitating medical conditions. The illness can hang on for months, even years, and annually drives about a million people to suicide around the world. Its biological mechanisms are uncertain, so no medicine can fix the cause of the problem. Anyone unfortunate enough to have one episode of major depressive disorder is likely to have more episodes, through-out life.

Although incurable, major depression is highly treatable. In the middle of the twentieth century, pharmacologists discovered that several drugs developed for other medical problems, taken daily, could reverse the symptoms of major depressive disorder within six to eight weeks. Dozens of other antidepressant drugs that have similar pharmacologic effects have been invented since that time. About two of every three people who have major depression and who take a sufficiently strong dose of an antidepressant daily for six to eight weeks will experience a significant reduction in the symptoms of depression. For those who had either no response or an incomplete response, a switch to one of the many other antidepressants approved by the US Food and Drug Administration may bring relief. But even people who do experience a satisfactory response remain at high risk for relapse. Psychiatrists have worked out a variety of medication tricks to boost response and avert relapse. Psychotherapy helps, too. For the most severely afflicted, electroconvulsive therapy can be lifesaving. The painfully slow search for better and safer treatments continues, occasionally yielding a promising new method to alleviate depression.

My primary clinical role as a psychiatrist for the past twenty-odd years in both inpatient and outpatient settings has been to try to help people who have not responded adequately to treatment for depression. The key to my approach is to focus on a question all too seldom asked: Why did the standard treatment not work for this person? This book uses nine patient stories to illustrate how I try to understand and help people who have failed to respond to antidepressant treatment. Let me assure the patients I have treated or consulted with that any resemblance between them and these composite cases is purely coincidental.

The stories that follow illustrate some of the ways anti
depressant treatment often goes awry. The plan of the book is to progress from the easiest to the hardest cases. The easiest cases are those in which the person has simply not had adequate treatment, so the first section discusses the standard approaches to effective antidepressant treatment and common obstacles to achieving it: overly conservative dosing, not adhering to treatment, and other impediments to adequate therapy, such as high sensitivity to side effects.

The second section looks at misdiagnosis: people who feel and appear depressed but do not presently have major depressive disorder and so cannot be expected to respond well to anti-depressants. Flaws within our diagnostic rules and methods often lead clinicians to diagnose major depression in people who are merely demoralized by life circumstances; people who have manias or hypomanias (milder manias) in addition to major depressive episodes, hence exhibiting some form of bipolar disorder; and people who have depressive symptoms while in a state of delirium or intoxication, that is, a disruption of consciousness because of gross, global abnormality in brain function (some might call this organic depression).

The third section looks at the cases that experts would classify truly as treatment resistant or treatment refractory. Here there is no doubt about the potential usefulness of antidepressants or about the persons poor response to standard treatments. Some of these patients once had major depressive disorder and responded partially to treatment but have not returned to their previous level of function. Some continue to have a clear major depressive syndrome despite fully adequate medication choices and levels.

Throughout each story, the reader will find numbered links to commentary that explains, extends, or discusses the point being made in the case vignette. Read independently of the case vignettes, this commentary serves as a brief and general survey of the common obstacles to effective antidepressant treatment and of strategies to overcome them.