The Essential Guide to Lithium Treatment
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1 The Essential Guide to Lithium Treatment
2
3 Michael Bauer Michael Gitlin The Essential Guide to Lithium Treatment
4 Michael Bauer Technische Universtät Dresden University Hospital Carl Gustav Carus Dresden Germany Michael Gitlin Geffen School of Medicine University of California Los Angeles Los Angeles, CA USA ISBN ISBN (ebook) DOI / Library of Congress Control Number: Springer International Publishing Switzerland 2016 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. Printed on acid-free paper This Springer imprint is published by Springer Nature The registered company is Springer International Publishing AG Switzerland
5 Preface More than 65 years after its discovery for the treatment of mania, lithium continues as the most valuable treatment option for bipolar disorder. In the areas of both basic pharmacology and in clinical efficacy, much has been discovered about lithium since its introduction into modern psychiatry in Lithium is an intriguing medication for several reasons: it is a simple element easily found in the periodic table, yet it has demonstrated a unique, striking efficacy in preventing mood episodes in patients with bipolar and unipolar mood disorders. For example, during the past 25 years, lithium s value as a suicide-preventing agent is increasingly acknowledged and has spurred new interest in its use. The ability of lithium to significantly reduce suicidal risk distinguishes it from the other mood-stabilizing agents currently available. Furthermore, basic research in the previous decade has demonstrated that lithium may possess neuroprotective properties in humans. These newer data suggest that lithium may even hold potential in preventing and treating dementia and other neurodegenerative diseases. This book is a practical, up-to-date guide to the optimal use of lithium for the short- and long-term treatment of mood disorders. It is intended primarily for use by clinicians physicians and other healthcare workers who use lithium to treat patients suffering from mood disorders. Thus, it addresses various aspects of effective and safe use of lithium in clinical practice. Among the subjects addressed are the pharmacology and mechanisms of action of lithium, its use for maintenance treatment, the role of lithium in the treatment of mania and depression and in suicide prevention, further clinical indications, the administration of lithium during pregnancy and the postpartum period, and adverse effects and their management. Relevant background information is provided on the diagnosis, classification, and natural course of mood disorders, and an overview of other treatments for bipolar disorder and major depression is included. Despite the fact that lithium has unique properties as an effective mood stabilizer as well as demonstrating anti-suicidal and antidepressant effects, lithium is dramatically underutilized in the treatment of patients with mood disorders in many countries. In contrast, lithium is ranked consistently as a first choice medication for the long-term treatment of bipolar disorders in all major national and international treatment guidelines. So, the question is why is it underprescribed? Despite the considerable efficacy and advantages achieved by lithium, it remains a medication that, compared with most psychotropic medications, is slightly more difficult to v
6 vi Preface handle, largely due to its narrow therapeutic index. This factor, along with concerns about its tolerability and long-term renal risks, probably explains why lithium is underutilized. There is also the perception that the frequent and reliable monitoring of lithium plasma concentrations is difficult. However, when used properly, and reliable lithium plasma concentrations monitored, it is relatively well tolerated and not too complicated to administer at all. Among these factors, one other reason for its underutilization is that lithium is inherently a generic drug with no major pharmaceutical firm sponsor that would finance its global marketing. In contrast, many other treatments have each enjoyed a substantial period of patent protection, leading to intense marketing of the medication to psychiatrists and patients alike. Both authors have more than 25 years of experience in research and clinical use of lithium. When used correctly, lithium unquestionably produces the most dramatic benefits of any medication in contemporary psychopharmacology. We have seen dramatic and often unique responses to lithium in many of our patients suffering severe and life-threatening mood disorders. Our main hope and goal, why we wrote this book, is that this practical guide to lithium treatment will be used much more often in clinical practice and will help patients and physicians. We would like to acknowledge our patients who have taken lithium who have provided us with much of the knowledge, experience, and wisdom we have shared in this book. A special debt is owed to Bruno-Müller-Oerlinghausen and Paul Grof who taught MB how to use lithium in mood disorders. MG would also like to thank Jenna Gonzalez, and MB Daniela Jany, for the administrative help they provided with such cheerfulness. Dresden, Germany Los Angeles, CA, USA Spring 2016 Michael Bauer Michael Gitlin
7 Contents 1 Diagnosis and Classification of Mood Disorders Introduction Symptoms of Mood Disorders Symptoms of Depression Symptoms of Mania and Hypomania Symptoms of Mixed Episodes Classification of Mood Disorders Major Depressive Disorder Bipolar Disorder How Common Is Bipolar Disorder? When Does Bipolar Disorder Start? Why Is Bipolar Disorder So Difficult to Diagnose Precisely? References Natural Course of Bipolar Disorder and Implications for Treatment Introduction Natural History of Bipolar Disorder Polarity Dominance in Bipolar Disorder Episodic Versus Chronic Nature of Bipolar Disorder The Natural History of Rapid Cycling Bipolar Disorder Stress and the Course of Bipolar Disorder Functional Outcome in Bipolar Disorder Quality of Life in Bipolar Individuals Bipolar II Disorder Suicide in Bipolar Disorder Treatment Phases in Bipolar Disorder References Lithium and Its History What Is Lithium? A Fascinating Element: Lithium s Discovery Early Applications and the Breakthrough in Psychiatry Lithium s Discovery: Also a History of Controversies vii
8 viii Contents 3.5 Position in Treatment Guidelines Renaissance of Lithium Treatment? References What Is Lithium and How Does It Work? Chemistry of Lithium Pharmacokinetic Properties of Lithium The Principal Pharmacodynamic Actions of Lithium Effects on Neurotransmitters Pharmacogenetics of Lithium References Maintenance Treatment with Lithium Introduction Goals of Maintenance and Long-Term Treatment When Should Maintenance Treatment Be Started? Pharmacological Maintenance Treatment in Mood Disorders Maintenance Treatment of Bipolar Disorder with Lithium Initial Evidence and Landmark Studies Growing Evidence for Lithium s Efficacy from Randomized Trials The Recent Evidence from Meta-analyses Predicting the Response to Lithium: How to Select the Right Person for Lithium Treatment? Lithium in Offspring of Bipolar Parents Lithium in Rapid Cycling Discontinuing Lithium Long-Term Treatment Does Lithium Treatment Lose Efficacy over Time in Long- Term Treatment? Does Lithium Treatment Lose Efficacy After Treatment Discontinuation? Position of Lithium for Maintenance Treatment in Guidelines Lithium Maintenance Treatment of Recurrent Unipolar Depression How Can Lithium Maintenance Treatment Be Optimized? References Treatment of Mania with Lithium Introduction Lithium as an Antimanic Medication: Recent Studies Combination Studies with Lithium for Acute Mania Meta-analyses of Antimanic Agents and Lithium Predictors of Response to Lithium for Acute Mania Lithium as a Treatment for Hypomania
9 Contents ix 6.7 Lithium s Place in Modern Practice and Treatment Guidelines in the Treatment of Acute Mania Technical Aspects of Lithium Treatment During Acute Mania Lithium Side Effects During Acute Treatment References Treatment of Depression with Lithium Introduction Lithium s Efficacy as Monotherapy in Unipolar and Bipolar Depression Lithium as an Adjunctive Antidepressant Combination Treatments with Lithium Lithium as an Antidepressant Accelerator Predictors of Response to Lithium as an Antidepressant Lithium s Antidepressant Role in Treatment/Practice Guidelines Techniques of Administration for Lithium s Use as an Antidepressant Place of Lithium in the Treatment of Acute Depression References Suicide Prevention with Lithium Introduction Evaluation of Suicidality Treatment of Suicidality Lithium Protection Against Suicide How It All Started Epidemiologically Based Evidence Controlled Studies and Systematic Reviews Lithium s Suicide-Preventing Effects: Clinical Implications Suicide-Preventing Effects of Lithium as a Trace Element in Drinking Water Does Lithium Also Reduce Acute Suicidal Ideation and Behavior? Potential Mechanisms of Action in Lithium s Anti- suicide Effects References Neuroprotection and Other Clinical Indications of Lithium Introduction Lithium: Neurobiology of Neuroprotection Neuroprotective and Cognitive Aspects of Lithium in Bipolar Disorder Lithium and Neuroprotection in Dementia Lithium in Other Central Nervous System Disorders (CNS)
10 x Contents Huntington s Disease (HD) Amyotrophic Lateral Sclerosis (ALS) Parkinson s Disease Cluster Headache Beyond Mood Disorders: Other Psychiatric Indications for Using Lithium Schizophrenia and Schizoaffective Disorder Obsessive-Compulsive Disorder and Pathological Gambling Administering Lithium in Nonpsychiatric Disorders Hyperthyroidism Hematological Indications Herpes Simplex Seborrheic Dermatitis Other Medical Conditions References Lithium During Pregnancy and in the Postpartum Period Introduction Course of Bipolar Disorder During Pregnancy and the Postpartum Period Potential Effects of Lithium in Pregnancy Lithium: Effects Related to Pregnancy and Its Course Lithium and Fetal Malformations Lithium and Neonatal Toxicity Lithium and Developmental Abnormalities Management of Lithium During Pregnancy and Delivery Lithium, Breastfeeding, and the Postpartum Period Clinical Decision-Making During Pregnancy for Women Taking Lithium Other Mood Stabilizers During Pregnancy and Postpartum Periods References Practical Management of Lithium Introduction Selection of Patients and Indications Contraindications for Lithium Therapy Drug Interactions with Lithium Before Starting Lithium Treatment How to Titrate Lithium? Therapeutic Lithium Level Monitoring During Lithium Treatment Treating Lithium Intoxication How to Withdraw Lithium Common Mistakes in Lithium Treatment
11 Contents xi Lithium During Special Circumstances Lithium Therapy and Anesthesia Combined Lithium and Electroconvulsive Therapy References Adverse Effects of Lithium and Their Management Introduction Side Effects: Acute and Long Term Long-Term Effects on Organ Systems Lithium and Renal Function Lithium and Thyroid Function Lithium and Hyperparathyroidism Lithium Toxicity References Beyond Lithium: Other Treatments for Bipolar Disorder Introduction Treatment of Acute Mania Second-Generation Antipsychotics Anticonvulsants Benzodiazepines Combination Treatments Treating Hypomania Treatment-Resistant Mania Other Treatments for Bipolar Depression First-Line Treatments for Bipolar Depression: Mood Stabilizers Combination Treatments for Bipolar Depression Antidepressants for Bipolar Depression Treatment of Bipolar II Depression Other Treatments for Bipolar Depression Other Maintenance Treatments for Bipolar Disorder Lamotrigine Valproate Second-Generation Antipsychotics Carbamazepine Other Agents Medication Combinations References Index
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13 About the Authors Michael Bauer, MD, PhD is professor of psychiatry and executive chair of the Department of Psychiatry and Psychotherapy at the Medical Faculty, Technische Universität Dresden, where he is also physician-in-chief at the Psychiatric Hospital and Outpatient Clinics of the University Hospital Carl Gustav Carus. He received his medical degree from Freie Universität Berlin School of Medicine and a PhD in molecular biology and biochemistry from Freie Universität Berlin. Together with Paul Grof and Bruno-Mueller-Oerlinghausen, he is the editor of the definitive scientific textbook Lithium in Neuropsychiatry: The Comprehensive Guide (from 2006) and has authored and coauthored more than 400 articles published in peer-reviewed journals and books, including The Lancet, Molecular Psychiatry, and The American Journal of Psychiatry, in the field of mood disorders. He is the president of the International Group for the Study of Lithium-Treated Patients (IGSLi), chairs the World Federation of Societies of Biological Psychiatry s (WFSBP) Task Force on Treatment Guidelines for Unipolar Depressive Disorders, and is project coordinator of the national consortium for the German Treatment Guidelines for Bipolar Disorder. He is editor in chief of the International Journal of Bipolar Disorders and Pharmacopsychiatry and editor of Der Nervenarzt. xiii
14 xiv About the Authors Michael J. Gitlin, MD is professor of clinical psychiatry at the Geffen School of Medicine at the University of California at Los Angeles (UCLA). He is currently the director of the Adult Division in the Department of Psychiatry, medical director of the Neuropsychiatric Behavioral Health Services, and director of the Mood Disorders Clinic. From 1980 until 2004, he was the medical director of the Aftercare Clinic, a research clinic in schizophrenia. He is the author of many scientific articles and book chapters as well as four books, including two editions of a solo-authored psychopharmacology textbook written for nonphysician therapists entitled The Psychotherapist s Guide to Psychopharmacology published by the Free Press, the coauthor of Psychotropic Drugs and Women with Dr. Victoria Hendrick, and the coauthor of Clinician s Guide to Bipolar Disorder: Integrating Pharmacology with Psychotherapy, with Dr. David Miklowitz. He served as chief of staff at the Neuropsychiatric Hospital from 1997 to Among his awards are Distinguished Educator Award in Teaching from the UCLA Department of Psychiatry (1999); Outstanding Housestaff Teaching Award, 1994 and 2008; Teacher of the Year from the Psychiatric Times in 2002; Dadone Clinical Teaching Award from the Geffen School of Medicine at UCLA in 2010; and the Leonard Tow Humanism in Medicine Award from the Geffen School of Medicine at UCLA in 2010.
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