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Michael S. Ritsner
Editor
Polypharmacy in Psychiatry
Practice
Volume I
Multiple Medication Use Strategies
Editor
Michael S. Ritsner
Technion - Israel
Institute of Technology
Sha'ar Menashe Mental Health Center
Hadera, Haifa, Israel
ISBN 978-94-007-5804-9 ISBN 978-94-007-5805-6 (eBook)
DOI 10.1007/978-94-007-5805-6
Springer Dordrecht Heidelberg New York London
Library of Congress Control Number: 2013932219
© Springer Science+Business Media Dordrecht 2013
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. Exempted from this legal reservation are brief excerpts in connection
with reviews or scholarly analysis or material supplied specifically for the purpose of being entered and
executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this
publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher’s
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for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to
prosecution under the respective Copyright Law.
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.
While the advice and information in this book are believed to be true and accurate at the date of
publication, neither the authors nor the editors nor the publisher can accept any legal responsibility
for any errors or omissions that may be made. The publisher makes no warranty, express or implied,
with respect to the material contained herein.
Printed on acid-free paper
Springer is part of Springer Science+Business Media (www.springer.com)
I dedicate this book to my dear
grandchildren Ron, Miriam, Diana and
Daniel Ritsner who are funny, smart,
obstinate, and sometimes downright willful
About the Editor
Michael S. Ritsner, M.D., Ph.D.
Dr. Ritsner, M.D., Ph.D. is a physician and scientist who spent his career of over
35 years caring for patients and studying the nature and treatment of mental illness.
Dr. Ritsner is a Professor of Psychiatry at the Rappaport Faculty of Medicine,
Technion – Israel Institute of Technology (Haifa), Israel.
Dr. Ritsner graduated from the Khabarovsk State Medical University, and
received his PhD in Psychiatry from the Siberian State Medical University in 1975
(Tomsk, Russia). After gaining clinical practice as a neurologist and clinical psy-
chiatrist he joined the Siberian State Research Center at the Russian Academy of
Medical Sciences (Tomsk) as a Head of the Psychiatric Genetics Department in
1981. In 1990 he emigrated to Israel where he chaired a Psychiatry Department
and the Research Unit at Talbieh Mental Health Center (Jerusalem). Since 1998
vii
viii About the Editor
Dr. Ritsner directs the Acute Department of the Sha’ar Menashe Mental Health
Center, and Cognitive & Psychobiology Research Laboratory affiliated to the
Rappaport Faculty of Medicine, Technion.
Particular areas of interest include schizophrenia spectrum disorders, genetic
epidemiology, neuropsychiatric biomarkers, the role of neurosteroids in schizophre-
nia, novel neuroprotective treatments, and cognitive and quality of life impairments.
Dr. Ritsner’s research has been supported by grants from the Stanley Foundation.
He also currently serves as Principal Investigator of a multi-site research team
searching and testing novel agents with neuroprotective properties for treatment of
the debilitating effects of schizophrenia and related psychotic disorders.
Dr. Ritsner is the co-author of two books on neuropsychiatry and editor of three
books and two handbooks, and has published more than 140 peer-reviewed journal
articles, reviews, and more than 20 book chapters. He has given more than 200
presentations including as invited speaker at scientific conferences and medical
education events.
This monograph is yet another milestone toward achieving his goals of provid-
ing a comprehensive up-to-date state-of-the-art overview of the literature that
addresses the challenges facing clinical and biological psychiatry. This series
follows 12 volumes:
1. Quality of Life Impairment in Schizophrenia, Mood and Anxiety Disorders. New
Perspectives on Research and Treatment. Ritsner, Michael S.; Awad, A. George
(Eds.), Springer, Dordrecht. The Netherlands, 2007, 388 p.
2. Neuroactive Steroids in Brain Functions, and Mental Health. Novel Strategies
for Research and Treatment. Ritsner, Michael S.; Weizman A. (Eds.), Springer
Science + Business Media, B.V., 2008. 559 p.
3. The Handbook of Neuropsychiatric Biomarkers, Endophenotypes, and Genes.
Volumes I–IV. Ritsner, Michael S. (Ed.), Springer Science + Business Media,
B.V., 2009.
• Volume I: Neuropsychological Endophenotypes and Biomarkers. 231 pp.
• Volume II: Neuroanatomical and Neuroimaging Endophenotypes and
Biomarkers. 244 pp.
• Volume III: Metabolic and Peripheral Biomarkers. 231 pp.
• Volume IV: Molecular Genetic and Genomic Markers. 232 pp.
4. Brain Protection in Schizophrenia, Mood and Cognitive Disorders. Ritsner,
Michael S. (Ed.), Springer Science + Business Media, B.V. 2010. 663 p.
5. Handbook of Schizophrenia Spectrum Disorders. Volumes I–III. Ritsner,
Michael S. (Ed.), Springer Science + Business Media, B.V. 2011.
• Volume I: Conceptual Issues and Neurobiological Advances. 494 pp.
• Volume II: Phenotypic and Endophenotypic Presentations. 526 pp.
• Volume III: Therapeutic Approaches, Comorbidity, and Outcomes. 461 pp.
6. Polypharmacy in Psychiatric Practice. Volumes I–II. Ritsner, Michael S. (Ed.),
Springer Science + Business Media, B.V. 2013.
About the Editor ix
Dr. Ritsner served as Associate Editor, Quality of Life Research (an international
journal of quality of life aspects of treatment, care and rehabilitation, Amsterdam,
The Netherlands); Board Member, American Journal of Neuroprotection and
Neuroregeneration (USA); CNS & Neurological Disorders-Drug Targets (Italy);
and member of the Scientific Committee, International Society for the Study of
Neuroprotection and Neuroplasticity (Romania). Referee activity: CNS Drugs,
Quality of Life Research, Psychiatry Research, Clinical Drug Investigation, Social
Psychiatry and Psychiatric Epidemiology, Biological Psychiatry, etc.
Web: http://md.technion.ac.il/lecturers/lecturer_desc.asp?lecturerID=393
Preface
To the best of my knowledge, this might be the first comprehensive, clinically
oriented two-volume collection on the polypharmacy (co-administration of more
than one medication) or the use of multiple preparations to treat psychotic, cognitive,
mood and anxiety disorders. Despite the large number of psychotropic medications
currently available, effective management of mental disorders continues to be a
challenging task. Although monotherapy may be desirable, most patients require
combinations of two or more psychotropic drugs. Polypharmacy aims to address
different aspects of treatment resistance, especially insufficient response of positive
and negative symptoms, cognitive disturbances, affective comorbidity, obsessive-
compulsive syndromes and side-effects of antipsychotic agents. At the same time,
evidence based guidelines in support of polypharmacy and augmentative strategies
are scant.
This monograph is divided into four parts. Volume I contains two parts including
chapters that serve as an introduction and overview of conceptual issues. Key topics
include: a rational polypharmacy, receptor binding targets, drug interactions,
preclinical and clinical investigation in this field, dosing regimens, multiple medica-
tion use in forensic psychiatry, a naturalistic trial, adjunctive strategies, and multiple
medication use for the treatment of somatic symptom disorders.
Volume II contains two parts including chapters that focus on antipsychotic
polypharmacy for schizophrenia; clinical practice in USA, Czech Republik, Ukraine,
and Italy; polypharmacy and associated phenomena; clozapine combinations; and
metabolic syndrome. The authors discuss combination therapy for bipolar disorder,
major depressive disorder, obsessive-compulsive syndromes in schizophrenia, and
potentially inappropriate medication use among elderly patients with dementia.
Finally, each volume includes an Appendix that contains ‘Annotated Bibliography
on Polypharmacy’ and ‘List of Psychotropic Medications’.
Since many of the contributors to this collection are internationally known
experts, they not only provide up-to-date state-of-the-art overviews, but also clarify
some of the ongoing controversies and future challenges and propose new insights
for future research. The contents of these volumes have been carefully planned,
organized, and edited. Of course, despite the assistance provided by the contributors,
xi
xii Preface
I alone remain responsible for the content of this monograph including any errors
or omissions.
Editing this book has been an exciting journey that brought several incredible
people into my life. First and foremost, I am grateful and thankful to all contributors
for their excellent cooperation. I wish to thank the entire staff, heads of departments,
and the medical director of the Shaar-Menashe Mental Health Center, Dr. Alexander
Grinshpoon, MD, MHA, PhD, for their commitment, and support. Thanks to
Peter Butler and Dr. Martijn Roelandse, publishing editors, who did their utmost to
promote this project. And of course, I would like to thank my lovely wife Stella for
her tolerance of me having my head stuck in my computer. Without her love,
patience and support I would not have completed this project.
I sincerely hope that this book will extend the knowledge in the complex field of
treatment of psychiatric disorders and will be of interest to a broad spectrum of
readers including psychiatrists, neurologists, neuroscientists, endocrinologists,
pharmacologists, general practitioners, geriatricians, graduate students, and health
care providers in the field of mental health.
Haifa Michael S. Ritsner
September, 2012
Contents
Part I Polypharmacy Treatment Strategies
1 Multiple Psychiatric Medications Use in Psychiatry:
How Rational Can It Be? ....................................................................... 3
Ahsan Y. Khan and Sheldon H. Preskorn
2 Receptor Binding Targets for Antipsychotic Efficacy .......................... 25
Maureen M. Grainger, Rebecca Ahlbrand, Paul S. Horn,
and Neil M. Richtand
3 Drug Interactions and Polypharmacy ................................................... 45
Jessica L. Gören and Ashley Tewksbury
4 Preclinical and Clinical Investigation of Antipsychotic
Polypharmacy: What Is the Evidence? ................................................. 75
Dimitrios Kontis and Eirini Theochari
5 Should High Dose or Very Long-Term Antipsychotic
Monotherapy Be Considered Before
Antipsychotic Polypharmacy? ............................................................... 107
Stephen M. Stahl and Debbi A. Morrissette
6 Multiple Medication Use of Neuropsychiatry in Forensic
Psychiatry: Findings from the Central State Forensic
Psychiatric Hospital of Saxony-Anhalt ................................................. 127
Joachim G. Witzel
Part II Augmentation Strategies
7 Antipsychotic Treatment Within a Naturalistic Trial—How Are
We Treating Schizophrenia Patients in the “Real-World”? ................ 137
Rebecca Schennach, Michael Obermeier, Florian Seemüller,
Daniela Krause, Richard Musil, Ilja Spellmann, Hans-Jürgen Möller,
and Michael Riedel
xiii
xiv Contents
8 A Multi-Target Drug Treatment in Schizophrenia
and Schizoaffective Disorder Using Adjunctive
Agents with Non-D2 Mechanisms of Action .......................................... 157
Michael S. Ritsner
9 Antidepressants in Schizophrenia: A Place for Them? ....................... 211
Viacheslav Terevnikov and Grigori Joffe
10 Stress Sensitization and Anticonvulsant Medication
in Psychiatric Patients ............................................................................ 233
Petr Bob
11 Multiple Medication Use in Somatic Symptom Disorders:
From Augmentation to Diminution Strategies ..................................... 243
Adrian P. Mundt
Appendix 1. Annotated Bibliography on Polypharmacy ............................. 255
Appendix 2. List of Psychotropic Medications ............................................. 267
Contents to Volume II ..................................................................................... 277
Contributors to Volume II .............................................................................. 279
Index ................................................................................................................. 283
Contributors
Rebecca Ahlbrand, B.S. Cincinnati Veterans Affairs Medical Center, Psychiatry
Service (V116A), Cincinnati, OH, USA
Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati
College of Medicine, Cincinnati, OH, USA
Petr Bob, Ph.D. Department of Psychiatry, 1st Faculty of Medicine, Center for
Neuropsychiatric Research of Traumatic Stress, Charles University, Prague, Czech
Republic
Jessica L. Gören, PharmD, BCPP Department of Pharmacy Practice, University
of Rhode Island, Kingston, RI, USA
Department of Psychiatry, Harvard Medical School, Boston, MA, USA
Maureen M. Grainger, B.S. Cincinnati Veterans Affairs Medical Center,
Psychiatry Service (V116A), Cincinnati, OH, USA
Paul S. Horn, Ph.D. Division of Neurology, Cincinnati Children’s Hospital
Medical Center, Cincinnati, OH, USA
Department of Mathematical Sciences, University of Cincinnati, Cincinnati,
OH, USA
Grigori Joffe, M.D., Ph.D. Department of Psychiatry, Helsinki University Central
Hospital (HUCH), Hospital District of Helsinki and Uusimaa, Helsinki, Finland
Ahsan Y. Khan, M.D. Department of Psychiatry and Behavioral Sciences, College
of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City,
OK, USA
Dimitrios Kontis, M.D., Ph.D. 1st Psychiatric Department, Psychiatric Hospital
of Attica, Athens, Greece
Daniela Krause, M.D. Department of Psychiatry and Psychotherapy, Faculty of
Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany
xv
xvi Contributors
Rena Kurs, B.A. Medical Library, Sha’ar Menashe Mental Health Center,
Hadera, Israel
Hans-Jürgen Möller, M.D. Department of Psychiatry and Psychotherapy, Faculty
of Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany
Debbi A. Morrissette, Ph.D. California State University, San Marcos, San Marcos,
CA, USA
Neuroscience Education Institute, Carlsbad, CA, USA
Adrian P. Mundt, M.D., Ph.D. Departamento de Psiquiatría y Salud Mental,
Clínica Psiquiátrica, Universitaria, Hospital Clínico Universidad de Chile, Santiago
de Chile, Chile
Unit for Social & Community Psychiatry, Barts & The London School of Medicine
& Dentistry, Queen Mary University of London, London, UK
Richard Musil, M.D. Department of Psychiatry and Psychotherapy, Faculty of
Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany
Michael Obermeier Department of Psychiatry and Psychotherapy, Faculty of
Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany
Sheldon H. Preskorn, M.D. University of Kansas School of Medicine-Wichita,
Wichita, KS, USA
Neil M. Richtand, M.D., Ph.D. Cincinnati Veterans Affairs Medical Center,
Psychiatry Service (V116A), Cincinnati, OH, USA
Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati
College of Medicine, Cincinnati, OH, USA
Michael Riedel, M.D. Department of Psychiatry and Psychotherapy, Faculty of
Medicine, Ludwig-Maximilians-University of Munich, Germany
Vincent-von-Paul-Hospital, Rottweil, Germany
Michael S. Ritsner, M.D., Ph.D. Rappaport Faculty of Medicine, Technion – Israel
Institute of Technology, Haifa and Chair, Acute Department, Sha’ar Menashe Mental
Health Center, Hadera, Israel
Rebecca Schennach, M.D. Department of Psychiatry and Psychotherapy, Faculty
of Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany
Florian Seemüller, M.D. Department of Psychiatry and Psychotherapy, Faculty of
Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany
Ilja Spellmann, M.D. Department of Psychiatry and Psychotherapy, Faculty of
Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany
Stephen M. Stahl, M.D., Ph.D. Neuroscience Education Institute, Carlsbad,
CA, USA
Contributors xvii
Department of Psychiatry, University of California, San Diego, CA, USA
Viacheslav Terevnikov, M.D. Department of Psychiatry, Kellokoski Hospital,
Hospital District of Helsinki and Uusimaa, Tuusula, Finland
Ashley Tewksbury, PharmD Department of Pharmacy Practice, University of
Rhode Island, Kingston, RI, USA
Community Health Network, Indianapolis, IN, USA
Eirini Theochari, M.D. 1st Psychiatric Department, Psychiatric Hospital of Attica,
Athens, Greece
Joachim G. Witzel, M.D. Central State Forensic Psychiatric Hospital of Saxony-
Anhalt, Stendal, Germany
Part I
Polypharmacy Treatment Strategies
