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Long established as the preeminent source in its field, the eagerly anticipated fifth edition of Dr Stahl's essential textbook of psychopharmacology is here! With its use of icons and figures that form Dr Stahl's unique 'visual language', the book is the single most readable source of information on disease and drug mechanisms for all students and mental health professionals seeking to understand and utilize current therapeutics, and to anticipate the future for novel medications. Every aspect of the book has been updated, with the clarity of explanation that only Dr Stahl can bring.
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University Printing House, Cambridge CB2 8BS, United Kingdom
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Cambridge University Press is part of the University of Cambridge.
It furthers the University’s mission by disseminating knowledge in the pursuit of education, learning, and research at the highest international levels of excellence.
Information on this title: www.cambridge.org/9781108838573
© Stephen M. Stahl 1996, 2000, 2008, 2013, 2021
This publication is in copyright. Subject to statutory exception and to the provisions of relevant collective licensing agreements, no reproduction of any part may take place without the written permission of Cambridge University Press.
First edition published 1996
Second edition published 2000
Third edition published 2008
Fourth edition published 2013
Fifth edition published 2021
Printed in Singapore by Markono Print Media Pte Ltd
A catalogue record for this publication is available from the British Library.
ISBN 978-1-108-83857-3 Hardback
ISBN 978-1-108-97163-8 Paperback
Cambridge University Press has no responsibility for the persistence or accuracy of URLs for external or third-party internet websites referred to in this publication and does not guarantee that any content on such websites is, or will remain, accurate or appropriate.
Every effort has been made in preparing this book to provide accurate and up-to-date information that is in accord with accepted standards and practice at the time of publication. Although case histories are drawn from actual cases, every effort has been made to disguise the identities of the individuals involved. Nevertheless, the authors, editors, and publishers can make no warranties that the information contained herein is totally free from error, not least because clinical standards are constantly changing through research and regulation. The authors, editors, and publishers therefore disclaim all liability for direct or consequential damages resulting from the use of material contained in this book. Readers are strongly advised to pay careful attention to information provided by the manufacturer of any drugs or equipment that they plan to use.
For this fifth edition of Stahl’s Essential Psychopharmacology you will notice that every figure in the book has been revised, refreshed, and updated with new colors, shading, and outlining. About half the figures are entirely new. The number of chapters has decreased by one, with merger of mood stabilizers into treatments for mood disorders; the text itself and the total number of figures and tables are all approximately the same in length and number, although all chapters have been edited, most of them extensively, with the details of what has changed listed below. The number of references has now been doubled. Overall, 14 drugs have new uses and indications presented, and 18 brand new drugs are introduced and discussed.
Highlights of what has been added or changed since the fourth edition include:
New coverage of interference RNA (iRNA) in basic neuroscience chapters
Restructuring all chapters to reflect neuroscience-based nomenclature, that is, drugs named for their mechanism of action rather than use
Thus, drugs for depression are not “antidepressants” but “monoamine reuptake inhibitors with antidepressant action”; drugs for psychosis are not “antipsychotics” but “serotonin/dopamine antagonists with antipsychotic actions,” etc.
The psychosis chapter has:
new coverage of the direct and indirect striatal dopamine pathways
new coverage of trace amines, receptors, and pharmacology
revision of the classic dopamine theory of psychosis
two new theories of psychosis (serotonin and glutamate)
coverage of dementia-related psychosis and Parkinson psychosis in addition to schizophrenia psychosis
updated coverage of new indications for drugs previously approved, including lurasidone, cariprazine, and brexpiprazole
describes five new drugs for psychosis: lumateperone approved, and xanomeline, pimavanserin, trace amine-associated receptor type 1 (TAAR1) agonists, and roluperidone in development
updated receptor binding data for all drugs
new coverage of tardive dyskinesia and new drug treatments: deutetrabenazine and valbenazine
new coverage of uses of serotonin–dopamine drugs for psychosis that are now used even more frequently for depression
The chapters on mood disorders have:
new coverage of mixed mood states
new coverage of GABAA (γ-aminobutyric acid A) receptor subtypes and neurosteroid binding sites
new coverage of neurotrophic growth factors and neuroplasticity in depression
new coverage of inflammation in depression
mood stabilizers redefined
new/expanded coverage of levomilnacipran, vortioxetine
new coverage of treating cognition in depression
new drugs: neuroactive steroids, ketamine/esketamine, dextromethorphan combinations, dextromethadone
expanded coverage of treatment resistance and augmentation treatments for monoamine reuptake inhibitors including brexpiprazole, ketamine, esketamine, and trials with cariprazine, pimavanserin
expanded coverage of new hypotheses of neuroplastic downstream changes following NMDA (N-methyl-D-aspartate) antagonist therapy with ketamine, esketamine, and others
expanded coverage of treating bipolar depression with new indications and new drugs lurasidone, cariprazine
The anxiety chapter has:
removal of obsessive–complusive disorder (OCD) to the impulsivity chapter
coverage of posttraumatic stress disorder (PTSD) as a traumatic disorder rather than anxiety disorder
GABA moved to mood chapter
revised discussions on treatments of individual anxiety disorders
renewed emphasis on combining psychotherapy with psychopharmacology for symptoms of anxiety
The pain chapter has:
new criteria for fibromyalgia diagnosis
The sleep chapter has:
much expanded coverage of orexin neuroscience
expanded coverage of histamine neuroscience
much expanded coverage of neurotransmitters across the sleep/wake cycle
presentation of concept of different threshold levels of drugs of different mechanisms in order to induce sleep
expanded coverage of dual orexin receptor antagonists including a new agent lemborexant
discussion of new H3 histamine antagonist, pitolisant, for narcolepsy
discussion of a new wake-promoting norepinephrine–dopamine reuptake inhibitor (NDRI), solriamfetol
expanded circadian rhythm discussion
The attention deficit hyperactivity disorder (ADHD) chapter has:
coverage of multiple new dosage formulations of methylphenidate and amphetamine
discussion of new drugs on the horizon: viloxazine, and others
a presentation of concept of threshold levels necessary for efficacy of stimulants in ADHD
expanded coverage of neurodevelopment in ADHD
The dementia chapter has:
new coverage of acetylcholine and cholinergic receptors
introduction of theories for the circuits of memory versus psychosis versus agitation in dementia
de-emphasis of the amyloid cascade hypothesis
new emphasis on new treatments emerging for the behavioral symptoms of dementia, including pimavanserin for psychosis in all-cause dementia, and brexpiprazole and dextromethorphan/bupropion for agitation in Alzheimer disease
expanded coverage of Alzheimer disease and new coverage of vascular dementia, dementia with Lewy bodies, frontotemporal dementia, and Parkinson dementia, clinical characteristics, and neuropathology
The final chapter on impulsivity, compulsivity, and substance abuse has:
new coverage of novel combinations of psychotherapy and hallucinogenic/dissociative drugs for treatment-resistant depression
updated and expanded coverage of opioid use disorder and its treatment
updated and expanded coverage of the endocannabinoid neurotransmitter system and cannabis use for recreation, abuse, and therapeutics
update on Ecstasy and psilocybin
update on impulsive–compulsive disorders
What has not changed in this new fifth edition is the didactic style of the first four editions: namely, this text attempts to present the fundamentals of psychopharmacology in simplified and readily readable form. We emphasize current formulations of disease mechanisms and also drug mechanisms. As in previous editions, although the total number of references has been doubled from the fourth edition, the text is not extensively referenced to original papers, but rather to textbooks and reviews and a few selected original papers, with only a limited reading list for each chapter, but preparing the reader to consult more sophisticated textbooks as well as the professional literature.
The organization of information continues to apply the principles of programmed learning for the reader, namely repetition and interaction, which has been shown to enhance retention. Therefore, it is suggested that novices first approach this text by going through it from beginning to end by reviewing only the color graphics and the legends for these graphics. Virtually everything covered in the text is also covered in the graphics and icons. Once having gone through all the color graphics in these chapters, it is recommended that the reader then go back to the beginning of the book, and read the entire text, reviewing the graphics at the same time. After the text has been read, the entire book can be rapidly reviewed again merely by referring to the various color graphics in the book. This mechanism of using the materials will create a certain amount of programmed learning by incorporating the elements of repetition, as well as interaction with visual learning through graphics. Hopefully, the visual concepts learned via graphics will reinforce abstract concepts learned from the written text, especially for those of you who are primarily “visual learners” (i.e., those who retain information better from visualizing concepts than from reading about them). For those of you who are already familiar with psychopharmacology, this book should provide easy reading from beginning to end. Going back and forth between the text and the graphics should provide interaction. Following review of the complete text, it should be simple to review the entire book by going through the graphics once again.
The fifth edition of Essential Psychopharmacology is the flagship of this book series, but not the entire fleet, as the Essential Psychopharmacology Series has further expanded. For those of you interested, there is an entire suite of dozens of books and extensive online information now available that accompany Essential Psychopharmacology, Fifth Edition. There are now six prescriber’s guides:
for psychotropic drugs, Stahl’s Essential Psychopharmacology: the Prescriber’s Guide, now in its seventh edition
for psychotropic drugs specifically for use in children and adolescents, Stahl’s Essential Psychopharmacology Prescribers Guide: Children and Adolescents
for neurology drugs, Essential Neuropharmacology: the Prescriber’s Guide, second edition.
for pain drugs: Essential Pain Pharmacology: the Prescriber’s Guide
for drugs to treat serious mental illnesses particularly in forensic settings, a new book, Management of Complex Treatment Resistant Psychotic Disorders (with Michael Cummings)
for the UK, there will soon be published a Cambridge Prescribers Guide for psychotropic drugs to fit into UK practice patterns (with Sep Hafizi and Peter Jones)
For those interested in how the textbook and prescriber’s guides get applied in clinical practice there are now three books of case studies:
Case Studies: Stahl’s Essential Psychopharmacology, covering 40 cases from my own clinical practice
Case Studies, 2nd edition, with cases from Tom Schwartz’s practice at State University of New York Syracuse
Case Studies, 3rd edition, with cases from the University of California Riverside Department of Psychiatry (with Takesha Cooper and Gerald Maguire)
For those teachers and students wanting to assess objectively their expertise, to pursue maintenance of certification credits for board recertification in psychiatry in the US, and for background on instructional design and how to teach, there are two books:
Stahl’s Self Assessment Examination in Psychiatry: Multiple Choice Questions for Clinicians, now in its third edition
Best Practices in Medical Teaching
For those interested in expanded visual coverage of specialty topics in psychopharmacology, there is the Stahl’s Illustrated series:
Antipsychotics: Treating Psychosis, Mania and Depression, 2nd edition
Anxiety, Stress, and PTSD
Attention Deficit Hyperactivity Disorder
Chronic Pain and Fibromyalgia
Substance Abuse and Impulsive Disorders
Violence: Neural Circuits, Genetics, and Treatment
Sleep and Sleep Wake Disorders
For practical and in-depth management tips and guidance, a newly introduced Handbook series:
The Clozapine Handbook (with Jonathan Meyer)
Handbook of Psychotropic Drug Levels (with Jonathan Meyer)
Suicide Prevention Handbook (with Christine Moutier and Anthony Pisani)
Finally, there is an ever-growing edited series of subspecialty topics:
Practical Psychopharmacology (applying evidence-based studies to treatment, with Joe Goldberg)
Violence in Psychiatry (with Katherine Warburton)
Decriminalizing Mental Illness (with Katherine Warburton)
Evil, Terrorism and Psychiatry (with Donatella Marazitti)
Next Generation Antidepressants
Essential CNS Drug Development
Cambridge Textbook of Neuroscience for Psychiatrists (with Mary-Ellen Lynall and Peter Jones)
Now, you also have the option of accessing all these books plus additional features online by going to Essential Psychopharmacology Online at www.stahlonline.org.In addition, www.stahlonline.org is now linked to:
the journal CNS Spectrums, www.journals.Cambridge.org/CNS,
of which I am the editor-in-chief, and which is the official journal of the Neuroscience Education Institute (NEI), free online to NEI members. This journal features readable and illustrated reviews of current topics in psychiatry, mental health, neurology, and the neurosciences as well as psychopharmacology
Access CME credits for this and other books in the Stahl series
Access the Master Psychopharmacology Program, an assessment-based certificate program that covers all of the content in Stahl’s Essential Psychopharmacology
Purchase downloadable PowerPoint slides of all the figures in this book
Hopefully the reader can appreciate that this is an incredibly exciting time for the fields of neuroscience and mental health, creating fascinating opportunities for clinicians to utilize current therapeutics and to anticipate future medications that are likely to transform the field of psychopharmacology. Best wishes for your first step on this fascinating journey.
Stephen M. Stahl, MD, PhD, DSc (Hon.)
In memory of Daniel X. Freedman, mentor, colleague, and scientific father
Released: May 1, 2021
CME credit expires: May 1, 2024
After completing this activity, you should be better able to:
Describe the neuropathology underlying mental health disorders
Describe the differential neurobiological targets for psychotropic medications
Link the mechanisms of psychotropic medications to their clinical targets
The Neuroscience Education Institute (NEI) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.
NEI designates this enduring material for a maximum of 61.5 AMA PRA Category 1 Credits TM. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Nurses and Physician Assistants: for your CE requirements, the ANCC and NCCPA will accept AMA PRA Category 1 Credits TM from organizations accredited by the ACCME. The content in this activity pertains to pharmacology and is worth 61.5 continuing education hours of pharmacotherapeutics.
Optional posttests and certificates of CME credit are available for each topical section of the book (total of nine sections). There is a fee for each posttest (varies per section) which is waived for NEI members.
1. Read the desired topical section
2. Pass the related posttest (70% score or higher), available only online at www.neiglobal.com/CME (under “Book”)
3. Print your certificate
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The content was peer-reviewed by an MD, PsyD, or PhD specializing in psychiatry to ensure the scientific accuracy and medical relevance of information presented and its independence from bias. NEI takes responsibility for the content, quality, and scientific integrity of this CME activity.
All individuals in a position to influence or control content are required to disclose any relevant financial relationships. Although potential conflicts of interest are identified and resolved prior to the activity being presented, it remains for the participant to determine whether outside interests reflect a possible bias in either the exposition or the conclusions presented.
Stephen M. Stahl, MD, PhD, DSc (Hon.)
Clinical Professor, Department of Psychiatry and Neuroscience, University of California, Riverside School of Medicine, Riverside, CA
Adjunct Professor, Department of Psychiatry, University of California, San Diego School of Medicine, La Jolla, CA
Honorary Visiting Senior Fellow, University of Cambridge, Cambridge, UK
Director of Psychopharmacology Services, California Department of State Hospitals, Sacramento, CA
Grant/Research: Acadia, Avanir, Braeburn, Intra-Cellular, Ironshore, Lilly, Neurocrine, Otsuka, Sunovion
Consultant/Advisor: Acadia, Alkermes, Allergan, Arbor, Axovant, Axsome, Celgene, ClearView, Concert, EMD Serono, Eisai, Ferring, Impel, Intra-Cellular, Ironshore, Janssen, Lilly, Lundbeck, Merck, Otsuka, Pfizer, Sage, Servier, Sunovion, Takeda, Taliaz, Teva, Tonix, Tris, Vifor
Board Member: Genomind
Meghan M. Grady, BA
Vice President, Content Development, Neuroscience Education Institute, Carlsbad, CA
No financial relationships to disclose.
Gabriela Alarcón, PhD
Medical Writer, Neuroscience Education Institute, Carlsbad, CAAll of Dr. Alarcón’s financial relationships are through her spouse/partner.
Employee (spouse/partner): Ashfield Healthcare Communications
William M. Sauvé, MD
Regional Medical Director, Greenbrook TMS NeuroHealth Centers, Virginia
Speakers Bureau: Avanir
Assistant Dean of Biomedicine; Associate Director, Outreach and Partnerships; Sanders-Brown Center on Aging; Sweeney-Nelms Professor in Alzheimer’s Disease Research, Alzheimer’s Disease Center; Associate Professor, Department of Physiology; University of Kentucky College of Medicine, Lexington, KY
Consultant/Advisor: AC Immune, Alector, AvroBio
The Planning Committee, Editorial, and Design Staff, and remaining Peer Reviewers have no financial relationships to disclose.
This educational activity may include discussion of unlabeled and/or investigational uses of agents that are not currently labeled for such use by the FDA. Please consult the product prescribing information for full disclosure of labeled uses.
A variety of resources addressing cultural and linguistic competency can be found at this link: www.neiglobal.com/go/cmeregs.
This activity is supported solely by the provider, NEI.
Suggested Reading and Selected References