This fully revised edition returns to the essential roots of what it means to become a neurobiologically empowered psychopharmacologist. This remains the essential text for all students and professionals in mental health seeking to understand and utilize current therapeutics.
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
Printed and bound in the United Kingdom by the MPG Books Group
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Every effort has been made in preparing this book to provide accurate and up-to-date information which 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.
Disorders of sleep and wakefulnessand their treatment
This chapter will provide a brief overview of the psychopharmacology of disorders
of sleep and wakefulness. Included here are short discussions of the symptoms, diagnostic
criteria, and treatments for disorders that cause insomnia, excessive daytime sleepiness,
or both. Clinical descriptions and formal criteria for how to diagnose sleep disorders
are mentioned here only in passing. The reader should consult standard reference sources
for this material. The discussion here will emphasize the links between various brain
circuits and their neurotransmitters and disorders that cause insomnia or sleepiness.
The goal of this chapter is to acquaint the reader with ideas about the clinical and
biological aspects of sleep and wakefulness, how various disorders can alter sleep
and wakefulness, and how many new and evolving treatments can resolve the symptoms
of insomnia and sleepiness.
The detection, assessment, and treatment of sleep/wake disorders are rapidly becoming standardized
parts of a psychiatric evaluation. Modern psychopharmacologists increasingly consider
sleep to be a psychiatric “vital sign,” requiring routine evaluation and symptomatic
treatment whenever sleep disorders are encountered. This is similar to the situation
of pain (Chapter 10), which is also increasingly being considered as another psychiatric “vital sign.”
That is, disorders of sleep (and pain) are so important, so pervasive, and cut across
so many psychiatric conditions that the elimination of these symptoms – no matter
what psychiatric disorder may be present – is increasingly recognized as necessary
in order to achieve full symptomatic remission for the patient.
Many of the treatments discussed in this chapter are covered in previous chapters. For details
of mechanisms of insomnia treatments that are also used for the treatment of depression,
the reader is referred to Chapter 7. For those insomnia treatments that are benzodiazepines and share the same mechanism
of action with various benzodiazepine anxiolytics, the reader is referred to Chapter 9. For various hypersomnia treatments, especially stimulants, the reader is
referred to Chapter 12 on ADHD and to Chapter 14 on drug abuse, which also discuss the use and abuse of stimulants. The discussion in this chapter is at the conceptual level, and not at the pragmatic level. The reader
should consult standard drug handbooks (such as Stahl’s Essential Psychopharmacology: the Prescriber’s Guide) for details of doses, side effects, drug interactions, and other issues relevant
to the prescribing of these drugs in clinical practice.
Neurobiology of sleep and wakefulness
The arousal spectrum
Although many experts approach insomnia and sleepiness by emphasizing the separate
and distinct disorders that cause them, many pragmatic psychopharmacologists approach insomnia or excessive
daytime sleepiness as important symptoms that cut across many conditions and that occur along a spectrum from deficient arousal
to excessive arousal (Figure 11-1). In this conceptualization, an awake, alert, creative and problem-solving person
has the right balance between too much and too little arousal (baseline brain functioning
in gray at the middle of the spectrum in Figure 11-1). As arousal increases beyond normal, during the day there is hypervigilance (Figure 11-1); if this increased, arousal occurs at night and there is insomnia (Figure 11-1, and overactivation of the brain in red at the right-hand side of the spectrum in
Figure 11-2). From a treatment perspective, insomnia can be conceptualized as a disorder of excessive
nighttime arousal, with hypnotics moving the patient from too much arousal to sleep
On the other hand, as arousal diminishes, symptoms crescendo from mere inattentiveness
to more severe forms of cognitive disturbances until the patient has excessive daytime
sleepiness with sleep attacks (Figure 11-1, and hypoactivation of the brain in blue at the left-hand side of the spectrum in
Figure 11-3). From a treatment perspective, sleepiness can be conceptualized as a disorder of
deficient daytime arousal, with wake-promoting agents moving the patient from too
little arousal to awake with normal alertness (Figure 11-3).
Note in Figure 11-1 that cognitive disturbance is the product of both too little and too much arousal,
consistent with the need of cortical pyramidal neurons to be optimally “tuned,” with
too much activity making them just as out of tune as too little. Note also in Figures 11-1 through 11-3 that the arousal spectrum is linked to the actions of five neurotransmitters shown
in the brains represented in these figures (i.e., histamine, dopamine, norepinephrine,
serotonin, and acetylcholine). Sometimes these neurotransmitter circuits as a group
are called the ascending reticular activating system, because they are known to work
together to regulate arousal. This same ascending neurotransmitter system is blocked
at several sites by many agents that cause sedation. Actions of sedating drugs on
these neurotransmitters are discussed in Chapter 5 on antipsychotics and illustrated in Figure 5-38. Figure 11-1 also shows that excessive arousal can extend past insomnia to panic, hallucinations,
and all the way to frank psychosis (far right-hand side of the spectrum).
The sleep/wake switch
We have discussed how the ascending neurotransmitter systems from the brainstem regulate
a cortical arousal system on a smooth continuum like a rheostat on a lighting system
or a volume button on a radio. There is another set of circuits in the hypothalamus
that regulate sleep and wake discontinuously, like an on/off switch. Not surprisingly,
this circuitry is called the sleep/wake switch (Figure 11-4). The “on” switch is known as the wake promoter and is localized within the tuberomammillary nucleus (TMN) of the hypothalamus (Figure 11-4A). The “off” switch is known as the sleep promoter and is localized within the ventrolateral preoptic (VLPO) nucleus of the hypothalamus
Two other sets of neurons are shown in Figure 11-4 as regulators of the sleep/wake switch: orexin-containing neurons of the lateral
hypothalamus (LAT) and melatonin-sensitive neurons of the suprachiasmatic nucleus
(SCN). The lateral hypothalamus serves to stabilize and promote wakefulness via a
peptide neurotransmitter known by two different names: orexin and hypocretin. These
lateral hypothalamic neurons and their orexin are lost in narcolepsy, especially narcolepsy
with cataplexy. New hypnotics on the horizon (orexin antagonists) block the receptors
for these neurotransmitters and are discussed later in this chapter. The SCN is the
brain’s internal clock, or pacemaker, and regulates circadian input to the sleep/wake
switch in response to how it is programmed by hormones such as melatonin and by the
light/dark cycle. Circadian rhythms and the SCN are discussed in Chapter 7 on antidepressants and illustrated in Figures 7-39 to 7-42.
Figure 11-1.Arousal spectrum of sleep and wakefulness. One’s state of arousal is more complicated than simply being “awake” or “asleep.”
Rather, arousal exists as if on a dimmer switch, with many phases along the spectrum.
Where on the spectrum one lies is influenced in large part by five key neurotransmitters:
histamine (HA), dopamine (DA), norepinephrine (NE), serotonin (5HT), and acetylcholine
(ACh). When there is good balance between too much and too little arousal (depicted
by the gray [baseline] color of the brain), one is awake, alert, and able to function
well. As the dial shifts to the right there is too much arousal, which may cause hypervigilance
and consequently insomnia at night. As arousal further increases this can cause cognitive
dysfunction, panic, and in extreme cases perhaps even hallucinations. On the other
hand, as arousal diminishes, individuals may experience inattentiveness, cognitive
dysfunction, sleepiness, and ultimately sleep.
The circadian wake drive is shown in Figure 11-5 over two full 24-hour cycles. Also shown in Figure 11-5 is the ultradian sleep cycle (a cycle faster than a day, showing cycling in and out
of REM and slow-wave sleep several times during the night). Homeostatic sleep drive,
illustrated as well in Figure 11-5, increases the drive for sleep as the day goes on, presumably due to fatigue, and
diminishes at night with rest. The novel neurotransmitter adenosine is linked to homeostatic
drive, and appears to accumulate as this drive increases during the day, and to diminish
at night. Caffeine is now known to be an antagonist of
Figure 11-2.Insomnia: excessive nighttime arousal? Insomnia is conceptualized as being related to hyperarousal at night, depicted here
as the brain being red (overactive). Agents that reduce brain activation, such as
positive allosteric modulators of GABAA receptors (e.g., benzodiazepines, “Z drugs”), histamine 1 antagonists, and serotonin
2A/2C antagonists, can shift one’s arousal state from hyperactive to sleep.
Figure 11-3.Excessive daytime sleepiness: deficient daytime arousal. Excessive sleepiness is conceptualized as being related to hypoarousal during the
day, depicted here as the brain being blue (hypoactive). Agents that increase brain
activation, such as the stimulants, modafinil, and caffeine, can shift one’s arousal
state from hypoactive to awake with normal alertness.
Figure 11-4.Sleep/wake switch. The hypothalamus is a key control center for sleep and wake, and the specific circuitry
that regulates sleep/wake (i.e., whether the dimmer switch is set all the way to the
left for sleep or is somewhere else along the continuum for wake) is called the sleep/wake
switch. The “off” setting, or sleep promoter, is localized within the ventrolateral
preoptic nucleus (VLPO) of the hypothalamus, while “on” – the wake promoter – is localized
within the tuberomammillary nucleus (TMN) of the hypothalamus. Two key neurotransmitters
regulate the sleep/wake switch: histamine from the TMN and GABA from the VLPO. (A)
When the TMN is active and histamine is released to the cortex and the VLPO, the wake
promoter is on and the sleep promoter inhibited. (B) When the VLPO is active and GABA
is released to the TMN, the sleep promoter is on and the wake promoter inhibited.
The sleep/wake switch is also regulated by orexin/hypocretin neurons in the lateral
hypothalamus (LAT), which stabilize wakefulness, and by the suprachiasmatic nucleus
(SCN) of the hypothalamus, which is the body’s internal clock and is activated by
melatonin, light, and activity to promote either sleep or wake.
Figure 11-5.Processes regulating sleep. Several processes that regulate sleep/wake are shown here. The circadian wake drive
is a result of input (light, melatonin, activity) to the suprachiasmatic nucleus.
Homeostatic sleep drive increases the longer one is awake and decreases with sleep.
As the day progresses, circadian wake drive diminishes and homeostatic sleep drive
increases until a tipping point is reached and the ventrolateral preoptic sleep promoter
(VLPO) is triggered to release GABA in the tuberomammillary nucleus (TMN) and inhibit
wakefulness. Sleep itself consists of multiple phases that recur in a cyclical manner;
this process is known as the ultradian cycle, and is depicted at the top of this figure.
adenosine, and this may explain in part its ability to promote wakefulness and diminish
fatigue, namely by opposing endogenous adenosine’s regulation of the homeostatic sleep
Two key neurotransmitters regulate the sleep/wake switch: histamine from the TMN and
GABA (γ-aminobutyric acid) from the VLPO. Thus, when the sleep/wake switch is on,
the wake promoter TMS is active and histamine is released (Figure 11-4). This occurs both in the cortex to facilitate arousal, and in the VLPO to inhibit
the sleep promoter. As the day progresses, circadian wake drive diminishes and homeostatic
sleep drive increases (Figure 11-5); eventually a tipping point is reached, and the VLPO sleep promoter is triggered,
the sleep/wake switch is turned off, and GABA is released in the TMN to inhibit wakefulness
Disorders characterized by excessive daytime sleepiness can be conceptualized as the
sleep/wake switch being off during the daytime. Wake-promoting treatments such as
modafinil given during the day tip the balance back to wakefulness by promoting the
release of histamine from TMN neurons. The exact mechanism of this enhancement of
histamine release by modafinil or stimulants is not known, but is currently hypothesized
to be related in part to a downstream consequence of the actions of wake-promoting
drugs on dopamine neurons, especially by blocking the dopamine transporter DAT.
On the other hand, disorders characterized by insomnia can be conceptualized as the
sleep/wake switch being on at night. Insomnia can be treated either by agents that
enhance GABA actions, and thus inhibit the wake promoter, or by agents that block
the action of histamine released from the wake promoter and act at postsynaptic H1 receptors.
Disorders characterized by a disturbance in circadian rhythm can be conceptualized
as either “phase delayed,” with the wake promoter and sleep/wake switch being turned
on too late in a normal 24-hour cycle, or “phase advanced,” with the wake promoter
and sleep/wake switch being turned on too early in a normal 24-hour cycle. That is,
individuals who are phase delayed, including many depressed patients and many normal
adolescents, still have their sleep/wake switch off when it is time to get up (see
discussion in Chapter 7 and Figure 7-39). Giving such individuals morning light and evening melatonin can reset the circadian
clock in the SCN so that it wakes the person up earlier. Other individuals may be
phase advanced, including many normal elderly people. Giving these individuals evening
light and morning melatonin can reset their SCNs so that the sleep/wake switch stays
off a bit longer, returning the patient to a normal rhythm.
Figure 11-6.Histamine is produced. Histidine (HIS), a precursor to histamine, is taken up into histamine nerve terminals
via a histidine transporter and converted into histamine by the enzyme histidine decarboxylase
(HDC). After synthesis, histamine is packaged into synaptic vesicles and stored until
its release into the synapse during neurotransmission.
Figure 11-7.Histamine’s action is terminated. Histamine can be broken down intracellularly by two enzymes. Histamine N-methyl-transferase (histamine NMT) converts histamine into N-methyl-histamine, which is then converted by monoamine oxidase B (MAO-B) into the
inactive substance N-methyl-indole-acetic acid (N-MIAA).
Histamine is one of the key neurotransmitters regulating wakefulness, and is the ultimate
target of many wake-promoting drugs (via downstream histamine release) and sleep-promoting
drugs (antihistamines). Histamine is produced from the amino acid histidine, which
is taken up into histamine neurons and converted to histamine by the enzyme histidine
decarboxylase (Figure 11-6). Histamine’s action is terminated by two enzymes working in sequence: histamine
N-methyl-transferase, which converts histamine to N-methyl-histamine, and MAO-B, which converts N-methyl-histamine into N-MIAA (N-methyl-indole-acetic acid), an inactive substance (Figure 11-7). Additional enzymes such as diamine oxidase can also terminate histamine action
outside of the brain. Note that there is no apparent reuptake pump for histamine.
Thus, histamine is likely to diffuse widely away from its synapse, just like dopamine
does in prefrontal cortex.
There are a number of histamine receptors (Figures 11-8 through 11-11). The postsynaptic histamine 1 (H1) receptor is best known (Figure 11-9A) because it is the target of “antihistamines” (i.e., H1 antagonists) (Figure 11-9B). When histamine itself acts at H1 receptors, it activates a G-protein-linked second-messenger system that activates
phosphatidyl inositol, and the transcription factor cFOS, and results in wakefulness,
normal alertness, and pro-cognitive actions (Figure 11-9A). When these H1 receptors are blocked in the brain, they interfere with the wake-promoting actions
of histamine, and thus can cause sedation, drowsiness, or sleep (Figure 11-9B).
Histamine 2 (H2) receptors, best known for their actions in gastric acid secretion and the target
of a number of anti-ulcer drugs, also exist in the brain (Figure 11-10). These postsynaptic receptors also activate a G-protein second-messenger system
with cAMP, phosphokinase A, and the gene product CREB. The function of H2 receptors in brain is still being clarified, but apparently is not linked directly
A third histamine receptor is present in brain, namely the H3 receptor (Figures 11-8 and 11-11). Synaptic H3 receptors are presynaptic (Figure 11-11A) and function as autoreceptors (Figure 11-11B). That is, when histamine binds to these receptors, it turns
Figure 11-8.Histamine receptors. Shown here are receptors for histamine that regulate its neurotransmission. Histamine
1 and histamine 2 receptors are postsynaptic, while histamine 3 receptors are presynaptic
autoreceptors. There is also a binding site for histamine on NMDA receptors – it can
act at the polyamine site, which is an allosteric modulatory site.
Figure 11-9.Histamine 1 receptors. (A) When histamine binds to postsynaptic histamine 1 receptors, it activates a G-protein-linked
second-messenger system that activates phosphatidyl inositol and the transcription
factor cFOS. This results in wakefulness and normal alertness. (B) Histamine 1 antagonists
prevent activation of this second messenger and thus can cause sleepiness.
Figure 11-10.Histamine 2 receptors. Histamine 2 receptors are present both in the body and in the brain. When histamine
binds to postsynaptic histamine 2 receptors it activates a G-protein-linked second-messenger
system with cAMP, phosphokinase A, and the gene product CREB. The function of histamine
2 receptors in the brain is not yet elucidated but does not appear to be directly
linked to wakefulness.
off further release of histamine (Figure 11-11B). One novel approach to new wake-promoting and pro-cognitive drugs is to block these
receptors, thus facilitating the release of histamine, allowing histamine to act at
H1 receptors to produce the desired effects (Figure 11-11C). Several H3 antagonists are in clinical development.
There is a fourth type of histamine receptor, H4, but these are not known to occur in the brain. Finally, histamine acts also at NMDA
(N-methyl-d-aspartate) receptors (Figure 11-8). Interestingly, when histamine diffuses away from its synapse to a glutamate synapse
containing NMDA receptors, it can act at an allosteric modulatory site called the
polyamine site, to alter the actions of glutamate at NMDA receptors (Figure 11-8). The role of histamine and function of this action are not well clarified.
Histamine neurons all arise from a single small area of the hypothalamus known as the tuberomammillary
nucleus (TMN), which is part of the sleep/wake switch illustrated in Figure 11-4. Thus, histamine plays an important role in arousal, wakefulness, and sleep. The
TMN is a small bilateral nucleus that provides histaminergic input to most brain regions
and to the spinal cord (Figure 11-12).
As you browse, save any image and then find it here for easy reference.
Preface to the fourth edition
For this fourth edition of Stahl’s Essential Psychopharmacology you will notice there is a new look and feel. With a new layout, displayed over two
columns, and an increased page size we have eliminated redundancies across chapters,
have added significant new material, and yet have decreased the overall size of the
Highlights of what has been added or changed since the 3rd edition include:
Integrating much of the basic neurosciences into the clinical chapters, thus reducing
the number of introductory chapters solely covering basic neurosciences.
Major revision of the psychosis chapter, including much more detailed coverage of
the neurocircuitry of schizophrenia, the role of glutamate, genomics, and neuroimaging.
One of the most extensively revised chapters is on antipsychotics, which now has:
new discussion and illustrations on how the current atypical antipsychotics act upon
serotonin, dopamine, and glutamate circuitry
new discussion of the roles of neurotransmitter receptors in the mechanisms of actions
of some but not all atypical antipsychotics
completely revamped visuals for displaying the relative binding properties of 17 individual
antipsychotics agents, based upon log binding data made qualitative and visual with
reorganization of the known atypical antipsychotics as
the “pines” (peens)
and a “rip”
inclusion of several new antipsychotics
extensive coverage of switching from one antipsychotic to another
new ideas about using high dosing and polypharmacy for treatment resistance and violence
The impulsivity–compulsivity and addiction chapter is another of the most extensively
revised chapters in this fourth edition, significantly expanding the drug abuse chapter
of the third edition to include now a large number of related “impulsive–compulsive”
disorders that hypothetically share the same brain circuitry:
neurocircuitry of impulsivity and reward involving the ventral striatum
neurocircuitry of compulsivity and habits including drug addiction and behavioral
addiction involving the dorsal striatum
“bottom-up” striatal drives and “top-down” inhibitory controls from the prefrontal
update on the neurobiology and available treatments for the drug addictions (stimulants,
nicotine, alcohol, opioids, hallucinogens, and others)
major new section on obesity, eating disorders, and food addiction, including the
role of hypothalamic circuits and new treatments for obesity
phentermine/topiramate ER (Qsymia)
obsessive–compulsive and spectrum disorders
gambling, impulsive violence, mania, ADHD and many others
One of the major themes emphasized in this new edition is the notion of symptom endophenotypes, or dimensions of psychopathology that cut across numerous syndromes. This is seen
perhaps most dramatically in the organization of numerous disorders of impulsivity/compulsivity,
where impulsivity and/or compulsivity are present in many psychiatric conditions and
thus “travel” trans-diagnostically without respecting the DSM (Diagnostic and Statistical Manual) of the American Psychiatric Association or the ICD (International Classification of Diseases). This is the future of psychiatry – the matching of symptom endophenotypes to hypothetically
malfunctioning brain circuits, regulated by genes, the environment, and neurotransmitters.
Hypothetically, inefficiency of information processing in these brain circuits creates
symptom expression in various psychiatric disorders that can be changed with psychopharmacologic
agents. Even the DSM recognizes this concept and calls it Research Domain Criteria (or RDoC). Thus, impulsivity and compulsivity can be seen as domains of psychopathology;
other domains include mood, cognition, anxiety, motivation, and many more. Each chapter
in this fourth edition discusses “symptoms and circuits” and how to exploit domains of psychopathology both to become a neurobiologically
empowered psychopharmacologist, and to select and combine treatments for individual
patients in psychopharmacology practice.
What has not changed in this new edition is the didactic style of the first three editions. 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, 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, reviewing only the color graphics and the legends
for those 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.
Expansion of Essential Psychopharmacology books
This fourth edition of Essential Psychopharmacology is the flagship, but not the entire fleet, as the Essential Psychopharmacology series has expanded now to an entire suite of products for the interested reader.
For those of you interested in specific prescribing information, there are now three
for psychotropic drugs, Stahl’s Essential Psychopharmacology: the Prescriber’s Guide
for neurology drugs, Essential Neuropharmacology: the Prescriber’s Guide
for pain drugs: Essential Pain Pharmacology: the Prescriber’s Guide
For those interested in how the textbook and prescriber’s guides get applied in clinical
practice there is a book covering 40 cases from my own clinical practice:
Case Studies: Stahl’s Essential Psychopharmacology
For teachers and students wanting to assess objectively their state of 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
Stahl’s Self-Assessment Examination in Psychiatry: Multiple Choice Questions for Clinicians
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 Use and Impulsive Disorders
Finally, there is an ever-growing edited series of subspecialty topics:
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. We are proud to announce the continuing update of this new website which allows
you to search online within the entire Essential Psychopharmacology suite of products. With publication of the fourth edition, two new features will
become available on the website:
downloadable slides of all the figures in the book
narrated animations of several figures in the textbook, hyperlinked to the online
version of the book, playable with a click
our new journal CNS Spectrums (www.journals.cambridge.org/CNS), of which I am the new editor-in-chief, and which is now the official journal of
the Neuroscience Education Institute (NEI), free online to NEI members. This journal
now features readable and illustrated reviews of current topics in psychiatry, mental
health, neurology, and the neurosciences as well as psychopharmacology
for CME credits for reading the books and the journal, and for completing numerous
additional programs both online and live
for access to the live course and playback encore features from the annual NEI Psychopharmacology
for access to the NEI Master Psychopharmacology Program, an online fellowship with
plans for expansion to a Cambridge University Health Partners co-accredited online
Masterclass and Certificate in Psychopharmacology, based upon live programs held on
campus in Cambridge and taught by University of Cambridge faculty, including myself,
having joined the faculty there as an Honorary Visiting Senior Fellow
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
Stephen M. Stahl, MD, PhD
Originally released: February 1, 2013
Reviewed and re-released: February 1, 2016
CME credit expires: January 31, 2019
This activity has been developed for prescribers specializing in psychiatry. All other health care providers interested in psychopharmacology are welcome for advanced study, especially primary care physicians, nurse practitioners, psychologists, and pharmacists.
Statement of need
Psychiatric illnesses have a neurobiological basis and are primarily treated by pharmacological agents; understanding each of these, as well as the relationship between them, is essential in order to select appropriate treatment for a patient. The field of psychopharmacology has experienced incredible growth; it has also experienced a major paradigm shift from a limited focus on neurotransmitters and receptors to an emphasis as well upon brain circuits, neuroimaging, genetics, and signal transduction cascades.
The following unmet needs and professional practice gaps regarding mental health were revealed following a critical analysis of activity feedback, expert faculty assessment, literature review, and through new medical knowledge:
Mental disorders are highly prevalent and carry substantial burden that can be alleviated through treatment; unfortunately, many patients with mental disorders do not receive treatment or receive suboptimal treatment.
There is a documented gap between evidence-based practice guidelines and actual care in clinical practice for patients with mental illnesses. This gap is due at least in part to lack of clinician confidence and knowledge in terms of appropriate usage of the therapeutic tools available to them.
To help address clinician performance gaps with respect to diagnosis and treatment of mental health disorders, quality improvement efforts need to provide education regarding (1) the fundamentals of neurobiology as it relates to the most recent research regarding the neurobiology of mental illnesses; (2) the mechanisms of action of treatment options for mental illnesses and the relationship to the pathophysiology of the disease states; and (3) new therapeutic tools and research that are likely to affect clinical practice.
After completing this activity, you should be better able to:
Apply fundamental principles of neurobiology to the assessment of psychiatric disease states
Differentiate the neurobiological targets for psychotropic medications
Link the relationship of psychotropic drug mechanism of action to the pathophysiology of disease states
Identify novel research and treatment approaches that are expected to affect clinical practice
Accreditation and credit designation statements
The Neuroscience Education Institute is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.
The Neuroscience Education Institute designates this enduring material for a maximum of 67.0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
for all of your CNE requirements for recertification, the ANCC will accept AMA PRA Category 1 Credits™ from organizations accredited by the ACCME. The content of this activity pertains to pharmacology and is worth 67.0 continuing education hours of pharmacotherapeutics.
the NCCPA accepts AMA PRA Category 1 Credits™ from organizations accredited by the AMA (providers accredited by the ACCME).
A certificate of participation for completing this activity will also be available.
Optional posttests and CME credit instructions
The estimated time for completion of this activity is 67 hours. Optional certificates of CME credit or participation are available for each topical section of the book (total of twelve sections). There is a fee for each posttest (varies per section) which is waived for NEI members.
Read the desired topical section, evaluating the content presented
Print your certificate (if a score of 70% or more is achieved)
Questions? call 888-535-5600, or email CustomerService@NEIglobal.com
The content was originally peer-reviewed in 2013 by 3 MDs and a PharmD to ensure the scientific accuracy and medical relevance of information presented and its independence from commercial bias. The content was reviewed again in 2016 to verify it is still up-to-date and accurate. The Neuroscience Education Institute takes responsibility for the content, quality, and scientific integrity of this CME activity.
Disclosed financial relationships with conflicts of interest have been reviewed by the NEI CME Advisory Board Chair and resolved.
Stephen M. Stahl, MD, PhD
Adjunct Professor, Department of Psychiatry, University of California, San Diego School of Medicine, La Jolla, CA
Honorary Visiting Senior Fellow, University of Cambridge, UK
Director of Psychopharmacology, California Department of State Hospitals, Sacramento, CA
Director, Content Development, Neuroscience Education Institute, Carlsbad, CA
No financial relationships to disclose
Debbi Ann Morrissette, PhD
Adjunct Professor, Biological Sciences, California State University, San Marcos
Medical Writer, Neuroscience Education Institute, Carlsbad, CA
No financial relationships to disclose
The 2013 Peer Reviewers and Design Staff had no financial relationships to disclose. The 2016 Peer Reviewer has no financial relationships to disclose.
Disclosure of Off-Label Use
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.
Participants have an implied responsibility to use the newly acquired information from this activity to enhance patient outcomes and their own professional development. The information presented in this educational activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this educational activity should not be used by clinicians without evaluation of their patients’ conditions and possible contraindications or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities. Primary references and full prescribing information should be consulted.