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
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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.
Transporters, receptors, and enzymes as targets of psychopharmacological drug action
Psychotropic drugs have many mechanisms of action, but they all target specific molecular
sites that have profound effects upon neurotransmission. It is thus necessary to understand
the anatomical infrastructure and chemical substrates of neurotransmission (Chapter 1) in order to grasp how psychotropic drugs work. Although there are over 100 essential
psychotropic drugs utilized in clinical practice today (see Stahl’s Essential Psychopharmacology: the Prescriber’s Guide), there are only a few sites of action for all these therapeutic agents (Figure 2-1). Specifically, about a third of psychotropic drugs target one of the transporters
for a neurotransmitter; another third target receptors coupled to G proteins; and
perhaps only 10% target enzymes. All three of these sites of action will be discussed
in this chapter. The balance of psychotropic drugs target various types of ion channels,
which will be discussed in Chapter 3. Thus, mastering how just a few molecular sites regulate neurotransmission allows
the psychopharmacologist to understand the theories about the mechanisms of action
of virtually all psychopharmacological agents.
Neurotransmitter transporters as targets of drug action
Classification and structure
Neuronal membranes normally serve to keep the internal milieu of the neuron constant
by acting as barriers to the intrusion of outside molecules and to the leakage of
internal molecules. However, selective permeability of the membrane is required to
allow discharge as well as uptake of specific molecules, to respond to the needs of
cellular functioning. Good examples of this are neurotransmitters, which are released
from neurons during neurotransmission and, in many cases, are also transported back
into presynaptic neurons as a recapture mechanism following their release. This recapture
– or reuptake – is done in order for neurotransmitter to be reused in a subsequent
neurotransmission. Also, once inside the neuron, most neurotransmitters are transported
again into synaptic vesicles for storage, protection from metabolism, and immediate
use during a volley of future neurotransmission.
Figure 2-1.The molecular targets of psychotropic drugs. There are only a few major sites of action for the wide expanse of psychotropic
drugs utilized in clinical practice. Approximately one-third of psychotropic drugs
target one of the twelve-transmembrane-region transporters for a neurotransmitter
(A), while another third target seven-transmembrane-region receptors coupled to G
proteins (B). The sites of action for the remaining third of psychotropic drugs include
enzymes (C), four-transmembrane-region ligand-gated ion channels (D), and six-transmembrane-region
voltage-sensitive ion channels (E).
Both types of neurotransmitter transport – presynaptic reuptake as well as vesicular
storage – utilize a molecular transporter belonging to a “superfamily” of twelve-transmembrane-region
proteins (Figures 2-1A and 2-2). That is, neurotransmitter transporters have in common the structure of going in
and out of the membrane 12 times (Figure 2-1A). These transporters are a type of receptor that binds to the neurotransmitter prior
to transporting that neurotransmitter across the membrane.
Recently, details of the structures of neurotransmitter transporters have been determined;
this has led to a proposed subclassification of neurotransmitter transporters. That
is, there are two major subclasses of plasma membrane transporters for neurotransmitters. Some of these transporters are presynaptic and others are
on glial membranes. The first subclass consists of sodium/chloride-coupled transporters, called the solute carrier SLC6 gene family, and includes transporters
for the monoamines serotonin, norepinephrine, and dopamine (Table 2-1 and Figure 2-2A) as well as for the neurotransmitter GABA (gamma-aminobutyric acid) and the amino
acid glycine (Table 2-2 and Figure 2-2A). The second subclass consists of high-affinity glutamate transporters, also called the solute carrier SLC1 gene family (Table 2-2 and Figure 2-2A).
In addition, there are three subclasses of intracellular synaptic vesicle transporters for neurotransmitters. The SLC18 gene family comprises the vesicular monoamine transporters (VMATs) for serotonin, norepinephrine, dopamine, and histamine and the vesicular acetylcholine transporter (VAChT). The SLC32 gene family consists of the vesicular inhibitory amino acid transporters (VIAATs). Finally, the SLC17 gene family consists of the vesicular glutamate transporters, such as VGluT1–3 (Table 2-3 and Figure 2-2B).
Monoamine transporters (SLC6 gene family) as targets of psychotropic drugs
Reuptake mechanisms for monoamines utilize unique presynaptic transporters (Figure 2-2A) but the same vesicular transporter in all three monoamine neurons (histamine neurons
also use the same vesicular
Table 2-1 Presynaptic monoamine transporters
Table 2-2 Neuronal and glial GABA and amino acid transporters
transporter) (Figure 2-2B). That is, the unique presynaptic transporter for serotonin is known as SERT, for
norepinephrine is known as NET, and for dopamine is known as DAT (Table 2-1 and Figure 2-2A). All three of these monoamines are then transported into synaptic vesicles of their
respective neurons by the same vesicular transporter, known as VMAT2 (vesicular monoamine transporter 2) (Figure 2-2B and Table 2-3).
Although the three presynaptic transporters – SERT, NET, and DAT – are unique in their
amino acid sequences and binding affinities for monoamines, each presynaptic monoamine
transporter nevertheless has appreciable affinity for amines other than the one matched
to its own neuron (Table 2-1). Thus, if other transportable neurotransmitters or drugs are in the vicinity of
a given monoamine transporter, they may also be transported into the presynaptic neuron
by hitchhiking a ride on certain transporters that can carry them into the neuron.
For example, the norepinephrine transporter (NET) has high affinity for the transport
of dopamine as well as for norepinephrine, the dopamine transporter (DAT) has high
affinity for the transport of amphetamines as well as for dopamine, and the serotonin
transporter (SERT) has high affinity for the transport of “ecstasy” (the drug of abuse
MDMA or 3,4-methylenedioxymethamphetamine) as well as for serotonin (Table 2-1).
How are neurotransmitters transported? Monoamines are not passively shuttled into
the presynaptic neuron, because it requires energy to concentrate monoamines into
a presynaptic neuron. That energy is provided by transporters in the SLC6 gene family
coupling the “downhill” transport of sodium (down a concentration gradient) with the
“uphill” transport of the monoamine (up a concentration gradient) (Figure 2-2A). Thus, the monoamine transporters are really sodium-dependent cotransporters; in
most cases, this involves the additional cotransport of chloride, and in some cases
the countertransport of
A.Sodium-potassium ATPase. Transport of many neurotransmitters into the presynaptic neuron is not passive,
but rather requires energy. This energy is supplied by sodium-potassium ATPase (adenosine
triphosphatase), an enzyme that is also sometimes referred to as the sodium pump.
Sodium-potassium ATPase continuously pumps sodium out of the neuron, creating a downhill
gradient. The “downhill” transport of sodium is coupled to the “uphill” transport
of the neurotransmitter. In many cases this also involves cotransport of chloride
and in some cases countertransport of potassium. Examples of neurotransmitter transporters
include the serotonin transporter (SERT), the norepinephrine transporter (NET), the
dopamine transporter (DAT), the GABA transporter (GAT), the glycine transporter (GlyT),
and the excitatory amino acid transporter (EAAT).
B.Vesicular transporters. Vesicular transporters package neurotransmitters into synaptic vesicles through
the use of a proton ATPase, or proton pump. The proton pump utilizes energy to pump
positively charged protons continuously out of the synaptic vesicle. Neurotransmitter
can then be transported into the synaptic vesicle, keeping the charge inside the vesicle
constant. Examples of vesicular transporters include the vesicular monoamine transporter
(VMAT2), which transports serotonin, norepinephrine, dopamine, and histamine; the
vesicular acetylcholine transporter (VAChT), which transports acetylcholine; the vesicular
inhibitory amino acid transporter (VIAAT), which transports GABA; and the vesicular
glutamate transporter (VGluT), which transports glutamate.
potassium. All of this is made possible by coupling monoamine transport to the activity
of sodium-potassium ATPase (adenosine triphosphatase), an enzyme sometimes called the “sodium pump” that creates
the downhill gradient for sodium by continuously pumping sodium out of the neuron
The structure of a monoamine transporter from the SLC6 family has recently been proposed
to have binding sites not only for the monoamine, but also for two sodium ions (Figure 2-2A). In addition, these transporters may exist as dimers, or two copies working together
with each other, but the manner in which they cooperate is not yet well understood
and is not shown in the figures. There are other sites on this transporter – not well
defined – for drugs such as antidepressants, which bind to the transporter and inhibit
reuptake of monoamines but do not bind to the substrate site and are not transported
into the neuron (thus they are allosteric, meaning “other site”).
In the absence of sodium, there is low affinity of the monoamine transporter for its
monoamine substrate, and thus binding of neither sodium nor monoamine. An example
of this is shown for the serotonin transporter SERT in Figure 2-2A, where some of the transport “wagons” have flat tires, indicating no binding of sodium
as well as absence of binding of serotonin to its substrate binding site, since the
transporter has low affinity for serotonin in the absence of sodium. The allosteric
site for antidepressant binding is also empty (the front seat in Figure 2-2A). However, in the presence of sodium ions, the tires are “inflated” by sodium binding
and serotonin can also bind to its substrate site on SERT. The situation is now primed
for serotonin transport back into the serotonergic neuron, along with cotransport
of sodium and chloride down the gradient and into the neuron and countertransport
of potassium out of the neuron (Figure 2-2A). But if a drug binds to an inhibitory allosteric site on SERT, this reduces the affinity of the serotonin transporter SERT for its substrate serotonin,
and serotonin binding is prevented.
Table 2-3 Vesicular neurotransmitter transporters
Why does this matter? Blocking the presynaptic monoamine transporter has a huge impact
on neurotransmission at any synapse that utilizes that neurotransmitter. The normal
recapture of neurotransmitter by the presynaptic neurotransmitter transporter in Figure 2-2A keeps the levels of this neurotransmitter from accumulating in the synapse. Normally,
following release from the presynaptic neuron, neurotransmitters only have time for
a brief dance on their synaptic receptors, and the party is soon over because the
monoamines climb back into the presynaptic neuron on their transporters (Figure 2-2A). If one wants to enhance normal synaptic activity of these neurotransmitters, or
restore their diminished synaptic activity, this can be accomplished by blocking these
transporters. Although this might not seem to be a very dramatic thing, the fact is
that this alteration in chemical neurotransmission – namely the enhancement of synaptic
monoamine action – is thought to underlie the clinical effects of all the agents that
block monoamine transporters, including most known antidepressants and stimulants.
Specifically, many antidepressants enhance serotonin, norepinephrine, or both, due
to actions on SERT and/or NET. Some antidepressants act on DAT, as do stimulants.
Also, recall that many antidepressants that block monoamine transporters are also
effective anxiolytics, reduce neuropathic pain, and have additional therapeutic actions
as well. Thus, it may come as no surprise that drugs that block monoamine transporters
are among the most frequently prescribed psychotropic drugs. In fact, about a third
of the currently prescribed essential psychotropic drugs act by targeting one or more
of the three monoamine transporters.
Other neurotransmitter transporters (SLC6 and SLC1 gene families) as targets of psychotropic
In addition to the three transporters for monoamines discussed in detail above, there
are several other transporters for various different neurotransmitters or their precursors.
Although this includes a dozen additional transporters, there is only one psychotropic
drug used clinically that is known to bind to any of these transporters. Thus, there
is a presynaptic transporter for choline, the precursor to the neurotransmitter acetylcholine, but no known drugs target
this transporter. There are also several transporters for the ubiquitous inhibitory neurotransmitter
GABA, known as GAT1–4 (Table 2-2). Although debate continues about the exact localization of these subtypes at presynaptic
neurons, neighboring glia, or even postsynaptic neurons, it is clear that a key presynaptic
transporter of GABA is the GAT1 transporter, which is selectively blocked by the anticonvulsant
tiagabine, thereby increasing synaptic GABA concentrations. In addition to anticonvulsant
actions, this increase in synaptic GABA may have therapeutic actions in anxiety, sleep
disorders, and pain. No other inhibitors of this transporter are available for clinical
Finally, there are multiple transporters for two amino acid neurotransmitters, glycine
and glutamate (Table 2-2). There are no drugs utilized in clinical practice that are known to block glycine
transporters, although new agents are in clinical trials for treating schizophrenia.
The glycine transporters, along with the choline and GABA transporters, are all members
of the same family to which the monoamine transporters belong and have a similar structure
(Figure 2-2A, Tables 2-1 and 2-2). However, the glutamate transporters belong to a unique family, SLC1, and have a unique
structure and somewhat different functions compared to those transporters of the SLC6
family (Table 2-2).
Specifically, there are several transporters for glutamate, known as excitatory amino
acid transporters 1–5, or EAAT1–5 (Table 2-2). The exact localization of these various transporters at presynaptic neurons, postsynaptic
neurons, or glia is still under investigation, but the uptake of glutamate into glia
is well known to be a key system for recapturing glutamate for reuse once it has been
released. Transport into glia results in conversion of glutamate into glutamine, and
then glutamine enters the presynaptic neuron for reconversion back into glutamate.
No drugs utilized in clinical practice are known to block glutamate transporters.
One difference between transport of neurotransmitters by the SLC6 gene family and
transport of glutamate by the SLC1 gene family is that glutamate does not seem to
cotransport chloride with sodium when it also cotransports glutamate. Also, glutamate
transport is almost always characterized by the countertransport of potassium, whereas
this is not always the case with SLC6 gene family transporters. Glutamate transporters
may work together as trimers rather than dimers, as the SLC6 transporters seem to
do. The functional significance of these differences remains obscure, but may become
more apparent if clinically useful psychopharmacologic agents that target glutamate
transporters are discovered. Since it may often be desirable to diminish rather than
enhance glutamate neurotransmission, the future utility of glutamate transporters
as therapeutic targets is also unclear.
Where are the transporters for histamine and neuropeptides?
It is an interesting observation that apparently not all neurotransmitters are regulated
by reuptake transporters. The central neurotransmitter histamine apparently does not
have a presynaptic transporter (although it is transported into synaptic vesicles
by VMAT2, the same transporter used by the monoamines – see Figure 2-2B). Histamine’s inactivation is thus thought to be entirely enzymatic. The same can
be said for neuropeptides, since reuptake pumps and presynaptic transporters have
not been found for them, and are thus thought to be lacking for this class of neurotransmitter.
Inactivation of neuropeptides is apparently by diffusion, sequestration, and enzymatic
destruction, but not by presynaptic transport. It is always possible that a transporter
will be discovered in the future for some of these neurotransmitters, but at the present
time there are no known presynaptic transporters for either histamine or neuropeptides.
Vesicular transporters: subtypes and function
Vesicular transporters for the monoamines (VMATs) are members of the SLC18 gene family
and have already been discussed above. They are shown in Figure 2-2B and listed in Table 2-3, as is the vesicular transporter for acetylcholine – also a member of the SLC18 gene
family but known as VAChT. The GABA vesicular transporter is a member of the SLC32 gene family and is called VIAAT (vesicular inhibitory amino acid transporter; Figure 2-2B and Table 2-3). Finally, vesicular transporters for glutamate, called vGluT1–3 (vesicular glutamate transporters 1, 2, and 3) are members
of the SLC17 gene family – and are also shown in Figure 2-2B and listed in Table 2-3. The SV2A transporter is a novel twelve-transmembrane-region synaptic vesicle transporter of
uncertain mechanism and with unclear substrates; it is localized within the synaptic
vesicle membrane and binds the anticonvulsant levetiracetam, perhaps interfering with neurotransmitter release and thereby reducing
How do neurotransmitters get inside synaptic vesicles? In the case of vesicular transporters,
storage of neurotransmitters is facilitated by a proton ATPase, known as the “proton
pump,” that utilizes energy to pump positively charged protons continuously out of
the synaptic vesicle (Figure 2-2B). The neurotransmitters can then be concentrated against a gradient by substituting
their own positive charge inside the vesicle for the positive charge of the proton
being pumped out. Thus, neurotransmitters are not so much transported as “antiported”
– i.e., they go in while the protons are actively transported out, keeping charge
inside the vesicle constant. This concept is shown in Figure 2-2B for the VMAT transporting dopamine in exchange for protons. Contrast this with Figure 2-2A, where a monoamine transporter on the presynaptic membrane is cotransporting a monoamine
along with sodium and chloride, but with the help of a sodium-potassium ATPase (sodium
pump) rather than a proton pump.
Vesicular transporters (SLC18 gene family) as targets of psychotropic drugs
Vesicular transporters for acetylcholine (SLC18 gene family), GABA (SLC32 gene family),
and glutamate (SLC17 gene family) are not known to be targeted by any drug utilized
by humans. However, vesicular transporters for monoamines in the SLC18 gene family,
or VMATs, particularly those in dopamine and norepinephrine neurons, are potently
targeted by several drugs including amphetamine, tetrabenazine, and reserpine. Amphetamine thus has two targets: monoamine transporters as well as VMATs.
In contrast, other stimulants such as methylphenidate and cocaine target only the monoamine transporters, and in much the same manner as described
for antidepressants (see Chapter 7).
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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, physician assistants, 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
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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.