Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications 4th Edition

Book Preface

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 book.

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
5HT7 receptors
5HT2C receptors
α1-adrenergic receptors
completely revamped visuals for displaying the relative binding properties of 17 individual antipsychotics agents, based upon log binding data made qualitative and visual with novel graphics
reorganization of the known atypical antipsychotics as
the “pines” (peens)
the “dones”
two “pips”
and a “rip”
inclusion of several new antipsychotics
iloperidone (Fanapt)
asenapine (Saphris)
lurasidone (Latuda)
extensive coverage of switching from one antipsychotic to another
new ideas about using high dosing and polypharmacy for treatment resistance and violence
new antipsychotics in the pipeline
brexpiprazole
cariprazine
selective glycine reuptake inhibitors (SGRIs, e.g., bitopertin [RG1678], Org25935, SSR103800)

The mood chapter has expanded coverage of stress, neurocircuitry, and genetics.
The antidepressant and mood stabilizer chapters have:
new discussion and illustrations on circadian rhythms
discussion of the roles of neurotransmitter receptors in the mechanisms of actions of some antidepressants
melatonin receptors
5HT1A receptors
5HT2C receptors
5HT3 receptors
5HT7 receptors
NMDA glutamate receptors
inclusion of several new antidepressants
agomelatine (Valdoxan)
vilazodone (Viibryd)
vortioxetine (LuAA21004)
ketamine (rapid onset for treatment resistance)

The anxiety chapter provides new coverage of the concepts of fear conditioning, fear extinction, and reconsolidation, with OCD moved to the impulsivity chapter.
The pain chapter updates neuropathic pain states.
The sleep/wake chapter provides expanded coverage of melatonin and new discussion of orexin pathways and orexin receptors, as well as new drugs targeting orexin receptors as antagonists, such as:
suvorexant/MK-6096
almorexant
SB-649868

The ADHD chapter includes new discussion on how norepinephrine and dopamine tune pyramidal neurons in prefrontal cortex, and expanded discussion on new treatments such as:
guanfacine ER (Intuniv)
lisdexamfetamine (Vyvanse)

The dementia chapter has been extensively revamped to emphasize the new diagnostic criteria for Alzheimer’s disease, and the integration of biomarkers into diagnostic schemes including:
Alzheimer’s diagnostics
CSF Aβ and tau levels
amyloid PET scans, FDG-PET scans, structural MRI scans
multiple new drugs in the pipeline targeting amyloid plaques, tangles, and tau
vaccines/immunotherapy (e.g., bapineuzumab, solenezumab, crenezumab), intravenous immunoglobulin
γ-secretase inhibitors (GSIs, e.g., semagacestat)
β-secretase inhibitors (e.g., LY2886721, SCH 1381252, CTS21666, others)

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 cortex
update on the neurobiology and available treatments for the drug addictions (stimulants, nicotine, alcohol, opioids, hallucinogens, and others)
behavioral addictions
major new section on obesity, eating disorders, and food addiction, including the role of hypothalamic circuits and new treatments for obesity
lorcaserin (Belviq)
phentermine/topiramate ER (Qsymia)
bupropion/naltrexone (Contrave)
zonisamide/naltrexone
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.