Anxiety disorders and anxiolytics
This chapter will provide a brief overview of anxiety disorders and their treatments.
Included here are descriptions of how the anxiety disorder subtypes overlap with each
other and with major depressive disorder. Clinical descriptions and formal criteria
for how to diagnose anxiety disorder subtypes are mentioned only in passing. The reader
should consult standard reference sources for this material. The discussion here will
emphasize how discoveries about the functioning of various brain circuits and neurotransmitters
– especially those centered on the amygdala – impact our understanding of fear and
worry, symptoms that cut across the entire spectrum of anxiety disorders.
The goal of this chapter is to acquaint the reader with ideas about the clinical and
biological aspects of anxiety disorders in order to understand the mechanisms of action
of the various treatments for these disorders discussed along the way. Many of these
treatments are extensively discussed in other chapters. For details of mechanisms
of anxiolytic agents used also for the treatment of depression (i.e., certain antidepressants),
the reader is referred to Chapter 7; for those anxiolytic agents used also for chronic pain (i.e., certain anticonvulsants),
the reader is referred to Chapter 10. 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.
Symptom dimensions in anxiety disorders
When is anxiety an anxiety disorder?
Anxiety is a normal emotion under circumstances of threat and is thought to be part
of the evolutionary “fight or flight” reaction of survival. Whereas it may be normal
or even adaptive to be anxious when a saber-tooth tiger (or its modern-day equivalent)
is attacking, there are many circumstances in which
the presence of anxiety is maladaptive and constitutes a psychiatric disorder. The
idea of anxiety as a psychiatric disorder is evolving rapidly, and is characterized
by the concept of core symptoms of excessive fear and worry (symptoms at the center
of anxiety disorders in
Figure 9-1), compared to major depression, which is characterized by core symptoms of depressed
mood or loss of interest (symptoms at the center of major depressive disorder in
Figure 9-1).
Anxiety disorders have considerable symptom overlap with major depression (see those
symptoms surrounding core features shown in Figure 9-1), particularly sleep disturbance, problems concentrating, fatigue, and psychomotor/arousal
symptoms. Each anxiety disorder also has a great deal of symptom overlap with other
anxiety disorders (Figures 9-2 through 9-5). Anxiety disorders are also extensively comorbid, not only with major depression,
but also with each other, since many patients qualify over time for a second or even
third concomitant anxiety disorder. Finally, anxiety disorders are frequently comorbid
with many other conditions such as substance abuse, attention deficit hyperactivity
disorder, bipolar disorder, pain disorders, sleep disorders, and more.
So, what is an anxiety disorder? These disorders all seem to maintain the core features
of some form of anxiety or fear coupled with some form of worry, but their natural
history over time shows them to morph from one into another, to evolve into full syndrome
expression of anxiety disorder symptoms (Figure 9-1) and then to recede into subsyndromal levels of symptoms only to reappear again as
the original anxiety disorder, a different anxiety disorder (Figures 9-2 through 9-5), or major depression (Figure 9-1). If anxiety disorders all share core symptoms of fear and worry (Figures 9-1 and 9-6) and, as we shall see later in this chapter, are all basically treated with the same
drugs, including many of the same drugs that treat major depression, the question
now arises, what is the difference between one anxiety disorder and another? Also,
one could ask, what is the difference between major depression and anxiety disorders?
Are all these entities really different disorders, or are they instead different aspects
of the same illness?
Overlapping symptoms of major depression and anxiety disorders
Although the core symptoms of major depression (depressed mood or loss of interest)
differ from the core symptoms of anxiety disorders (fear and worry), there is a great
deal of overlap with the other symptoms considered diagnostic both for a major depressive
episode and for several different anxiety disorders
(
Figure 9-1). These overlapping symptoms include problems with sleep, concentration, and fatigue
as well as psychomotor/arousal symptoms (
Figure 9-1). It is thus easy to see how the gain or loss of just a few additional symptoms can
morph a major depressive episode into an anxiety disorder (
Figure 9-1) or one anxiety disorder into another (
Figures 9-2 through
9-5).
From a therapeutic point of view, it may matter little what the specific diagnosis
is across this spectrum of disorders (Figures 9-1 through 9-5). That is, first-line psychopharmacological treatments may not be much different
for a patient who currently qualifies for a major depressive episode plus the symptom
of anxiety (but not an anxiety disorder) versus a patient who currently qualifies
for a major depressive episode plus a comorbid anxiety disorder with full criteria
anxiety symptoms. Although it can be useful to make specific diagnoses for following
patients over time and for documenting the evolution of symptoms, the emphasis from
a psychopharmacological point of view is increasingly to take a symptom-based therapeutic
strategy to patients with any of these disorders because the brain is not organized
according to the DSM, but according to brain
circuits with topographical localization of function. That is, specific treatments
can be tailored to the individual patient by deconstructing whatever disorder the
patient has into a list of the specific symptoms a given patient is experiencing (see
Figures 9-2 through
9-5), and then matching these symptoms to hypothetically malfunctioning brain circuits
regulated by specific neurotransmitters in order to rationally select and combine
psychopharmacological treatments to eliminate all symptoms and get the patient to
remission.
Overlapping symptoms of different anxiety disorders
Although there are different diagnostic criteria for different anxiety disorders (Figures 9-2 though 9-5), these are constantly changing, and many do not even consider obsessive–compulsive
disorder to be an anxiety disorder any longer (OCD is discussed in Chapter 14 on impulsivity). All anxiety disorders have overlapping symptoms of anxiety/fear
coupled with worry (Figure 9-6). Remarkable progress has been made in
understanding the circuitry underlying the core symptom of anxiety/fear based upon
an explosion of neurobiological research on the amygdala (
Figures 9-7 through
9-14). The links between the amygdala, fear circuits, and treatments for the symptom of
anxiety/fear across the spectrum of anxiety disorders are discussed throughout the
rest of this chapter.
Worry is the second core symptom shared across the spectrum of anxiety disorders (Figure 9-7). This symptom is hypothetically linked to the functioning of cortico-striato-thalamo-cortical
(CSTC) loops. The links between the CSTC circuits, “worry loops,” and treatments for
the symptom of worry across the spectrum of anxiety disorders are discussed later
in this chapter (see also Figures 9-15 through 9-17, 9-26, and 9-29). We shall see that what differentiates one anxiety disorder from another may not
be the anatomical localization, or the neurotransmitters regulating fear and worry
in each of these disorders (Figures 9-6 and 9-7), but the specific nature of malfunctioning within these same circuits in various
anxiety disorders. That is, in generalized anxiety disorder (GAD), malfunctioning
in the amygdala and CSTC worry loops may be hypothetically persistent, and unremitting,
yet not severe (Figure 9-2), whereas malfunctioning may be theoretically intermittent but catastrophic in an
unexpected manner for panic disorder (Figure 9-3) or in an expected manner for social anxiety (Figure 9-4). Circuit malfunctioning may be traumatic in origin and conditioned in posttraumatic
stress disorder (PTSD: Figure 9-5).