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.
Anxiety, Trauma, and Treatment
This chapter will provide a brief overview of anxiety disorders, traumatic disorders, and their symptoms and their treatments. Included here are descriptions of how the symptoms of anxiety disorders overlap with each other, and also with the symptoms of major depressive disorder and with the symptoms of trauma and stress-related disorders. Clinical descriptions and formal diagnostic criteria are mentioned here only in passing. The reader should consult standard reference sources for this material. The discussion here will emphasize how the functioning of various brain circuits and neurotransmitters – especially those centered on the amygdala – impact our understanding of the symptoms of fear, worry, and traumatic memories.
The goal of this chapter is to acquaint the reader with ideas about the clinical and biological aspects of anxiety/traumatic symptoms in order to understand the mechanisms of action of the various treatments. Many of the psychopharmacological treatments are extensively discussed in other chapters. For details of mechanisms of the many agents used to treat anxiety that are also used to treat unipolar depression (monoamine reuptake inhibitors), the reader is referred to Chapter 7 on mood disorders and their treatments; for those agents used to treat anxiety and traumatic disorders that are also used to treat chronic pain (i.e., certain ion-channel-inhibiting anticonvulsants), the reader is referred to Chapter 9 on chronic pain and its treatment. Although all psychiatric disorders can benefit from psychotherapy, anxiety/traumatic disorders may be especially effectively treated with psychotherapy. In many cases, psychotherapy for anxiety disorders can be even more effective than drug treatment or can enhance the efficacy of anxiolytic agents. Novel psychotherapies aiming to prevent or reverse fear conditioning and fear reconsolidation are mentioned briefly here but for more details of psychotherapy for anxiety, the reader is referred to general psychiatry and clinical psychology texts as well as to books by the author that cover both psychopharmacology and psychotherapy (see reference list). The discussion of anxiety and its disorders in this chapter emphasizes the neurobiology of anxiety and the mechanism of action of drugs for anxiety. 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.
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 or excessive 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 8-1), 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 8-1). Some disorders associated with the symptoms of anxiety such as obsessive–compulsive disorder (OCD) are no longer classified as anxiety disorders in some diagnostic manuals, and here OCD is discussed in Chapter 13 on impulsive and compulsive disorders. Other disorders associated with the symptoms of anxiety such as posttraumatic stress disorder (PTSD) are also no longer classified as anxiety disorders in certain diagnostic manuals, but are discussed here in this chapter.
Anxiety disorders have considerable symptom overlap with major depression (see those symptoms surrounding core features shown in Figure 8-1), particularly sleep disturbance, problems concentrating, and fatigue and psychomotor/arousal symptoms. Each anxiety disorder also has a great deal of symptom overlap with other anxiety disorders (Figures 8-2 through 8-5; see also Figure 13-30). 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 (Figures 8-2 through 8-5). Finally, anxiety disorders are frequently comorbid with many other conditions such as substance abuse, attention deficit hyperactivity disorder (ADHD), 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 8-1) and then to recede into subsyndromal levels of symptoms, only to reappear again as the original anxiety disorder, a different anxiety disorder (Figures 8-2 through 8-5), or major depression (Figure 8-1). If anxiety disorders all share core symptoms of fear and worry (Figures 8-1 and 8-6) – 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 as to what the difference is between one anxiety disorder and another. Also, one could ask what the difference is between major depression and anxiety disorders. Are all these entities really different disorders or are they instead different aspects of the same illness?
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 for both a major depression episode and for several different anxiety disorders (Figure 8-1). These overlapping symptoms include problems with sleep, concentration, and fatigue as well as psychomotor/arousal symptoms (Figure 8-1). 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 8-1) or one anxiety disorder into another (Figures 8-2 through 8-5).
From a therapeutic point of view, it may matter little what the specific diagnosis is across this spectrum of disorders (Figures 8-1 through 8-5). That is, 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. 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 for 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 8-2 through 8-5). These symptoms are then matched to hypothetically malfunctioning brain circuits, regulated by specific neurotransmitters, in order to rationally select and combine psychopharmacological treatments to eliminate symptoms by increasing the efficiency of information processing in the malfunctioning brain circuits, and thereby get the patient into remission. This was discussed extensively in Chapter 6 on mood disorders and illustrated in Figures 6-42 through 6-44.
Although there are different diagnostic criteria for different anxiety disorders (Figures 8-2 through 8-5), these are constantly changing and many do not even consider OCD or PTSD to be anxiety disorders any longer (OCD is discussed in Chapter 13 on impulsivity). All anxiety disorders have overlapping symptoms of anxiety/fear coupled with worry (Figure 8-6). 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 8-7 through 8-14). The links between the amygdala, fear circuits, and treatments for the symptom of anxiety/fear across the spectrum of anxiety, trauma, and stress disorders are discussed throughout the rest of this chapter.
Worry is the second core symptom shared across the spectrum of anxiety disorders (Figure 8-7). This symptom is hypothetically linked to the functioning of cortico-striato-thalamo-cortical(CSTC) loops. The links between the CSTC “worry loops” and treatments for the symptom of worry across the spectrum of anxiety disorders are discussed later in this chapter (see also Figures 8-15 through 8-20). 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 8-6 and 8-7), but the specific nature of malfunctioning within these same circuits in various anxiety disorders. That is, in generalized anxiety disorder, malfunctioning in the amygdala and CSTC worry loops may be hypothetically persistent, and unremitting, yet not severe (Figure 8-2), whereas malfunctioning may be theoretically intermittent but catastrophic in an unexpected manner for panic disorder (Figure 8-3) or in an expected manner for social anxiety (Figure 8-4). Circuit malfunctioning may be traumatic in origin and conditioned in PTSD (Figure 8-5).