Anxious Patients

Overview

Clinical challenges in the diagnosis and treatment of anxiety are abundant in the general hospital setting: discerning normal from pathologic anxiety, differentiating medical from psychiatric causes, and choosing effective therapeutic approaches. In addition to a knowledge of medical and psychiatric differential diagnoses, the clinician may rely on a variety of strategies and interventions that involve pharmacologic, cognitive-behavioral, interpersonal, and psychodynamic skills. The ubiquity of anxiety and the non-specific nature of anxiety symptoms can confound the care of the patient. Pathologic anxiety symptoms and behavior may be attributed to other physical causes or, when viewed as “only anxiety,” may be prematurely dismissed as insignificant.

Anxiety refers to a state of anticipation of alarming future events, whereas fear is a result of perceived imminent threat. The former is the same distressing experience of dread and foreboding as the latter, except that it derives from an unknown internal stimulus or is inappropriate to the reality of the current situation. Anxiety is manifested in the physical, affective, cognitive, and behavioral domains. The possible physical symptoms of anxiety reflect autonomic arousal and include an array of bodily perturbations ( Table 13-1 ). The anxious state ranges from edginess and unease to terror and panic. Cognitively, the experience is one of worry, apprehension, and thoughts concerned with emotional or bodily danger. Behaviorally, anxiety triggers a multitude of responses concerned with diminishing or avoiding the distress.

The importance of recognizing and attending to the suffering of the anxious patient is not always readily apparent, given the universality of the experience of anxiety. Anxiety is expected and normal as a transient response to stress and may be a necessary cue for adaptation and coping. Excessive or pathologic anxiety, however, is no more a normal state than is the production of excess thyroid hormone.

Pathologic anxiety is distinguished from a normal emotional response by four criteria: autonomy, intensity, duration, and behavior. Autonomy refers to suffering that, to some extent, has a life of its own, with a minimal basis in recognizable environmental stimuli. Intensity refers to the level of distress; the severity of symptoms is such that the patient's level of anguish moves the physician to offer relief. The duration of suffering also can define anxiety as pathologic. Symptoms that are persistent rather than transient, possibly adaptive, indicate a disorder and they are a call to evaluation and treatment. Finally, behavior is a critical criterion; if anxiety impairs coping, if normal function is disrupted, or if behavior such as avoidance or withdrawal results, the anxiety is of a pathologic nature.

Stereotyped syndromes of pathologic anxiety are described in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM). Changes in the DSM-5 diagnostic criteria for anxiety disorders include the re-categorization of obsessive–compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and acute stress disorder. These syndromes will all be included in this chapter given the pervasiveness of anxiety and fear that is common to all of these disorders. In epidemiologic studies, anxiety disorders have been found to be among the most common psychiatric disorders in the general population. This observation predicts that a significant percentage of the general hospital population would also suffer from anxiety symptoms. Some patients suffer from an anxiety disorder before admission to the hospital for medical care, but medical and surgical settings are also associated with the onset of anxiety symptoms as a consequence of hospitalization, medical illness, or treatment (e.g., adjustment disorder with anxious mood and organic anxiety disorder).

The Nature and Origin of Anxiety

Despite the protean physiologic manifestations of anxiety, the experience of anxiety can be divided into two broad categories: (1) an acute, severe, and brief wave of intense anxiety with impressive cognitive, physiologic, and behavioral components, and (2) a lower-grade persistent distress, quantitatively distinct and also with some qualitative differences. Pharmacologic and epidemiologic observations suggest a clinically relevant distinction between these two states.

In light of phenomenologic similarities, fear and anxiety most likely reflect a common underlying neurophysiology. The first category of anxiety resembles acute fear or alarm in response to life-threatening danger: a cognitive state of terror, helplessness, or sense of impending disaster or doom, with autonomic but primarily sympathetic activation, and an urgency to flee or seek safety. The second type of anxiety corresponds to a state of alertness with a heightened sense of vigilance to possible threats and with less intense levels of inhibition, physical distress, and behavioral impairment.

The two fear states resemble the clinical syndromes of panic attacks and generalized or anticipatory anxiety. As innate responses for protecting the organism and enhancing survival, panic and vigilance are normal when faced with threatening stimuli. As anxiety or psychopathologic symptoms, other factors besides actual physical threat must be implicated as triggers or causes. Of several explanatory models proposed, the biological model places emphasis on the nervous system, the psychodynamic on meanings and memories, and the behavioral on learning.

Animal and neuronal receptor studies suggest that a number of central systems are involved in fear and pathologic anxiety. The alarm or panic mechanism is likely to have a critical component involving central noradrenergic mechanisms, with particular importance placed on a small retropontine nucleus, the primary source of the brain's norepinephrine, the locus ceruleus (LC). When this key to sympathetic activation is stimulated in monkeys, for example, an acute fear response can be elicited with distress vocalizations, fear behaviors, and flight. Furthermore, destruction of the LC leads to abnormal complacency in the face of threat. Biochemical perturbations that increase LC firing similarly elicit anxious responses in animals and humans that are blocked by agents that decrease LC firing, some of which are in clinical practice as anti-panic agents (e.g., antidepressants, alprazolam).

Another critical system involves limbic system structures, including the amygdala and septohippocampal areas. An important role of the limbic system is to scan the environment for life-supporting and life-threatening cues, as well as to monitor internal or bodily sensations, and to integrate these with memory and cognitive inputs in assessing the degree of threat and need for action to maintain safety.

Vigilance, or its psychopathologic equivalent, generalized anxiety, most probably involves limbic system activity: limbic alert. Benzodiazepine receptors in high concentrations in relevant limbic system structures may play a role in modulating limbic alert, arousal, and behavioral inhibition by increased binding of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). As one might expect, there are neuronal connections between the LC and the limbic system. An increased firing rate of LC neurons may serve as a rheostat to generate levels of arousal from vigilance to alarm.

A number of neurotransmitters are implicated as modulators of both the limbic alert and the central alarm systems. For example, LC firing is regulated by the α ₂ -noradrenergic autoreceptors as well as by 5-hydroxytryptamine (5-HT), serotonin receptors, GABA-benzodiazepine receptors, and opioid and other receptors. The limbic system also has important GABA-benzodiazepine receptor and serotonergic modulations. Peptides, such as cholecystokinin, have also been implicated as potential activators of the alarm system, and an accruing body of work points to abnormalities in corticotropin-releasing factor and hypothalamic–pituitary axis function as critical in the genesis and maintenance of pathologic affective states. As a critical function, the central security system is endowed with redundancy of regulation.

When inappropriately activated, vigilance and alarm (the stereotyped functions of the security system) are manifested as psychopathology: anxiety states. The more sustained, variably intense, but distressing arousal state of vigilance (i.e., preparation for threat) becomes generalized anxiety. The sudden, stereotyped, and intense (but false) alarm response is a panic attack.

Cognitive-behavioral formulations of anxiety disorders, although attending to possible differences in biological reactivity, focus primary attention on the information processing and behavioral reactions that characterize an individual's anxiety experience. Although anxiety patterns may stem from a variety of experiences, including (mis)information, observational learning, and direct conditioning events with real or perceived trauma, the enduring consequences of such learning can be found in current patterns of behavior. In cognitive-behavioral formulations, emphasis is placed on the role of thoughts and beliefs (cognitions) in activating anxiety, as well as on the role of avoidance or other escape responses in maintaining both fear and faulty thinking patterns. Faulty cognitions are frequently marked by the over-prediction of the likelihood or degree of catastrophe of negative events and may focus on external experiences (e.g., “my colleagues will laugh at me if I ask this question”) or internal experiences (e.g., “I am going to lose control if this anxiety gets worse”). Intolerance and catastrophic misinterpretations of the anxiety experience itself play a role in a variety of anxiety conditions and can help propel mild anxiety into a full, intense panic attack. Attempts to neutralize anxious feelings, with avoidance or compulsive behavior, can serve to lock in anxiety reactions and help to develop the chronic arousal and anticipatory anxiety that marks many anxiety disorders.

Recent evidence has offered a bridge between neurobiological and cognitive-behavioral understandings of anxiety. Increased attention has been paid to the consolidation of memories after traumatic experiences and potential therapeutic interventions (e.g., blocking of the noradrenergic or glucocorticoid systems to decrease the potential for developing PTSD after trauma). Knowledge of the N -methyl-D-aspartate (NMDA) system's involvement in the extinction of learned behaviors has offered the possibility of pharmacologic enhancement of cognitive-behavioral therapy (CBT) techniques. D-cycloserine, a partial NMDA agonist, has facilitated treatment of specific phobias, obsessive–compulsive disorder (OCD), panic disorder, and social anxiety disorders when combined with CBT.

Developmental experiences receive particular emphasis in psychodynamic approaches to anxiety. Although Freud's early writing implied a more physiologic basis for anxiety attacks in terms of undischarged libido, later emphasis was on anxiety as a signal of threat to the ego, signals elicited because of events and situations with similarities (symbolic or actual) to early developmental experiences that were threatening to the vulnerable child (traumatic anxiety), such as separations, losses, certain constellations of relationships, and symbolic objects or events (e.g., snakes, successes). More recently, psychodynamic thinking has emphasized object relations and the use of internalized objects to maintain affective stability under stress.

Phobic disorders, associated with the experience of panic, anticipatory anxiety, or no anxiety symptoms at all (depending on the success of avoidance behavior), serve to illustrate the different models of understanding anxiety. The biological view recognizes the stereotyped nature of phobias. Most of the objects and situations in everyday life that truly threaten us are rarely selected as phobic stimuli; children, who proceed normally through a variety of developmental phobias (e.g., strangers, separation, darkness), rarely become phobic of objects and situations that parents attempt to associate with danger (e.g., electric outlets and roads), and most phobic stimuli have meaning in the context of biological preparedness and were presumably selected through evolution. Most human phobias are of objects and situations that make sense in the context of enhancing survival before the dawn of civilization: places of restricted escape, groups of strangers, heights, and snakes, for example. Social phobias—for example, fear of scrutiny by others—resemble the intense discomfort elicited in primates introduced into a new colony or in any animal simply being stared at. A glare is a threat. When panic attacks and anticipatory anxiety heighten the general sense of danger and insecurity, a variety of phobias may be manifested as part of the patient's increased concern with security and safety.

The principal explanatory models in psychiatry of how a normal protective system might become the source of distress and dysfunction include the biological (with its emphasis on constitutional vulnerability), the cognitive-behavioral (with its emphasis on self-perpetuating patterns of cognitions and behaviors), and the psychodynamic (with its emphasis on meanings, memories, and internal representations derived from developmental experience). The pragmatic and pluralistic modern clinician should not regard these models as mutually exclusive. Potential biological vulnerabilities, for example, may never become manifest without specific developmental experiences, sustained adversity, or trauma. Accumulating evidence indicates that for anxiety disorders, as with affective and psychotic disorders, biological systems are responsive to, and perturbable by, environmental influences. Potentially dysregulated (i.e., anxiety-prone) neurobiological systems may remain homeostatic until developmental experience, life events, or other stressors disturb them. An integrated model predicts risk for manifested anxiety disorders as a consequence of constitutional vulnerability shaped by developmental experience (whether harmful or protective) and, in later (adult) life, either activated or influenced by environmental factors and maintained by ongoing chains of maladaptive cognitions and avoidance responses.

Anxiety in the Medical Setting

Although some distress from anxiety is expected as a routine consequence of hospitalization, anxiety may also be a significant clinical issue in the treatment of patients in a medical setting. The hospitalized patient encounters a world of both internal and external dangers: assaults on bodily integrity in the form of uncomfortable procedures and forced intimacy with strangers; the atmosphere of illness, pain, and death; and separation from loved ones and familiar surroundings. The patient typically experiences uncertainty about his or her illness and its implications for the patient's capacity to work and maintain social and family relationships. Just as depression has been described as a “psychobiological final common pathway” of a number of interacting determinants, it is likely that anxiety too represents a multiple-determined expression of the variety of psychological, biological, and social factors having impact on the patient.

The anxious patient can be a diagnostic challenge. The presence of anxiety may represent the patient's reaction to the meaning and implications of medical illness or to the medical setting, a manifestation of the physical disorder itself, or the expression of an underlying psychiatric disorder. The distinction between anxiety as a symptom and anxiety as a syndrome, may be difficult to make in the medical setting, where there may be an overlap between normal situational anxiety or fear, anxiety-like symptoms resulting from a variety of organic disease states and their treatments, and the characteristic presentation of anxiety disorders.

Methodological obstacles surface in attempts to identify the nature and prevalence of anxiety in medical patients. Studies of anxiety in the medical setting are often difficult to interpret because of a lack of clarity of case definition and assessment measures, heterogeneity of the study populations, absence of appropriate control groups, and the non-specific and often transitory nature of the anxiety symptoms themselves.

Approximately 60% of patients with psychiatric conditions are treated by primary care practitioners; the most common disorders are depression and anxiety. In a study of patients who presented to a group of primary care physicians, anxiety was the fifth most common diagnosis overall; others suggest this may be an underestimate. Anxiety is the chief complaint of 11% of patients presenting in primary care settings. This prevalence is mirrored by the high rate of prescribing benzodiazepines by primary care physicians. Panic disorder has a reported prevalence of 1% to 2% in the general population, as compared with 6% to 10% of patients in a primary care setting and 10% to 14% of patients in a cardiology practice. Patients with anxiety disorders, furthermore, are but a subgroup of those for whom anxiety is a complicating factor in their diagnosis and treatment in the hospital.

In view of the likely frequency of normal anxiety in this setting, there must be special circumstances surrounding those patients identified by primary caregivers as deserving psychiatric attention. Although some overly anxious patients go unrecognized, those who generate concern have impressed their caregivers in some way by the autonomy, intensity, duration, or behavior associated with their distress. Several typical scenarios of anxiety in the general hospital can be recognized.