Chapter 47 Anxiety and Depression
Overview
Epidemiology
Neurobiology and Genetics
The neurobiology of both depressive and anxiety disorders is complex and incompletely understood. In contrast to illnesses such as Parkinson’s or Huntington’s disease, no single area of brain pathology or anatomic lesion has been implicated in the development of anxiety or depression; rather, these illnesses appear to be mediated by dysregulation of complex interactions between neural circuits (Nestler et al., 2002). In depression, most lines of investigation have involved dysregulation of the hypothalamic-pituitary axis (HPA) and hippocampus, along with investigations of neural circuitry mediating mood, reward, sleep, appetite, motivation, and cognition. In particular, hyperactivity of the HPA axis in some depressed patients has been found to lead to hippocampal volume reduction, likely by reduction of brain-derived neurotrophic factor (BDNF) and changes in the mechanisms that mediate BDNF expression. However, whether reduced hippocampal volume is a partial cause or merely a result of depression is currently unclear, and it is not seen in all patients diagnosed with depression. Although epidemiologic studies show that depression appears highly heritable, with some studies showing that 40 to 50% of the risk may be genetic, no one gene appears implicated, and depression likely is the phenotypic expression of multiple genetic vulnerabilities, coupled with environmental stresses (physical/emotional trauma, viral illness), physical factors (e.g., preexisting or comorbid medical illnesses such as hypothyroidism or stroke), and random processes during brain development (Nestler et al., 2002).
Anxiety, Major Depression, and Medical Illnesses
Interaction of Depression, Anxiety, and Medical Illness
Management of patients with comorbid medical illness and anxiety or depression is complex. Such patients have higher rates of unexplained symptoms than patients without these disorders, even after adjusting for the severity of medical illness (Katon and Walker, 1998). An increasing body of literature suggests that patients with medical illness and comorbid depression/anxiety adapt more poorly to chronic symptoms, such as fatigue or pain, and tend to focus on both symptoms of their physical illnesses and physical symptoms associated with other organ symptoms. Not surprisingly, patients with medical illness and comorbid depression have 50% higher medical costs than patients with medical illness alone (Katon, 2003). Comorbid patients are more functionally impaired and have more lost workdays, poorer quality of life, and higher rates of medical utilization (Simon, 2003). Disease management is also complicated by higher rates of nonadherence to treatment and self-care regimens, as well as higher rates of risk behaviors (e.g., smoking, overeating, sedentary lifestyle). Response to antidepressant treatment may be less robust, as evidenced by patients with cardiovascular disease, stroke, and diabetes (Katon, 2003).
Diagnosis and Screening of Mood and Anxiety Disorders
Diagnosis of Mood Disorders
The essential feature of a major depressive episode is a period lasting at least 2 weeks during which the patient experiences depressed mood or loss of interest or pleasure in almost all activities, a distinct change in usual self, and clinically significant distress or changes in functioning. It is accompanied by a constellation of other symptoms, such as changes in sleep, eating, energy, motivation, and concentration; difficulty making decisions; and often feelings of hopelessness, worthlessness and guilt (Box 47-1). Patients may ruminate about death, feel that life is not worth living, have thoughts about suicide, may make plans to kill themselves, or make attempts. Many patients complain of memory difficulties, become easily distracted, and describe an inability to think clearly. Patients often pace, wring their hands or have an inability to sit still; conversely, they may become greatly slowed or immobilized. In some patients, irritable mood may predominate more than sadness, or they may have explosive, angry outbursts (Fava and Rosenbaum, 1999). Irritability is especially noted in depressed children and adolescents. In its most severe forms—major depression with psychotic features—patients may hear voices telling them to kill themselves or may develop delusional beliefs, such as having a serious illness despite numerous tests providing no evidence (APA, 2000).
Box 47-1 Diagnostic Criteria for Major Depressive Episode
From American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed, text revision. Washington, DC, APA, 2000.
The essential feature of dysthymia is a chronically depressed mood that occurs most days for at least 2 years. Patients may have a variety of other symptoms, such as feelings of inadequacy, generalized loss of interest or pleasure, social withdrawal, feelings of guilt or brooding about the past, and decreased activity, productivity, or effectiveness (Box 47-2). Neurovegetative symptoms such as insomnia or hypersomnia, poor appetite or overeating, low energy, and poor concentration may be present but are less common than in major depressive episodes. These patients may state that they have been depressed for as long as they can remember and cannot recall episodes of recovery or remission of symptoms. In addition, dysthymic patients may periodically have superimposed major depressive episodes, often called “double depression” (APA, 2000).
Box 47-2 Diagnostic Criteria for Dysthymic Disorder
From American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed, text revision. Washington, DC, APA, 2000.
Note: In children and adolescents, mood can be irritable and duration must be at least 1 year.
Unipolar Depression vs. Bipolar Depression
Distinguishing unipolar from bipolar depression remains a critical distinction and poses one of the greatest clinical challenges for professionals who treat mood disorders. Misdiagnosis of bipolar disorder can lead to mistreatment (typically with antidepressants alone), worsening of mood, switches into mania or mixed states (i.e., presence of both manic and depressive symptoms), rapid mood swings, worsening psychosocial impairment, greater suicide attempts, and higher mortality (Goldberg and Ernst, 2002; Goldberg and Truman, 2003; Schneck et al., 2008). Treatment of bipolar depression is rarely straightforward and often requires multiple medications and medication trials. Antidepressants do not appear to be especially helpful in the treatment of bipolar disorder, and antidepressants have not yet been shown to improve outcome compared to mood stabilizers alone (Sachs et al., 2007). Although no symptom is pathognomonic for bipolar depression, certain features of depression may suggest that a patient’s depression is a manifestation of bipolar illness. Bipolar depression can present similar to unipolar depression, but some depression features may help distinguish the two (Ghaemi et al., 2004; Perlis et al., 2006) (Table 47-1). If a primary care physician makes a diagnosis of bipolar disorder, the patient is best served by referral to a mental health provider, preferably with expertise in treating mood disorders.
Feature | Bipolar | Unipolar |
---|---|---|
Substance abuse | Very high | Moderate |
Family history | Almost uniform | Sometimes |
Seasonality | Common | Occasional |
First episode before age 25 years | Very common | Sometimes |
Postpartum illness | Very common | Sometimes |
Psychotic features before age 35 | Highly predictive | Uncommon |
Atypical features | Common | Occasional |
Rapid on/off pattern | Typical | Unusual |
Recurrent major depressive episodes (>3) | Common | Unusual |
Antidepressant-induced mania/hypomania | Predictive | Uncommon |
Brief episodes (<3 months) | Suggestive | Unusual (duration usually >3 months) |
Antidepressant tolerance | Suggestive | Uncommon |
Mixed depression (presence of hypomanic features within depressive episode) | Predictive | Rare |
Tension, edginess, fearfulness | More common | Less common |
Somatic symptoms (muscular, respiratory, genitourinary) | Less common | More common |
Modified from Kaye NS. Is your depressed patient bipolar? J Am Board Fam Pract 2005;18:271-281; and Perlis RH, Brown E, Baker RW, Nierenberg AA. Clinical features of bipolar depression versus major depressive disorder in large multicenter trials. Am J Psychiatry 2006;163:225-231.
Screening Tools for Depression
Screening for Bipolar Disorder
Although no laboratory or imaging tests currently exist to distinguish unipolar depression from bipolar depression, screening questionnaires, as well as certain features of a patient’s history and symptomatology, may prove helpful. The Mood Disorder Questionnaire (MDQ) is a tool that combines DSM-IV criteria and clinical experience to screen for bipolar disorder in primary care settings (Hirschfeld et al., 2000). It is a brief, 1-page self-report questionnaire with 13 yes/no items and two additional questions regarding functioning and timing of mood symptoms, and typically can be completed in 5 minutes or less. Seven or more positive responses to questions about manic symptoms, plus positive responses to the severity of impairment (moderate or severe) and coincident timing of symptoms yields a positive screen. Specificity and sensitivity of the MDQ vary widely by clinical setting, having the best combination of the two when given to patients with suspected mood symptoms (93% specificity; 58% sensitivity) but performs more poorly in general community samples (97% specificity; 28% sensitivity) (Hirschfeld et al., 2003; Hirschfeld et al., 2005). Other screening tools for bipolar disorder do not offer the ease of use and higher reliability and validity of the MDQ.
Diagnosis of Anxiety Disorders
The essential feature of generalized anxiety disorder is excessive anxiety and worry about a number of events or activities, occurring most days over 6 months. Patients have difficulty controlling the worry, report subjective distress, and may experience difficulties in social or occupational functioning. The intensity, duration, or frequency of the worry is out of proportion to the actual likelihood or impact of the feared event. Patients must have at least three associated physical symptoms, including restlessness, irritability, muscle tension, disturbed sleep, fatigability, and difficulty concentrating. The list of associated symptoms can be thought of as symptoms of inner tension (restlessness or edginess, irritability, muscle tension) and symptoms associated with the fatiguing effects of chronic anxiety (fatigue, concentration difficulties, sleep disturbance) (Box 47-3).
Box 47-3 Diagnostic Criteria for Generalized Anxiety Disorder
From American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed, text revision. Washington, DC, APA, 2000.
Panic attacks, a collection of distressing physical, cognitive, and emotional symptoms, may occur in a variety of anxiety disorders, such as specific phobias, social phobias, PTSD, and acute stress disorder. Panic attacks are discrete periods of intense fear in the absence of real danger, accompanied by at least 4 of 13 cognitive and physical symptoms (Box 47-4). The attacks have a sudden onset, build to a peak quickly, and are often accompanied by feelings of doom, imminent danger, and a need to escape. Symptoms of panic attacks can include somatic complaints (e.g., sweating, chills), cardiovascular symptoms (pounding heart, accelerated heart rate, chest pain), neurologic symptoms (trembling, unsteadiness, lightheadedness, paresthesias), GI symptoms (choking sensations, nausea), and pulmonary symptoms (shortness of breath). In addition, patients with panic attacks may worry they are dying, “going crazy,” or have the sensation of being detached from reality.
Box 47-4 Diagnostic Criteria for Panic Attack
From the American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed, text revision. Washington, DC, APA, 2000.
Patients with panic disorder experience recurrent, unexpected panic attacks, followed by at least 1 month of persistent worry that they will suffer another panic attack. Panic disorder patients may begin to avoid places where a prior attack occurred or where help may not be available; such avoidance can lead to the development of agoraphobia and typically worsens their psychosocial functioning (Box 47-5).