Chapter 26: Depression PDF - Behavioral Medicine

Barry University Library Access Provided by: Behavioral Medicine: A Guide for Clinical Practice, 5e Chapter 26: Depression Y. Pritham Raj; John F. Christensen; & Mit...

Barry University Library Access Provided by: Behavioral Medicine: A Guide for Clinical Practice, 5e Chapter 26: Depression Y. Pritham Raj; John F. Christensen; & Mitchell D. Feldman INTRODUCTION Depression is common, disabling, and often underrecognized in general medical practice. More than 300 million people are affected by depression worldwide. Stigma of mental illness and other psychosocial barriers such as negative expectations often diminish the motivation of individuals with depression to seek care. Even when recognized, depression is often inadequately addressed by practitioners who lack either the time or training to provide timely, effective, evidence­based treatment. Despite evidence that depression is quite treatable, and the widespread availability of evidence­ based assessment and treatment guidelines, overall outcomes remain poor. About 3/4 of patients seeking care for depression are treated in primary care rather than by mental health professionals. This chapter focuses on the core knowledge and skills needed by general medical practitioners to effectively assess and manage major depressive disorder (MDD). We also review other related depressive disorders as updated in the DSM­5 including: disruptive mood dysregulation disorder, persistent depressive disorder (dysthymia), premenstrual dysphoric disorder (PMDD), adjustment disorder with depressed mood, substance/medication­induced depressive disorder, depressive disorder due to another medical condition, bipolar disorder/bipolar depression, and other specified and unspecified depressive disorders. In diagnosing depression, we emphasize the routine use of brief patient self­assessment tools such as the nine­item Patient Health Questionnaire (PHQ­9). The U.S. Preventive Services Task Force (USPSTF) guidelines recommend screening the general adult population “when adequate systems are in place to ensure accurate diagnosis, effective treatment, and appropriate follow­up.” Unfortunately, despite the publication of such screening recommendations, adoption of the use of rating scales by providers has been poor. The national depression screening rate was less than 5% of all adult ambulatory care visits according to the National Ambulatory Medical Care Survey (2005–2015). Increased use of screening and rating instruments in depression should provide pivotal leverage needed to improve outcomes for depression, especially since measurement­based care (MBC) is the new standard in the management of MDD and has been shown to improve clinical outcomes. DEPRESSIVE DISORDERS: MAJOR DEPRESSION & RELATED CONDITIONS Major depressive disorder (MDD) is associated with considerable disability, morbidity, and mortality. Epidemiologic studies demonstrate that MDD causes as much or more disability and social and role impairment than other chronic illnesses such as diabetes, arthritis, hypertension, and coronary artery disease. The hallmark of MDD is when five or more of nine cardinal symptoms of depression are present during the same 2­week period with at least one of the symptoms being either depressed mood or loss of interest or pleasure (anhedonia). The symptoms must cause clinically significant distress and not be attributable to the effects of a substance or another medical condition (see Table 26­1). Table 26­1. Diagnosis of major depression. 1. Depressed mood 2. Anhedonia (lack of interest or pleasure in almost all activities) 3. Sleep disorder (insomnia or hypersomnia) 4. Appetite loss, weight loss; appetite gain, weight gain 5. Fatigue or loss of energy 6. Psychomotor retardation or agitation 7. Trouble concentrating or trouble making decisions 8. Low2025­2­16 Downloaded self­esteem 5:19 or guilt P Your IP is Chapter9.26: Depression, Recurrent Y.of thoughts Pritham death orRaj; John suicidal F. Christensen; & Mitchell D. Feldman ideation Page 1 / 39 ©2025 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility Five symptoms from the above are required to make the diagnosis of depression and must include depressed mood and/or anhedonia. The symptoms must have been present most of the day, nearly every day, for 2 weeks. causes as much or more disability and social and role impairment than other chronic illnesses such as diabetes, arthritis, hypertension, and coronary Barry University Library artery disease. The hallmark of MDD is when five or more of nine cardinal symptoms of depression are present during the same 2­week period with at Access Provided by: least one of the symptoms being either depressed mood or loss of interest or pleasure (anhedonia). The symptoms must cause clinically significant distress and not be attributable to the effects of a substance or another medical condition (see Table 26­1). Table 26­1. Diagnosis of major depression. 1. Depressed mood 2. Anhedonia (lack of interest or pleasure in almost all activities) 3. Sleep disorder (insomnia or hypersomnia) 4. Appetite loss, weight loss; appetite gain, weight gain 5. Fatigue or loss of energy 6. Psychomotor retardation or agitation 7. Trouble concentrating or trouble making decisions 8. Low self­esteem or guilt 9. Recurrent thoughts of death or suicidal ideation Five symptoms from the above are required to make the diagnosis of depression and must include depressed mood and/or anhedonia. The symptoms must have been present most of the day, nearly every day, for 2 weeks. MDD is a well­documented and common comorbidity in many medical conditions, especially severe physical disorders such as cancer, stroke, and acute coronary syndrome. A large 1­year U.S. prevalence study found that patients with chronic medical diseases were nearly three times as likely to get depressed compared to healthy controls. When present as a comorbidity, depression accounts for significant increases in disability, morbidity, and mortality. The etiologic and sustaining relationships between depression and many other medical conditions appear to be bidirectional. For example, preexisting depression is a predictor of future atherosclerotic coronary artery disease (CAD), and CAD is associated with MDD. In several studies, 17– 44% of patients with CAD have a comorbid diagnosis of major depression which in turn puts them at greater risk for sudden cardiac death. Depressed patients with heart disease (coronary artery disease and congestive heart failure) have increased risk of reinfarction after myocardial infarction (MI) and up to a threefold increase in all­cause mortality, even after controlling for all other identifiable and measurable cardiac risk factors. Diabetes mellitus (DM) and depression also have a bidirectional relationship. The relative risk for developing type 2 diabetes mellitus in depressed patients is reported as high as 1.6, while the relative risk for developing depression in a patient with DM is around 1.2. Patients with comorbid diabetes and depression have worse glycemic control, more microvascular and macrovascular complications and greater all­cause mortality. High inflammatory states (e.g., high plasma c­reactive protein levels) in patients with depression are associated with metabolic alterations that predict responses to both traditional antidepressants as well as some experimental anti­inflammatory therapies such as infliximab that will be briefly discussed later in this chapter. Major depression is associated with adverse health habits, such as addictions (tobacco and alcohol use disorders in particular), poor diet, overeating, and sedentary lifestyle, which in turn can contribute to the development of metabolic syndrome and other general medical illnesses. Conversely, functional impairment stemming from these chronic illnesses predispose to development of new depression. From an etiologic perspective, variables such as genetic vulnerability, childhood adversity (neglect and abuse), and stressful life events all contribute to the development of depression itself as well as to lifestyle risks such as obesity, sedentary behavior, and smoking that themselves predispose to chronic general medical illnesses. Chronic care of general medical illness requires self­management behaviors to optimize treatment. In fact, much of primary care medicine involves lifestyle modification counseling, including diet modification, promotion of physical activity, regulation of substances (especially alcohol and caffeine), tobacco cessation, and medication adherence for maintenance of health. Studies show that depression adversely impacts self­management, at least partly due to the fact that depressed patients are less likely to be adherent with lifestyle modification plans than nondepressed patients. Depressed diabetic patients have decreased adherence to diet and suffer more lapses in refills of oral hypoglycemic medications. Depressed patients with heart disease or stroke show decreased adherence to treatment recommendations such as taking daily aspirin and participating in exercise rehabilitation programs. This nonadherence in post­MI patients predicts increased rehospitalization rates and overall mortality. Major depressive disorder, with or without general medical comorbidity generally is a chronic, recurring illness, with varying cycles of exacerbation and remission. Furthermore, these exacerbations or new episodes of depression tend to occur more frequently and with greater severity as the patient ages. Disruptive mood dysregulation disorder is a depressive disorder highlighted by severe recurrent temper outbursts manifested verbally and/or Downloaded 2025­2­16 behaviorally that are out 5:19 P Your IP of proportion toisa situation or provocation. The outbursts, such as verbal rages or physical aggression, occur on average, Chapter 26: Depression, Y. Pritham Raj; three or more times per week and are often John F. Christensen; accompanied & Mitchellirritable by persistently D. Feldman Page 2 / 39 mood most of the day, nearly every day—a feature that makes it ©2025 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility challenging to differentiate from the episodic irritability often seen in bipolar disorder as a manic­equivalent feature. The diagnosis should not be made for the first time before age 6 years or after age 18, which also presents a challenge when teasing out this disorder from bipolar disorder, where disease or stroke show decreased adherence to treatment recommendations such as taking daily aspirin and participating in exercise rehabilitation Barry University Library programs. This nonadherence in post­MI patients predicts increased rehospitalization rates and overall mortality. Major depressive disorder, with or Access Provided by: without general medical comorbidity generally is a chronic, recurring illness, with varying cycles of exacerbation and remission. Furthermore, these exacerbations or new episodes of depression tend to occur more frequently and with greater severity as the patient ages. Disruptive mood dysregulation disorder is a depressive disorder highlighted by severe recurrent temper outbursts manifested verbally and/or behaviorally that are out of proportion to a situation or provocation. The outbursts, such as verbal rages or physical aggression, occur on average, three or more times per week and are often accompanied by persistently irritable mood most of the day, nearly every day—a feature that makes it challenging to differentiate from the episodic irritability often seen in bipolar disorder as a manic­equivalent feature. The diagnosis should not be made for the first time before age 6 years or after age 18, which also presents a challenge when teasing out this disorder from bipolar disorder, where symptoms typically emerge earlier than age 25. Persistent depressive disorder (dysthymia) represents a consolidation of DSM­IV defined chronic MDD and dysthymic disorder—a less severe but more chronic form of depressive illness that is also associated with significant disability. This disorder is diagnosed when depressed mood and at least two other symptoms of depression have been present “more than half the days” during the previous 2 years (or 1 year for children or adolescents). Persistent depressive disorder has been shown to respond to treatment with antidepressant medication. If full criteria for a major depressive episode are ever met (five of nine criteria) during the course of illness, the patient should be given a diagnosis of major depressive disorder. Premenstrual dysphoric disorder (PMDD) is a condition affecting 3–8% of menstruating women. It is diagnosed when in the majority of menstrual cycles at least five symptoms of affective, behavioral and/or somatic dysregulation are present in the week antecedent to the onset of menses (luteal phase), start to improve within a few days after the onset of menses, and attenuate or resolve in the week post­menses. One or more of the following symptoms must be present: mood swings (affective lability), irritability/anger, depressed mood, or marked anxiety. As with other mood disorders, the symptoms must cause significant distress or interference with usual activities. It may be considered a severe form of premenstrual syndrome (PMS) and is treated best by serotonin reuptake inhibitors or ovulation suppression via contraception. Substance/medication­induced depressive disorder is a disturbance in mood characterized by depression (not delirium) that develops during or soon after substance intoxication or withdrawal (e.g., amphetamine) or after exposure to a medication (e.g., interferon). It is well known that illicit substances can lead to depression. Alcohol is a prototypical substance that acts as a depressant. In fact, nearly one­third of people with major depression also have a pattern of problem drinking, making substance­induced depressive disorder difficult to separate from MDD. Many providers overlook substances as an etiology of depression either because of lack of screening or underreporting of use by the patient. We recommend evidence­based screening programs such as the Screening, Brief Intervention, and Referral to Treatment (SBIRT) practice to aid in the assessment of the severity of substance use (screening forms available at: http://www.sbirtoregon.org/screening­forms/). Specifically, the Alcohol Use Disorders Identification Test (AUDIT) and the Drug Abuse Screening Test (DAST­10) should be administered to adult patients who screen positive for substance abuse to identify, reduce, and prevent problematic use of substances that contribute to myriad disorders including depression. Several medications have been implicated in the development of depression or suicidal ideation. According to one study, more than a third of all Americans were prescribed one or more drugs that have been tied to depression or suicidal ideation. In general, high­quality studies in this area are lacking, often making it difficult to ascertain causal relationships between medications and medication­induced depression. Some experts suggest that isotretinoin and alpha­interferons pose the highest risk of medication­induced depressive disorder, while corticosteroids, varenicline, progesterone inserts, and finasteride pose a moderately high risk. Depressive disorders due to another medical condition refers to psychiatric syndromes thought to result from the direct physiological consequence of a general medical condition (e.g., hypothyroidism). Treatment focuses on resolution of the underlying general medical problem or withdrawal of the offending medication, although specific psychiatric treatment may also be useful. For example, in the case of hypothyroidism, it is paramount to treat with levothyroxine to a TSH around 1.5 mU/L (perhaps slightly higher in elderly adults) to target both the medical and depressive symptoms. The use of antidepressants alone would be inappropriate. Other specified and unspecified depressive disorders are categories for presentations in which symptoms of depression are either not of adequate duration or symptom severity to meet diagnostic criteria of other depressive disorders but yet cause clinically significant distress. Adjustment disorder with depressed mood is now listed under the trauma­ and stressor­related disorders such as posttraumatic stress disorder (PTSD). It is a commonly occurring disorder following an identifiable stressor, such as divorce or job loss, when marked distress and emotional or behavioral symptoms occur within 3 months of the onset of the stressor. It may occur with mixed anxiety symptoms. The symptoms must not represent normal bereavement, and thus a “normal” reaction to a distressing life event should not be diagnosed as an adjustment disorder. Once the stressor or its consequences have terminated, the symptoms do not persist for more than an additional 6 months. When a stressor precipitates a depressive condition that meets the severity and symptom criteria for major depression, the diagnosis of major depression is made, regardless of the condition’s etiologic relationship to an identifiable stressor. Downloaded 2025­2­16 5:19 P Your IP is One of the Chapter 26:controversies Depression,with the DSM­5 Y. Pritham Raj;definition of MDD surrounded John F. Christensen; theD. & Mitchell elimination Feldman of the bereavement exclusion criterion, suggesting that Pagegrief 3 / 39 ©2025 McGraw might not Hill. All Rights be considered a normalReserved. Terms process. The of Use revision Privacy makes Policy it easier Notice MDD to diagnose Accessibility in patients who would have previously been considered to be grieving a loss. Ultimately, careful clinical judgment is required to separate MDD from bereavement based on the patient’s history and cultural norms of expressing grief, much of which may still fall well within the normal range for the grieving patient. (PTSD). It is a commonly occurring disorder following an identifiable stressor, such as divorce or job loss, when marked distress and emotional or behavioral symptoms occur within 3 months of the onset of the stressor. It may occur with mixed anxiety symptoms. The symptoms Barrymust University Library not represent normal bereavement, and thus a “normal” reaction to a distressing life event should not be diagnosed as an adjustment disorder. Once Access theby: Provided stressor or its consequences have terminated, the symptoms do not persist for more than an additional 6 months. When a stressor precipitates a depressive condition that meets the severity and symptom criteria for major depression, the diagnosis of major depression is made, regardless of the condition’s etiologic relationship to an identifiable stressor. One of the controversies with the DSM­5 definition of MDD surrounded the elimination of the bereavement exclusion criterion, suggesting that grief might not be considered a normal process. The revision makes it easier to diagnose MDD in patients who would have previously been considered to be grieving a loss. Ultimately, careful clinical judgment is required to separate MDD from bereavement based on the patient’s history and cultural norms of expressing grief, much of which may still fall well within the normal range for the grieving patient. Bipolar disorder is a common and severe mental illness, occurring in about 3–4% of the general population, causing significant disability, and carrying 80–85% genetic heritability. Up to 30% of primary care patients treated for depression actually have bipolar disorder. Bipolar I disorder refers to patients with a history of at least one episode meeting full criteria for major depression and at least one other distinct episode meeting criteria for mania. Other bipolar spectrum disorders such as bipolar II disorder (a condition marked by episodes of major depression and at least one documented episode of hypomania, not mania) and cyclothymic disorder (no episodes meeting full criteria for either major depression or mania/hypomania) are probably much more common, thought to occur in approximately 4–6% of the population. Bipolar depression refers to an episode of illness meeting criteria for major depression/major depressive episode (MDE) in a patient with a history of either mania or hypomania. Studies in general medicine indicate that 60% of people with bipolar disorder are in the depressed phase when they go to their primary care provider for help. In bipolar II disorder, symptomatic patients are almost always in the depressed phase rather than the hypomanic phase. Few patients actually seek care during periods of hypomania since these are often pleasant periods of respite from the more prominent, frequent depressive episodes. It can be very difficult for providers to differentiate an episode of major depression from an episode of bipolar depression because the two conditions are phenotypically identical. Thus, bipolar II disorder is arguably one of the most challenging disorders to diagnose in all of psychiatry. It is extremely important, however, to distinguish between major depression and bipolar depression, because although the two conditions present with similar, mostly overlapping symptoms, they are treated very differently. Evidence for the best treatment of bipolar depression, however, is still somewhat limited and controversial. Only three medications, quetiapine, lurasidone, and a combination product (olanzapine and fluoxetine) have received Food and Drug Administration (FDA) approval for the treatment of acute bipolar depression. Lamotrigine has FDA approval for maintenance treatment of bipolar depression, but it is not yet approved for acute bipolar depression. Many experts recommend adding an antidepressant for bipolar depression only when combined with two mood stabilizers (e.g., lithium, valproate, carbamazepine, or atypical antipsychotic) at maximum dose as augmentation for residual symptoms of depression. Bipolar depression should not be treated with an antidepressant alone. Such “unopposed” treatment (i.e., antidepressant without mood stabilizer) increases the likelihood of precipitating an affective “switch” from depression to mania. Failure to elicit a history of mania or hypomania by the medical practitioner can lead, therefore, to such a switch occurring after treatment with an antidepressant, with attendant risks of erratic or irrational behavior; poor judgment in social, occupational, economic, or interpersonal situations; psychosis; and even suicide. The section on differential diagnosis offers guidelines to help providers make the diagnosis of bipolar depression in patients presenting with the symptom profile of major depression. Peripartum depression encompasses the period during pregnancy or in the 4 weeks following delivery, a period fraught with hormonal and psychological variability. The USPSTF recommends screening all pregnant and postpartum women for perinatal depression, but still it is frequently overlooked in the postpartum period as “baby blues” can also be seen during the adjustment period. Between 3% and 6% of women will experience the onset of a major depressive episode in the peripartum period with 50% of “postpartum” major depressive episodes beginning prior to delivery. Postpartum depression occurs in about 10–20% of childbearing women. A major debate in psychiatry involves whether antidepressants should be used in pregnant or postpartum women who may be breastfeeding. Most experts suggest that SSRI and SNRI antidepressants (other than paroxetine in the first trimester due to congenital heart defect risk), if used during pregnancy, should be continued if the benefits outweigh the risks, since birth defects and other risks such as persistent pulmonary hypertension of the newborn (PPHN) or discontinuation syndrome are thought to be small. Thus far there are no FDA­approved medications for peripartum depression, although the new intravenous medication option, brexanolone (a neuroactive steroid and positive allosteric modulator of GABA­A receptors), has pending approval for moderate­to­severe postpartum depression after successful phase 3 trials. Sertraline and paroxetine have the lowest expression in breast milk among the SSRI medications. In addition to the premenstrual and peripartum stages previously mentioned, the perimenopausal (menopause transition and early postmenopausal) reproductive stage is also associated with increased risk for MDE and subthreshold depressive symptoms. Evidence generally suggests that most midlife women who experience a major depressive episode during perimenopause have experienced a prior episode of depression. Midlife depression presents with classic depressive symptoms commonly in combination with menopause symptoms (i.e., vasomotor symptoms and sleep disturbance), and psychosocial Downloaded challenges. 2025­2­16 5:19 Diagnosis P Your IPinvolves is identification of menopausal stage, assessment of co­occurring psychiatric and menopause Chapter 26: Depression, Y. Pritham Raj; John F. symptoms, appreciation of the psychosocial factors Christensen; common in&midlife, Mitchell D. Feldman differential PageProven diagnoses, and the use of validated screening instruments. 4 / 39 ©2025 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility therapeutic options for depression (i.e., antidepressants and psychotherapy) are the frontline treatments for perimenopausal depression. Although estrogen therapy is not approved to treat perimenopausal depression, there is evidence that it has antidepressant effects in perimenopausal women, phase 3 trials. Sertraline and paroxetine have the lowest expression in breast milk among the SSRI medications. Barry University Library In addition to the premenstrual and peripartum stages previously mentioned, the perimenopausal (menopause transition and early Access postmenopausal) Provided by: reproductive stage is also associated with increased risk for MDE and subthreshold depressive symptoms. Evidence generally suggests that most midlife women who experience a major depressive episode during perimenopause have experienced a prior episode of depression. Midlife depression presents with classic depressive symptoms commonly in combination with menopause symptoms (i.e., vasomotor symptoms and sleep disturbance), and psychosocial challenges. Diagnosis involves identification of menopausal stage, assessment of co­occurring psychiatric and menopause symptoms, appreciation of the psychosocial factors common in midlife, differential diagnoses, and the use of validated screening instruments. Proven therapeutic options for depression (i.e., antidepressants and psychotherapy) are the frontline treatments for perimenopausal depression. Although estrogen therapy is not approved to treat perimenopausal depression, there is evidence that it has antidepressant effects in perimenopausal women, particularly those with concomitant vasomotor symptoms. Seasonal pattern depression occurs when onset and remission of episodes of depression are temporally related to a particular time of the year, occurring at least over a 2­year cycle without any nonseasonal depressive episodes during that time. One of the main reasons for the change in nomenclature from seasonal affective disorder (SAD) to depression with seasonal pattern is the misconception that SAD was a disorder unto itself. It is simply a specifier for the underlying mood disorder (depression or bipolar disorder) as one cannot have SAD in isolation. The prevalence of depression with seasonal pattern is 4–6% in the United States with most experiencing their symptoms in the fall­winter months, although this can vary with latitude, age, and sex. Latitudes far north or south of the equator are more at risk. For example, 1% of Florida residents and 9% of those who live in New England or Alaska suffer from seasonal depression. About 10% of patients with seasonal pattern depression experience symptoms during spring–summer months, although this too can vary. Younger persons and women tend to have a higher burden of winter depressive episodes (4:1 ratio of women to men). The treatment of this condition can involve light therapy (see “Light Therapy” section) especially in winter months when the days are shorter. In summer months, the focus is often on preserving proper sleep–wake schedules and avoiding disruptions that longer days and perhaps summer vacations can pose. Burnout, while not a DSM disorder, is an important issue when discussing depression (see Chapters 6, 36, & 49). Burnout rates among medical professionals are increasing with rates now twice as high as in other professions even after adjusting for factors such as age, sex, level of education, and hours worked in the past week. A good working definition for burnout is a long­term stress reaction characterized by depersonalization, including cynical or negative attitudes toward patients; emotional exhaustion; a feeling of decreased personal achievement; and a lack of empathy for patients. Burnout is thought to have at least a 15% overlap with symptoms of depression. Many experts suggest that burnout is basically a depressive syndrome caused by chronic stressors found in the workplace. EPIDEMIOLOGY The prevalence of major depression is 6.7% of all U.S. adults and the estimated lifetime risk of a major depressive episode is around 30%. The prevalence of major depressive episode (MDE) among adult females is almost two times that seen in males. Reasons for gender differences in the prevalence of depression have not been fully elucidated, but both biological and sociocultural factors are thought to contribute. The prevalence rates of depression (and suicide) are far higher in transgender individuals with rates hovering around 50%. Key factors implicated in these markedly elevated rates for transgender individuals include discrimination, stigma, lack of acceptance, and abuse compared to gender binary individuals. In addition, MDD rates are highest among adults reporting two or more races. Among the protective factors in the prevention of depression are high education and socioeconomic advantage. In ambulatory medical settings, numerous studies report a 10–15% prevalence of major depression, with a substantially higher rate (20–40%) in patients with coexisting medical problems, particularly in those with diseases associated with strong biological or psychological predispositions to depression (e.g., stroke, Parkinson disease, traumatic brain injury, diabetes, coronary atherosclerotic disease, pancreatic cancer, and other terminal illnesses). Individuals aged 18–25 (10.9%) have the highest prevalence, and depression­related suicide is the second leading cause of death for this group. Because the mean age at onset of MDD is 32.5 years old, an apparent first episode of depression in an older patient should prompt a thorough evaluation to exclude underlying disease and/or medication effects. While MDD occurs in no more than about 5% of community dwelling older adults, rates of up to 10% are found in primary care settings and are much higher in nursing homes and after an acute hospitalization. In addition to genetic vulnerabilities, cognitive diathesis, and stress, a common pathway to depression in older adults is thought to be curtailment of daily activities. Major depression is often misdiagnosed in elderly primary care patients as a sign of aging, and cognitive impairment may also complicate accurate diagnosis. Some medications commonly prescribed in the elderly population may actually precipitate the onset of depression or cause symptoms like fatigue and poor concentration, which may mimic depressive symptoms. ETIOLOGY Downloaded 2025­2­16 5:19 P Your IP is MDD represents Chapter a heterogeneous 26: Depression, group Y. Pritham Raj;ofJohn disorders. It is likely that F. Christensen; futureD. & Mitchell research Feldmanwill eventually provide diagnostic specificity to these disorders, Page 5 / 39 leadingMcGraw ©2025 to more targeted and effective Hill. All Rights treatments. Reserved. Terms For present of Use purposes, Privacy Policyhowever, Notice the clinical manifestation of a major depressive episode should be Accessibility considered a final common psychobiological pathway among multiple candidate etiologic determinants. Advances in genetic, anatomic, physiologic, and immunologic studies already point the way toward a more precise biological understanding of this common and disabling condition. depression in older adults is thought to be curtailment of daily activities. Major depression is often misdiagnosed in elderly primary care patients as a sign of aging, and cognitive impairment may also complicate accurate diagnosis. Some medications commonly prescribed in theBarry University elderly Library population may actually precipitate the onset of depression or cause symptoms like fatigue and poor concentration, which may mimic depressive symptoms. Access Provided by: ETIOLOGY MDD represents a heterogeneous group of disorders. It is likely that future research will eventually provide diagnostic specificity to these disorders, leading to more targeted and effective treatments. For present purposes, however, the clinical manifestation of a major depressive episode should be considered a final common psychobiological pathway among multiple candidate etiologic determinants. Advances in genetic, anatomic, physiologic, and immunologic studies already point the way toward a more precise biological understanding of this common and disabling condition. THE EMERGING BIOLOGY OF DEPRESSION: ADVANCES IN GENETICS, ANATOMY, PHYSIOLOGY, & IMMUNOLOGY Recurrent major depression has been shown to have a heritability of 35–40%, and genetic linkage and twin studies have begun to identify specific regions of the genome thought to be candidates for carrying depression susceptibility. One interesting candidate gene is the serotonin transporter gene (5­HTT), which makes functional sense since many antidepressants seem to work through binding to the 5­HTT protein. Case­control association studies of the serotonin receptor gene HTR2A and major depression have yielded similar mixed results as for the 5HTT gene. More recently, researchers at the University of Maryland School of Medicine identified another gene of interest, the Slc6a15 gene in the D2 neurons of the nucleus accumbens (the “reward center” of the brain). Postmortem pathologic studies, along with functional and structural imaging studies, have converged to help identify key anatomic loci of depressive illness, including the hippocampus, the dorsolateral prefrontal cortex, the anterior cingulate cortex, and the amygdala. Animal and human studies confirm volumetric decreases in the hippocampus in depressive illness in individuals with a history of adverse childhood events. Antidepressant medications appear to induce neurogenesis (increases in volume) in the hippocampus, possibly through increases in brain­derived neurotrophic factor (BDNF). From the physiologic point of view, a considerable body of emerging evidence conceptually and experimentally points to dysregulation of distributed brain networks and second messenger abnormalities as the underlying neurobiological abnormalities in recurrent mood disorders. This contrasts with earlier theories postulating that neurotransmitter deficiencies (e.g., decreases in norepinephrine, serotonin, and/or dopamine) serve as the biological substrate of depression. Clinically, it is important that patients with depression not have an impression that they somehow have a brain “deficiency.” It is more appropriate to discuss the physiology of depression as a state where the brain may be using the neurotransmitters it produces in an inefficient manner, which is what pharmacotherapy and even psychotherapy targets. Lastly, immunologic studies have consistently found abnormalities of cytokines associated with depressive illness. High levels of several proinflammatory components of the immune system, such as interleukin­6, C­reactive protein, tumor necrosis factor (TNF)­α, or neopterin, in patients suffering from depression point to the involvement of an inflammatory process in the pathophysiology of MDD (see Chapter 36). A large­scale epidemiological study in MDD clearly demonstrated that severe infections and autoimmune disorders are lifetime risk factors for development of MDD. Advances in all these biological correlates of depression hold great promise for the development of more specific and more effective treatments of depressive disorders in the not too distant future. SOCIAL & PSYCHOLOGICAL FACTORS High Stress & Low Support From a societal perspective, significant life stress and/or lack of social support predisposes to development of MDD. Life stress that involves loss, for example, death of a parent or spouse, the end of a relationship, and events involving loss of self­esteem, such as termination from a job, create particular vulnerability for depression. Low social support, both independently and in the face of significant stress also predisposes to depressive disorder. Low perceived social support, that is, the extent to which an individual believes himself or herself to lack a supportive social network, creates a higher risk than any absolute or objective measure. (It is worth noting that these same risk factors of high stress and low support tend to increase risk for all illnesses, whether psychiatric or general medical illnesses.) The stress caused by natural disasters also increases the vulnerability of survivors to depression. While the psychiatric impact of such disasters includes increased prevalence rates of PTSD, substance abuse, and other conditions, the increased rate of depression itself is significant and measurable. For example, children and adults in the tsunami­affected areas of southwestern Thailand showed significantly increased and persistent rates of depression—ranging from 6% to 30% depending upon level of exposure and level of life disruption. Similarly, war has always been a stressor with major mental Downloaded health5:19 2025­2­16 consequences. Key drivers of vulnerability to stress include: any personal or family psychiatric history, history of previous P Your IP is trauma (including Chapter childhood 26: Depression, sexual abuse), Y. Pritham lowF. Raj; John intelligence, Christensen;limited socialD. & Mitchell supports, Feldmanand childhood separation from parents or divorce of parents Page 6 /in 39 ©2025 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility early childhood. With increased life expectancy and the aging of the population in the United States, spousal caregiving of persons with disability, including dementia, is The stress caused by natural disasters also increases the vulnerability of survivors to depression. While the psychiatric impact ofBarry suchUniversity disasters Library Access Provided by: includes increased prevalence rates of PTSD, substance abuse, and other conditions, the increased rate of depression itself is significant and measurable. For example, children and adults in the tsunami­affected areas of southwestern Thailand showed significantly increased and persistent rates of depression—ranging from 6% to 30% depending upon level of exposure and level of life disruption. Similarly, war has always been a stressor with major mental health consequences. Key drivers of vulnerability to stress include: any personal or family psychiatric history, history of previous trauma (including childhood sexual abuse), low intelligence, limited social supports, and childhood separation from parents or divorce of parents in early childhood. With increased life expectancy and the aging of the population in the United States, spousal caregiving of persons with disability, including dementia, is increasing. Caregivers (most often the female partner) of spouses with major neurocognitive disorder (e.g., Alzheimer disease) experience extreme physical and emotional burden. The role of caregiver presents a situation of both high stress and increasingly low support (as the caregiver progressively loses any emotionally meaningful relationship with the patient). Up to 40% of caregivers of patients with progressive dementia suffer from significant depressive symptoms or major depression. Postpartum “baby blues” typically occurs in 50–80% of women within 1–5 days of childbirth and lasts up to 1 week. As discussed earlier, this “normal” reaction should be distinguished from depression with peripartum onset (previously postpartum depression), which occurs in 10–15% of women in the first 3–6 months after childbirth. Postpartum psychosis, which occurs in 0.5–2.0/1000 deliveries and typically begins 2–3 days after delivery, is most common in individuals with a personal or family history of bipolar disorder. The tragic case of Andrea Yates, who drowned her five young children in Houston, Texas in 2001 during a period of postpartum depression and psychosis, highlights the depth of psychosis that can accompany underlying bipolar disorder. Postpartum psychosis is a highly acute psychiatric illness that usually requires mood stabilizers such as neuroleptic medications or lithium, and psychiatric referral (see Chapter 16). DIAGNOSIS The criteria for major depression require that five of nine symptoms be present for a 2­week period (see Table 26­1). One of these nine symptoms must be either a persistent depressed mood (present most of the day, nearly every day) o r pervasive anhedonia (from the Greek meaning “without pleasure”). Clinicians should realize that a depressed mood is not synonymous with major depression and is neither necessary nor sufficient for a diagnosis of major depression. Sadness (or tearfulness) does not constitute major depression and, conversely, major depression can be diagnosed without the presence of depressed mood (if pervasive anhedonia is present), a presentation that is more common in the elderly. Organizing these nine symptoms into clusters of four hallmarks can facilitate clinical evaluation: (1) depressed mood; (2) anhedonia; (3) physical symptoms (sleep disorder, appetite problem, fatigue, and psychomotor changes); and (4) psychological symptoms (difficulty concentrating or indecisiveness, guilt or low self­esteem, and thoughts of death). Physical symptoms predict a favorable response to biological intervention. For example, when middle insomnia is present (awaking at 3 or 4 a.m. with an inability to return to sleep) and when a diurnal variation in mood is present (feeling more depressed in the morning), patients are more likely to respond to biological interventions. The Fallacy of “Good Reasons” Depression is often mistakenly believed to be an “expected” result of stressful life events. Studies of individuals under stress (e.g., terminal cancer or natural disaster) show rates of major depression above the general population rate, but these rates do not typically exceed 50%. Although sad or depressed affect is an expected accompaniment of a stressful event, the full syndrome of major depression does not appear in everyone. Thus, life stressors including bereavement may seem to provide “good reasons” for sadness, but a stressful event, in itself, should not be considered a rationale to withhold depression treatment. If a major depressive syndrome emerges following a stressful life situation, the medical provider should treat it appropriately. The Confound of Overlapping Etiology A comorbid general medical condition (such as cancer or Parkinson disease) may seemingly “cause” many of the physical symptoms of major depression, such as fatigue, anorexia, or psychomotor retardation. These symptoms may lead clinicians to discount their relevance and thus disregard the possibility of a treatable depression. However, it is important to include these symptoms in the initial diagnostic approach to depression in the medically ill and to exclude them only if they are clearly and fully accounted for by the physical illness. Although this “inclusive” approach might seem to result in the overdiagnosis of MDD or depressive disorder due to a medical disorder; studies in stroke, Parkinson disease, hospitalized elderly, and traumatic brain injury indicate that the problem of overdiagnosis is quite low when compared with the underdiagnosis of depression. Downloaded THE MEDICAL2025­2­16INTERVIEW 5:19 P Your IP is Chapter 26: Depression, Y. Pritham Raj; John F. Christensen; & Mitchell D. Feldman Page 7 / 39 ©2025 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility Build Trust by Responding to Distress depression, such as fatigue, anorexia, or psychomotor retardation. These symptoms may lead clinicians to discount their relevance and thus disregard the possibility of a treatable depression. However, it is important to include these symptoms in the initial diagnostic approach Barry to depression in the University Library medically ill and to exclude them only if they are clearly and fully accounted for by the physical illness. Although this “inclusive” approach might seem Access Provided by: to result in the overdiagnosis of MDD or depressive disorder due to a medical disorder; studies in stroke, Parkinson disease, hospitalized elderly, and traumatic brain injury indicate that the problem of overdiagnosis is quite low when compared with the underdiagnosis of depression. THE MEDICAL INTERVIEW Build Trust by Responding to Distress The medical interview holds the key to the assessment of major depression. Efficient assessment involves attention to data­gathering as well as rapport­building with the patient. Physicians should be alert for nonverbal cues of depression: for example, a sad mood may be communicated by downcast eyes, slow speech, wrinkled brow, or a tearful affect. When a depressed mood is detected or emotional distress is suspected, clinicians should first respond empathically to this distress, by demonstrating a caring attitude, and using attentive silence or direct reflective and empathic statements, such as “I can see you’re having some trouble,” or “It sounds like you’ve been under a lot of stress lately,” or “You seem down right now.” Responding directly to the patient’s distress builds trust and encourages the patient to share the feelings that may underlie a depressive illness. Use Direct, Open­Ended Questioning Use open­ended questions and facilitation techniques to provide patients with the opportunity to discuss the issues that may be troubling (see Chapter 1). In gathering data for assessment, clinicians should focus on anhedonia (e.g., “What do you enjoy doing these days?”) and depressed mood (e.g., “How has your mood been the last few weeks?” or “Have you been feeling sad, blue, or down in the dumps?”). These simple questions can effectively uncover an underlying depression in most patients, despite the fact that many depressed patients in the general medical setting initially present with physical and bodily symptoms (e.g., headache, fatigue, and insomnia). Involve the Family Optimal assessment and management of the depressed patient is enhanced by involvement of one or more significant other(s). A spouse, partner, parent, or others can help the physician gather useful information regarding the patient’s mood, activities, behaviors, and history. In fact, because of stigma, denial, and other psychosocial barriers, other persons often provide much more accurate information regarding depressive illness than the self­report of the patient. Additionally, clinical changes (improvement or worsening) are often more quickly recognized by loved ones than the patient herself due in large part to habituation to the symptoms of depression. The Patient Health Questionnaire: Screening, Assessment, Engagement, & Monitoring The PHQ­2 consists of the first two items of the PHQ­9 and is a convenient and evidence­based approach to depression screening in primary care. PHQ­ 2 scores can range from 0 to 6; a cut­point of ≥3 is considered positive and should prompt administration of the full PHQ­9. Some experts advocate use of the full PHQ­9 (Appendix 26­A) to screen “red flag” patients, that is, those likely to be at high risk of major depression. “Red flag” patients generally include those with chronic medical illness (e.g., diabetes), and patients with persistent unexplained medical complaints. This one­step approach, combining screening and assessment, can simplify operational strategies. Appendix 26­A. Patient Health Questionnaire—PHQ­9. Name _______________________ Physician _____________________ Date _______________ Over the last 2 weeks, how often have you been bothered by any of the following problems? Not Several More Than Nearly At All Days Half the Days Every Day (0) (1) (2) (3) 1. Feeling down, depressed, or hopeless? □ □ □ □ 2. Little interest or pleasure in doing things? □ □ □ □ 3. Trouble falling or staying asleep, or sleeping too much? □ □ □ □ Downloaded 2025­2­16 5:19 P Your IP is Chapter 26: Depression, 4. Feeling Y. Pritham tired or having Raj; John F. Christensen; & Mitchell D. Feldman little energy? □ □ □ □ Page 8 / 39 ©2025 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility 5. Poor appetite or overeating? □ □ □ □ include those with chronic medical illness (e.g., diabetes), and patients with persistent unexplained medical complaints. This one­step approach, combining screening and assessment, can simplify operational strategies. Barry University Library Access Provided by: Appendix 26­A. Patient Health Questionnaire—PHQ­9. Name _______________________ Physician _____________________ Date _______________ Over the last 2 weeks, how often have you been bothered by any of the following problems? Not Several More Than Nearly At All Days Half the Days Every Day (0) (1) (2) (3) 1. Feeling down, depressed, or hopeless? □ □ □ □ 2. Little interest or pleasure in doing things? □ □ □ □ 3. Trouble falling or staying asleep, or sleeping too much? □ □ □ □ 4. Feeling tired or having little energy? □ □ □ □ 5. Poor appetite or overeating? □ □ □ □ 6. Feeling bad about yourself—or that you are a failure or have let yourself or your family down? □ □ □ □ 7. Trouble concentrating on things, such as reading the newspaper or watching television? □ □ □ □ 8. Moving or speaking so slowly that other people could have noticed? Or the opposite—being so □ □ □ □ fidgety or restless that you have been moving around a lot more than usual? 9. Thoughts that you would be better off dead or of hurting yourself in some way?* □ □ □ □ 10. If you are experiencing any of the problems on this form, how difficult have these problems made it for you to do your work, take care of things at home, or get along with other people? □ Not difficult at all □ Somewhat difficult □ Very difficult □ Extremely difficult Office Use Only Number of Symptoms: ________ _____ Severity Score: __________ *If you have had thoughts that you would be better off dead or of hurting yourself in some way, please discuss this with your doctor, go to a hospital emergency room, or call 911. The PHQ­9 is an assessment and severity tool that has been validated for use in general medical as well as specialty psychiatric settings. A score of 10 or more has an 88% sensitivity and specificity for the diagnosis of major depression. Furthermore, the tool also can be used effectively to track patients’ symptom severity and improvement over time. The instrument and scoring key are in Appendices 26­A and 26­B. Appendix 26­B. Scoring the PHQ­9. How to Score the Patient Health Questionnaire (PHQ­9) The PHQ­9 can assist in diagnosing depression, as well as planning and monitoring depression treatment. There are three steps to scoring the PHQ­9: Number of Depressive Symptoms, Severity Score, and Functional Assessment. The Number of Depressive Symptoms is used to aid in making the diagnosis Downloaded 2025­2­16 5:19 P Your IP is of Depression. The PHQ­9 Severity Score and Functional Assessment are measured at initial assessment and regularly after treatment begins to determine Chapter 26: Depression, Y. Pritham Raj; John F. Christensen; & Mitchell D. Feldman Page 9 / 39 ©2025the severityHill. McGraw of depression All Rightsand to evaluate Terms Reserved. patient of progress. Use Privacy Policy Notice Accessibility Number of Depressive Symptoms (Diagnosis) more has an 88% sensitivity and specificity for the diagnosis of major depression. Furthermore, the tool also can be used effectively to track patients’ symptom severity and improvement over time. The instrument and scoring key are in Appendices 26­A and 26­B. Barry University Library Access Provided by: Appendix 26­B. Scoring the PHQ­9. How to Score the Patient Health Questionnaire (PHQ­9) The PHQ­9 can assist in diagnosing depression, as well as planning and monitoring depression treatment. There are three steps to scoring the PHQ­9: Number of Depressive Symptoms, Severity Score, and Functional Assessment. The Number of Depressive Symptoms is used to aid in making the diagnosis of Depression. The PHQ­9 Severity Score and Functional Assessment are measured at initial assessment and regularly after treatment begins to determine the severity of depression and to evaluate patient progress. Number of Depressive Symptoms (Diagnosis) 1. For questions 1–8, count the number of symptoms the patient checked as “More than half the days” or “Nearly every day.” For question 9, count the question positive if the patient checks “Several days,” “More than half the days,” or “Nearly every day.” 2. Use the following interpretation grid to diagnose depression subtypes: 0–2 PHQ symptoms Not clinically depressed 3–4 PHQ symptoms* Other depressive syndrome 5 or more PHQ symptoms* Major depression Severity Score 1. Assign a score to each response by the number value under the answer headings (Not at all = 0; Several days = 1; More than half the days = 2; and Nearly every day = 3). 2. Total the values for each response to obtain the severity score. 3. Use the following interpretation grid: 0–4 Not clinically depressed 5–9 Mild depression 10–14 Moderate depression ≥15 Severe depression Functional Assessment The final question on the PHQ­9 asks the patient how emotional difficulties or problems impact work, things at home, or relationships with other people and if this has caused difficulty for 2 years or more. Patient responses can be one of four: “Not difficult at all”; “Somewhat difficult”; “Very difficult”; or “Extremely difficult.” If the patient selects one of the last two responses, “Very difficult” or “Extremely difficult,” his or her functionality at work, at home, or in relationships with other people is significantly impaired. If the patient has had difficulty with these problems for 2 years or more, consider the diagnosis of dysthymia (chronic depression). *PHQ­9 items #1 or #2 must be one of the symptoms checked. PHQ­9 is adapted from PRIME­MD Today. Developed by Drs. Robert L. Spitzer, Janet B.W. Williams, Kurt Kroenke and colleagues, with an educational grant from Pfizer Inc. No permission required to reproduce, translate, display or distribute. Downloaded 2025­2­16 5:19 P Your IP is Chapter BARRIERS26: Depression, Y. Pritham Raj; John F. Christensen; & Mitchell D. Feldman TO DIAGNOSIS Page 10 / 39 ©2025 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility Patient Barriers: Somatic Presentations & Stigma  *PHQ­9 items #1 or #2 must be one of the symptoms checked. Barry University Library Access Provided by: PHQ­9 is adapted from PRIME­MD Today. Developed by Drs. Robert L. Spitzer, Janet B.W. Williams, Kurt Kroenke and colleagues, with an educational grant from Pfizer Inc. No permission required to reproduce, translate, display or distribute. BARRIERS TO DIAGNOSIS Patient Barriers: Somatic Presentations & Stigma Primary care patients with major depression often present with physical complaints, such as pain (headache, backache), fatigue, insomnia, dizziness, or gastrointestinal (GI) problems rather than mood complaints. Many of these patients are willing to acknowledge feelings of depressed mood and to consider the possibility that biologically mediated depression may also cause or exacerbate their physical problems. Some somatically preoccupied patients, however, are reluctant to consider that depression may contribute to their physical symptoms. In these patients, evaluating both general medical and psychiatric problems simultaneously saves time, expense, and frustration for both clinician and patient. Many patients and families (particularly in some cultures) are reluctant to accept the diagnosis of depression because of associated social stigma. Providers can help overcome this barrier by explaining to patients and families that depression is a common and treatable illness, like other medical illnesses. The hope is that with more awareness and destigmatization of depression, the societal burden of the disorder may diminish. Clinician Barriers Depression is often undetected or is not adequately treated in the medical setting. Some providers avoid depression diagnoses because they harbor the same stigmatizing attitudes toward depression that many of their patients feel. In addition, inadequate knowledge and skill, lack of time, reluctance to “open up” new domains of emotional distress, habits leading to low value care (e.g., failing to titrate antidepressant medications in a timely fashion), and misaligned financial incentives all operate as barriers to physician recognition and treatment. However, early recognition of behavioral and psychiatric disorders is ultimately time efficient, while minimizing the cost and risk of extended, unnecessary workups for nonspecific physical complaints. SUICIDE There is one death by suicide every 12 minutes in the United States, making suicide one of the top 10 causes of death in all age groups. Roughly 90% of suicide deaths can be traced back to mental illness, most often depression. Suicide risk must be evaluated in all patients with symptoms of depression. Risk factors for completed suicide include gender (elderly white males are at highest risk), alcoholism, psychosis, chronic physical illness, lack of social support, recent humiliation, descent from mania, and use of lethal methods (e.g., gun rather than overdose of pills). Increased risk of suicide has also been noted among depressed adolescents and among LGBTQ (lesbian, gay, bisexual, transgender, and questioning) patients. Explicit suicidal intent, hopelessness, and a well­formulated plan indicate relatively higher risk. Many patients who eventually commit suicide visit a primary care provider in the weeks or months before they take their lives. PCPs are sometimes reluctant to explore suicidal ideation in the mistaken belief that asking about suicide may actually increase a patient’s risk. However, assessment of suicidal tendencies usually reassures patients, reduces anxiety for both patient and provider, and facilitates partnership in suicide prevention. The assessment of suicidal ideation is best approached gradually albeit systematically after an examination of Question 9 of the PHQ­9 (or other pertinent suicide questions from alternative depression screening tools), with general questions like, “I notice you marked positive the question about having thoughts about death or hurting yourself in some way on the depression screening tool. When did you last have such thoughts or feel that life is not worth living?” These questions should be followed by asking more specifically about a history of suicide attempts, any specific current plans, hopelessness, impulsivity, and any specific current intentions. Once a patient reveals suicidal ideation, the medical provider should always consider psychiatric consultation and/or hospitalization if the suicidal thoughts are active. However, if there is no intent to act on these thoughts and outpatient management is being considered as a next step, the clinician should assess the following: delirium (using a cognitive screening test), psychosis (screening for auditory and visual hallucinations are considered the standard of care for the nonpsychiatrist), and of course, depression. To complete the assessment, it is often helpful to restate what the patient plans to do next (and perhaps offer a suggestion if needed) after the evaluation. It is also important to gather collateral information on the safety of the patient from a third party either in person or by phone. A time­honored summary statement that would appropriately capture the key elements of a systematic inpatient safety evaluation that can also be adapted for the outpatient setting is: “Patient says that she is no longer feeling suicidal. There is no evidence of delirium or psychotic features. She acknowledges her family problems and says that counseling makes sense. She has agreed to a follow­up appointment at the mental health center tomorrow and plans to call her employer today to say she will be back at work next week. She has discussed these plans with her husband who agrees to be seen with Downloaded her at the5:19 2025­2­16 initial P psychiatric Your IP is assessment following discharge. Patient no longer needs constant observation.” Chapter 26: Depression, Y. Pritham Raj; John F. Christensen; & Mitchell D. Feldman Page 11 / 39 The useMcGraw ©2025 of a “no suicide Hill. All contract” is controversial. Rights Reserved. TermsThe contract of Use was formally Privacy recommended Policy Notice in 1973 and involves asking the patient to promise that he Accessibility or she will contact the physician (or other appropriate caregiver) if there is a danger of losing control of a suicidal impulse. In using such a “contract” however, providers need to realize that there is no convincing empirical evidence to support its validity. In fact, most experts specifically advise against important to gather collateral information on the safety of the patient from a third party either in person or by phone. Barry University Library A time­honored summary statement that would appropriately capture the key elements of a systematic inpatient safety evaluation that can also be Access Provided by: adapted for the outpatient setting is: “Patient says that she is no longer feeling suicidal. There is no evidence of delirium or psychotic features. She acknowledges her family problems and says that counseling makes sense. She has agreed to a follow­up appointment at the mental health center tomorrow and plans to call her employer today to say she will be back at work next week. She has discussed these plans with her husband who agrees to be seen with her at the initial psychiatric assessment following discharge. Patient no longer needs constant observation.” The use of a “no suicide contract” is controversial. The contract was formally recommended in 1973 and involves asking the patient to promise that he or she will contact the physician (or other appropriate caregiver) if there is a danger of losing control of a suicidal impulse. In using such a “contract” however, providers need to realize that there is no convincing empirical evidence to support its validity. In fact, most experts specifically advise against its use, arguing that a mechanistic pursuit of obtaining a “contract” can functionally undermine an open relationship and lead providers into a false sense of security. The main utility of the “contract” may be as a tool to discuss the strength of the individual’s suicidal ideas. In all cases when treating depression, providers must evaluate suicidality at the initiation of treatment and throughout the treatment program. Routine use of the PHQ­9 can aid in assessing suicide risk at the initiation of treatment and, of equal importance, can also aid in the recognition of any subsequent or treatment­emergent suicide risk. Because the risk of suicide sometimes increases within the first few weeks of treatment and can emerge at any point in the subsequent treatment, regular and routine use of the PHQ­9 can function as an efficient and effective suicide reassessment tool. The Columbia­Suicide Severity Rating Scale is also a useful clinician­administered instrument (http://www.cssrs.columbia.edu/about_cssrs.html). Vincent Van Gogh—At Eternity’s Gate PHYSICAL EXAMINATION There are no specific diagnostic signs of depression in the physical exam. A careful medical history and physical examination are required for the evaluation of depression at all ages, but especially in the elderly. Some medical “mimics” of depression (e.g., hypothyroidism and Cushing syndrome) present with classic physical signs. LABORATORY STUDIES No laboratory studies can be used to diagnose major depression reliably or specifically. A general but targeted laboratory screen may be useful in Downloaded 2025­2­16 selected patients 5:19other to rule out P Your IP is that may mimic or exacerbate depression: chemistry profile (the highest value test), TSH, urine drug conditions Chapter 26: Depression, Y. Pritham Raj; John F. Christensen; & Mitchell D. Feldman Page 12 / 39 screen, and perhaps a complete blood count in patients reporting bleeding (such as menstruating women) or when treating with medication that can ©2025 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility affect hematological lines. In treatment­resistant cases, or when indicated, vitamin levels, urinalysis, brain imaging, or even electroencephalogram (EEG) or lumbar puncture (LP) can be considered, particularly if there are fluctuations in mental status, but these studies are not part of the standard evaluation of depression at all ages, but especially in the elderly. Some medical “mimics” of depression (e.g., hypothyroidism and Cushing syndrome) present with classic physical signs. Barry University Library Access Provided by: LABORATORY STUDIES No laboratory studies can be used to diagnose major depression reliably or specifically. A general but targeted laboratory screen may be useful in selected patients to rule out other conditions that may mimic or exacerbate depression: chemistry profile (the highest value test), TSH, urine drug screen, and perhaps a complete blood count in patients reporting bleeding (such as menstruating women) or when treating with medication that can affect hematological lines. In treatment­resistant cases, or when indicated, vitamin levels, urinalysis, brain imaging, or even electroencephalogram (EEG) or lumbar puncture (LP) can be considered, particularly if there are fluctuations in mental status, but these studies are not part of the standard workup. Patients over age 40 usually require an electrocardiogram (ECG) to rule out conduction disturbances or bradycardia when considering treatment with a tricyclic antidepressant (TCA), certain antipsychotics, or citalopram at doses greater than 40 mg/d, since those doses may be associated with prolonged QT intervals and arrhythmias. DIFFERENTIAL DIAGNOSIS Mental Disorders Other mental disorders often present with symptoms similar to depression; in addition, depression often presents in combination with other mental disorders. In the presence of psychiatric comorbidity, effective treatment of depression may lead to improvement in the other condition as well. Modifications of treatment, however, may be necessary depending on the particular comorbidity present. Major Depressive Disorder Versus Bipolar Depression It is critically important to distinguish MDD from bipolar depression. The signs and symptoms of the two disorders are identical. One key historical question helps to differentiate the two conditions: Did the patient ever experience clinical mania or hypomania? The symptoms of a manic episode are listed in Table 26­2, the most common of which include an elated or irritable mood, racing thoughts, poor judgment in interpersonal, sexual, or financial situations, and excess energy for 1 week (or less if hospitalization is required). Criteria for hypomania are the same but are less intense and not disruptive of normal functioning but last at least 4 days. To uncover a possible history of mania/hypomania, the provider should ask about any personal or family history of treatment of mania/hypomania/bipolar disorder and consider asking a 2­question screen for mood lability that may help distinguish patients with bipolar II disorder from patients with unipolar major depression. The 2 questions are: “Are you a person who frequently experiences ups and downs in mood over life?” and “Do these mood swings occur without cause?” A positive response to at least 1 question indicates mood lability and an increased likelihood of bipolar disorder. Table 26­2. Criteria for manic episode. A. A distinct period of abnormally and persistently elevated, expansive, or irritable mood, lasting at least 1 week (or any duration if hospitalization is necessary). B. During the period of mood disturbance, three (or more) of the following symptoms have persisted (four if the mood is only irritable) and have been present to a significant degree: 1. Inflated self­esteem or grandiosity 2. Decreased need for sleep (e.g., feels rested after only 3 hours of sleep) 3. More talkative than usual or pressure to keep talking 4. Flight of ideas or subjective experience that thoughts are racing 5. Distractibility (i.e., attention too easily drawn to unimportant or irrelevant external stimuli) 6. Increase in goal­directed activity (either socially, at work or school, or sexually) or psychomotor agitation 7. Excessive involvement in pleasurable activities that have a high potential for painful consequences (e.g., engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments) The mood disturbance is sufficiently severe to cause marked impairment in occupational functioning or in usual social activities or relationships with others, or to necessitate hospitalization to prevent harm to self or others, or there are psychotic features. The Mood Disorders Questionnaire (MDQ) may be helpful in making a diagnosis of bipolar disorder (Table 26­3), though its sensitivity and specificity are not high enough to be used as a stand­alone tool. Even if there is no history of mania/hypomania, if the individual has a strong family history of Downloaded 2025­2­16 bipolar disorder, 5:19 must the clinician P Your IP is that at least one­third of bipolar patients have depression as their index mood episode. Such a history consider Chapter 26: Depression, Y. Pritham Raj; John F. Christensen; & Mitchell D. Feldman Page 13 / 39 should ©2025 help makeHill. McGraw theAll clinician Rightsalert to potential Reserved. mood Terms switches of Use withPolicy Privacy antidepressant Notice treatment. Accessibility Table 26­3. The MDQ and scoring guide.  The mood disturbance is sufficiently severe to cause marked impairment in occupational functioning or in usual social activities or relationships with Barry University Library others, or to necessitate hospitalization to prevent harm to self or others, or there are psychotic features. Access Provided by: The Mood Disorders Questionnaire (MDQ) may be helpful in making a diagnosis of bipolar disorder (Table 26­3), though its sensitivity and specificity are not high enough to be used as a stand­alone tool. Even if there is no history of mania/hypomania, if the individual has a strong family history of bipolar disorder, the clinician must consider that at least one­third of bipolar patients have depression as their index mood episode. Such a history should help make the clinician alert to potential mood switches with antidepressant treatment. Table 26­3. The MDQ and scoring guide. THE MOOD DISORDER QUESTIONNAIRE Instructions: Please answer each question as best you can. 1 Has there ever been a period of time when you were not your usual self and … YES NO … you felt so good or so hyper that other people thought you were not your normal self or you were so hyper that you got into ○ ○ trouble? … you were so irritable that you shouted at people or started fights or arguments? ○ ○ … you felt much more self­confident than usual? ○ ○ … you got much less sleep than usual and found you didn’t really miss it? ○ ○ … you were much more talkative or spoke much faster than usual? ○ ○ … thoughts raced through your head or you couldn’t slow your mind down? ○ ○ … you were so easily distracted by things around you that you had trouble concentrating or staying on track? ○ ○ … you had much more energy than usual? ○ ○ … you were much more active or did many more things than usual? ○ ○ … you were much more social or outgoing than usual, for example, you telephoned friends in the middle of the night? ○ ○ … you were much more interested in sex than usual? ○ ○ … you did things that were unusual for you or that other people might have thought were excessive, foolish or risky? ○ ○ … spending money got you or your family into trouble? ○ ○ 2 If you checked YES to more than one of the above, have several of these ever happened during the same period ○ ○ of time? 3 How much of a problem did any of these cause you—like being unable to work; having family, money or legal ○ ○ troubles; getting into arguments or fights? Please circle one response only. No problem Minor problem Moderate problem Serious problem 4 Have any of your blood relatives (i.e., children, siblings, parents, grandparents, aunts, uncles) had manic­ ○ ○ depressive illness or bipolar disorder? Downloaded 2025­2­16 5:19 P Your IP is Chapter 26: Depression, 5 Has Y. Prithamever a health professional Raj;told John F. that you Christensen; you have&manic­depressive Mitchell D. Feldman illness or bipolar disorder? ○ Page ○ 14 / 39 ©2025 McGraw Hill. All Rights Reserved. Terms of Use Privacy Policy Notice Accessibility Positive Screen (all three of the following criteria must be met) Question 1: 7 of 13 positive (yes) responses + Question 2: positive (yes) response + Question 3: “moderate” or “serious” response  Please circle one response only. Barry University Library Access Provided by: No problem Minor problem Moderate problem Serious problem 4 Have any of your blood relatives (i.e., children, siblings, parents, grandparents, aunts, uncles) had manic­ ○ ○ depressive illness or bipolar disorder? 5 Has a health professional ever told you that you have manic­depressive illness or bipolar disorder? ○ ○ Positive Screen (all three of the following criteria must be met) Question 1: 7 of 13 positive (yes) responses + Question 2: positive (yes) response + Question 3: “moderate” or “serious” response Adapted from Hirschfeld RM, Williams JB, Spitzer RL, et al. Development and validation of a screening instrument for bipolar spectrum disorder: The Mood Disorder Questionnaire. Am J Psychiatry 2000;157(11):1873­1875. Copyright 2000 by The University of Texas Medical Branch. All rights reserved. This instrument is designed for screening purposes only and is not to be used as a diagnostic tool. Anxiety Disorders Anxiety and depression commonly co­occur in medical patients. Most patients with depression suffer from anxiety symptoms or an anxiety disorder, and most patients with an anxiety disorder have depressive symptoms or meet criteria for major depression. The most common anxiety disorders in medical outpatients are generalized anxiety disorder (GAD), panic disorder (PD), and social anxiety disorder (social phobia). Treatment of the major depression by itself, however, often helps to resolve or improve these other coexisting conditions (see Chapter 27), especially since many antidepressant medications have proven safe and effective for treating many of the anxiety disorders, PTSD, and OCD. Somatic Symptom & Related Disorders Depression often presents with unexplained bodily complaints. It can therefore be challenging to differentiate between a depressive illness and somatic symptom disorder, which includes previously used terms such as medically unexplained symptoms (see Chapter 29). Depressive disorders are highly treatable, but somatic symptom disorders can be more chronic and refractory to treatment. Somatic symptom disorders are usually best managed conservatively with a focus on improved functioning, whereas depression should be treated aggressively with the goal of complete recovery/remission. Any of the somatic symptom disorders (illness anxiety disorder, conversion disorder, factitious disorder, etc.) can present comorbidly with major depression. Approximately 50% of patients with persistent unexplained physical complaints suffer from depression. Effective treatment of major depression as well as short, focused, regular visits to talk about the somatic complaints usually improves the severity, intensity, and functional impairment of a comorbid somatic symptom disorder. Substance­Related & Addictive Disorders The substance­related disorders encompass 10 separate classes of drugs that are not fully distinct. Patients with alcohol use disorder or other substance use disorders commonly have comorbid major depression. Unfortunately, a recent study found that only a small fraction (2.4%) of primary care adult patients with depression and severe alcohol use were screened for depression (given a PHQ­9 within 30 days of alcohol screening). Conversely, all patients diagnosed with depression should be screened for comorbid substance use disorders. Major depression, even in the context of substance dependence, deserves treatment in its own right, as long as the treatment plan attends to potential complications from continuing substance abuse. Furthermore, effective treatment of depression (especially nonpharmacological therapies such as cognitive behavioral therapy) may help ameliorate the alcohol and/or other substance use problems and does not generally lead to increased complications. However, in most cases, treating the substance use disorder first is a key to addressing the depressive symptoms. Some patients will benefit from referral to specialty mental health or substance abuse treatment facilities for their addiction issues, and some severely ill patients will need treatment in settings with the capacity to treat “dual diagnosis” patients (those with both a substance use disorder and a primary mood or thought disorder). Personality Disorders Personality disorders represent enduring character patterns that are deeply ingrained and are not generally amenable to alteration (see Chapter 30). They often complicate the diagnosis and management of mood disorders. Because patients with certain personality disorders can be difficult and demanding, providers often try to minimize contact and, in some cases, lose empathy with such individuals. Unfortunately, this may lead to failure to diagnose depression. What often helps the most when interacting with a personality­disordered patient is acknowledging any countertransference Downloaded 2025­2­16 issues that may 5:19 be present P Your to by pausing IP imagine is what the patient’s life is like and to then listen empathically without judgement. In the words of Dr. Chapter 26: Depression, Y. Pritham Raj; John F. Christensen; & Mitchell D. Feldman Page 15 / 39 Morton ©2025 McGraw Hill. All Rights Reserved. Terms of “the Swartz from Massachusetts General Hospital, Use patient wants Privacy Policyto know the doctor Notice cares before he cares what the doctor knows.” Beyond Accessibility these techniques, effective treatment of major depression often improves functioning when the depression coexists with a personality disorder, even if the underlying personality disorder is itself not fundamentally changed. Personality Disorders Barry University Library Personality disorders represent enduring character patterns that are deeply ingrained and are not generally amenable to alteration Access(see Chapter Provided by: 30). They often complicate the diagnosis and management of mood disorders. Because patients with certain personality disorders can be difficult and demanding, providers often try to minimize contact and, in some cases, lose empathy with such individuals. Unfortunately, this may lead to failure to diagnose depression. What often helps the most when interacting with a personality­disordered patient is acknowledging any countertransference issues that may be present by pausing to imagine what the patient’s life is like and to then listen empathically without judgement. In the words of Dr. Morton Swartz from Massachusetts General Hospital, “the patient wants to know the doctor cares before he cares what the doctor knows.” Beyond these techniques, effective treatment of major depression often improves functioning when the depression coexists with a personality disorder, even if the underlying personality disorder is itself not fundamentally changed. Neurocognitive Disorders (Formerly Dementia) In its early stages, mild neurocognitive disorder can be often difficult to distinguish from depression. Depression often leads to reversible cognitive impairment in the form of decreased concentration, memory difficulties, impaired decision­making ability, difficulty planning and organizing, and difficulty getting started on tasks. These are also impairments that can result from an insidious and irreversible neurodegenerative process. Likewise, the effect of neurocognitive disorder on a person’s functioning can lead to depressed mood. When diagnostic uncertainty exists, the Cornell Scale for Depression in Dementia (CSDD) is considered the gold standard in the assessment. Because the cognitive impairments of MDD are reversible, clinicians should treat the depressive component (with both medication and counseling) and observe for changes in the patient’s cognitive symptom cluster. The term “pseudodementia” is used to describe treatable depression presenting with features of cognitive impairment. While it is useful for clinicians to understand that depression may be associated with cognitive impairment, clinicians should avoid use of this terminology. In actual practice, some patients for whom the concept of “pseudodementia” is considered may actually suffer from both conditions. Furthermore, late­onset depression (even reversible late­onset depression) is itself predictive of future dementia. Depression due to General Medical Conditions or Medications Approximately 10–15% of all depression is considered to be the direct physiologic result of a medical illness, such as hypothyroidism, pancreatic cancer, Parkinson disease, or stroke (Table 26­4). Because there are no clear criteria to help guide clinicians in their evaluation, this diagnosis is ultimately made by clinical inference, considering the timing of the depression in relation to the physical illness. Limited data seem to indicate that standard treatments for major depression are effective in these cases. Table 26­4. General medical conditions with high prevalence of depression. Disease/Condition Lewy body disease End­stage renal failure Parkinson disease Stroke Cancer or AIDS Chronic fatigue Diabetes mellitus Chronic pai