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1946 SECTION 24: Psychosocial Disorders angiotensin-converting enzyme inhibitors, which can increase serum lithium concentrations and the risk of toxicity. 96 Older adults taking lithium can display signs of toxicity even if the level is within the therapeutic window. 96 See Chapter 181, “Lithium, ” for further details of toxicity and treatment. Three anticonvulsants have also been approved to treat bipolar disorder: valproate, carbamazepine, and lamotrigine. The literature regarding their use in older adults is sparse.  PSYCHOSIS AND SCHIZOPHRENIA Several disorders, such as schizophrenia, psychosis associated with dementias, and more acute processes such as delirium, can present with symptoms of psychosis (hallucinations and delusions) in geriatric patients. The prevalence of schizophrenia in older adults is around 0.1% to 0.5%. 97-99 The majority of patients with schizophrenia develop the dis ease in the second or third decade of life (considered early-onset schizophrenia), meaning that most geriatric patients with schizophrenia have had the disorder since they were much younger. 100 There are two other groups of patients with schizophrenia: late-onset schizophrenia (over 40 years old) and very-late-onset schizophrenia-like psychosis (over 60 years old). 100 Individuals with late-onset schizophrenia have many of the same symptoms as patients with early-onset schizophrenia, but late-onset patients have fewer problems with learning, abstraction, and flexibility. 101 The diagnosis of very-late-onset schizophrenia and primary psychotic disorders is rare.100 Very-late-onset patients tend to have fewer negative symptoms, greater risk of tardive dyskinesia, and evidence of a neurodegenerative process rather than a neurodevelopmental process. Schizophrenia in geriatric patients involves a complex interplay of the psychiatric, medical, and social factors. Nonadherence to medical ther apy is common.102 Mortality secondary to cardiovascular disease is more than twice as common compared with the general population, likely due to high rates of smoking, diabetes mellitus, hypertension, and obesity in schizophrenic patients. Older patients with schizophrenia often have a more sedentary lifestyle and a worse diet. 102 Atypical antipsychotics used for treatment increase the risk of metabolic syndrome and weight gain, which in turn increase the risk of cardiovascular diseases. 103 The use of typical antipsychotics is limited because of the higher risk of tardive dyskinesia. 104 The cumulative annual incidence of tardive dyskinesia in patients over 45 years old treated with low-dose typical antipsychotics is about 26%, which is five to six times greater than in younger patients. Antipsychotic medications should be carefully selected and doses titrated upward slowly with close monitoring for side effects. Older patients with schizophrenia can also benefit from adjunctive psychoso cial interventions. For example, Functional Adaptation Skills Training, a group therapy targeting everyday life skills, improves the functional capabilities of older patients with schizophrenia. 105-107  EATING DISORDERS There is little information regarding eating disorders such as anorexia nervosa and bulimia nervosa in older adults. A study of women over 50 years old found that about 13% reported some form of current eating disorder symptoms. Binge eating and purging in the absence of binge eating were the most common symptoms.

DERS There is little information regarding eating disorders such as anorexia nervosa and bulimia nervosa in older adults. A study of women over 50 years old found that about 13% reported some form of current eating disorder symptoms. Binge eating and purging in the absence of binge eating were the most common symptoms. 108 Approximately 71% of women in the study were trying to lose weight.108 Another review identified 48 cases of eating disorders in adults over 50 years old. In this article, 88% were female and 60% were over 65 years old. The most frequent diagnosis was anorexia nervosa (81% of cases). 109 Of the 48 cases, 79% had the onset of eating disorders later in life.109 Importantly, this study identified a strong connection between eating disorders and other psychiatric conditions (60% of cases), with major depression being the most important. Eating disorders were often preceded by a stressful event such as widowhood, bereavement, or marriage difficulties. 109 Of the 48 patients reviewed, 21% of the patients died from complications of their eating disorder.109 Diagnosis is difficult and is made by excluding any physical or medi cal cause of unexplained weight loss. Eating disorders in older patients are treated similarly to those in any other age group, with a combination of cognitive-behavioral treatment and pharmacotherapy. Acknowledgments: Special thanks to prior authors of this chapter, Dr. Kristen Barrio and Dr. Kevin Biese. REFERENCES The complete reference list is available online at www.TintinalliEM.com. TABLE 289-1 Differential Diagnosis of Depression •   Neurologic: CNS infection, CNS tumor, cerebrovascular accident, Alzheimer’s disease, traumatic brain injury, multiple sclerosis, Parkinson’s disease, Huntington’s disease, normal pressure hydrocephalus •   Endocrine/metabolic: hypothyroidism, hyperthyroidism, Addison’s disease, Cushing’s disease, hyperparathyroidism, hypoglycemia, porphyria, severe anemia •   Infectious: meningitis, encephalitis, Lyme disease, human immunodeficiency virus, encephalopathy, Epstein-Barr virus, tertiary syphilis •  Inflammatory:  systemic lupus erythematosus •   Medication side effects: steroids, neurologic or psychiatric medications (especially withdrawal from), β-blockers, calcium channel blockers, hormone therapies, chemotherapy drugs •  Substances  of abuse: withdrawal from cocaine and amphetamines, alcohol, opiates •   Other psychiatric disorders: bipolar, posttraumatic stress disorder, substance abuse, anxiety disorder CHAPTER Mood and Anxiety Disorders Tracy M. DeSelm INTRODUCTION Mood disorders, which include depressive disorders and bipolar disor ders, are the most common mental health complaints presenting to the ED, accounting for about half of mental health–related visits, behind anxiety and substance use disorders (about 25% each). 1 Trends for ED visits for depressive disorders, bipolar disorders, and suicide ideation are sharply increasing. 2-5 The prevalence of depression and bipolar disorders in the ED patient population is twice that of the general population.6 This chapter discusses the depressive disorders, bipolar disorders, and anxiety disorders. Substance use disorders are discussed in detail in Chapter 292.  DEPRESSIVE DISORDERS Depressive disorders appear to affect women twice as often as men. Adolescents, 7 the elderly (especially nursing home patients),8 and people living below the poverty level 9 appear to be particularly vulnerable populations for depression. Increased rates of depressive disorders are seen with chronic illnesses, including CNS diseases, 10,11 cardiovascular disorders,12 cancer,13 and chronic obstructive pulmonary disease.14 PATHOPHYSIOLOGY The pathophysiology of depressive disorders includes genetic, biologi cal, and psychosocial factors.

s for depression. Increased rates of depressive disorders are seen with chronic illnesses, including CNS diseases, 10,11 cardiovascular disorders,12 cancer,13 and chronic obstructive pulmonary disease.14 PATHOPHYSIOLOGY The pathophysiology of depressive disorders includes genetic, biologi cal, and psychosocial factors. A genetic predisposition heightens sus ceptibility.15,16 Malfunctioning monoamine neurotransmitters (especially serotonin, norepinephrine, and dopamine)17-19 are implicated and may explain the effectiveness of some current medical therapies. Abnormal γ-aminobutyric acid and glutamate levels in various areas of the brain have been noted. 20 Abnormal neurocircuitry that links the prefrontal cortex to the amygdala, ventral striatum and pallidum, medial thalamus, hypothalamus, and the periaqueductal gray areas has been shown in mood disor ders.21 Early childhood stress may alter corticotropin-releasing hormone cells in the hypothalamus to heighten future stress responses.22,23 A large number of medical disorders, medications, and substances of abuse may cause depressive symptoms ( Table 289-1). A thorough Tintinalli_Sec24_p1933-1966.indd 1946 8/2/19 5:19 PM

.21 Early childhood stress may alter corticotropin-releasing hormone cells in the hypothalamus to heighten future stress responses.22,23 A large number of medical disorders, medications, and substances of abuse may cause depressive symptoms ( Table 289-1). A thorough Tintinalli_Sec24_p1933-1966.indd 1946 8/2/19 5:19 PM CHAPTER 289:  Mood and Anxiety Disor ders      1947 history, examination, and appropriate laboratory studies will help differentiate the disorders. Strongly consider medical causes of the depressive symptoms in patients with new-onset symptoms of depression, in the elderly, and in those with complex medical problems. CLINICAL FEATURES OF DEPRESSION The most common type of depressive disorder is major depressive disorder. Clinical features are listed in Table 289-2. Depressive disorders are often unrecognized in the ED, as the investigation of somatic complaints usually takes priority during patient evaluation. 24,25 Vague complaints and repeat ED visits,26 especially in patients with nonspecific abdominal pain,27 suggest the need for additional questioning regarding symptoms of depression. The two simple questions in the Patient Health Questionnaire-2 have been validated as a screening tool for depressive disorders in the primary care setting 28 but may also be useful in the ED: 1. During the past month, have you been bothered by feeling down, depressed, or hopeless? 2. During the past month, have you been bothered by little interest or pleasure in doing things? Other screening tools used in the primary care setting include the SAD PERSONS scale, 29-31 Patient Health Questionnaire-9 Self-Assess ment Tool,32 the Geriatric Depression Scale, 33 and the Beck Depression Inventory for Primary Care.34 DETERMINATION OF SUICIDE RISK The most important part of the evaluation of depression is the assessment of suicide risk. Use straightforward, nonjudgmental ques tions regarding the patient’s suicide or homicidal thoughts or intent, and seek corroborative information from family members, friends, law enforcement, EMS, and outside providers. If the patient is at potential risk for harm to self or others, perform a thorough search for weapons, medicines, and potentially harmful items; place the patient in a safe environment with monitoring; and consider initiating a precautionary, safety, or involuntary hold. Complete the appropriate history taking (including potential access to guns) with outside source verification, physical examination to include a mental status evaluation, and laboratory studies. Detailed evaluation of patients with mental health disorders is provided in Chapter 286, “Mental Health Disorders: ED Evaluation and Disposition. ” Alcohol and drug abuse are important suicide risk comorbidities. 35 Patients cannot be adequately evaluated for depression or suicidal intent until they are no longer intoxicated. This does not necessarily mean an alcohol level of 0, but rather a return to normal or baseline cognition. A guide for the evaluation of suicide risk and disposition determi nation in ED patients is provided by the Suicide Prevention Resource Center36 and begins with the Decision Support Tool (Table 289-3). If the patient answers yes to any of the questions in Table 289-3, then an emergency psychiatric consultation is warranted. If all answers are “no, ” then a brief intervention is suggested to include follow-up resources. The Emergency Department Safety Assessment and Follow- Up Evaluation study demonstrated that a brief intervention in the ED, including resources and a follow-up phone call for at-risk patients who are being discharged, showed an absolute reduction in suicide attempt risk by 5%.

suggested to include follow-up resources. The Emergency Department Safety Assessment and Follow- Up Evaluation study demonstrated that a brief intervention in the ED, including resources and a follow-up phone call for at-risk patients who are being discharged, showed an absolute reduction in suicide attempt risk by 5%. TREATMENT OF DEPRESSIVE DISORDERS Antidepressants are usually prescribed by primary care physicians or psychiatrists for depression, neurogenic pain, or smoking cessation. The side effect profiles, potential serious adverse effects, and toxicities of common antidepressants are reviewed in Table 289-4 and in the Toxi cology section of this text. Antidepressant therapy is typically not initi ated in the ED, although resumption of a well-tolerated, recently stopped medication may be considered. Antidepressants take about 2 to 3 weeks to have clinical effects and may initially place a patient at increased risk of suicide. Ideally, ED antidepressant prescriptions should be discussed with the follow-up practitioner and should include an arranged visit within a week. Antidepressants may pose fetal risk, so the risks and benefits during pregnancy and lactation must be weighed carefully under the guidance of a psychiatrist and obstetrician. The major categories of antidepressants in use today are the selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and atypical antidepressants (Table 289-4). Heterocyclic antidepressants and monoamine oxidase inhibitors are used infrequently due to adverse effects and drug–drug interactions.  SELECTIVE SEROTONIN REUPTAKE INHIBITORS AND SEROTONIN-NOREPINEPHRINE REUPTAKE INHIBITORS The mainstays of current antidepressant therapy are the SSRIs and SNRIs, which increase the amount of intrasynaptic serotonin or sero tonin and norepinephrine, respectively. A significant advantage of SSRIs and SNRIs over other classes of antidepressants is their high therapeutic index and favorable side effect profile. Common side effects for the SSRIs include nausea and vomiting, drowsiness, headache, changes in sleep patterns, sexual dysfunction, cognitive dysfunction, and precipitation of mania in bipolar patients. SSRIs may initially increase suicidal ideation, and the U.S. Food and Drug Administration currently requires that all antidepressants carry a black box warning that antidepressants may increase suicide risk in patients <25 years old. When SSRIs are TABLE 289-2 Diagnostic Criteria for Major Depressive Disorder* •  Depressed  mood •  Anhedonia  (decreased interest or pleasure) •  Significant  weight loss or gain •  Insomnia  or hypersomnia •  Psychomotor  retardation or agitation •  Fatigue  or loss of energy •  Feelings  of worthlessness or excessive guilt •  Difficulty  with concentration or indecisiveness •  Suicidal  ideation, with or without a plan *The patient needs to have five or more of the symptoms for 2 weeks; one symptom has to be depressed mood or anhedonia. Symptoms cannot be due to substance abuse or a medical condition. Symptoms must be significant enough to impair normal functioning. Source: Data from Diagnostic and Statistical Manual of Mental Disorders , 5th ed. Arlington, VA: American Psychiatric Association; 2013. TABLE 289-3 Suicide Prevention Resource Center Decision Support Tool 36* Transition question: Confirm suicidal ideation. Have you had recent thoughts of killing yourself? Is there other evidence of suicidal thought, such as reports from family or friends? This confirms that suicide risk exists and one should move forward to questions 1 to 6. A “yes” response to any question below indicates the need for emergency psychiatric consultation. 1. Thoughts of carrying out a plan. Have you been thinking about how you might kill yourself? 2.

ch as reports from family or friends? This confirms that suicide risk exists and one should move forward to questions 1 to 6. A “yes” response to any question below indicates the need for emergency psychiatric consultation. 1. Thoughts of carrying out a plan. Have you been thinking about how you might kill yourself? 2. Suicide intent. Do you have intention of killing yourself? 3. Past suicide attempt. Have you ever tried in the past? 4. Significant mental health conditions. Have you had treatment for mental health problems? 5. Substance use disorder. Do you have a history of alcohol or substance abuse? Have you used drugs or medication for nonmedical reasons in the past month? 6. Irritability/agitation/aggression. Have you been feeling anxious or agitated? Having conflicts or getting into fights? Is there direct evidence of irritability, agitation, or aggression? Source: Suicide Prevention Resource Center. (2015). Caring for adult patients with suicide risk: A consensus guide for emergency departments. Waltham, MA: Education Development Center, Inc. www .sprc.org/ed-guide. Tintinalli_Sec24_p1933-1966.indd 1947 8/2/19 5:19 PM

t evidence of irritability, agitation, or aggression? Source: Suicide Prevention Resource Center. (2015). Caring for adult patients with suicide risk: A consensus guide for emergency departments. Waltham, MA: Education Development Center, Inc. www .sprc.org/ed-guide. Tintinalli_Sec24_p1933-1966.indd 1947 8/2/19 5:19 PM 1948 SECTION 24: Psychosocial Disorders abruptly stopped or rapidly decreased in dosage, a withdrawal syn drome may occur, characterized by flulike symptoms, including nausea, vomiting, fatigue, myalgias, vertigo, headache, insomnia, and paresthe sias. Although these symptoms are not life threatening, they may be very uncomfortable for the patient. SNRIs are very similar to SSRIs in side effect profile, although they may cause elevated blood pressure and result in less sexual dysfunction. Withdrawal may also occur several days after discontinuation or rapid decrease in dosage of an SNRI. Serotonin Syndrome Serotonin syndrome , a potentially lifethreatening adverse drug reaction, may occur in patients taking SSRIs (or any other antidepressant) when used in combination with another agent that has serotonergic activity such as monoamine oxidase inhibi tors, opiates (including tramadol), CNS stimulants (including cocaine, ecstasy), serotonin agonists, St. John’s wort, lithium, dextrometho rphan, risperidone, olanzapine, ondansetron, and metoclopramide. The syndrome is manifested by neuromuscular hyperactivity (tremor, myoclonus, hyperreflexia/clonus, seizures), altered mental status (restlessness, agitation, excitement, confusion), autonomic hyperactivity (tachycardia, tachypnea, fever, diaphoresis), and GI irritability (nausea, vomiting, diarrhea). Treatment consists of discontinuing the affecting agents, administering benzodiazepines, and supportive care.  ATYPICAL ANTIDEPRESSANTS Atypical antidepressants include bupropion, mirtazapine, and tra zodone. Bupropion, a dopamine reuptake inhibitor, is also used for smoking cessation.

ty (nausea, vomiting, diarrhea). Treatment consists of discontinuing the affecting agents, administering benzodiazepines, and supportive care.  ATYPICAL ANTIDEPRESSANTS Atypical antidepressants include bupropion, mirtazapine, and tra zodone. Bupropion, a dopamine reuptake inhibitor, is also used for smoking cessation. It typically causes less weight gain and less sexual TABLE 289-4 Commonly Used Antidepressants in the United States Agent (Generic/Brand Names) Mechanism of Action Common Adverse Effects of Class Starting Dose Comments Selective serotonin reuptake inhibitors (SSRIs) Block presynaptic serotonin uptake N/V, drowsiness, HA, dizziness, insomnia, agitation, mania, paresthesias, sexual/cognitive dysfunction, weight gain Insufficient clinical studies to determine safety in pregnancy Citalopram/Celexa     10–20 milligrams once a day Lower doses if anxiety prominent Fluoxetine/Prozac     10–20 milligrams once a day First line for children/adolescents Fluvoxamine/Luvox     50 milligrams at night More sedating, shorter half-life Paroxetine/Paxil     10–20 milligrams once a day More anticholinergic, more sedating, more withdrawal symptoms Sertraline/Zoloft     25–50 milligrams once a day Okay in breastfeeding patients Escitalopram/Lexapro     5–10 milligrams once a day Okay in breastfeeding patients Serotonin norepinephrine reuptake inhibitors (SNRIs) Blocks presynaptic serotonin and norepinephrine uptake Same as for SSRIs, except less sexual dysfunction, elevated BP, urinary hesitancy/retention Insufficient clinical studies to determine safety in pregnancy Duloxetine/Cymbalta     30 milligrams once a day More withdrawal symptoms; may increase anxiety Venlafaxine/Effexor     37.5–50 milligrams once a day More withdrawal symptoms Desvenlafaxine/Pristiq     50 milligrams once a day Synthetic active metabolite of venlafaxine Atypicals Bupropion/Wellbutrin , Zyban Bupropion/Wellbutrin sustained release Bupropion/Wellbutrin extended release Dopamine and norepinephrine reuptake inhibitor Seizures, dry mouth, nausea, agitation and irritability, aggressive behavior, insomnia, HA 50–75 milligrams 3 times a day 150 milligrams once a day, increase to twice a day after 3 days When used with linezolid can precipitate serotonin syndrome Seizures associated with doses >450 milligrams; contraindicated if underlying seizure disorders or risk factors for seizure; history of anorexia or bulimia; abrupt discontinuation of alcohol, benzodiazepines, or antiepileptic drugs; less sexual dysfunction, less weight gain, used for smoking cessation Mirtazapine/Remeron DA and NE reuptake inhibitor Increases release of NE, serotonin by antagonizing inhibitor receptors Dry mouth, nausea, restlessness, insomnia, HA, pharyngitis, constipation, dizziness, somnolence, weight gain, malaise 15 milligrams once a day More weight gain, more sedation, good choice for oncology patients with failure to thrive Trazodone/Desyrel Serotonin antagonist and reuptake inhibitor; antagonist at histamine and α-adrenergic receptors Marked sedation, priapism, orthostatic hypotension, ventricular dysrhythmias in patients with known cardiac disease 50 milligrams once a day Also used in insomnia, prominent sedation Heterocyclics Blockage of presynaptic reuptake of NE, serotonin Cardiotoxic: prolonged QTc /AV block Anticholinergic: sedation, dry mouth, tachycardia, constipation

orthostatic hypotension, ventricular dysrhythmias in patients with known cardiac disease 50 milligrams once a day Also used in insomnia, prominent sedation Heterocyclics Blockage of presynaptic reuptake of NE, serotonin Cardiotoxic: prolonged QTc /AV block Anticholinergic: sedation, dry mouth, tachycardia, constipation Amitriptyline/Elavil     25 milligrams once a day Also used for chronic/neurogenic pain control, low therapeutic index Nortriptyline/Pamelor     25 milligrams at night Metabolite of amitriptyline, although less sedating Abbreviations: AV = atrioventricular; BP = blood pressure; DA = dopamine; HA = headache; NE = norepinephrine; N/V = nausea and vomiting. Tintinalli_Sec24_p1933-1966.indd 1948 8/2/19 5:19 PM

ntrol, low therapeutic index Nortriptyline/Pamelor     25 milligrams at night Metabolite of amitriptyline, although less sedating Abbreviations: AV = atrioventricular; BP = blood pressure; DA = dopamine; HA = headache; NE = norepinephrine; N/V = nausea and vomiting. Tintinalli_Sec24_p1933-1966.indd 1948 8/2/19 5:19 PM CHAPTER 289:  Mood and Anxiety Disor ders      1949 dysfunction than other antidepressants. Trazodone is a serotonin antagonist and reuptake inhibitor that is more sedating than other antidepressants with less anticholinergic effects and is commonly used as a sleep aid. Mirtazapine is related to the heterocyclic antidepressants, tends to cause weight gain, and has a more rapid onset of action of about 1 week. As with the other antidepressants, these medications may cause withdrawal when abruptly stopped. Although not approved by the U.S. Food and Drug Administration, ketamine is being studied for treatment-refractory depression, as its onset of action is much faster than current therapies. 38 Ketamine’s longterm efficacy and side effect profile need further investigation. 39  HETEROCYCLIC ANTIDEPRESSANTS Heterocyclic antidepressants, once commonly used for depression, are prescribed less often now due to low therapeutic index, many possible side effects at prescribed doses, and dangerous overdose potential. The side effects are mainly anticholinergic related and cardiotoxic, including prolonged QT c interval and atrioventricular block. One agent in this category, amitriptyline, is commonly prescribed for chronic or neuro genic pain.  MONOAMINE OXIDASE INHIBITORS Monoamine oxidase inhibitors are rarely used first line in treating depression because of potentially lethal drug–drug and dietary interac tions. Monoamine oxidase inhibitors block oxidative deamination of tyramine and may precipitate a sometimes fatal hypertensive crisis when certain drugs (sympathomimetic amines, levodopa, narcotics, and heterocyclic antidepressants) or tyramine-containing foods or beverages (aged cheese, beer, and wine) are co-ingested. DISPOSITION The disposition of the depressed patient is based on the assessment of harm to self or others, the ability to care for one’s self, level of supportive environment at home, and complicating medical or substance abuse problems. Any combination of the above may require psychiatric consultation for admission evaluation. Patients who may safely go home need specific, timely follow-up plans with a primary care provider, psychiatrist, or other appropriate counselor. “No-harm” contracts between ED providers and patients are not recommended. Two helpful websites for both practitioners and patients are www.samhsa.gov (Substance Abuse and Mental Health Services Administration) and www.sprc.org (Suicide Prevention Resource Center). An ED-specific guide regarding safe patient disposition is found at www.sprc.org/edguide. SPECIAL CONSIDERATIONS Mood disorders in the elderly are discussed in Chapter 288, “Mental Health Disorders of the Elderly, ” and mood disorders in children are discussed in Chapter 149, “Behavioral Disorders in Children. ”  POSTPARTUM DEPRESSION Postpartum depression affects 10% to 15% of women within 1 year of delivery, 40 but typically occurs within the first month. In one urban pediatric ED, one third of postpartum patients screened positive for depression. 41 Symptoms are extreme fatigue, ambivalent feelings about caring for the newborn, guilt about those feelings, and the other classic major depressive disorder symptoms. Low energy is in excess of the normal fatigue felt by most postpartum women. Risk factors for postpartum depression are prior depression, young age, low socioeconomic status, and partner abuse. 42 Recognition in the ED is important to identify and mitigate infant vulnerability.

assic major depressive disorder symptoms. Low energy is in excess of the normal fatigue felt by most postpartum women. Risk factors for postpartum depression are prior depression, young age, low socioeconomic status, and partner abuse. 42 Recognition in the ED is important to identify and mitigate infant vulnerability.  CROSS-CULTURAL ISSUES Surveys of depressive disorders show a wide range of prevalence across diverse cultures, although it is unclear how much of this difference is due to each culture’s definition and expressions of depressive disorders. Non-Western cultures may emphasize somatic symptoms of depres sion, whereas in Western cultures, it may be more acceptable to express psychological complaints. Avoid stereotyping, but acknowledge the possibility of cultural influence in symptom description.  BIPOLAR DISORDERS Bipolar disorders, previously called manic-depressive disorder, are the other major type of mood disorder and are characterized by mania, typically cycling with periods of depression. The depressive periods tend to last longer than the manic periods. Mania can be diagnosed if there is a distinct period of elevated, expansive, or irritable mood for at least 1 week. 43 This behavior must be associated with three of the following symptoms: inflated self-esteem or grandiosity, decreased need for sleep, pressured speech, flight of ideas or racing thoughts, distractibility, increase in goal-directed activity or psychomotor agitation, or involve ment in high-risk activities (often sexual or financial in nature). These symptoms must cause marked impairment in usual functioning and must not be attributable to medical disease or substance abuse. 43 Mania may exist with or without psychotic features. Bipolar disorder is divided into several subtypes including bipolar I (mania, with or without major depressive episodes), bipolar II (intermittent hypomania with depres sive episodes), and cyclothymic (recurrent dysthymic and hypomania episodes). A “mixed” state is one in which the patient meets the criteria for a manic episode plus depressive disorder symptoms for at least 1 week. Bipolar disorders affect men and women equally and have no race/ethnicity predilection. PATHOPHYSIOLOGY The pathogenesis of bipolar disorder is likely multifactorial. There is a strong genetic component, with about 50% of all bipolar patients having a parent with a mood disorder. 44 The concordance rate is 40% in monozygotic twins compared with 6% in dizygotic twins.45 Areas of the brain involved in normal emotional responses, ventral prefrontal networks and limbic regions, demonstrate decreased connectivity on functional MRIs in bipolar patients. 45 Environmental factors, such as negative life events, increase the likelihood of developing bipolar disorder in predis posed persons.46 CLINICAL FEATURES The manic patient may seem “fun, ” energetic, and expansive, but beware; the patient may quickly become irritable or even hostile if plans are antagonized by providers or family members. Manic patients may experience grandiose or delusional ideas and loss of cognitive abilities, with little insight. The initial evaluation of the manic patient is similar to that of patients with other psychiatric disorders and is discussed in Chapter 286. Consider nonpsychiatric causes of agitation, such as thyroid disease, acute toxic ingestions (cocaine, stimulants), and drug withdrawal (antidepressants, alcohol, benzodiazepines). Consider other psychiatric diseases, such as schizophrenia and attention deficit disorder, as features may mimic the manic phase of bipolar disorder. Patients exhibiting mania should be questioned about a previous history of depressive disorder, because most bipolar disorder patients are initially diagnosed with depressive disorder.

psychiatric diseases, such as schizophrenia and attention deficit disorder, as features may mimic the manic phase of bipolar disorder. Patients exhibiting mania should be questioned about a previous history of depressive disorder, because most bipolar disorder patients are initially diagnosed with depressive disorder. TREATMENT OF BIPOLAR DISORDER Treatment for bipolar disorder is complex, often requires more than one medication, and thus should not be initiated by the emergency physi cian, except for treatment of acute agitation (see Chapter 287, “ Acute Agitation”) or to restart lithium or an anticonvulsant medication that has been recently stopped. Medications to treat the acutely manic patient include “mood stabilizers, ” such as lithium, valproic acid, or carba mazepine, with or without the addition of an antipsychotic (such as haloperidol) or a benzodiazepine (Table 289-5). The same mood sta bilizers may also be used for maintenance therapy. Lithium and valproic Tintinalli_Sec24_p1933-1966.indd 1949 8/2/19 5:19 PM 1950 SECTION 24: Psychosocial Disorders TABLE 289-5 Medications Used for Bipolar Disorder Generic Name Brand Name Mechanism of Action Side Effects (BLACK BOX WARNING IN CAPS) Usual Starting Dose Comments Lithium carbonate Eskalith , Lithonate , Lithotabs ? increase NE function ? increase serotonin function TOXICITY closely related to serum lithium levels: diarrhea, vomiting, tremor, mild ataxia, drowsiness or muscular weakness. Initially: nausea, dry mouth, excessive thirst, tremors, polyuria, peripheral edema, cognitive impairment Long-term: polyuria, diabetes insipidus, goiter, hypothyroidism, rashes, leukocytosis 300 milligrams 2 or 3 times a day Effective for both acute and maintenance therapy Narrow therapeutic window; toxicity common; symptoms may be delayed up to 48 h in acute overdose Avoid giving with NSAIDs, ACE inhibitors, or diuretics to avoid toxicity.

, diabetes insipidus, goiter, hypothyroidism, rashes, leukocytosis 300 milligrams 2 or 3 times a day Effective for both acute and maintenance therapy Narrow therapeutic window; toxicity common; symptoms may be delayed up to 48 h in acute overdose Avoid giving with NSAIDs, ACE inhibitors, or diuretics to avoid toxicity. Dose is lower in elderly and patients with renal dysfunction Valproic acid Depakene , Depakote  (12 h), Depakote Sprinkles  (12 h), Depacon  (IV) Antiepileptic; enhances transmission of GABA HEPATOTOXICITY, FETAL RISK, PANCREATITIS, weight gain, nausea, vomiting, hair loss, bruising, tremor, thrombocytopenia 250 milligrams 2 or 3 times a day Effective for both acute and maintenance therapy Can monitor drug levels Monitor liver and platelet function May be used alone to treat BD, or in combination with antipsychotic or lithium Carbamazepine Tegretol Antiepileptic; stabilizes sodium channels, potentiates GABA receptors AGRANULOCYTOSIS, STEVENS-JOHNSON SYNDROME/TOXIC EPIDERMAL NECROLYSIS, nausea, vomiting, hyponatremia, rash, leukopenia 100–200 milligrams 1 or 2 times a day Effective for acute or maintenance therapy Can monitor drug levels Monitor LFTs May be better in rapid cycling disorder Do not use with antipsychotics Many drug interactions with similarly livermetabolized medications OCP failure Lamotrigine Lamictal Antiepileptic; sodium channel blockade STEVENS-JOHNSON SYNDROME/TOXIC EPIDERMAL NECROLYSIS—rare complications but potentially fatal; nausea, vomiting, fatigue, dizziness 25 milligrams once a day (unless on other antiepileptic medication) Used with more severe depressive symptoms Dose adjustment required with other antiepileptic Progestin-only OCP failure Requires slower dose titration when used with valproic acid Olanzapine Zyprexa Antipsychotic; muscarinic; dopamine and serotonin antagonist INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS, sedation, constipation, dry mouth, glucose intolerance, orthostatic hypotension, hyperlipidemia 2.5–5.0 milligrams 1 or 2 times a day May be used in combination with lithium or valproic acid Injection cannot be given within 1 h of injectable benzodiazepine Quetiapine Seroquel Antipsychotic; dopamine, serotonin, and adrenergic antagonist INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS, SUICIDAL THOUGHTS AND BEHAVIORS WITH ANTIDEPRESSANT DRUGS, headache, dry mouth, weight gain, sedation, dizziness, orthostatic hypotension 25–50 milligrams 1 or 2 times a day May be used in combination with lithium or valproic acid Risperidone Risperdal Antipsychotic; serotonin and dopamine antagonist INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS, extrapyramidal side effects, prolactin elevation, sedation, dyspepsia, nausea, weight gain 0.25–1 milligram 1 or 2 times a day May be used with lithium or valproic acid Use lower doses in elderly due to orthostasis risk Aripiprazole Abilify Antipsychotic; partial agonist of dopamine/serotonin receptors; antagonist of other serotonin receptors INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS, SUICIDAL THOUGHTS AND BEHAVIORS WITH ANTIDEPRESSANT DRUGS, headache, nausea, vomiting, extrapyramidal symptoms, especially akathisia 2–10 milligrams once a day May be used with lithium or valproic acid Ziprasidone Geodon Antipsychotic; serotonin and dopamine antagonist; adrenergic antagonist; agonist at other serotonin receptors INCREASED RISK OF DEATH IN DEMENTIA- RELATED PSYCHOSIS; rash, weight gain, constipation, nausea, tremor, extrapyramidal side effects, sedation, vision changes 40 milligrams twice a day May be used with lithium or valproic acid Lurasidone Latuda Antipsychotic; serotonin and dopamine antagonist; adrenergic antagonist; agonist at other serotonin rece

ENTIA- RELATED PSYCHOSIS; rash, weight gain, constipation, nausea, tremor, extrapyramidal side effects, sedation, vision changes 40 milligrams twice a day May be used with lithium or valproic acid Lurasidone Latuda Antipsychotic; serotonin and dopamine antagonist; adrenergic antagonist; agonist at other serotonin rece ptors INCREASED RISK OF DEATH IN DEMENTIA- RELATED PSYCHOSIS, nausea, vomiting, extrapyramidal side effects, sedation, anxiety 20 milligrams once a day Abbreviations: ACE = angiotensin-converting enzyme; BD = bipolar disorder; GABA = γ-aminobutyric acid; LFTs = liver function tests; NE = norepinephrine; OCP = oral contraceptive pill. Tintinalli_Sec24_p1933-1966.indd 1950 8/2/19 5:19 PM

ptors INCREASED RISK OF DEATH IN DEMENTIA- RELATED PSYCHOSIS, nausea, vomiting, extrapyramidal side effects, sedation, anxiety 20 milligrams once a day Abbreviations: ACE = angiotensin-converting enzyme; BD = bipolar disorder; GABA = γ-aminobutyric acid; LFTs = liver function tests; NE = norepinephrine; OCP = oral contraceptive pill. Tintinalli_Sec24_p1933-1966.indd 1950 8/2/19 5:19 PM CHAPTER 289:  Mood and Anxiety Disor ders      1951 acid may be combined with an atypical antipsychotic medication for bipolar maintenance therapy. Lithium has a narrow therapeutic index and requires frequent monitoring. Patients taking lithium must avoid dehydration to prevent toxic levels from accumulating. The efficacy of antidepressant use in bipolar disorder is unclear because of the possible risk of precipitating mania. DISPOSITION Disposition of the bipolar disorder patient is similar to that of the depressive disorder patient, including careful assessment of suicide risk. Lack of insight to the loss of cognitive abilities and delusional ideas may put the patient at significant risk for self-harm, though not explicitly expressed. Bipolar disorder patients who are exhibiting psychotic features or are at risk for harm to self or others need psychiatrist evaluation for admission.  ANXIETY DISORDERS Anxiety is the most common mental health disorder overall, although second behind mood disorder in ED presentation, 1 accounting for approximately 1% of all ED visits. ED patients with anxiety are more likely to be women, nonelderly, and non-Hispanic whites. 48 Patients with anxiety disorders seek medical care about twice as often as non-anxiety patients and are high users of the ED. 49,50 This is partly due to the fact that anxiety disorders, especially panic disorder, may mimic life-threatening conditions, such as acute coronary syndrome. Anxiety disorders are often associated with mood disorders, 51 alcohol abuse,52 personality disorders,53 and other anxiety disorders.51 Anxiety disorders are characterized by excessive fear or worry about real or imagined events. Fears often adversely impact both physical and psychological health. PATHOPHYSIOLOGY The pathophysiology of anxiety disorder is multifactorial. Dysregula tion of γ-aminobutyric acid inhibitory neurotransmission and increased excitatory neurotransmitters, specifically serotonin, have been impli cated and may explain the utility of SSRIs and benzodiazepines to treat anxiety disorder. Hyperactivity in the limbic regions, especially the amygdala, and the inability of executive cortex areas to modulate the limbic response to stimuli may contribute. 54 There appears to be a genetic role, especially in panic disorder,44 although it does not seem to be as strong a predictor as in other psychological illnesses. Exposure to stressful events, especially in childhood, is a risk factor for development of anxiety disorder. 55 A specific stressful event precedes the development of posttraumatic stress disorder. CLINICAL FEATURES Anxiety disorders are a heterogeneous group, although they share many common somatic and cognitive symptoms ( Table 289-6), with timing, severity, and associated beliefs separating the different types. General ized anxiety disorder, panic disorder, and posttraumatic stress disorder are discussed here.  GENERALIZED ANXIETY DISORDER The Diagnostic and Statistical Manual of Mental Disorders, 5th edition, defines patients with generalized anxiety disorder as having chronic excessive anxiety and worry about real or imagined events, occurring more days than not, for at least 6 months. 43 The symptoms cause sig nificant impairment in daily functioning and are generally recognized by the patient as excessive and inappropriate.

ines patients with generalized anxiety disorder as having chronic excessive anxiety and worry about real or imagined events, occurring more days than not, for at least 6 months. 43 The symptoms cause sig nificant impairment in daily functioning and are generally recognized by the patient as excessive and inappropriate. The anxiety and worry are associated with three or more of the following symptoms: restlessness or being keyed up or on edge, irritability, muscle tension, being eas ily fatigued, difficulty concentrating or “mind going blank, ” and sleep disturbance. Patients with generalized anxiety disorder may have inter spersed, more intense panic attacks.  PANIC DISORDER Panic disorder (“panic attack”) is a common, often chronic illness characterized by recurrent, spontaneous panic attacks. Panic attacks are short-lived episodes of anxiety or intense fear accompanied by a range of somatic symptoms (commonly cardiac, GI, or neurologic), usually peaking within 10 minutes and but that may last up to an hour. The Diagnostic and Statistical Manual of Mental Disorders, 5th edition, criteria for panic disorder also stipulate that the panic attack must be followed by 1 month of persistent concern about having additional attacks, worry about the implications of the attack or its consequences, or a significant change in behavior related to the attacks. It cannot be better accounted for by another psychiatric or medical disorder. 43 Panic disorder may occur with or without agoraphobia (irrational fear of crowded spaces); panic disorder with agoraphobia may be severely disabling both socially and occupationally. Because of the often debilitating symptoms, panic disorder patients are high users of the ED. In one Canadian study, 25% of patients presenting to the ED with chest pain were ultimately diagnosed with panic disorder. 57 Underrecognition of anxiety disorders, which are treatable, continues the cycle of overutilization of medical resources. Panic disorder may have an association with several medi cal disorders, including asthma, 58 hypertension, 59 interstitial cystitis, 60 migraine headaches,61 and cardiovascular disease.62 The long-held association between mitral valve prolapse is less clear.63  POSTTRAUMATIC STRESS DISORDER/ACUTE STRESS DISORDER Posttraumatic stress disorder (PTSD) patients have all experienced or witnessed an intense traumatic event, such as rape, combat, natural disaster, child abuse, chronic exposure to an extreme stressor, or motor vehicle crash. The prevalence of PTSD within the first several months after a motor vehicle crash is 25% to 40%, and in 15% of patients, PTSD will persist. 64 Elderly patients are at higher risk, with 21% having significant PTSD at 6 months.65 Diagnostic criteria state that the patient has to be exposed to the stressor and that the response involved intense fear, hopelessness, or horror.43 This is followed by “intrusive recollection, ” which would include one or more of the following: recurrent distressing dreams of the event, acting or feeling as if the event were recurring (“flashbacks”), and intense psychological distress with or without physiologic reactivity upon exposure to internal or external cues that symbolize the traumatic event. There may also be avoidance of stimuli associated with the trauma and a numbing of general responsiveness. Hyperarousal demonstrated by hypervigilance or exaggerated startle may occur. The symptoms have to be present for at least a month and cause significant impairment in functioning and cannot be better explained by another psychiatric or medical cause. 43 Acute stress disorder is diagnosed when the same symptoms of PTSD last between 2 days and 1 month.

ervigilance or exaggerated startle may occur. The symptoms have to be present for at least a month and cause significant impairment in functioning and cannot be better explained by another psychiatric or medical cause. 43 Acute stress disorder is diagnosed when the same symptoms of PTSD last between 2 days and 1 month. Feinberg and colleagues found a direct correlation between development of PTSD after a motor vehicle crash and persistent moderate to severe axial pain. 66 At discharge of TABLE 289-6 Symptoms of Anxiety Disorders Physical Symptoms Cognitive Symptoms Palpitations, pounding heart, tachycardia Fear of losing control or “going crazy” Sweating Derealization (feeling of unreality) or depersonalization (feeling detached from oneself) Trembling or shaking Inability to concentrate Feeling of choking Obsessions and compulsions Chest pain or discomfort Feeling generally ill at ease Nausea or abdominal distress Fear of dying Feeling dizzy, unsteady, lightheaded, or faint Paresthesias Chills or hot flashes Difficulty sleeping Increased muscle aches or soreness Tintinalli_Sec24_p1933-1966.indd 1951 8/2/19 5:19 PM