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Mental and Behavioral Health The U.S. Preventive Services Task Force (USPSTF) recom- TABLE 45. Factors That Increase Risk for Suicide mends screening all patients for depression; adequate systems | Chronic suicidal ideation should be in place to ensure accurate diagnosis, effective treat- | Major mental illness or personality disorder ment, and appropriate follow-up. For such general population | History of prior suicide attempts screening, the two-question PHQ-?2 is effective and easy to use. If a patient provides a positive response to either of the ques- History of substance use disorder tions (“Over the past 2 weeks, have you felt down, depressed, | Chronic pain j

The U.S. Preventive Services Task Force (USPSTF) recom- TABLE 45. Factors That Increase Risk for Suicide mends screening all patients for depression; adequate systems | Chronic suicidal ideation should be in place to ensure accurate diagnosis, effective treat- | Major mental illness or personality disorder ment, and appropriate follow-up. For such general population | History of prior suicide attempts screening, the two-question PHQ-?2 is effective and easy to use. If a patient provides a positive response to either of the ques- History of substance use disorder tions (“Over the past 2 weeks, have you felt down, depressed, | Chronic pain j or hopeless?” and “Over the past 2 weeks, have you felt little | Chronic medical condition interest or pleasure in doing things?”), further investigation | Limited coping skills for depression, including inquiring about suicidal ideation, is | Unstable or turbulent psychosocial status (e.g., unstable warranted. | housing, erratic relationships, marginal employment) Depressed patients must be specifically asked about Limited ability to identify reasons for living suicidal ideation and behavior. Positive or equivocal answers Information from Sall J, Brenner L, Millikan Bell AM, et al. Assessment and should be followed by questions related to means and management of patients at risk for suicide: synopsis of the 2019 U.S. Department intent; assessment of risk factors for suicide (Table 45); and of Veterans Affairs and U.S. Department of Defense clinical practice guidelines. Ann Intern Med. 2019;171:343-53. [PMID: 31450237] doi:10.7326/M19-0687 the development of a plan for evaluation and care, which may include referral to the emergency department or a psychiatrist. Symptoms of MDD and other mood disorders are outlined in Table 46. Diagnosis For a diagnosis of MDD, symptoms cannot be attributable to Major Depressive Disorder a medical condition, medication, or substance use and must cause The DSM-5 criteria for diagnosis of major depressive disorder significant functional impairment. Clinicians should screen (MDD) require the presence of at least five symptoms, at least patients with depression for any history of elevated mood, which one of which must be depressed mood or anhedonia, nearly suggests bipolar disorder. Prescribing antidepressant monother- every day or all of the time during the same 2-week period. apy to a patient with bipolar disorder may precipitate mania.

or hopeless?” and “Over the past 2 weeks, have you felt little | Chronic medical condition interest or pleasure in doing things?”), further investigation | Limited coping skills for depression, including inquiring about suicidal ideation, is | Unstable or turbulent psychosocial status (e.g., unstable warranted. | housing, erratic relationships, marginal employment) Depressed patients must be specifically asked about Limited ability to identify reasons for living suicidal ideation and behavior. Positive or equivocal answers Information from Sall J, Brenner L, Millikan Bell AM, et al. Assessment and should be followed by questions related to means and management of patients at risk for suicide: synopsis of the 2019 U.S. Department intent; assessment of risk factors for suicide (Table 45); and of Veterans Affairs and U.S. Department of Defense clinical practice guidelines. Ann Intern Med. 2019;171:343-53. [PMID: 31450237] doi:10.7326/M19-0687 the development of a plan for evaluation and care, which may include referral to the emergency department or a psychiatrist. Symptoms of MDD and other mood disorders are outlined in Table 46. Diagnosis For a diagnosis of MDD, symptoms cannot be attributable to Major Depressive Disorder a medical condition, medication, or substance use and must cause The DSM-5 criteria for diagnosis of major depressive disorder significant functional impairment. Clinicians should screen (MDD) require the presence of at least five symptoms, at least patients with depression for any history of elevated mood, which one of which must be depressed mood or anhedonia, nearly suggests bipolar disorder. Prescribing antidepressant monother- every day or all of the time during the same 2-week period. apy to a patient with bipolar disorder may precipitate mania. TABLE 46. Symptom Criteria for Diagnosis of Common Mood Disorders

or hopeless?” and “Over the past 2 weeks, have you felt little | Chronic medical condition interest or pleasure in doing things?”), further investigation | Limited coping skills for depression, including inquiring about suicidal ideation, is | Unstable or turbulent psychosocial status (e.g., unstable warranted. | housing, erratic relationships, marginal employment) Depressed patients must be specifically asked about Limited ability to identify reasons for living suicidal ideation and behavior. Positive or equivocal answers Information from Sall J, Brenner L, Millikan Bell AM, et al. Assessment and should be followed by questions related to means and management of patients at risk for suicide: synopsis of the 2019 U.S. Department intent; assessment of risk factors for suicide (Table 45); and of Veterans Affairs and U.S. Department of Defense clinical practice guidelines. Ann Intern Med. 2019;171:343-53. [PMID: 31450237] doi:10.7326/M19-0687 the development of a plan for evaluation and care, which may include referral to the emergency department or a psychiatrist. Symptoms of MDD and other mood disorders are outlined in Table 46. Diagnosis For a diagnosis of MDD, symptoms cannot be attributable to Major Depressive Disorder a medical condition, medication, or substance use and must cause The DSM-5 criteria for diagnosis of major depressive disorder significant functional impairment. Clinicians should screen (MDD) require the presence of at least five symptoms, at least patients with depression for any history of elevated mood, which one of which must be depressed mood or anhedonia, nearly suggests bipolar disorder. Prescribing antidepressant monother- every day or all of the time during the same 2-week period. apy to a patient with bipolar disorder may precipitate mania. TABLE 46. Symptom Criteria for Diagnosis of Common Mood Disorders Major Depressive Disorder

or hopeless?” and “Over the past 2 weeks, have you felt little | Chronic medical condition interest or pleasure in doing things?”), further investigation | Limited coping skills for depression, including inquiring about suicidal ideation, is | Unstable or turbulent psychosocial status (e.g., unstable warranted. | housing, erratic relationships, marginal employment) Depressed patients must be specifically asked about Limited ability to identify reasons for living suicidal ideation and behavior. Positive or equivocal answers Information from Sall J, Brenner L, Millikan Bell AM, et al. Assessment and should be followed by questions related to means and management of patients at risk for suicide: synopsis of the 2019 U.S. Department intent; assessment of risk factors for suicide (Table 45); and of Veterans Affairs and U.S. Department of Defense clinical practice guidelines. Ann Intern Med. 2019;171:343-53. [PMID: 31450237] doi:10.7326/M19-0687 the development of a plan for evaluation and care, which may include referral to the emergency department or a psychiatrist. Symptoms of MDD and other mood disorders are outlined in Table 46. Diagnosis For a diagnosis of MDD, symptoms cannot be attributable to Major Depressive Disorder a medical condition, medication, or substance use and must cause The DSM-5 criteria for diagnosis of major depressive disorder significant functional impairment. Clinicians should screen (MDD) require the presence of at least five symptoms, at least patients with depression for any history of elevated mood, which one of which must be depressed mood or anhedonia, nearly suggests bipolar disorder. Prescribing antidepressant monother- every day or all of the time during the same 2-week period. apy to a patient with bipolar disorder may precipitate mania. TABLE 46. Symptom Criteria for Diagnosis of Common Mood Disorders Major Depressive Disorder Five or more of the symptoms listed below (at least one of the symptoms must be depressed mood or anhedonia) nearly every day or all of the time during the same 2-wk period:

or hopeless?” and “Over the past 2 weeks, have you felt little | Chronic medical condition interest or pleasure in doing things?”), further investigation | Limited coping skills for depression, including inquiring about suicidal ideation, is | Unstable or turbulent psychosocial status (e.g., unstable warranted. | housing, erratic relationships, marginal employment) Depressed patients must be specifically asked about Limited ability to identify reasons for living suicidal ideation and behavior. Positive or equivocal answers Information from Sall J, Brenner L, Millikan Bell AM, et al. Assessment and should be followed by questions related to means and management of patients at risk for suicide: synopsis of the 2019 U.S. Department intent; assessment of risk factors for suicide (Table 45); and of Veterans Affairs and U.S. Department of Defense clinical practice guidelines. Ann Intern Med. 2019;171:343-53. [PMID: 31450237] doi:10.7326/M19-0687 the development of a plan for evaluation and care, which may include referral to the emergency department or a psychiatrist. Symptoms of MDD and other mood disorders are outlined in Table 46. Diagnosis For a diagnosis of MDD, symptoms cannot be attributable to Major Depressive Disorder a medical condition, medication, or substance use and must cause The DSM-5 criteria for diagnosis of major depressive disorder significant functional impairment. Clinicians should screen (MDD) require the presence of at least five symptoms, at least patients with depression for any history of elevated mood, which one of which must be depressed mood or anhedonia, nearly suggests bipolar disorder. Prescribing antidepressant monother- every day or all of the time during the same 2-week period. apy to a patient with bipolar disorder may precipitate mania. TABLE 46. Symptom Criteria for Diagnosis of Common Mood Disorders Major Depressive Disorder Five or more of the symptoms listed below (at least one of the symptoms must be depressed mood or anhedonia) nearly every day or all of the time during the same 2-wk period: Depressed mood

or hopeless?” and “Over the past 2 weeks, have you felt little | Chronic medical condition interest or pleasure in doing things?”), further investigation | Limited coping skills for depression, including inquiring about suicidal ideation, is | Unstable or turbulent psychosocial status (e.g., unstable warranted. | housing, erratic relationships, marginal employment) Depressed patients must be specifically asked about Limited ability to identify reasons for living suicidal ideation and behavior. Positive or equivocal answers Information from Sall J, Brenner L, Millikan Bell AM, et al. Assessment and should be followed by questions related to means and management of patients at risk for suicide: synopsis of the 2019 U.S. Department intent; assessment of risk factors for suicide (Table 45); and of Veterans Affairs and U.S. Department of Defense clinical practice guidelines. Ann Intern Med. 2019;171:343-53. [PMID: 31450237] doi:10.7326/M19-0687 the development of a plan for evaluation and care, which may include referral to the emergency department or a psychiatrist. Symptoms of MDD and other mood disorders are outlined in Table 46. Diagnosis For a diagnosis of MDD, symptoms cannot be attributable to Major Depressive Disorder a medical condition, medication, or substance use and must cause The DSM-5 criteria for diagnosis of major depressive disorder significant functional impairment. Clinicians should screen (MDD) require the presence of at least five symptoms, at least patients with depression for any history of elevated mood, which one of which must be depressed mood or anhedonia, nearly suggests bipolar disorder. Prescribing antidepressant monother- every day or all of the time during the same 2-week period. apy to a patient with bipolar disorder may precipitate mania. TABLE 46. Symptom Criteria for Diagnosis of Common Mood Disorders Major Depressive Disorder Five or more of the symptoms listed below (at least one of the symptoms must be depressed mood or anhedonia) nearly every day or all of the time during the same 2-wk period: Depressed mood Anhedonia

or hopeless?” and “Over the past 2 weeks, have you felt little | Chronic medical condition interest or pleasure in doing things?”), further investigation | Limited coping skills for depression, including inquiring about suicidal ideation, is | Unstable or turbulent psychosocial status (e.g., unstable warranted. | housing, erratic relationships, marginal employment) Depressed patients must be specifically asked about Limited ability to identify reasons for living suicidal ideation and behavior. Positive or equivocal answers Information from Sall J, Brenner L, Millikan Bell AM, et al. Assessment and should be followed by questions related to means and management of patients at risk for suicide: synopsis of the 2019 U.S. Department intent; assessment of risk factors for suicide (Table 45); and of Veterans Affairs and U.S. Department of Defense clinical practice guidelines. Ann Intern Med. 2019;171:343-53. [PMID: 31450237] doi:10.7326/M19-0687 the development of a plan for evaluation and care, which may include referral to the emergency department or a psychiatrist. Symptoms of MDD and other mood disorders are outlined in Table 46. Diagnosis For a diagnosis of MDD, symptoms cannot be attributable to Major Depressive Disorder a medical condition, medication, or substance use and must cause The DSM-5 criteria for diagnosis of major depressive disorder significant functional impairment. Clinicians should screen (MDD) require the presence of at least five symptoms, at least patients with depression for any history of elevated mood, which one of which must be depressed mood or anhedonia, nearly suggests bipolar disorder. Prescribing antidepressant monother- every day or all of the time during the same 2-week period. apy to a patient with bipolar disorder may precipitate mania. TABLE 46. Symptom Criteria for Diagnosis of Common Mood Disorders Major Depressive Disorder Five or more of the symptoms listed below (at least one of the symptoms must be depressed mood or anhedonia) nearly every day or all of the time during the same 2-wk period: Depressed mood Anhedonia Insomnia/hypersomnia

or hopeless?” and “Over the past 2 weeks, have you felt little | Chronic medical condition interest or pleasure in doing things?”), further investigation | Limited coping skills for depression, including inquiring about suicidal ideation, is | Unstable or turbulent psychosocial status (e.g., unstable warranted. | housing, erratic relationships, marginal employment) Depressed patients must be specifically asked about Limited ability to identify reasons for living suicidal ideation and behavior. Positive or equivocal answers Information from Sall J, Brenner L, Millikan Bell AM, et al. Assessment and should be followed by questions related to means and management of patients at risk for suicide: synopsis of the 2019 U.S. Department intent; assessment of risk factors for suicide (Table 45); and of Veterans Affairs and U.S. Department of Defense clinical practice guidelines. Ann Intern Med. 2019;171:343-53. [PMID: 31450237] doi:10.7326/M19-0687 the development of a plan for evaluation and care, which may include referral to the emergency department or a psychiatrist. Symptoms of MDD and other mood disorders are outlined in Table 46. Diagnosis For a diagnosis of MDD, symptoms cannot be attributable to Major Depressive Disorder a medical condition, medication, or substance use and must cause The DSM-5 criteria for diagnosis of major depressive disorder significant functional impairment. Clinicians should screen (MDD) require the presence of at least five symptoms, at least patients with depression for any history of elevated mood, which one of which must be depressed mood or anhedonia, nearly suggests bipolar disorder. Prescribing antidepressant monother- every day or all of the time during the same 2-week period. apy to a patient with bipolar disorder may precipitate mania. TABLE 46. Symptom Criteria for Diagnosis of Common Mood Disorders Major Depressive Disorder Five or more of the symptoms listed below (at least one of the symptoms must be depressed mood or anhedonia) nearly every day or all of the time during the same 2-wk period: Depressed mood Anhedonia Insomnia/hypersomnia Weight loss/gain, appetite increase/decrease

TABLE 46. Symptom Criteria for Diagnosis of Common Mood Disorders Major Depressive Disorder Five or more of the symptoms listed below (at least one of the symptoms must be depressed mood or anhedonia) nearly every day or all of the time during the same 2-wk period: Depressed mood Anhedonia Insomnia/hypersomnia Weight loss/gain, appetite increase/decrease Fatigue/decreased energy Psychomotor agitation/retardation Decreased concentration Feelings of worthlessness or excessive/inappropriate guilt Recurrent thoughts of death, suicidal ideation, or suicide attempt Persistent Depressive Disorder Depressed mood most of the time for 2 y plus two of the following: Appetite change Fatigue or low energy Decreased self-esteem Insomnia or hypersomnia Poor concentration Hopelessness Seasonal Affective Disorder Symptoms of major depressive disorder, mania, or hypomania occurring in autumn/winter and remitting in the spring | (Continued on the next page) 74

Mental and Behavioral Health TABLE 46. Symptom Criteria for Diagnosis of Common Mood Disorders (Continued) | Premenstrual Dysphoric Disorder | Atleast one primary symptom (mood swings, irritability or anger, hopelessness or depressed mood, anxiety) plus four additional symptoms: | Mood swings Irritability or anger Hopelessness or depressed mood | Anxiety | Appetite change Anhedonia Fatigue | Difficulty concentrating Feelings of loss of control Sleep disturbance | Physical symptoms: breast pain, bloating, myalgias, weight gain | Peripartum Depression | Symptoms of major depressive disorder occurring during or within 4 wk after pregnancy | Persistent Complex Bereavement Disorder ; Labile emotions, sadness, loneliness, and fleeting hallucinations for >12 mo | Intense longing for or preoccupation with the deceased a Feelings of emptiness, inability to live | Sl | Bipolar Disorder 1/2 = a | | | Symptoms of depression plus at least one episode of mania/hypomania. Mania requires at least 7 consecutive days of severe, abnormally expansive, euphoric, or irritable mood plus at least three of the below additional symptoms (four if the patient reports || irritable mood only). Hypomania requires at least 4 consecutive days of symptoms without severe impairment based on presence of | symptoms listed below. | Irritable, expansive/elevated mood | Inflated self-esteem | Increased talkativeness | Flight of ideas | Distractibility | | Decreased need for sleep | Increased goal-directed activity | Excessive risk-taking behavior L

| Symptoms of depression plus at least one episode of mania/hypomania. Mania requires at least 7 consecutive days of severe, abnormally expansive, euphoric, or irritable mood plus at least three of the below additional symptoms (four if the patient reports || irritable mood only). Hypomania requires at least 4 consecutive days of symptoms without severe impairment based on presence of | symptoms listed below. | Irritable, expansive/elevated mood | Inflated self-esteem | Increased talkativeness | Flight of ideas | Distractibility | | Decreased need for sleep | Increased goal-directed activity | Excessive risk-taking behavior L Persistent Depressive Disorder arising during autumn or winter and subsiding the following Previously known as dysthymia, persistent depressive disor- spring for at least 2 consecutive years (MDD with seasonal pat- der is characterized by depressed mood most of the time for tern); seasonal episodes of depression should substantially at least 2 years with at least two associated symptoms (see outnumber nonseasonal episodes. The diagnostic criteria are Table 46). The burden of symptoms is less than in MDD but otherwise the same as for MDD. still cause impairment of social or occupational functioning. Symptoms can temporarily resolve but do not abate for more Premenstrual Dysphoric Disorder than 2 months at a time. Premenstrual dysphoric disorder consists of symptoms of mood disturbance that develop the week before menses, remit Seasonal Affective Disorder within a week after menses, and occur with most menstrual Seasonal affective disorder (SAD) is defined as MDD, mania, or cycles during a given year (see Table 46). hypomania with recurrent seasonal onset and resolution. SAD is not a separate diagnostic entity; rather, it is a subtype of each Peripartum Depression of these mood disorders (with the specifier “with seasonal pat- Peripartum depression affects 7% of pregnant or postpar- tern”). The most common form of SAD is MDD with symptoms tum women and is characterized as MDD occurring during

Persistent Depressive Disorder arising during autumn or winter and subsiding the following Previously known as dysthymia, persistent depressive disor- spring for at least 2 consecutive years (MDD with seasonal pat- der is characterized by depressed mood most of the time for tern); seasonal episodes of depression should substantially at least 2 years with at least two associated symptoms (see outnumber nonseasonal episodes. The diagnostic criteria are Table 46). The burden of symptoms is less than in MDD but otherwise the same as for MDD. still cause impairment of social or occupational functioning. Symptoms can temporarily resolve but do not abate for more Premenstrual Dysphoric Disorder than 2 months at a time. Premenstrual dysphoric disorder consists of symptoms of mood disturbance that develop the week before menses, remit Seasonal Affective Disorder within a week after menses, and occur with most menstrual Seasonal affective disorder (SAD) is defined as MDD, mania, or cycles during a given year (see Table 46). hypomania with recurrent seasonal onset and resolution. SAD is not a separate diagnostic entity; rather, it is a subtype of each Peripartum Depression of these mood disorders (with the specifier “with seasonal pat- Peripartum depression affects 7% of pregnant or postpar- tern”). The most common form of SAD is MDD with symptoms tum women and is characterized as MDD occurring during 75

Mental and Behavioral Health pregnancy or within 4 weeks after delivery. It is not consid- psychological therapies are available as second-line options ered a separate mood disorder; instead, it is a subtype of (Table 47). MDD with the specifier “with peripartum onset.” The Four classes of SGAs are available: selective serotonin USPSTF recommends counseling interventions, such as reuptake inhibitors (SSRIs), serotonin-norepinephrine reup- cognitive behavioral therapy (CBT) and interpersonal ther- take inhibitors (SNRIs), serotonin modulators, and atypical apy, to prevent peripartum depression in at-risk patients. antidepressants (Table 48). Drug selection should be based However, there are no accurate screening tools for identify- on side effect profiles and patient-specific characteristics. ing women at risk for perinatal depression. Instead, the Side effects are common, and patient education regarding USPSTF recommends the pragmatic approach of offering adverse effects can improve adherence. SSRIs are generally counseling interventions or referral to women with one or well tolerated but can cause reduced sexual desire, anorgas- more of the following risk factors: history of depression, mia, and delayed orgasm. Bupropion causes fewer sexual current depressive symptoms (that do not reach a diagnostic side effects, but it is contraindicated in patients with seizure threshold), low income, adolescent or single parenthood, disorders or a history of anorexia nervosa or bulimia. SSRIs, unplanned pregnancy, recent intimate partner violence, SNRIs, bupropion, and monoamine oxidase inhibitors all elevated anxiety symptoms, gestational or pregestational have the potential to cause serotonin syndrome, particularly diabetes, pregnancy complications, or a history of signifi- if used in combination with one another or with other cant negative life events. specific medications (including metoclopramide, tramadol, and linezolid) (see MKSAP 19 Pulmonary and Critical Care Persistent Complex Bereavement Disorder Medicine). Grief is a normal response to interpersonal loss, such as Medication should be started at a low dosage and gradu- death of a loved one. The grief process varies, but most ally titrated to achieve a clinical response while monitoring for patients functionally adapt to loss within 12 months. adverse effects. Therapeutic response can be objectively meas- Pathologic grief persists longer and is associated with sig- ured by comparing scores on the PHQ-9 before and during nificant impairment of function. This response to grief is treatment. A decrease in score of at least 50% indicates a termed complicated grief or persistent complex bereave- response to treatment; a decrease to a score of less than 5 indi- ment disorder (as proposed in DSM-5 as a future diagnostic cates remission. If initial monotherapy fails to achieve an classification) (see Table 46). Up to 10% of bereaved patients adequate response within 6 to 12 weeks, the next therapeutic develop persistent complex bereavement disorder, but the steps are guided by the initial choice of therapy and the pres- incidence is doubled in patients with other mood disorders. ence of any response. If a partial response occurs, increasing Other risk factors include older age, loss of a spouse or child, the dosage of the chosen medication or adding psychotherapy and sudden death of a loved one. A major life loss can also (ifnot already used) may be appropriate. If no response is seen, induce other mood disorders; therefore, clinicians should maintain a high index of suspicion for these disorders in the bereaved patient. TABLE 47. Common Psychological Interventions to Treat Depression

pregnancy or within 4 weeks after delivery. It is not consid- psychological therapies are available as second-line options ered a separate mood disorder; instead, it is a subtype of (Table 47). MDD with the specifier “with peripartum onset.” The Four classes of SGAs are available: selective serotonin USPSTF recommends counseling interventions, such as reuptake inhibitors (SSRIs), serotonin-norepinephrine reup- cognitive behavioral therapy (CBT) and interpersonal ther- take inhibitors (SNRIs), serotonin modulators, and atypical apy, to prevent peripartum depression in at-risk patients. antidepressants (Table 48). Drug selection should be based However, there are no accurate screening tools for identify- on side effect profiles and patient-specific characteristics. ing women at risk for perinatal depression. Instead, the Side effects are common, and patient education regarding USPSTF recommends the pragmatic approach of offering adverse effects can improve adherence. SSRIs are generally counseling interventions or referral to women with one or well tolerated but can cause reduced sexual desire, anorgas- more of the following risk factors: history of depression, mia, and delayed orgasm. Bupropion causes fewer sexual current depressive symptoms (that do not reach a diagnostic side effects, but it is contraindicated in patients with seizure threshold), low income, adolescent or single parenthood, disorders or a history of anorexia nervosa or bulimia. SSRIs, unplanned pregnancy, recent intimate partner violence, SNRIs, bupropion, and monoamine oxidase inhibitors all elevated anxiety symptoms, gestational or pregestational have the potential to cause serotonin syndrome, particularly diabetes, pregnancy complications, or a history of signifi- if used in combination with one another or with other cant negative life events. specific medications (including metoclopramide, tramadol, and linezolid) (see MKSAP 19 Pulmonary and Critical Care Persistent Complex Bereavement Disorder Medicine). Grief is a normal response to interpersonal loss, such as Medication should be started at a low dosage and gradu- death of a loved one. The grief process varies, but most ally titrated to achieve a clinical response while monitoring for patients functionally adapt to loss within 12 months. adverse effects. Therapeutic response can be objectively meas- Pathologic grief persists longer and is associated with sig- ured by comparing scores on the PHQ-9 before and during nificant impairment of function. This response to grief is treatment. A decrease in score of at least 50% indicates a termed complicated grief or persistent complex bereave- response to treatment; a decrease to a score of less than 5 indi- ment disorder (as proposed in DSM-5 as a future diagnostic cates remission. If initial monotherapy fails to achieve an classification) (see Table 46). Up to 10% of bereaved patients adequate response within 6 to 12 weeks, the next therapeutic develop persistent complex bereavement disorder, but the steps are guided by the initial choice of therapy and the pres- incidence is doubled in patients with other mood disorders. ence of any response. If a partial response occurs, increasing Other risk factors include older age, loss of a spouse or child, the dosage of the chosen medication or adding psychotherapy and sudden death of a loved one. A major life loss can also (ifnot already used) may be appropriate. If no response is seen, induce other mood disorders; therefore, clinicians should maintain a high index of suspicion for these disorders in the bereaved patient. TABLE 47. Common Psychological Interventions to Treat Depression Adjustment Disorder With Depressed Mood Intervention Description Patients may exhibit depressive symptoms in response to a Acceptance and Uses mindfulness techniques to | stress- or trauma-related life event. Adjustment disorder with commitment therapy overcome negative thoughts and accept difficulties | depressed mood is present when symptoms can be clearly linked to an identifiable stressor but criteria for other depres- Cognitive therapy Helps patients correct false self- | beliefs and negative thoughts | sive disorders are not met. Symptoms resolve within 6 months of resolution of the stressor. | Cognitive behavioral Includes a behavioral component | therapy in cognitive therapy, such as activity scheduling and homework Management | Interpersonal therapy Focuses on relationships and how Most patients with MDD can be successfully managed in the | to address issues related to them primary care setting. Referral to a psychiatrist is indicated for Psychodynamic therapy Focuses on conscious and patients with severe depression, failure of initial therapy, unconscious feelings and complex psychiatric comorbidities, or high suicide risk (see experiences

Adjustment Disorder With Depressed Mood Intervention Description Patients may exhibit depressive symptoms in response to a Acceptance and Uses mindfulness techniques to | stress- or trauma-related life event. Adjustment disorder with commitment therapy overcome negative thoughts and accept difficulties | depressed mood is present when symptoms can be clearly linked to an identifiable stressor but criteria for other depres- Cognitive therapy Helps patients correct false self- | beliefs and negative thoughts | sive disorders are not met. Symptoms resolve within 6 months of resolution of the stressor. | Cognitive behavioral Includes a behavioral component | therapy in cognitive therapy, such as activity scheduling and homework Management | Interpersonal therapy Focuses on relationships and how Most patients with MDD can be successfully managed in the | to address issues related to them primary care setting. Referral to a psychiatrist is indicated for Psychodynamic therapy Focuses on conscious and patients with severe depression, failure of initial therapy, unconscious feelings and complex psychiatric comorbidities, or high suicide risk (see experiences Table 45). For initial acute therapy, either CBT or second- Third-wave cognitive Targets thought processes to help behavioral therapy persons with awareness and generation antidepressants (SGAs) are indicated, with the | acceptance choice of treatment based on a discussion of side effects, cost, i Reproduced with permission from Qaseem A, Barry MJ, Kansagara D; Clinical accessibility, and patient preferences. It is unclear whether Guidelines Committee of the American College of Physicians. Nonpharmacologic combination therapy with CBT and medication is more effec- versus pharmacologic treatment of adult patients with major depressive disorder: | aclinical practice guideline from the American College of Physicians. Ann Intern tive than either treatment modality alone, but combination Med. 2016;164:351. [PMID: 26857948] doi:10.7326/M15-2570. © 2016, American | College of Physicians. therapy is reasonable in moderate to severe disease. Other

Table 45). For initial acute therapy, either CBT or second- Third-wave cognitive Targets thought processes to help behavioral therapy persons with awareness and generation antidepressants (SGAs) are indicated, with the | acceptance choice of treatment based on a discussion of side effects, cost, i Reproduced with permission from Qaseem A, Barry MJ, Kansagara D; Clinical accessibility, and patient preferences. It is unclear whether Guidelines Committee of the American College of Physicians. Nonpharmacologic combination therapy with CBT and medication is more effec- versus pharmacologic treatment of adult patients with major depressive disorder: | aclinical practice guideline from the American College of Physicians. Ann Intern tive than either treatment modality alone, but combination Med. 2016;164:351. [PMID: 26857948] doi:10.7326/M15-2570. © 2016, American | College of Physicians. therapy is reasonable in moderate to severe disease. Other 76

Mental and Behavioral Health TABLE 48. Dosages and Comparative Adverse Effects of Second-Generation Antidepressants | Drug Dosage (mg/d) Comparative or Drug-Specific Adverse Effects? | Selective Serotonin Reuptake Inhibitors (SSRIs) Citalopram 20-40 Possible increased risk for QT interval prolongation and torsades de pointes (dosages | >40 mg/d) | Escitalopram 10-20 QT prolongation (less than with citalopram) | Fluoxetine 10-80 Lowest rates of discontinuation syndrome compared with other SSRIs Fluvoxamine 40-120 NA | Paroxetine 20-60 Highest rates of sexual dysfunction among SSRIs; higher rates of weight gain; highest rates of discontinuation syndrome Sertraline 50-200 Higher incidence of diarrhea Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) Venlafaxine 75-375 Higher rates of nausea and vomiting; higher rates of discontinuation due to adverse events than with SSRIs as a class; highest rates of discontinuation syndrome Venlafaxine XR 75-225 Desvenlafaxine 50-100 Same as venlafaxine | Duloxetine 60-120 Same as venlafaxine, but lower rates of adverse events and discontinuation syndrome | than with other SNRIs Serotonin Modulators | Nefazodone 200-600 NA Atypical Antidepressants

Desvenlafaxine 50-100 Same as venlafaxine | Duloxetine 60-120 Same as venlafaxine, but lower rates of adverse events and discontinuation syndrome | than with other SNRIs Serotonin Modulators | Nefazodone 200-600 NA Atypical Antidepressants Bupropion 200-450 Lower rate of sexual adverse events than with escitalopram, fluoxetine, paroxetine, and a sertraline Bupropion SR 150-400 NA = not available; SR = sustained release; XR = extended release. *Common adverse effects associated with second-generation antidepressants include constipation, diarrhea, dizziness, headache, insomnia, nausea, sexual adverse events, and | somnolence. Adapted with permission from Qaseem A, Barry MJ, Kansagara D; Clinical Guidelines Committee of the American College of Physicians. Nonpharmacologic versus pharmacologic treatment of adult patients with major depressive disorder: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2016;164:350-9. [PMID: 26857948] | doi:10.7326/M15-2570. ©2016, American College of Physicians.

Adapted with permission from Qaseem A, Barry MJ, Kansagara D; Clinical Guidelines Committee of the American College of Physicians. Nonpharmacologic versus pharmacologic treatment of adult patients with major depressive disorder: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2016;164:350-9. [PMID: 26857948] | doi:10.7326/M15-2570. ©2016, American College of Physicians. switching to another SGA or adding a second agent with or therapy (treatment after resolution of a major depressive epi- without psychotherapy is indicated. A second-line approach is sode) for 4 to 9 months in patients who responded to acute the addition of an antipsychotic drug. FDA-approved antide- therapy. The antidepressant dosage that was effective in acute pressant-antipsychotic combinations include olanzapine with treatment should be maintained in the continuation phase, fluoxetine, and aripiprazole or quetiapine with any antide- and if psychotherapy was used, it should be continued. pressant. In cases of resistant depression, electroconvulsive Patients with three or more previous major depressive epi- therapy is also safe and effective, although transient memory sodes, persistent depressive disorder, or residual depressive loss is a common adverse effect. symptoms should receive long-term maintenance therapy at a Esketamine is a glutamate receptor modulator deliv- similar dosage. When long-term drug therapy is not indicated ered via nasal inhalation that has recently shown promise or must be stopped for other reasons, antidepressant medica- as an adjunctive therapy for MDD with suicidal ideation and tions should be gradually tapered to avoid discontinuation treatment-resistant depression. Unlike most pharmacologic syndrome. The most common symptoms associated with dis- treatments for depression, its antidepressant effect is imme- continuation syndrome are dizziness, fatigue, headache, and diate. Given the lack of data on long-term safety and efficacy nausea, typically occurring within 1 to 7 days of rapidly dis- and the complexity of managing severe treatment-resistant continuing antidepressants. depression, referral to a psychiatrist to determine treatment appropriateness is reasonable. Special Populations Approximately half of patients who respond to appropri- Persistent complex bereavement disorder may respond to both ate initial therapy (CBT or SGA monotherapy) develop recur- psychotherapy and pharmacologic therapy, which should be rent depression after 1 year without continued treatment. The targeted to specific symptoms. SSRIs and SNRIs have demon- American Psychiatric Association recommends continuation strated benefit in patients with depressive symptoms.

switching to another SGA or adding a second agent with or therapy (treatment after resolution of a major depressive epi- without psychotherapy is indicated. A second-line approach is sode) for 4 to 9 months in patients who responded to acute the addition of an antipsychotic drug. FDA-approved antide- therapy. The antidepressant dosage that was effective in acute pressant-antipsychotic combinations include olanzapine with treatment should be maintained in the continuation phase, fluoxetine, and aripiprazole or quetiapine with any antide- and if psychotherapy was used, it should be continued. pressant. In cases of resistant depression, electroconvulsive Patients with three or more previous major depressive epi- therapy is also safe and effective, although transient memory sodes, persistent depressive disorder, or residual depressive loss is a common adverse effect. symptoms should receive long-term maintenance therapy at a Esketamine is a glutamate receptor modulator deliv- similar dosage. When long-term drug therapy is not indicated ered via nasal inhalation that has recently shown promise or must be stopped for other reasons, antidepressant medica- as an adjunctive therapy for MDD with suicidal ideation and tions should be gradually tapered to avoid discontinuation treatment-resistant depression. Unlike most pharmacologic syndrome. The most common symptoms associated with dis- treatments for depression, its antidepressant effect is imme- continuation syndrome are dizziness, fatigue, headache, and diate. Given the lack of data on long-term safety and efficacy nausea, typically occurring within 1 to 7 days of rapidly dis- and the complexity of managing severe treatment-resistant continuing antidepressants. depression, referral to a psychiatrist to determine treatment appropriateness is reasonable. Special Populations Approximately half of patients who respond to appropri- Persistent complex bereavement disorder may respond to both ate initial therapy (CBT or SGA monotherapy) develop recur- psychotherapy and pharmacologic therapy, which should be rent depression after 1 year without continued treatment. The targeted to specific symptoms. SSRIs and SNRIs have demon- American Psychiatric Association recommends continuation strated benefit in patients with depressive symptoms. 77

Mental and Behavioral Health Premenstrual dysphoric disorder and peripartum depres- sion are treated similarly to other forms of depression, but e The U.S. Preventive Services Task Force advises screen- with additional attention to drug safety during pregnancy. ing all patients for depression at primary care visits. SSRIs and SNRIs are associated with a low risk for teratogenic- ¢ For initial acute treatment of major depressive disorder, HVC ity, except for paroxetine, which may be linked to congenital options include cognitive behavioral therapy or second- cardiac malformations. All antidepressant medications are generation antidepressants after consideration and dis- safe with breastfeeding. cussion of side effects, cost, accessibility, and patient MDD with seasonal pattern can be effectively treated with preferences; combination therapy is a reasonable option, CBT and SGAs. Daily exposure to 10,000 lux of visible light for especially in moderate to severe disease. 30 to 60 minutes is also beneficial. Patients with concomitant pain syndromes may derive e Peripartum depression may occur during pregnancy or

Premenstrual dysphoric disorder and peripartum depres- sion are treated similarly to other forms of depression, but e The U.S. Preventive Services Task Force advises screen- with additional attention to drug safety during pregnancy. ing all patients for depression at primary care visits. SSRIs and SNRIs are associated with a low risk for teratogenic- ¢ For initial acute treatment of major depressive disorder, HVC ity, except for paroxetine, which may be linked to congenital options include cognitive behavioral therapy or second- cardiac malformations. All antidepressant medications are generation antidepressants after consideration and dis- safe with breastfeeding. cussion of side effects, cost, accessibility, and patient MDD with seasonal pattern can be effectively treated with preferences; combination therapy is a reasonable option, CBT and SGAs. Daily exposure to 10,000 lux of visible light for especially in moderate to severe disease. 30 to 60 minutes is also beneficial. Patients with concomitant pain syndromes may derive e Peripartum depression may occur during pregnancy or additional analgesic benefit from the use of SNRIs. within 4 weeks after delivery; treatment is similar to that for other forms of depression but with close atten- Bipolar Disorder tion to drug safety in pregnancy. Bipolar disorder is characterized by major depressive episodes ¢ Referral to a psychiatrist is indicated for patients with and periods of mania or hypomania. The prevalence is 1% to severe depression, failure of initial therapy, complex 3%, and women are affected slightly more often than are men. psychiatric comorbidities, or high suicide risk. Onset typically occurs in early adulthood, and more than half e Clinicians must assess patients with depression for any of patients initially present with a major depressive episode. history of elevated mood, which would suggest bipolar Bipolar disorder is the most expensive mental health problem disorder; prescribing antidepressant monotherapy to a and carries a high lifetime suicide risk. patient with bipolar disorder may precipitate a manic Bipolar disorder is divided into two main categories: bipo- episode. lar 1 and bipolar 2. Diagnosis of bipolar 1 disorder requires at least one episode of mania that is not explained by a medication effect, substance use, or a medical condition. The DSM-5 defines mania as an episode of at least 7 consecutive days of irritable, Anxiety Disorders expansive, or elevated mood that interferes with social or occu- Anxiety disorders are common, especially in women. The

additional analgesic benefit from the use of SNRIs. within 4 weeks after delivery; treatment is similar to that for other forms of depression but with close atten- Bipolar Disorder tion to drug safety in pregnancy. Bipolar disorder is characterized by major depressive episodes ¢ Referral to a psychiatrist is indicated for patients with and periods of mania or hypomania. The prevalence is 1% to severe depression, failure of initial therapy, complex 3%, and women are affected slightly more often than are men. psychiatric comorbidities, or high suicide risk. Onset typically occurs in early adulthood, and more than half e Clinicians must assess patients with depression for any of patients initially present with a major depressive episode. history of elevated mood, which would suggest bipolar Bipolar disorder is the most expensive mental health problem disorder; prescribing antidepressant monotherapy to a and carries a high lifetime suicide risk. patient with bipolar disorder may precipitate a manic Bipolar disorder is divided into two main categories: bipo- episode. lar 1 and bipolar 2. Diagnosis of bipolar 1 disorder requires at least one episode of mania that is not explained by a medication effect, substance use, or a medical condition. The DSM-5 defines mania as an episode of at least 7 consecutive days of irritable, Anxiety Disorders expansive, or elevated mood that interferes with social or occu- Anxiety disorders are common, especially in women. The pational functioning and has at least three associated symptoms Women’s Preventive Services Initiative suggests screening for

additional analgesic benefit from the use of SNRIs. within 4 weeks after delivery; treatment is similar to that for other forms of depression but with close atten- Bipolar Disorder tion to drug safety in pregnancy. Bipolar disorder is characterized by major depressive episodes ¢ Referral to a psychiatrist is indicated for patients with and periods of mania or hypomania. The prevalence is 1% to severe depression, failure of initial therapy, complex 3%, and women are affected slightly more often than are men. psychiatric comorbidities, or high suicide risk. Onset typically occurs in early adulthood, and more than half e Clinicians must assess patients with depression for any of patients initially present with a major depressive episode. history of elevated mood, which would suggest bipolar Bipolar disorder is the most expensive mental health problem disorder; prescribing antidepressant monotherapy to a and carries a high lifetime suicide risk. patient with bipolar disorder may precipitate a manic Bipolar disorder is divided into two main categories: bipo- episode. lar 1 and bipolar 2. Diagnosis of bipolar 1 disorder requires at least one episode of mania that is not explained by a medication effect, substance use, or a medical condition. The DSM-5 defines mania as an episode of at least 7 consecutive days of irritable, Anxiety Disorders expansive, or elevated mood that interferes with social or occu- Anxiety disorders are common, especially in women. The pational functioning and has at least three associated symptoms Women’s Preventive Services Initiative suggests screening for (see Table 46). Most patients with bipolar 1 disorder also experi- anxiety in all women, including those who are pregnant or in

additional analgesic benefit from the use of SNRIs. within 4 weeks after delivery; treatment is similar to that for other forms of depression but with close atten- Bipolar Disorder tion to drug safety in pregnancy. Bipolar disorder is characterized by major depressive episodes ¢ Referral to a psychiatrist is indicated for patients with and periods of mania or hypomania. The prevalence is 1% to severe depression, failure of initial therapy, complex 3%, and women are affected slightly more often than are men. psychiatric comorbidities, or high suicide risk. Onset typically occurs in early adulthood, and more than half e Clinicians must assess patients with depression for any of patients initially present with a major depressive episode. history of elevated mood, which would suggest bipolar Bipolar disorder is the most expensive mental health problem disorder; prescribing antidepressant monotherapy to a and carries a high lifetime suicide risk. patient with bipolar disorder may precipitate a manic Bipolar disorder is divided into two main categories: bipo- episode. lar 1 and bipolar 2. Diagnosis of bipolar 1 disorder requires at least one episode of mania that is not explained by a medication effect, substance use, or a medical condition. The DSM-5 defines mania as an episode of at least 7 consecutive days of irritable, Anxiety Disorders expansive, or elevated mood that interferes with social or occu- Anxiety disorders are common, especially in women. The pational functioning and has at least three associated symptoms Women’s Preventive Services Initiative suggests screening for (see Table 46). Most patients with bipolar 1 disorder also experi- anxiety in all women, including those who are pregnant or in ence major depressive episodes, and many experience periods the postpartum period. The USPSTF does not provide a recom- of hypomania. Hypomania is defined by the same criteria as mendation regarding screening for anxiety, and there are no

(see Table 46). Most patients with bipolar 1 disorder also experi- anxiety in all women, including those who are pregnant or in ence major depressive episodes, and many experience periods the postpartum period. The USPSTF does not provide a recom- of hypomania. Hypomania is defined by the same criteria as mendation regarding screening for anxiety, and there are no mania, except the duration is at least 4 consecutive days and recommendations regarding screening for anxiety in men. symptoms do not cause severe functional impairment. Screening for anxiety may be combined with depression Patients with bipolar 2 disorder have periods of both screening by using tools such as the PHQ-4 and the Hospital hypomania and major depression but never mania. Cyclothymic Anxiety and Depression Scale.

symptoms do not cause severe functional impairment. Screening for anxiety may be combined with depression Patients with bipolar 2 disorder have periods of both screening by using tools such as the PHQ-4 and the Hospital hypomania and major depression but never mania. Cyclothymic Anxiety and Depression Scale. disorder is characterized by multiple episodes of hypomanic and depressive symptoms that do not meet criteria for hypo- Generalized Anxiety Disorder mania or major depression. Generalized anxiety disorder (GAD) is characterized by exces- Identification of bipolar disorder by primary care physi- sive anxiety about activities or events (occupation, school) that cians is critical because treatment of bipolar disorder with a patient finds difficult to control and occurs more days than antidepressant therapy alone can precipitate mania. In evalu- not for at least 6 months. The anxiety causes significant dis- ating patients with depressive symptoms, clinicians should tress and functional impairment. Diagnosis also requires the inquire about previous episodes consistent with mania or presence of three of the following physical symptoms hypomania, age at onset of any mood symptoms, and family (DSM-5): restlessness, being easily fatigued, irritability, muscle history of mood disorders. tension, sleep disturbance, and difficulty concentrating. Treatment of bipolar disorder should be directed by a The lifetime prevalence of GAD is 5% to 10%, and women are psychiatrist. First-line medications include lithium, valproic affected more often than are men. As many as 50% of individu- acid, carbamazepine, and lamotrigine; psychotherapy plays an als with mood disorders experience a comorbid anxiety disor- adjunctive role. Patients with acute mania typically require der during their lifetime. one of the aforementioned medications plus an atypical anti- Patients with significant anxiety or multiple unexplained psychotic agent (aripiprazole, olanzapine, quetiapine). Severe physical symptoms should be screened for GAD using the bipolar depression may require a combination of first-line GAD-7 screening tool (www.adaa.org/sites/default/files/ medications or adjunctive antipsychotics (fluoxetine plus GAD-7_Anxiety-updated_0.pdf). The shorter-form GAD-2 can olanzapine). Quetiapine is also effective as monotherapy for be administered in less time and may be equivalent to the bipolar depression. GAD-7 in screening for GAD in primary care populations. The

disorder is characterized by multiple episodes of hypomanic and depressive symptoms that do not meet criteria for hypo- Generalized Anxiety Disorder mania or major depression. Generalized anxiety disorder (GAD) is characterized by exces- Identification of bipolar disorder by primary care physi- sive anxiety about activities or events (occupation, school) that cians is critical because treatment of bipolar disorder with a patient finds difficult to control and occurs more days than antidepressant therapy alone can precipitate mania. In evalu- not for at least 6 months. The anxiety causes significant dis- ating patients with depressive symptoms, clinicians should tress and functional impairment. Diagnosis also requires the inquire about previous episodes consistent with mania or presence of three of the following physical symptoms hypomania, age at onset of any mood symptoms, and family (DSM-5): restlessness, being easily fatigued, irritability, muscle history of mood disorders. tension, sleep disturbance, and difficulty concentrating. Treatment of bipolar disorder should be directed by a The lifetime prevalence of GAD is 5% to 10%, and women are psychiatrist. First-line medications include lithium, valproic affected more often than are men. As many as 50% of individu- acid, carbamazepine, and lamotrigine; psychotherapy plays an als with mood disorders experience a comorbid anxiety disor- adjunctive role. Patients with acute mania typically require der during their lifetime. one of the aforementioned medications plus an atypical anti- Patients with significant anxiety or multiple unexplained psychotic agent (aripiprazole, olanzapine, quetiapine). Severe physical symptoms should be screened for GAD using the bipolar depression may require a combination of first-line GAD-7 screening tool (www.adaa.org/sites/default/files/ medications or adjunctive antipsychotics (fluoxetine plus GAD-7_Anxiety-updated_0.pdf). The shorter-form GAD-2 can olanzapine). Quetiapine is also effective as monotherapy for be administered in less time and may be equivalent to the bipolar depression. GAD-7 in screening for GAD in primary care populations. The 78

Mental and Behavioral Health initial evaluation of suspected GAD focuses on excluding anxi- Panic Disorder ety as a physiologic effect of another medical condition (e.g., Panic attacks are characterized by sudden onset and rapid hyperthyroidism; substance use disorder; medication effect; escalation (within minutes) of extreme fear or anxiety along and symptom-driven anxiety, such as anxiety secondary to with at least four of the following: fear of dying, fear of los- dyspnea). ing control, palpitations, diaphoresis, tremor, dyspnea, sen- CBT and pharmacotherapy are equally effective in the sation of choking, chest pain, nausea, dizziness, chills or treatment of moderate-severity GAD, but patients with comor- heat sensations, paresthesia, and derealization (perception bid mood disorders are best treated with a medication that that the world is not real). Panic attacks are commonly targets their concomitant illnesses. SSRIs, SNRIs, buspirone, encountered in the primary care setting both as a primary and tricyclic antidepressants are all effective in the treatment symptom of psychiatric illness and as a symptom associated of GAD (Table 49). SSRIs and SNRIs are preferred first-line with other medical conditions (asthma, arrhythmias, drugs because they have fewer side effects than tricyclic anti- hyperthyroidism). Exclusion of secondary causes is a cru- depressants and effectively treat comorbid behavioral disor- cial step in the evaluation of panic attacks. Patients who ders (unlike buspirone, which is thought to be effective for experience panic attacks may also have comorbid depres- anxiety alone). For patients with severe GAD leading to pro- sion and other anxiety disorders (GAD, posttraumatic stress found functional impairment or with severe comorbid mood disorder [PTSD)). disorders, a combined approach of pharmacotherapy with Panic attacks are a key feature of panic disorder but are referral for psychotherapy is preferred, and further evaluation not pathognomonic; up to one third of all adults will experi- by a psychiatrist is recommended. Although often prescribed, ence a panic attack during their lifetime in the absence of benzodiazepines are limited in their effectiveness to short- underlying panic disorder. DSM-5 diagnostic criteria for panic term control of severe symptoms during the initial treatment disorder include both persistent (>1 month) panic attacks and phase. Side effects and risk for addiction preclude longer-term persistent worry about the recurrence of panic attacks or

initial evaluation of suspected GAD focuses on excluding anxi- Panic Disorder ety as a physiologic effect of another medical condition (e.g., Panic attacks are characterized by sudden onset and rapid hyperthyroidism; substance use disorder; medication effect; escalation (within minutes) of extreme fear or anxiety along and symptom-driven anxiety, such as anxiety secondary to with at least four of the following: fear of dying, fear of los- dyspnea). ing control, palpitations, diaphoresis, tremor, dyspnea, sen- CBT and pharmacotherapy are equally effective in the sation of choking, chest pain, nausea, dizziness, chills or treatment of moderate-severity GAD, but patients with comor- heat sensations, paresthesia, and derealization (perception bid mood disorders are best treated with a medication that that the world is not real). Panic attacks are commonly targets their concomitant illnesses. SSRIs, SNRIs, buspirone, encountered in the primary care setting both as a primary and tricyclic antidepressants are all effective in the treatment symptom of psychiatric illness and as a symptom associated of GAD (Table 49). SSRIs and SNRIs are preferred first-line with other medical conditions (asthma, arrhythmias, drugs because they have fewer side effects than tricyclic anti- hyperthyroidism). Exclusion of secondary causes is a cru- depressants and effectively treat comorbid behavioral disor- cial step in the evaluation of panic attacks. Patients who ders (unlike buspirone, which is thought to be effective for experience panic attacks may also have comorbid depres- anxiety alone). For patients with severe GAD leading to pro- sion and other anxiety disorders (GAD, posttraumatic stress found functional impairment or with severe comorbid mood disorder [PTSD)). disorders, a combined approach of pharmacotherapy with Panic attacks are a key feature of panic disorder but are referral for psychotherapy is preferred, and further evaluation not pathognomonic; up to one third of all adults will experi- by a psychiatrist is recommended. Although often prescribed, ence a panic attack during their lifetime in the absence of benzodiazepines are limited in their effectiveness to short- underlying panic disorder. DSM-5 diagnostic criteria for panic term control of severe symptoms during the initial treatment disorder include both persistent (>1 month) panic attacks and phase. Side effects and risk for addiction preclude longer-term persistent worry about the recurrence of panic attacks or use (>2-4 weeks). The GAD-7 can be useful for monitoring maladaptive behavior changes secondary to the attacks (e.g., response to treatment. avoidance of previous triggers).

initial evaluation of suspected GAD focuses on excluding anxi- Panic Disorder ety as a physiologic effect of another medical condition (e.g., Panic attacks are characterized by sudden onset and rapid hyperthyroidism; substance use disorder; medication effect; escalation (within minutes) of extreme fear or anxiety along and symptom-driven anxiety, such as anxiety secondary to with at least four of the following: fear of dying, fear of los- dyspnea). ing control, palpitations, diaphoresis, tremor, dyspnea, sen- CBT and pharmacotherapy are equally effective in the sation of choking, chest pain, nausea, dizziness, chills or treatment of moderate-severity GAD, but patients with comor- heat sensations, paresthesia, and derealization (perception bid mood disorders are best treated with a medication that that the world is not real). Panic attacks are commonly targets their concomitant illnesses. SSRIs, SNRIs, buspirone, encountered in the primary care setting both as a primary and tricyclic antidepressants are all effective in the treatment symptom of psychiatric illness and as a symptom associated of GAD (Table 49). SSRIs and SNRIs are preferred first-line with other medical conditions (asthma, arrhythmias, drugs because they have fewer side effects than tricyclic anti- hyperthyroidism). Exclusion of secondary causes is a cru- depressants and effectively treat comorbid behavioral disor- cial step in the evaluation of panic attacks. Patients who ders (unlike buspirone, which is thought to be effective for experience panic attacks may also have comorbid depres- anxiety alone). For patients with severe GAD leading to pro- sion and other anxiety disorders (GAD, posttraumatic stress found functional impairment or with severe comorbid mood disorder [PTSD)). disorders, a combined approach of pharmacotherapy with Panic attacks are a key feature of panic disorder but are referral for psychotherapy is preferred, and further evaluation not pathognomonic; up to one third of all adults will experi- by a psychiatrist is recommended. Although often prescribed, ence a panic attack during their lifetime in the absence of benzodiazepines are limited in their effectiveness to short- underlying panic disorder. DSM-5 diagnostic criteria for panic term control of severe symptoms during the initial treatment disorder include both persistent (>1 month) panic attacks and phase. Side effects and risk for addiction preclude longer-term persistent worry about the recurrence of panic attacks or use (>2-4 weeks). The GAD-7 can be useful for monitoring maladaptive behavior changes secondary to the attacks (e.g., response to treatment. avoidance of previous triggers). TABLE 49, Pharmacotherapy for Generalized Anxiety Disorder

use (>2-4 weeks). The GAD-7 can be useful for monitoring maladaptive behavior changes secondary to the attacks (e.g., response to treatment. avoidance of previous triggers). TABLE 49, Pharmacotherapy for Generalized Anxiety Disorder | Class of Agent Specific Agent, Therapeutic Adverse Effects and Notes Dose First-line medications: As a class: nausea, diarrhea, decreased appetite, restlessness, SSRIs and SNRIs insomnia, somnolence, impaired sexual function, and hyponatremia SSRI Escitalopram, 10-20 mg/d OT prolongation 10 mg/d is the maximum dose recommended for elderly adults and those with hepatic impairment SSRI Paroxetine, 20-60 mg/d More sexual dysfunction, weight gain, and sedation; discontinuation syndrome not uncommon Increased drug interactions, including strong CYP2D6 inhibition SSRI Sertraline, 50-200 mg/d Higher incidence of gastrointestinal distress SNRI Duloxetine, 60-120 mg/d Gastrointestinal distress (less than with venlafaxine) SNRI Venlafaxine extended-release, Higher incidence of gastrointestinal distress; increased blood 75-225 mg/d pressure Second-line medications Azapirones Buspirone, 15-30 mg/d Ineffective for comorbid disorders; dizziness, drowsiness Benzodiazepines Alprazolam, 0.25-1 mg/d; As a class: falls, memory impairment, risk for dependence lorazepam, 0.5-2 mg/d

Azapirones Buspirone, 15-30 mg/d Ineffective for comorbid disorders; dizziness, drowsiness Benzodiazepines Alprazolam, 0.25-1 mg/d; As a class: falls, memory impairment, risk for dependence lorazepam, 0.5-2 mg/d Anticonvulsant Pregabalin, 150-600 mg/d Sedation, dizziness, peripheral edema Used as an adjuvant to first-line medications Use with caution in patients with renal impairment Antihistamine Hydroxyzine, 50-100 mg 4 times Sedation, dry mouth, confusion, and urine retention daily SNRI = serotonin-norepinephrine reuptake inhibitor; SSRI = selective serotonin reuptake inhibitor. | \ | | Adapted with permission from DeMartini J, Patel G, Fancher TL. Generalized anxiety disorder. Ann Intern Med. 2019; 170:ITC49-64. [PMID: 30934083] doi:10.7326/AITC201904020. | | | | ©2019, American College of Physicians. 79

Mental and Behavioral Health Treatment of panic disorder involves CBT, pharmaco- and alterations in arousal and reactivity (irritability, exagger- therapy, or both. SSRIs and SNRIs are first-line medications ated startle, sleep disturbance). Symptoms typically begin because of their favorable side effect profile and efficacy. Short within 4 weeks of the traumatic event and need to be present courses of benzodiazepines can be used for acute symptom for more than 1 month. control, but long-term use is discouraged. CBT remains the cornerstone of treatment for PTSD. Therapy focuses on generalized behavioral processing and Social Anxiety Disorder treatment of associated symptoms. Mindfulness therapies are Previously known as social phobia, social anxiety disorder is also emerging as an effective treatment for reducing PTSD associated with excessive anxiety or fear of criticism or humil- symptoms. Antidepressants, including SSRIs (paroxetine, ser- iation in social or performance situations. Patients with social traline), SNRIs (venlafaxine), and nefazodone, are effective anxiety disorder may experience palpitations, flushing, dysp- adjunctive therapies. Interest in treating PTSD with cannabi- nea, chest pain, or even panic attacks in these situations. To noid therapy is growing, and PTSD is a common indication in meet DSM-5 diagnostic criteria, symptoms must be present for many state medical cannabis programs. However, there is a at least 6 months and cause significant functional impairment. paucity of quality research to support cannabis as an effective Patients usually understand that their anxiety is excessive but intervention, particularly in light of the heterogeneity of avail-

Treatment of panic disorder involves CBT, pharmaco- and alterations in arousal and reactivity (irritability, exagger- therapy, or both. SSRIs and SNRIs are first-line medications ated startle, sleep disturbance). Symptoms typically begin because of their favorable side effect profile and efficacy. Short within 4 weeks of the traumatic event and need to be present courses of benzodiazepines can be used for acute symptom for more than 1 month. control, but long-term use is discouraged. CBT remains the cornerstone of treatment for PTSD. Therapy focuses on generalized behavioral processing and Social Anxiety Disorder treatment of associated symptoms. Mindfulness therapies are Previously known as social phobia, social anxiety disorder is also emerging as an effective treatment for reducing PTSD associated with excessive anxiety or fear of criticism or humil- symptoms. Antidepressants, including SSRIs (paroxetine, ser- iation in social or performance situations. Patients with social traline), SNRIs (venlafaxine), and nefazodone, are effective anxiety disorder may experience palpitations, flushing, dysp- adjunctive therapies. Interest in treating PTSD with cannabi- nea, chest pain, or even panic attacks in these situations. To noid therapy is growing, and PTSD is a common indication in meet DSM-5 diagnostic criteria, symptoms must be present for many state medical cannabis programs. However, there is a at least 6 months and cause significant functional impairment. paucity of quality research to support cannabis as an effective Patients usually understand that their anxiety is excessive but intervention, particularly in light of the heterogeneity of avail- continue to avoid social situations that trigger anxiety. Both able cannabis products. CBT and pharmacotherapy with SSRIs and SNRIs are effective for treatment of social anxiety disorder, although overall evi- ¢ Cognitive behavioral therapy is first-line treatment for HVC dence is of low quality. For patients with social anxiety disor- posttraumatic stress disorder. der restricted to performance situations, CBT is preferred.

continue to avoid social situations that trigger anxiety. Both able cannabis products. CBT and pharmacotherapy with SSRIs and SNRIs are effective for treatment of social anxiety disorder, although overall evi- ¢ Cognitive behavioral therapy is first-line treatment for HVC dence is of low quality. For patients with social anxiety disor- posttraumatic stress disorder. der restricted to performance situations, CBT is preferred. HVC ¢ Cognitive behavioral therapy and pharmacotherapy are Obsessive-Compulsive Disorder equally effective in the treatment of generalized anxiety Obsessive-compulsive disorder (OCD) has a lifetime prevalence disorder, but patients with comorbid mood disorders of approximately 2%. Patients with OCD experience obsessions are best treated with a medication that targets their (recurrent and intrusive thoughts, images, or impulses causing concomitant illnesses. distress) and compulsions (repetitive behaviors [hand washing, ¢ Cognitive behavioral therapy and pharmacotherapy with counting] done to alleviate obsession-related anxiety). These selective serotonin reuptake inhibitors and serotonin- behaviors cause significant functional impairment through norepinephrine reuptake inhibitors are effective for wasted time and disrupted social interactions. OCD is often treatment of social anxiety disorder and panic disorder. accompanied by other mental health disorders. CBT is first-line treatment for OCD. CBT is more effective than pharmacotherapy alone, but SSRIs may be beneficial as Posttraumatic Stress Disorder adjunct therapy in patients with severe symptoms or inadequate PTSD is an increasingly recognized disorder triggered by at response to CBT. The tricyclic antidepressant clomipramine is an

treatment of social anxiety disorder and panic disorder. accompanied by other mental health disorders. CBT is first-line treatment for OCD. CBT is more effective than pharmacotherapy alone, but SSRIs may be beneficial as Posttraumatic Stress Disorder adjunct therapy in patients with severe symptoms or inadequate PTSD is an increasingly recognized disorder triggered by at response to CBT. The tricyclic antidepressant clomipramine is an least one of the following: direct experience of or witnessing a alternative, although side effects are common. For patients traumatic situation, learning that a loved one experienced a treated with medication, the American Psychiatric Association violent or accidental event, or repeated or excessive exposure recommends continued treatment for at least 1 to 2 years.

least one of the following: direct experience of or witnessing a alternative, although side effects are common. For patients traumatic situation, learning that a loved one experienced a treated with medication, the American Psychiatric Association violent or accidental event, or repeated or excessive exposure recommends continued treatment for at least 1 to 2 years. to details of a traumatic event (e.g., a social worker repeatedly exposed to cases of child abuse). Prevalence varies by popula- tion, gender identity, socioeconomic class, and profession, Substance Use Disorders with increased rates of PTSD seen in first responders, mem- Tobacco bers of the military, and marginalized populations. PTSD often Despite a significant shift in public health behaviors and atti- occurs concomitantly with mood disorders and other anxiety tudes over the past 30 years, tobacco use remains the most disorders and is associated with increased risk for substance common cause of preventable death in the United States, with use and other medical conditions, including cardiovascular or all-cause mortality three to five times higher in smokers than autoimmune disease. in nonsmokers. Tobacco use increases the risk for multiple Diagnosis of PTSD can be challenging because of the types of cancer, pulmonary diseases, diabetes, osteoporosis, patient’s desire to avoid discussing the event and the fre- and cardiovascular conditions. The benefits of quitting tobacco quency of concomitant psychiatric disorders. The DSM-5 diag- use begin immediately, and over decades, risks for many of the nostic criteria for PTSD are complex. In general, PTSD is associated conditions decrease substantially. characterized by intrusive memories of the traumatic event The USPSTF recommends that clinicians ask all adults (recurrent nightmares or flashbacks), persistent avoidance of about tobacco use, advise them to stop using tobacco, and pro- reminders or triggers (people or places), persistent negative vide behavioral interventions and approved pharmacotherapy changes in thoughts and mood (negative beliefs, anhedonia), to adult tobacco users (Table 50). Abrupt cessation of tobacco

to details of a traumatic event (e.g., a social worker repeatedly exposed to cases of child abuse). Prevalence varies by popula- tion, gender identity, socioeconomic class, and profession, Substance Use Disorders with increased rates of PTSD seen in first responders, mem- Tobacco bers of the military, and marginalized populations. PTSD often Despite a significant shift in public health behaviors and atti- occurs concomitantly with mood disorders and other anxiety tudes over the past 30 years, tobacco use remains the most disorders and is associated with increased risk for substance common cause of preventable death in the United States, with use and other medical conditions, including cardiovascular or all-cause mortality three to five times higher in smokers than autoimmune disease. in nonsmokers. Tobacco use increases the risk for multiple Diagnosis of PTSD can be challenging because of the types of cancer, pulmonary diseases, diabetes, osteoporosis, patient’s desire to avoid discussing the event and the fre- and cardiovascular conditions. The benefits of quitting tobacco quency of concomitant psychiatric disorders. The DSM-5 diag- use begin immediately, and over decades, risks for many of the nostic criteria for PTSD are complex. In general, PTSD is associated conditions decrease substantially. characterized by intrusive memories of the traumatic event The USPSTF recommends that clinicians ask all adults (recurrent nightmares or flashbacks), persistent avoidance of about tobacco use, advise them to stop using tobacco, and pro- reminders or triggers (people or places), persistent negative vide behavioral interventions and approved pharmacotherapy changes in thoughts and mood (negative beliefs, anhedonia), to adult tobacco users (Table 50). Abrupt cessation of tobacco 80

Mental and Behavioral Health TABLE 50. Tobacco Cessation: The 5 A’s nicotine-containing aerosol also includes other chemicals (e.g., formaldehyde, propylene glycol, and heavy metals) that may be ASK about tobacco use at every encounter harmful. E-cigarette associated lung injury may occur and Identify and document tobacco use result in severe acute pulmonary disease and death; it is highly Consider a systematic process (e.g., asking about tobacco | associated with vaping products that contain tetrahydrocan- use when taking vital signs) nabinol and vitamin E acetate. Use of e-cigarettes may also act ADVISE patients to quit tobacco use | as a “gateway” for young people, leading to smoking more tra- Strong, clear, personalized message ditional tobacco products. The National Academy of Sciences ASSESS willingness to quit | concluded that e-cigarettes are not without biological effects,

TABLE 50. Tobacco Cessation: The 5 A’s nicotine-containing aerosol also includes other chemicals (e.g., formaldehyde, propylene glycol, and heavy metals) that may be ASK about tobacco use at every encounter harmful. E-cigarette associated lung injury may occur and Identify and document tobacco use result in severe acute pulmonary disease and death; it is highly Consider a systematic process (e.g., asking about tobacco | associated with vaping products that contain tetrahydrocan- use when taking vital signs) nabinol and vitamin E acetate. Use of e-cigarettes may also act ADVISE patients to quit tobacco use | as a “gateway” for young people, leading to smoking more tra- Strong, clear, personalized message ditional tobacco products. The National Academy of Sciences ASSESS willingness to quit | concluded that e-cigarettes are not without biological effects, Not everyone is ready to try to quit | including dependence, although not to the extent of combusti- ble tobacco cigarettes. The implications for long-term effects on If not ready, offer motivational counseling morbidity and mortality remain unclear. E-cigarettes should | ASSIST in quitting | not be recommended for smoking cessation. | Seta quit date

Not everyone is ready to try to quit | including dependence, although not to the extent of combusti- ble tobacco cigarettes. The implications for long-term effects on If not ready, offer motivational counseling morbidity and mortality remain unclear. E-cigarettes should | ASSIST in quitting | not be recommended for smoking cessation. | Seta quit date | Behavioral changes: alternatives, skills | Alcohol Pharmacotherapy | Heavy alcohol use is the third leading cause of preventable death in the United States, and alcohol-related costs, the Support: environment, triggers majority of which are related to binge drinking, are estimated ARRANGE follow-up to exceed more than $250 billion annually. Individuals with In person, telephone, electronic disordered alcohol use often interact with the health care sys- Monitor progress, side effects, withdrawal tem but rarely receive appropriate treatment; less than 10% of

| Behavioral changes: alternatives, skills | Alcohol Pharmacotherapy | Heavy alcohol use is the third leading cause of preventable death in the United States, and alcohol-related costs, the Support: environment, triggers majority of which are related to binge drinking, are estimated ARRANGE follow-up to exceed more than $250 billion annually. Individuals with In person, telephone, electronic disordered alcohol use often interact with the health care sys- Monitor progress, side effects, withdrawal tem but rarely receive appropriate treatment; less than 10% of Adapted from Fiore MC, Jaen C, Baker T, et al. Treating tobacco use and patients who may benefit from treatment for alcohol use dependence: 2008 update. Clinical Practice Guideline. Rockville, MD: US Department of Health and Human Services. 2008. www.ncbi.nlm.nih.gov/books/ disorder receive it. | NBK63952/. The USPSTF recommends routine screening for unhealthy alcohol use. Recommended screening tools include the Alcohol use may result in higher long-term abstinence rates than grad- Use Disorders Identification Test (AUDIT) (https://pubs.niaaa. ually decreasing use, and combining behavioral counseling nih.gov/publications/Audit.pdf), the abbreviated AUDIT- with pharmacotherapy is more effective than either modality Consumption (AUDIT-C) (https://www.hepatitis.va.gov/ alone. Effective counseling and behavioral resources include alcohol/treatment/audit-c.asp), and the single-question screen problem-solving guidance (e.g., developing a quit plan and “How many times in the past year have you had five (four for overcoming barriers), motivational interviewing, social sup- women and adults age >65 years) or more drinks in 1 day?”. port, and telephone quit lines. There is a dose-response rela- Patients with a positive screening result should be assessed for tionship between the intensity and frequency of counseling the presence of alcohol use disorder. Severity of the disorder and quit rates, which seem to plateau after 90 minutes of total and related health consequences, including hepatic, cardiac, counseling. and neurologic sequelae, should also be assessed. Comorbid All smokers without contraindications should addition- psychiatric, chronic pain, and substance use disorders are ally receive at least one of seven FDA-approved treatments for often present and require interdisciplinary treatment and smoking cessation (Table 51). Varenicline is superior to other subspecialty referral. treatments; combining varenicline with nicotine replacement Treatment should be tailored to the patient’s risk level is the most effective strategy. Moderate- and high-dose prepa- (Table 52) and includes psychotherapy (CBT) and pharmaco- rations of nicotine replacement therapy are more effective therapy (Table 53). Patients with liver disease, especially those than lower-dose ones, and combining more than one type of with alcohol-related liver disease, should be counseled against nicotine replacement therapy (short-acting and long-acting) is the use of alcohol. Naltrexone and acamprosate are both rec- more effective than monotherapy. Initiation of therapy, espe- ommended as first-line pharmacologic therapy for moderate cially varenicline, before smoking is stopped may also increase to severe alcohol use disorder. The choice between naltrexone quitting success rates. For stable patients with cardiovascular and acamprosate should be directed by pharmacologic consid- disease and hospitalized patients with acute coronary syn- erations, patient preference, and the presence of comorbidi- drome, the American College of Cardiology recommends ties. Patients with alcohol-related liver disease, at-risk patients either varenicline or combined short- and long-acting nico- who do not respond to brief interventions, and patients with tine replacement therapy as first-line therapies. alcohol use disorder who do not respond to office-based thera- Although tobacco use has decreased overall, increasing pies should be referred to addiction specialists. use of electronic nicotine delivery systems (also known as Alcohol withdrawal is a common complication of alcohol e-cigarettes and vaping), particularly among young people, is use disorder. Minor symptoms, such as tremulousness, dia- creating new health concerns. Although e-cigarettes may phoresis, and palpitations, can occur 6 hours after the last have a benefit of harm reduction for established smokers, the drink. Alcoholic hallucinosis (hallucinations without clouding

Adapted from Fiore MC, Jaen C, Baker T, et al. Treating tobacco use and patients who may benefit from treatment for alcohol use dependence: 2008 update. Clinical Practice Guideline. Rockville, MD: US Department of Health and Human Services. 2008. www.ncbi.nlm.nih.gov/books/ disorder receive it. | NBK63952/. The USPSTF recommends routine screening for unhealthy alcohol use. Recommended screening tools include the Alcohol use may result in higher long-term abstinence rates than grad- Use Disorders Identification Test (AUDIT) (https://pubs.niaaa. ually decreasing use, and combining behavioral counseling nih.gov/publications/Audit.pdf), the abbreviated AUDIT- with pharmacotherapy is more effective than either modality Consumption (AUDIT-C) (https://www.hepatitis.va.gov/ alone. Effective counseling and behavioral resources include alcohol/treatment/audit-c.asp), and the single-question screen problem-solving guidance (e.g., developing a quit plan and “How many times in the past year have you had five (four for overcoming barriers), motivational interviewing, social sup- women and adults age >65 years) or more drinks in 1 day?”. port, and telephone quit lines. There is a dose-response rela- Patients with a positive screening result should be assessed for tionship between the intensity and frequency of counseling the presence of alcohol use disorder. Severity of the disorder and quit rates, which seem to plateau after 90 minutes of total and related health consequences, including hepatic, cardiac, counseling. and neurologic sequelae, should also be assessed. Comorbid All smokers without contraindications should addition- psychiatric, chronic pain, and substance use disorders are ally receive at least one of seven FDA-approved treatments for often present and require interdisciplinary treatment and smoking cessation (Table 51). Varenicline is superior to other subspecialty referral. treatments; combining varenicline with nicotine replacement Treatment should be tailored to the patient’s risk level is the most effective strategy. Moderate- and high-dose prepa- (Table 52) and includes psychotherapy (CBT) and pharmaco- rations of nicotine replacement therapy are more effective therapy (Table 53). Patients with liver disease, especially those than lower-dose ones, and combining more than one type of with alcohol-related liver disease, should be counseled against nicotine replacement therapy (short-acting and long-acting) is the use of alcohol. Naltrexone and acamprosate are both rec- more effective than monotherapy. Initiation of therapy, espe- ommended as first-line pharmacologic therapy for moderate cially varenicline, before smoking is stopped may also increase to severe alcohol use disorder. The choice between naltrexone quitting success rates. For stable patients with cardiovascular and acamprosate should be directed by pharmacologic consid- disease and hospitalized patients with acute coronary syn- erations, patient preference, and the presence of comorbidi- drome, the American College of Cardiology recommends ties. Patients with alcohol-related liver disease, at-risk patients either varenicline or combined short- and long-acting nico- who do not respond to brief interventions, and patients with tine replacement therapy as first-line therapies. alcohol use disorder who do not respond to office-based thera- Although tobacco use has decreased overall, increasing pies should be referred to addiction specialists. use of electronic nicotine delivery systems (also known as Alcohol withdrawal is a common complication of alcohol e-cigarettes and vaping), particularly among young people, is use disorder. Minor symptoms, such as tremulousness, dia- creating new health concerns. Although e-cigarettes may phoresis, and palpitations, can occur 6 hours after the last have a benefit of harm reduction for established smokers, the drink. Alcoholic hallucinosis (hallucinations without clouding 81

TABLE 51. Approved Medications for Treatment of Tobacco Use Product Advantages Disadvantages Precautions Side Effects Long-Acting Nicotine patch Place and forget; Passive—no action to Use with caution within Skin reaction (50% of available over the take when craving 2 wk of a cardiac event? patients), vivid dreams counter; can decrease occurs or sleep disturbances morning cravings if worn at night Bupropion SR (twice Less weight gain; Side effects not Do not use in patients Insomnia (40%), dry daily) and XL(once antidepressant benefit uncommon with seizure disorders, mouth, headache, daily) current use of anxiety, rash Passive—no action to bupropion or MAO take with cravings; inhibitors, electrolyte prescription required abnormalities, or eating disorders; monitor blood pressure

Bupropion SR (twice Less weight gain; Side effects not Do not use in patients Insomnia (40%), dry daily) and XL(once antidepressant benefit uncommon with seizure disorders, mouth, headache, daily) current use of anxiety, rash Passive—no action to bupropion or MAO take with cravings; inhibitors, electrolyte prescription required abnormalities, or eating disorders; monitor blood pressure | Varenicline Reduces withdrawal; Passive—no action to Avoid with severe Nausea (30%), insomnia, may prevent relapse take with cravings kidney disease; evaluate vivid dreams/ P — — for mental illness and nightmares rescription require MOHIOEMOGU | Short-Acting

| Varenicline Reduces withdrawal; Passive—no action to Avoid with severe Nausea (30%), insomnia, may prevent relapse take with cravings kidney disease; evaluate vivid dreams/ P — — for mental illness and nightmares rescription require MOHIOEMOGU | Short-Acting Nicotine gum Use as needed; can self- Difficult to chew, poor Proper use is “chew and Jaw pain; nausea if dose; available over the taste park (at cheek)” swallowing saliva counter Use with caution within 2 wk of a cardiac event? Nicotine inhaler Use as needed; mimics Costly; visible; requires Caution within 2 wk of a Cough, throat irritation hand-mouth behavior prescription cardiac event? Nicotine nasal spray Use as needed; rapid Costly; visible; requires Use with caution in Nasal irritation; possible relief of symptoms prescription patients with asthma or dependence nasal/sinus problems Use with caution within 2 wk of a cardiac event?

Nicotine nasal spray Use as needed; rapid Costly; visible; requires Use with caution in Nasal irritation; possible relief of symptoms prescription patients with asthma or dependence nasal/sinus problems Use with caution within 2 wk of a cardiac event? Nicotine lozenge Ease of use; available Slightly more costly than Caution within 2 wk of Hiccups, nausea, over the counter; gum cardiac event? heartburn flexible dosing MAO = monoamine oxidase; SR = sustained release; XL= extended release. Recent myocardial infarction, severe angina, or life-threatening arrhythmia. | Adapted with permission from Patel MS, Steinberg MB. In the clinic. Smoking cessation. Ann Intern Med. 2016:164:ITC33-48. [PMID: 26926702] doi:10.7326/AITC201603010. | ©2016, American College of Physicians. of the sensorium) is typically seen 12 to 24 hours after cessa- progress to severe withdrawal (delirium tremens). Delirium tion, and withdrawal seizures may occur within 12 to 48 hours tremens usually begins 48 to 96 hours after the last alcoholic of cessation of alcohol use. These effects are treated expec- drink and manifests as autonomic activation (e.g., hyperten- tantly, although a significant percentage of patients will sion, tachycardia) and altered mental status. It is often TABLE 52. Alcohol Use Categories | | Category Definition Health Consequences | Moderate- or lower-risk No more than four drinks on a single day or Uncommon | alcohol use 14 drinks/wk for men; for men >65 years of age |

TABLE 52. Alcohol Use Categories | | Category Definition Health Consequences | Moderate- or lower-risk No more than four drinks on a single day or Uncommon | alcohol use 14 drinks/wk for men; for men >65 years of age | and women, no more than three drinks ona single | | day or seven drinks in a week | Hazardous or When thresholds for lower-risk alcohol use are Increased risk for alcohol-related social and legal at-risk drinking exceeded consequences Harmful alcohol use Pattern of drinking that causes health consequences _ Alcohol use disorder When the individual meets at least 2 of the 11 DSM-5 Patients with moderate to severe alcohol use criteria disorder (more than three criteria met) may benefit | from more intensive treatment 82

Mental and Behavioral Health TABLE 53. Pharmacotherapy for Alcohol Use Disorder | Medication and Indication Mechanism Side Effects Notes | Typical Dosage? | Naltrexone Relapse Opioid antagonist that may Nausea, indigestion, Contraindicated with | revention reduce the subjective reward headache, fatigue concurrent opioid use; offer le Oral,50-100mg seacy: g ! associated with alcohol use : with concomitant opioid use| | daily Depressive symptoms dizardere | Soca . abet medication-associated Avoid in patients with | | magmonly BPaunS decompensated cirrhosis, | Potential for precipitated acute hepatitis, or liver | opioid withdrawal with opioid _ failure; use with caution in | | use patients with hepatitis or | compensated cirrhosis |

magmonly BPaunS decompensated cirrhosis, | Potential for precipitated acute hepatitis, or liver | opioid withdrawal with opioid _ failure; use with caution in | | use patients with hepatitis or | compensated cirrhosis | | Acamprosate Relapse May antagonize glutamate- Diarrhea, nausea/vomiting, Can be used in patients with | | 666 h prevention mediated neuronal myalgia, rash, dizziness, alcohol-related liver disease | ti Up he Ie hyperexcitability and reduce palpitations Avetelln eemeneth | | UmMes Cary prolonged (but not acute) ‘ re WENO Pale ra WINREVELe | | withdrawal @inBternis Rarely associated with kidney kidney impairment (eGFR ymp impairment <30 mL/min/1.73 m?); second- | line therapy in mild to | | moderate kidney impairment | | and g requires reduced dosage? 9g |

| Acamprosate Relapse May antagonize glutamate- Diarrhea, nausea/vomiting, Can be used in patients with | | 666 h prevention mediated neuronal myalgia, rash, dizziness, alcohol-related liver disease | ti Up he Ie hyperexcitability and reduce palpitations Avetelln eemeneth | | UmMes Cary prolonged (but not acute) ‘ re WENO Pale ra WINREVELe | | withdrawal @inBternis Rarely associated with kidney kidney impairment (eGFR ymp impairment <30 mL/min/1.73 m?); second- | line therapy in mild to | | moderate kidney impairment | | and g requires reduced dosage? 9g | | May be used with naltrexone | Medication adherence may | be challenging Disulfiram Prevention of Aldehyde dehydrogenase Drowsiness, rash Potential for many drug-drug 2 drinking and inhibition results in ills : interactions se IE relapse prevention acetaldehyde accumulation with alcohol use, leading to Rutaly, inecieationassocated severe hepatotoxicity, optic : Patient must be abstinent . neuritis, peripheral 212 h before medication | unpleasant symptoms neuropathy administration | (alcohol-disulfiram reaction) Avoid in patients with hepatic impairment or cardiovascular disease

| May be used with naltrexone | Medication adherence may | be challenging Disulfiram Prevention of Aldehyde dehydrogenase Drowsiness, rash Potential for many drug-drug 2 drinking and inhibition results in ills : interactions se IE relapse prevention acetaldehyde accumulation with alcohol use, leading to Rutaly, inecieationassocated severe hepatotoxicity, optic : Patient must be abstinent . neuritis, peripheral 212 h before medication | unpleasant symptoms neuropathy administration | (alcohol-disulfiram reaction) Avoid in patients with hepatic impairment or cardiovascular disease Most appropriate for patients with strong motivation to be abstinent and with support to promote medication adherence

Most appropriate for patients with strong motivation to be abstinent and with support to promote medication adherence eGFR = estimated glomerular filtration rate. *Naltrexone, disulfiram, and acamprosate are all FDA pregnancy category C (animal studies indicate potential fetal risk or have not been conducted, and no or insufficient human studies have been done; drugs in this category should be used in pregnant or lactating women only when potential benefits justify potential risk to the fetus or infant). ®Information from Reus VI, Fochtmann LJ, Bukstein O, et al. The American Psychiatric Association practice guideline for the pharmacological treatment of patients with alcohol use | disorder. Am J Psychiatry. 2018;175:86-90. [PMID: 29301420] doi:10.1176/appi.ajp.2017.1750101 | Adapted with permission from Edelman EJ, Fiellin DA. In the clinic. Alcohol use. Ann Intern Med. 2016;164:ITC10. [PMID: 26747315]. doi:10.7326/AITC201601050. © 2016, | American College of Physicians.

®Information from Reus VI, Fochtmann LJ, Bukstein O, et al. The American Psychiatric Association practice guideline for the pharmacological treatment of patients with alcohol use | disorder. Am J Psychiatry. 2018;175:86-90. [PMID: 29301420] doi:10.1176/appi.ajp.2017.1750101 | Adapted with permission from Edelman EJ, Fiellin DA. In the clinic. Alcohol use. Ann Intern Med. 2016;164:ITC10. [PMID: 26747315]. doi:10.7326/AITC201601050. © 2016, | American College of Physicians. preceded by mild symptoms of withdrawal or withdrawal Drugs seizures. Illicit drug use occurs in 9% of the U.S. population. The most Many patients with alcohol withdrawal require hospitali- commonly used drugs are cannabis, prescription drugs, zation, although some low-risk patients can be safely managed cocaine, hallucinogens, inhalants, heroin, and fentanyl. in the outpatient setting. The Prediction of Alcohol Withdrawal Internists play a central role in prevention, diagnosis, and Severity Scale (PAWSS) is a 10-item scale with high positive management of substance use disorders, including identifying and negative likelihood ratios for predicting severe alcohol and managing medical comorbidities and reducing harm. withdrawal syndrome. Benzodiazepines are the safest and Effective communication and screening can also help identify most effective method to manage withdrawal (Table 54). After patients at risk for drug interactions. The USPSTF recom- initial dosing to control symptoms acutely, a symptom- mends screening for the use of illegal or nonprescribed psy- triggered approach using standardized instruments, such as choactive drugs in all adults aged 18 years or older as long as the Clinical Institute Withdrawal Assessment for Alcohol, the physician can provide access to further diagnostic and Revised (CIWA-Ar), should be used to measure the severity of treatment services. The USPTF makes no recommendation withdrawal and guide treatment. Phenobarbital, propofol, and regarding routine screening for illicit drug use in adolescents, dexmedetomidine may be useful in refractory cases. as there is insufficient evidence regarding the risks and

preceded by mild symptoms of withdrawal or withdrawal Drugs seizures. Illicit drug use occurs in 9% of the U.S. population. The most Many patients with alcohol withdrawal require hospitali- commonly used drugs are cannabis, prescription drugs, zation, although some low-risk patients can be safely managed cocaine, hallucinogens, inhalants, heroin, and fentanyl. in the outpatient setting. The Prediction of Alcohol Withdrawal Internists play a central role in prevention, diagnosis, and Severity Scale (PAWSS) is a 10-item scale with high positive management of substance use disorders, including identifying and negative likelihood ratios for predicting severe alcohol and managing medical comorbidities and reducing harm. withdrawal syndrome. Benzodiazepines are the safest and Effective communication and screening can also help identify most effective method to manage withdrawal (Table 54). After patients at risk for drug interactions. The USPSTF recom- initial dosing to control symptoms acutely, a symptom- mends screening for the use of illegal or nonprescribed psy- triggered approach using standardized instruments, such as choactive drugs in all adults aged 18 years or older as long as the Clinical Institute Withdrawal Assessment for Alcohol, the physician can provide access to further diagnostic and Revised (CIWA-Ar), should be used to measure the severity of treatment services. The USPTF makes no recommendation withdrawal and guide treatment. Phenobarbital, propofol, and regarding routine screening for illicit drug use in adolescents, dexmedetomidine may be useful in refractory cases. as there is insufficient evidence regarding the risks and 83

Mental and Behavioral Health TABLE 54. Pharmacotherapy for Alcohol Withdrawal Medication Indication Side Effects Notes Benzodiazepines? Treatment or prophylaxis for Oversedation, paradoxical Caution in patients with alcohol withdrawal syndrome hyperactivity, depression, respiratory or hepatic impairment addictive potential Dexmedetomidine Adjunctive treatment of severe Bradycardia Clinical use increasing despite alcohol withdrawal symptoms in lack of evidence of clear benefit an ICU setting | Gabapentin Treatment of mild alcohol Oversedation, abuse potential Caution in patients with kidney withdrawal symptoms disease Phenobarbital Treatment of status epilepticus Respiratory depression requiring Used in combination therapy for and delirium tremens airway protection severe cases Propofol Treatment of status epilepticus Respiratory depression requiring Caution in patients with severe and delirium tremens airway protection cardiac disease GABA = -aminobutyric acid; NMDA = N-methyl-D-aspartate. | *Benzodiazepines are FDA pregnancy category X (contraindicated in pregnancy) or D (positive evidence of risk).

Propofol Treatment of status epilepticus Respiratory depression requiring Caution in patients with severe and delirium tremens airway protection cardiac disease GABA = -aminobutyric acid; NMDA = N-methyl-D-aspartate. | *Benzodiazepines are FDA pregnancy category X (contraindicated in pregnancy) or D (positive evidence of risk). benefits of this practice. Several screening tools are available, pharmacotherapy. Psychosocial support and counseling may including the four-question National Institute on Drug also be provided, although evidence of effectiveness is lacking. Abuse Quick Screen. Treatment primarily involves psycho- A major complication of opioid use is overdose. The risk therapeutic support. Internists also play a role in harm for opioid overdose is increased with higher doses and concur- reduction, ensuring that at-risk patients (such as injection rent benzodiazepine prescription. Although nonfatal prescrip- drug users) receive appropriate vaccinations and referrals to tion opioid overdose presents an opportunity for intervention, needle exchange services. most patients continue to receive opioids, and those receiving the highest dosage had the highest risk for repeated overdose. Marijuana Nonmedical use of prescription opioids is a strong risk factor Marijuana remains the most commonly used illicit drug, a for heroin use, although the transition to heroin occurs at a definition that is increasingly challenging in the current regu- low rate and is influenced by drug cost and availability. latory atmosphere, in which state laws allowing medical and Intranasal naloxone is an important adjunct therapy in recreational cannabis use are expanding rapidly while federal opioid use disorder, with evidence demonstrating a reduction law continues to classify cannabis as a schedule I substance. in overdose death when used. Naloxone kits and overdose Evidence shows that cannabis use is increasing and that a prevention education should be provided to patients at majority of U.S. adults accept recreational legalization of increased risk for overdose, such as those receiving daily doses cannabis. of 50 morphine milligram equivalents per day or more or Cannabis use has been associated with long-term medical those concurrently taking a benzodiazepine. Certain comorbid

benefits of this practice. Several screening tools are available, pharmacotherapy. Psychosocial support and counseling may including the four-question National Institute on Drug also be provided, although evidence of effectiveness is lacking. Abuse Quick Screen. Treatment primarily involves psycho- A major complication of opioid use is overdose. The risk therapeutic support. Internists also play a role in harm for opioid overdose is increased with higher doses and concur- reduction, ensuring that at-risk patients (such as injection rent benzodiazepine prescription. Although nonfatal prescrip- drug users) receive appropriate vaccinations and referrals to tion opioid overdose presents an opportunity for intervention, needle exchange services. most patients continue to receive opioids, and those receiving the highest dosage had the highest risk for repeated overdose. Marijuana Nonmedical use of prescription opioids is a strong risk factor Marijuana remains the most commonly used illicit drug, a for heroin use, although the transition to heroin occurs at a definition that is increasingly challenging in the current regu- low rate and is influenced by drug cost and availability. latory atmosphere, in which state laws allowing medical and Intranasal naloxone is an important adjunct therapy in recreational cannabis use are expanding rapidly while federal opioid use disorder, with evidence demonstrating a reduction law continues to classify cannabis as a schedule I substance. in overdose death when used. Naloxone kits and overdose Evidence shows that cannabis use is increasing and that a prevention education should be provided to patients at majority of U.S. adults accept recreational legalization of increased risk for overdose, such as those receiving daily doses cannabis. of 50 morphine milligram equivalents per day or more or Cannabis use has been associated with long-term medical those concurrently taking a benzodiazepine. Certain comorbid and psychological adverse effects, including reduced cognitive conditions, including COPD, obstructive sleep apnea, other function, depression, and anxiety. Pulmonary complications, substance use disorders, and mental health disorders, also such as worsening of underlying asthma, may occur. Cannabis increase the risk for opioid-related death. Other patients at hyperemesis syndrome, a recognized complication of heavy high risk for overdose are those illicitly using opioids or stimu- cannabis use, is characterized by recurrent nausea and vomit- lants contaminated with opioids, those with a history of opi- ing that is often relieved by prolonged hot showers. oid misuse who have recently been released from incarceration, and individuals receiving treatment for opioid use disorder. Opioids Friends, family members, and caretakers may also receive

and psychological adverse effects, including reduced cognitive conditions, including COPD, obstructive sleep apnea, other function, depression, and anxiety. Pulmonary complications, substance use disorders, and mental health disorders, also such as worsening of underlying asthma, may occur. Cannabis increase the risk for opioid-related death. Other patients at hyperemesis syndrome, a recognized complication of heavy high risk for overdose are those illicitly using opioids or stimu- cannabis use, is characterized by recurrent nausea and vomit- lants contaminated with opioids, those with a history of opi- ing that is often relieved by prolonged hot showers. oid misuse who have recently been released from incarceration, and individuals receiving treatment for opioid use disorder. Opioids Friends, family members, and caretakers may also receive Prescription opioid use has emerged as a major cause of mor- prescriptions and training in naloxone use. bidity and mortality, necessitating coordinated medical and Opioid withdrawal is a common syndrome that results policy responses (see Pain for a discussion of opioid risk assess- from either abrupt cessation of long-term opioid use or the

Prescription opioid use has emerged as a major cause of mor- prescriptions and training in naloxone use. bidity and mortality, necessitating coordinated medical and Opioid withdrawal is a common syndrome that results policy responses (see Pain for a discussion of opioid risk assess- from either abrupt cessation of long-term opioid use or the ment and mitigation). Opioid use disorder is characterized by administration of an opioid antagonist (naloxone). Onset of use of opioids in increasing amounts or for longer than symptoms varies from immediate to several days later, depend- intended, continued use of opioids despite impaired social ing on whether an opioid antagonist was administered and the functioning, repeated episodes of withdrawal, abandonment of duration of action of the opioid. Symptoms are nonspecific and important events or activities, and physical and psychological include nausea, vomiting, diarrhea, and restlessness. Treatment problems. Internists are increasingly treating opioid use disor- depends on the individual situation; options include support- der with pharmacotherapy in the office (Table 55), and most ive care (e.g., antiemetics, benzodiazepines) and long-acting patients with opioid use disorder will require extended opioid agonists (e.g., methadone, buprenorphine). 84

Mental and Behavioral Health TABLE 55. Pharmacotherapy for Opioid Use Disorder | Medication Uses Side Effects and Risks Precautions Notes Methadone Medication-assisted Sedation, prolongation of — Prolonged, variable half- U.S. schedule II treatment for OUD the OT interval; similar to life with incomplete cross- For outpatient addiction other opioids in terms of tolerance with other treatment, only available long-term use opioids; requires low through state-licensed initiation dose and slow Risk for respiratory programs titration depression and overdose Potential for drug interactions with inducers or inhibitors of the P450 system

Methadone Medication-assisted Sedation, prolongation of — Prolonged, variable half- U.S. schedule II treatment for OUD the OT interval; similar to life with incomplete cross- For outpatient addiction other opioids in terms of tolerance with other treatment, only available long-term use opioids; requires low through state-licensed initiation dose and slow Risk for respiratory programs titration depression and overdose Potential for drug interactions with inducers or inhibitors of the P450 system Buprenorphine- Medication-assisted Nausea, constipation, Risk for precipitated U.S. schedule Ill naloxone treatment for OUD headache, insomnia opioid withdrawal if Requires specialized initiated too soon in Pain management for Decreased risk for training (8-hour course) to | opioid-tolerant patient patients with concurrent overdose; naloxone obtain federal waiver to after last use of full opioid OUD and pain syndromes component activates if prescribe agonist requiring opioids (e.g., patient injects medication cancer-related pain)

Buprenorphine- Medication-assisted Nausea, constipation, Risk for precipitated U.S. schedule Ill naloxone treatment for OUD headache, insomnia opioid withdrawal if Requires specialized initiated too soon in Pain management for Decreased risk for training (8-hour course) to | opioid-tolerant patient patients with concurrent overdose; naloxone obtain federal waiver to after last use of full opioid OUD and pain syndromes component activates if prescribe agonist requiring opioids (e.g., patient injects medication cancer-related pain) Buprenorphine Inpatient withdrawal Nausea, constipation, Risk for precipitated U.S. schedule III management headache, insomnia opioid withdrawal if Requires federal waiver initiated too soon after Maintenance, particularly Rarely associated with last use of full opioid Once-monthly injection for pregnant women overdose, usually in agonist formulation available combination with other sedating agents

Buprenorphine Inpatient withdrawal Nausea, constipation, Risk for precipitated U.S. schedule III management headache, insomnia opioid withdrawal if Requires federal waiver initiated too soon after Maintenance, particularly Rarely associated with last use of full opioid Once-monthly injection for pregnant women overdose, usually in agonist formulation available combination with other sedating agents Naltrexone IM Maintenance Nausea, fatigue, dizziness, Risk for overdose if a dose Some variability in length | injection site reaction is missed and the patient of time for full opioid | relapses blockade Periodic monitoring of liver enzymes is recommended; impaired metabolism in liver disease

Periodic monitoring of liver enzymes is recommended; impaired metabolism in liver disease Oral Bridge before IM Nausea, headache, Periodic monitoring of naltrexone; maintenance in dizziness, elevated liver enzymes is highly supervised settings aminotransferase levels recommended; impaired metabolism in liver disease IM = intramuscular; OUD = opioid use disorder. Adapted with permission from Pace CA, Samet JH. In the clinic. Substance use disorders. Ann Intern Med. 2016;164:ITC58-ITC59. [PMID: 27043992] doi:10.7326/AITC201604050. © 2016, American College of Physicians.

Oral Bridge before IM Nausea, headache, Periodic monitoring of naltrexone; maintenance in dizziness, elevated liver enzymes is highly supervised settings aminotransferase levels recommended; impaired metabolism in liver disease IM = intramuscular; OUD = opioid use disorder. Adapted with permission from Pace CA, Samet JH. In the clinic. Substance use disorders. Ann Intern Med. 2016;164:ITC58-ITC59. [PMID: 27043992] doi:10.7326/AITC201604050. © 2016, American College of Physicians. Stimulants and Hallucinogens Methamphetamines, cocaine, and substituted cathinones (“bath e Patients at risk for opioid overdose, including those pre- HVC salts”) are stimulants of abuse that cause various associated con- scribed high-dose opioids and those being treated for or ditions encountered in acute care settings. Management of toxic- in recovery from opioid use disorder, should be offered ity of drugs of abuse, including stimulants and hallucinogens, is naloxone. discussed in MKSAP 19 Pulmonary and Critical Care Medicine. e All patients with opioid use disorder require extended treatment consisting of both psychosocial support and e Clinicians should ask all adults about tobacco use, advise medication. them to stop using tobacco, and provide behavioral interventions and approved pharmacotherapy to adult tobacco users. Personality Disorders Personality disorders involve consistent patterns of interper- e Patients diagnosed with alcohol use disorder often require sonal behavior and perceptions that are inflexible, diverge both psychotherapeutic and pharmacologic approaches to significantly from the behavioral standards of the person’s ensure safety and minimize relapse; naltrexone and culture, and cause substantial functional impairment and acamprosate are first-line pharmacologic therapies. emotional distress. Development of these disorders usually (Continued) occurs in adolescence, and the prevalence in the United States

Stimulants and Hallucinogens Methamphetamines, cocaine, and substituted cathinones (“bath e Patients at risk for opioid overdose, including those pre- HVC salts”) are stimulants of abuse that cause various associated con- scribed high-dose opioids and those being treated for or ditions encountered in acute care settings. Management of toxic- in recovery from opioid use disorder, should be offered ity of drugs of abuse, including stimulants and hallucinogens, is naloxone. discussed in MKSAP 19 Pulmonary and Critical Care Medicine. e All patients with opioid use disorder require extended treatment consisting of both psychosocial support and e Clinicians should ask all adults about tobacco use, advise medication. them to stop using tobacco, and provide behavioral interventions and approved pharmacotherapy to adult tobacco users. Personality Disorders Personality disorders involve consistent patterns of interper- e Patients diagnosed with alcohol use disorder often require sonal behavior and perceptions that are inflexible, diverge both psychotherapeutic and pharmacologic approaches to significantly from the behavioral standards of the person’s ensure safety and minimize relapse; naltrexone and culture, and cause substantial functional impairment and acamprosate are first-line pharmacologic therapies. emotional distress. Development of these disorders usually (Continued) occurs in adolescence, and the prevalence in the United States 85

Mental and Behavioral Health is estimated at 10% to 15%. Comorbid psychiatric illness is Somatic Symptom and common. Three clusters of personality disorders have been defined on the basis of symptoms (Table 56). Related Disorders Personality disorders add challenges to patient care and Previously known as somatoform disorders, somatic symptom can serve as a substantial barrier to care. Physicians should and related disorders are characterized by medically unex- have open, sensitive discussions of the personality disorder plained symptoms that cause emotional distress and psycho- diagnosis with the patient and emphasize the purpose of care. social impairment. Prevalence is as high as 4%, and primary Such discussion may also make the patient more receptive care is a common setting for presentation. Patients with these to referral to a mental health professional. Establishing a disorders have very high health care utilization rates yet are relationship based on trust and clear boundaries can help often dissatisfied with their care. Before diagnosing any of facilitate care. Pharmacotherapy is a subject of ongoing inves- these disorders, clinicians should thoroughly evaluate for and tigation; however, no medications specifically treat personality optimize treatment of medical disease and other psychiatric disorders. Medications may be used to improve specific symp- disorders (e.g., depression, GAD). Many unexplained medical toms (e.g., mood stabilizers for impulsivity). Dialectical behav- problems are related to unidentified organic pathology, and ioral therapy can help patients improve coping mechanisms patients with known medical disease may have a concurrent

disorders. Medications may be used to improve specific symp- disorders (e.g., depression, GAD). Many unexplained medical toms (e.g., mood stabilizers for impulsivity). Dialectical behav- problems are related to unidentified organic pathology, and ioral therapy can help patients improve coping mechanisms patients with known medical disease may have a concurrent and behaviors. somatic symptom or related disorder. Medically unexplained symptoms that do not rise to the level of a psychiatric disorder are discussed in Common TABLE 56. Personality Disorders Symptoms.

and behaviors. somatic symptom or related disorder. Medically unexplained symptoms that do not rise to the level of a psychiatric disorder are discussed in Common TABLE 56. Personality Disorders Symptoms. Cluster A: Odd or Eccentric Thinking and Behaviors Types Paranoid: pervasive distrust of others; unjustified suspicion of others; unjustified suspicions regarding their partners or Somatic symptom disorder (previously called somatization spouses; overly hostile reactions to perceived insults disorder) is characterized by one or more somatic symptoms Schizoid: prefer to be alone and lack interest in relationships; that have been present for at least 6 months. These symptoms seem indifferent, cold, and unresponsive to social cues; take cause significant distress or interference with life and are asso- pleasure in few activities ciated with excessive thoughts, behaviors, and feelings related Schizotypal: manifest odd thinking, beliefs (e.g., their thoughts to the symptoms. When the main symptom is pain, “somatic are magical and can influence others, events have hidden meaning), dress, and other behaviors symptom disorder with predominant pain” is the diagnosis (previously referred to as pain disorder). Cluster B: Dramatic or Unpredictable Thinking and Behaviors, Emotional Illness anxiety disorder (formerly known as hypochon- driasis) is characterized by excessive concern about health and Antisocial: engage in such behaviors as lying, stealing, and other aggressive and violent behaviors; disregard others’ preoccupation with health-related activities (e.g., measuring feelings, rights, and safety; lack remorse for these behaviors; pulse). In contrast to somatic symptom disorder, no symptoms often experience recurrent legal problems or only mild somatic symptoms are present in illness anxiety Borderline: have chaotic relationships (idealized and devalued) disorder. and a fragile self-image; fear abandonment; experience labile Conversion disorder, involves at least one symptom of and intense emotions (e.g., anger), sense of emptiness; engage in impulsive and risky behaviors (e.g., gambling, sex); neurologic dysfunction (abnormal sensation or motor func- may manifest self-injury and suicidality tion) that is unexplained by a medical condition and not con- Histrionic: excessive emotionality and attention-seeking sistent with examination findings. Conversion disorder does behavior; dramatic; often seductive or sexually provocative; not represent fabrication of symptoms but rather unexplained melodramatic symptoms that do not have a pathophysiologic basis. These Narcissistic: grandiose and inflated self-perceptions; desire symptoms, which are functionally limiting, occur during attention times of substantial physical, emotional, or psychological Cluster C: Anxious and Fearful Thinking and Behaviors stress. Avoidant: feel inadequate and are sensitive to criticism; Somatic symptom and related disorders must be differen- extremely shy and socially inhibited and avoid activities that tiated from factitious disorder and malingering. Factitious involve interactions with others, especially strangers disorder (formerly called Munchausen syndrome) is an inten- Dependent: excessively dependent on others (“clingy”) and tional fabrication of symptoms or injury to oneself or another fear being alone; lack self-confidence and tolerate poor treatment by others without clear external benefit. Malingering occurs when a patient feigns medical problems for gain; thus, malingering is Obsessive-compulsive: perfectionistic and preoccupied with orderliness and rules; controlling of situations and others; rigid not a psychiatric diagnosis. regarding values; not the same as obsessive-compulsive disorder, which is an anxiety disorder Management Reproduced with permission from Schneider RK, Levenson JL. Psychiatry Essentials When treating patients with somatic symptom and related dis- for Primary Care. Philadelphia: American College of Physicians; 2008. orders, clinicians should acknowledge the patient’s symptoms

Cluster A: Odd or Eccentric Thinking and Behaviors Types Paranoid: pervasive distrust of others; unjustified suspicion of others; unjustified suspicions regarding their partners or Somatic symptom disorder (previously called somatization spouses; overly hostile reactions to perceived insults disorder) is characterized by one or more somatic symptoms Schizoid: prefer to be alone and lack interest in relationships; that have been present for at least 6 months. These symptoms seem indifferent, cold, and unresponsive to social cues; take cause significant distress or interference with life and are asso- pleasure in few activities ciated with excessive thoughts, behaviors, and feelings related Schizotypal: manifest odd thinking, beliefs (e.g., their thoughts to the symptoms. When the main symptom is pain, “somatic are magical and can influence others, events have hidden meaning), dress, and other behaviors symptom disorder with predominant pain” is the diagnosis (previously referred to as pain disorder). Cluster B: Dramatic or Unpredictable Thinking and Behaviors, Emotional Illness anxiety disorder (formerly known as hypochon- driasis) is characterized by excessive concern about health and Antisocial: engage in such behaviors as lying, stealing, and other aggressive and violent behaviors; disregard others’ preoccupation with health-related activities (e.g., measuring feelings, rights, and safety; lack remorse for these behaviors; pulse). In contrast to somatic symptom disorder, no symptoms often experience recurrent legal problems or only mild somatic symptoms are present in illness anxiety Borderline: have chaotic relationships (idealized and devalued) disorder. and a fragile self-image; fear abandonment; experience labile Conversion disorder, involves at least one symptom of and intense emotions (e.g., anger), sense of emptiness; engage in impulsive and risky behaviors (e.g., gambling, sex); neurologic dysfunction (abnormal sensation or motor func- may manifest self-injury and suicidality tion) that is unexplained by a medical condition and not con- Histrionic: excessive emotionality and attention-seeking sistent with examination findings. Conversion disorder does behavior; dramatic; often seductive or sexually provocative; not represent fabrication of symptoms but rather unexplained melodramatic symptoms that do not have a pathophysiologic basis. These Narcissistic: grandiose and inflated self-perceptions; desire symptoms, which are functionally limiting, occur during attention times of substantial physical, emotional, or psychological Cluster C: Anxious and Fearful Thinking and Behaviors stress. Avoidant: feel inadequate and are sensitive to criticism; Somatic symptom and related disorders must be differen- extremely shy and socially inhibited and avoid activities that tiated from factitious disorder and malingering. Factitious involve interactions with others, especially strangers disorder (formerly called Munchausen syndrome) is an inten- Dependent: excessively dependent on others (“clingy”) and tional fabrication of symptoms or injury to oneself or another fear being alone; lack self-confidence and tolerate poor treatment by others without clear external benefit. Malingering occurs when a patient feigns medical problems for gain; thus, malingering is Obsessive-compulsive: perfectionistic and preoccupied with orderliness and rules; controlling of situations and others; rigid not a psychiatric diagnosis. regarding values; not the same as obsessive-compulsive disorder, which is an anxiety disorder Management Reproduced with permission from Schneider RK, Levenson JL. Psychiatry Essentials When treating patients with somatic symptom and related dis- for Primary Care. Philadelphia: American College of Physicians; 2008. orders, clinicians should acknowledge the patient’s symptoms 86

Mental and Behavioral Health and focus on improving coping mechanisms and establishing Clues to the presence of an eating disorder on physical regularly scheduled visits. Diagnostic testing and referral to examination include findings suggesting malnutrition (muscle specialists should not be requested solely to provide reassur- wasting, xerosis, and lanugo) and/or self-induced vomiting ance. CBT is effective for patients with somatic symptom disor- (erosion of dental enamel, parotid gland enlargement, and der who are willing to undergo psychotherapy; antidepressant scarring or calluses on the dorsum of the hand). drugs also have demonstrated benefit. Illness anxiety disorder may respond to CBT, whereas disease education is the primary Medical Complications treatment for conversion disorder. Multiple medical problems due to malnutrition can develop in patients with anorexia nervosa. Patients often exhibit signs of a hypometabolic state, including bradycardia, hypoten- HVC e When treating patients with somatic symptom and sion, hypothermia, and decreased gastrointestinal motility. related disorders, clinicians should acknowledge the Electrolyte abnormalities (hypokalemia, hypomagnesemia, patient’s symptoms and focus on improving coping and hypophosphatemia) can cause dysrhythmia and contrib- mechanisms and establishing regularly scheduled visits. ute to increased mortality. Refeeding syndrome can worsen these electrolyte disturbances; prevention requires gradual,

and focus on improving coping mechanisms and establishing Clues to the presence of an eating disorder on physical regularly scheduled visits. Diagnostic testing and referral to examination include findings suggesting malnutrition (muscle specialists should not be requested solely to provide reassur- wasting, xerosis, and lanugo) and/or self-induced vomiting ance. CBT is effective for patients with somatic symptom disor- (erosion of dental enamel, parotid gland enlargement, and der who are willing to undergo psychotherapy; antidepressant scarring or calluses on the dorsum of the hand). drugs also have demonstrated benefit. Illness anxiety disorder may respond to CBT, whereas disease education is the primary Medical Complications treatment for conversion disorder. Multiple medical problems due to malnutrition can develop in patients with anorexia nervosa. Patients often exhibit signs of a hypometabolic state, including bradycardia, hypoten- HVC e When treating patients with somatic symptom and sion, hypothermia, and decreased gastrointestinal motility. related disorders, clinicians should acknowledge the Electrolyte abnormalities (hypokalemia, hypomagnesemia, patient’s symptoms and focus on improving coping and hypophosphatemia) can cause dysrhythmia and contrib- mechanisms and establishing regularly scheduled visits. ute to increased mortality. Refeeding syndrome can worsen these electrolyte disturbances; prevention requires gradual, Eating Disorders carefully monitored increase of nutritional intake. Osteopenia and osteoporosis are common and may not be fully reversible Types if anorexia occurred during peak bone development in adoles- Approximately 3% of the U.S. population has an eating disor- cence. Amenorrhea, anemia, and peripheral edema also occur der. Disorders most likely to be encountered by internists frequently and usually resolve with recovery from anorexia include anorexia nervosa, bulimia nervosa, and binge eating nervosa. disorder. Purging behaviors may also cause electrolyte abnormali- Anorexia nervosa is characterized by fear of weight gain ties. Self-induced vomiting may lead to upper gastrointestinal and a distorted body image, with restriction of caloric intake problems (esophagitis, esophageal tears), and laxative abuse relative to metabolic requirements that leads to below-normal may cause colonic dysmotility. body weight. DSM-5 further divides the disorder into sub- types: restricting type (no episodes of food binges or purging) Treatment and binge eating/purging type. Women are affected three to four times more often than are men, and onset most often The primary goal of treatment is reestablishing normal weight

Eating Disorders carefully monitored increase of nutritional intake. Osteopenia and osteoporosis are common and may not be fully reversible Types if anorexia occurred during peak bone development in adoles- Approximately 3% of the U.S. population has an eating disor- cence. Amenorrhea, anemia, and peripheral edema also occur der. Disorders most likely to be encountered by internists frequently and usually resolve with recovery from anorexia include anorexia nervosa, bulimia nervosa, and binge eating nervosa. disorder. Purging behaviors may also cause electrolyte abnormali- Anorexia nervosa is characterized by fear of weight gain ties. Self-induced vomiting may lead to upper gastrointestinal and a distorted body image, with restriction of caloric intake problems (esophagitis, esophageal tears), and laxative abuse relative to metabolic requirements that leads to below-normal may cause colonic dysmotility. body weight. DSM-5 further divides the disorder into sub- types: restricting type (no episodes of food binges or purging) Treatment and binge eating/purging type. Women are affected three to four times more often than are men, and onset most often The primary goal of treatment is reestablishing normal weight occurs in adolescence. and eating behaviors. Psychotherapy, family therapy, and

Eating Disorders carefully monitored increase of nutritional intake. Osteopenia and osteoporosis are common and may not be fully reversible Types if anorexia occurred during peak bone development in adoles- Approximately 3% of the U.S. population has an eating disor- cence. Amenorrhea, anemia, and peripheral edema also occur der. Disorders most likely to be encountered by internists frequently and usually resolve with recovery from anorexia include anorexia nervosa, bulimia nervosa, and binge eating nervosa. disorder. Purging behaviors may also cause electrolyte abnormali- Anorexia nervosa is characterized by fear of weight gain ties. Self-induced vomiting may lead to upper gastrointestinal and a distorted body image, with restriction of caloric intake problems (esophagitis, esophageal tears), and laxative abuse relative to metabolic requirements that leads to below-normal may cause colonic dysmotility. body weight. DSM-5 further divides the disorder into sub- types: restricting type (no episodes of food binges or purging) Treatment and binge eating/purging type. Women are affected three to four times more often than are men, and onset most often The primary goal of treatment is reestablishing normal weight occurs in adolescence. and eating behaviors. Psychotherapy, family therapy, and In bulimia nervosa, patients engage in binge eating fol- monitored dietary intake are the mainstays of treatment of anorexia nervosa. In some circumstances, hospitalization is lowed by compensatory behaviors to prevent weight gain at least once weekly for 3 months. Compensatory behaviors required to ensure adequate emotional support, appropriate

In bulimia nervosa, patients engage in binge eating fol- monitored dietary intake are the mainstays of treatment of anorexia nervosa. In some circumstances, hospitalization is lowed by compensatory behaviors to prevent weight gain at least once weekly for 3 months. Compensatory behaviors required to ensure adequate emotional support, appropriate include self-induced vomiting, laxative abuse, fasting, and intake, and monitoring for refeeding syndrome. Involvement excessive exercise. Binge eating is defined as eating substan- of a clinical nutritionist should be considered. Antidepressant tially more food than most people would consume within a therapy has not proved effective in treating anorexia nervosa, period of time. Similar to anorexia nervosa, patients with although low-dose olanzapine may be considered as adjunc- bulimia nervosa have a distorted body image. The key differ- tive therapy for patients not responding to psychotherapy and ence between the binge eating/purging type of anorexia ner- nutritional interventions. CBT is the most effective interven- vosa and bulimia nervosa is that patients with anorexia have tion for bulimia nervosa and binge eating disorder; antide- significant weight loss. Prevalence is three times greater in pressant therapy may be beneficial. Lisdexamfetamine and women than in men, and the median age of onset is 18 years. topiramate have also shown promise as adjunctive therapies to Binge eating disorder is more common than anorexia and CBT in patients with binge eating disorder, and lisdexamfeta- bulimia nervosa. It is characterized by binge eating and feel- mine is FDA approved for this indication. Bupropion should be ings of loss of control around food that occur an average of at avoided in patients with bulimia nervosa or anorexia nervosa least once weekly for 3 months. Binging episodes include at because of increased risk for seizures.

bulimia nervosa. It is characterized by binge eating and feel- mine is FDA approved for this indication. Bupropion should be ings of loss of control around food that occur an average of at avoided in patients with bulimia nervosa or anorexia nervosa least once weekly for 3 months. Binging episodes include at because of increased risk for seizures. least three of the following characteristics: abnormally rapid consumption, eating until uncomfortably full, consuming e Psychotherapy and monitored dietary intake are the HVC large amounts of food when not hungry, eating alone owing to primary treatments for anorexia nervosa; antidepressant embarrassment, and feelings of guilt related to overconsump- therapy is not effective. tion. These characteristics distinguish binge eating disorder ¢ Cognitive behavioral therapy is the most effective inter- from overeating. The lack of compensatory behaviors to avoid vention for bulimia nervosa and binge eating disorder; weight gain differentiates binge eating disorder from bulimia antidepressant therapy, lisdexamfetamine, and topiramate nervosa. Concurrent psychiatric disease, including personal- may also be beneficial. ity, mood, and substance use disorders, is common. 87