Hypertension is a widespread, under-recognized, and undertreated cause of morbidity and mortality in the United States and is associated with several psychiatric illnesses. Left untreated, hypertension can have significant consequences, including increased risk of stroke, coronary heart disease, heart failure, chronic kidney failure, and death. Approximately 70 million adults in the United States have hypertension, but only 60% of them have been diagnosed, and of those only 50% have their blood pressure under control.¹ In 2013, 360,000 deaths in the United States were attributed to hypertension.²

Hypertension is associated with major depressive disorder, generalized anxiety disorder, bipolar disorder, and schizophrenia.^3-5 Additionally, impulsive eating disorders, substance abuse, anxiety, and depression are associated with a hypertension diagnosis, although patients with panic disorder develop hypertension at a younger age.⁶ A 2007 study found a 61% prevalence of hypertension in those with bipolar disorder compared with 41% among the general population.⁷ The strong link between bipolar disorder and hypertension might be because of a common disease mechanism; both are associated with hyperactive cellular calcium signaling and increased platelet intracellular calcium ion concentrations.⁸

Hypertension not only is common among patients with psychiatric illness, it likely contributes to worse clinical outcomes. Studies across different cultures have found higher mortality rates in individuals with mental illness.^9-11 Persons with schizophrenia and other severe mental illnesses may lose ≥25 years of life expectancy, with the primary cause of death being cardiovascular disease, not suicide.¹² Patients with depression have a 50% greater risk of cardiovascular disease, which is equivalent to the risk of smoking.¹³ 

Schizophrenia is strongly associated with numerous comorbidities and has been linked significantly to an elevated 10-year cardiac risk after controlling for body mass index.⁵ The high rate of non-treatment of hypertension for patients with schizophrenia (62.4%) is especially concerning.¹⁴

Because of the well-documented morbidity and mortality of hypertension and its increased prevalence and undertreatment in the psychiatric population, mental health providers are in an important position to recognize hypertension and evaluate its inherent risks to direct their patients toward proper treatment. This article reviews:

• the signs and symptoms of hypertension
• the mental health provider’s role in the evaluation and diagnosis
• how psychotropic drugs influence blood pressure and drug–drug interactions
• the management of hypertension in psychiatric patients, including strategies for counseling and lifestyle management.

Diagnosing hypertension

Hypertension is defined as a blood pressure >140/90 mm Hg, the average of ≥2 properly measured readings at ≥2 visits in a medical setting.¹⁵ The proper equipment, including a well-fitting blood pressure cuff, and technique to measure blood pressure are essential to avoid misdiagnosis. The patient should be at rest for ≥5 minutes, without active pain or emotional distress.

Most cases of hypertension (90% to 95%) are primary, commonly called essential hypertension. However, the differential diagnosis also should consider secondary causes, which may include:

• obesity
• medications
• chronic alcohol use
• methamphetamine or cocaine use
• primary kidney disease
• atherosclerotic renal artery stenosis
• obstructive sleep apnea
• hypothyroidism
• primary hyperaldosteronism
• narrowing of the aorta
• Cushing syndrome
• primary hyperparathyroidism
• polycythemia
• pheochromocytoma.

Medical evaluation. Once the diagnosis of hypertension is made, a medical evaluation is indicated to determine if the patient has end-organ damage from the elevated pressures, such as renal disease or heart disease, to identify other modifiable cardiovascular risk factors, such as hyperlipidemia, and to screen for secondary causes of hypertension. This evaluation includes¹⁵:

• a physical exam
• review of medications
• lipid profile
• urinalysis to screen for proteinuria
• serum electrolytes and creatinine
• electrocardiogram to screen for left ventricular hypertrophy or prior infarction
• fasting glucose or hemoglobin A1_c to screen for type 2 diabetes mellitus.

Psychotropic drugs. In psychiatric patients, the evaluation must consider the potential impact psychotropic drug effects and drug–drug interactions can have on blood pressure (Table 2). For example, patients taking both diuretics and lithium are at increased risk for dehydration and increased serum lithium levels, which could cause severe neurologic symptoms and renal insufficiency.¹⁶ Several antihypertensives when taken with venlafaxine can increase blood pressure, but antihypertensives with α-1 blocking psychotropics can decrease blood pressure. Monoamine oxidase inhibitors can cause hypotension or hypertension with various classes of antihypertensives. Stimulants, such as methylphenidate, atomoxetine, dextroamphetamine, armodafinil, or modafinil, alone or combined with antihypertensives, can cause hypertension.¹⁷

Substance abuse, particularly alcohol, methamphetamine, and cocaine, can cause difficulty controlling blood pressure. Patients with refractory hypertension should have a reassessment of substance abuse as a potential cause.

Screening guidelines for mental health providers

For many patients with severe mental illness, visits to their mental health providers might be their only contact with the medical system. Therefore, screening in the mental health settings could detect cases that otherwise would be missed.

Screening recommendations. The U.S. Preventive Services Task Force recommends screening for hypertension in the general population beginning at age 18.¹⁸ Adults age 18 to 39 with normal blood pressure (<130/85 mm Hg) and no other risk factors (eg, overweight, obese, or African American) can be screened every 3 years. Those with risk factors or a blood pressure of 130/85 to 139/89 mm Hg and adults age ≥40 should have annual screenings.

Ideally, psychiatrists and other mental health providers should monitor blood pressure at each visit, especially in patients taking psychotropics because of their higher risk for hypertension.

Optimizing treatment. Once the diagnosis of essential hypertension is established, identifying psychiatric comorbidities and the severity of psychiatric symptoms are important to optimize treatment adherence. Patients with increased depressive symptoms are less likely to comply with antihypertensive medication,¹⁹ and patients with confirmed depression are 3 times more likely to not adhere to medical treatment recommendations than non-depressed patients.²⁰

Physicians’ attitudes toward hypertension also can affect patients’ compliance and blood pressure control.²¹ Psychiatrists should be empathetic and motivational toward patients attempting to control their blood pressure. The Seventh Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure states, “Motivation improves when patients have positive experiences with, and trust in, the clinician. Empathy builds trust and is a potent motivator.”²²

Treatment and management

Treatment of hypertension significantly reduces the risk of stroke, myocardial infarction, renal injury, heart failure, and premature death. Studies show that treatment that reduces systolic blood pressure by 12 mm Hg over 10 years will prevent 1 death for every 11 patients with essential hypertension. In those with concomitant cardiovascular disease or target organ damage, such a reduction would prevent death in 1 of every 9 patients treated.¹⁵Blood pressure goals. The 2014 Eighth Joint National Committee Guideline for Management of High Blood Pressure in Adults provides guidance on blood pressure goals depending on patients’ underlying medical history (Figure).²³ Based on expert opinion and randomized controlled studies, blood pressure goals for patients without diabetes or chronic kidney disease (CKD)—an estimated or measured glomerular filtration rate (GFR) of ≤60 mL/min/1.73 m²—depend on age: <140/90 mm Hg for age 18 to 59 and <150/90 mm Hg for age ≥60. For patients with diabetes or CKD, the blood pressure goal is <140/90 mm Hg, regardless of age.

However, not all experts agree on these specific blood pressure goals. A major trial (SPRINT) published in 2015 found that intensive blood pressure goals do benefit higher-risk, non-diabetic patients.²⁴ Specifically, the study randomized patients age ≥50 with systolic blood pressure of 130 to 180 mm Hg and increased cardiovascular risk to systolic blood pressure targets of <140 mm Hg (standard) or <120 mm Hg (intensive). Characteristics of increased cardiovascular risk were clinical or subclinical cardiovascular disease other than stroke, CKD with GFR of 20 to 60 mL/min/1.73 m², age ≥75, or Framingham 10-year coronary heart disease risk score ≥15%. Intensive treatment significantly reduced overall mortality and the rate of acute coronary syndrome, myocardial infarction, heart failure, stroke, or cardiovascular death. However, the results of this study have not been assimilated into any recent guidelines. Therefore, consider a goal of <120 mm Hg for non-diabetic patients age ≥50 with any of these factors.

Lifestyle modifications. Psychiatrists are well equipped to motivate and encourage behavioral modification in patients with hypertension. Counseling and structured training courses could help to effectively lower blood pressure.²⁵ Patients should receive education on lifestyle modifications including:

• weight reduction
• physical activity
• moderate alcohol consumption
• decreased sodium consumption
• implementation of the Dietary Approaches to Stop Hypertension (DASH) or Mediterranean diets.¹⁵

Maintaining a normal body weight is ideal, but weight reduction of 10 lb can reduce blood pressure in overweight patients. The DASH diet, consisting of fruits, vegetables, low-fat dairy products, high calcium and potassium intake, and reduced saturated and total fat intake can decrease systolic blood pressure from 8 to 14 mm Hg. Reduction of sodium intake to ≤2,400 mg/d can reduce systolic blood pressure from 2 to 8 mm Hg. Regular aerobic exercise of 30 minutes a day most days of the week can reduce systolic blood pressure up to 9 mm Hg. Patients also should be encouraged to quit smoking. Patients who implement ≥2 these modifications get better results.

Antihypertensive medications. Patients who do not reach their goals with lifestyle measures alone should receive antihypertensive medications. Most patients will require ≥2 agents to control their blood pressure. Clinical trials show that some patient subgroups have better outcomes with different first-line agents.

For example, in non-African American patients, thiazide diuretics, calcium channel blockers, angiotensin receptor blockers, and angiotensin-converting enzyme inhibitors are first-line treatments (Table 3). For African American patients without CKD, first-line treatments should be thiazide diuretics and calcium channel blockers, because angiotensin-converting enzyme inhibitors and angiotensin receptor blockers do not reduce cardiovascular events as effectively. African American patients with CKD and proteinuria, however, benefit from angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and are preferred first-line agents. However, blood pressure control is a more important factor in improving outcomes than the choice of medication.

Psychiatrists’ role. Psychiatrists should aim to collaborate with the primary care provider when treating hypertension. However, when integrative care is not possible, they should start a first-line medication with follow-up in 1 month or sooner for patients with severe hypertension (>160/100 mm Hg) or significant comorbidities (eg, CKD, congestive heart failure, coronary disease). Patients with blood pressure >160/100 mm Hg often are started on a thiazide diuretic with one other medication because a single agent usually does not achieve goal blood pressure. Patients with CKD need close monitoring of potassium and creatinine when starting angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy, usually within 1 to 2 days of starting or adjusting their medication. Adjust or add medication dosages monthly until blood pressure goals are reached.

A general internist, cardiologist, or nephrologist who has expertise in managing complex cases should oversee care of a psychiatric patient in any of the following scenarios:

• suspected secondary cause of hypertension
• adverse reaction to antihypertensive medications
• complicated comorbid conditions (ie, creatinine >1.8 mg/dL, worsening renal failure, hyperkalemia, heart failure, coronary disease)
• blood pressure >180/120 mm Hg
• requires ≥3 antihypertensive medications.

Summing up

Hypertension is a significant comorbidity in many psychiatric patients, but usually is asymptomatic. Often the psychiatrist or other mental health provider will diagnose hypertension because of their frequent contact with these patients. Once the diagnosis is made, an initial evaluation can direct lifestyle modifications. Patients who continue to have significant elevation of blood pressure should start pharmacotherapy, either by the psychiatrist or by ensuring follow-up with a primary care physician. The psychiatrist may be able to manage cases of essential hypertension, but always must be vigilant for potential drug–disease or drug–drug interactions during treatment. A team-based approach may improve health outcomes in psychiatric patients.

Hypertension is a widespread, under-recognized, and undertreated cause of morbidity and mortality in the United States and is associated with several psychiatric illnesses. Left untreated, hypertension can have significant consequences, including increased risk of stroke, coronary heart disease, heart failure, chronic kidney failure, and death. Approximately 70 million adults in the United States have hypertension, but only 60% of them have been diagnosed, and of those only 50% have their blood pressure under control.¹ In 2013, 360,000 deaths in the United States were attributed to hypertension.²

Hypertension is associated with major depressive disorder, generalized anxiety disorder, bipolar disorder, and schizophrenia.^3-5 Additionally, impulsive eating disorders, substance abuse, anxiety, and depression are associated with a hypertension diagnosis, although patients with panic disorder develop hypertension at a younger age.⁶ A 2007 study found a 61% prevalence of hypertension in those with bipolar disorder compared with 41% among the general population.⁷ The strong link between bipolar disorder and hypertension might be because of a common disease mechanism; both are associated with hyperactive cellular calcium signaling and increased platelet intracellular calcium ion concentrations.⁸

Hypertension not only is common among patients with psychiatric illness, it likely contributes to worse clinical outcomes. Studies across different cultures have found higher mortality rates in individuals with mental illness.^9-11 Persons with schizophrenia and other severe mental illnesses may lose ≥25 years of life expectancy, with the primary cause of death being cardiovascular disease, not suicide.¹² Patients with depression have a 50% greater risk of cardiovascular disease, which is equivalent to the risk of smoking.¹³ 

Schizophrenia is strongly associated with numerous comorbidities and has been linked significantly to an elevated 10-year cardiac risk after controlling for body mass index.⁵ The high rate of non-treatment of hypertension for patients with schizophrenia (62.4%) is especially concerning.¹⁴

Because of the well-documented morbidity and mortality of hypertension and its increased prevalence and undertreatment in the psychiatric population, mental health providers are in an important position to recognize hypertension and evaluate its inherent risks to direct their patients toward proper treatment. This article reviews:

• the signs and symptoms of hypertension
• the mental health provider’s role in the evaluation and diagnosis
• how psychotropic drugs influence blood pressure and drug–drug interactions
• the management of hypertension in psychiatric patients, including strategies for counseling and lifestyle management.

Diagnosing hypertension

Hypertension is defined as a blood pressure >140/90 mm Hg, the average of ≥2 properly measured readings at ≥2 visits in a medical setting.¹⁵ The proper equipment, including a well-fitting blood pressure cuff, and technique to measure blood pressure are essential to avoid misdiagnosis. The patient should be at rest for ≥5 minutes, without active pain or emotional distress.

Most cases of hypertension (90% to 95%) are primary, commonly called essential hypertension. However, the differential diagnosis also should consider secondary causes, which may include:

• obesity
• medications
• chronic alcohol use
• methamphetamine or cocaine use
• primary kidney disease
• atherosclerotic renal artery stenosis
• obstructive sleep apnea
• hypothyroidism
• primary hyperaldosteronism
• narrowing of the aorta
• Cushing syndrome
• primary hyperparathyroidism
• polycythemia
• pheochromocytoma.

Medical evaluation. Once the diagnosis of hypertension is made, a medical evaluation is indicated to determine if the patient has end-organ damage from the elevated pressures, such as renal disease or heart disease, to identify other modifiable cardiovascular risk factors, such as hyperlipidemia, and to screen for secondary causes of hypertension. This evaluation includes¹⁵:

• a physical exam
• review of medications
• lipid profile
• urinalysis to screen for proteinuria
• serum electrolytes and creatinine
• electrocardiogram to screen for left ventricular hypertrophy or prior infarction
• fasting glucose or hemoglobin A1_c to screen for type 2 diabetes mellitus.

Psychotropic drugs. In psychiatric patients, the evaluation must consider the potential impact psychotropic drug effects and drug–drug interactions can have on blood pressure (Table 2). For example, patients taking both diuretics and lithium are at increased risk for dehydration and increased serum lithium levels, which could cause severe neurologic symptoms and renal insufficiency.¹⁶ Several antihypertensives when taken with venlafaxine can increase blood pressure, but antihypertensives with α-1 blocking psychotropics can decrease blood pressure. Monoamine oxidase inhibitors can cause hypotension or hypertension with various classes of antihypertensives. Stimulants, such as methylphenidate, atomoxetine, dextroamphetamine, armodafinil, or modafinil, alone or combined with antihypertensives, can cause hypertension.¹⁷

Substance abuse, particularly alcohol, methamphetamine, and cocaine, can cause difficulty controlling blood pressure. Patients with refractory hypertension should have a reassessment of substance abuse as a potential cause.

Screening guidelines for mental health providers

For many patients with severe mental illness, visits to their mental health providers might be their only contact with the medical system. Therefore, screening in the mental health settings could detect cases that otherwise would be missed.

Screening recommendations. The U.S. Preventive Services Task Force recommends screening for hypertension in the general population beginning at age 18.¹⁸ Adults age 18 to 39 with normal blood pressure (<130/85 mm Hg) and no other risk factors (eg, overweight, obese, or African American) can be screened every 3 years. Those with risk factors or a blood pressure of 130/85 to 139/89 mm Hg and adults age ≥40 should have annual screenings.

Ideally, psychiatrists and other mental health providers should monitor blood pressure at each visit, especially in patients taking psychotropics because of their higher risk for hypertension.

Optimizing treatment. Once the diagnosis of essential hypertension is established, identifying psychiatric comorbidities and the severity of psychiatric symptoms are important to optimize treatment adherence. Patients with increased depressive symptoms are less likely to comply with antihypertensive medication,¹⁹ and patients with confirmed depression are 3 times more likely to not adhere to medical treatment recommendations than non-depressed patients.²⁰

Physicians’ attitudes toward hypertension also can affect patients’ compliance and blood pressure control.²¹ Psychiatrists should be empathetic and motivational toward patients attempting to control their blood pressure. The Seventh Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure states, “Motivation improves when patients have positive experiences with, and trust in, the clinician. Empathy builds trust and is a potent motivator.”²²

Treatment and management

Treatment of hypertension significantly reduces the risk of stroke, myocardial infarction, renal injury, heart failure, and premature death. Studies show that treatment that reduces systolic blood pressure by 12 mm Hg over 10 years will prevent 1 death for every 11 patients with essential hypertension. In those with concomitant cardiovascular disease or target organ damage, such a reduction would prevent death in 1 of every 9 patients treated.¹⁵Blood pressure goals. The 2014 Eighth Joint National Committee Guideline for Management of High Blood Pressure in Adults provides guidance on blood pressure goals depending on patients’ underlying medical history (Figure).²³ Based on expert opinion and randomized controlled studies, blood pressure goals for patients without diabetes or chronic kidney disease (CKD)—an estimated or measured glomerular filtration rate (GFR) of ≤60 mL/min/1.73 m²—depend on age: <140/90 mm Hg for age 18 to 59 and <150/90 mm Hg for age ≥60. For patients with diabetes or CKD, the blood pressure goal is <140/90 mm Hg, regardless of age.

However, not all experts agree on these specific blood pressure goals. A major trial (SPRINT) published in 2015 found that intensive blood pressure goals do benefit higher-risk, non-diabetic patients.²⁴ Specifically, the study randomized patients age ≥50 with systolic blood pressure of 130 to 180 mm Hg and increased cardiovascular risk to systolic blood pressure targets of <140 mm Hg (standard) or <120 mm Hg (intensive). Characteristics of increased cardiovascular risk were clinical or subclinical cardiovascular disease other than stroke, CKD with GFR of 20 to 60 mL/min/1.73 m², age ≥75, or Framingham 10-year coronary heart disease risk score ≥15%. Intensive treatment significantly reduced overall mortality and the rate of acute coronary syndrome, myocardial infarction, heart failure, stroke, or cardiovascular death. However, the results of this study have not been assimilated into any recent guidelines. Therefore, consider a goal of <120 mm Hg for non-diabetic patients age ≥50 with any of these factors.

Lifestyle modifications. Psychiatrists are well equipped to motivate and encourage behavioral modification in patients with hypertension. Counseling and structured training courses could help to effectively lower blood pressure.²⁵ Patients should receive education on lifestyle modifications including:

• weight reduction
• physical activity
• moderate alcohol consumption
• decreased sodium consumption
• implementation of the Dietary Approaches to Stop Hypertension (DASH) or Mediterranean diets.¹⁵

Maintaining a normal body weight is ideal, but weight reduction of 10 lb can reduce blood pressure in overweight patients. The DASH diet, consisting of fruits, vegetables, low-fat dairy products, high calcium and potassium intake, and reduced saturated and total fat intake can decrease systolic blood pressure from 8 to 14 mm Hg. Reduction of sodium intake to ≤2,400 mg/d can reduce systolic blood pressure from 2 to 8 mm Hg. Regular aerobic exercise of 30 minutes a day most days of the week can reduce systolic blood pressure up to 9 mm Hg. Patients also should be encouraged to quit smoking. Patients who implement ≥2 these modifications get better results.

Antihypertensive medications. Patients who do not reach their goals with lifestyle measures alone should receive antihypertensive medications. Most patients will require ≥2 agents to control their blood pressure. Clinical trials show that some patient subgroups have better outcomes with different first-line agents.

For example, in non-African American patients, thiazide diuretics, calcium channel blockers, angiotensin receptor blockers, and angiotensin-converting enzyme inhibitors are first-line treatments (Table 3). For African American patients without CKD, first-line treatments should be thiazide diuretics and calcium channel blockers, because angiotensin-converting enzyme inhibitors and angiotensin receptor blockers do not reduce cardiovascular events as effectively. African American patients with CKD and proteinuria, however, benefit from angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and are preferred first-line agents. However, blood pressure control is a more important factor in improving outcomes than the choice of medication.

Psychiatrists’ role. Psychiatrists should aim to collaborate with the primary care provider when treating hypertension. However, when integrative care is not possible, they should start a first-line medication with follow-up in 1 month or sooner for patients with severe hypertension (>160/100 mm Hg) or significant comorbidities (eg, CKD, congestive heart failure, coronary disease). Patients with blood pressure >160/100 mm Hg often are started on a thiazide diuretic with one other medication because a single agent usually does not achieve goal blood pressure. Patients with CKD need close monitoring of potassium and creatinine when starting angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy, usually within 1 to 2 days of starting or adjusting their medication. Adjust or add medication dosages monthly until blood pressure goals are reached.

A general internist, cardiologist, or nephrologist who has expertise in managing complex cases should oversee care of a psychiatric patient in any of the following scenarios:

• suspected secondary cause of hypertension
• adverse reaction to antihypertensive medications
• complicated comorbid conditions (ie, creatinine >1.8 mg/dL, worsening renal failure, hyperkalemia, heart failure, coronary disease)
• blood pressure >180/120 mm Hg
• requires ≥3 antihypertensive medications.

Summing up

Hypertension is a significant comorbidity in many psychiatric patients, but usually is asymptomatic. Often the psychiatrist or other mental health provider will diagnose hypertension because of their frequent contact with these patients. Once the diagnosis is made, an initial evaluation can direct lifestyle modifications. Patients who continue to have significant elevation of blood pressure should start pharmacotherapy, either by the psychiatrist or by ensuring follow-up with a primary care physician. The psychiatrist may be able to manage cases of essential hypertension, but always must be vigilant for potential drug–disease or drug–drug interactions during treatment. A team-based approach may improve health outcomes in psychiatric patients.

Hypertension is a widespread, under-recognized, and undertreated cause of morbidity and mortality in the United States and is associated with several psychiatric illnesses. Left untreated, hypertension can have significant consequences, including increased risk of stroke, coronary heart disease, heart failure, chronic kidney failure, and death. Approximately 70 million adults in the United States have hypertension, but only 60% of them have been diagnosed, and of those only 50% have their blood pressure under control.¹ In 2013, 360,000 deaths in the United States were attributed to hypertension.²

Hypertension is associated with major depressive disorder, generalized anxiety disorder, bipolar disorder, and schizophrenia.^3-5 Additionally, impulsive eating disorders, substance abuse, anxiety, and depression are associated with a hypertension diagnosis, although patients with panic disorder develop hypertension at a younger age.⁶ A 2007 study found a 61% prevalence of hypertension in those with bipolar disorder compared with 41% among the general population.⁷ The strong link between bipolar disorder and hypertension might be because of a common disease mechanism; both are associated with hyperactive cellular calcium signaling and increased platelet intracellular calcium ion concentrations.⁸

Hypertension not only is common among patients with psychiatric illness, it likely contributes to worse clinical outcomes. Studies across different cultures have found higher mortality rates in individuals with mental illness.^9-11 Persons with schizophrenia and other severe mental illnesses may lose ≥25 years of life expectancy, with the primary cause of death being cardiovascular disease, not suicide.¹² Patients with depression have a 50% greater risk of cardiovascular disease, which is equivalent to the risk of smoking.¹³ 

Schizophrenia is strongly associated with numerous comorbidities and has been linked significantly to an elevated 10-year cardiac risk after controlling for body mass index.⁵ The high rate of non-treatment of hypertension for patients with schizophrenia (62.4%) is especially concerning.¹⁴

Because of the well-documented morbidity and mortality of hypertension and its increased prevalence and undertreatment in the psychiatric population, mental health providers are in an important position to recognize hypertension and evaluate its inherent risks to direct their patients toward proper treatment. This article reviews:

• the signs and symptoms of hypertension
• the mental health provider’s role in the evaluation and diagnosis
• how psychotropic drugs influence blood pressure and drug–drug interactions
• the management of hypertension in psychiatric patients, including strategies for counseling and lifestyle management.

Diagnosing hypertension

Hypertension is defined as a blood pressure >140/90 mm Hg, the average of ≥2 properly measured readings at ≥2 visits in a medical setting.¹⁵ The proper equipment, including a well-fitting blood pressure cuff, and technique to measure blood pressure are essential to avoid misdiagnosis. The patient should be at rest for ≥5 minutes, without active pain or emotional distress.

Most cases of hypertension (90% to 95%) are primary, commonly called essential hypertension. However, the differential diagnosis also should consider secondary causes, which may include:

• obesity
• medications
• chronic alcohol use
• methamphetamine or cocaine use
• primary kidney disease
• atherosclerotic renal artery stenosis
• obstructive sleep apnea
• hypothyroidism
• primary hyperaldosteronism
• narrowing of the aorta
• Cushing syndrome
• primary hyperparathyroidism
• polycythemia
• pheochromocytoma.

Medical evaluation. Once the diagnosis of hypertension is made, a medical evaluation is indicated to determine if the patient has end-organ damage from the elevated pressures, such as renal disease or heart disease, to identify other modifiable cardiovascular risk factors, such as hyperlipidemia, and to screen for secondary causes of hypertension. This evaluation includes¹⁵:

• a physical exam
• review of medications
• lipid profile
• urinalysis to screen for proteinuria
• serum electrolytes and creatinine
• electrocardiogram to screen for left ventricular hypertrophy or prior infarction
• fasting glucose or hemoglobin A1_c to screen for type 2 diabetes mellitus.

Psychotropic drugs. In psychiatric patients, the evaluation must consider the potential impact psychotropic drug effects and drug–drug interactions can have on blood pressure (Table 2). For example, patients taking both diuretics and lithium are at increased risk for dehydration and increased serum lithium levels, which could cause severe neurologic symptoms and renal insufficiency.¹⁶ Several antihypertensives when taken with venlafaxine can increase blood pressure, but antihypertensives with α-1 blocking psychotropics can decrease blood pressure. Monoamine oxidase inhibitors can cause hypotension or hypertension with various classes of antihypertensives. Stimulants, such as methylphenidate, atomoxetine, dextroamphetamine, armodafinil, or modafinil, alone or combined with antihypertensives, can cause hypertension.¹⁷

Substance abuse, particularly alcohol, methamphetamine, and cocaine, can cause difficulty controlling blood pressure. Patients with refractory hypertension should have a reassessment of substance abuse as a potential cause.

Screening guidelines for mental health providers

For many patients with severe mental illness, visits to their mental health providers might be their only contact with the medical system. Therefore, screening in the mental health settings could detect cases that otherwise would be missed.

Screening recommendations. The U.S. Preventive Services Task Force recommends screening for hypertension in the general population beginning at age 18.¹⁸ Adults age 18 to 39 with normal blood pressure (<130/85 mm Hg) and no other risk factors (eg, overweight, obese, or African American) can be screened every 3 years. Those with risk factors or a blood pressure of 130/85 to 139/89 mm Hg and adults age ≥40 should have annual screenings.

Ideally, psychiatrists and other mental health providers should monitor blood pressure at each visit, especially in patients taking psychotropics because of their higher risk for hypertension.

Optimizing treatment. Once the diagnosis of essential hypertension is established, identifying psychiatric comorbidities and the severity of psychiatric symptoms are important to optimize treatment adherence. Patients with increased depressive symptoms are less likely to comply with antihypertensive medication,¹⁹ and patients with confirmed depression are 3 times more likely to not adhere to medical treatment recommendations than non-depressed patients.²⁰

Physicians’ attitudes toward hypertension also can affect patients’ compliance and blood pressure control.²¹ Psychiatrists should be empathetic and motivational toward patients attempting to control their blood pressure. The Seventh Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure states, “Motivation improves when patients have positive experiences with, and trust in, the clinician. Empathy builds trust and is a potent motivator.”²²

Treatment and management

Treatment of hypertension significantly reduces the risk of stroke, myocardial infarction, renal injury, heart failure, and premature death. Studies show that treatment that reduces systolic blood pressure by 12 mm Hg over 10 years will prevent 1 death for every 11 patients with essential hypertension. In those with concomitant cardiovascular disease or target organ damage, such a reduction would prevent death in 1 of every 9 patients treated.¹⁵Blood pressure goals. The 2014 Eighth Joint National Committee Guideline for Management of High Blood Pressure in Adults provides guidance on blood pressure goals depending on patients’ underlying medical history (Figure).²³ Based on expert opinion and randomized controlled studies, blood pressure goals for patients without diabetes or chronic kidney disease (CKD)—an estimated or measured glomerular filtration rate (GFR) of ≤60 mL/min/1.73 m²—depend on age: <140/90 mm Hg for age 18 to 59 and <150/90 mm Hg for age ≥60. For patients with diabetes or CKD, the blood pressure goal is <140/90 mm Hg, regardless of age.

However, not all experts agree on these specific blood pressure goals. A major trial (SPRINT) published in 2015 found that intensive blood pressure goals do benefit higher-risk, non-diabetic patients.²⁴ Specifically, the study randomized patients age ≥50 with systolic blood pressure of 130 to 180 mm Hg and increased cardiovascular risk to systolic blood pressure targets of <140 mm Hg (standard) or <120 mm Hg (intensive). Characteristics of increased cardiovascular risk were clinical or subclinical cardiovascular disease other than stroke, CKD with GFR of 20 to 60 mL/min/1.73 m², age ≥75, or Framingham 10-year coronary heart disease risk score ≥15%. Intensive treatment significantly reduced overall mortality and the rate of acute coronary syndrome, myocardial infarction, heart failure, stroke, or cardiovascular death. However, the results of this study have not been assimilated into any recent guidelines. Therefore, consider a goal of <120 mm Hg for non-diabetic patients age ≥50 with any of these factors.

Lifestyle modifications. Psychiatrists are well equipped to motivate and encourage behavioral modification in patients with hypertension. Counseling and structured training courses could help to effectively lower blood pressure.²⁵ Patients should receive education on lifestyle modifications including:

• weight reduction
• physical activity
• moderate alcohol consumption
• decreased sodium consumption
• implementation of the Dietary Approaches to Stop Hypertension (DASH) or Mediterranean diets.¹⁵

Maintaining a normal body weight is ideal, but weight reduction of 10 lb can reduce blood pressure in overweight patients. The DASH diet, consisting of fruits, vegetables, low-fat dairy products, high calcium and potassium intake, and reduced saturated and total fat intake can decrease systolic blood pressure from 8 to 14 mm Hg. Reduction of sodium intake to ≤2,400 mg/d can reduce systolic blood pressure from 2 to 8 mm Hg. Regular aerobic exercise of 30 minutes a day most days of the week can reduce systolic blood pressure up to 9 mm Hg. Patients also should be encouraged to quit smoking. Patients who implement ≥2 these modifications get better results.

Antihypertensive medications. Patients who do not reach their goals with lifestyle measures alone should receive antihypertensive medications. Most patients will require ≥2 agents to control their blood pressure. Clinical trials show that some patient subgroups have better outcomes with different first-line agents.

For example, in non-African American patients, thiazide diuretics, calcium channel blockers, angiotensin receptor blockers, and angiotensin-converting enzyme inhibitors are first-line treatments (Table 3). For African American patients without CKD, first-line treatments should be thiazide diuretics and calcium channel blockers, because angiotensin-converting enzyme inhibitors and angiotensin receptor blockers do not reduce cardiovascular events as effectively. African American patients with CKD and proteinuria, however, benefit from angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and are preferred first-line agents. However, blood pressure control is a more important factor in improving outcomes than the choice of medication.

Psychiatrists’ role. Psychiatrists should aim to collaborate with the primary care provider when treating hypertension. However, when integrative care is not possible, they should start a first-line medication with follow-up in 1 month or sooner for patients with severe hypertension (>160/100 mm Hg) or significant comorbidities (eg, CKD, congestive heart failure, coronary disease). Patients with blood pressure >160/100 mm Hg often are started on a thiazide diuretic with one other medication because a single agent usually does not achieve goal blood pressure. Patients with CKD need close monitoring of potassium and creatinine when starting angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy, usually within 1 to 2 days of starting or adjusting their medication. Adjust or add medication dosages monthly until blood pressure goals are reached.

A general internist, cardiologist, or nephrologist who has expertise in managing complex cases should oversee care of a psychiatric patient in any of the following scenarios:

• suspected secondary cause of hypertension
• adverse reaction to antihypertensive medications
• complicated comorbid conditions (ie, creatinine >1.8 mg/dL, worsening renal failure, hyperkalemia, heart failure, coronary disease)
• blood pressure >180/120 mm Hg
• requires ≥3 antihypertensive medications.

Summing up

Hypertension is a significant comorbidity in many psychiatric patients, but usually is asymptomatic. Often the psychiatrist or other mental health provider will diagnose hypertension because of their frequent contact with these patients. Once the diagnosis is made, an initial evaluation can direct lifestyle modifications. Patients who continue to have significant elevation of blood pressure should start pharmacotherapy, either by the psychiatrist or by ensuring follow-up with a primary care physician. The psychiatrist may be able to manage cases of essential hypertension, but always must be vigilant for potential drug–disease or drug–drug interactions during treatment. A team-based approach may improve health outcomes in psychiatric patients.

The article “Residual symptoms of schizophrenia: What are realistic treatment goals?” (Evidence-Based Reviews, Current Psychiatry, March 2017, p. 34-40) often referred to residual symptoms occurring in patients who have achieved “remission.” For example, the article states that “Of the 236 patients achieving remission at discharge, 94% had at least 1 residual symptom and 69% had at least 4 residual symptoms.”¹ Use of “remission” in this article is incorrect. “Remission” refers to the complete disappearance or elimination of symptoms—not treatments that are successful but incomplete in terms of eliminating symptoms of that disease.

Certainly most treatments for schizophrenia and other chronic psychiatric disorders leave some significant residual symptoms. However, the term “remission” should be reserved only for treatment that is sufficiently successful so that no significant residual symptoms remain.

Leonard Korn, MD
Psychiatrist
Portsmouth Regional Hospital
Portsmouth, New Hampshire

Reference

1. Schennach R, Riedel M, Obermeier M, et al. What are residual symptoms in schizophrenia spectrum disorder? Clinical description and 1-year persistence within a naturalistic trial. Eur Arch Psychiatry Clin Neurosci. 2015;265(2):107-116.

The authors respond

Dr. Korn makes a valid, relevant point about the correct use of the term “remission” with regard to the residual symptoms of schizophrenia. Although use of “remission” in the context of our article might seem to defy logic, our use of the term is predicated on the Consensus Criteria for remission, which allows for mild symptoms of core schizophrenia psychopathology.¹

In 2005, the Remission in Schizophrenia Working Group published an operationally defined criterion for remission using a threshold of severity for core symptoms. The Consensus Criteria aimed to provide researchers and clinicians with a well- defined method to gauge outcomes and facilitate comparisons of the effectiveness of therapy in the long-term treatment of schizophrenia.² The Consensus Criteria for remission is a highly debated and dynamic topic. Within 5 years after being published, 6 post hoc analyses tested these criteria against other remission criteria in schizophrenia.³

At the beginning of our article, we cited the naturalistic trial by Schennach et al,¹ which investigated the discrepancy between remission status using the Consensus Criteria and remaining impairments or “residual symptoms” found in remitted patients. This trial also examined these remaining symptoms that persisted in 236 remitted patients. The symptoms most commonly found were: blunted affect, conceptual disorganization, passive/apathetic social withdrawal, emotional withdrawal, lack of judgment and insight, and poor attention.¹

We agree with Dr. Korn’s comment, “Certainly most treatments of schizophrenia and other chronic psychiatric disorders leave some significant residual symptoms.” It is this reason why we find it difficult to eliminate symptoms of schizophrenia with currently available treatment options.

We also agree with his comment, “… the term ‘remission’ should be reserved only for treatment that is sufficiently successful so that no significant residual symptoms remain.” Defining remission as an absolute elimination of symptoms using currently available treatment options might not be practical for schizophrenia. This statement is based on the paucity of occurrences of complete remission or elimination of symptoms in our own patients. Therefore, in our article, we chose not to address the criteria or define the remission of schizophrenia. The primary focus was treating residual symptoms and providing realistic therapeutic goals.

In the future, we expect more effective treatment approaches, and advanced therapeutic goals will incite revisions to the remission criteria to meet even higher treatment expectations. We hope future research will focus on addressing residual symptoms, finding a potential cure for schizophrenia, and better defining the term “remission” and absolute nature for this most complex, chronic illness.

Ahsan Khan, MD, DFAPA, DABAM
Armor Correctional Health Services, Inc.
Oklahoma City, Oklahoma
Department of Psychiatry andBehavioral Neuroscience
Saint Louis University School of Medicine
St. Louis, Missouri

Mona Ghavami, MD
Clinical Documentation Specialist
St. Joseph Medical Center
Kansas City, Missouri

George D. Ide, MD
Post-Graduate Research
CenterPointe Health System
St. Charles, Missouri

Rachna Kalia, MD
Clinical Assistant Professor
Department of Psychiatry and Behavioral Sciences
University of Kansas School ofMedicine-Wichita
Wichita, Kansas

The article “Residual symptoms of schizophrenia: What are realistic treatment goals?” (Evidence-Based Reviews, Current Psychiatry, March 2017, p. 34-40) often referred to residual symptoms occurring in patients who have achieved “remission.” For example, the article states that “Of the 236 patients achieving remission at discharge, 94% had at least 1 residual symptom and 69% had at least 4 residual symptoms.”¹ Use of “remission” in this article is incorrect. “Remission” refers to the complete disappearance or elimination of symptoms—not treatments that are successful but incomplete in terms of eliminating symptoms of that disease.

Certainly most treatments for schizophrenia and other chronic psychiatric disorders leave some significant residual symptoms. However, the term “remission” should be reserved only for treatment that is sufficiently successful so that no significant residual symptoms remain.

Leonard Korn, MD
Psychiatrist
Portsmouth Regional Hospital
Portsmouth, New Hampshire

Reference

1. Schennach R, Riedel M, Obermeier M, et al. What are residual symptoms in schizophrenia spectrum disorder? Clinical description and 1-year persistence within a naturalistic trial. Eur Arch Psychiatry Clin Neurosci. 2015;265(2):107-116.

The authors respond

Dr. Korn makes a valid, relevant point about the correct use of the term “remission” with regard to the residual symptoms of schizophrenia. Although use of “remission” in the context of our article might seem to defy logic, our use of the term is predicated on the Consensus Criteria for remission, which allows for mild symptoms of core schizophrenia psychopathology.¹

In 2005, the Remission in Schizophrenia Working Group published an operationally defined criterion for remission using a threshold of severity for core symptoms. The Consensus Criteria aimed to provide researchers and clinicians with a well- defined method to gauge outcomes and facilitate comparisons of the effectiveness of therapy in the long-term treatment of schizophrenia.² The Consensus Criteria for remission is a highly debated and dynamic topic. Within 5 years after being published, 6 post hoc analyses tested these criteria against other remission criteria in schizophrenia.³

At the beginning of our article, we cited the naturalistic trial by Schennach et al,¹ which investigated the discrepancy between remission status using the Consensus Criteria and remaining impairments or “residual symptoms” found in remitted patients. This trial also examined these remaining symptoms that persisted in 236 remitted patients. The symptoms most commonly found were: blunted affect, conceptual disorganization, passive/apathetic social withdrawal, emotional withdrawal, lack of judgment and insight, and poor attention.¹

We agree with Dr. Korn’s comment, “Certainly most treatments of schizophrenia and other chronic psychiatric disorders leave some significant residual symptoms.” It is this reason why we find it difficult to eliminate symptoms of schizophrenia with currently available treatment options.

We also agree with his comment, “… the term ‘remission’ should be reserved only for treatment that is sufficiently successful so that no significant residual symptoms remain.” Defining remission as an absolute elimination of symptoms using currently available treatment options might not be practical for schizophrenia. This statement is based on the paucity of occurrences of complete remission or elimination of symptoms in our own patients. Therefore, in our article, we chose not to address the criteria or define the remission of schizophrenia. The primary focus was treating residual symptoms and providing realistic therapeutic goals.

In the future, we expect more effective treatment approaches, and advanced therapeutic goals will incite revisions to the remission criteria to meet even higher treatment expectations. We hope future research will focus on addressing residual symptoms, finding a potential cure for schizophrenia, and better defining the term “remission” and absolute nature for this most complex, chronic illness.

Ahsan Khan, MD, DFAPA, DABAM
Armor Correctional Health Services, Inc.
Oklahoma City, Oklahoma
Department of Psychiatry andBehavioral Neuroscience
Saint Louis University School of Medicine
St. Louis, Missouri

Mona Ghavami, MD
Clinical Documentation Specialist
St. Joseph Medical Center
Kansas City, Missouri

George D. Ide, MD
Post-Graduate Research
CenterPointe Health System
St. Charles, Missouri

Rachna Kalia, MD
Clinical Assistant Professor
Department of Psychiatry and Behavioral Sciences
University of Kansas School ofMedicine-Wichita
Wichita, Kansas

The article “Residual symptoms of schizophrenia: What are realistic treatment goals?” (Evidence-Based Reviews, Current Psychiatry, March 2017, p. 34-40) often referred to residual symptoms occurring in patients who have achieved “remission.” For example, the article states that “Of the 236 patients achieving remission at discharge, 94% had at least 1 residual symptom and 69% had at least 4 residual symptoms.”¹ Use of “remission” in this article is incorrect. “Remission” refers to the complete disappearance or elimination of symptoms—not treatments that are successful but incomplete in terms of eliminating symptoms of that disease.

Certainly most treatments for schizophrenia and other chronic psychiatric disorders leave some significant residual symptoms. However, the term “remission” should be reserved only for treatment that is sufficiently successful so that no significant residual symptoms remain.

Leonard Korn, MD
Psychiatrist
Portsmouth Regional Hospital
Portsmouth, New Hampshire

Reference

1. Schennach R, Riedel M, Obermeier M, et al. What are residual symptoms in schizophrenia spectrum disorder? Clinical description and 1-year persistence within a naturalistic trial. Eur Arch Psychiatry Clin Neurosci. 2015;265(2):107-116.

The authors respond

Dr. Korn makes a valid, relevant point about the correct use of the term “remission” with regard to the residual symptoms of schizophrenia. Although use of “remission” in the context of our article might seem to defy logic, our use of the term is predicated on the Consensus Criteria for remission, which allows for mild symptoms of core schizophrenia psychopathology.¹

In 2005, the Remission in Schizophrenia Working Group published an operationally defined criterion for remission using a threshold of severity for core symptoms. The Consensus Criteria aimed to provide researchers and clinicians with a well- defined method to gauge outcomes and facilitate comparisons of the effectiveness of therapy in the long-term treatment of schizophrenia.² The Consensus Criteria for remission is a highly debated and dynamic topic. Within 5 years after being published, 6 post hoc analyses tested these criteria against other remission criteria in schizophrenia.³

At the beginning of our article, we cited the naturalistic trial by Schennach et al,¹ which investigated the discrepancy between remission status using the Consensus Criteria and remaining impairments or “residual symptoms” found in remitted patients. This trial also examined these remaining symptoms that persisted in 236 remitted patients. The symptoms most commonly found were: blunted affect, conceptual disorganization, passive/apathetic social withdrawal, emotional withdrawal, lack of judgment and insight, and poor attention.¹

We agree with Dr. Korn’s comment, “Certainly most treatments of schizophrenia and other chronic psychiatric disorders leave some significant residual symptoms.” It is this reason why we find it difficult to eliminate symptoms of schizophrenia with currently available treatment options.

We also agree with his comment, “… the term ‘remission’ should be reserved only for treatment that is sufficiently successful so that no significant residual symptoms remain.” Defining remission as an absolute elimination of symptoms using currently available treatment options might not be practical for schizophrenia. This statement is based on the paucity of occurrences of complete remission or elimination of symptoms in our own patients. Therefore, in our article, we chose not to address the criteria or define the remission of schizophrenia. The primary focus was treating residual symptoms and providing realistic therapeutic goals.

In the future, we expect more effective treatment approaches, and advanced therapeutic goals will incite revisions to the remission criteria to meet even higher treatment expectations. We hope future research will focus on addressing residual symptoms, finding a potential cure for schizophrenia, and better defining the term “remission” and absolute nature for this most complex, chronic illness.

Ahsan Khan, MD, DFAPA, DABAM
Armor Correctional Health Services, Inc.
Oklahoma City, Oklahoma
Department of Psychiatry andBehavioral Neuroscience
Saint Louis University School of Medicine
St. Louis, Missouri

Mona Ghavami, MD
Clinical Documentation Specialist
St. Joseph Medical Center
Kansas City, Missouri

George D. Ide, MD
Post-Graduate Research
CenterPointe Health System
St. Charles, Missouri

Rachna Kalia, MD
Clinical Assistant Professor
Department of Psychiatry and Behavioral Sciences
University of Kansas School ofMedicine-Wichita
Wichita, Kansas

Patient surveys reveal communication to be one of the most important competencies a physician should possess.¹ However, communication is not only what is spoken. A physician’s nonverbal communication or “body language” sets the trajectory for treatment from the moment the patient first sees the physician. Body language includes all forms of communication other than words,² such as vocal tone, posture, and facial and body movements. Being mindful of such behaviors can provide physicians with greater access to their patients. Effective nonverbal communication can have significant effects on patient engagement, compliance, and outcome.

First impressions

The physician’s nonverbal behavior is crucial to the patient’s impression of his (her) physician.³ Appropriate eye gaze, proper distance or forward lean, direct body orientation, uncrossed legs and arms, and arm symmetry also have been associated with patient reports of satisfaction.^3,4 A physician who displays these affiliative non­verbal behaviors is more likely to engage with the patient and be rated higher for patient satisfaction.^5,6 Once a patient has developed rapport and an alliance with the physician and is satisfied with care, you likely will see improvements in patient adherence.

Adherence to treatment

The physician’s ability to verbally and nonverbally communicate a safe, encouraging, and efficient relationship is crucial for patient adherence to treatment. Patients report greater alliance with their physicians when they perceive genuine engagement and concern.⁷ The physician showing interest impacts the patient’s rating of the relationship⁶ and provides confidence that the physician is sensitive and understanding.⁸ As a result, the patient is more trusting and communicative, which allows for greater progress in the patient’s care because it often leads to attending appointments as well as medication adherence.⁹

Medication nonadherence is a complex issue that is influenced by several factors,¹⁰ but it is widely accepted that lack of communication and patient education are important factors.¹¹ Nonverbal communication can help the clinician to distinguish patients who are unwilling to take medication from those who are willing but unable to do so.¹¹

Overall adherence with care also can be affected by nonverbal behaviors. Positive perception of the physician’s tone of voice has been associated with greater attendance at appointments,¹² greater referral rates to alcohol abuse treatment clinics,¹³ and lower rates of malpractice among surgeons.¹⁴ Such trends demonstrate the influence that effective nonverbal communication could have on health care costs by reducing doctor shopping and malpractice rates and increasing effective care.

Outcomes

Physician’s positive nonverbal communication has been linked to positive patient outcomes. Physical therapists who smile, nod, and maintain eye contact compared with those who do not smile or look away from the patient, have been shown to achieve greater short- and long-term improvements in functioning of their patients.¹⁵ Perceptions of physicians as distant or detached are associated with poorer patient outcomes.^5,6,16 Pain patients with high nonverbal support from their physicians show increased pain tolerance and reduction in the amount of pain expressed, compared with those interacting with low nonverbal support physicians.¹⁷ Patients respond more to care if they feel their physician is engaged and sensitive to their needs.

There is much to gain if a physician is mindful of his body language. As Henry A. Nasrallah, MD, Editor-in-Chief of Current Psychiatry wrote in one of his editorials, physicians can exert a far more positive placebo effect through their behavior and relatedness to a patient than the classic placebo.¹⁸

Patient surveys reveal communication to be one of the most important competencies a physician should possess.¹ However, communication is not only what is spoken. A physician’s nonverbal communication or “body language” sets the trajectory for treatment from the moment the patient first sees the physician. Body language includes all forms of communication other than words,² such as vocal tone, posture, and facial and body movements. Being mindful of such behaviors can provide physicians with greater access to their patients. Effective nonverbal communication can have significant effects on patient engagement, compliance, and outcome.

First impressions

The physician’s nonverbal behavior is crucial to the patient’s impression of his (her) physician.³ Appropriate eye gaze, proper distance or forward lean, direct body orientation, uncrossed legs and arms, and arm symmetry also have been associated with patient reports of satisfaction.^3,4 A physician who displays these affiliative non­verbal behaviors is more likely to engage with the patient and be rated higher for patient satisfaction.^5,6 Once a patient has developed rapport and an alliance with the physician and is satisfied with care, you likely will see improvements in patient adherence.

Adherence to treatment

The physician’s ability to verbally and nonverbally communicate a safe, encouraging, and efficient relationship is crucial for patient adherence to treatment. Patients report greater alliance with their physicians when they perceive genuine engagement and concern.⁷ The physician showing interest impacts the patient’s rating of the relationship⁶ and provides confidence that the physician is sensitive and understanding.⁸ As a result, the patient is more trusting and communicative, which allows for greater progress in the patient’s care because it often leads to attending appointments as well as medication adherence.⁹

Medication nonadherence is a complex issue that is influenced by several factors,¹⁰ but it is widely accepted that lack of communication and patient education are important factors.¹¹ Nonverbal communication can help the clinician to distinguish patients who are unwilling to take medication from those who are willing but unable to do so.¹¹

Overall adherence with care also can be affected by nonverbal behaviors. Positive perception of the physician’s tone of voice has been associated with greater attendance at appointments,¹² greater referral rates to alcohol abuse treatment clinics,¹³ and lower rates of malpractice among surgeons.¹⁴ Such trends demonstrate the influence that effective nonverbal communication could have on health care costs by reducing doctor shopping and malpractice rates and increasing effective care.

Outcomes

Physician’s positive nonverbal communication has been linked to positive patient outcomes. Physical therapists who smile, nod, and maintain eye contact compared with those who do not smile or look away from the patient, have been shown to achieve greater short- and long-term improvements in functioning of their patients.¹⁵ Perceptions of physicians as distant or detached are associated with poorer patient outcomes.^5,6,16 Pain patients with high nonverbal support from their physicians show increased pain tolerance and reduction in the amount of pain expressed, compared with those interacting with low nonverbal support physicians.¹⁷ Patients respond more to care if they feel their physician is engaged and sensitive to their needs.

There is much to gain if a physician is mindful of his body language. As Henry A. Nasrallah, MD, Editor-in-Chief of Current Psychiatry wrote in one of his editorials, physicians can exert a far more positive placebo effect through their behavior and relatedness to a patient than the classic placebo.¹⁸

Patient surveys reveal communication to be one of the most important competencies a physician should possess.¹ However, communication is not only what is spoken. A physician’s nonverbal communication or “body language” sets the trajectory for treatment from the moment the patient first sees the physician. Body language includes all forms of communication other than words,² such as vocal tone, posture, and facial and body movements. Being mindful of such behaviors can provide physicians with greater access to their patients. Effective nonverbal communication can have significant effects on patient engagement, compliance, and outcome.

First impressions

The physician’s nonverbal behavior is crucial to the patient’s impression of his (her) physician.³ Appropriate eye gaze, proper distance or forward lean, direct body orientation, uncrossed legs and arms, and arm symmetry also have been associated with patient reports of satisfaction.^3,4 A physician who displays these affiliative non­verbal behaviors is more likely to engage with the patient and be rated higher for patient satisfaction.^5,6 Once a patient has developed rapport and an alliance with the physician and is satisfied with care, you likely will see improvements in patient adherence.

Adherence to treatment

The physician’s ability to verbally and nonverbally communicate a safe, encouraging, and efficient relationship is crucial for patient adherence to treatment. Patients report greater alliance with their physicians when they perceive genuine engagement and concern.⁷ The physician showing interest impacts the patient’s rating of the relationship⁶ and provides confidence that the physician is sensitive and understanding.⁸ As a result, the patient is more trusting and communicative, which allows for greater progress in the patient’s care because it often leads to attending appointments as well as medication adherence.⁹

Medication nonadherence is a complex issue that is influenced by several factors,¹⁰ but it is widely accepted that lack of communication and patient education are important factors.¹¹ Nonverbal communication can help the clinician to distinguish patients who are unwilling to take medication from those who are willing but unable to do so.¹¹

Overall adherence with care also can be affected by nonverbal behaviors. Positive perception of the physician’s tone of voice has been associated with greater attendance at appointments,¹² greater referral rates to alcohol abuse treatment clinics,¹³ and lower rates of malpractice among surgeons.¹⁴ Such trends demonstrate the influence that effective nonverbal communication could have on health care costs by reducing doctor shopping and malpractice rates and increasing effective care.

Outcomes

Physician’s positive nonverbal communication has been linked to positive patient outcomes. Physical therapists who smile, nod, and maintain eye contact compared with those who do not smile or look away from the patient, have been shown to achieve greater short- and long-term improvements in functioning of their patients.¹⁵ Perceptions of physicians as distant or detached are associated with poorer patient outcomes.^5,6,16 Pain patients with high nonverbal support from their physicians show increased pain tolerance and reduction in the amount of pain expressed, compared with those interacting with low nonverbal support physicians.¹⁷ Patients respond more to care if they feel their physician is engaged and sensitive to their needs.

There is much to gain if a physician is mindful of his body language. As Henry A. Nasrallah, MD, Editor-in-Chief of Current Psychiatry wrote in one of his editorials, physicians can exert a far more positive placebo effect through their behavior and relatedness to a patient than the classic placebo.¹⁸

Practicing medicine without a license is a crime, but it seems to have become a hollow law. Politicians are now cynically legalizing it by granting prescribing privileges to individuals with no prior foundation of medical training. Perhaps it is because of serious ignorance of the difference between psychiatry and psychology or MD and PhD degrees. Or perhaps it is a quid pro quo to generous donors to their re-election campaigns who seek a convenient shortcut to the 28,000 hours it takes to become a psychiatrist in 8 years of medical school and psychiatric residency—and that comes after 4 years of college.

I recently consulted an attorney to discuss some legal documents. When he asked me what my line of work is, I then asked him if he knew the difference between a psychiatrist and a psychologist. He hesitated before admitting in an embarrassed tone that he did not really know and thought that they were all “shrinks” and very similar. I then informed him that both go through undergraduate college education, albeit taking very different courses, with pre-med scientific emphasis for future psychiatric physicians and predominately psychology emphasis for future psychologists.

However, psychiatrists then attend medical school for 4 years and rotate on multiple hospital-based medical specialties, such as internal medicine, surgery, pediatrics, obstetrics and gynecology, family medicine, neurology, pathology, psychiatry, ophthalmology, dermatology, anesthesia, radiology, otolaryngology, etc.

Psychologists, on the other hand, take additional advanced psychology courses in graduate school and write a dissertation that requires quite a bit of library time. After getting a MD, future psychiatrists spend 4 years in extensive training in residency programs across inpatient wards and outpatient clinics, assessing the physical and mental health of seriously sick patients with emphasis on both pharma­cological and psycho­therapeutic treatments for serious psychiatric disorders in patients, the majority of whom have comorbid medical conditions as well. Psychologists, on the other hand, spend 1 year of internship after getting their PhD or PsyD degree, essentially focused on developing counseling and psychotherapy skills. By the time they complete their training, psychologists and psychiatrists have disparate skills: heavily medical and pharmacological skills in psychiatrists and strong psycho­therapeutic skills in psychologists.

After this long explanation, I asked the attorney what he thought about psychologists seeking prescription privileges. He was astounded that psychologists would attempt to expand this scope of practice through state legislations rather than going through medical training like all physicians. “That would be like practicing medicine without a license, which is a felony,” he said. He wryly added that his fellow malpractice and litigation lawyers will be the big winners while poorly treated patients will be the biggest losers. Being an avid runner, he also added that such a short-cut to prescribe without the requisite years of medial training reminded him of Rosie Ruiz, who snuck into the Boston marathon a couple of miles before the finish line and “won” the race, before she was caught and discredited.¹

Psychology is a respected mental health discipline with strong psychotherapy training and orientation. For decades, psychologists have vigorously criticized the medical model of mental disorders that psychiatric physicians employ to diagnose and treat brain disorders that disrupt thinking, emotions, mood, cognition, and behavior. However, about 25 years ago, a small group of militant psychologists brazenly decided to lobby state legislatures to give them the right to prescribe psychotropics, although they have no formal medical training. Psychiatric physicians, represented by the American Psychiatric Association (APA), strongly opposed this initiative and regarded it as reckless disregard of the obvious need for extensive medical training to be able to prescribe drugs that affect every organ in the body, not only the brain. Psychiatric medications are associated with serious risks of morbidity and mortality.² The ability to safely prescribe any medication represents the tip of a huge iceberg of 8 years of rigorous medical school education and specialty training. Yet, one of the early proponents of prescription privileges for psychologists, Patrick De Leon, sarcastically likened the ability to prescribe drugs to learning how to operate a desktop computer!

Not all psychologists agreed with the political campaign to lobby state legislatures to pass a law authorizing prescriptive privileges for psychologists.^3-6 In fact, most academic psychologists oppose it.⁷ Most of the early supporters had a PsyD degree from professional schools of psychology, not a PhD degree in psychology, which is obtained from a university department of psychology. The National Alliance on Mental Illness is opposed to psychologists prescribing medications.⁸ Psychiatrists are outraged by this hazardous “solution” to the shortage of psychiatrists and point to the many potential dangers to patients. Some suggested that this is a quick way to enhance psychologists’ income and to generate more revenue for their professional journals and meetings with lucrative pharmaceutical ads and exhibit booths.

The campaign is ongoing, as Idaho became the fifth state to adopt such an ill-conceived “solution” to increasing access to mental health care, despite valiant effort by the APA to lobby against such laws. Although New Mexico (2002), Louisiana (2004), Illinois (2014), and Iowa (2016) have passed prescriptive authority for psychologists before Idaho, the APA has defeated such measures in numerous other states. But the painful truth is that this has been a lengthy political chess game in which psychologists have been gradually gaining ground and “capturing more pieces.”

Here is a brief, common sense rationale as to the need for full medical training necessary before safely and accurately prescribing medications, most of which are synthetic molecules, which are essentially foreign substances, with both benefits and risks detailed in the FDA-approved label of each drug that reaches the medical marketplace.

First: Making an accurate clinical diagnosis. If a patient presents with depression, the clinician must rule out other possible causes before diagnosing it as primary major depressive disorder for which an antidepressant can be prescribed. The panoply of secondary depressions, which are not treated with antidepressants, includes a variety of recreational drug-induced mood changes and dysphoria and depression induced by numerous prescription drugs (such as antihypertensives, hormonal contraceptives, steroids, interferon, proton pump inhibitors, H2 blockers, malaria drugs, etc.).

After drug-induced depression is ruled out, the clinician must rule out the possibility that an underlying medical condition might be causing the depression, which includes disorders such as hypothyroidism and other endocrinopathies, anemia, stroke, heart disease, hyperkalemia, lupus and other auto­immune disorders, cancer, Parkinsonism, etc. Therefore, a targeted exploration of past and current medical history, accompanied by a battery of lab tests (complete blood count, electrolytes, liver and kidney function tests, metabolic profile, thyroid-stimulating hormone, etc.) must be done to systematically arrive at the correct diagnosis. Only then can the proper treatment plan be determined, which may or may not include prescribing an antidepressant.
Conclusion: Medical training and psychiatric residency are required for an accurate diagnosis of a mental disorder. Even physicians with no psychiatric training might not have the full repertoire of knowledge needed to systematically rule out secondary depression.

Second: Drug selection. Psychiatric drugs can have various iatrogenic effects. Thus, the selection of an appropriate prescription medication from the available array of drugs approved for a given psychiatric indication must be safe and consistent with the patient’s medical history and must not potentially exacerbate ≥1 comorbid medical conditions.
Conclusion: Medical training and psychiatric residency are required.

Third: Knowledge of metabolic pathways of each psychiatric medication to be prescribed as well as the metabolic pathway of all other medications (psychiatric and non-psychiatric) the patient receives is essential to avoid adverse drug–drug interactions. This includes the hepatic enzymes (cytochromes), which often are responsible for metabolizing all the psychiatric and non-psychiatric drugs a patient is receiving. Knowledge of inhibitors and inducers of various cytochrome enzymes is vital for selecting a medication that does not cause a pharmacokinetic adverse reaction that can produce serious adverse effects (even death, such as with QTc prolongation) or can cause loss of efficacy of ≥1 medications that the patient is receiving, in addition to the anti­depressant. Also, in addition to evaluating hepatic pathways, knowledge of renal excretion of the drug to be selected and the status of the patient’s kidney function or impairment must be evaluated.
Conclusion: Medical training is required.

Practicing medicine without a license is a crime, but it seems to have become a hollow law. Politicians are now cynically legalizing it by granting prescribing privileges to individuals with no prior foundation of medical training. Perhaps it is because of serious ignorance of the difference between psychiatry and psychology or MD and PhD degrees. Or perhaps it is a quid pro quo to generous donors to their re-election campaigns who seek a convenient shortcut to the 28,000 hours it takes to become a psychiatrist in 8 years of medical school and psychiatric residency—and that comes after 4 years of college.

I recently consulted an attorney to discuss some legal documents. When he asked me what my line of work is, I then asked him if he knew the difference between a psychiatrist and a psychologist. He hesitated before admitting in an embarrassed tone that he did not really know and thought that they were all “shrinks” and very similar. I then informed him that both go through undergraduate college education, albeit taking very different courses, with pre-med scientific emphasis for future psychiatric physicians and predominately psychology emphasis for future psychologists.

However, psychiatrists then attend medical school for 4 years and rotate on multiple hospital-based medical specialties, such as internal medicine, surgery, pediatrics, obstetrics and gynecology, family medicine, neurology, pathology, psychiatry, ophthalmology, dermatology, anesthesia, radiology, otolaryngology, etc.

Psychologists, on the other hand, take additional advanced psychology courses in graduate school and write a dissertation that requires quite a bit of library time. After getting a MD, future psychiatrists spend 4 years in extensive training in residency programs across inpatient wards and outpatient clinics, assessing the physical and mental health of seriously sick patients with emphasis on both pharma­cological and psycho­therapeutic treatments for serious psychiatric disorders in patients, the majority of whom have comorbid medical conditions as well. Psychologists, on the other hand, spend 1 year of internship after getting their PhD or PsyD degree, essentially focused on developing counseling and psychotherapy skills. By the time they complete their training, psychologists and psychiatrists have disparate skills: heavily medical and pharmacological skills in psychiatrists and strong psycho­therapeutic skills in psychologists.

After this long explanation, I asked the attorney what he thought about psychologists seeking prescription privileges. He was astounded that psychologists would attempt to expand this scope of practice through state legislations rather than going through medical training like all physicians. “That would be like practicing medicine without a license, which is a felony,” he said. He wryly added that his fellow malpractice and litigation lawyers will be the big winners while poorly treated patients will be the biggest losers. Being an avid runner, he also added that such a short-cut to prescribe without the requisite years of medial training reminded him of Rosie Ruiz, who snuck into the Boston marathon a couple of miles before the finish line and “won” the race, before she was caught and discredited.¹

Psychology is a respected mental health discipline with strong psychotherapy training and orientation. For decades, psychologists have vigorously criticized the medical model of mental disorders that psychiatric physicians employ to diagnose and treat brain disorders that disrupt thinking, emotions, mood, cognition, and behavior. However, about 25 years ago, a small group of militant psychologists brazenly decided to lobby state legislatures to give them the right to prescribe psychotropics, although they have no formal medical training. Psychiatric physicians, represented by the American Psychiatric Association (APA), strongly opposed this initiative and regarded it as reckless disregard of the obvious need for extensive medical training to be able to prescribe drugs that affect every organ in the body, not only the brain. Psychiatric medications are associated with serious risks of morbidity and mortality.² The ability to safely prescribe any medication represents the tip of a huge iceberg of 8 years of rigorous medical school education and specialty training. Yet, one of the early proponents of prescription privileges for psychologists, Patrick De Leon, sarcastically likened the ability to prescribe drugs to learning how to operate a desktop computer!

Not all psychologists agreed with the political campaign to lobby state legislatures to pass a law authorizing prescriptive privileges for psychologists.^3-6 In fact, most academic psychologists oppose it.⁷ Most of the early supporters had a PsyD degree from professional schools of psychology, not a PhD degree in psychology, which is obtained from a university department of psychology. The National Alliance on Mental Illness is opposed to psychologists prescribing medications.⁸ Psychiatrists are outraged by this hazardous “solution” to the shortage of psychiatrists and point to the many potential dangers to patients. Some suggested that this is a quick way to enhance psychologists’ income and to generate more revenue for their professional journals and meetings with lucrative pharmaceutical ads and exhibit booths.

The campaign is ongoing, as Idaho became the fifth state to adopt such an ill-conceived “solution” to increasing access to mental health care, despite valiant effort by the APA to lobby against such laws. Although New Mexico (2002), Louisiana (2004), Illinois (2014), and Iowa (2016) have passed prescriptive authority for psychologists before Idaho, the APA has defeated such measures in numerous other states. But the painful truth is that this has been a lengthy political chess game in which psychologists have been gradually gaining ground and “capturing more pieces.”

Here is a brief, common sense rationale as to the need for full medical training necessary before safely and accurately prescribing medications, most of which are synthetic molecules, which are essentially foreign substances, with both benefits and risks detailed in the FDA-approved label of each drug that reaches the medical marketplace.

First: Making an accurate clinical diagnosis. If a patient presents with depression, the clinician must rule out other possible causes before diagnosing it as primary major depressive disorder for which an antidepressant can be prescribed. The panoply of secondary depressions, which are not treated with antidepressants, includes a variety of recreational drug-induced mood changes and dysphoria and depression induced by numerous prescription drugs (such as antihypertensives, hormonal contraceptives, steroids, interferon, proton pump inhibitors, H2 blockers, malaria drugs, etc.).

After drug-induced depression is ruled out, the clinician must rule out the possibility that an underlying medical condition might be causing the depression, which includes disorders such as hypothyroidism and other endocrinopathies, anemia, stroke, heart disease, hyperkalemia, lupus and other auto­immune disorders, cancer, Parkinsonism, etc. Therefore, a targeted exploration of past and current medical history, accompanied by a battery of lab tests (complete blood count, electrolytes, liver and kidney function tests, metabolic profile, thyroid-stimulating hormone, etc.) must be done to systematically arrive at the correct diagnosis. Only then can the proper treatment plan be determined, which may or may not include prescribing an antidepressant.
Conclusion: Medical training and psychiatric residency are required for an accurate diagnosis of a mental disorder. Even physicians with no psychiatric training might not have the full repertoire of knowledge needed to systematically rule out secondary depression.

Second: Drug selection. Psychiatric drugs can have various iatrogenic effects. Thus, the selection of an appropriate prescription medication from the available array of drugs approved for a given psychiatric indication must be safe and consistent with the patient’s medical history and must not potentially exacerbate ≥1 comorbid medical conditions.
Conclusion: Medical training and psychiatric residency are required.

Third: Knowledge of metabolic pathways of each psychiatric medication to be prescribed as well as the metabolic pathway of all other medications (psychiatric and non-psychiatric) the patient receives is essential to avoid adverse drug–drug interactions. This includes the hepatic enzymes (cytochromes), which often are responsible for metabolizing all the psychiatric and non-psychiatric drugs a patient is receiving. Knowledge of inhibitors and inducers of various cytochrome enzymes is vital for selecting a medication that does not cause a pharmacokinetic adverse reaction that can produce serious adverse effects (even death, such as with QTc prolongation) or can cause loss of efficacy of ≥1 medications that the patient is receiving, in addition to the anti­depressant. Also, in addition to evaluating hepatic pathways, knowledge of renal excretion of the drug to be selected and the status of the patient’s kidney function or impairment must be evaluated.
Conclusion: Medical training is required.

Practicing medicine without a license is a crime, but it seems to have become a hollow law. Politicians are now cynically legalizing it by granting prescribing privileges to individuals with no prior foundation of medical training. Perhaps it is because of serious ignorance of the difference between psychiatry and psychology or MD and PhD degrees. Or perhaps it is a quid pro quo to generous donors to their re-election campaigns who seek a convenient shortcut to the 28,000 hours it takes to become a psychiatrist in 8 years of medical school and psychiatric residency—and that comes after 4 years of college.

I recently consulted an attorney to discuss some legal documents. When he asked me what my line of work is, I then asked him if he knew the difference between a psychiatrist and a psychologist. He hesitated before admitting in an embarrassed tone that he did not really know and thought that they were all “shrinks” and very similar. I then informed him that both go through undergraduate college education, albeit taking very different courses, with pre-med scientific emphasis for future psychiatric physicians and predominately psychology emphasis for future psychologists.

However, psychiatrists then attend medical school for 4 years and rotate on multiple hospital-based medical specialties, such as internal medicine, surgery, pediatrics, obstetrics and gynecology, family medicine, neurology, pathology, psychiatry, ophthalmology, dermatology, anesthesia, radiology, otolaryngology, etc.

Psychologists, on the other hand, take additional advanced psychology courses in graduate school and write a dissertation that requires quite a bit of library time. After getting a MD, future psychiatrists spend 4 years in extensive training in residency programs across inpatient wards and outpatient clinics, assessing the physical and mental health of seriously sick patients with emphasis on both pharma­cological and psycho­therapeutic treatments for serious psychiatric disorders in patients, the majority of whom have comorbid medical conditions as well. Psychologists, on the other hand, spend 1 year of internship after getting their PhD or PsyD degree, essentially focused on developing counseling and psychotherapy skills. By the time they complete their training, psychologists and psychiatrists have disparate skills: heavily medical and pharmacological skills in psychiatrists and strong psycho­therapeutic skills in psychologists.

After this long explanation, I asked the attorney what he thought about psychologists seeking prescription privileges. He was astounded that psychologists would attempt to expand this scope of practice through state legislations rather than going through medical training like all physicians. “That would be like practicing medicine without a license, which is a felony,” he said. He wryly added that his fellow malpractice and litigation lawyers will be the big winners while poorly treated patients will be the biggest losers. Being an avid runner, he also added that such a short-cut to prescribe without the requisite years of medial training reminded him of Rosie Ruiz, who snuck into the Boston marathon a couple of miles before the finish line and “won” the race, before she was caught and discredited.¹

Psychology is a respected mental health discipline with strong psychotherapy training and orientation. For decades, psychologists have vigorously criticized the medical model of mental disorders that psychiatric physicians employ to diagnose and treat brain disorders that disrupt thinking, emotions, mood, cognition, and behavior. However, about 25 years ago, a small group of militant psychologists brazenly decided to lobby state legislatures to give them the right to prescribe psychotropics, although they have no formal medical training. Psychiatric physicians, represented by the American Psychiatric Association (APA), strongly opposed this initiative and regarded it as reckless disregard of the obvious need for extensive medical training to be able to prescribe drugs that affect every organ in the body, not only the brain. Psychiatric medications are associated with serious risks of morbidity and mortality.² The ability to safely prescribe any medication represents the tip of a huge iceberg of 8 years of rigorous medical school education and specialty training. Yet, one of the early proponents of prescription privileges for psychologists, Patrick De Leon, sarcastically likened the ability to prescribe drugs to learning how to operate a desktop computer!

Not all psychologists agreed with the political campaign to lobby state legislatures to pass a law authorizing prescriptive privileges for psychologists.^3-6 In fact, most academic psychologists oppose it.⁷ Most of the early supporters had a PsyD degree from professional schools of psychology, not a PhD degree in psychology, which is obtained from a university department of psychology. The National Alliance on Mental Illness is opposed to psychologists prescribing medications.⁸ Psychiatrists are outraged by this hazardous “solution” to the shortage of psychiatrists and point to the many potential dangers to patients. Some suggested that this is a quick way to enhance psychologists’ income and to generate more revenue for their professional journals and meetings with lucrative pharmaceutical ads and exhibit booths.

The campaign is ongoing, as Idaho became the fifth state to adopt such an ill-conceived “solution” to increasing access to mental health care, despite valiant effort by the APA to lobby against such laws. Although New Mexico (2002), Louisiana (2004), Illinois (2014), and Iowa (2016) have passed prescriptive authority for psychologists before Idaho, the APA has defeated such measures in numerous other states. But the painful truth is that this has been a lengthy political chess game in which psychologists have been gradually gaining ground and “capturing more pieces.”

Here is a brief, common sense rationale as to the need for full medical training necessary before safely and accurately prescribing medications, most of which are synthetic molecules, which are essentially foreign substances, with both benefits and risks detailed in the FDA-approved label of each drug that reaches the medical marketplace.

First: Making an accurate clinical diagnosis. If a patient presents with depression, the clinician must rule out other possible causes before diagnosing it as primary major depressive disorder for which an antidepressant can be prescribed. The panoply of secondary depressions, which are not treated with antidepressants, includes a variety of recreational drug-induced mood changes and dysphoria and depression induced by numerous prescription drugs (such as antihypertensives, hormonal contraceptives, steroids, interferon, proton pump inhibitors, H2 blockers, malaria drugs, etc.).

After drug-induced depression is ruled out, the clinician must rule out the possibility that an underlying medical condition might be causing the depression, which includes disorders such as hypothyroidism and other endocrinopathies, anemia, stroke, heart disease, hyperkalemia, lupus and other auto­immune disorders, cancer, Parkinsonism, etc. Therefore, a targeted exploration of past and current medical history, accompanied by a battery of lab tests (complete blood count, electrolytes, liver and kidney function tests, metabolic profile, thyroid-stimulating hormone, etc.) must be done to systematically arrive at the correct diagnosis. Only then can the proper treatment plan be determined, which may or may not include prescribing an antidepressant.
Conclusion: Medical training and psychiatric residency are required for an accurate diagnosis of a mental disorder. Even physicians with no psychiatric training might not have the full repertoire of knowledge needed to systematically rule out secondary depression.

Second: Drug selection. Psychiatric drugs can have various iatrogenic effects. Thus, the selection of an appropriate prescription medication from the available array of drugs approved for a given psychiatric indication must be safe and consistent with the patient’s medical history and must not potentially exacerbate ≥1 comorbid medical conditions.
Conclusion: Medical training and psychiatric residency are required.

Third: Knowledge of metabolic pathways of each psychiatric medication to be prescribed as well as the metabolic pathway of all other medications (psychiatric and non-psychiatric) the patient receives is essential to avoid adverse drug–drug interactions. This includes the hepatic enzymes (cytochromes), which often are responsible for metabolizing all the psychiatric and non-psychiatric drugs a patient is receiving. Knowledge of inhibitors and inducers of various cytochrome enzymes is vital for selecting a medication that does not cause a pharmacokinetic adverse reaction that can produce serious adverse effects (even death, such as with QTc prolongation) or can cause loss of efficacy of ≥1 medications that the patient is receiving, in addition to the anti­depressant. Also, in addition to evaluating hepatic pathways, knowledge of renal excretion of the drug to be selected and the status of the patient’s kidney function or impairment must be evaluated.
Conclusion: Medical training is required.

Photo by Aaron Logan

It may be possible to disrupt thrombosis without increasing the risk of bleeding, according to preclinical research published in Nature Communications.

“We have found a new thrombosis target that does not increase bleeding risk,” said study author Daniel I. Simon, MD, of University Hospitals Cleveland Medical Center in Cleveland, Ohio.

“Our discovery indicates that you can identify a new pathway and target that mediates blood clotting but does not affect our body’s natural processes to stop bleeding.”

The new pathway centers around a pair of protein receptors. One—Mac-1—is found on the surface of leukocytes recruited to sites of blood vessel injury, and the other—GPIbα—resides on the surface of platelets.

When the receptors interact, they trigger cascades of signals that amplify both inflammation and clotting.

The researchers found that genetically engineered mice, either without the Mac-1 receptor or with a mutant form of the receptor, could not bind GPIbα on platelets. As a result, the mice had delayed clot formation in response to artery injury.

However, these mice had similar platelet counts, platelet activation, plasma coagulation activity, and bleeding time as wild-type mice.

Additional experiments in mice showed that an antibody targeting Mac-1:GPIba inhibits thrombus formation.

And glucosamine, a small-molecule inhibitor of Mac-1:GPIba binding, inhibits thrombus formation without increasing bleeding risk.

Mice exposed to glucosamine were still able to successfully stop minor bleeding, like tail cuts, and maintain normal coagulation and platelet function.

The researchers believe these findings could lead to the development of better antithrombotic agents, as “the interaction between leukocyte Mac-1 and platelet GPIba is positioned as a novel and targetable mediator of thrombosis but not hemostasis.”

“Current anticlotting drugs and antiplatelet agents are effective in reducing heart attack and stroke but are associated with increased bleeding and transfusion,” Dr Simon said. “We have learned that bleeding and transfusion complications are equally as bad from a prognosis standpoint as heart attack or stroke.” 

Photo by Aaron Logan

It may be possible to disrupt thrombosis without increasing the risk of bleeding, according to preclinical research published in Nature Communications.

“We have found a new thrombosis target that does not increase bleeding risk,” said study author Daniel I. Simon, MD, of University Hospitals Cleveland Medical Center in Cleveland, Ohio.

“Our discovery indicates that you can identify a new pathway and target that mediates blood clotting but does not affect our body’s natural processes to stop bleeding.”

The new pathway centers around a pair of protein receptors. One—Mac-1—is found on the surface of leukocytes recruited to sites of blood vessel injury, and the other—GPIbα—resides on the surface of platelets.

When the receptors interact, they trigger cascades of signals that amplify both inflammation and clotting.

The researchers found that genetically engineered mice, either without the Mac-1 receptor or with a mutant form of the receptor, could not bind GPIbα on platelets. As a result, the mice had delayed clot formation in response to artery injury.

However, these mice had similar platelet counts, platelet activation, plasma coagulation activity, and bleeding time as wild-type mice.

Additional experiments in mice showed that an antibody targeting Mac-1:GPIba inhibits thrombus formation.

And glucosamine, a small-molecule inhibitor of Mac-1:GPIba binding, inhibits thrombus formation without increasing bleeding risk.

Mice exposed to glucosamine were still able to successfully stop minor bleeding, like tail cuts, and maintain normal coagulation and platelet function.

The researchers believe these findings could lead to the development of better antithrombotic agents, as “the interaction between leukocyte Mac-1 and platelet GPIba is positioned as a novel and targetable mediator of thrombosis but not hemostasis.”

“Current anticlotting drugs and antiplatelet agents are effective in reducing heart attack and stroke but are associated with increased bleeding and transfusion,” Dr Simon said. “We have learned that bleeding and transfusion complications are equally as bad from a prognosis standpoint as heart attack or stroke.” 

Photo by Aaron Logan

It may be possible to disrupt thrombosis without increasing the risk of bleeding, according to preclinical research published in Nature Communications.

“We have found a new thrombosis target that does not increase bleeding risk,” said study author Daniel I. Simon, MD, of University Hospitals Cleveland Medical Center in Cleveland, Ohio.

“Our discovery indicates that you can identify a new pathway and target that mediates blood clotting but does not affect our body’s natural processes to stop bleeding.”

The new pathway centers around a pair of protein receptors. One—Mac-1—is found on the surface of leukocytes recruited to sites of blood vessel injury, and the other—GPIbα—resides on the surface of platelets.

When the receptors interact, they trigger cascades of signals that amplify both inflammation and clotting.

The researchers found that genetically engineered mice, either without the Mac-1 receptor or with a mutant form of the receptor, could not bind GPIbα on platelets. As a result, the mice had delayed clot formation in response to artery injury.

However, these mice had similar platelet counts, platelet activation, plasma coagulation activity, and bleeding time as wild-type mice.

Additional experiments in mice showed that an antibody targeting Mac-1:GPIba inhibits thrombus formation.

And glucosamine, a small-molecule inhibitor of Mac-1:GPIba binding, inhibits thrombus formation without increasing bleeding risk.

Mice exposed to glucosamine were still able to successfully stop minor bleeding, like tail cuts, and maintain normal coagulation and platelet function.

The researchers believe these findings could lead to the development of better antithrombotic agents, as “the interaction between leukocyte Mac-1 and platelet GPIba is positioned as a novel and targetable mediator of thrombosis but not hemostasis.”

“Current anticlotting drugs and antiplatelet agents are effective in reducing heart attack and stroke but are associated with increased bleeding and transfusion,” Dr Simon said. “We have learned that bleeding and transfusion complications are equally as bad from a prognosis standpoint as heart attack or stroke.” 

Red blood cells

A gene known to prevent autoimmune diseases is a key regulator in iron uptake, according to research published in Cell Reports.

“We found previously that, when mice lack the gene Regnase-1, they suffer from severe autoimmune diseases and anemia,” said study author Masanori Yoshinaga, MD, of Kyoto University in Japan.

“At first, we assumed that anemia was a secondary effect, but, after detailed analysis, we found that the 2 symptoms develop independently.”

Continued study of mice with a Regnase-1 mutation revealed a functional defect in the principal site for iron absorption in the body, the duodenum.

“The next step was to find the role of Regnase-1 in iron-uptake maintenance,” Dr Yoshinaga said. “We started by looking at the most important iron-uptake gene, Transferrin Receptor 1, or TfR1.”

“Our results showed that Regnase-1 degrades the mRNA of TfR1, thereby inhibiting the synthesis of the TfR1 protein and, additionally, that it likely regulates other important iron-controlling genes.”

“Further analysis of Regnase-1 in iron-related homeostasis may provide insight into the mechanisms causing anemia and other iron-related disorders, perhaps eventually leading to new methods of treatment,” said study author Osamu Takeuchi, MD, PhD, of Kyoto University. 

Red blood cells

A gene known to prevent autoimmune diseases is a key regulator in iron uptake, according to research published in Cell Reports.

“We found previously that, when mice lack the gene Regnase-1, they suffer from severe autoimmune diseases and anemia,” said study author Masanori Yoshinaga, MD, of Kyoto University in Japan.

“At first, we assumed that anemia was a secondary effect, but, after detailed analysis, we found that the 2 symptoms develop independently.”

Continued study of mice with a Regnase-1 mutation revealed a functional defect in the principal site for iron absorption in the body, the duodenum.

“The next step was to find the role of Regnase-1 in iron-uptake maintenance,” Dr Yoshinaga said. “We started by looking at the most important iron-uptake gene, Transferrin Receptor 1, or TfR1.”

“Our results showed that Regnase-1 degrades the mRNA of TfR1, thereby inhibiting the synthesis of the TfR1 protein and, additionally, that it likely regulates other important iron-controlling genes.”

“Further analysis of Regnase-1 in iron-related homeostasis may provide insight into the mechanisms causing anemia and other iron-related disorders, perhaps eventually leading to new methods of treatment,” said study author Osamu Takeuchi, MD, PhD, of Kyoto University. 

Red blood cells

A gene known to prevent autoimmune diseases is a key regulator in iron uptake, according to research published in Cell Reports.

“We found previously that, when mice lack the gene Regnase-1, they suffer from severe autoimmune diseases and anemia,” said study author Masanori Yoshinaga, MD, of Kyoto University in Japan.

“At first, we assumed that anemia was a secondary effect, but, after detailed analysis, we found that the 2 symptoms develop independently.”

Continued study of mice with a Regnase-1 mutation revealed a functional defect in the principal site for iron absorption in the body, the duodenum.

“The next step was to find the role of Regnase-1 in iron-uptake maintenance,” Dr Yoshinaga said. “We started by looking at the most important iron-uptake gene, Transferrin Receptor 1, or TfR1.”

“Our results showed that Regnase-1 degrades the mRNA of TfR1, thereby inhibiting the synthesis of the TfR1 protein and, additionally, that it likely regulates other important iron-controlling genes.”

“Further analysis of Regnase-1 in iron-related homeostasis may provide insight into the mechanisms causing anemia and other iron-related disorders, perhaps eventually leading to new methods of treatment,” said study author Osamu Takeuchi, MD, PhD, of Kyoto University. 

CASE › A 68-year-old woman with hypertension and hyperlipidemia comes into your office for evaluation of a 30-minute episode of sudden-onset right-hand weakness and difficulty speaking that occurred 4 days earlier. The patient, who is also a smoker, has come in at the insistence of her daughter. On examination, her blood pressure (BP) is 145/88 mm Hg and her heart rate is 76 beats/minute and regular. She appears well and her language function is normal. The rest of her examination is normal. How would you proceed?

Stroke—the death of nerve cells due to a lack of blood supply from either infarction or hemorrhage—strikes nearly 800,000 people in the United States every year.^1,2 Of these events, 130,000 are fatal, making stroke the fifth leading cause of death.³ Effective, early evaluation and cause-specific treatment are crucial parts of stroke care.

Data indicate that evaluation of symptoms suggestive of stroke within 24 hours of an event confers substantial benefit.

Research has helped to clarify the critical role primary care physicians play in recognizing, triaging, and managing stroke and transient ischemic attacks (TIA). This article reviews what we know about the different ways that a stroke and a TIA can present, the appropriate diagnostic work-up for patients presenting with symptoms of either event, and management strategies for subacute care (24 hours to up to 14 days after a stroke has occurred).^4,5 Unless otherwise specified, this review will focus on ischemic stroke because 87% of strokes are attributable to ischemia.¹

A follow-up to this article on secondary stroke prevention will appear in the journal next month.

IMAGE: © 2017 ALEX NUBAUM C/O THE ISPOT

Look to onset more than type of symptoms for clues

Stroke presents as a sudden onset of neurologic deficits (language, motor, sensory, cerebellar, or brainstem functions) (TABLE 1⁴). Because presenting symptoms can vary widely, sudden onset, rather than particular symptoms, should raise a red flag for potential stroke.

The differential diagnosis includes: seizure, complex migraine, medication effect (eg, slurred speech or confusion after taking a central nervous system [CNS] depressant), toxin exposure, electrolyte abnormalities (especially hypoglycemia), concussion/trauma, infection of the CNS, peripheral vertigo, demyelination, intracranial mass, Bell’s palsy, and psychogenic disorders. The history and physical, along with laboratory findings and brain imaging (detailed later in this article), will guide the FP toward (or away from) these various etiologies.

Optimal triage is a subject of ongoing interest and research

If stroke or TIA remains a possibility after an initial assessment, it’s time to stratify patients by risk.

One of the most widely accepted tools is the ABCD² score (see TABLE 2⁶). Clinicians can employ the ABCD² risk stratification tool when trying to determine whether it is reasonable to pursue an expedited work-up (ie, <1 day) in the outpatient setting or recommend that the patient be evaluated in an emergency department (ED). The 90-day stroke rate following a TIA ranges from 3% with an ABCD² score of 0 to 3 to 18% with a score of 6 or 7. A score of 0 to 3 is considered relatively low risk; in the absence of other compelling factors, rapid outpatient evaluation is appropriate. For patients with an ABCD² score ≥4, referral to the ED or direct admission to the hospital is advised.

The validity of the ABCD² score for risk stratification has been studied extensively with conflicting results.^7-10 As with any assessment tool, it should be used as a guide, and should not supplant a full assessment of the patient or the judgment of the examining physician. In making the decision regarding inpatient or outpatient evaluation, it’s also important to consider available resources, access to specialists, and patient preference.

In a 2016 population-based study, the 30-day recurrent stroke/TIA rate for patients hospitalized for TIA was 3% compared with 10.7% for those discharged from the ED with referral to a stroke clinic and 10.6% for those discharged from the ED without a referral to a stroke clinic.¹¹ These data suggest that only patients for whom you have a low clinical suspicion of stroke/TIA should be worked up as outpatients, and that hospital admission is advised in moderate- and high-risk cases. The findings also highlight the critical role that primary care physicians can play in triaging and managing these patients for secondary prevention.

CASE › This patient’s recent history of sudden-onset right-sided weakness and expressive language dysfunction is suspicious for left hemispheric ischemia. She has several risk factors for stroke, and her ABCD² score is 5 (hypertension, age ≥60 years, unilateral weakness, and duration 10-59 min), which places her at moderate risk. Thus, the recommendation would be to have her go directly to an ED for rapid evaluation.

The diagnostic work-up

Even when a patient is sent to the ED, the FP plays a critical role in his or her continuing care. FPs will often coordinate with inpatient care and manage transition of care to the outpatient setting. (And in many communities, the ED or hospital physicians may themselves be family practitioners.)

In terms of care, not even an aspirin should be administered in a case like this because the patient has not yet had any neuroimaging, and differentiation of ischemic from hemorrhagic stroke cannot be made on clinical grounds alone. Once an ischemic stroke is confirmed, determining the etiology is critical given the significant management differences between the different types of stroke (atherosclerotic, cardioembolic, lacunar, or other).

Which imaging method, and when?

While a computerized tomography (CT) scan is the preferred initial imaging strategy for acute stroke to discern the ischemic type from the hemorrhagic, MRI is preferred for the evaluation of acute ischemic stroke because the method has a higher sensitivity for infarction and a greater ability to identify findings (such as demyelination) that would suggest an alternative diagnosis.

Because presenting symptoms can vary widely, sudden onset, rather than particular symptoms, should raise the red flag for potential stroke.

In addition to evaluating the brain parenchyma, physicians must also assess the cerebral vasculature. CT angiography (CTA) or MR angiography (MRA) of the head and neck are preferred over carotid ultrasound because they are capable of evaluating the entire cerebrovascular system^12,13 and can be instrumental in identifying potential causes of stroke, as well as guiding therapeutic decisions. Carotid ultrasound is a reasonable alternative for patients presenting with symptoms indicative of anterior circulation involvement when CTA and MRA are unavailable or contraindicated, but it will not identify intracranial vascular disease, proximal common carotid disease, or vertebrobasilar disease.

Getting to the cause of suspected stroke: Labs and other diagnostic tests

A routine work-up includes BP checks, routine labs (complete blood count, complete metabolic panel, coagulation profile, and troponin), an electrocardiogram (EKG), a transthoracic echocardiogram (TTE) with bubble study if possible, and a minimum of 24 to 48 hours of cardiac rhythm monitoring. Cardiac rhythm monitoring should be extended in the setting of clinical concern for unidentified paroxysmal atrial fibrillation, such as an embolism without a proximal vascular source, multiple embolic infarcts in different vascular territories, a dilated left atrium, or other risk factors for atrial fibrillation that include smoking, systolic hypertension, diabetes, and heart failure (see TABLE 3^12,13,17,18).^14-16 This standard diagnostic work-up will identify the cause of stroke in 70% to 80% of patients.¹⁹

Additional investigations to consider if the etiology is not yet elucidated include a transesophageal echocardiogram (TEE), cerebral angiography, a coagulopathy evaluation, a lumbar puncture, and a vasculitis work-up. If available, consultation with a neurologist is appropriate for any patient who has had a stroke or TIA. Patients with unclear etiologies or for whom there are questions concerning strategies for preventing secondary stroke should be referred to Neurology and preferably a stroke specialist.

Timing matters, even when symptoms have resolved (ie, TIA).^11,20 The EXPRESS trial¹⁷ (the Early use of eXisting PREventive Strategies for Stroke) looked at the effect of urgent assessment and treatment (≤1 day) of patients presenting with a TIA or minor stroke on the risk of recurrent stroke within 90 days. The diagnostic work-up included brain and vascular imaging together with an EKG. This intensive approach led to an absolute risk reduction of 8.2% (from 10.3% to 2.1%) in the risk of recurrent stroke at 90 days (number needed to treat [NNT]=12).¹⁷

Expedited work-up and treatment was also recently evaluated in a non-trial, real-world setting and was associated with reducing recurrent stroke by more than half the rate reported in older studies.²⁰ Overall, the data suggest that evaluation within 24 hours confers substantial benefit, and that this evaluation can happen in an outpatient setting.^21-23

Acute management: Use of tPA

Once imaging rules out intracranial hemorrhage, patients should be treated with tissue plasminogen activator (tPA) or an endovascular intervention as per guidelines.²⁴ For patients with ischemic stroke ineligible for tPA or endovascular treatments, the initial focus is to determine the etiology of the symptoms so that the best strategies for prevention of secondary stroke may be employed.

Aspirin should be provided within 24 to 48 hours to all patients after intracranial hemorrhage is ruled out. Aspirin should be delayed for 24 hours in those given thrombolytics. The initial recommended dose of aspirin is 325 mg with continued low-dose (81 mg) aspirin daily.¹³ The addition of clopidogrel to aspirin within 24 hours of an event and continued for 21 days, followed by aspirin alone, was shown to be beneficial in a Chinese population with high-risk TIA (ABCD² score ≥4) or minor stroke (National Institutes of Health Stroke Scale [NIHSS] ≤3).²⁵ Anticoagulation with heparin, warfarin, or a novel oral anticoagulant is generally not indicated in the acute setting due to the risk of hemorrhagic transformation.

Acute BP management depends upon the type of stroke (ischemic or hemorrhagic), eligibility for thrombolytics, timing of presentation, and possible comorbidities such as myocardial infarction or aortic dissection (see TABLE 4^13,26). In the absence of contraindications, high-intensity statins should be initiated in all patients able to take oral medications.

CASE › You appropriately referred your patient to the local ED. A head CT with head and neck CTA was performed. While the head CT did not show any abnormalities, the CTA demonstrated high-grade left internal carotid artery stenosis. The patient was given an initial dose of aspirin 325 mg and a high-intensity statin and admitted for further management. An MRI revealed a small shower of emboli in the left hemisphere, confirming the diagnosis of stroke over TIA. Labs were marginally remarkable with a low-density lipoprotein level of 115 mg/dL and an HbA1c of 6.2. Telemetry monitoring did not reveal any arrhythmias, and TTE was normal. BP remained in the high-normal to low-hypertensive range.

Timing matters, even when symptoms have resolved, such as with a TIA.

A Vascular Surgery consultation was obtained and the patient underwent a left carotid endarterectomy the following day. She did well without surgical complications. Her BP medications were adjusted; a combination of an angiotensin-converting enzyme inhibitor and a thiazide diuretic achieved a goal BP <140/90 mm Hg.

Permissive hypertension was not indicated due to her presentation >48 hours beyond the acute event. Low-dose aspirin and a high-intensity statin were continued, for secondary stroke prevention in the setting of atherosclerotic disease. She received smoking cessation counseling, which will continue.

CORRESPONDENCE
Stephen A. Martin, MD, EdM, Barre Family Health Center, 151 Worcester Road, Barre, MA 01005; [email protected].

CASE › A 68-year-old woman with hypertension and hyperlipidemia comes into your office for evaluation of a 30-minute episode of sudden-onset right-hand weakness and difficulty speaking that occurred 4 days earlier. The patient, who is also a smoker, has come in at the insistence of her daughter. On examination, her blood pressure (BP) is 145/88 mm Hg and her heart rate is 76 beats/minute and regular. She appears well and her language function is normal. The rest of her examination is normal. How would you proceed?

Stroke—the death of nerve cells due to a lack of blood supply from either infarction or hemorrhage—strikes nearly 800,000 people in the United States every year.^1,2 Of these events, 130,000 are fatal, making stroke the fifth leading cause of death.³ Effective, early evaluation and cause-specific treatment are crucial parts of stroke care.

Data indicate that evaluation of symptoms suggestive of stroke within 24 hours of an event confers substantial benefit.

Research has helped to clarify the critical role primary care physicians play in recognizing, triaging, and managing stroke and transient ischemic attacks (TIA). This article reviews what we know about the different ways that a stroke and a TIA can present, the appropriate diagnostic work-up for patients presenting with symptoms of either event, and management strategies for subacute care (24 hours to up to 14 days after a stroke has occurred).^4,5 Unless otherwise specified, this review will focus on ischemic stroke because 87% of strokes are attributable to ischemia.¹

A follow-up to this article on secondary stroke prevention will appear in the journal next month.

IMAGE: © 2017 ALEX NUBAUM C/O THE ISPOT

Look to onset more than type of symptoms for clues

Stroke presents as a sudden onset of neurologic deficits (language, motor, sensory, cerebellar, or brainstem functions) (TABLE 1⁴). Because presenting symptoms can vary widely, sudden onset, rather than particular symptoms, should raise a red flag for potential stroke.

The differential diagnosis includes: seizure, complex migraine, medication effect (eg, slurred speech or confusion after taking a central nervous system [CNS] depressant), toxin exposure, electrolyte abnormalities (especially hypoglycemia), concussion/trauma, infection of the CNS, peripheral vertigo, demyelination, intracranial mass, Bell’s palsy, and psychogenic disorders. The history and physical, along with laboratory findings and brain imaging (detailed later in this article), will guide the FP toward (or away from) these various etiologies.

Optimal triage is a subject of ongoing interest and research

If stroke or TIA remains a possibility after an initial assessment, it’s time to stratify patients by risk.

One of the most widely accepted tools is the ABCD² score (see TABLE 2⁶). Clinicians can employ the ABCD² risk stratification tool when trying to determine whether it is reasonable to pursue an expedited work-up (ie, <1 day) in the outpatient setting or recommend that the patient be evaluated in an emergency department (ED). The 90-day stroke rate following a TIA ranges from 3% with an ABCD² score of 0 to 3 to 18% with a score of 6 or 7. A score of 0 to 3 is considered relatively low risk; in the absence of other compelling factors, rapid outpatient evaluation is appropriate. For patients with an ABCD² score ≥4, referral to the ED or direct admission to the hospital is advised.

The validity of the ABCD² score for risk stratification has been studied extensively with conflicting results.^7-10 As with any assessment tool, it should be used as a guide, and should not supplant a full assessment of the patient or the judgment of the examining physician. In making the decision regarding inpatient or outpatient evaluation, it’s also important to consider available resources, access to specialists, and patient preference.

In a 2016 population-based study, the 30-day recurrent stroke/TIA rate for patients hospitalized for TIA was 3% compared with 10.7% for those discharged from the ED with referral to a stroke clinic and 10.6% for those discharged from the ED without a referral to a stroke clinic.¹¹ These data suggest that only patients for whom you have a low clinical suspicion of stroke/TIA should be worked up as outpatients, and that hospital admission is advised in moderate- and high-risk cases. The findings also highlight the critical role that primary care physicians can play in triaging and managing these patients for secondary prevention.

CASE › This patient’s recent history of sudden-onset right-sided weakness and expressive language dysfunction is suspicious for left hemispheric ischemia. She has several risk factors for stroke, and her ABCD² score is 5 (hypertension, age ≥60 years, unilateral weakness, and duration 10-59 min), which places her at moderate risk. Thus, the recommendation would be to have her go directly to an ED for rapid evaluation.

The diagnostic work-up

Even when a patient is sent to the ED, the FP plays a critical role in his or her continuing care. FPs will often coordinate with inpatient care and manage transition of care to the outpatient setting. (And in many communities, the ED or hospital physicians may themselves be family practitioners.)

In terms of care, not even an aspirin should be administered in a case like this because the patient has not yet had any neuroimaging, and differentiation of ischemic from hemorrhagic stroke cannot be made on clinical grounds alone. Once an ischemic stroke is confirmed, determining the etiology is critical given the significant management differences between the different types of stroke (atherosclerotic, cardioembolic, lacunar, or other).

Which imaging method, and when?

While a computerized tomography (CT) scan is the preferred initial imaging strategy for acute stroke to discern the ischemic type from the hemorrhagic, MRI is preferred for the evaluation of acute ischemic stroke because the method has a higher sensitivity for infarction and a greater ability to identify findings (such as demyelination) that would suggest an alternative diagnosis.

Because presenting symptoms can vary widely, sudden onset, rather than particular symptoms, should raise the red flag for potential stroke.

In addition to evaluating the brain parenchyma, physicians must also assess the cerebral vasculature. CT angiography (CTA) or MR angiography (MRA) of the head and neck are preferred over carotid ultrasound because they are capable of evaluating the entire cerebrovascular system^12,13 and can be instrumental in identifying potential causes of stroke, as well as guiding therapeutic decisions. Carotid ultrasound is a reasonable alternative for patients presenting with symptoms indicative of anterior circulation involvement when CTA and MRA are unavailable or contraindicated, but it will not identify intracranial vascular disease, proximal common carotid disease, or vertebrobasilar disease.

Getting to the cause of suspected stroke: Labs and other diagnostic tests

A routine work-up includes BP checks, routine labs (complete blood count, complete metabolic panel, coagulation profile, and troponin), an electrocardiogram (EKG), a transthoracic echocardiogram (TTE) with bubble study if possible, and a minimum of 24 to 48 hours of cardiac rhythm monitoring. Cardiac rhythm monitoring should be extended in the setting of clinical concern for unidentified paroxysmal atrial fibrillation, such as an embolism without a proximal vascular source, multiple embolic infarcts in different vascular territories, a dilated left atrium, or other risk factors for atrial fibrillation that include smoking, systolic hypertension, diabetes, and heart failure (see TABLE 3^12,13,17,18).^14-16 This standard diagnostic work-up will identify the cause of stroke in 70% to 80% of patients.¹⁹

Additional investigations to consider if the etiology is not yet elucidated include a transesophageal echocardiogram (TEE), cerebral angiography, a coagulopathy evaluation, a lumbar puncture, and a vasculitis work-up. If available, consultation with a neurologist is appropriate for any patient who has had a stroke or TIA. Patients with unclear etiologies or for whom there are questions concerning strategies for preventing secondary stroke should be referred to Neurology and preferably a stroke specialist.

Timing matters, even when symptoms have resolved (ie, TIA).^11,20 The EXPRESS trial¹⁷ (the Early use of eXisting PREventive Strategies for Stroke) looked at the effect of urgent assessment and treatment (≤1 day) of patients presenting with a TIA or minor stroke on the risk of recurrent stroke within 90 days. The diagnostic work-up included brain and vascular imaging together with an EKG. This intensive approach led to an absolute risk reduction of 8.2% (from 10.3% to 2.1%) in the risk of recurrent stroke at 90 days (number needed to treat [NNT]=12).¹⁷

Expedited work-up and treatment was also recently evaluated in a non-trial, real-world setting and was associated with reducing recurrent stroke by more than half the rate reported in older studies.²⁰ Overall, the data suggest that evaluation within 24 hours confers substantial benefit, and that this evaluation can happen in an outpatient setting.^21-23

Acute management: Use of tPA

Once imaging rules out intracranial hemorrhage, patients should be treated with tissue plasminogen activator (tPA) or an endovascular intervention as per guidelines.²⁴ For patients with ischemic stroke ineligible for tPA or endovascular treatments, the initial focus is to determine the etiology of the symptoms so that the best strategies for prevention of secondary stroke may be employed.

Aspirin should be provided within 24 to 48 hours to all patients after intracranial hemorrhage is ruled out. Aspirin should be delayed for 24 hours in those given thrombolytics. The initial recommended dose of aspirin is 325 mg with continued low-dose (81 mg) aspirin daily.¹³ The addition of clopidogrel to aspirin within 24 hours of an event and continued for 21 days, followed by aspirin alone, was shown to be beneficial in a Chinese population with high-risk TIA (ABCD² score ≥4) or minor stroke (National Institutes of Health Stroke Scale [NIHSS] ≤3).²⁵ Anticoagulation with heparin, warfarin, or a novel oral anticoagulant is generally not indicated in the acute setting due to the risk of hemorrhagic transformation.

Acute BP management depends upon the type of stroke (ischemic or hemorrhagic), eligibility for thrombolytics, timing of presentation, and possible comorbidities such as myocardial infarction or aortic dissection (see TABLE 4^13,26). In the absence of contraindications, high-intensity statins should be initiated in all patients able to take oral medications.

CASE › You appropriately referred your patient to the local ED. A head CT with head and neck CTA was performed. While the head CT did not show any abnormalities, the CTA demonstrated high-grade left internal carotid artery stenosis. The patient was given an initial dose of aspirin 325 mg and a high-intensity statin and admitted for further management. An MRI revealed a small shower of emboli in the left hemisphere, confirming the diagnosis of stroke over TIA. Labs were marginally remarkable with a low-density lipoprotein level of 115 mg/dL and an HbA1c of 6.2. Telemetry monitoring did not reveal any arrhythmias, and TTE was normal. BP remained in the high-normal to low-hypertensive range.

Timing matters, even when symptoms have resolved, such as with a TIA.

A Vascular Surgery consultation was obtained and the patient underwent a left carotid endarterectomy the following day. She did well without surgical complications. Her BP medications were adjusted; a combination of an angiotensin-converting enzyme inhibitor and a thiazide diuretic achieved a goal BP <140/90 mm Hg.

Permissive hypertension was not indicated due to her presentation >48 hours beyond the acute event. Low-dose aspirin and a high-intensity statin were continued, for secondary stroke prevention in the setting of atherosclerotic disease. She received smoking cessation counseling, which will continue.

CORRESPONDENCE
Stephen A. Martin, MD, EdM, Barre Family Health Center, 151 Worcester Road, Barre, MA 01005; [email protected].

CASE › A 68-year-old woman with hypertension and hyperlipidemia comes into your office for evaluation of a 30-minute episode of sudden-onset right-hand weakness and difficulty speaking that occurred 4 days earlier. The patient, who is also a smoker, has come in at the insistence of her daughter. On examination, her blood pressure (BP) is 145/88 mm Hg and her heart rate is 76 beats/minute and regular. She appears well and her language function is normal. The rest of her examination is normal. How would you proceed?

Stroke—the death of nerve cells due to a lack of blood supply from either infarction or hemorrhage—strikes nearly 800,000 people in the United States every year.^1,2 Of these events, 130,000 are fatal, making stroke the fifth leading cause of death.³ Effective, early evaluation and cause-specific treatment are crucial parts of stroke care.

Data indicate that evaluation of symptoms suggestive of stroke within 24 hours of an event confers substantial benefit.

Research has helped to clarify the critical role primary care physicians play in recognizing, triaging, and managing stroke and transient ischemic attacks (TIA). This article reviews what we know about the different ways that a stroke and a TIA can present, the appropriate diagnostic work-up for patients presenting with symptoms of either event, and management strategies for subacute care (24 hours to up to 14 days after a stroke has occurred).^4,5 Unless otherwise specified, this review will focus on ischemic stroke because 87% of strokes are attributable to ischemia.¹

A follow-up to this article on secondary stroke prevention will appear in the journal next month.

IMAGE: © 2017 ALEX NUBAUM C/O THE ISPOT

Look to onset more than type of symptoms for clues

Stroke presents as a sudden onset of neurologic deficits (language, motor, sensory, cerebellar, or brainstem functions) (TABLE 1⁴). Because presenting symptoms can vary widely, sudden onset, rather than particular symptoms, should raise a red flag for potential stroke.

The differential diagnosis includes: seizure, complex migraine, medication effect (eg, slurred speech or confusion after taking a central nervous system [CNS] depressant), toxin exposure, electrolyte abnormalities (especially hypoglycemia), concussion/trauma, infection of the CNS, peripheral vertigo, demyelination, intracranial mass, Bell’s palsy, and psychogenic disorders. The history and physical, along with laboratory findings and brain imaging (detailed later in this article), will guide the FP toward (or away from) these various etiologies.

Optimal triage is a subject of ongoing interest and research

If stroke or TIA remains a possibility after an initial assessment, it’s time to stratify patients by risk.

One of the most widely accepted tools is the ABCD² score (see TABLE 2⁶). Clinicians can employ the ABCD² risk stratification tool when trying to determine whether it is reasonable to pursue an expedited work-up (ie, <1 day) in the outpatient setting or recommend that the patient be evaluated in an emergency department (ED). The 90-day stroke rate following a TIA ranges from 3% with an ABCD² score of 0 to 3 to 18% with a score of 6 or 7. A score of 0 to 3 is considered relatively low risk; in the absence of other compelling factors, rapid outpatient evaluation is appropriate. For patients with an ABCD² score ≥4, referral to the ED or direct admission to the hospital is advised.

The validity of the ABCD² score for risk stratification has been studied extensively with conflicting results.^7-10 As with any assessment tool, it should be used as a guide, and should not supplant a full assessment of the patient or the judgment of the examining physician. In making the decision regarding inpatient or outpatient evaluation, it’s also important to consider available resources, access to specialists, and patient preference.

In a 2016 population-based study, the 30-day recurrent stroke/TIA rate for patients hospitalized for TIA was 3% compared with 10.7% for those discharged from the ED with referral to a stroke clinic and 10.6% for those discharged from the ED without a referral to a stroke clinic.¹¹ These data suggest that only patients for whom you have a low clinical suspicion of stroke/TIA should be worked up as outpatients, and that hospital admission is advised in moderate- and high-risk cases. The findings also highlight the critical role that primary care physicians can play in triaging and managing these patients for secondary prevention.

CASE › This patient’s recent history of sudden-onset right-sided weakness and expressive language dysfunction is suspicious for left hemispheric ischemia. She has several risk factors for stroke, and her ABCD² score is 5 (hypertension, age ≥60 years, unilateral weakness, and duration 10-59 min), which places her at moderate risk. Thus, the recommendation would be to have her go directly to an ED for rapid evaluation.

The diagnostic work-up

Even when a patient is sent to the ED, the FP plays a critical role in his or her continuing care. FPs will often coordinate with inpatient care and manage transition of care to the outpatient setting. (And in many communities, the ED or hospital physicians may themselves be family practitioners.)

In terms of care, not even an aspirin should be administered in a case like this because the patient has not yet had any neuroimaging, and differentiation of ischemic from hemorrhagic stroke cannot be made on clinical grounds alone. Once an ischemic stroke is confirmed, determining the etiology is critical given the significant management differences between the different types of stroke (atherosclerotic, cardioembolic, lacunar, or other).

Which imaging method, and when?

While a computerized tomography (CT) scan is the preferred initial imaging strategy for acute stroke to discern the ischemic type from the hemorrhagic, MRI is preferred for the evaluation of acute ischemic stroke because the method has a higher sensitivity for infarction and a greater ability to identify findings (such as demyelination) that would suggest an alternative diagnosis.

Because presenting symptoms can vary widely, sudden onset, rather than particular symptoms, should raise the red flag for potential stroke.

In addition to evaluating the brain parenchyma, physicians must also assess the cerebral vasculature. CT angiography (CTA) or MR angiography (MRA) of the head and neck are preferred over carotid ultrasound because they are capable of evaluating the entire cerebrovascular system^12,13 and can be instrumental in identifying potential causes of stroke, as well as guiding therapeutic decisions. Carotid ultrasound is a reasonable alternative for patients presenting with symptoms indicative of anterior circulation involvement when CTA and MRA are unavailable or contraindicated, but it will not identify intracranial vascular disease, proximal common carotid disease, or vertebrobasilar disease.

Getting to the cause of suspected stroke: Labs and other diagnostic tests

A routine work-up includes BP checks, routine labs (complete blood count, complete metabolic panel, coagulation profile, and troponin), an electrocardiogram (EKG), a transthoracic echocardiogram (TTE) with bubble study if possible, and a minimum of 24 to 48 hours of cardiac rhythm monitoring. Cardiac rhythm monitoring should be extended in the setting of clinical concern for unidentified paroxysmal atrial fibrillation, such as an embolism without a proximal vascular source, multiple embolic infarcts in different vascular territories, a dilated left atrium, or other risk factors for atrial fibrillation that include smoking, systolic hypertension, diabetes, and heart failure (see TABLE 3^12,13,17,18).^14-16 This standard diagnostic work-up will identify the cause of stroke in 70% to 80% of patients.¹⁹

Additional investigations to consider if the etiology is not yet elucidated include a transesophageal echocardiogram (TEE), cerebral angiography, a coagulopathy evaluation, a lumbar puncture, and a vasculitis work-up. If available, consultation with a neurologist is appropriate for any patient who has had a stroke or TIA. Patients with unclear etiologies or for whom there are questions concerning strategies for preventing secondary stroke should be referred to Neurology and preferably a stroke specialist.

Timing matters, even when symptoms have resolved (ie, TIA).^11,20 The EXPRESS trial¹⁷ (the Early use of eXisting PREventive Strategies for Stroke) looked at the effect of urgent assessment and treatment (≤1 day) of patients presenting with a TIA or minor stroke on the risk of recurrent stroke within 90 days. The diagnostic work-up included brain and vascular imaging together with an EKG. This intensive approach led to an absolute risk reduction of 8.2% (from 10.3% to 2.1%) in the risk of recurrent stroke at 90 days (number needed to treat [NNT]=12).¹⁷

Expedited work-up and treatment was also recently evaluated in a non-trial, real-world setting and was associated with reducing recurrent stroke by more than half the rate reported in older studies.²⁰ Overall, the data suggest that evaluation within 24 hours confers substantial benefit, and that this evaluation can happen in an outpatient setting.^21-23

Acute management: Use of tPA

Once imaging rules out intracranial hemorrhage, patients should be treated with tissue plasminogen activator (tPA) or an endovascular intervention as per guidelines.²⁴ For patients with ischemic stroke ineligible for tPA or endovascular treatments, the initial focus is to determine the etiology of the symptoms so that the best strategies for prevention of secondary stroke may be employed.

Aspirin should be provided within 24 to 48 hours to all patients after intracranial hemorrhage is ruled out. Aspirin should be delayed for 24 hours in those given thrombolytics. The initial recommended dose of aspirin is 325 mg with continued low-dose (81 mg) aspirin daily.¹³ The addition of clopidogrel to aspirin within 24 hours of an event and continued for 21 days, followed by aspirin alone, was shown to be beneficial in a Chinese population with high-risk TIA (ABCD² score ≥4) or minor stroke (National Institutes of Health Stroke Scale [NIHSS] ≤3).²⁵ Anticoagulation with heparin, warfarin, or a novel oral anticoagulant is generally not indicated in the acute setting due to the risk of hemorrhagic transformation.

Acute BP management depends upon the type of stroke (ischemic or hemorrhagic), eligibility for thrombolytics, timing of presentation, and possible comorbidities such as myocardial infarction or aortic dissection (see TABLE 4^13,26). In the absence of contraindications, high-intensity statins should be initiated in all patients able to take oral medications.

CASE › You appropriately referred your patient to the local ED. A head CT with head and neck CTA was performed. While the head CT did not show any abnormalities, the CTA demonstrated high-grade left internal carotid artery stenosis. The patient was given an initial dose of aspirin 325 mg and a high-intensity statin and admitted for further management. An MRI revealed a small shower of emboli in the left hemisphere, confirming the diagnosis of stroke over TIA. Labs were marginally remarkable with a low-density lipoprotein level of 115 mg/dL and an HbA1c of 6.2. Telemetry monitoring did not reveal any arrhythmias, and TTE was normal. BP remained in the high-normal to low-hypertensive range.

Timing matters, even when symptoms have resolved, such as with a TIA.

A Vascular Surgery consultation was obtained and the patient underwent a left carotid endarterectomy the following day. She did well without surgical complications. Her BP medications were adjusted; a combination of an angiotensin-converting enzyme inhibitor and a thiazide diuretic achieved a goal BP <140/90 mm Hg.

Permissive hypertension was not indicated due to her presentation >48 hours beyond the acute event. Low-dose aspirin and a high-intensity statin were continued, for secondary stroke prevention in the setting of atherosclerotic disease. She received smoking cessation counseling, which will continue.

CORRESPONDENCE
Stephen A. Martin, MD, EdM, Barre Family Health Center, 151 Worcester Road, Barre, MA 01005; [email protected].

Antihemophilic factor

The European Medicines Agency’s (EMA’s) Committee for Orphan Medicinal Products has issued a positive opinion recommending orphan designation for CB 2679d/ISU304 for the treatment of hemophilia B.

CB 2679d is a coagulation factor IX variant that has demonstrated, in preclinical studies, the potential to normalize factor IX levels via a daily subcutaneous injection.

The product is being developed by Catalyst Biosciences and ISU Abxis. ISU Abxis plans to initiate a phase 1/2 study of CB 2679d in individuals with severe hemophilia B this month in South Korea.

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.

The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.

The EMA’s Committee for Orphan Medicinal Products adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The commission typically makes a decision within 30 days of the submission. 

Antihemophilic factor

The European Medicines Agency’s (EMA’s) Committee for Orphan Medicinal Products has issued a positive opinion recommending orphan designation for CB 2679d/ISU304 for the treatment of hemophilia B.

CB 2679d is a coagulation factor IX variant that has demonstrated, in preclinical studies, the potential to normalize factor IX levels via a daily subcutaneous injection.

The product is being developed by Catalyst Biosciences and ISU Abxis. ISU Abxis plans to initiate a phase 1/2 study of CB 2679d in individuals with severe hemophilia B this month in South Korea.

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.

The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.

The EMA’s Committee for Orphan Medicinal Products adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The commission typically makes a decision within 30 days of the submission. 

Antihemophilic factor

The European Medicines Agency’s (EMA’s) Committee for Orphan Medicinal Products has issued a positive opinion recommending orphan designation for CB 2679d/ISU304 for the treatment of hemophilia B.

CB 2679d is a coagulation factor IX variant that has demonstrated, in preclinical studies, the potential to normalize factor IX levels via a daily subcutaneous injection.

The product is being developed by Catalyst Biosciences and ISU Abxis. ISU Abxis plans to initiate a phase 1/2 study of CB 2679d in individuals with severe hemophilia B this month in South Korea.

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.

The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.

The EMA’s Committee for Orphan Medicinal Products adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The commission typically makes a decision within 30 days of the submission. 

Based on the clinical presentation and skin biopsy results, the patient was given a diagnosis of cutaneous sarcoidosis. The biopsy from the right side of his nose demonstrated sarcoidal granulomas. A biopsy of one of the tattoo nodules showed sarcoidal granulomas, and close inspection revealed red tattoo pigment within the granulomatous inflammation. X-rays showed bilateral hilar lymphadenopathy, which was consistent with pulmonary sarcoidosis, and the lace-like appearance of the middle and distal phalanges was consistent with skeletal sarcoidosis.

Systemic sarcoidosis is an idiopathic, granulomatous disease that affects multiple organ systems, but primarily the lungs and lymphatic system. Cutaneous sarcoidosis can occur as a manifestation of systemic sarcoidosis. It may present as asymptomatic red or skin-colored papules and firm nodules within tattoos, old scars, or permanent makeup. Sarcoidosis usually occurs in red, black, or blue-black areas of tattoos, in which the pigment acts as a nidus for granuloma formation.

The first-line treatment for limited papules is a high-potency topical corticosteroid (eg, clobetasol 0.05% ointment applied twice weekly) and an intralesional corticosteroid (eg, triamcinolone, one 5-10 mg/mL injection every 4 weeks). Antimalarials such as hydroxychloroquine or methotrexate can also be helpful. Midpotency topical corticosteroids such as triamcinolone 0.1% cream and doxycycline hyclate have been reported to clear cutaneous lesions in tattoos. Oral corticosteroids are often effective for severe cutaneous sarcoidosis, but their multiple adverse effects (eg, diabetes and adrenal suppression) prevent prolonged use except in very low doses in conjunction with other therapies.

The nodules on this patient’s nose were successfully treated with intralesional triamcinolone 5 mg/mL. No treatment was initiated for the tattoo nodules because they were asymptomatic and the patient wasn’t bothered by their appearance. The patient’s hand swelling improved with a treatment of prednisone 10 mg/d. The rheumatologist considered a steroid-sparing immunosuppressive agent such as methotrexate; however, the patient was lost to follow-up.

Adapted from: Zhang J, Jansen R, Lim HW. Nodules on nose and tattoos. J Fam Pract. 2015;64:241-243.

Based on the clinical presentation and skin biopsy results, the patient was given a diagnosis of cutaneous sarcoidosis. The biopsy from the right side of his nose demonstrated sarcoidal granulomas. A biopsy of one of the tattoo nodules showed sarcoidal granulomas, and close inspection revealed red tattoo pigment within the granulomatous inflammation. X-rays showed bilateral hilar lymphadenopathy, which was consistent with pulmonary sarcoidosis, and the lace-like appearance of the middle and distal phalanges was consistent with skeletal sarcoidosis.

Systemic sarcoidosis is an idiopathic, granulomatous disease that affects multiple organ systems, but primarily the lungs and lymphatic system. Cutaneous sarcoidosis can occur as a manifestation of systemic sarcoidosis. It may present as asymptomatic red or skin-colored papules and firm nodules within tattoos, old scars, or permanent makeup. Sarcoidosis usually occurs in red, black, or blue-black areas of tattoos, in which the pigment acts as a nidus for granuloma formation.

The first-line treatment for limited papules is a high-potency topical corticosteroid (eg, clobetasol 0.05% ointment applied twice weekly) and an intralesional corticosteroid (eg, triamcinolone, one 5-10 mg/mL injection every 4 weeks). Antimalarials such as hydroxychloroquine or methotrexate can also be helpful. Midpotency topical corticosteroids such as triamcinolone 0.1% cream and doxycycline hyclate have been reported to clear cutaneous lesions in tattoos. Oral corticosteroids are often effective for severe cutaneous sarcoidosis, but their multiple adverse effects (eg, diabetes and adrenal suppression) prevent prolonged use except in very low doses in conjunction with other therapies.

The nodules on this patient’s nose were successfully treated with intralesional triamcinolone 5 mg/mL. No treatment was initiated for the tattoo nodules because they were asymptomatic and the patient wasn’t bothered by their appearance. The patient’s hand swelling improved with a treatment of prednisone 10 mg/d. The rheumatologist considered a steroid-sparing immunosuppressive agent such as methotrexate; however, the patient was lost to follow-up.

Adapted from: Zhang J, Jansen R, Lim HW. Nodules on nose and tattoos. J Fam Pract. 2015;64:241-243.

Based on the clinical presentation and skin biopsy results, the patient was given a diagnosis of cutaneous sarcoidosis. The biopsy from the right side of his nose demonstrated sarcoidal granulomas. A biopsy of one of the tattoo nodules showed sarcoidal granulomas, and close inspection revealed red tattoo pigment within the granulomatous inflammation. X-rays showed bilateral hilar lymphadenopathy, which was consistent with pulmonary sarcoidosis, and the lace-like appearance of the middle and distal phalanges was consistent with skeletal sarcoidosis.

Systemic sarcoidosis is an idiopathic, granulomatous disease that affects multiple organ systems, but primarily the lungs and lymphatic system. Cutaneous sarcoidosis can occur as a manifestation of systemic sarcoidosis. It may present as asymptomatic red or skin-colored papules and firm nodules within tattoos, old scars, or permanent makeup. Sarcoidosis usually occurs in red, black, or blue-black areas of tattoos, in which the pigment acts as a nidus for granuloma formation.

The first-line treatment for limited papules is a high-potency topical corticosteroid (eg, clobetasol 0.05% ointment applied twice weekly) and an intralesional corticosteroid (eg, triamcinolone, one 5-10 mg/mL injection every 4 weeks). Antimalarials such as hydroxychloroquine or methotrexate can also be helpful. Midpotency topical corticosteroids such as triamcinolone 0.1% cream and doxycycline hyclate have been reported to clear cutaneous lesions in tattoos. Oral corticosteroids are often effective for severe cutaneous sarcoidosis, but their multiple adverse effects (eg, diabetes and adrenal suppression) prevent prolonged use except in very low doses in conjunction with other therapies.

The nodules on this patient’s nose were successfully treated with intralesional triamcinolone 5 mg/mL. No treatment was initiated for the tattoo nodules because they were asymptomatic and the patient wasn’t bothered by their appearance. The patient’s hand swelling improved with a treatment of prednisone 10 mg/d. The rheumatologist considered a steroid-sparing immunosuppressive agent such as methotrexate; however, the patient was lost to follow-up.

Adapted from: Zhang J, Jansen R, Lim HW. Nodules on nose and tattoos. J Fam Pract. 2015;64:241-243.

EVIDENCE SUMMARY

A meta-analysis of 24 RCTs examined the effect of pseudoephedrine on BP and heart rate.¹ Just 5 of the 24 studies specifically included hypertensive patients. In the population of patients with hypertension, the meta-analysis showed a small (1.2 mm Hg) rise in systolic BP with pseudoephedrine that was statistically significant (95% confidence interval [CI], 0.56-1.84 mm Hg), but the slight changes in diastolic BP and heart rate were not significant. No patient-oriented outcomes were measured.

The highest quality study within this group was a randomized, double-blind, placebo-controlled crossover study with 28 patients given sustained-release pseudoephedrine 120 mg twice daily for 72 hours, with BP measurements taken at 48 and 72 hours.² The study was powered to identify an increase in systolic BP of 11 mm Hg, but the results showed just a 3.1 mm Hg rise in systolic BP at 48 hours (see TABLE^1-7 for CI and other data).

In another double-blind, placebo-controlled RCT of 29 adults with hypertension (only 25 were included in the data analysis), there was no significant elevation in BP when oral pseudoephedrine was administered over the course of 3 days.³

Across the 5 studies in the meta-analysis, immediate-release and sustained-release forms of pseudoephedrine were included, hypertension was described as controlled but definitions of control were not always specified, and study length varied from 2 hours to 4 weeks.^2-6 Patients on antihypertensive medications were included in some of the studies; patients who had active cardiovascular disease, peripheral vascular disease, and/or cerebrovascular disease were excluded.

One study specifically looked at the effects of a single dose of pseudoephedrine on BP in patients treated with 2 different beta-blockers and found no significant change from baseline, but this study was not powered to show differences less than 5 mm Hg.⁶ The study did show a change of 1 to 2 mm Hg in systolic BP, but this was not statistically significant.

An absence of information on older patients

There is a paucity of literature on treating older adults and medically complex patients (eg, those with uncontrolled or secondary causes of hypertension, cerebrovascular disease, coronary artery disease) with decongestants, as they were excluded in all studies. And the available evidence does not include reports of adverse events other than changes in BP.

EVIDENCE SUMMARY

A meta-analysis of 24 RCTs examined the effect of pseudoephedrine on BP and heart rate.¹ Just 5 of the 24 studies specifically included hypertensive patients. In the population of patients with hypertension, the meta-analysis showed a small (1.2 mm Hg) rise in systolic BP with pseudoephedrine that was statistically significant (95% confidence interval [CI], 0.56-1.84 mm Hg), but the slight changes in diastolic BP and heart rate were not significant. No patient-oriented outcomes were measured.

The highest quality study within this group was a randomized, double-blind, placebo-controlled crossover study with 28 patients given sustained-release pseudoephedrine 120 mg twice daily for 72 hours, with BP measurements taken at 48 and 72 hours.² The study was powered to identify an increase in systolic BP of 11 mm Hg, but the results showed just a 3.1 mm Hg rise in systolic BP at 48 hours (see TABLE^1-7 for CI and other data).

In another double-blind, placebo-controlled RCT of 29 adults with hypertension (only 25 were included in the data analysis), there was no significant elevation in BP when oral pseudoephedrine was administered over the course of 3 days.³

Across the 5 studies in the meta-analysis, immediate-release and sustained-release forms of pseudoephedrine were included, hypertension was described as controlled but definitions of control were not always specified, and study length varied from 2 hours to 4 weeks.^2-6 Patients on antihypertensive medications were included in some of the studies; patients who had active cardiovascular disease, peripheral vascular disease, and/or cerebrovascular disease were excluded.

One study specifically looked at the effects of a single dose of pseudoephedrine on BP in patients treated with 2 different beta-blockers and found no significant change from baseline, but this study was not powered to show differences less than 5 mm Hg.⁶ The study did show a change of 1 to 2 mm Hg in systolic BP, but this was not statistically significant.

An absence of information on older patients

There is a paucity of literature on treating older adults and medically complex patients (eg, those with uncontrolled or secondary causes of hypertension, cerebrovascular disease, coronary artery disease) with decongestants, as they were excluded in all studies. And the available evidence does not include reports of adverse events other than changes in BP.

EVIDENCE SUMMARY

A meta-analysis of 24 RCTs examined the effect of pseudoephedrine on BP and heart rate.¹ Just 5 of the 24 studies specifically included hypertensive patients. In the population of patients with hypertension, the meta-analysis showed a small (1.2 mm Hg) rise in systolic BP with pseudoephedrine that was statistically significant (95% confidence interval [CI], 0.56-1.84 mm Hg), but the slight changes in diastolic BP and heart rate were not significant. No patient-oriented outcomes were measured.

The highest quality study within this group was a randomized, double-blind, placebo-controlled crossover study with 28 patients given sustained-release pseudoephedrine 120 mg twice daily for 72 hours, with BP measurements taken at 48 and 72 hours.² The study was powered to identify an increase in systolic BP of 11 mm Hg, but the results showed just a 3.1 mm Hg rise in systolic BP at 48 hours (see TABLE^1-7 for CI and other data).

In another double-blind, placebo-controlled RCT of 29 adults with hypertension (only 25 were included in the data analysis), there was no significant elevation in BP when oral pseudoephedrine was administered over the course of 3 days.³

Across the 5 studies in the meta-analysis, immediate-release and sustained-release forms of pseudoephedrine were included, hypertension was described as controlled but definitions of control were not always specified, and study length varied from 2 hours to 4 weeks.^2-6 Patients on antihypertensive medications were included in some of the studies; patients who had active cardiovascular disease, peripheral vascular disease, and/or cerebrovascular disease were excluded.

One study specifically looked at the effects of a single dose of pseudoephedrine on BP in patients treated with 2 different beta-blockers and found no significant change from baseline, but this study was not powered to show differences less than 5 mm Hg.⁶ The study did show a change of 1 to 2 mm Hg in systolic BP, but this was not statistically significant.

An absence of information on older patients

There is a paucity of literature on treating older adults and medically complex patients (eg, those with uncontrolled or secondary causes of hypertension, cerebrovascular disease, coronary artery disease) with decongestants, as they were excluded in all studies. And the available evidence does not include reports of adverse events other than changes in BP.