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How to diagnose and manage hypertension in a psychiatric patient: increased risk of morbidity and mortality; be vigilant in drug-disease, drug-drug interactions.

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 [greater than or equal to] 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 under-treatment 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 [greater than or equal to] 2 properly measured readings at [greater than or equal to] 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 [greater than or equal to] 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.

Common medications, including several psychiatric drugs, also can contribute to elevated blood pressure (Table 1).

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 includes (15):

* 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 [Al.sub.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 [alpha]-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 [greater than or equal to] 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. (15)

Blood 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 [less than or equal to] 60 mL/ min/1.73 [m.sup.2]--depend on age: <140/ 90 mm Hg for age 18 to 59 and <150/90 mm Hg for age [greater than or equal to] 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 [greater than or equal to] 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 sub-clinical cardiovascular disease other than stroke, CKD with GFR of 20 to 60 mL/min/ 1.73 [m.sup.2], age [greater than or equal to] 75, or Framingham 10-year coronary heart disease risk score [greater than or equal to] 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 [greater than or equal to] 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 [less than or equal 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 [greater than or equal to] 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 [greater than or equal to] 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 [greater than or equal to] 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.

Clinical Point

A study found a 61% prevalence of hypertension among those with bipolar disorder compared with 41% in the general population

Clinical Point

Several antihypertensives when taken with venlafaxine can increase blood pressure

Clinical Point

Patients with increased depressive symptoms are less likely to comply with antihypertensive medication

Clinical Point

For patients with diabetes or CKD, the blood pressure goal is <140/90 mm Hg; for non-diabetic patients age [greater than or equal to] 50, consider a goal of <120 mm Hg

Clinical Point

Motivate and educate patients on lifestyle modifications, such as weight reduction, exercise, and alcohol and sodium intake

Clinical Point

When possible, Collaborate with the primary care physician; adjust or add medication dosages monthly until the goal is reached

Disclosures

The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

Related Resources

* National High Blood Pressure Education Program. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Bethesda, MD: U.S. Department of Health and Human Services; 2004.

* Framingham heart study, www.framinghamheartstudy. org/risk-functions/cardiovascular-disease/10-yearrisk.php.

Drug Brand Names

Armodafinil * Nuvigil Atomoxetine * Strattera Cyclosporlne * Sandimmune Dextroamphetamine * Dexedrine, ProCentra Lithium * Eskalith, Lithobid Methylphenldate * Concerta, Ritalin Modafinil * Provigil Tacrolimus * Protopic, Hecoria, Prograf Venlafaxine * Effexor

Robert M. McCarron, DO Associate Professor Director, Pain Psychiatry and Behavioral Sciences Director, Internal Medicine/ Psychiatry Residency Department of Anesthesiology, Division of Pain Medicine Department of Psychiatry and Behavioral Sciences Department of Internal Medicine University of California, Davis, School of Medicine Sacramento, California Member, Current Psychiatry Editorial Board

Craig R. Keenan, MD Professor Program Director, Internal Medicine Residency Program Department of Internal Medicine University of California, Davis, School of Medicine Sacramento, California

Banoo Lashai, MD Resident Physician Department of Psychiatry Richmond University Medical Center New York, New York

John C. Onate, MD Associate Professor Department of Psychiatry of Behavioral Sciences Medical Director Sacramento County Primary Care Clinic Sacramento, California

References

(1.) Centers for Disease Control and Prevention (CDC). Vital signs: awareness and treatment of uncontrolled hypertension among adults--United States, 20032010. MMWR Morb Mortal Wkly Rep. 2012;61: 703-709.

(2.) Mozzafarian D, Benjamin EJ, Go AS, et al; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics--2015 update: a report from the American Heart Association. Circulation. 2015;131(4):e29-e322.

(3.) Carroll D, Phillips AC, Gale CR, et al. Generalized anxiety and major depressive disorders, their comorbidity and hypertension in middle-aged men. Psychosom Med. 2010; 72(1):16-19.

(4.) Leboyer M, Soreca I, Scott J, et al. Can bipolar disorder be viewed as a multi-system inflammatory disease? J Affect Disord. 2012;141(1):1-10.

(5.) Goff DC, Sullivan LM, McEvoy JP, et al. A comparison of ten-year cardiac risk estimates in schizophrenia patients from the CATIE study and matched controls. Schizophr Res. 2005;80(l):45-53.

(6.) Stein DJ, Aguilar-Gaxiola S, Alonso J, et al. Associations between mental disorders and subsequent onset of hypertension. Gen Hosp Psychiatry. 2014;36(2):142-149.

(7.) Birkenaes AB, Opjordsmoen S, Brunborg C, et al. The level of cardiovascular risk factors in bipolar disorder equals that of schizophrenia: a comparative study. J Clin Psychiatry. 2007;68(6):917-923.

(8.) Izzo JL, Black HR, Goodfriend TL. Hypertension primer: the essentials of high blood pressure. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2008.

(9.) Osby U, Correia N, Brandt L, et al. Mortality and causes of death in schizophrenia in Stockholm County, Sweden. Schizophr Res. 2000;45(l-2):21-28.

(10.) Brown S, Inskip H, Barraclough B. Causes of the excess mortality of schizophrenia. Br J Psychiatry. 2000;177:212-217.

(11.) Auquier P, Lancon C, Rouillon F, et al. Mortality in schizophrenia. Pharmacoepidemiol Drug Saf. 2007;16(12): 1308-1312.

(12.) Newcomer JW, Hennekens CH. Severe mental illness and risk of cardiovascular disease. JAMA. 2007298(15): 1794-1796.

(13.) Bowis J, Parvanova A, McDaid D, et al. Mental and Physical Health Charter: bridging the gap between mental and physical health. https://www.idf.org/sites/default/files/ Mental%2520and%2520Physical%2520Health%2520Cha rter%2520-%2520FINAL.pdf. Published October 7, 2009. Accessed March 6, 2017.

(14.) Nasrallah HA, Meyer JM, Goff DC, et al. Low rates of treatment for hypertension, dyslipidemia and diabetes in schizophrenia: data from the CATIE schizophrenia trial sample at baseline. Schizophr Res. 2006;86(l-3):15-22.

(15.) Chobanian AV, Bakris GL, Black HR, et al; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289(19):2560-2571.

(16.) Handler J. Lithium and antihypertensive medication: a potentially dangerous interaction. J Clin Hypertens (Greenwich). 2009;11(12):738-742.

(17.) National Collaborating Centre for Mental Health (UK). Depression in adults with a chronic physical health problem: treatment and Management Appendix 16: table of drug interactions, http://www.ncbi.nlmjlih.gov/books/ NBK82914. Published 2010. Accessed March 6, 2017.

(18.) Siu AL; U.S. Preventive Services Task Force. Screening for high blood pressure in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2015:163(10):778-786.

(19.) Wang PS, Bohn RL, Knight E, et al. Noncompliance with antihypertensive medications: the impact of depressive symptoms and psychosocial factors. J Gen Intern Med. 2002;17(7):504-511.

(20.) DiMatteo MR, Lepper HS, Croghan TW. Depression is a risk factor for noncompliance with medical treatment: metaanalysis of the effects of anxiety and depression on patient adherence. Arch Intern Med. 2000;160(14):2101-2107.

(21.) Consoli SM, Lemogne C, Levy A, et al. Physicians' degree of motivation regarding their perception of hypertension, and blood pressure control. J Hypertens. 2010;28(6):1330-1339.

(22.) National High Blood Pressure Education Program. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Improving Hypertension Control. Bethesda, MD: U.S. Department of Health and Human Services; 2004:61-64.

(23.) James PA, Oparil S, Carter BL, et al. 2014 evidence-based guidelineforthemanagementofhighbloodpressureinadults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507-520.

(24.) The SPRINT Research Group; Wright JT Jr, Williamson JD, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373(22):2103-2016.

(25.) Boulware LE, Daumit GL, Frick KD, et al. An evidence-based review of patient-centered behavioral interventions for hypertension. Am J Prev Med. 200121 (3):221-232.

Bottom Line

Recognize and manage hypertension in psychiatric patients with the proper technique for taking blood pressure and conducting an evaluation that accounts for the effects of psychotropic drugs. Lifestyle modifications can control blood pressure in many patients, but antihypertensive therapy is indicated in refractory cases.

Caption: Figure Blood pressure goals in adults
Table 1
Medications that can elevate
blood pressure

Nonsteroidal anti-inflammatory agents

Corticosteroids

Anabolic steroids

Serotonin reuptake inhibitors

Serotonin-norepinephrine reuptake inhibitors

Tricyclic antidepressants

Monoamine oxidase inhibitors

Cyclosporine

Tacrolimus

Erythropoietin

Methylphenidate

Amphetamines

Decongestants

Oral contraceptives

Table 2
Drug-drug interactions between psychotropic
medications and antihypertensive agents

Antihypertensive    Psychotropic         Caution
medication class    medications

Diuretics           Lithium              Watch for dehydration
                                         and increased serum
                                         lithium level

Several taken at    Venlafaxine          Watch for increased
the same time                            blood pressure

Several taken at    Psychotropics with   Watch for potential
the same time       high [alpha]-1       hypotension
                    blockade

Any class           Monoamine oxidase    Hypotension
                    inhibitors           ([alpha]-1 blockade)

                                         Hypertension
                                         (food with
                                         tyramine may cause
                                         catecholamine surge
                                         and hypertensive
                                         crisis)

Any class           Stimulants           Watch for increased
                                         blood pressure

Table 3
Choice of initial drug therapy for hypertension

Patient group                First-line agents

African American patients    Thiazide diuretic
without CKD                  Calcium channel blocker

Non-African American         Thiazide diuretic
patients without CKD         Calcium channel blocker
                             Angiotensin-converting enzyme
                             Inhibitor or angiotensin
                             receptor blocker

African American             With proteinuria
patients with CKD            Angiotensin-converting enzyme inhibitor
                             or angiotensin receptor blocker
                             Without proteinuria
                             Thiazide diuretic
                             Calcium channel blocker
                             Angiotensin-converting enzyme inhibitor
                             or angiotensin receptor blocker

Non-African American         Angiotensin-converting enzyme inhibitor
patients with CKD            or angiotensin receptor blocker

Patients with type 2         Treatment based on ethnicity and CKD,
diabetes mellitus            as above

CKD: chronic kidney disease

Source: Reference 23
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Title Annotation:Med/Psych Update: HYPERTENSION
Author:McCarron, Robert M.; Keenan, Craig R.; Lashai, Banoo; Onate, John C.
Publication:Current Psychiatry
Geographic Code:1USA
Date:Jun 1, 2017
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