Management of Hypertension Complicated by Psychiatric Comorbidity

Diverse psychosocial forces can impact hypertension and its clinical care. Chronic mental stress is possibly a cause of essential hypertension. Opinions on this are polarized, no doubt partly because the occupational health litigation dimensions of the subject are so divisive. White coat hypertension has psychologic roots that remain enigmatic; introversion and shyness have been implicated. The apparent blood pressure (BP) surges of labile hypertension can be real, artifactual, or illusory; psychologic factors are operative in some instances via panic attacks and episodic life stress. Panic disorder not uncommonly coexists with hypertension, confounding the diagnosis of pheochromocytoma and influencing antihypertensive drug choices; panic attacks can masquerade as hypertensive emergencies. Obsessive compulsive disorder can transform home BP measurement into a compulsive, ritualized component of the illness. Depressive illness and schizophrenia may coexist with hypertension through prescribed psychotropic drugs causing weight gain and BP elevation. Attitudinal barriers to treatment, beyond explicit psychopathology, do exist; antidrug ideology, psychologic denial, and indifference to life itself are examples.

In nearly 40 years of medical practice involving primarily the care of patients with high BP in Canberra, Australia; Ann Arbor, Michigan; and Melbourne, Australia, it has been impressed on one of the authors (ME) that some patients are extraordinarily difficult to help. These are the patients who make the heart sink when their names are seen on the patient list for the day, because of past and ongoing therapeutic failure with them.

This failure is usually not a result of them having the most severe hypertension. More often than not, it results from the presence of psychiatric illness coexisting with their hypertension or a personality that impinges adversely, in various ways, on the doctor‐patient therapeutic alliance. Patients with psychiatric comorbidity are common in hypertension clinics. This can result from medical referral biases, with somatic symptoms or morbid health preoccupations in depression and anxiety disorders leading to the initial medical presentation and subsequent referral. In addition, the prevalence of some psychiatric illness is genuinely increased in patients with essential hypertension; an example is panic disorder. ¹ Further, some drugs used in psychiatric care can cause hypertension secondary to weight gain.

In this commentary, we try to formulate the common psychosocial reasons for therapeutic failure with hypertensive patients and describe some of the characteristics of everyone's “difficult” patient. This could only be possible with the input of both the clinical experience of the hypertensionologist (ME) and the psychiatric expertise of his wife (RS), who tried to make sense of his uncomprehending and psychiatrically naive complaints at the end of the working day. Together, we have prepared this commentary in the hope that in the future, treatment of the problem patient might be a little less daunting.

PANIC DISORDER

The prevalence of panic disorder is increased in patients with essential hypertension. This represents a special case of a broader phenomenon, the high level of anxiety disorder, often undiagnosed, in medical practice in general. ² With panic disorder and hypertension, there is almost certainly a true increase in comorbidity, ¹ but medical referral and attendance biases also contribute to the apparent link. Further, some antihypertensive drugs seem capable of initiating panic disorder. α‐Adrenergic drugs that cause recurring postural hypotension accompanied by dizziness, palpitations, and sweating are a case in point. The mechanism appears to be analogous to that operating when recurrent cardiac arrhythmias, particularly supraventricular tachycardia, cause panic disorder by sensitizing the patient to cardiac symptoms. ³

The presence of panic disorder can confound hypertension diagnoses. A panic attack accompanied by marked BP increase can lead to a misdiagnosis of hypertension sufficiently severe to constitute a medical emergency. Differentiating panic disorder from pheochromocytoma can be difficult, which is explicitly acknowledged in the use of the term pseudopheochromocytoma applied in patients in whom anxiety disorder masquerades as an adrenal medullary tumor. ⁴ , ⁵ Similar symptoms can occur with both, accompanied by BP surges. Twenty‐four‐hour urinary catecholamine excretion can be misleading; urinary adrenaline excretion can be elevated 2‐ to 3‐fold in patients with panic disorder if the collection period includes a panic attack. The invariable sense of dread at the very onset of panic attack, not typical of a pheochromocytoma episode, is a helpful discriminator.

Hypertensive patients with anxiety disorder can generate worrying symptoms by hyperventilating, which often leads to unnecessary medical investigations. ⁶ Persons experiencing panic can also misinterpret their symptoms as drug side effects. These “side effects” are to be curtailed by the doctor or in a short order all antihypertensives in the pharmacopeia will be tried, but discontinued, on spurious grounds. Panic disorder usually responds well to selective serotonin reuptake‐blocking drugs and to cognitive behavior therapy, alone or in combination. β‐Adrenergic‐blocking drugs are a useful addition, helpful in treating both the panic disorder and the hypertension.

WHITE COAT HYPERTENSION

In some patients, BP is materially higher at the time of medical consultation than when self‐recorded in the home or measured with 24‐hour ambulatory monitoring; this is the so‐called white coat effect. ⁷ Despite these forms of BP measurement being regarded as the gold standard, the error occasionally can be in the home BP record, such as in the patient who takes multiple measurements, searching for their “best” (lowest) BP level, which might perhaps be found after a hot shower and duly recorded. Not surprisingly, the clinic BP in persons such as these will be higher.

Much more usual is active elevation of BP at the time of the medical consultation. The precise origins of the white coat effect remain uncertain. It is sometimes attributed to a stereotyped, conditioned anxiety response, but this is unlikely because if it is true, extinction of the response would be expected with the flooding exposure of repeated clinic visits and BP measurements. The white coat effect usually persists across multiple visits, ⁷ often for many years.

Our personal experience is that the white coat effect seems to be prominent in shy and rather self‐conscious patients for whom the uncomfortable intimacy of the consultation is the trigger for the BP elevation (and not uncommonly, blushing). There is systematic support for this idea in a Japanese study ⁸ in which researchers found that white coat reactors scored low on the Eysenck extroversion scale (ie, they had high introversion). Eysenck argued that the highly introverted, in particular, find social interactions aversive. Further support comes from a study in Italian patients ⁹ that reported that the white coat phenomenon was highly correlated with an increase in BP during public speaking, a stereotypic challenge to the introverted. Patients with white coat hypertension do not have greater BP response across the board to stressors in general.

Does this formulation provide a strategy for overcoming the measurement artifact that white coat hypertension entails? Not really; training the patient in BP self‐recording remains the preferred option.

LABILE HYPERTENSION

BP is very fluid in its responses to the internal environment and to life events. White coat hypertension has its origins in this phenomenon. In some patients, the day‐to‐day variability of BP seems to be greater than usual (as distinct from white coat hypertension, which is a constant in the clinic ⁷ ). This is used as a diagnostic discriminator, in their being categorized as labile hypertensives. To some, family physicians and medical generalists in particular, this diagnostic designation ranks in importance with some other recognized hypertension subclasses, such as essential, secondary, and malignant hypertension. Hypertension specialists are less accepting of the existence of labile hypertension as a discrete entity. Some deny its existence. ¹⁰ Others would suggest that although excess BP lability can be illusory, or artifactual, it is sometimes real and diagnostically important (Table I).

Table I.

Potential Causes of Labile Hypertension

Episodic life stresses

Panic disorder

“Autonomic crises”

Borderline hypertension (illusory)

Auscultatory gap (artifactual)

Pheochromocytoma

In some patients, such as those with panic disorder or episodic life stresses, labile hypertension is real enough and psychogenic. In people with severe, recurring life stresses, BP can be the “barometer” of their level of distress. Others may perhaps have inexplicable surges of sympathetic nervous system activity sometimes categorized as autonomic epilepsy: a murky, poorly understood characteristic of a few patients with essential hypertension.

In some patients, such as those with borderline BP elevation, lability of hypertension is illusory. ¹⁰ BP recorded in the clinic, while actually showing the usual degree of variability, creates an illusion of greater fluctuation than normal by oscillating around the cutoff for the diagnosis of established hypertension. ¹⁰ In other patients, high BP lability is artifactual, a consequence of the auscultatory gap phenomenon in which there is a premature disappearance of sounds with subsequent return as the cuff is further deflated. Labile hypertension diagnosed from hospital charts is notoriously of this form. Some careful interns and residents, in avoiding the auscultatory gap artifact by estimating the BP by pulse as a preliminary measure, have recorded the BP accurately, while those who are less careful have missed the true systolic pressure and recorded the lower BP when the disappearing auscultatory sounds reappear.

The labile hypertension not to be missed is that accompanying pheochromocytoma. Extreme BP variability, with associated symptoms, is the clinical hallmark of this dangerous tumor of the adrenal medulla and sympathetic chain. Measurement of catecholamines and their metabolite in urine and/or plasma will be needed to confirm the diagnosis.

CHRONIC MENTAL STRESS

The notion that chronic mental stress can cause hypertension was an idea in the past often banished to the realm of medical folklore. The general public has needed little persuasion that the link exists, sometimes even using the word “hypertensive” as a psychologic descriptor for describing excitable or agitated behavior. Many personally relate to the “tense” in “hypertension” and may be too ready to attribute their elevated BP to stress in their job or in their domestic life.

Although some uncertainty still exists concerning the role of stress in the pathogenesis of human hypertension, clinical, epidemiologic, and laboratory research does provide increasingly strong support. ¹¹ , ¹² Our own recent research seems to identify the presence of stress biomarkers in patients with essential hypertension. ¹³ In our own country, in an admittedly contentious judgment, an Australian governmental body, the Specialist Medical Review Council, ruled that stress, including stress in the workplace, is one proven cause of hypertension. ¹⁴

How effective are relaxation therapies, such as relaxation training, meditation, and yoga, and structured stress reduction strategies in domestic and working lives as antihypertensive therapy? Certainly much less effective than expected from this account. Among nonpharmacologic therapies, weight reduction and exercise outrank relaxation therapies and stress reduction strategies in antihypertensive efficacy. ¹⁵

DEPRESSIVE ILNESS

Patients with depression commonly present with somatic complaints and are incidentally found to have elevated BP. Their negativity can make them sensitive to adverse drug effects. If they are seen by their primary care physicians as “problem patients,” they will be more likely than usual to be referred to a hypertension specialist. Depressive illness seems to be common in hospital hypertension clinics, due primarily to this bias in hypertension detection and medical referral.

Essential hypertension and depressive illness do not seem to be causally linked other than through adverse drug effects. In the old days, this was due to some antihypertensive drugs causing depressive illness; centrally acting antihypertensives such as reserpine and methyldopa could do this. Now the wheel has turned, with psychotropic drugs sometimes causing hypertension, primarily through promoting weight gain; this leads to hypertension as a component of the metabolic syndrome. ¹⁶ , ¹⁷

SCHIZOPHRENIA

Much of what has been said about drug‐induced hypertension in patients with depressive illness applies also for those with schizophrenia. Classic antipsychotic drugs, novel antipsychotics such as olanzapine, antidepressants of all types (including selective norepinephrine and serotonin reuptake blockers such as venlafaxine), and selective serotonin reuptake inhibitors, including paroxetine, prescribed for accompanying depressive illness can cause extreme weight gain, diabetes, and hypertension in patients with schizophrenia. ¹⁶ , ¹⁷ The tendency for individual psychotropic drugs to cause weight gain is variable, both between patients and across drug classes. Some psychotropic drugs are much more likely than others to cause weight gain (Table II). These should be avoided if possible in those patients who have developed the metabolic syndrome. Schizophrenia is often associated with other cardiac risk factors such as smoking and physical inactivity, making avoidance of obesity and hypertension doubly important.

Table II.

Metabolic Syndrome From Psychotropic Drugs: Differing Potential for Weight Gain^a

Selective serotonin reuptake inhibitors:

For example, more weight gain with paroxetine than citalopram

Novel antipsychotics:

Weight gain for clozapine > olanzapine > quetiapine

Selective norepinephrine and serotonin reuptake inhibitors:

Weight gain and independent BP elevation common with venlafaxine

Selective stimulator of norepinephrine and serotonin release:

Weight gain common with mirtazapine

aSome psychotropic drugs are more likely than others to cause weight gain. 17

ANTIHYPERTENSIVE DRUG CHOICES IN OBESITY‐RELATED HYPERTENSION

What antihypertensive medication is preferred in psychotropic drug‐induced obesity‐related hypertension? Although this remains somewhat speculative, there are some pointers. A case for preferential prescribing of antiadrenergic antihypertensive drugs that target the known pathophysiology of obesity‐related hypertension, activation of the sympathetic nervous system, ¹⁸ can be advocated on theoretic grounds, but at present there is little empiric evidence to support this.

Perhaps more important is the requirement that chosen antihypertensives do not cause weight gain or increase insulin resistance, predisposing to the development of diabetes. High‐dose diuretics are best avoided, if possible, on the latter grounds. β‐Adrenergic‐blocking drugs also are not ideal, ¹⁹ having been found in large trials to cause some weight gain, perhaps 1 to 2 kg on average, and to predispose to the development of diabetes. ¹⁹ , ²⁰ Angiotensin‐converting enzyme inhibitors and angiotensin receptor blockers have been especially recommended, as they appear to be antidiabetic. ²¹ The imidazoline‐binding agents such as rilmenidine and moxonidine, which are not available in United States, inhibit sympathetic outflow from the brain, cause weight loss of 1 to 2 kg on average, and increase insulin sensitivity. ²⁰ , ²² Perhaps this is a drug class of the future for obesity‐related hypertension?

PSYCHOSOCIAL FACTORS COMPROMISING COMPLIANCE WITH TREATMENT INSTRUCTIONS

Overall, compliance with treatment instructions is not good in patients with essential hypertension. This perhaps is not surprising for an illness in which treatment rather than relieving existing symptoms aims to achieve the delayed benefits of future freedom from myocardial infarction and stroke. Psychiatric illness can further impair compliance. Negativity and lack of volition in those with comorbid depressive illness or schizophrenia compromises medications taking. So do anxiety disorders; in this case the reason is that somaticized symptoms of anxiety are mistaken for adverse effects of the antihypertensive drugs and the drugs are then stopped. Patients can have high levels of hostility, including some with obsessive compulsive illness, which tends to turn the therapeutic encounter into an unproductive tug‐of‐war with the physician; treatment recommendations can be resisted. Undiagnosed alcohol abuse, a cause of hypertension, can unfavorably influence attitudes toward health care. Some patients have a strongly held doctrinaire distrust of medication, which they view as potentially toxic, and are reluctant to start treatment, or if they do, they surreptitiously reduce the dose. Some patients may not really wish to get well at all. There are those whose reaction to illness, because of secondary gain or for reasons known only to themselves, prevents recovery. These can be the most difficult patients of all to treat, even for doctors with specialty psychiatric training.

PATIENTS NOT TO BE TRAINED IN HOME BP SELF‐MEASUREMENT

When BP measured in the doctor's office or the clinic is misleading, skewed by a white coat effect, self‐measurement at home is recommended. Psychiatric comorbidity, however, can render home BP measurement a burden for the doctor and patient alike.

Generalized Anxiety Disorder

Home BP measurement should be orderly, along a regular and proscribed path, with BP values perhaps being carefully tabulated to give a helpful overall depiction of the situation to the doctor at the next medical visit. In patients with generalized anxiety disorder, the timing of BP measurement is often chaotic, driven by the presence of symptoms of anxiety which suggest to the patient that BP is high. When it is, because of the acute anxiety, a path of escalating anxiety and escalating BP may commence, perhaps continuing throughout the day with literally dozens of measurements and more often than not terminating in an anguished late evening phone call to the doctor. Home BP measurement may be too anxiety‐engendering for some patients to tolerate.

Obsessive‐Compulsive Disorder

Tabulated home BP measurements, perhaps with an overall summary, are a very helpful aid to the doctor when patients attend clinic visits. Some occupational groups—engineers and accountants come to mind—do this comprehensively and well, often providing elaborate computer printouts of graphs constructed over months derived from 3 or 4 daily BP measurements. This level of attention to detail is usually not really necessary but is helpful nevertheless.

In patients with obsessive‐compulsive disorder, the repeated measurement of BP is sometimes taken to extraordinary levels, with perhaps 40 to 50 measurements daily, this activity sometimes replaces other prior compulsions, such as ritual hand washing. In these cases, home BP measurement has become an expression of the patients' illness and they are better off not doing it.

ATTITUDINAL BARRIERS TO TREATMENT

Beyond psychiatric diagnosis, attitudinal barriers to effective treatment of hypertension may be present. Such barriers can be ideologic, as in a zealotry that takes the form of the opinion that “drugs are poison and made by a corrupt pharmaceutical industry.” Denial can be a barrier, as in the patients who persistently search for their “best” BP, taking home BP measurements under circumstances they have learned will yield lower BP values, such as after a hot bath. An overvaluing of the power of positive thinking can also be a barrier to treatment in patients who believe that they should be able to control their BP by strength of will alone, such that a need to take antihypertensive medication equates with failure and personal weakness. It can actually represent indifference to survival, particularly, it seems, in elderly men. We have found that the magic words to motivate here are “strokes” and “grandchildren”—antihypertensive medication‐taking can be driven by fear of the first and love for the second!

Disclosure:

Murray Esler, MBBS, PhD, is a member of the Speakers' Bureau for Solvay Australia, Boehringer Ingelhein Australia, and AstraZeneca Australia. Dr Esler is Chair of the Cardiovascular Board of Solvay. He receives no research funding from these companies and holds no stock in them.