Why Don't We Pay More Attention to the Effects of Stress on Our Patients?

We live in an age of extraordinary scientific advances, where cures for cancer and heart disease appear to be just around the corner. We can implant stents, defibrillators, and new knee joints in our patients, and treat them with ever more powerful drugs—it seems only a matter of time before we start putting statins in breakfast cereals. When you read the pages of The New England Journal of Medicine, you will see beautiful three‐dimensional colored diagrams of receptors, enzymes, and second messengers, which give you the impression that the age of precise scientific medicine has arrived, and in a way of course it has. But there is also a disconnect between these scientific advances and what happens in everyday clinical practice, where much of the illness that we see is unexplained and unresponsive to treatment. For every obese patient who has a genetic leptin deficiency that can be cured by administering leptin, ¹ there are tens of thousands of patients in whom no neat molecular model can explain the obesity. In primary care, which represents the front line in the war against disease, the most common symptoms that bring patients to their doctors fall into a ragbag category of “medically unexplained symptoms.” ² These include individual symptoms such as dizziness and dyspnea and aggregates such as chronic fatigue syndrome and irritable bowel disease. One common attribute of all of these is that no specific organ dysfunction can be found; such patients are subjected to numerous diagnostic tests and then referred to specialists. A second attribute is that a large number of these patients are depressed or anxious, or both. This, of course, might be written off as a natural reaction to the chronicity of the symptoms and the inability of physicians to diagnose and cure them, but it would not explain why such patients should have a higher rate of anxiety and depression than patients with similar complaints in whom an organic pathology was established. ²

STRESS AND CHRONIC DISEASE

A plausible explanation for such symptoms is that they are due to stress. But although there is general agreement that psychologic or psychiatric factors play an important role in patients with unexplained symptoms, ³ stress is not often considered as the primary suspect. It can be argued that the problem lies with the personality of the patients—they are neurotic or have an increased sensitivity to bodily symptoms. While this May be true, the point about stress is that it is, like beauty, in the eye of the beholder. What is stressful to you is not necessarily stressful for me. Thus, it is essentially an interactive process and will depend just as much on the personality of the patient as on the nature of the stressor. In addition to being depressed or anxious, patients with unexplained medical symptoms May have a history of childhood or adult trauma ³ ; similar symptoms have been reported in soldiers returning from war. This was originally described after the Civil War and more recently after the Gulf War. Despite extensive searching for a toxic chemical that could explain Gulf War syndrome, none has been found, and the consensus is that the effects are due to excessive stress. ⁴

The effects of stress cut across the spectrum of chronic disease. At the other end of the spectrum from the patients with unexplained symptoms, there is coronary heart disease, which is the leading cause of death in this country. While it has traditionally been attributed to risk factors such as high cholesterol, high blood pressure, and smoking, all of these May be directly or indirectly related to chronic stress. The recent case‐control INTERHEART study ⁵ , ⁶ provides some of the strongest evidence yet that stress is a major risk factor, despite the inherent limitations of crosssectional studies. It reported that four types of stress—at home, at work, financial, or major life events—are also major risk factors that operate independently of the big three traditional ones. For severe global stress (an aggregate measure of the four types), the effect size was somewhat less than smoking but comparable with a diagnosis of hypertension and abdominal obesity.

Despite its importance, the role of stress has been almost completely ignored by the medical profession, although it is often advocated by patients as the root cause of their problems. One reason why stress is so unfashionable in medical circles is that it is regarded as a vague concept that cannot be defined easily. In fact, there is a relatively straightforward definition: Stress is a situation which the individual perceives to be a threat to his or her well being, over which he or she has little control. The stress response is a normal component of our physiology, and there is a huge amount of hard science describing the psychologic, physiologic, and biochemical pathways through which it operates. So why hasn't it got more attention?

For one thing, in clinical medicine, stress is nobody's baby. Despite its ubiquity and the increasing specialization of medicine, there are no stress specialists. Although most patients will admit to stress when asked, they don't go to see their doctor complaining of stress: They complain of shortness of breath, dizzy spells, or palpitations. When their family doctor fails to make a diagnosis, they are referred to a pulmonologist, neurologist, or cardiologist. Each specialist evaluates dysfunction in the favored organ (the lung, the brain, or the heart), and finding none, ends up writing the patient off as neurotic.

THE DOMINANCE OF VIRCHOW'S MODEL OF DISEASE

As physicians, we have all been brought up on the biomedical or mechanical model of disease, which has been strengthened by recent advances in areas such as molecular biology and genomics. In this model, ⁷ which was first established by Virchow in his classic text Die Cellularpathologie (Cellular Pathology, published in 1858), all disease results from cellular abnormalities. He opposed the thenprevalent idea that disease was an affliction of the body at large or of one of its humors (blood, phlegm, yellow bile, and black bile)—with their respective related moods (sanguine, phlegmatic, choleric, and melancholic). To take one example, in the biomedical model palpitations are caused by an irregular heart rhythm such as atrial fibrillation. This can be cured by cardioversion or radio frequency ablation, after which the symptoms go away. In reality, most palpitations occur with a normal heart rhythm, and many are due to anxiety. ⁸ Cardiologists have little interest in evaluating stress because they have no simple test like an echocardiogram or blood test that will reliably diagnose it, and no specific procedure or medication that can be prescribed that will cure it.

A related problem is how to measure stress. Many physicians view stress in the same way that Virchow viewed the four humors—as a concept that has no scientific merit because it can't be measured (or even defined). This is wrong. There are actually a huge number of possible instruments for measuring stress, using either questionnaires or interviews. Studies such as INTERHEART used a relatively small number of questions to evaluate stress, providing powerful information; its measurement is not necessarily difficult or expensive. However, evaluating patients' symptoms by a numerical score from a standardized questionnaire is an idea that is foreign to many physicians. Cardiologists have now got used to the concept of BMI (body mass index), but few know what a BDI score means (it stands for Beck Depression Inventory), despite the fact that an elevated BDI is just as powerful a predictor of the risk of cardiac events in their patients as an elevated BMI. ⁹

A third problem is that there is no straightforward treatment. The thing we doctors like to do most is to effect a permanent cure for our patients' problems. To diagnose stress as a patient's main problem brings us few, if any, rewards. The patient will not thank us, and our therapeutic options are limited. We can advise lifestyle changes, but we tend to do so halfheartedly because we know that few patients will succeed in implementing them. We May refer the patient to a psychiatrist, which May be associated with a stigma and cost, or we May prescribe clonazepam or, if we are bolder, an antidepressant. A variety of psychosocial treatments such as cognitive behavior therapy have been tried for patients with medically unexplained symptoms, but the results have been disappointing. ¹⁰

A final problem is the hydra‐like nature of stress. There are no specific symptoms or consequences that clearly define it. It is everywhere and nowhere. Stress is everywhere because it affects so many disease processes and their treatment. Generalized anxiety disorder, which May be one of the commonest manifestations of stress (affecting 2%–5% of the population), ¹¹ May present with a chameleon‐like array of symptoms: These include general autonomic arousal (palpitations, dyspnea), chest pain, gastrointestinal symptoms, and dizziness. It has also been reported to predict hypertension. ¹² On the other hand, stress is nowhere—because it is rarely looked for and rarely diagnosed.

DEALING WITH STRESS

So what do we do about this? Health care costs are likely to continue to rise for the foreseeable future. Most of this is due to chronic disease, much of which, in turn, is preventable. A good example is cardiovascular disease. While the epidemic of obesity gets much of the blame, there is evidence that stress May also be important here, since people often eat junk food to relieve stress, ¹³ and the hypothalamo‐pituitary‐adrenal axis has been implicated in the formation of abdominal obesity. ¹⁴

We also need better ways of dealing with stress. It is unlikely that we are going to be able to prevent it, given the increasing complexity of our society, but there are all sorts of ways by which people can learn to handle it better. Unfortunately, the health care system is not geared to this. It is organized almost exclusively around the biomedical model of making an organfocused diagnosis and providing organfocused treatment. The growing specialization of medicine has reached the stage where physicians do not just focus on one organ, but only part of it‐cardiologists now include, among other subspecialties, electricians who focus on the conducting systems of the heart, and plumbers who focus on keeping the pipes open. The result is that doctors are looking more and more at the trees, and are losing sight of the forest. Like any organic entity, the patient is more than the sum of his or her organs, and this May be one reason for the continuing success of alternative medicine, where therapy focuses on the whole patient, not just a single organ. While Virchow's model of disease was a huge advance, perhaps we should acknowledge that humors do play an important role in human disease.