The Pain-Depression Conundrum: Bridging the Body and Mind

Pain and depression seem to go hand in hand. What person with intractable pain would not, understandably, be depressed? Yet the relationship of these conditions is complex and unpredictable. Indeed, people in pain are not invariably depressed, although approximately one third of patients with pain do experience comorbid depression. By contrast, three fourths of those with depression will present with physical symptoms, including pain.

The Pain-Depression Conundrum: Bridging the Body and Mind

Author: Rollin M. Gallagher, MD, MPH
Medical Writer: Sophia Cariati, MA

 October 2, 2002;
 Medscape clinical upate based on session presented at the 21st Annual Scientific Meeting of the American Pain Society.

Certainly, individuals with pain-related disorders are at risk for depression. In fact, some research suggests that pain can be the best indicator of depression, especially among the elderly. A number of studies also suggest that depression can augment the impairment associated with pain. In a 24-month study of 228 elderly patients with depression or pain living in retirement communities, Mossey and colleagues evaluated the severity of depression and pain and their impact on functional activity. Initially, almost 50% of the patients who did not suffer depression reported limitations associated with their pain. Over the course of 2 years, however, people who began experiencing depressive symptoms also began reporting more impairment associated with the pain. In addition, high levels of depression were consistently associated with high levels of pain-associated impairment, and in the presence of pain, even low levels of depression were associated with increased healthcare utilization.

The relationship between pain and depression clearly is complex and still emerging. Recent research shows that serotonin and norepinephrine may modulate pain as well as mood. Understanding the shared pathophysiology of these phenomena will help clinicians to manage both conditions and ultimately help their patients to achieve remission. This Clinical Update will detail the epidemiologic, neurobiologic, and pharmacologic correlates of pain and depression.

Pain and Depression in Primary Care

Painful or uncomfortable physical symptoms are among the most common reasons individuals seek medical care. In a recent study, 107 HMO participants were asked to record all symptoms they experienced during a given 3-week period. The results revealed that each person experienced at least 1 symptom, including backache, headache, or stomach pain, every 3-4 days. Yet patients reported less than 6% of these problems to a physician.

When and why, then, do people bring their aches and pains to the doctor? Evidence suggests that people seek out medical care when symptoms become worrisome, interfere with their daily lives, or are disabling. In addition, studies show that when depression, anxiety, panic, or other psychiatric conditions are present, symptoms are more likely to reach this threshold. In fact, persons who seek healthcare for fatigue, migraine headaches, and gastrointestinal complaints experience more stressful life events, more distress, and are more likely to have an anxiety or depressive disorder than are those who do not seek care.

Several studies of irritable bowel syndrome (IBS) poignantly demonstrate the role of psychiatric disorders in healthcare-seeking behavior for corporeal aches and pains. Drossman and colleagues studied 72 patients with IBS who sought medical care, 82 persons with IBS who had not sought medical care, and 84 healthy subjects. They found that patients with IBS who seek care and those with IBS who do not seek care experience the same symptoms. However, IBS patients who seek help from a physician are significantly more likely to have psychiatric disorders, abnormal personality patterns, and more life stress.

In fact, evidence suggests that half of all high medical care users are psychologically distressed. What specific psychiatric disorders are most common among this group? According to a study by Katon and colleagues, 40% have depressive disorders, 22% have generalized anxiety disorder, 20% have somatization disorders, 12% have panic disorder, and 5% are alcohol abusers.

Statistics on the relationship between specific common physical symptoms and psychiatric disorders in primary care patients illustrate the pervasiveness of this comorbidity. Kroenke and colleagues found that the presence of any physical symptom increased the likelihood of a diagnosis of a mood or anxiety disorder by as much as 3-fold. Furthermore, 34% of patients with joint or limb pain, 38% of patients with back pain, 40% of patients with headache, 46% of patients with chest pain, and 43% of patients with abdominal pain also had a mood disorder.

While psychological problems may be prevalent among high healthcare users, what specific symptoms prompt most patients to seek out medical care? Physical symptoms account for half of all primary care physician visits. And while physical symptoms restrict the activities of Americans an average of 9.7 days annually, most of these physical manifestations are never explained by a disease or injury (Figures 1, 2).

Figure 1. Medical symptoms associated with current major depression.


Figure 2. Medical symptoms associated with lifetime major depression.

Kroenke, a leading researcher of symptoms in patient samples, reviewed the records of 1000 patients over 3 years to examine the incidence, evaluations performed, and outcome of symptoms commonly reported in primary care. At some point during the study period, approximately 9% of patients had presented with chronic pain, 8% with fatigue, and 5% with dizziness, headache, edema, low back pain, dysphoria, insomnia, and abdominal pain. Despite the high incidence of symptoms, only 16% of new physical symptoms reported were ever linked to physical injury or disease-related pathology.
The Links Between Physical and Psychological Complaints

Whether explained or unexplained, the number and severity of symptoms have been shown to rise with number and severity of psychological complaints. Patients with anxiety or depressive disorders are more apt to complain of multiple symptoms. Likewise, as the number of physical symptoms increases so does the risk of experiencing anxiety and depression. Evidence further suggests that stressful life events, psychological distress, and depressive and anxiety disorders are associated with a range of medical symptoms with no identified pathology.

In a study of 500 primary care adult patients, Kroenke found a number of independent predictors of mental disorders. These included recent stress, 6 or more physical symptoms, higher reported severity of symptoms, lower self-rating of overall health, age younger than 50 years, and physician perception of the encounter as difficult. In addition, patients with depressive or anxiety disorders were more likely to experience unmet expectations after the visit (20% vs 8%, P < .001) and to report persistent psychiatric symptoms 3 months after the initial visit, compared with those without such disorders. Thus, this subgroup of patients may warrant closer psychiatric evaluation.
Barriers to Recognizing Depression in Primary Care

Despite its pervasiveness in the primary care setting, depression goes undetected in the majority of cases. Studies have found that 50% of patients who experience major depression are not diagnosed by their primary care physicians. Several factors are thought to contribute to this phenomenon, including time and cost restrictions. In addition, 50% to 80% of patients with depression initially present with a physical symptom. These individuals are significantly less likely to receive an accurate psychiatric diagnosis than are those who tell their physician they’re feeling “down.” Medical school curricula that teach students to rule out physical disease before considering mental disorders may also contribute to these missed diagnoses. Because of the frequency of depression and anxiety in medically ill populations, relative to the rare conditions students are taught to look for, this is akin to the proverbial problem of teaching the students “to look for zebras (medical disorders) in a herd of horses.” Thus, high rates of unnecessary tests are ordered, driving up the cost of care, increasing the chance of a spurious positive finding and the risk of prolonging the illness, with secondary consequences for the patient.

Since most Americans receive their only mental health care in the primary care setting, improving recognition rates of depression in primary care has important public health implications. In fact, citing the ability to reduce clinical morbidity, the United States Preventive Services Task Force recently recommended depression screening for all adults in primary care settings.

International studies confirm that the relationship between somatic symptoms and depression is not a uniquely Western phenomenon. Simon and colleagues analyzed World Health Organization data to examine this phenomenon in more than 5400 patients at 15 primary care centers in 14 countries. As is the case in the United States, approximately 10% of these patients were diagnosed with major depression. Forty-five percent to 95% of depressed patients reported only somatic symptoms. Half reported multiple unexplained symptoms and 11% denied psychological symptoms of depression when questioned. Purely somatic presentation was more common in patients who lacked an ongoing relationship with their doctor, perhaps because of the issues of trust and stigmatization of depression.

Chronic Pain and Depression

Does chronic pain cause the depression or does depression cause the pain? Current evidence supports both relationships. Research shows that patients with persistent or chronic pain are at risk for developing an anxiety or depressive disorder. A recent analysis of data from the World Health Organization, found that 22% of primary care patients complained of persistent pain, which was defined as experiencing at least 6 months of pain plus disability because of the pain and/or receipt of medical care for the pain. Those with persistent pain were 4 times more likely to have an anxiety or depressive disorder than were pain-free individuals.

A host of other psychological and social factors may also be involved in the development of chronic pain. Gureje and colleagues analyzed data from the World Health Organization to examine persistent pain in more than 3000 primary care patients around the world. Researchers found that 49% of patients who experienced persistent pain at baseline continued to have persistent pain 12 months later. The best independent predictor of persistent pain was the number of pain sites. Psychiatric disorder, poor self-rated overall health, and occupational related disability were also found to be independently associated with chronic pain. Furthermore, persistent pain at baseline predicted the onset of a psychological disorder with the same strength that a baseline psychological disorder predicted the onset of persistent pain.

In their review of the epidemiology of pain and depression in primary care, Von Korff and Simon made 4 broad generalizations. They are as follows:

* Pain is as strongly associated with anxiety as with depressive disorders;
* The number of pain sites (diffuseness of pain) and the extent to which pain interferes in daily life are the characteristics that most strongly predict depression;
* Certain psychological symptoms of depression, including low energy, sleep disturbances, and worry, are common among pain patients whereas guilt and loneliness are not; and
* Psychological distress and disability often surface and resolve early during the course of a pain disorder that evolves into a chronic condition.

Based upon their findings, these researchers hypothesized that pain and psychological illness have reciprocal psychological and behavioral effects. They proposed 2 theories about the mechanisms underlying the pain-depression comorbidity: (1) some individuals are genetically susceptible to both physical and psychological symptoms and a state in which psychological distress amplifies unpleasant physical sensations; (2) the physical and psychological stress of pain may induce or aggravate psychological distress.

Other, more recent models of the relationship between pain and mood blend the evidence from studies of neurobiological and biobehavioral concepts such as sensitization, conditioning, and kindling to explain the comorbidity of pain and depression.

The Neurochemical Connection Between Pain and Depression

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Rollin M. Gallagher, MD, MPH
Professor of Psychiatry, Anesthesiology, and Public Health and Director of Pain Medicine, MCP Hahnemann School of Medicine, Philadelphia, Pennsylvania; Director, Pain Medicine and Comprehensive Rehabilitation Center, Graduate Hospital, Philadelphia, Pennsylvania


Rollin M. Gallagher, MD, MPH, has disclosed that he has served as advisor or consultant to Lilly, Janssen, Purdue, and Endo Pharmaceuticals.


Sophia Cariati, MA
Freelance Health & Science Writer, New York, NY.

Disclosure: Sophia Cariati has no significant financial interests to disclose.


Priscilla Scherer, RN
Editor, Medscape Neurology & Neurosurgery
Reviewed by Lindsay 8-10-2010

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