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Abstract

Chronic pain affects up to 20% of the population and costs as much as $635 billion per year in the United States alone. The management of chronic pain is fragmented among medical providers of varying specialties, and evidence-based treatments are often not readily available. Psychiatric comorbidity, which compounds chronic pain treatment, is common. Further complicating the problem are the challenges created by opioid medications, the use of which has increased dramatically in recent decades. Integrated-care psychiatrists are uniquely situated to help navigate this complex landscape and help primary care providers and patients access effective treatments. This article summarizes a number of evidence-based treatments for chronic pain and suggests ways in which an integrated-care psychiatrist may incorporate them into practice.
The management of chronic pain has become more challenging in recent years. Pain is the most common symptom in the general population and the most common presenting somatic symptom for medical outpatients (1). Approximately 20% of the population is thought to be dealing with chronic pain, and patients with chronic pain attend primary care appointments up to five times more often than do those without (2, 3). Opioid medications, which have been increasingly used to treat chronic noncancer pain over the past three decades, have been found to be ineffective at treating most chronic pain and have been associated with a host of serious adverse outcomes, including increased rates of overdose, death, and opioid use disorders (47). As primary care providers (PCPs) attempt to follow guidelines (8) and regulations for treating chronic pain conditions, they often face the reality that alternative options to address chronic pain (e.g., cognitive-behavioral therapy, intensive multidisciplinary treatment programs) are often not immediately accessible to or affordable for patients. In addition, the high frequency of psychiatric comorbidities further compounds the complexity of managing these difficulties. Patients with pain complaints are 2.5–10 times more likely to screen positive for anxiety or depressive disorders, both of which are associated with worse pain outcomes (9, 10).
Beyond the pain experienced, chronic pain is associated with difficulty maintaining relationships, disability, and decreased ability to carry out everyday activities, as well as medical comorbidity and mortality (2, 1113). Given the ubiquitous nature of pain, the estimated cost of $560–$635 billion per year (14, 15), and the association of chronic pain with the opioid epidemic (16), effectively managing chronic pain is one of the most important issues facing public health and medicine. The Institute of Medicine has stated that doing so will necessitate a “cultural transformation in the way pain is understood, assessed, and treated” (17).
Current assessment and treatment of pain is often segmented and piecemeal. In practice as usual, patients with chronic pain can be shuttled among pain experts, primary care providers, addiction services, physical therapists, and mental health specialists, often with each in different locations with separate medical records systems. This fragmented system may cause significant delay, confusion over provider role and treatment plan, and poor patient outcomes (see Box 1).

BOX 1. CASE EXAMPLE

Mr. B, a 51-year-old man, presented to his primary care provider (PCP) for evaluation of his worsening chronic low-back pain. His pain was progressing despite regular use of ibuprofen, acetaminophen, cyclobenzaprine, and oxycodone, and he occasionally missed work because of it. He was also taking 20 mg of citalopram daily, which he had used for four years for depression. The PCP provided medication refills, increased citalopram to 30 mg daily, and referred the patient for physical therapy. Mr. B returned four weeks later requesting prescription refills and an increase in his oxycodone dose. He had attended one physical therapy appointment but did not return because his back hurt more after the appointment than before. The PCP referred Mr. B to a pain medicine specialist and to a psychotherapist because the depression had not improved. The pain specialist also referred Mr. B to physical therapy, but he did not make another appointment. Mr. B did not see the psychotherapist because he felt that his depression was due to his pain, and thus he didn’t think “just talking about it” would be helpful. When he returned to his PCP, Mr. B was frustrated and anxious because he worried that he would lose his job if his pain did not improve.
Integrated-care psychiatrists and other behavioral health providers are uniquely qualified to aid in the management of chronic pain conditions and have the potential to improve the dissemination of effective treatments to a greater number of patients using well-established and emerging models of care. Although integrated-care psychiatrists may not be directly delivering psychotherapy or care management, they are often involved in planning and implementing practice redesign and directing patients or primary care providers to appropriate resources. Outlined below are a number of evidence-based chronic pain treatment strategies to assist current or future integrated-care psychiatrists in becoming effective partners in the treatment of chronic pain. We will return later in this article to the case example of Mr. B to demonstrate how the implementation of these strategies may have led to an improved outcome.

The Role of Integrated Care

The term “integrated care” encompasses a variety of approaches and models of blending mental health and primary care services. “Collaborative care” is a specific model of integrated care consisting of the following elements: team approach, population-based care, measurement-based treatment to target, evidence-based care, and accountability (18, 19). In the past 10 years, a number of studies have demonstrated that the concepts of collaborative care can be applied with success to managing chronic pain (2023). Treating underlying psychiatric conditions alone has been shown to improve pain outcomes (24), and integrated care can provide quicker access to treatment and improved outcomes in a range of comorbid mental health conditions (25). Given the comorbidity of anxiety and depression with chronic pain, targeted depression and anxiety screening in individuals who are dealing with chronic pain provides an opportunity to intervene and treat problems that may hinder improvement in pain (9, 10).
Aside from simply treating underlying mood or anxiety disorders, integrated-care providers also have the opportunity to adapt their practices to better address chronic pain directly. The integrated-care psychiatrist can support the primary care practice in management of these patients through several strategies: expanding knowledge of pharmacologic treatment strategies pertinent to chronic pain; increasing awareness and availability of evidence-based psychological therapies; and incorporating coaching on healthy behaviors in the areas of self-management, exercise, and sleep.
Critical to achieving and demonstrating success in integrated care are the use of clinical outcome measures and treating to a target outcome. A 50% reduction in measured symptoms with a validated tool has been identified as the target for which to strive in behavioral health, and the treatment plan should be adjusted every 10–12 weeks if the goal has not been achieved (19).
When measuring pain outcomes, it is important to quantify not only pain severity but also functional status. The Brief Pain Inventory (BPI) is a valid and widely used instrument that has been utilized in a number of collaborative care studies (22, 26). It consists of four numerical rating scales of pain intensity (current, worst, least, and average in the past week), as well as measures of pain’s interference on functioning in seven areas (general activity, mood, walking ability, work, relations with other people, sleep, and enjoyment of life) (27). A one-point change on its 0–10 scoring scale has been considered clinically important (28, 29). The BPI’s generalizability among a wide variety of pain conditions and ease of use make it a recommended tool for treating pain in integrated practices, although other tools may be useful as well (3033). The Patient Health Questionnaire (PHQ-9) (34) and Generalized Anxiety Disorder 7-Item Scale (GAD-7) (35) for depression and anxiety, respectively, or similar tools, should be incorporated into chronic pain treatment, given the importance of identifying and treating these disorders for those individuals with chronic pain.

Pharmacologic Treatment

The integrated-care psychiatrist has the opportunity to provide considerable assistance to primary care colleagues by becoming more familiar with psychotropic treatment options and dosing recommendations for common pain syndromes, including fibromyalgia, migraine headaches, low-back pain, irritable bowel syndrome, neuropathic pain, and others. Agents that may serve dual roles treating psychiatric and pain-related symptoms include serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and gabapentinoids (3638). Recommendations regarding starting doses, titration plans, and treatments goals could be made to PCPs, with guidance provided on safety and monitoring parameters. Cross-titration schedules may be outlined when recommendations are made to switch pharmacologic classes (e.g., selective serotonin reuptake inhibitor to SNRI, or SNRI to TCA).
Additionally, a number of opportunities exist for integrated-care psychiatrists to assist in dealing with the changing landscape of opioid prescribing and its consequences. Despite there being few chronic pain conditions for which long-term opioid use is indicated, opioids are still commonly prescribed, and PCPs often care for or inherit patients on treatment regimens that are outside the recommended parameters of the Centers for Disease Control and Prevention’s Guideline for Prescribing Opioids for Chronic Pain (8). PCPs may have inadequate training or limited confidence to approach difficult conversations and management decisions around inappropriate long-term opioid use (39).
Beyond implementing screening tools such as the Screener and Opioid Assessment for Patients with Pain (SOAPP) or Opioid Risk Tool to identify patients at high risk of addiction (40, 41), integrated-care psychiatrists may serve as consultative support for PCPs who either have identified a need to address opioid use disorders or have recommended a change in pain management treatment with which the patient may not agree. These topics can be challenging to discuss with patients and the changes even more difficult to implement. In the first scenario, the role of the integrated-care psychiatrist may consist of a range of options, from directly providing or supporting substance use treatment in the primary care setting with medication-assisted treatment (42) to linking individuals with specialized addiction services. In the second example, when a treatment change away from opioids is recommended, the plan for an opioid taper may be met with patient reluctance, fear, or anger but also PCP concerns about her or his ability to adequately treat pain throughout the taper and maintain a therapeutic relationship. An integrated model to educate the patient and support the PCP in this endeavor can provide improved outcomes for the patient, including decreased pain interference, improved pain self-efficacy, and reduced perceived opioid problems, as was recently demonstrated by Sullivan et al (43).

Psychological Approaches

The integrated-care psychiatrist should be familiar with psychotherapeutic approaches to treat pain but may or may not choose to become the evidence-based therapist for a practice. He or she may help facilitate access to psychological treatment either within or outside of the primary care practice by identifying appropriately trained therapists, facilitating training for existing providers, and incorporating treatments into collaborative models of care. Recent guidelines published by the American College of Physicians (ACP) emphasize nonpharmacologic interventions as first-line treatments for chronic low-back pain; therefore it is essential for integrated-care psychiatrists to be familiar with the evidence and connect patients with appropriate resources or treatments (44).

Cognitive-Behavioral Therapy

The role of cognitive-behavioral therapy (CBT) in managing chronic pain has long been established (45, 46), and CBT is widely recommended for a multitude of pain-related conditions. Underlying the use of CBT is the recognition that beliefs, attitudes, and behaviors play a fundamental role in the experience of pain. Standard protocols emphasize the importance of the patient’s role in managing chronic pain by teaching patients how to manage their thoughts, beliefs, attitudes, and emotions related to pain (47). A variety of CBT strategies and protocols for treating chronic pain exist (4652); common elements of these are presented in Box 2. Cognitive restructuring in areas such as catastrophizing, attitudes toward coping, and disability beliefs has proven to be a particularly important component of effective CBT for chronic pain (4854). Using a group format for delivering CBT is an effective way of extending the reach of the treatment to a larger population than would be possible in individual care.
BOX 2. ELEMENTS OF COGNITIVE-BEHAVIORAL THERAPY FOR CHRONIC PAIN
Cognitive restructuring
Pacing
Goal setting
Relaxation
Meditation
Activity scheduling
Values clarification
Communication skills training
A 2010 randomized controlled trial by Lamb et al demonstrated the effectiveness of a group cognitive-behavioral intervention for chronic pain in primary care (55, 56). The intervention, the Back Skills Training (BeST) program (57), was delivered by health care providers of different specialties (nurses, physical therapists, psychologists, and occupational therapists) after they were trained over the course of only two days. It focused on behaviors and beliefs about physical activity and avoidance of activity, and positive findings were seen in disability, pain intensity, depression, and quality of life. Additional analysis showed the treatment to be cost effective. On the basis of the positive results and scalability of the intervention combined with the limited provider training needed to implement it, the BeST program shows great promise for use in integrated care.
Further extending the potential reach of CBT, an Internet-based pilot study of a brief, interactive, CBT self-help intervention by Carpenter et al had favorable outcomes related to chronic low-back pain (49) and highlights a possible future chronic pain treatment option that would be ideal to complement an integrated-care practice.

Acceptance and Commitment Therapy

Acceptance and commitment therapy, which focuses on neutral acceptance of positive and negative experiences, identification of values, and goal-directed action, has a growing body of empirical research supporting its use in chronic pain management (5861). Wetherell et al compared the therapy with CBT for chronic pain and found no significant differences in pain-related outcomes. They also found that acceptance and commitment therapy participants were more satisfied than were CBT participants. Another analysis of acceptance and commitment therapy for chronic pain analyzed three-year follow-up of participants and yielded evidence for statistical and clinical significance of improvements (60). These findings indicate that acceptance and commitment therapy may be an effective integrated-treatment approach for patients with chronic pain.

Mindfulness-Based Stress Reduction

Treatment of chronic low-back pain with mindfulness-based stress reduction (MBSR) was shown to be efficacious in two recent trials (62, 63). In the trial comparing MBSR with CBT and usual care, the MBSR group improved more than did the usual-care group in pain and functional limitations at 26 weeks, and the pain improvement persisted at 52 weeks (62). The mindfulness-based stress reduction and CBT treatments were found to be equally beneficial. A notable finding was that the improvements occurred despite only slightly more than half of the participants attending at least six of the eight sessions. The other trial compared MBSR to health education and saw improved function at eight weeks in the MBSR group but no change in pain intensity that was statistically significant. Although studied less for chronic pain than for other psychological strategies, mindfulness-based stress reduction may also be a useful tool for managing chronic pain.

Self-Management

Self-management, which has demonstrated efficacy in managing chronic pain in primary care (64, 65), has been defined as a patient’s ability “to manage the symptoms, treatment, physical and psychological consequences and lifestyle changes inherent in living with a chronic condition” (66). Just as in dealing with other chronic medical conditions, helping patients develop long-term strategies to manage their pain-related difficulties can lead to improved functioning and reduced disability. Better understanding the concepts of self-management and how they have been applied in integrated settings will help the integrated-care psychiatrist incorporate them into models of care such as those involving care managers. It may also help them in advising PCPs on strategies for improving patient engagement in their care.
Self-management focuses on interactive collaboration between the patient and health care provider, in contrast to passive communication in which the patient receives information or directive care; personal responsibility is emphasized. Aspects of self-management programs overlap with other treatments, such as psychological treatments, and have a number of core features: building self-efficacy, self-monitoring, goal setting, action planning, decision making, problem solving, self-tailoring, and partnering with health care providers (64, 67).
In the Stepped Care for Affective Disorders and Musculoskeletal Pain trial, Kroenke et al studied a multistep intervention for patients with depression and musculoskeletal pain (21). They hypothesized that the combination of effective antidepressant treatment and a chronic pain self-management program would be more beneficial than would either alone. Step 1 consisted of working with a nurse care manager for 12 weeks to optimize antidepressant treatment, and step 2 consisted of six sessions of a self-management program delivered over 12 weeks with a focus on self-efficacy and social support to manage pain symptoms. The self-management intervention involved education about chronic pain. Clinically significant improvements in depression, pain severity, or both were noted in the intervention group at 12 months. A follow-up analysis demonstrated that those in the intervention group significantly increased time spent in self-management behaviors and reported greater self-efficacy in managing pain and depression. A dose-response relationship was noted between the number of pain self-management sessions attended and the improvement in depression and pain (68).
Overall evidence for self-management interventions for chronic pain is positive, and their ability to be delivered in discrete time periods makes them favorable for the integrated-care psychiatrist who is considering expanding treatment models for chronic pain.

Exercise

Exercise in various forms has been a mainstay in treatment of chronic pain for years; however, patients with chronic pain often avoid activity or exercise out of fear of exacerbating their condition. Recent meta-analyses continue to support the role of exercise in improving pain and functioning in patients with chronic pain (69, 70). O’Connor et al reviewed walking exercise for a variety of common chronic pain conditions including low-back pain, osteoarthritis, and fibromyalgia and found that walking provided improvement in pain intensity and sustained improvement in functioning (70). In the recently published review of nonpharmacologic therapies specifically for low-back pain for an ACP Clinical Practice Guideline, the authors found moderate strength of evidence for general exercise over usual care in pain and function. They also noted that motor-controlled exercise, which is intended to strengthen and coordinate the spine and surrounding muscles, was slightly more effective for pain or function than was general exercise (69). These findings, which represent only a portion of trials demonstrating the benefits of exercise in chronic pain management, support incorporating exercise into integrated-care treatment models.

Sleep

As many as 89% of patients with chronic pain report sleep complaints, and 53% of those who are seen in pain clinics have clinically significant insomnia (7173). Additionally, sleep-disordered breathing is extremely common in patients with chronic pain taking opioids and should be considered in anyone prescribed these medications (74, 75). Thus sleep disturbances, as with depression and anxiety, are among the most common comorbid symptoms with chronic pain. CBT for insomnia (CBT-I) has proven to be one of the most effective treatments for insomnia and has begun to be studied to assess its utility for chronic pain. A helpful 2014 summary of the literature on CBT-I for comorbid chronic pain and insomnia suggested that sleep symptoms improved in patients with these conditions (76). The results for pain were mixed, with some improvement seen in pain interference, but not pain intensity, even when combined with aspects of CBT for pain. Although further study may reveal more benefits for pain, the current body of evidence suggests that effectively treating chronic pain requires more intervention than CBT-I alone.

Complementary Approaches

Although most integrated-care psychiatrists are not likely to implement them directly, it is important for them to be aware of evidence-based complementary practices for chronic pain, which may be of interest to patients and beneficial to them. In an effort to succinctly facilitate that awareness, the most relevant and strongly supported findings of a recent meta-analysis for low-back pain (69) and a review of approaches for a variety of pain conditions (77) are summarized as follows: acupuncture, yoga, and tai chi were found to be beneficial for chronic low-back pain; acupuncture and tai chi were largely supported for osteoarthritis of the knee; adequately dosed massage therapy benefited neck pain in the short term; and relaxation techniques helped those with severe headaches and migraines. Even limited familiarity with the most empirically supported strategies may help integrated-care psychiatrists add value to patient’s care and limit use of those treatments that are less well supported. They may be recommended directly to patients, disseminated to PCPs, or incorporated into multidisciplinary collaborative-care models.

Additional Collaborative-Care Management Models in Primary Care

Many of the studies discussed above utilized single-treatment strategies, but the complexity of chronic pain often necessitates combination treatment utilizing multiple approaches (78). Collaborative care delivered by care managers has shown great promise for delivering multidisciplinary chronic pain treatment and may be ideal in primary care settings as an alternative pathway for patients presenting to the PCP with pain. Psychiatrists may play integral roles in adapting these models to their own settings and serving in supervisory roles to other care team members.
The Study of the Effectiveness of a Collaborative Approach to Pain trial, by Dobscha et al, involved a multifaceted collaborative-care intervention with a psychologist care manager for chronic pain in primary care. After an assessment by the care manager and discussion with an internist, recommendations were communicated to the patient’s primary care providers, and the patients were offered a four-session workshop described as an activating intervention to manage chronic pain. The care manager then called every two months for the next year to reassess patients, review cases with an internist, and make treatment recommendations as needed. Statistically significant improvements in disability, pain intensity, and depression scores resulted, and gains were maintained in most domains at 12 months (20, 79).
Bair et al conducted an Evaluation of Stepped Care for Chronic Pain for veterans of the Iraq and Afghanistan conflicts (23). The intervention consisted of nurse care managers delivering 12 weeks of algorithm-based analgesic optimization and self-management strategies (step 1), followed by 12 weeks of CBT (step 2). Step 1 included education about chronic pain and encouragement to limit bed rest, resume activities, and perform recommend exercises, including walking. At nine months, decreases in pain, disability, and pain interference were seen.
Using a telecare collaborative strategy, Kroenke et al discovered that using automated symptom monitoring by phone, and nurse care managers to optimize nonopioid analgesics using algorithms, led to significantly more patients having improvement in pain outcomes at 12 months (22). The delivery by telephone suggests that the intervention may be more accessible to individuals, such as those in rural areas, with limited access to other treatments.
As is outlined in the above examples, a number of varied collaborative-care models have been shown to be effective for chronic pain. Utilizing interprofessional team members to assist in care delivery greatly expands access and enhances the care that can be provided by an integrated-care team in the primary care setting.

Application to Current Care

Integrated-care psychiatrists are well positioned to incorporate into integrated clinical practice the evidence-based pain management strategies outlined in this article. Doing so is becoming more financially viable to a wider range of practices as payment models supporting integrated care evolve, such as Accountable Care Organizations, value-based purchasing strategies, and other innovative models (80). An important milestone for sustaining integrated care occurred on January 1, 2017, when the Centers for Medicare and Medicaid Services implemented new rules for Medicare payments for collaborative care and other integrated behavioral health services. These changes allow practices to bill for services including psychiatric consultation and care manager activities, and other payers are expected to follow suit (81).
The menu of options for chronic pain integrated care includes psychological treatments, improved self-management strategies, and pharmacological treatments, which can be tailored to meet the needs, preferences, and resources of the patient and the practice. Depending on the setting, the integrated psychiatrist’s role in treating chronic pain may consist of serving as a source of information to the PCP, an advocate for a collaborative-care model, or a direct treating provider for psychiatric problems, chronic pain, or substance use disorders.
In the case of Mr. B (see Box 3), the integrated psychiatrist developed screening processes for depression in patients with chronic pain, reviewed progress and treatment plans with a NCM who was delivering self-management recommendations, made recommendations for pharmacological treatments, and helped link the patient with psychological treatment delivered by another member of the integrated-care team. The integrated-care team involvement would continue until a predefined treatment target (e.g., BPI and PHQ-9 score reductions) is achieved or a higher intensity of care is needed.

BOX 3. AN INTEGRATED APPROACH FOR MR. B

Mr. B presented to his PCP for worsening chronic low-back pain. He scored 19 on the PHQ-9 and 8 on the BPI. The PCP referred the patient to the practice’s nurse care manager (NCM) for help with depression management, and the NCM was able to meet briefly with Mr. B at the end of the appointment. In the weekly review of the NCM’s panel with the integrated-care psychiatrist, Mr. B’s history was discussed, with dedicated focus given to the depression and chronic pain history. The following suggestions were made and were communicated to Mr. B’s PCP: switch antidepressants from citalopram to duloxetine for both depression and chronic pain; have the NCM provide brief, scripted education regarding chronic pain management, including walking, muscle relaxation, and deep breathing; and refer Mr. B to a newly developed six-session CBT for pain group delivered biweekly by the practice’s integrated clinical social worker. Mr. B was skeptical, but agreed to attend one CBT session. He did not want to stop the citalopram because it had been somewhat helpful in the past, but he agreed to increase it from 20 to 40 mg daily. The recommendations were communicated to the PCP, who agreed with them. The NCM and Mr. B also developed goals, including walking 10 minutes three times per week and spending 5 minutes per day practicing deep breathing or muscle relaxation.
The NCM called Mr. B two weeks later to remind him of the upcoming CBT session and inquire about his progress with the goals and medication change. He had felt so good after his first 10-minute walk that he walked for 30-minutes the following day, which unfortunately caused his back pain to increase. Therefore, he opted to not exercise again. He had not had problems with the increased citalopram dose but was disappointed that it had not been beneficial. The NCM discussed exercise pacing and reviewed their previous discussion about the timeline for the medication change to be effective. They also reestablished goals. He again agreed to attend the CBT session but admitted that he probably would not have gone if he had not talked with the NCM.
At the CBT group the following week, Mr. B was surprised to find two other group members dealing with problems that were similar to his. He chuckled when he heard that one attendee had recently found yoga helpful for his back pain; however, he did decide to give walking another try. He also found that he could identify with some of the thoughts discussed in the cognitive restructuring exercises. He decided to come back for the next session two weeks later.
At his next phone call with the NCM, Mr. B was still not feeling that the increased citalopram dose had been helpful and was more open to a medication change. The NCM discussed his progress with the integrated-care psychiatrist, and a switch to duloxetine was again recommended. Over the next several weeks, Mr. B continued to attend the CBT sessions, ultimately making five out of six sessions. He increased his walking to 20 minutes three times per week and even attended one yoga session when the NCM talked to him about research showing that it could be helpful for back pain. When he saw his PCP three months later his PHQ-9 score had decreased to 8, his BPI to 4, and he was feeling more confident about his ability to manage his low-back pain. He had not missed work in over a month, and his anxiety about his job had subsided. With the improvement in his pain he had begun to use slightly less oxycodone, which opened the door for his PCP to further discuss tapering the medication.
The current milieu of chronic pain management is fractured, expensive, and insufficient. Integrated-care psychiatrists can play a crucial role in improving not only our patients’ pain outcomes but also our primary care colleagues’ confidence in managing chronic pain. Assessing the needs of the primary care practice and the psychiatrist’s skill set will help determine which options for individual practices are most feasible and beneficial.

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Information & Authors

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History

Published in print: Summer 2017
Published online: 18 July 2017

Keywords

  1. Psychiatry/general
  2. Pain
  3. Drug/Substance Abuse
  4. Primary care

Authors

Details

William B. Leasure, M.D. [email protected]
Dr. W. B. Leasure is with the Department of Psychiatry and Psychology, Division of Integrated Behavioral Health, and Dr. E. L. Leasure is with Primary Care Internal Medicine, both at the Mayo Clinic, Rochester, Minnesota.
Emily L. Leasure, M.D.
Dr. W. B. Leasure is with the Department of Psychiatry and Psychology, Division of Integrated Behavioral Health, and Dr. E. L. Leasure is with Primary Care Internal Medicine, both at the Mayo Clinic, Rochester, Minnesota.

Notes

Send correspondence to Dr. W. B. Leasure (e-mail: [email protected]).

Competing Interests

The authors report no financial relationships with commercial interests.

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