A 42-year-old man presented to his primary  care physician with chief complaints of fatigue and worsening of severe chronic thoracic and lumbar back pain that he attributed to routine daily activity at his job, not to any specific antecedent trauma. Over-the-counter nonsteroidal anti-inflammatory agents and analgesics had provided moderate pain relief. A heating pad, which he had been using daily, often for several hours at a time, offered significant pain relief.

AN UNCOMMON CAUSE OF HYPERPIGMENTATION

Erythema ab igne is an uncommon thermally induced eruption associated with periods of repeated exposure of the skin to warm stimuli. It has been reported after holding a kerosene stove between the knees¹ and after balancing a laptop computer on the thighs,² but hot water bottles and heating pads³ are the most commonly reported causes.

Clinical findings and a compatible history are critical to the diagnosis. The involved area should have a history of heat exposure, followed by the development of asymptomatic persistent erythema and, in long-standing cases, hyperpigmentation in a distinct reticulate (netlike) distribution. Telangiectasias and atrophy may occur in advanced disease. In extreme presentations, bullae may develop.⁴

OTHER POTENTIAL CAUSES

Based on the history and findings on physical examination, conditions to consider in the differential diagnosis can include reticular eruptions such as livedo reticularis (associated with cold temperature changes), hypercoagulable states (antiphospholipid antibody syndrome, Sneddon syndrome), and connective tissue diseases (systemic lupus erythematosus).

Other causes of hyperpigmentation such as postinflammatory hyperpigmentation (associated with a prior eruption) and stasis dermatitis (found in areas of poor venous drainage) may also be considered.

The frequent application of an external agent such as a drug or lotion, or even the use of a heating pad if it is made from rubber or is finished with an allergenic dye, raises the possibility of allergic contact dermatitis, but this was not likely in our patient because of the lack of pruritus and active dermatitis. Repeated application of a stimulus such as a heating pad with frequent rubbing can also precipitate lichen simplex chronicus, with thickened, hyperkeratotic skin. Another cause of hyperpigmentation on the back is notalgia paresthetica, which is typically unilateral, over the shoulder blades, and is associated with pain, pruritus, or other neurologic symptoms. Again, these were not present in our patient.

TREATMENT OPTIONS

The first-line treatment for erythema ab igne is to stop exposure to the offending heat source. The hyperpigmentation may slowly fade over several years. Cosmetic treatments such as laser therapy and depigmenting creams can be tried for persistent hyperpigmentation. Patients may be monitored for the small increased risk of cutaneous malignancies—particularly squamous cell carcinoma—arising within regions of erythema ab igne, particularly if atrophic or nonhealing in nature.

Clinicians should recognize the differential diagnosis of erythema ab igne in the appropriate clinical setting and provide the patient counseling regarding this preventable dermatosis.

A 42-year-old man presented to his primary  care physician with chief complaints of fatigue and worsening of severe chronic thoracic and lumbar back pain that he attributed to routine daily activity at his job, not to any specific antecedent trauma. Over-the-counter nonsteroidal anti-inflammatory agents and analgesics had provided moderate pain relief. A heating pad, which he had been using daily, often for several hours at a time, offered significant pain relief.

AN UNCOMMON CAUSE OF HYPERPIGMENTATION

Erythema ab igne is an uncommon thermally induced eruption associated with periods of repeated exposure of the skin to warm stimuli. It has been reported after holding a kerosene stove between the knees¹ and after balancing a laptop computer on the thighs,² but hot water bottles and heating pads³ are the most commonly reported causes.

Clinical findings and a compatible history are critical to the diagnosis. The involved area should have a history of heat exposure, followed by the development of asymptomatic persistent erythema and, in long-standing cases, hyperpigmentation in a distinct reticulate (netlike) distribution. Telangiectasias and atrophy may occur in advanced disease. In extreme presentations, bullae may develop.⁴

OTHER POTENTIAL CAUSES

Based on the history and findings on physical examination, conditions to consider in the differential diagnosis can include reticular eruptions such as livedo reticularis (associated with cold temperature changes), hypercoagulable states (antiphospholipid antibody syndrome, Sneddon syndrome), and connective tissue diseases (systemic lupus erythematosus).

Other causes of hyperpigmentation such as postinflammatory hyperpigmentation (associated with a prior eruption) and stasis dermatitis (found in areas of poor venous drainage) may also be considered.

The frequent application of an external agent such as a drug or lotion, or even the use of a heating pad if it is made from rubber or is finished with an allergenic dye, raises the possibility of allergic contact dermatitis, but this was not likely in our patient because of the lack of pruritus and active dermatitis. Repeated application of a stimulus such as a heating pad with frequent rubbing can also precipitate lichen simplex chronicus, with thickened, hyperkeratotic skin. Another cause of hyperpigmentation on the back is notalgia paresthetica, which is typically unilateral, over the shoulder blades, and is associated with pain, pruritus, or other neurologic symptoms. Again, these were not present in our patient.

TREATMENT OPTIONS

The first-line treatment for erythema ab igne is to stop exposure to the offending heat source. The hyperpigmentation may slowly fade over several years. Cosmetic treatments such as laser therapy and depigmenting creams can be tried for persistent hyperpigmentation. Patients may be monitored for the small increased risk of cutaneous malignancies—particularly squamous cell carcinoma—arising within regions of erythema ab igne, particularly if atrophic or nonhealing in nature.

Clinicians should recognize the differential diagnosis of erythema ab igne in the appropriate clinical setting and provide the patient counseling regarding this preventable dermatosis.

A 42-year-old man presented to his primary  care physician with chief complaints of fatigue and worsening of severe chronic thoracic and lumbar back pain that he attributed to routine daily activity at his job, not to any specific antecedent trauma. Over-the-counter nonsteroidal anti-inflammatory agents and analgesics had provided moderate pain relief. A heating pad, which he had been using daily, often for several hours at a time, offered significant pain relief.

AN UNCOMMON CAUSE OF HYPERPIGMENTATION

Erythema ab igne is an uncommon thermally induced eruption associated with periods of repeated exposure of the skin to warm stimuli. It has been reported after holding a kerosene stove between the knees¹ and after balancing a laptop computer on the thighs,² but hot water bottles and heating pads³ are the most commonly reported causes.

Clinical findings and a compatible history are critical to the diagnosis. The involved area should have a history of heat exposure, followed by the development of asymptomatic persistent erythema and, in long-standing cases, hyperpigmentation in a distinct reticulate (netlike) distribution. Telangiectasias and atrophy may occur in advanced disease. In extreme presentations, bullae may develop.⁴

OTHER POTENTIAL CAUSES

Based on the history and findings on physical examination, conditions to consider in the differential diagnosis can include reticular eruptions such as livedo reticularis (associated with cold temperature changes), hypercoagulable states (antiphospholipid antibody syndrome, Sneddon syndrome), and connective tissue diseases (systemic lupus erythematosus).

Other causes of hyperpigmentation such as postinflammatory hyperpigmentation (associated with a prior eruption) and stasis dermatitis (found in areas of poor venous drainage) may also be considered.

The frequent application of an external agent such as a drug or lotion, or even the use of a heating pad if it is made from rubber or is finished with an allergenic dye, raises the possibility of allergic contact dermatitis, but this was not likely in our patient because of the lack of pruritus and active dermatitis. Repeated application of a stimulus such as a heating pad with frequent rubbing can also precipitate lichen simplex chronicus, with thickened, hyperkeratotic skin. Another cause of hyperpigmentation on the back is notalgia paresthetica, which is typically unilateral, over the shoulder blades, and is associated with pain, pruritus, or other neurologic symptoms. Again, these were not present in our patient.

TREATMENT OPTIONS

The first-line treatment for erythema ab igne is to stop exposure to the offending heat source. The hyperpigmentation may slowly fade over several years. Cosmetic treatments such as laser therapy and depigmenting creams can be tried for persistent hyperpigmentation. Patients may be monitored for the small increased risk of cutaneous malignancies—particularly squamous cell carcinoma—arising within regions of erythema ab igne, particularly if atrophic or nonhealing in nature.

Clinicians should recognize the differential diagnosis of erythema ab igne in the appropriate clinical setting and provide the patient counseling regarding this preventable dermatosis.

We thank those who reviewed manuscripts submitted to the Cleveland Clinic Journal of Medicine in 2017. Reviewing papers for the Journal—both for specialty content and for relevance to our readership—is an arduous task that involves considerable time and effort. Our publication decisions depend in no small part on the timely efforts of reviewers, and we are indebted to them for contributing their expertise this past year.

—Brian F. Mandell, MD, PhD, Editor in Chief

We thank those who reviewed manuscripts submitted to the Cleveland Clinic Journal of Medicine in 2017. Reviewing papers for the Journal—both for specialty content and for relevance to our readership—is an arduous task that involves considerable time and effort. Our publication decisions depend in no small part on the timely efforts of reviewers, and we are indebted to them for contributing their expertise this past year.

—Brian F. Mandell, MD, PhD, Editor in Chief

We thank those who reviewed manuscripts submitted to the Cleveland Clinic Journal of Medicine in 2017. Reviewing papers for the Journal—both for specialty content and for relevance to our readership—is an arduous task that involves considerable time and effort. Our publication decisions depend in no small part on the timely efforts of reviewers, and we are indebted to them for contributing their expertise this past year.

—Brian F. Mandell, MD, PhD, Editor in Chief

Health care gets little love in the State of the Union, the head of the CDC resigns, cancer rates after colonoscopy may heading in the wrong direction, and the Senate has its say on a 20-week abortion ban.

Listen to the MDedge Daily News podcast for all the details on today’s top news.

Health care gets little love in the State of the Union, the head of the CDC resigns, cancer rates after colonoscopy may heading in the wrong direction, and the Senate has its say on a 20-week abortion ban.

Listen to the MDedge Daily News podcast for all the details on today’s top news.

Health care gets little love in the State of the Union, the head of the CDC resigns, cancer rates after colonoscopy may heading in the wrong direction, and the Senate has its say on a 20-week abortion ban.

Listen to the MDedge Daily News podcast for all the details on today’s top news.

SNOWMASS, COLO. – One of the toughest tasks in all of preventive cardiology is to convince statin-phobic patients at increased cardiovascular risk that they should take a statin, Robert A. Vogel, MD, observed.

“The two hardest challenges I have in my practice are getting people to stop smoking and getting people who have fear of statins to take statins. That’s half my practice. If I could conquer those two goals it would be like climbing Mount Everest,” declared Dr. Vogel, a cardiologist at the University of Colorado, Denver.

Bruce Jancin/Frontline Medical News

What about the safety of the PCSK9 inhibitors?

Dr. Vogel is the U.S. national coordinator for the ongoing phase 3 ODYSSEY Outcomes Study, which is due to report initial results at the 2018 annual meeting of the American College of Cardiology. So far, albeit with only a couple of years worth of data in the large randomized outcome trials, the PCSK9 inhibitors haven’t been associated with muscle problems, cognitive impairment, hepatic dysfunction, or hemorrhagic stroke.

“I think we will eventually see an increased risk of hemorrhagic stroke. I don’t know why we wouldn’t because the mechanism is an antiplatelet mechanism, as with statins. But I don’t know what the incidence will be,” he said.

The EBBINGHAUS substudy of the ongoing FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) of the PCSK9 inhibitor evolocumab(Repatha) provides welcome data on cognition. EBBINGHAUS included 1,974 patients with atherosclerotic cardiovascular disease and normal cognition at baseline who underwent serial testing using the Cambridge Neuropsychological Test Automated Battery over the course of 2 years of prospective follow-up. No signal was seen of any impairment in spatial working memory, learning ability, or the elements of executive function, including planning, organization, and attention. Nor did structured assessment of patient self-reported everyday cognition differ between the active treatment and control arms. Ditto for investigators’ assessment of cognitive adverse events. Moreover, when it did occur, measurable cognitive decline proved unrelated to achieved LDL cholesterol level.

“Two-year data is not 20-year data. And cognitive decline is of great concern. Those of us in this field are going to remain vigilant and look for this, but at least for the present, when you put a patient on a PCSK9 inhibitor and see an LDL drop to 15 or 10 mg/dL – and you will see that happen – the data so far say we do not see cognitive decline,” Dr. Vogel said.

He reported serving as a paid consultant to the National Football League and receiving a research grant from and serving on the speakers bureau for Sanofi.

[email protected]

SNOWMASS, COLO. – One of the toughest tasks in all of preventive cardiology is to convince statin-phobic patients at increased cardiovascular risk that they should take a statin, Robert A. Vogel, MD, observed.

“The two hardest challenges I have in my practice are getting people to stop smoking and getting people who have fear of statins to take statins. That’s half my practice. If I could conquer those two goals it would be like climbing Mount Everest,” declared Dr. Vogel, a cardiologist at the University of Colorado, Denver.

Bruce Jancin/Frontline Medical News

What about the safety of the PCSK9 inhibitors?

Dr. Vogel is the U.S. national coordinator for the ongoing phase 3 ODYSSEY Outcomes Study, which is due to report initial results at the 2018 annual meeting of the American College of Cardiology. So far, albeit with only a couple of years worth of data in the large randomized outcome trials, the PCSK9 inhibitors haven’t been associated with muscle problems, cognitive impairment, hepatic dysfunction, or hemorrhagic stroke.

“I think we will eventually see an increased risk of hemorrhagic stroke. I don’t know why we wouldn’t because the mechanism is an antiplatelet mechanism, as with statins. But I don’t know what the incidence will be,” he said.

The EBBINGHAUS substudy of the ongoing FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) of the PCSK9 inhibitor evolocumab(Repatha) provides welcome data on cognition. EBBINGHAUS included 1,974 patients with atherosclerotic cardiovascular disease and normal cognition at baseline who underwent serial testing using the Cambridge Neuropsychological Test Automated Battery over the course of 2 years of prospective follow-up. No signal was seen of any impairment in spatial working memory, learning ability, or the elements of executive function, including planning, organization, and attention. Nor did structured assessment of patient self-reported everyday cognition differ between the active treatment and control arms. Ditto for investigators’ assessment of cognitive adverse events. Moreover, when it did occur, measurable cognitive decline proved unrelated to achieved LDL cholesterol level.

“Two-year data is not 20-year data. And cognitive decline is of great concern. Those of us in this field are going to remain vigilant and look for this, but at least for the present, when you put a patient on a PCSK9 inhibitor and see an LDL drop to 15 or 10 mg/dL – and you will see that happen – the data so far say we do not see cognitive decline,” Dr. Vogel said.

He reported serving as a paid consultant to the National Football League and receiving a research grant from and serving on the speakers bureau for Sanofi.

[email protected]

SNOWMASS, COLO. – One of the toughest tasks in all of preventive cardiology is to convince statin-phobic patients at increased cardiovascular risk that they should take a statin, Robert A. Vogel, MD, observed.

“The two hardest challenges I have in my practice are getting people to stop smoking and getting people who have fear of statins to take statins. That’s half my practice. If I could conquer those two goals it would be like climbing Mount Everest,” declared Dr. Vogel, a cardiologist at the University of Colorado, Denver.

Bruce Jancin/Frontline Medical News

What about the safety of the PCSK9 inhibitors?

Dr. Vogel is the U.S. national coordinator for the ongoing phase 3 ODYSSEY Outcomes Study, which is due to report initial results at the 2018 annual meeting of the American College of Cardiology. So far, albeit with only a couple of years worth of data in the large randomized outcome trials, the PCSK9 inhibitors haven’t been associated with muscle problems, cognitive impairment, hepatic dysfunction, or hemorrhagic stroke.

“I think we will eventually see an increased risk of hemorrhagic stroke. I don’t know why we wouldn’t because the mechanism is an antiplatelet mechanism, as with statins. But I don’t know what the incidence will be,” he said.

The EBBINGHAUS substudy of the ongoing FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) of the PCSK9 inhibitor evolocumab(Repatha) provides welcome data on cognition. EBBINGHAUS included 1,974 patients with atherosclerotic cardiovascular disease and normal cognition at baseline who underwent serial testing using the Cambridge Neuropsychological Test Automated Battery over the course of 2 years of prospective follow-up. No signal was seen of any impairment in spatial working memory, learning ability, or the elements of executive function, including planning, organization, and attention. Nor did structured assessment of patient self-reported everyday cognition differ between the active treatment and control arms. Ditto for investigators’ assessment of cognitive adverse events. Moreover, when it did occur, measurable cognitive decline proved unrelated to achieved LDL cholesterol level.

“Two-year data is not 20-year data. And cognitive decline is of great concern. Those of us in this field are going to remain vigilant and look for this, but at least for the present, when you put a patient on a PCSK9 inhibitor and see an LDL drop to 15 or 10 mg/dL – and you will see that happen – the data so far say we do not see cognitive decline,” Dr. Vogel said.

He reported serving as a paid consultant to the National Football League and receiving a research grant from and serving on the speakers bureau for Sanofi.

[email protected]

The VHA is the largest healthcare delivery system in the U.S. It includes 146 medical centers (VAMCs), 1,063 community-based outpatient centers (CBOCs) and various other sites of care. General Omar Bradley, the first VA Secretary, established education as one of VA’s 4 statutory missions in Policy Memorandum No.2.¹ In addition to training physicians to care for active-duty service members and veterans, 38 USC §7302 directs the VA to assist in providing an adequate supply of health personnel. The 4 statutory missions of the VA are inclusive of not only developing, operating, and maintaining a health care system for veterans, but also including contingency support services as part of emergency preparedness, conducting research, and offering a program of education for health professions.

Background

Today, with few exceptions, the VHA does not act as a graduate medical education (GME) sponsoring institution. Through its Office of Academic Affiliations (OAA), the VHA develops partnerships with Liaison Committee for Medical Education (LCME)/American Osteopathic Association (AOA)-approved medical colleges/universities and with institutions that sponsor Accreditation Council for Graduate Medical Education (ACGME)/AOA-accredited residency program-sponsoring institutions. These collaborations include 144 out of 149 allopathic medical schools and all 34 osteopathic medical schools. The VHA provided training to 43,565 medical residents and 24,683 medical students through these partnerships in 2017.² Since funding of the GME positions is not provided through the Centers for Medicare & Medicaid Services (CMS), program sponsors may use these partnerships to expand GME positions beyond their funding (but not ACGME) cap.

The gap between supply and demand of physicians continues to grow nationally.^3,4 This gap is particularly significant in rural and other underserved areas. U.S. Census Bureau data show that about 5 million veterans (24%) live in rural areas.⁵ Compared with the urban veteran population, the rural veteran experiences higher disease prevalence and lower physical and mental quality-of-life scores.⁶ Addressing the problem of physician shortages is a mission-critical priority for the VHA.⁷

With an eye toward enhancing 2 of the 4 statutory missions of the VA and to mitigate the shortage of physicians and improve the access of veterans to VHA medical services, on August 7, 2014, the Veterans Access, Choice, and Accountability Act of 2014 (Public Law [PL] 113-146), known as the Choice Act was enacted.⁸ Title III, §301(b) of the Choice Act requires VHA to increase GME residency positions by:

Establishing new medical residency programs, or ensuring that already established medical residency programs have a sufficient number of residency positions, at any VHA medical facility that is: (a) experiencing a shortage of physicians and (b) located in a community that is designated as a health professional shortage area.

The legislation specifies that priority must be placed on medical occupations that experience the largest staffing shortages throughout the VHA and “programs in primary care, mental health, and any other specialty that the Secretary of the VA determines appropriate.” The Choice Act authorized the VHA to increase the number of GME residency positions by up to 1,500 over a 5-year period. In December 2016, as amended by PL 114–315, Title VI, §617(a), this authorization was extended by another 5 years for a total of 10 years and will run through 2024.⁹

GME Development/Distribution

To distribute these newly created GME positions as mandated by Congress, the OAA is using a system with 3 types of request for proposal (RFP) applications. These include planning, infrastructure, and position grants. This phased approach was taken with the understanding that the development of new training sites requires a properly staffed education office and dedicated faculty time. Planning and infrastructure grants provide start-up funds for smaller VAMCs, allowing them to keep facility resources focused on their clinical mission.

Planning grants (of up to $250,000 over 2 years) primarily were designed for VA facilities with no or low numbers of physician residents at the desired teaching location. Priority was given to facilities in rural and/or underserved areas as well as those developing new affiliations. Applications were reviewed by OAA staff along with peer-selected Designated Education Officers (DEOs) from VA facilities across the nation that were not applying for the grants. Awards were based on the priorities mentioned earlier, with additional credit for programs focused on 2 VHA fundamental services areas—primary care and/or mental health training. Facilities receiving planning grants were mentored by an OAA physician staff member, anticipating a 2- to 3-year time line to request positions and begin GME training.

Infrastructure grants (of up to $520,000 used over 2-3 years) were designed as bridge funds after approval of Veterans Access, Choice, and Accountability Act (VACAA) GME positions. Infrastructure grants are appropriate to sustain a local education office, develop VA faculty, purchase equipment, and make minor modifications to the clinical space in the VAMCs or CBOCs to enhance the learning environment during the period before VA supportive funds from the Veterans Equitable Resource Allocation (VERA) (similar to indirect GME funds from CMS) become available. Applications were managed the same as planning grant submissions.

Position RFPs, unlike planning and infrastructure RFPs, are available to all VAMCs. The primary purpose of the VACAA Position RFP is to fund new positions in primary care and psychiatry. Graduate medical education positions in subspecialty programs also are considered when there is documentation of critical need to improve access to these services. Applications were reviewed by OAA staff along with selected DEOs from VA facilities around the U.S. Award criteria prioritized primary care (family medicine, internal medicine, geriatrics), and mental health (psychiatry and psychiatry subspecialties). Priority also was given to positions in areas with a documented shortage of physicians and areas with high concentrations of veterans.

Current Progress

To date the OAA has offered 3 RFP cycles consisting of planning/infrastructure grants, and 4 RFP cycles for salary/benefit support for additional resident full-time equivalent (FTE) positions. Resident positions were defined as residency or fellowship FTEs that were part of an ACGME or AOA-accredited training program. Figure 1 illustrates the geographic distribution of awarded GME positions. 

In primary care specialties (family medicine, internal medicine, and geriatrics, a total of 349.4 FTE positions have been approved (Table 1). Due to a low number of applications, only 6.3 of these positions were awarded in geriatrics. In mental health, 167.6 FTE positions have been approved, whereas in critical needs specialties (needed to support rural/underserved healthcare and improve specialty access) 256.5 FTE positions have been added. 

Discussion

There are several important desired short-term outcomes from VACAA. The first is improved access to high-quality care for both rural and urban veterans. There is an emphasis on primary care and mental health because shortages in these areas across the U.S. are well established.^3,4,10 Likewise, rural areas have been prioritized because often there is a disparity of care. 

One area of concern is the small number of applicants in geriatrics. Even with VACAA specifically targeting geriatrics as a primary care specialty, we have only received enough applications to approve 6.3 positions over the first 3 years of the program. As the veteran and overall population in the U.S. ages, it is important to develop a medical workforce that is willing and able to address their needs.

The VACAA statute is not intended to alter medical students’ career choice but rather to provide funded positions for those choosing primary care, geriatrics, psychiatry (including psychiatric subspecialties), and experience in the VA clinical settings. The hope is that this experience will encourage practitioners to competently care for veterans after training in the VA and/or other civilian settings.

By enabling smaller VA facilities to become training sites through planning and infrastructure grants, residents have the opportunity to gain experience in more rural settings. Physicians who choose to train in rural areas are likely to spend time practicing in those areas after they complete training.¹⁵ The process of developing facilities with no GME into training sitestakes time and resources. Establishing an education office and choosing site directors and core faculty are all important steps that must be done before resident rotations begin. Resources provided through VACAA have enabled the VHA to reduce the number of VAMCs with no GME activity to just 3.

Another benefit of VACAA GME expansion is the opportunity to engage new LCME/AOA-accredited medical schools and ACGME/AOA-accredited residency-sponsoring institutions.^16,17 Representatives of these institutions may have perceived a reluctance of their local VAs to develop GME affiliations in the past. This statute has enabled many VAMCs to use nontraditional training sites and modalities to overcome barriers and create new academic affiliations.

However, VACAA only provides funds for training that occurs in established VA sites of care. This can hinder the development of partnerships where other funding sources are required for non-VA rotations. Another VACAA limitation is that it does not fund undergraduate medical education as does the Armed Forces Health Professional Scholarship Program (HPSP). In addition, the primary financial relationship is between the VA and the sponsoring institution, thus VHA cannot send residents to underserved locations.

Conclusion

The VHA has a rich tradition of educating physician and other health care providers in the U.S. More than 60% of U.S. trained physicians received a portion of their training through VHA.² Through VACAA GME expansion initiative, the 113th Congress has asked VHA to continue its important training mission “to bind up the Nations wounds” and “to care for him who shall have borne the battle.”¹⁸

Acknowledgments
In memoriam – Robert Louis Jesse MD, PhD. Dr. Jesse, the Chief of the Office of Academic Affiliations passed away on September 2, 2017, at age 64. He had an illustrious medical career as a cardiologist and served in many leadership roles including Principal Deputy Under Secretary for Health in the U.S. Department of Veterans Affairs. His expertise, visionary leadership, and friendship will be missed by all involved in the VA’s academic training mission but particularly by those of us who worked for and with him at OAA.

The VHA is the largest healthcare delivery system in the U.S. It includes 146 medical centers (VAMCs), 1,063 community-based outpatient centers (CBOCs) and various other sites of care. General Omar Bradley, the first VA Secretary, established education as one of VA’s 4 statutory missions in Policy Memorandum No.2.¹ In addition to training physicians to care for active-duty service members and veterans, 38 USC §7302 directs the VA to assist in providing an adequate supply of health personnel. The 4 statutory missions of the VA are inclusive of not only developing, operating, and maintaining a health care system for veterans, but also including contingency support services as part of emergency preparedness, conducting research, and offering a program of education for health professions.

Background

Today, with few exceptions, the VHA does not act as a graduate medical education (GME) sponsoring institution. Through its Office of Academic Affiliations (OAA), the VHA develops partnerships with Liaison Committee for Medical Education (LCME)/American Osteopathic Association (AOA)-approved medical colleges/universities and with institutions that sponsor Accreditation Council for Graduate Medical Education (ACGME)/AOA-accredited residency program-sponsoring institutions. These collaborations include 144 out of 149 allopathic medical schools and all 34 osteopathic medical schools. The VHA provided training to 43,565 medical residents and 24,683 medical students through these partnerships in 2017.² Since funding of the GME positions is not provided through the Centers for Medicare & Medicaid Services (CMS), program sponsors may use these partnerships to expand GME positions beyond their funding (but not ACGME) cap.

The gap between supply and demand of physicians continues to grow nationally.^3,4 This gap is particularly significant in rural and other underserved areas. U.S. Census Bureau data show that about 5 million veterans (24%) live in rural areas.⁵ Compared with the urban veteran population, the rural veteran experiences higher disease prevalence and lower physical and mental quality-of-life scores.⁶ Addressing the problem of physician shortages is a mission-critical priority for the VHA.⁷

With an eye toward enhancing 2 of the 4 statutory missions of the VA and to mitigate the shortage of physicians and improve the access of veterans to VHA medical services, on August 7, 2014, the Veterans Access, Choice, and Accountability Act of 2014 (Public Law [PL] 113-146), known as the Choice Act was enacted.⁸ Title III, §301(b) of the Choice Act requires VHA to increase GME residency positions by:

Establishing new medical residency programs, or ensuring that already established medical residency programs have a sufficient number of residency positions, at any VHA medical facility that is: (a) experiencing a shortage of physicians and (b) located in a community that is designated as a health professional shortage area.

The legislation specifies that priority must be placed on medical occupations that experience the largest staffing shortages throughout the VHA and “programs in primary care, mental health, and any other specialty that the Secretary of the VA determines appropriate.” The Choice Act authorized the VHA to increase the number of GME residency positions by up to 1,500 over a 5-year period. In December 2016, as amended by PL 114–315, Title VI, §617(a), this authorization was extended by another 5 years for a total of 10 years and will run through 2024.⁹

GME Development/Distribution

To distribute these newly created GME positions as mandated by Congress, the OAA is using a system with 3 types of request for proposal (RFP) applications. These include planning, infrastructure, and position grants. This phased approach was taken with the understanding that the development of new training sites requires a properly staffed education office and dedicated faculty time. Planning and infrastructure grants provide start-up funds for smaller VAMCs, allowing them to keep facility resources focused on their clinical mission.

Planning grants (of up to $250,000 over 2 years) primarily were designed for VA facilities with no or low numbers of physician residents at the desired teaching location. Priority was given to facilities in rural and/or underserved areas as well as those developing new affiliations. Applications were reviewed by OAA staff along with peer-selected Designated Education Officers (DEOs) from VA facilities across the nation that were not applying for the grants. Awards were based on the priorities mentioned earlier, with additional credit for programs focused on 2 VHA fundamental services areas—primary care and/or mental health training. Facilities receiving planning grants were mentored by an OAA physician staff member, anticipating a 2- to 3-year time line to request positions and begin GME training.

Infrastructure grants (of up to $520,000 used over 2-3 years) were designed as bridge funds after approval of Veterans Access, Choice, and Accountability Act (VACAA) GME positions. Infrastructure grants are appropriate to sustain a local education office, develop VA faculty, purchase equipment, and make minor modifications to the clinical space in the VAMCs or CBOCs to enhance the learning environment during the period before VA supportive funds from the Veterans Equitable Resource Allocation (VERA) (similar to indirect GME funds from CMS) become available. Applications were managed the same as planning grant submissions.

Position RFPs, unlike planning and infrastructure RFPs, are available to all VAMCs. The primary purpose of the VACAA Position RFP is to fund new positions in primary care and psychiatry. Graduate medical education positions in subspecialty programs also are considered when there is documentation of critical need to improve access to these services. Applications were reviewed by OAA staff along with selected DEOs from VA facilities around the U.S. Award criteria prioritized primary care (family medicine, internal medicine, geriatrics), and mental health (psychiatry and psychiatry subspecialties). Priority also was given to positions in areas with a documented shortage of physicians and areas with high concentrations of veterans.

Current Progress

To date the OAA has offered 3 RFP cycles consisting of planning/infrastructure grants, and 4 RFP cycles for salary/benefit support for additional resident full-time equivalent (FTE) positions. Resident positions were defined as residency or fellowship FTEs that were part of an ACGME or AOA-accredited training program. Figure 1 illustrates the geographic distribution of awarded GME positions. 

In primary care specialties (family medicine, internal medicine, and geriatrics, a total of 349.4 FTE positions have been approved (Table 1). Due to a low number of applications, only 6.3 of these positions were awarded in geriatrics. In mental health, 167.6 FTE positions have been approved, whereas in critical needs specialties (needed to support rural/underserved healthcare and improve specialty access) 256.5 FTE positions have been added. 

Discussion

There are several important desired short-term outcomes from VACAA. The first is improved access to high-quality care for both rural and urban veterans. There is an emphasis on primary care and mental health because shortages in these areas across the U.S. are well established.^3,4,10 Likewise, rural areas have been prioritized because often there is a disparity of care. 

One area of concern is the small number of applicants in geriatrics. Even with VACAA specifically targeting geriatrics as a primary care specialty, we have only received enough applications to approve 6.3 positions over the first 3 years of the program. As the veteran and overall population in the U.S. ages, it is important to develop a medical workforce that is willing and able to address their needs.

The VACAA statute is not intended to alter medical students’ career choice but rather to provide funded positions for those choosing primary care, geriatrics, psychiatry (including psychiatric subspecialties), and experience in the VA clinical settings. The hope is that this experience will encourage practitioners to competently care for veterans after training in the VA and/or other civilian settings.

By enabling smaller VA facilities to become training sites through planning and infrastructure grants, residents have the opportunity to gain experience in more rural settings. Physicians who choose to train in rural areas are likely to spend time practicing in those areas after they complete training.¹⁵ The process of developing facilities with no GME into training sitestakes time and resources. Establishing an education office and choosing site directors and core faculty are all important steps that must be done before resident rotations begin. Resources provided through VACAA have enabled the VHA to reduce the number of VAMCs with no GME activity to just 3.

Another benefit of VACAA GME expansion is the opportunity to engage new LCME/AOA-accredited medical schools and ACGME/AOA-accredited residency-sponsoring institutions.^16,17 Representatives of these institutions may have perceived a reluctance of their local VAs to develop GME affiliations in the past. This statute has enabled many VAMCs to use nontraditional training sites and modalities to overcome barriers and create new academic affiliations.

However, VACAA only provides funds for training that occurs in established VA sites of care. This can hinder the development of partnerships where other funding sources are required for non-VA rotations. Another VACAA limitation is that it does not fund undergraduate medical education as does the Armed Forces Health Professional Scholarship Program (HPSP). In addition, the primary financial relationship is between the VA and the sponsoring institution, thus VHA cannot send residents to underserved locations.

Conclusion

The VHA has a rich tradition of educating physician and other health care providers in the U.S. More than 60% of U.S. trained physicians received a portion of their training through VHA.² Through VACAA GME expansion initiative, the 113th Congress has asked VHA to continue its important training mission “to bind up the Nations wounds” and “to care for him who shall have borne the battle.”¹⁸

Acknowledgments
In memoriam – Robert Louis Jesse MD, PhD. Dr. Jesse, the Chief of the Office of Academic Affiliations passed away on September 2, 2017, at age 64. He had an illustrious medical career as a cardiologist and served in many leadership roles including Principal Deputy Under Secretary for Health in the U.S. Department of Veterans Affairs. His expertise, visionary leadership, and friendship will be missed by all involved in the VA’s academic training mission but particularly by those of us who worked for and with him at OAA.

The VHA is the largest healthcare delivery system in the U.S. It includes 146 medical centers (VAMCs), 1,063 community-based outpatient centers (CBOCs) and various other sites of care. General Omar Bradley, the first VA Secretary, established education as one of VA’s 4 statutory missions in Policy Memorandum No.2.¹ In addition to training physicians to care for active-duty service members and veterans, 38 USC §7302 directs the VA to assist in providing an adequate supply of health personnel. The 4 statutory missions of the VA are inclusive of not only developing, operating, and maintaining a health care system for veterans, but also including contingency support services as part of emergency preparedness, conducting research, and offering a program of education for health professions.

Background

Today, with few exceptions, the VHA does not act as a graduate medical education (GME) sponsoring institution. Through its Office of Academic Affiliations (OAA), the VHA develops partnerships with Liaison Committee for Medical Education (LCME)/American Osteopathic Association (AOA)-approved medical colleges/universities and with institutions that sponsor Accreditation Council for Graduate Medical Education (ACGME)/AOA-accredited residency program-sponsoring institutions. These collaborations include 144 out of 149 allopathic medical schools and all 34 osteopathic medical schools. The VHA provided training to 43,565 medical residents and 24,683 medical students through these partnerships in 2017.² Since funding of the GME positions is not provided through the Centers for Medicare & Medicaid Services (CMS), program sponsors may use these partnerships to expand GME positions beyond their funding (but not ACGME) cap.

The gap between supply and demand of physicians continues to grow nationally.^3,4 This gap is particularly significant in rural and other underserved areas. U.S. Census Bureau data show that about 5 million veterans (24%) live in rural areas.⁵ Compared with the urban veteran population, the rural veteran experiences higher disease prevalence and lower physical and mental quality-of-life scores.⁶ Addressing the problem of physician shortages is a mission-critical priority for the VHA.⁷

With an eye toward enhancing 2 of the 4 statutory missions of the VA and to mitigate the shortage of physicians and improve the access of veterans to VHA medical services, on August 7, 2014, the Veterans Access, Choice, and Accountability Act of 2014 (Public Law [PL] 113-146), known as the Choice Act was enacted.⁸ Title III, §301(b) of the Choice Act requires VHA to increase GME residency positions by:

Establishing new medical residency programs, or ensuring that already established medical residency programs have a sufficient number of residency positions, at any VHA medical facility that is: (a) experiencing a shortage of physicians and (b) located in a community that is designated as a health professional shortage area.

The legislation specifies that priority must be placed on medical occupations that experience the largest staffing shortages throughout the VHA and “programs in primary care, mental health, and any other specialty that the Secretary of the VA determines appropriate.” The Choice Act authorized the VHA to increase the number of GME residency positions by up to 1,500 over a 5-year period. In December 2016, as amended by PL 114–315, Title VI, §617(a), this authorization was extended by another 5 years for a total of 10 years and will run through 2024.⁹

GME Development/Distribution

To distribute these newly created GME positions as mandated by Congress, the OAA is using a system with 3 types of request for proposal (RFP) applications. These include planning, infrastructure, and position grants. This phased approach was taken with the understanding that the development of new training sites requires a properly staffed education office and dedicated faculty time. Planning and infrastructure grants provide start-up funds for smaller VAMCs, allowing them to keep facility resources focused on their clinical mission.

Planning grants (of up to $250,000 over 2 years) primarily were designed for VA facilities with no or low numbers of physician residents at the desired teaching location. Priority was given to facilities in rural and/or underserved areas as well as those developing new affiliations. Applications were reviewed by OAA staff along with peer-selected Designated Education Officers (DEOs) from VA facilities across the nation that were not applying for the grants. Awards were based on the priorities mentioned earlier, with additional credit for programs focused on 2 VHA fundamental services areas—primary care and/or mental health training. Facilities receiving planning grants were mentored by an OAA physician staff member, anticipating a 2- to 3-year time line to request positions and begin GME training.

Infrastructure grants (of up to $520,000 used over 2-3 years) were designed as bridge funds after approval of Veterans Access, Choice, and Accountability Act (VACAA) GME positions. Infrastructure grants are appropriate to sustain a local education office, develop VA faculty, purchase equipment, and make minor modifications to the clinical space in the VAMCs or CBOCs to enhance the learning environment during the period before VA supportive funds from the Veterans Equitable Resource Allocation (VERA) (similar to indirect GME funds from CMS) become available. Applications were managed the same as planning grant submissions.

Position RFPs, unlike planning and infrastructure RFPs, are available to all VAMCs. The primary purpose of the VACAA Position RFP is to fund new positions in primary care and psychiatry. Graduate medical education positions in subspecialty programs also are considered when there is documentation of critical need to improve access to these services. Applications were reviewed by OAA staff along with selected DEOs from VA facilities around the U.S. Award criteria prioritized primary care (family medicine, internal medicine, geriatrics), and mental health (psychiatry and psychiatry subspecialties). Priority also was given to positions in areas with a documented shortage of physicians and areas with high concentrations of veterans.

Current Progress

To date the OAA has offered 3 RFP cycles consisting of planning/infrastructure grants, and 4 RFP cycles for salary/benefit support for additional resident full-time equivalent (FTE) positions. Resident positions were defined as residency or fellowship FTEs that were part of an ACGME or AOA-accredited training program. Figure 1 illustrates the geographic distribution of awarded GME positions. 

In primary care specialties (family medicine, internal medicine, and geriatrics, a total of 349.4 FTE positions have been approved (Table 1). Due to a low number of applications, only 6.3 of these positions were awarded in geriatrics. In mental health, 167.6 FTE positions have been approved, whereas in critical needs specialties (needed to support rural/underserved healthcare and improve specialty access) 256.5 FTE positions have been added. 

Discussion

There are several important desired short-term outcomes from VACAA. The first is improved access to high-quality care for both rural and urban veterans. There is an emphasis on primary care and mental health because shortages in these areas across the U.S. are well established.^3,4,10 Likewise, rural areas have been prioritized because often there is a disparity of care. 

One area of concern is the small number of applicants in geriatrics. Even with VACAA specifically targeting geriatrics as a primary care specialty, we have only received enough applications to approve 6.3 positions over the first 3 years of the program. As the veteran and overall population in the U.S. ages, it is important to develop a medical workforce that is willing and able to address their needs.

The VACAA statute is not intended to alter medical students’ career choice but rather to provide funded positions for those choosing primary care, geriatrics, psychiatry (including psychiatric subspecialties), and experience in the VA clinical settings. The hope is that this experience will encourage practitioners to competently care for veterans after training in the VA and/or other civilian settings.

By enabling smaller VA facilities to become training sites through planning and infrastructure grants, residents have the opportunity to gain experience in more rural settings. Physicians who choose to train in rural areas are likely to spend time practicing in those areas after they complete training.¹⁵ The process of developing facilities with no GME into training sitestakes time and resources. Establishing an education office and choosing site directors and core faculty are all important steps that must be done before resident rotations begin. Resources provided through VACAA have enabled the VHA to reduce the number of VAMCs with no GME activity to just 3.

Another benefit of VACAA GME expansion is the opportunity to engage new LCME/AOA-accredited medical schools and ACGME/AOA-accredited residency-sponsoring institutions.^16,17 Representatives of these institutions may have perceived a reluctance of their local VAs to develop GME affiliations in the past. This statute has enabled many VAMCs to use nontraditional training sites and modalities to overcome barriers and create new academic affiliations.

However, VACAA only provides funds for training that occurs in established VA sites of care. This can hinder the development of partnerships where other funding sources are required for non-VA rotations. Another VACAA limitation is that it does not fund undergraduate medical education as does the Armed Forces Health Professional Scholarship Program (HPSP). In addition, the primary financial relationship is between the VA and the sponsoring institution, thus VHA cannot send residents to underserved locations.

Conclusion

The VHA has a rich tradition of educating physician and other health care providers in the U.S. More than 60% of U.S. trained physicians received a portion of their training through VHA.² Through VACAA GME expansion initiative, the 113th Congress has asked VHA to continue its important training mission “to bind up the Nations wounds” and “to care for him who shall have borne the battle.”¹⁸

Acknowledgments
In memoriam – Robert Louis Jesse MD, PhD. Dr. Jesse, the Chief of the Office of Academic Affiliations passed away on September 2, 2017, at age 64. He had an illustrious medical career as a cardiologist and served in many leadership roles including Principal Deputy Under Secretary for Health in the U.S. Department of Veterans Affairs. His expertise, visionary leadership, and friendship will be missed by all involved in the VA’s academic training mission but particularly by those of us who worked for and with him at OAA.

Click here to access the February 2018 Digital Edition.

Table of Contents

• A Year 3 Progress Report on Graduate Medical Education Expansion in the Veterans Choice Act
• Postpartum Psychosis in a Young VA Patient: Diagnosis, Implications, and Treatment Recommendations
• Veteran With Alcohol Use Disorder and Acute Pancreatitis
• Misleading Diagnosis of Idiopathic Pulmonary Fibrosis: A Clinical Concern
• Addressing the Needs of Patients With Chronic Pain
• Singing Praises, Naming Names
• The Clinicians’ Role in Building a System of Care: Army Behavioral Health Since 2001

Click here to access the February 2018 Digital Edition.

Table of Contents

• A Year 3 Progress Report on Graduate Medical Education Expansion in the Veterans Choice Act
• Postpartum Psychosis in a Young VA Patient: Diagnosis, Implications, and Treatment Recommendations
• Veteran With Alcohol Use Disorder and Acute Pancreatitis
• Misleading Diagnosis of Idiopathic Pulmonary Fibrosis: A Clinical Concern
• Addressing the Needs of Patients With Chronic Pain
• Singing Praises, Naming Names
• The Clinicians’ Role in Building a System of Care: Army Behavioral Health Since 2001

Click here to access the February 2018 Digital Edition.

Table of Contents

• A Year 3 Progress Report on Graduate Medical Education Expansion in the Veterans Choice Act
• Postpartum Psychosis in a Young VA Patient: Diagnosis, Implications, and Treatment Recommendations
• Veteran With Alcohol Use Disorder and Acute Pancreatitis
• Misleading Diagnosis of Idiopathic Pulmonary Fibrosis: A Clinical Concern
• Addressing the Needs of Patients With Chronic Pain
• Singing Praises, Naming Names
• The Clinicians’ Role in Building a System of Care: Army Behavioral Health Since 2001

Rituximab, a B-cell–depleting agent, has been found safe and effective in clinical trials of patients with multiple sclerosis and patients with rheumatoid arthritis, among others. However, progressive multifocal leukoencephalopathy (PML) and malignancies have been reported in patients with lymphoma, rheumatoid arthritis, and lupus who also received multiple immunosuppressive therapies, say researchers from Wayne State University in Michigan and University of Chicago in Illinois. In studies with ocrelizumab, which also depletes B-cells, adverse effects (AEs) have included infections, such as, herpes virus-associated infection, and neoplasms.

Although most research has found rituximab and ocrelizumab safe and effective, there is a “paucity of literature” on the safety of continuous B-cell depletion over a long period, the researchers say. They conducted a retrospective study involving 29 patients with immune-mediated neurologic disorders who received continuous cycles of rituximab infusions every 6 to 9 months for up to 7 years. Although small, the study was longer than the trials with ocrelizumab in multiple sclerosis . The mean duration of treatment was 51 months; with a mean of 9 treatment cycles.

The researchers found a low incidence of adverse events and prolonged rituximab-induced B-cell depletion did not lead to any life-threatening AEs, including malignancy. Overall, 32 AEs were reported. Four were serious; 3 were noted after 9 cycles (48 months), and 1 after 11 cycles (60 months). There were no cases of PML or malignancies. Repeated rituximab infusions were well tolerated The rate of AEs remained low over the 7-year observation period.

Source:
Memon AB, Javed A, Caon C, et al. PLoS ONE. 2018;13(1):e0190425.
doi: 10.1371/journal.pone.0190425.

Rituximab, a B-cell–depleting agent, has been found safe and effective in clinical trials of patients with multiple sclerosis and patients with rheumatoid arthritis, among others. However, progressive multifocal leukoencephalopathy (PML) and malignancies have been reported in patients with lymphoma, rheumatoid arthritis, and lupus who also received multiple immunosuppressive therapies, say researchers from Wayne State University in Michigan and University of Chicago in Illinois. In studies with ocrelizumab, which also depletes B-cells, adverse effects (AEs) have included infections, such as, herpes virus-associated infection, and neoplasms.

Although most research has found rituximab and ocrelizumab safe and effective, there is a “paucity of literature” on the safety of continuous B-cell depletion over a long period, the researchers say. They conducted a retrospective study involving 29 patients with immune-mediated neurologic disorders who received continuous cycles of rituximab infusions every 6 to 9 months for up to 7 years. Although small, the study was longer than the trials with ocrelizumab in multiple sclerosis . The mean duration of treatment was 51 months; with a mean of 9 treatment cycles.

The researchers found a low incidence of adverse events and prolonged rituximab-induced B-cell depletion did not lead to any life-threatening AEs, including malignancy. Overall, 32 AEs were reported. Four were serious; 3 were noted after 9 cycles (48 months), and 1 after 11 cycles (60 months). There were no cases of PML or malignancies. Repeated rituximab infusions were well tolerated The rate of AEs remained low over the 7-year observation period.

Source:
Memon AB, Javed A, Caon C, et al. PLoS ONE. 2018;13(1):e0190425.
doi: 10.1371/journal.pone.0190425.

Rituximab, a B-cell–depleting agent, has been found safe and effective in clinical trials of patients with multiple sclerosis and patients with rheumatoid arthritis, among others. However, progressive multifocal leukoencephalopathy (PML) and malignancies have been reported in patients with lymphoma, rheumatoid arthritis, and lupus who also received multiple immunosuppressive therapies, say researchers from Wayne State University in Michigan and University of Chicago in Illinois. In studies with ocrelizumab, which also depletes B-cells, adverse effects (AEs) have included infections, such as, herpes virus-associated infection, and neoplasms.

Although most research has found rituximab and ocrelizumab safe and effective, there is a “paucity of literature” on the safety of continuous B-cell depletion over a long period, the researchers say. They conducted a retrospective study involving 29 patients with immune-mediated neurologic disorders who received continuous cycles of rituximab infusions every 6 to 9 months for up to 7 years. Although small, the study was longer than the trials with ocrelizumab in multiple sclerosis . The mean duration of treatment was 51 months; with a mean of 9 treatment cycles.

The researchers found a low incidence of adverse events and prolonged rituximab-induced B-cell depletion did not lead to any life-threatening AEs, including malignancy. Overall, 32 AEs were reported. Four were serious; 3 were noted after 9 cycles (48 months), and 1 after 11 cycles (60 months). There were no cases of PML or malignancies. Repeated rituximab infusions were well tolerated The rate of AEs remained low over the 7-year observation period.

Source:
Memon AB, Javed A, Caon C, et al. PLoS ONE. 2018;13(1):e0190425.
doi: 10.1371/journal.pone.0190425.

Vasoactive intestinal peptide (VIP) appears to play an important role in the pathology of eosinophilic esophagitis (EoE) by recruiting mast cells and eosinophils that contribute to EoE’s hallmark symptoms of dysphagia and esophageal dysmotility, investigators reported in the February issue of Cellular and Molecular Gastroenterology and Hepatology.

Blocking one of three VIP receptors – chemoattractant receptor-homologous molecule expressed on Th2 (CRTH2) – could reduce eosinophil infiltration and mast cell numbers in the esophagus, wrote Alok K. Verma, PhD, a postodoctoral fellow at Tulane University in New Orleans, and his colleagues.

“We suggest that inhibiting the VIP–CRTH2 axis may ameliorate the dysphagia, stricture, and motility dysfunction of chronic EoE,” they wrote in a research letter to Cellular and Molecular Gastroenterology and Hepatology.

Several cytokines and chemokines, notably interleukin-5 and eotaxin-3, have been fingered as suspects in eosinophil infiltration, but whether chemokines other than eotaxin play a role has not been well documented, the investigators noted.

They hypothesized that VIP may be a chemoattractant that draws eosinophils into perineural areas of the muscular mucosa of the esophagus.

To test this idea, they looked at VIP-expression in samples from patients both with and without EoE and found that VIP expression was low among controls (without EoE); they also found that eosinophils were seen to accumulate near VIP-expressing nerve cells in biopsy samples from patients with EoE.

When they performed in vitro studies of VIP binding and immunologic functions, they found that eosinophils primarily express the CRTH2 receptor rather than the vasoactive intestinal peptide receptor 1 (VPAC-1) or VPAC-2.

They also demonstrated that VIP’s effects on eosinophil motility was similar to that of eotaxin and that, when they pretreated eosinophils with a CRTH2 inhibitor, esoinophil motility was hampered.

The investigators next looked at biopsy specimens from patients with EoE and found that eosinophils that express CRTH2 accumulated in the epithelial mucosa.

To see whether (as they and other researchers had suspected) VIP and its interaction with the CRTH2 receptor might play a role in mast cell recruitment, they performed immunofluorescence analyses and confirmed the presence of the CRTH2 receptor on tryptase-positive mast cells in the esophageal mucosa of patients with EoE.

“These findings suggest that, similar to eosinophils, mast cells accumulate via interaction of the CRTH2 receptor with neutrally derived VIP,” they wrote.

Finally, to see whether a reduction in peak eosinophil levels in patients with EoE with a CRTH2 antagonist – as seen in prior studies – could also ameliorate the negative effects of mast cells on esophageal function, they looked at the effects of CRTH2 inhibition in a mouse model of human EoE.

They found that, in the mice treated with a CRTH2 blocker, each segment of the esophagus had significant reductions in both eosinophil infiltration and mast cell numbers (P less than .05 for each).

The work was supported in part by grants from the National Institutes of Health and the Tulane Edward G. Schlieder Educational Foundation. Senior author Anil Mishra, PhD, disclosed serving as a consultant for Axcan Pharma, Aptalis, Elite Biosciences, Calypso Biotech SA, and Enumeral Biomedical. The remaining authors disclosed no conflicts of interest.

SOURCE: Verma AK et al. Cell Mol Gastroenterol Hepatol. 2018;5[1]:99-100.e7.

Vasoactive intestinal peptide (VIP) appears to play an important role in the pathology of eosinophilic esophagitis (EoE) by recruiting mast cells and eosinophils that contribute to EoE’s hallmark symptoms of dysphagia and esophageal dysmotility, investigators reported in the February issue of Cellular and Molecular Gastroenterology and Hepatology.

Blocking one of three VIP receptors – chemoattractant receptor-homologous molecule expressed on Th2 (CRTH2) – could reduce eosinophil infiltration and mast cell numbers in the esophagus, wrote Alok K. Verma, PhD, a postodoctoral fellow at Tulane University in New Orleans, and his colleagues.

“We suggest that inhibiting the VIP–CRTH2 axis may ameliorate the dysphagia, stricture, and motility dysfunction of chronic EoE,” they wrote in a research letter to Cellular and Molecular Gastroenterology and Hepatology.

Several cytokines and chemokines, notably interleukin-5 and eotaxin-3, have been fingered as suspects in eosinophil infiltration, but whether chemokines other than eotaxin play a role has not been well documented, the investigators noted.

They hypothesized that VIP may be a chemoattractant that draws eosinophils into perineural areas of the muscular mucosa of the esophagus.

To test this idea, they looked at VIP-expression in samples from patients both with and without EoE and found that VIP expression was low among controls (without EoE); they also found that eosinophils were seen to accumulate near VIP-expressing nerve cells in biopsy samples from patients with EoE.

When they performed in vitro studies of VIP binding and immunologic functions, they found that eosinophils primarily express the CRTH2 receptor rather than the vasoactive intestinal peptide receptor 1 (VPAC-1) or VPAC-2.

They also demonstrated that VIP’s effects on eosinophil motility was similar to that of eotaxin and that, when they pretreated eosinophils with a CRTH2 inhibitor, esoinophil motility was hampered.

The investigators next looked at biopsy specimens from patients with EoE and found that eosinophils that express CRTH2 accumulated in the epithelial mucosa.

To see whether (as they and other researchers had suspected) VIP and its interaction with the CRTH2 receptor might play a role in mast cell recruitment, they performed immunofluorescence analyses and confirmed the presence of the CRTH2 receptor on tryptase-positive mast cells in the esophageal mucosa of patients with EoE.

“These findings suggest that, similar to eosinophils, mast cells accumulate via interaction of the CRTH2 receptor with neutrally derived VIP,” they wrote.

Finally, to see whether a reduction in peak eosinophil levels in patients with EoE with a CRTH2 antagonist – as seen in prior studies – could also ameliorate the negative effects of mast cells on esophageal function, they looked at the effects of CRTH2 inhibition in a mouse model of human EoE.

They found that, in the mice treated with a CRTH2 blocker, each segment of the esophagus had significant reductions in both eosinophil infiltration and mast cell numbers (P less than .05 for each).

The work was supported in part by grants from the National Institutes of Health and the Tulane Edward G. Schlieder Educational Foundation. Senior author Anil Mishra, PhD, disclosed serving as a consultant for Axcan Pharma, Aptalis, Elite Biosciences, Calypso Biotech SA, and Enumeral Biomedical. The remaining authors disclosed no conflicts of interest.

SOURCE: Verma AK et al. Cell Mol Gastroenterol Hepatol. 2018;5[1]:99-100.e7.

Vasoactive intestinal peptide (VIP) appears to play an important role in the pathology of eosinophilic esophagitis (EoE) by recruiting mast cells and eosinophils that contribute to EoE’s hallmark symptoms of dysphagia and esophageal dysmotility, investigators reported in the February issue of Cellular and Molecular Gastroenterology and Hepatology.

Blocking one of three VIP receptors – chemoattractant receptor-homologous molecule expressed on Th2 (CRTH2) – could reduce eosinophil infiltration and mast cell numbers in the esophagus, wrote Alok K. Verma, PhD, a postodoctoral fellow at Tulane University in New Orleans, and his colleagues.

“We suggest that inhibiting the VIP–CRTH2 axis may ameliorate the dysphagia, stricture, and motility dysfunction of chronic EoE,” they wrote in a research letter to Cellular and Molecular Gastroenterology and Hepatology.

Several cytokines and chemokines, notably interleukin-5 and eotaxin-3, have been fingered as suspects in eosinophil infiltration, but whether chemokines other than eotaxin play a role has not been well documented, the investigators noted.

They hypothesized that VIP may be a chemoattractant that draws eosinophils into perineural areas of the muscular mucosa of the esophagus.

To test this idea, they looked at VIP-expression in samples from patients both with and without EoE and found that VIP expression was low among controls (without EoE); they also found that eosinophils were seen to accumulate near VIP-expressing nerve cells in biopsy samples from patients with EoE.

When they performed in vitro studies of VIP binding and immunologic functions, they found that eosinophils primarily express the CRTH2 receptor rather than the vasoactive intestinal peptide receptor 1 (VPAC-1) or VPAC-2.

They also demonstrated that VIP’s effects on eosinophil motility was similar to that of eotaxin and that, when they pretreated eosinophils with a CRTH2 inhibitor, esoinophil motility was hampered.

The investigators next looked at biopsy specimens from patients with EoE and found that eosinophils that express CRTH2 accumulated in the epithelial mucosa.

To see whether (as they and other researchers had suspected) VIP and its interaction with the CRTH2 receptor might play a role in mast cell recruitment, they performed immunofluorescence analyses and confirmed the presence of the CRTH2 receptor on tryptase-positive mast cells in the esophageal mucosa of patients with EoE.

“These findings suggest that, similar to eosinophils, mast cells accumulate via interaction of the CRTH2 receptor with neutrally derived VIP,” they wrote.

Finally, to see whether a reduction in peak eosinophil levels in patients with EoE with a CRTH2 antagonist – as seen in prior studies – could also ameliorate the negative effects of mast cells on esophageal function, they looked at the effects of CRTH2 inhibition in a mouse model of human EoE.

They found that, in the mice treated with a CRTH2 blocker, each segment of the esophagus had significant reductions in both eosinophil infiltration and mast cell numbers (P less than .05 for each).

The work was supported in part by grants from the National Institutes of Health and the Tulane Edward G. Schlieder Educational Foundation. Senior author Anil Mishra, PhD, disclosed serving as a consultant for Axcan Pharma, Aptalis, Elite Biosciences, Calypso Biotech SA, and Enumeral Biomedical. The remaining authors disclosed no conflicts of interest.

SOURCE: Verma AK et al. Cell Mol Gastroenterol Hepatol. 2018;5[1]:99-100.e7.

As a group, anxiety disorders are the most common mental illness in the Unites States, affecting 40 million adults. There is a nearly 30% lifetime prevalence of anxiety disorders in the general population.¹ DSM-5 anxiety disorders include generalized anxiety disorder, social anxiety disorder (social phobia), panic disorder, specific phobia, and separation anxiety disorder. Although DSM-IV-TR also classified obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD) as anxiety disorders, these diagnoses were reclassified in DSM-5. Anxiety also is a frequent symptom of many other psychiatric disorders, especially major depressive disorder.

Although benzodiazepines have many potential uses, they also carry risks that prescribers should recognize. This article reviews some of the risks of benzodiazepine use, identifies patients with higher risks of adverse effects, and presents a practical approach to prescribing these medications.

A wide range of risks

Abuse and addiction. Perhaps the most commonly recognized risk associated with benzodiazepine use is the potential for abuse and addiction.⁴ Prolonged benzodiazepine use typically results in physiologic tolerance, requiring higher dosing to achieve the same initial effect.⁵ American Psychiatric Association practice guidelines recognize the potential for benzodiazepine use to result in symptoms of dependence, including cravings and withdrawal, stating that “with ongoing use, all benzodiazepines will produce physiological dependence in most patients.”⁶ High-potency, short-acting compounds such as alprazolam have a higher risk for dependence, toxicity, and abuse.⁷ However, long-acting benzodiazepines (such as clonazepam) also can be habit-forming.⁸ Because of these properties, it is generally advisable to avoid prescribing benzo­diazepines (and short-acting compounds in particular) when treating patients with current or past substance use disorders, except when treating withdrawal.⁹

Limited efficacy for other disorders. Although benzodiazepines can help reduce anxiety in patients with anxiety disorders, they have shown less promise in treating other disorders in which anxiety is a common symptom. Treating PTSD with benzodiazepines does not appear to offer any advantage over placebo, and may even result in increased symptoms over time.^10,11 There is limited evidence supporting the use of benzodiazepines to treat OCD.^12,13 Patients with borderline personality disorder who are treated with benzodiazepines may experience an increase in behavioral dysregulation.¹⁴

Physical ailments. Benzodiazepines can affect comorbid physical ailments. One study found that long-term benzodiazepine use among patients with comorbid pain disorders was correlated with high utilization of medical services and high disability levels.¹⁵ Benzodiazepine use also has been associated with an increased risk of exacerbating respiratory conditions, such as chronic obstructive pulmonary disease,¹⁶ and increased risk of pneumonia.^17,18

Pregnancy and breastfeeding. Benzo­diazepines carry risks for women who are pregnant or breastfeeding. Benzodiazepine use during pregnancy may increase the relative risk of major malformations and oral clefts. It also may result in neonatal lethargy, sedation, and weight loss. Benzodiazepine withdrawal symptoms can occur in the neonate.¹⁹ Benzodiazepines are secreted in breast milk and can result in sedation among breastfed infants.²⁰

Geriatric patients. Older adults may be particularly vulnerable to the adverse effects of benzodiazepines. The Beers Criteria for Potentially Inappropriate Medication Use in Older Adults recommends against prescribing benzodiazepines to geriatric patients.²¹ Benzodiazepine use has been associated with an increased risk for falls among older adults,^22,23 with an increased risk of fractures²⁴ that can be fatal.²⁵ Benzodiazepines also have been associated with an increased risk of cognitive dysfunction and dementia.^26,27 Despite the documented risks of using benzodiazepines in geriatric patients, benzodiazepines continue to be frequently prescribed to this age group.^28,29 One study found that the rate of prescribing benzo­diazepines by primary care physicians increased from 2003 to 2012, primarily among older adults with no diagnosis of pain or a psychiatric disorder.³⁰

Mortality. Benzodiazepine use also carries an increased risk of mortality. Benzo­diazepine users are at increased risk of motor vehicle accidents because of difficulty maintaining road position.³¹ Some research has shown that patients with schizophrenia treated with benzodiazepines have an increased risk of death compared with those who are prescribed antipsychotics or antidepressants.³² Another study showed that patients with schizophrenia who were prescribed benzodiazepines had a greater risk of death by suicide and accidental poisoning.³³ Benzodiazepine use has been associated with suicidal ideation and an increased risk of suicide.³⁴ Prescription opioids and benzodiazepines are the top 2 causes of overdose-related deaths (benzo­diazepines are involved in approximately 31% of fatal overdoses³⁵), and from 2002 to 2015 there was a 4.3-fold increase in deaths from benzodiazepine overdose in the United States.³⁶ CDC guidelines recommend against co-prescribing opioids and benzodiazepines because of the risk of death by respiratory depression.³⁷ As of August 2016, the FDA required black-box warnings for opioids and benzodiazepines regarding the risk of respiratory depression and death when these agents are used in combination, noting that “If these medicines are prescribed together, limit the dosages and duration of each drug to the minimum possible while achieving the desired clinical effect.”^38,39

A sensible approach to prescribing

Given the risks posed by benzodiazepines, what would constitute a sensible approach to their use? Clearly, there are some patients for whom benzodiazepine use should be minimized or avoided (Table 3). In a patient who is deemed a good candidate for benzo­diazepines, a long-acting agent may be preferable because of the increased risk of dependence associated with short-acting compounds. Start with a low dose, and use the lowest dose that adequately treats the patient’s symptoms.⁴⁰ Using scheduled rather than “as-needed” dosing may help reduce behavioral escape patterns that reinforce anxiety and dependence in the long term.

Before starting a patient on a benzo­diazepine, discuss with him (her) the risks of use and an exit plan to discontinue the medication. For example, a benzodiazepine may be prescribed at the same time as a selective serotonin reuptake inhibitor (SSRI), with the goal of weaning off the benzodiazepine once the SSRI has achieved efficacy.⁶ Inform the patient that prescribing or treatment may be terminated if it is discovered that the patient is abusing or diverting the medication (regularly reviewing the state prescription monitoring program database can help determine if this has occurred). Strongly consider using non-benzodiazepine treatments for anxiety with (or eventually in place of) benzodiazepines (Table 4⁴¹).

As a group, anxiety disorders are the most common mental illness in the Unites States, affecting 40 million adults. There is a nearly 30% lifetime prevalence of anxiety disorders in the general population.¹ DSM-5 anxiety disorders include generalized anxiety disorder, social anxiety disorder (social phobia), panic disorder, specific phobia, and separation anxiety disorder. Although DSM-IV-TR also classified obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD) as anxiety disorders, these diagnoses were reclassified in DSM-5. Anxiety also is a frequent symptom of many other psychiatric disorders, especially major depressive disorder.

Although benzodiazepines have many potential uses, they also carry risks that prescribers should recognize. This article reviews some of the risks of benzodiazepine use, identifies patients with higher risks of adverse effects, and presents a practical approach to prescribing these medications.

A wide range of risks

Abuse and addiction. Perhaps the most commonly recognized risk associated with benzodiazepine use is the potential for abuse and addiction.⁴ Prolonged benzodiazepine use typically results in physiologic tolerance, requiring higher dosing to achieve the same initial effect.⁵ American Psychiatric Association practice guidelines recognize the potential for benzodiazepine use to result in symptoms of dependence, including cravings and withdrawal, stating that “with ongoing use, all benzodiazepines will produce physiological dependence in most patients.”⁶ High-potency, short-acting compounds such as alprazolam have a higher risk for dependence, toxicity, and abuse.⁷ However, long-acting benzodiazepines (such as clonazepam) also can be habit-forming.⁸ Because of these properties, it is generally advisable to avoid prescribing benzo­diazepines (and short-acting compounds in particular) when treating patients with current or past substance use disorders, except when treating withdrawal.⁹

Limited efficacy for other disorders. Although benzodiazepines can help reduce anxiety in patients with anxiety disorders, they have shown less promise in treating other disorders in which anxiety is a common symptom. Treating PTSD with benzodiazepines does not appear to offer any advantage over placebo, and may even result in increased symptoms over time.^10,11 There is limited evidence supporting the use of benzodiazepines to treat OCD.^12,13 Patients with borderline personality disorder who are treated with benzodiazepines may experience an increase in behavioral dysregulation.¹⁴

Physical ailments. Benzodiazepines can affect comorbid physical ailments. One study found that long-term benzodiazepine use among patients with comorbid pain disorders was correlated with high utilization of medical services and high disability levels.¹⁵ Benzodiazepine use also has been associated with an increased risk of exacerbating respiratory conditions, such as chronic obstructive pulmonary disease,¹⁶ and increased risk of pneumonia.^17,18

Pregnancy and breastfeeding. Benzo­diazepines carry risks for women who are pregnant or breastfeeding. Benzodiazepine use during pregnancy may increase the relative risk of major malformations and oral clefts. It also may result in neonatal lethargy, sedation, and weight loss. Benzodiazepine withdrawal symptoms can occur in the neonate.¹⁹ Benzodiazepines are secreted in breast milk and can result in sedation among breastfed infants.²⁰

Geriatric patients. Older adults may be particularly vulnerable to the adverse effects of benzodiazepines. The Beers Criteria for Potentially Inappropriate Medication Use in Older Adults recommends against prescribing benzodiazepines to geriatric patients.²¹ Benzodiazepine use has been associated with an increased risk for falls among older adults,^22,23 with an increased risk of fractures²⁴ that can be fatal.²⁵ Benzodiazepines also have been associated with an increased risk of cognitive dysfunction and dementia.^26,27 Despite the documented risks of using benzodiazepines in geriatric patients, benzodiazepines continue to be frequently prescribed to this age group.^28,29 One study found that the rate of prescribing benzo­diazepines by primary care physicians increased from 2003 to 2012, primarily among older adults with no diagnosis of pain or a psychiatric disorder.³⁰

Mortality. Benzodiazepine use also carries an increased risk of mortality. Benzo­diazepine users are at increased risk of motor vehicle accidents because of difficulty maintaining road position.³¹ Some research has shown that patients with schizophrenia treated with benzodiazepines have an increased risk of death compared with those who are prescribed antipsychotics or antidepressants.³² Another study showed that patients with schizophrenia who were prescribed benzodiazepines had a greater risk of death by suicide and accidental poisoning.³³ Benzodiazepine use has been associated with suicidal ideation and an increased risk of suicide.³⁴ Prescription opioids and benzodiazepines are the top 2 causes of overdose-related deaths (benzo­diazepines are involved in approximately 31% of fatal overdoses³⁵), and from 2002 to 2015 there was a 4.3-fold increase in deaths from benzodiazepine overdose in the United States.³⁶ CDC guidelines recommend against co-prescribing opioids and benzodiazepines because of the risk of death by respiratory depression.³⁷ As of August 2016, the FDA required black-box warnings for opioids and benzodiazepines regarding the risk of respiratory depression and death when these agents are used in combination, noting that “If these medicines are prescribed together, limit the dosages and duration of each drug to the minimum possible while achieving the desired clinical effect.”^38,39

A sensible approach to prescribing

Given the risks posed by benzodiazepines, what would constitute a sensible approach to their use? Clearly, there are some patients for whom benzodiazepine use should be minimized or avoided (Table 3). In a patient who is deemed a good candidate for benzo­diazepines, a long-acting agent may be preferable because of the increased risk of dependence associated with short-acting compounds. Start with a low dose, and use the lowest dose that adequately treats the patient’s symptoms.⁴⁰ Using scheduled rather than “as-needed” dosing may help reduce behavioral escape patterns that reinforce anxiety and dependence in the long term.

Before starting a patient on a benzo­diazepine, discuss with him (her) the risks of use and an exit plan to discontinue the medication. For example, a benzodiazepine may be prescribed at the same time as a selective serotonin reuptake inhibitor (SSRI), with the goal of weaning off the benzodiazepine once the SSRI has achieved efficacy.⁶ Inform the patient that prescribing or treatment may be terminated if it is discovered that the patient is abusing or diverting the medication (regularly reviewing the state prescription monitoring program database can help determine if this has occurred). Strongly consider using non-benzodiazepine treatments for anxiety with (or eventually in place of) benzodiazepines (Table 4⁴¹).

As a group, anxiety disorders are the most common mental illness in the Unites States, affecting 40 million adults. There is a nearly 30% lifetime prevalence of anxiety disorders in the general population.¹ DSM-5 anxiety disorders include generalized anxiety disorder, social anxiety disorder (social phobia), panic disorder, specific phobia, and separation anxiety disorder. Although DSM-IV-TR also classified obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD) as anxiety disorders, these diagnoses were reclassified in DSM-5. Anxiety also is a frequent symptom of many other psychiatric disorders, especially major depressive disorder.

Although benzodiazepines have many potential uses, they also carry risks that prescribers should recognize. This article reviews some of the risks of benzodiazepine use, identifies patients with higher risks of adverse effects, and presents a practical approach to prescribing these medications.

A wide range of risks

Abuse and addiction. Perhaps the most commonly recognized risk associated with benzodiazepine use is the potential for abuse and addiction.⁴ Prolonged benzodiazepine use typically results in physiologic tolerance, requiring higher dosing to achieve the same initial effect.⁵ American Psychiatric Association practice guidelines recognize the potential for benzodiazepine use to result in symptoms of dependence, including cravings and withdrawal, stating that “with ongoing use, all benzodiazepines will produce physiological dependence in most patients.”⁶ High-potency, short-acting compounds such as alprazolam have a higher risk for dependence, toxicity, and abuse.⁷ However, long-acting benzodiazepines (such as clonazepam) also can be habit-forming.⁸ Because of these properties, it is generally advisable to avoid prescribing benzo­diazepines (and short-acting compounds in particular) when treating patients with current or past substance use disorders, except when treating withdrawal.⁹

Limited efficacy for other disorders. Although benzodiazepines can help reduce anxiety in patients with anxiety disorders, they have shown less promise in treating other disorders in which anxiety is a common symptom. Treating PTSD with benzodiazepines does not appear to offer any advantage over placebo, and may even result in increased symptoms over time.^10,11 There is limited evidence supporting the use of benzodiazepines to treat OCD.^12,13 Patients with borderline personality disorder who are treated with benzodiazepines may experience an increase in behavioral dysregulation.¹⁴

Physical ailments. Benzodiazepines can affect comorbid physical ailments. One study found that long-term benzodiazepine use among patients with comorbid pain disorders was correlated with high utilization of medical services and high disability levels.¹⁵ Benzodiazepine use also has been associated with an increased risk of exacerbating respiratory conditions, such as chronic obstructive pulmonary disease,¹⁶ and increased risk of pneumonia.^17,18

Pregnancy and breastfeeding. Benzo­diazepines carry risks for women who are pregnant or breastfeeding. Benzodiazepine use during pregnancy may increase the relative risk of major malformations and oral clefts. It also may result in neonatal lethargy, sedation, and weight loss. Benzodiazepine withdrawal symptoms can occur in the neonate.¹⁹ Benzodiazepines are secreted in breast milk and can result in sedation among breastfed infants.²⁰

Geriatric patients. Older adults may be particularly vulnerable to the adverse effects of benzodiazepines. The Beers Criteria for Potentially Inappropriate Medication Use in Older Adults recommends against prescribing benzodiazepines to geriatric patients.²¹ Benzodiazepine use has been associated with an increased risk for falls among older adults,^22,23 with an increased risk of fractures²⁴ that can be fatal.²⁵ Benzodiazepines also have been associated with an increased risk of cognitive dysfunction and dementia.^26,27 Despite the documented risks of using benzodiazepines in geriatric patients, benzodiazepines continue to be frequently prescribed to this age group.^28,29 One study found that the rate of prescribing benzo­diazepines by primary care physicians increased from 2003 to 2012, primarily among older adults with no diagnosis of pain or a psychiatric disorder.³⁰

Mortality. Benzodiazepine use also carries an increased risk of mortality. Benzo­diazepine users are at increased risk of motor vehicle accidents because of difficulty maintaining road position.³¹ Some research has shown that patients with schizophrenia treated with benzodiazepines have an increased risk of death compared with those who are prescribed antipsychotics or antidepressants.³² Another study showed that patients with schizophrenia who were prescribed benzodiazepines had a greater risk of death by suicide and accidental poisoning.³³ Benzodiazepine use has been associated with suicidal ideation and an increased risk of suicide.³⁴ Prescription opioids and benzodiazepines are the top 2 causes of overdose-related deaths (benzo­diazepines are involved in approximately 31% of fatal overdoses³⁵), and from 2002 to 2015 there was a 4.3-fold increase in deaths from benzodiazepine overdose in the United States.³⁶ CDC guidelines recommend against co-prescribing opioids and benzodiazepines because of the risk of death by respiratory depression.³⁷ As of August 2016, the FDA required black-box warnings for opioids and benzodiazepines regarding the risk of respiratory depression and death when these agents are used in combination, noting that “If these medicines are prescribed together, limit the dosages and duration of each drug to the minimum possible while achieving the desired clinical effect.”^38,39

A sensible approach to prescribing

Given the risks posed by benzodiazepines, what would constitute a sensible approach to their use? Clearly, there are some patients for whom benzodiazepine use should be minimized or avoided (Table 3). In a patient who is deemed a good candidate for benzo­diazepines, a long-acting agent may be preferable because of the increased risk of dependence associated with short-acting compounds. Start with a low dose, and use the lowest dose that adequately treats the patient’s symptoms.⁴⁰ Using scheduled rather than “as-needed” dosing may help reduce behavioral escape patterns that reinforce anxiety and dependence in the long term.

Before starting a patient on a benzo­diazepine, discuss with him (her) the risks of use and an exit plan to discontinue the medication. For example, a benzodiazepine may be prescribed at the same time as a selective serotonin reuptake inhibitor (SSRI), with the goal of weaning off the benzodiazepine once the SSRI has achieved efficacy.⁶ Inform the patient that prescribing or treatment may be terminated if it is discovered that the patient is abusing or diverting the medication (regularly reviewing the state prescription monitoring program database can help determine if this has occurred). Strongly consider using non-benzodiazepine treatments for anxiety with (or eventually in place of) benzodiazepines (Table 4⁴¹).

Compulsive sexual behavior (CSB), also referred to as sexual addiction or hypersexuality, is characterized by repetitive and intense preoccupations with sexual fantasies, urges, and behaviors that are distressing to the individual and/or result in psychosocial impairment. Individuals with CSB often perceive their sexual behavior to be excessive but are unable to control it. CSB can involve fantasies and urges in addition to or in place of the behavior but must cause clinically significant distress and interference in daily life to qualify as a disorder.

Because of the lack of large-scale, population-based epidemiological studies assessing CSB, its true prevalence among adults is unknown. A study of 204 psychiatric inpatients found a current prevalence of 4.4%,¹ while a university-based survey estimated the prevalence of CSB at approximately 2%.² Others have estimated that the prevalence is between 3% to 6% of adults in the United States,^3,4 with males comprising the majority (≥80%) of affected individuals.⁵

CSB usually develops during late adolescence/early adulthood, and most who present for treatment are male.⁵ Mood states, including depression, happiness, and loneliness, may trigger CSB.⁶ Many individuals report feelings of dissociation while engaging in CSB-related behaviors, whereas others report feeling important, powerful, excited, or gratified.

Why CSB is difficult to diagnose

Although CSB may be common, it usually goes undiagnosed. This potentially problematic behavior often is not diagnosed because of:

• Shame and secrecy. Embarrassment and shame, which are fundamental to CSB, appear to explain, in part, why few patients volunteer information regarding this behavior unless specifically asked.¹
• Patient lack of knowledge. Patients often do not know that their behavior can be successfully treated.
• Clinician lack of knowledge. Few health care professionals have education or training in CSB. A lack of recognition of CSB also may be due to our limited understanding regarding the limits of sexual normality. In addition, the classification of CSB is unclear and not agreed upon (Box^7-9), and moral judgments often are involved in understanding sexual behaviors.¹⁰

Box
Classifying compulsive sexual behavior

No consensus on diagnostic criteria

Accurately diagnosing CSB is difficult because of a lack of consensus about the diagnostic criteria for the disorder. Christenson et al¹¹ developed an early set of criteria for CSB as part of a larger survey of impulse control disorders. They used the following 2 criteria to diagnose CSB: (1) excessive or uncontrolled sexual behavior(s) or sexual thoughts/urges to engage in behavior, and (2) these behaviors or thoughts/urges lead to significant distress, social or occupational impairment, or legal and financial consequences.^11,12

During the DSM-5 revision process, a second approach to the diagnostic criteria was proposed for hypersexuality disorder. Under the proposed criteria for hypersexuality, a person would meet the diagnosis if ≥3 of the following were endorsed over a 6-month period: (a) time consumed by sexual fantasies, urges, or behaviors repetitively interferes with other important (non-sexual) goals, activities, and obligations; (b) repetitively engaging in sexual fantasies, urges, or behaviors in response to dysphoric mood states; (c) repetitively engaging in sexual fantasies, urges, or behaviors in response to stressful life events; (d) repetitive but unsuccessful efforts to control or significantly reduce these sexual fantasies, urges, or behaviors; and (e) repetitively engaging in sexual behaviors while disregarding the risk for physical or emotional harm to self or others.⁹

These 2 proposed approaches to diagnosis are somewhat similar. Both suggest that the core underlying issues involve sexual urges or behaviors that are difficult to control and that lead to psychosocial dysfunction. Differences in the criteria, however, could result in different rates of CSB diagnosis; therefore, further research will need to determine which diagnostic approach reflects the neurobiology underlying CSB.

Avoid misdiagnosis

Before making a diagnosis of CSB, it is important for clinicians to consider whether they are stigmatizing “negative consequences,” distress, or social impairment based on unconscious bias toward certain sexual behaviors. In addition, we need to ensure that we are not holding sex to different standards than other behaviors (for example, there are many things in life we do that result in negative consequences and yet do not classify as a mental disorder, such as indulging in less healthy food choices). Furthermore, excessive sexual behaviors might be associated with the normal coming out process for LGBTQ individuals, partner relationship problems, or sexual/gender identity. Therefore, the behavior needs to be assessed in the context of these psychosocial environmental factors.

Differential diagnosis

Various psychiatric disorders also may include excessive sexual behavior as part of their clinical presentation, and it is important to differentiate that behavior from CSB.

Bipolar disorder. Excessive sexual behavior can occur as part of a manic episode in bipolar disorder. If the problematic sexual behavior also occurs when the person’s mood is stable, the individual may have CSB and bipolar disorder. This distinction is important because the treatment for bipolar disorder is often different for CSB, because anticonvulsants have only case reports attesting to their use in CSB.

Substance abuse. Excessive sexual behavior can occur when a person is abusing substances, particularly stimulants such as cocaine and amphetamines.¹³ If the sexual behavior does not occur when the person is not using drugs, then the appropriate diagnosis would not likely be CSB.

Obsessive-compulsive disorder (OCD). Individuals with OCD often are preoccupied with sexual themes and feel that they think about sex excessively.¹⁴ Although patients with OCD may be preoccupied with thoughts of sex, the key difference is that persons with CSB report feeling excited by these thoughts and derive pleasure from the behavior, whereas the sexual thoughts of OCD are perceived as unpleasant.

Other disorders that may give rise to hypersexual behavior include neurocognitive disorders, attention-deficit/hyperactivity disorder, autism spectrum disorders, and depressive disorders.

Adverse effects of medication. It is important to ask the patient whether he (she)developed CSB after starting a medication. Certain medications (eg, medications for Parkinson’s disease or restless leg syndrome, or aripiprazole to treat depression or psychosis) may cause patients to engage in problematic sexual behavior.^15,16 If the sexual behavior decreases or stops when the medication dosage is reduced or the medication is stopped, a diagnosis of CSB would not be appropriate.

Comorbidity is common

Research suggests that approximately one-half of adults with CSB meet criteria for at least 1 other psychiatric disorder, such as mood, anxiety, substance use, impulse control, or personality disorders. A study of men with CSB (N = 103) found that 71% met criteria for a mood disorder, 40% for an anxiety disorder, 41% for a substance use disorder, and 24% for an impulse control disorder such as gambling disorder.¹⁷ Therefore, to successfully treat CSB, clinicians also may need to focus on how and to what extent these co-occurring disorders drive the sexual behavior.

Co-occurring medical conditions also are common among individuals with CSB. Medical concerns may include unwanted pregnancy, sexually transmitted infections, and HIV/AIDS. Thus, treating psychiatric comorbidities and providing education about sexual health, with referrals to primary care specialists, often are part of CSB treatment.

Neuroimaging and cognition

One imaging study that compared participants with and without CSB found that participants with CSB had higher activity in the ventral striatum, anterior cingulate cortex, and amygdala relative to controls during a cue-reactivity functional MRI task.¹⁸ These findings show notable similarities to the patterns of activation seen in patients addicted to drugs when assessed using drug-craving paradigms. An additional neuroimaging study assessing patients with hypersexuality using diffusion tensor imaging noted that diffusivity in a prefrontal white matter tract within a superior frontal region was greater in patients with CSB.¹⁸ This study also indicated that there was a negative correlation between observed diffusion in the noted location and overall severity score for CSB symptoms such as frequency of urges or behaviors.

In terms of cognition, a preliminary assessment of young adults with CSB compared with healthy controls did not find any differences between groups across several tasks, although the previously mentioned diffusion tensor imaging study reported elevated impulsivity in CSB.¹⁸

Approaches to treatment

Most people with CSB are reluctant to mention it to their health care providers, and most physicians are generally uncomfortable talking about sex with their patients, in part, because of a lack of training.¹⁹ Patients are more likely to bring up the topic when they are receiving treatment for anxiety, depression, or substance abuse. Therefore, clinicians must consider that sexual behavior might be associated with a coping mechanism, distressing outcome, or comorbid condition in these patients.

Pharmacologic treatment

Evidence for the pharmacologic treatment of CSB consists primarily of small, open-label studies, case series, or retrospective analyses, except for 1 double-blind, placebo-controlled study. Based on this evidence, there may be several pharma­cologic treatment options for patients with CSB; however, there are no FDA-approved medications for CSB.

Antidepressants. One of the most thoroughly documented categories of pharmacologic treatment for CSB is selective serotonin reuptake inhibitors (SSRIs). Several retrospective analyses and case series have reported on the general efficacy of SSRIs in reducing symptoms of CSB.^20-23 Citalopram, the only treatment for CSB that has been assessed using a double-blind, placebo-controlled methodology, was associated with significant decreases in CSB symptoms, including sexual desire/drive, frequency of masturbation, and pornography use.²⁴

In addition to SSRIs, several additional case reports have suggested that other classes of antidepressants, such as serotonin-norepinephrine reuptake inhibitors and tricyclic antidepressants, or stimulants may be beneficial when treating CSB.²⁵ Several case reports have indicated significant improvement of CSB symptoms using clomipramine.²² A retrospective study of nefazodone also has suggested that it may be an option for treating CSB. Patients reported notable reductions in the frequency of sexual obsessions/compulsions while taking nefazodone and reported no notable sexual adverse effects.²⁶ One branded version of nefazodone, Serzone, was associated with rare but severe liver problems and was withdrawn from the U.S. market in 2004.

Although some initial evidence regarding antidepressant use, particularly SSRIs, to treat CSB has suggested that these medications may be potentially beneficial, the findings are far from conclusive, with only 1 controlled trial and only single-subject case reports for many of the medications studied.

Naltrexone, an opioid antagonist, has received support from available cases, open-label studies, and retrospective analyses.^17,27 Although evidence for the use of naltrexone in CSB is limited to case reports and retrospective analyses, results have been positive. Naltrexone has shown notable decreases in CSB symptom severity when used as monotherapy and when used in combination with other treatments.

Anticonvulsants. Several case reports have suggested that certain anticonvulsants may be beneficial for treating CSB. Topiramate may be a particularly useful option.²⁸ Other anticonvulsants showing benefit for CSB in case reports include valproic acid, lamotrigine, and levetiracetam.¹⁸

Psychotherapy

Evidence supporting specific types of psychotherapy for CSB is limited and largely drawn from uncontrolled studies and case reports.

Cognitive-behavioral therapy (CBT) is one of the more common psychotherapeutic options used for CSB. Several uncontrolled studies and case reports have found that CBT is beneficial for CSB, although methodologies have varied.

Several cases found that combining CBT with motivational interviewing was associated with significant reductions in sexual behaviors, such as frequency of sexual partners and amount of time spent online during work hours.^29,30 Group CBT also has been shown to be effective for CSB.³¹

Acceptance and commitment therapy (ACT) has received some initial support, with 1 uncontrolled study and 1 controlled study.^32,33 The controlled study used 12 sessions of individual ACT compared with a wait-list condition.³² Improvements in CSB symptoms were maintained for 3 months. The overall reduction in problematic Internet pornography use was reported as 92% immediately after the study ended, and 86% after 3 months.

Marital/relationship therapy has been used successfully in several case series and case reports, although no studies have assessed its efficacy in treating CSB using a randomized protocol. In 1 case report, the researcher found that participation in marital sex therapy elicited notable improvements over the course of 1 year and 20 sessions.³⁴

Compulsive sexual behavior (CSB), also referred to as sexual addiction or hypersexuality, is characterized by repetitive and intense preoccupations with sexual fantasies, urges, and behaviors that are distressing to the individual and/or result in psychosocial impairment. Individuals with CSB often perceive their sexual behavior to be excessive but are unable to control it. CSB can involve fantasies and urges in addition to or in place of the behavior but must cause clinically significant distress and interference in daily life to qualify as a disorder.

Because of the lack of large-scale, population-based epidemiological studies assessing CSB, its true prevalence among adults is unknown. A study of 204 psychiatric inpatients found a current prevalence of 4.4%,¹ while a university-based survey estimated the prevalence of CSB at approximately 2%.² Others have estimated that the prevalence is between 3% to 6% of adults in the United States,^3,4 with males comprising the majority (≥80%) of affected individuals.⁵

CSB usually develops during late adolescence/early adulthood, and most who present for treatment are male.⁵ Mood states, including depression, happiness, and loneliness, may trigger CSB.⁶ Many individuals report feelings of dissociation while engaging in CSB-related behaviors, whereas others report feeling important, powerful, excited, or gratified.

Why CSB is difficult to diagnose

Although CSB may be common, it usually goes undiagnosed. This potentially problematic behavior often is not diagnosed because of:

• Shame and secrecy. Embarrassment and shame, which are fundamental to CSB, appear to explain, in part, why few patients volunteer information regarding this behavior unless specifically asked.¹
• Patient lack of knowledge. Patients often do not know that their behavior can be successfully treated.
• Clinician lack of knowledge. Few health care professionals have education or training in CSB. A lack of recognition of CSB also may be due to our limited understanding regarding the limits of sexual normality. In addition, the classification of CSB is unclear and not agreed upon (Box^7-9), and moral judgments often are involved in understanding sexual behaviors.¹⁰

Box
Classifying compulsive sexual behavior

No consensus on diagnostic criteria

Accurately diagnosing CSB is difficult because of a lack of consensus about the diagnostic criteria for the disorder. Christenson et al¹¹ developed an early set of criteria for CSB as part of a larger survey of impulse control disorders. They used the following 2 criteria to diagnose CSB: (1) excessive or uncontrolled sexual behavior(s) or sexual thoughts/urges to engage in behavior, and (2) these behaviors or thoughts/urges lead to significant distress, social or occupational impairment, or legal and financial consequences.^11,12

During the DSM-5 revision process, a second approach to the diagnostic criteria was proposed for hypersexuality disorder. Under the proposed criteria for hypersexuality, a person would meet the diagnosis if ≥3 of the following were endorsed over a 6-month period: (a) time consumed by sexual fantasies, urges, or behaviors repetitively interferes with other important (non-sexual) goals, activities, and obligations; (b) repetitively engaging in sexual fantasies, urges, or behaviors in response to dysphoric mood states; (c) repetitively engaging in sexual fantasies, urges, or behaviors in response to stressful life events; (d) repetitive but unsuccessful efforts to control or significantly reduce these sexual fantasies, urges, or behaviors; and (e) repetitively engaging in sexual behaviors while disregarding the risk for physical or emotional harm to self or others.⁹

These 2 proposed approaches to diagnosis are somewhat similar. Both suggest that the core underlying issues involve sexual urges or behaviors that are difficult to control and that lead to psychosocial dysfunction. Differences in the criteria, however, could result in different rates of CSB diagnosis; therefore, further research will need to determine which diagnostic approach reflects the neurobiology underlying CSB.

Avoid misdiagnosis

Before making a diagnosis of CSB, it is important for clinicians to consider whether they are stigmatizing “negative consequences,” distress, or social impairment based on unconscious bias toward certain sexual behaviors. In addition, we need to ensure that we are not holding sex to different standards than other behaviors (for example, there are many things in life we do that result in negative consequences and yet do not classify as a mental disorder, such as indulging in less healthy food choices). Furthermore, excessive sexual behaviors might be associated with the normal coming out process for LGBTQ individuals, partner relationship problems, or sexual/gender identity. Therefore, the behavior needs to be assessed in the context of these psychosocial environmental factors.

Differential diagnosis

Various psychiatric disorders also may include excessive sexual behavior as part of their clinical presentation, and it is important to differentiate that behavior from CSB.

Bipolar disorder. Excessive sexual behavior can occur as part of a manic episode in bipolar disorder. If the problematic sexual behavior also occurs when the person’s mood is stable, the individual may have CSB and bipolar disorder. This distinction is important because the treatment for bipolar disorder is often different for CSB, because anticonvulsants have only case reports attesting to their use in CSB.

Substance abuse. Excessive sexual behavior can occur when a person is abusing substances, particularly stimulants such as cocaine and amphetamines.¹³ If the sexual behavior does not occur when the person is not using drugs, then the appropriate diagnosis would not likely be CSB.

Obsessive-compulsive disorder (OCD). Individuals with OCD often are preoccupied with sexual themes and feel that they think about sex excessively.¹⁴ Although patients with OCD may be preoccupied with thoughts of sex, the key difference is that persons with CSB report feeling excited by these thoughts and derive pleasure from the behavior, whereas the sexual thoughts of OCD are perceived as unpleasant.

Other disorders that may give rise to hypersexual behavior include neurocognitive disorders, attention-deficit/hyperactivity disorder, autism spectrum disorders, and depressive disorders.

Adverse effects of medication. It is important to ask the patient whether he (she)developed CSB after starting a medication. Certain medications (eg, medications for Parkinson’s disease or restless leg syndrome, or aripiprazole to treat depression or psychosis) may cause patients to engage in problematic sexual behavior.^15,16 If the sexual behavior decreases or stops when the medication dosage is reduced or the medication is stopped, a diagnosis of CSB would not be appropriate.

Comorbidity is common

Research suggests that approximately one-half of adults with CSB meet criteria for at least 1 other psychiatric disorder, such as mood, anxiety, substance use, impulse control, or personality disorders. A study of men with CSB (N = 103) found that 71% met criteria for a mood disorder, 40% for an anxiety disorder, 41% for a substance use disorder, and 24% for an impulse control disorder such as gambling disorder.¹⁷ Therefore, to successfully treat CSB, clinicians also may need to focus on how and to what extent these co-occurring disorders drive the sexual behavior.

Co-occurring medical conditions also are common among individuals with CSB. Medical concerns may include unwanted pregnancy, sexually transmitted infections, and HIV/AIDS. Thus, treating psychiatric comorbidities and providing education about sexual health, with referrals to primary care specialists, often are part of CSB treatment.

Neuroimaging and cognition

One imaging study that compared participants with and without CSB found that participants with CSB had higher activity in the ventral striatum, anterior cingulate cortex, and amygdala relative to controls during a cue-reactivity functional MRI task.¹⁸ These findings show notable similarities to the patterns of activation seen in patients addicted to drugs when assessed using drug-craving paradigms. An additional neuroimaging study assessing patients with hypersexuality using diffusion tensor imaging noted that diffusivity in a prefrontal white matter tract within a superior frontal region was greater in patients with CSB.¹⁸ This study also indicated that there was a negative correlation between observed diffusion in the noted location and overall severity score for CSB symptoms such as frequency of urges or behaviors.

In terms of cognition, a preliminary assessment of young adults with CSB compared with healthy controls did not find any differences between groups across several tasks, although the previously mentioned diffusion tensor imaging study reported elevated impulsivity in CSB.¹⁸

Approaches to treatment

Most people with CSB are reluctant to mention it to their health care providers, and most physicians are generally uncomfortable talking about sex with their patients, in part, because of a lack of training.¹⁹ Patients are more likely to bring up the topic when they are receiving treatment for anxiety, depression, or substance abuse. Therefore, clinicians must consider that sexual behavior might be associated with a coping mechanism, distressing outcome, or comorbid condition in these patients.

Pharmacologic treatment

Evidence for the pharmacologic treatment of CSB consists primarily of small, open-label studies, case series, or retrospective analyses, except for 1 double-blind, placebo-controlled study. Based on this evidence, there may be several pharma­cologic treatment options for patients with CSB; however, there are no FDA-approved medications for CSB.

Antidepressants. One of the most thoroughly documented categories of pharmacologic treatment for CSB is selective serotonin reuptake inhibitors (SSRIs). Several retrospective analyses and case series have reported on the general efficacy of SSRIs in reducing symptoms of CSB.^20-23 Citalopram, the only treatment for CSB that has been assessed using a double-blind, placebo-controlled methodology, was associated with significant decreases in CSB symptoms, including sexual desire/drive, frequency of masturbation, and pornography use.²⁴

In addition to SSRIs, several additional case reports have suggested that other classes of antidepressants, such as serotonin-norepinephrine reuptake inhibitors and tricyclic antidepressants, or stimulants may be beneficial when treating CSB.²⁵ Several case reports have indicated significant improvement of CSB symptoms using clomipramine.²² A retrospective study of nefazodone also has suggested that it may be an option for treating CSB. Patients reported notable reductions in the frequency of sexual obsessions/compulsions while taking nefazodone and reported no notable sexual adverse effects.²⁶ One branded version of nefazodone, Serzone, was associated with rare but severe liver problems and was withdrawn from the U.S. market in 2004.

Although some initial evidence regarding antidepressant use, particularly SSRIs, to treat CSB has suggested that these medications may be potentially beneficial, the findings are far from conclusive, with only 1 controlled trial and only single-subject case reports for many of the medications studied.

Naltrexone, an opioid antagonist, has received support from available cases, open-label studies, and retrospective analyses.^17,27 Although evidence for the use of naltrexone in CSB is limited to case reports and retrospective analyses, results have been positive. Naltrexone has shown notable decreases in CSB symptom severity when used as monotherapy and when used in combination with other treatments.

Anticonvulsants. Several case reports have suggested that certain anticonvulsants may be beneficial for treating CSB. Topiramate may be a particularly useful option.²⁸ Other anticonvulsants showing benefit for CSB in case reports include valproic acid, lamotrigine, and levetiracetam.¹⁸

Psychotherapy

Evidence supporting specific types of psychotherapy for CSB is limited and largely drawn from uncontrolled studies and case reports.

Cognitive-behavioral therapy (CBT) is one of the more common psychotherapeutic options used for CSB. Several uncontrolled studies and case reports have found that CBT is beneficial for CSB, although methodologies have varied.

Several cases found that combining CBT with motivational interviewing was associated with significant reductions in sexual behaviors, such as frequency of sexual partners and amount of time spent online during work hours.^29,30 Group CBT also has been shown to be effective for CSB.³¹

Acceptance and commitment therapy (ACT) has received some initial support, with 1 uncontrolled study and 1 controlled study.^32,33 The controlled study used 12 sessions of individual ACT compared with a wait-list condition.³² Improvements in CSB symptoms were maintained for 3 months. The overall reduction in problematic Internet pornography use was reported as 92% immediately after the study ended, and 86% after 3 months.

Marital/relationship therapy has been used successfully in several case series and case reports, although no studies have assessed its efficacy in treating CSB using a randomized protocol. In 1 case report, the researcher found that participation in marital sex therapy elicited notable improvements over the course of 1 year and 20 sessions.³⁴

Compulsive sexual behavior (CSB), also referred to as sexual addiction or hypersexuality, is characterized by repetitive and intense preoccupations with sexual fantasies, urges, and behaviors that are distressing to the individual and/or result in psychosocial impairment. Individuals with CSB often perceive their sexual behavior to be excessive but are unable to control it. CSB can involve fantasies and urges in addition to or in place of the behavior but must cause clinically significant distress and interference in daily life to qualify as a disorder.

Because of the lack of large-scale, population-based epidemiological studies assessing CSB, its true prevalence among adults is unknown. A study of 204 psychiatric inpatients found a current prevalence of 4.4%,¹ while a university-based survey estimated the prevalence of CSB at approximately 2%.² Others have estimated that the prevalence is between 3% to 6% of adults in the United States,^3,4 with males comprising the majority (≥80%) of affected individuals.⁵

CSB usually develops during late adolescence/early adulthood, and most who present for treatment are male.⁵ Mood states, including depression, happiness, and loneliness, may trigger CSB.⁶ Many individuals report feelings of dissociation while engaging in CSB-related behaviors, whereas others report feeling important, powerful, excited, or gratified.

Why CSB is difficult to diagnose

Although CSB may be common, it usually goes undiagnosed. This potentially problematic behavior often is not diagnosed because of:

• Shame and secrecy. Embarrassment and shame, which are fundamental to CSB, appear to explain, in part, why few patients volunteer information regarding this behavior unless specifically asked.¹
• Patient lack of knowledge. Patients often do not know that their behavior can be successfully treated.
• Clinician lack of knowledge. Few health care professionals have education or training in CSB. A lack of recognition of CSB also may be due to our limited understanding regarding the limits of sexual normality. In addition, the classification of CSB is unclear and not agreed upon (Box^7-9), and moral judgments often are involved in understanding sexual behaviors.¹⁰

Box
Classifying compulsive sexual behavior

No consensus on diagnostic criteria

Accurately diagnosing CSB is difficult because of a lack of consensus about the diagnostic criteria for the disorder. Christenson et al¹¹ developed an early set of criteria for CSB as part of a larger survey of impulse control disorders. They used the following 2 criteria to diagnose CSB: (1) excessive or uncontrolled sexual behavior(s) or sexual thoughts/urges to engage in behavior, and (2) these behaviors or thoughts/urges lead to significant distress, social or occupational impairment, or legal and financial consequences.^11,12

During the DSM-5 revision process, a second approach to the diagnostic criteria was proposed for hypersexuality disorder. Under the proposed criteria for hypersexuality, a person would meet the diagnosis if ≥3 of the following were endorsed over a 6-month period: (a) time consumed by sexual fantasies, urges, or behaviors repetitively interferes with other important (non-sexual) goals, activities, and obligations; (b) repetitively engaging in sexual fantasies, urges, or behaviors in response to dysphoric mood states; (c) repetitively engaging in sexual fantasies, urges, or behaviors in response to stressful life events; (d) repetitive but unsuccessful efforts to control or significantly reduce these sexual fantasies, urges, or behaviors; and (e) repetitively engaging in sexual behaviors while disregarding the risk for physical or emotional harm to self or others.⁹

These 2 proposed approaches to diagnosis are somewhat similar. Both suggest that the core underlying issues involve sexual urges or behaviors that are difficult to control and that lead to psychosocial dysfunction. Differences in the criteria, however, could result in different rates of CSB diagnosis; therefore, further research will need to determine which diagnostic approach reflects the neurobiology underlying CSB.

Avoid misdiagnosis

Before making a diagnosis of CSB, it is important for clinicians to consider whether they are stigmatizing “negative consequences,” distress, or social impairment based on unconscious bias toward certain sexual behaviors. In addition, we need to ensure that we are not holding sex to different standards than other behaviors (for example, there are many things in life we do that result in negative consequences and yet do not classify as a mental disorder, such as indulging in less healthy food choices). Furthermore, excessive sexual behaviors might be associated with the normal coming out process for LGBTQ individuals, partner relationship problems, or sexual/gender identity. Therefore, the behavior needs to be assessed in the context of these psychosocial environmental factors.

Differential diagnosis

Various psychiatric disorders also may include excessive sexual behavior as part of their clinical presentation, and it is important to differentiate that behavior from CSB.

Bipolar disorder. Excessive sexual behavior can occur as part of a manic episode in bipolar disorder. If the problematic sexual behavior also occurs when the person’s mood is stable, the individual may have CSB and bipolar disorder. This distinction is important because the treatment for bipolar disorder is often different for CSB, because anticonvulsants have only case reports attesting to their use in CSB.

Substance abuse. Excessive sexual behavior can occur when a person is abusing substances, particularly stimulants such as cocaine and amphetamines.¹³ If the sexual behavior does not occur when the person is not using drugs, then the appropriate diagnosis would not likely be CSB.

Obsessive-compulsive disorder (OCD). Individuals with OCD often are preoccupied with sexual themes and feel that they think about sex excessively.¹⁴ Although patients with OCD may be preoccupied with thoughts of sex, the key difference is that persons with CSB report feeling excited by these thoughts and derive pleasure from the behavior, whereas the sexual thoughts of OCD are perceived as unpleasant.

Other disorders that may give rise to hypersexual behavior include neurocognitive disorders, attention-deficit/hyperactivity disorder, autism spectrum disorders, and depressive disorders.

Adverse effects of medication. It is important to ask the patient whether he (she)developed CSB after starting a medication. Certain medications (eg, medications for Parkinson’s disease or restless leg syndrome, or aripiprazole to treat depression or psychosis) may cause patients to engage in problematic sexual behavior.^15,16 If the sexual behavior decreases or stops when the medication dosage is reduced or the medication is stopped, a diagnosis of CSB would not be appropriate.

Comorbidity is common

Research suggests that approximately one-half of adults with CSB meet criteria for at least 1 other psychiatric disorder, such as mood, anxiety, substance use, impulse control, or personality disorders. A study of men with CSB (N = 103) found that 71% met criteria for a mood disorder, 40% for an anxiety disorder, 41% for a substance use disorder, and 24% for an impulse control disorder such as gambling disorder.¹⁷ Therefore, to successfully treat CSB, clinicians also may need to focus on how and to what extent these co-occurring disorders drive the sexual behavior.

Co-occurring medical conditions also are common among individuals with CSB. Medical concerns may include unwanted pregnancy, sexually transmitted infections, and HIV/AIDS. Thus, treating psychiatric comorbidities and providing education about sexual health, with referrals to primary care specialists, often are part of CSB treatment.

Neuroimaging and cognition

One imaging study that compared participants with and without CSB found that participants with CSB had higher activity in the ventral striatum, anterior cingulate cortex, and amygdala relative to controls during a cue-reactivity functional MRI task.¹⁸ These findings show notable similarities to the patterns of activation seen in patients addicted to drugs when assessed using drug-craving paradigms. An additional neuroimaging study assessing patients with hypersexuality using diffusion tensor imaging noted that diffusivity in a prefrontal white matter tract within a superior frontal region was greater in patients with CSB.¹⁸ This study also indicated that there was a negative correlation between observed diffusion in the noted location and overall severity score for CSB symptoms such as frequency of urges or behaviors.

In terms of cognition, a preliminary assessment of young adults with CSB compared with healthy controls did not find any differences between groups across several tasks, although the previously mentioned diffusion tensor imaging study reported elevated impulsivity in CSB.¹⁸

Approaches to treatment

Most people with CSB are reluctant to mention it to their health care providers, and most physicians are generally uncomfortable talking about sex with their patients, in part, because of a lack of training.¹⁹ Patients are more likely to bring up the topic when they are receiving treatment for anxiety, depression, or substance abuse. Therefore, clinicians must consider that sexual behavior might be associated with a coping mechanism, distressing outcome, or comorbid condition in these patients.

Pharmacologic treatment

Evidence for the pharmacologic treatment of CSB consists primarily of small, open-label studies, case series, or retrospective analyses, except for 1 double-blind, placebo-controlled study. Based on this evidence, there may be several pharma­cologic treatment options for patients with CSB; however, there are no FDA-approved medications for CSB.

Antidepressants. One of the most thoroughly documented categories of pharmacologic treatment for CSB is selective serotonin reuptake inhibitors (SSRIs). Several retrospective analyses and case series have reported on the general efficacy of SSRIs in reducing symptoms of CSB.^20-23 Citalopram, the only treatment for CSB that has been assessed using a double-blind, placebo-controlled methodology, was associated with significant decreases in CSB symptoms, including sexual desire/drive, frequency of masturbation, and pornography use.²⁴

In addition to SSRIs, several additional case reports have suggested that other classes of antidepressants, such as serotonin-norepinephrine reuptake inhibitors and tricyclic antidepressants, or stimulants may be beneficial when treating CSB.²⁵ Several case reports have indicated significant improvement of CSB symptoms using clomipramine.²² A retrospective study of nefazodone also has suggested that it may be an option for treating CSB. Patients reported notable reductions in the frequency of sexual obsessions/compulsions while taking nefazodone and reported no notable sexual adverse effects.²⁶ One branded version of nefazodone, Serzone, was associated with rare but severe liver problems and was withdrawn from the U.S. market in 2004.

Although some initial evidence regarding antidepressant use, particularly SSRIs, to treat CSB has suggested that these medications may be potentially beneficial, the findings are far from conclusive, with only 1 controlled trial and only single-subject case reports for many of the medications studied.

Naltrexone, an opioid antagonist, has received support from available cases, open-label studies, and retrospective analyses.^17,27 Although evidence for the use of naltrexone in CSB is limited to case reports and retrospective analyses, results have been positive. Naltrexone has shown notable decreases in CSB symptom severity when used as monotherapy and when used in combination with other treatments.

Anticonvulsants. Several case reports have suggested that certain anticonvulsants may be beneficial for treating CSB. Topiramate may be a particularly useful option.²⁸ Other anticonvulsants showing benefit for CSB in case reports include valproic acid, lamotrigine, and levetiracetam.¹⁸

Psychotherapy

Evidence supporting specific types of psychotherapy for CSB is limited and largely drawn from uncontrolled studies and case reports.

Cognitive-behavioral therapy (CBT) is one of the more common psychotherapeutic options used for CSB. Several uncontrolled studies and case reports have found that CBT is beneficial for CSB, although methodologies have varied.

Several cases found that combining CBT with motivational interviewing was associated with significant reductions in sexual behaviors, such as frequency of sexual partners and amount of time spent online during work hours.^29,30 Group CBT also has been shown to be effective for CSB.³¹

Acceptance and commitment therapy (ACT) has received some initial support, with 1 uncontrolled study and 1 controlled study.^32,33 The controlled study used 12 sessions of individual ACT compared with a wait-list condition.³² Improvements in CSB symptoms were maintained for 3 months. The overall reduction in problematic Internet pornography use was reported as 92% immediately after the study ended, and 86% after 3 months.

Marital/relationship therapy has been used successfully in several case series and case reports, although no studies have assessed its efficacy in treating CSB using a randomized protocol. In 1 case report, the researcher found that participation in marital sex therapy elicited notable improvements over the course of 1 year and 20 sessions.³⁴