Can geospatial mapping fill in the gaps in areas lagging behind in global efforts to end the HIV epidemic?

That’s what Diego Cuadros, PhD, assistant professor of health geography and disease modeling at the University of Cincinnati, set out to learn using geospatial data combined with prevalence data to identify the most underserved areas in Sub-Saharan Africa (SSA) for HIV services.

Study findings, which were published Nov. 24 in PLOS Global Public Health, highlight that as many as 1.5 million people living with HIV (PLHIV) in SSA have more than an hour’s motorized travel time both ways to access care, while roughly 3 million must set aside, at minimum, 30 minutes. When the only mode of transportation is walking, as much as 95.3% of underserved areas are faced with at least 30 minutes travel time.

This is simply the tip of the overall problem, Dr. Cuadros told this news organization.

“We are able to estimate how many people [whose] quality of life is being affected by HIV because they are not on treatment and most probably, HIV incidence is high in those areas. But [it’s not as simple as just] increasing the number of health care facilities,” he said. “We need to find strategies to be able to cover this population.”

Dr. Cuadros also noted that the problem goes both ways. “It’s hard for them to move, and it’s [also] hard to reach them,” he explained.
 

Mapping care, or lack thereof

Dr. Cuadros and team used two primary sources of data to generate high-resolution maps of underserved SSA areas: estimated number of PLHIV between the ages of 15 and 49 years in 47 SSA countries paired with population density and global map of travel time to the nearest health facility by motorized and nonmotorized (that is, walking) transportation. Combining these data allowed them to then detail the distance from access to care for every 5 km².

The mapping exercise showed that 90.5% of the total territory, in which about 7 million PLHIV resided, had more than 10 minutes motorized travel time to the nearest health care facility, while 74.6% were within 30 minutes, and 58.9% were within 60 minutes. Increases in threshold travel times (from 10 to 60 minutes) corresponded directly to declines in the average proportion of underserved areas (from 80.9% to 42.6%). However, in certain countries like Sudan and Mauritania, 99.4% of the areas were underserved at the 10 minute threshold, while more than 90% were underserved at the 60 minute threshold.

Corresponding rates for nonmotorized access to health services were similar: 88.7% (~17.6 million) PLHIV had 10 minutes walking time to health care services, while 57.8% (~11.5 million) had at least 30 minutes, and 33.0% (~6.6 million), at least 60 minutes. Likewise, as threshold times increased from 10 to 60 minutes, the percentage of affected PLHIV declined (to roughly 50% in two-thirds of the countries). But more than 70% of PLHIV resided in underserved areas in countries like Equatorial Guinea, Eritrea, South Sudan, and Sudan.
 

Geographical allocation of health service facilities underscores treatment gaps

“We think that most PLHIV live in urban areas or close to urban areas, and most of the health care facilities in Africa are concentrated in those areas. But [roughly 8 million people with HIV] are living in rural areas, and for most, movement is very difficult,” explained Dr. Cuadros, meaning that the majority are not on treatment despite the high incidence of HIV.

Inarguably, the pandemic has interrupted HIV services and treatment substantially on the African continent, further challenging any efforts to translate these study findings into actionable strategies.

“We’ve known for quite a while that distance and travel times and travel expenses are known risks for nonadherence, for lack of access to diagnostics, for people at risk for exposure,” Chris Beyrer, MD, MPH, Desmond M. Tutu Professor of Public Health and Human Rights at the Johns Hopkins Bloomberg School of Public Health, Baltimore, said in an interview. (Dr. Beyrer was not involved in the study.)

“What’s new is the ability to really look at this across geographies and really home in on how many people face very long times and distances for travel. That’s a really important contribution,” he said.

Dr. Cuadros pointed out that these hard-to-reach populations are key to achieving the UNAID’s HIV elimination targets. “We’re going to have these pockets of transmission that are going to be really important for epidemic control,” he explained.

Toward that end, the onus appears to extend well beyond solutions that emphasize difficulty in reaching people from the provider perspective. “There’s quite a lot of what you might want to think of as blaming the victim for when people miss appointments, don’t appear to be adherent, [or] can’t stay reliably suppressed,” said Dr. Beyrer.

“It’s really important for providers in general to include in history and intake how far people have come, what their challenges are with travel, to really pay attention to those issues. Having this elegant analysis, this level of detail, is an important first step,” he added.

Dr. Cuadros has disclosed no relevant financial relationships. Dr. Beyrer reports a consulting agreement with Merck.

A version of this article first appeared on Medscape.com.

Can geospatial mapping fill in the gaps in areas lagging behind in global efforts to end the HIV epidemic?

That’s what Diego Cuadros, PhD, assistant professor of health geography and disease modeling at the University of Cincinnati, set out to learn using geospatial data combined with prevalence data to identify the most underserved areas in Sub-Saharan Africa (SSA) for HIV services.

Study findings, which were published Nov. 24 in PLOS Global Public Health, highlight that as many as 1.5 million people living with HIV (PLHIV) in SSA have more than an hour’s motorized travel time both ways to access care, while roughly 3 million must set aside, at minimum, 30 minutes. When the only mode of transportation is walking, as much as 95.3% of underserved areas are faced with at least 30 minutes travel time.

This is simply the tip of the overall problem, Dr. Cuadros told this news organization.

“We are able to estimate how many people [whose] quality of life is being affected by HIV because they are not on treatment and most probably, HIV incidence is high in those areas. But [it’s not as simple as just] increasing the number of health care facilities,” he said. “We need to find strategies to be able to cover this population.”

Dr. Cuadros also noted that the problem goes both ways. “It’s hard for them to move, and it’s [also] hard to reach them,” he explained.
 

Mapping care, or lack thereof

Dr. Cuadros and team used two primary sources of data to generate high-resolution maps of underserved SSA areas: estimated number of PLHIV between the ages of 15 and 49 years in 47 SSA countries paired with population density and global map of travel time to the nearest health facility by motorized and nonmotorized (that is, walking) transportation. Combining these data allowed them to then detail the distance from access to care for every 5 km².

The mapping exercise showed that 90.5% of the total territory, in which about 7 million PLHIV resided, had more than 10 minutes motorized travel time to the nearest health care facility, while 74.6% were within 30 minutes, and 58.9% were within 60 minutes. Increases in threshold travel times (from 10 to 60 minutes) corresponded directly to declines in the average proportion of underserved areas (from 80.9% to 42.6%). However, in certain countries like Sudan and Mauritania, 99.4% of the areas were underserved at the 10 minute threshold, while more than 90% were underserved at the 60 minute threshold.

Corresponding rates for nonmotorized access to health services were similar: 88.7% (~17.6 million) PLHIV had 10 minutes walking time to health care services, while 57.8% (~11.5 million) had at least 30 minutes, and 33.0% (~6.6 million), at least 60 minutes. Likewise, as threshold times increased from 10 to 60 minutes, the percentage of affected PLHIV declined (to roughly 50% in two-thirds of the countries). But more than 70% of PLHIV resided in underserved areas in countries like Equatorial Guinea, Eritrea, South Sudan, and Sudan.
 

Geographical allocation of health service facilities underscores treatment gaps

“We think that most PLHIV live in urban areas or close to urban areas, and most of the health care facilities in Africa are concentrated in those areas. But [roughly 8 million people with HIV] are living in rural areas, and for most, movement is very difficult,” explained Dr. Cuadros, meaning that the majority are not on treatment despite the high incidence of HIV.

Inarguably, the pandemic has interrupted HIV services and treatment substantially on the African continent, further challenging any efforts to translate these study findings into actionable strategies.

“We’ve known for quite a while that distance and travel times and travel expenses are known risks for nonadherence, for lack of access to diagnostics, for people at risk for exposure,” Chris Beyrer, MD, MPH, Desmond M. Tutu Professor of Public Health and Human Rights at the Johns Hopkins Bloomberg School of Public Health, Baltimore, said in an interview. (Dr. Beyrer was not involved in the study.)

“What’s new is the ability to really look at this across geographies and really home in on how many people face very long times and distances for travel. That’s a really important contribution,” he said.

Dr. Cuadros pointed out that these hard-to-reach populations are key to achieving the UNAID’s HIV elimination targets. “We’re going to have these pockets of transmission that are going to be really important for epidemic control,” he explained.

Toward that end, the onus appears to extend well beyond solutions that emphasize difficulty in reaching people from the provider perspective. “There’s quite a lot of what you might want to think of as blaming the victim for when people miss appointments, don’t appear to be adherent, [or] can’t stay reliably suppressed,” said Dr. Beyrer.

“It’s really important for providers in general to include in history and intake how far people have come, what their challenges are with travel, to really pay attention to those issues. Having this elegant analysis, this level of detail, is an important first step,” he added.

Dr. Cuadros has disclosed no relevant financial relationships. Dr. Beyrer reports a consulting agreement with Merck.

A version of this article first appeared on Medscape.com.

Can geospatial mapping fill in the gaps in areas lagging behind in global efforts to end the HIV epidemic?

That’s what Diego Cuadros, PhD, assistant professor of health geography and disease modeling at the University of Cincinnati, set out to learn using geospatial data combined with prevalence data to identify the most underserved areas in Sub-Saharan Africa (SSA) for HIV services.

Study findings, which were published Nov. 24 in PLOS Global Public Health, highlight that as many as 1.5 million people living with HIV (PLHIV) in SSA have more than an hour’s motorized travel time both ways to access care, while roughly 3 million must set aside, at minimum, 30 minutes. When the only mode of transportation is walking, as much as 95.3% of underserved areas are faced with at least 30 minutes travel time.

This is simply the tip of the overall problem, Dr. Cuadros told this news organization.

“We are able to estimate how many people [whose] quality of life is being affected by HIV because they are not on treatment and most probably, HIV incidence is high in those areas. But [it’s not as simple as just] increasing the number of health care facilities,” he said. “We need to find strategies to be able to cover this population.”

Dr. Cuadros also noted that the problem goes both ways. “It’s hard for them to move, and it’s [also] hard to reach them,” he explained.
 

Mapping care, or lack thereof

Dr. Cuadros and team used two primary sources of data to generate high-resolution maps of underserved SSA areas: estimated number of PLHIV between the ages of 15 and 49 years in 47 SSA countries paired with population density and global map of travel time to the nearest health facility by motorized and nonmotorized (that is, walking) transportation. Combining these data allowed them to then detail the distance from access to care for every 5 km².

The mapping exercise showed that 90.5% of the total territory, in which about 7 million PLHIV resided, had more than 10 minutes motorized travel time to the nearest health care facility, while 74.6% were within 30 minutes, and 58.9% were within 60 minutes. Increases in threshold travel times (from 10 to 60 minutes) corresponded directly to declines in the average proportion of underserved areas (from 80.9% to 42.6%). However, in certain countries like Sudan and Mauritania, 99.4% of the areas were underserved at the 10 minute threshold, while more than 90% were underserved at the 60 minute threshold.

Corresponding rates for nonmotorized access to health services were similar: 88.7% (~17.6 million) PLHIV had 10 minutes walking time to health care services, while 57.8% (~11.5 million) had at least 30 minutes, and 33.0% (~6.6 million), at least 60 minutes. Likewise, as threshold times increased from 10 to 60 minutes, the percentage of affected PLHIV declined (to roughly 50% in two-thirds of the countries). But more than 70% of PLHIV resided in underserved areas in countries like Equatorial Guinea, Eritrea, South Sudan, and Sudan.
 

Geographical allocation of health service facilities underscores treatment gaps

“We think that most PLHIV live in urban areas or close to urban areas, and most of the health care facilities in Africa are concentrated in those areas. But [roughly 8 million people with HIV] are living in rural areas, and for most, movement is very difficult,” explained Dr. Cuadros, meaning that the majority are not on treatment despite the high incidence of HIV.

Inarguably, the pandemic has interrupted HIV services and treatment substantially on the African continent, further challenging any efforts to translate these study findings into actionable strategies.

“We’ve known for quite a while that distance and travel times and travel expenses are known risks for nonadherence, for lack of access to diagnostics, for people at risk for exposure,” Chris Beyrer, MD, MPH, Desmond M. Tutu Professor of Public Health and Human Rights at the Johns Hopkins Bloomberg School of Public Health, Baltimore, said in an interview. (Dr. Beyrer was not involved in the study.)

“What’s new is the ability to really look at this across geographies and really home in on how many people face very long times and distances for travel. That’s a really important contribution,” he said.

Dr. Cuadros pointed out that these hard-to-reach populations are key to achieving the UNAID’s HIV elimination targets. “We’re going to have these pockets of transmission that are going to be really important for epidemic control,” he explained.

Toward that end, the onus appears to extend well beyond solutions that emphasize difficulty in reaching people from the provider perspective. “There’s quite a lot of what you might want to think of as blaming the victim for when people miss appointments, don’t appear to be adherent, [or] can’t stay reliably suppressed,” said Dr. Beyrer.

“It’s really important for providers in general to include in history and intake how far people have come, what their challenges are with travel, to really pay attention to those issues. Having this elegant analysis, this level of detail, is an important first step,” he added.

Dr. Cuadros has disclosed no relevant financial relationships. Dr. Beyrer reports a consulting agreement with Merck.

A version of this article first appeared on Medscape.com.

According to Iltefat H. Hamzavi, MD, the initial clinical assessment for hidradenitis suppurativa (HS) includes posing two questions to patients: Have you had outbreaks of boils during the past 6 months? Where and how many boils have you had?

If the answer to the first question is “yes” and the patient has had at least two boils in intertriginous areas, that person likely has HS, a disease of apocrine gland–bearing skin that occurs in 1%-4% of people, has a higher prevalence in Blacks, compared with Whites, and affects more women than men by a 3:1 ratio.

“Current treatments offer limited efficacy, and the disease is chronic and recurrent,” Dr. Hamzavi, of the department of dermatology at Henry Ford Health System, Detroit, said during MedscapeLive’s annual Las Vegas Dermatology Seminar. “You often see nodules, abscesses, fistulae, and scarring,” with all different skin types represented in the majority of patients.

Typical HS lesions appear as inflamed nodules, abscesses, draining fistulas, and scars as well as double-headed “tombstone” comedones, he said. These are typically located in the axilla, intermammary folds, in the groin, around the genitals, and on the buttocks. Atypical lesions can also occur – often folliculitis and open comedones in locations such as the waistline, the neck, and behind the ears.

The differential diagnosis is wide-ranging and includes bacterial abscess, inflamed cyst, folliculitis, pilonidal sinus, cellulitis, and cutaneous Crohn’s disease. Pain may appear out of proportion to the physical examination.

“There is a window of opportunity to treat HS, early in the disease process,” Dr. Hamzavi said. “There are no definitive cures for HS but lots of treatment options.”

According to clinical management guidelines published by the United States and Canadian Hidradenitis Suppurativa Foundations, options for moderate stage disease include antibiotics, antiandrogens, retinoids, immunosuppression/biologics, deroofing, and limited excision with primary closure. Options for severe disease include radical excision.

“HS requires a mix of medical and procedural treatments based on the number of nodules,” Dr. Hamzavi said. “Because the disease has so many different phases, there is no perfect outcome measure yet, but progress is being made.”

In 2018, an effort to develop a consensus core outcome set of domains regarding what to measure in clinical trials of HS was launched; it is known as the Hidradenitis Suppurativa Core Outcomes Set International Collaboration (HISTORIC). It was formed as a collaboration between the International Dermatology Outcome Measures (IDEOM) initiative, the Cochrane Skin Group – Core Outcome Set Initiative (CSG-COUSIN), and Zealand University Hospital, Roskilde.

HISTORIC is now part of the partnership with CSG-COUSIN and this work continues onward. Core domains as defined by the group include pain, physical signs, HS-specific quality of life, global assessment, and disease progression. “For now, we are mostly using some objective measures and some patient-reported outcomes with the addition of ultrasound in some centers,” Dr. Hamzavi said.

He underscored the importance of lifestyle modifications in patients with HS, including smoking cessation and weight loss, as well as decreasing pressure/friction on lesions, using warm compresses, and modifying diet. “This generally involves a low-inflammatory diet: Low carbohydrate, low dairy, and higher protein content, but there is much work needed to understand the role of diet in HS,” he said.

“This is a tough disease, but the compassion you offer these patients will be paid back to you a thousandfold. They tend to be some of the happiest and most appreciative patients you will ever have in your practice.”

Dr. Hamzavi disclosed that he has been a clinical investigator for Clinuvel, Incyte, Pfizer, Avita, and Ferndale Labs. He has also been a consultant for Pfizer, AbbVie, Novartis, and Aclaris, and has received a grant from Estee Lauder.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

According to Iltefat H. Hamzavi, MD, the initial clinical assessment for hidradenitis suppurativa (HS) includes posing two questions to patients: Have you had outbreaks of boils during the past 6 months? Where and how many boils have you had?

If the answer to the first question is “yes” and the patient has had at least two boils in intertriginous areas, that person likely has HS, a disease of apocrine gland–bearing skin that occurs in 1%-4% of people, has a higher prevalence in Blacks, compared with Whites, and affects more women than men by a 3:1 ratio.

“Current treatments offer limited efficacy, and the disease is chronic and recurrent,” Dr. Hamzavi, of the department of dermatology at Henry Ford Health System, Detroit, said during MedscapeLive’s annual Las Vegas Dermatology Seminar. “You often see nodules, abscesses, fistulae, and scarring,” with all different skin types represented in the majority of patients.

Typical HS lesions appear as inflamed nodules, abscesses, draining fistulas, and scars as well as double-headed “tombstone” comedones, he said. These are typically located in the axilla, intermammary folds, in the groin, around the genitals, and on the buttocks. Atypical lesions can also occur – often folliculitis and open comedones in locations such as the waistline, the neck, and behind the ears.

The differential diagnosis is wide-ranging and includes bacterial abscess, inflamed cyst, folliculitis, pilonidal sinus, cellulitis, and cutaneous Crohn’s disease. Pain may appear out of proportion to the physical examination.

“There is a window of opportunity to treat HS, early in the disease process,” Dr. Hamzavi said. “There are no definitive cures for HS but lots of treatment options.”

According to clinical management guidelines published by the United States and Canadian Hidradenitis Suppurativa Foundations, options for moderate stage disease include antibiotics, antiandrogens, retinoids, immunosuppression/biologics, deroofing, and limited excision with primary closure. Options for severe disease include radical excision.

“HS requires a mix of medical and procedural treatments based on the number of nodules,” Dr. Hamzavi said. “Because the disease has so many different phases, there is no perfect outcome measure yet, but progress is being made.”

In 2018, an effort to develop a consensus core outcome set of domains regarding what to measure in clinical trials of HS was launched; it is known as the Hidradenitis Suppurativa Core Outcomes Set International Collaboration (HISTORIC). It was formed as a collaboration between the International Dermatology Outcome Measures (IDEOM) initiative, the Cochrane Skin Group – Core Outcome Set Initiative (CSG-COUSIN), and Zealand University Hospital, Roskilde.

HISTORIC is now part of the partnership with CSG-COUSIN and this work continues onward. Core domains as defined by the group include pain, physical signs, HS-specific quality of life, global assessment, and disease progression. “For now, we are mostly using some objective measures and some patient-reported outcomes with the addition of ultrasound in some centers,” Dr. Hamzavi said.

He underscored the importance of lifestyle modifications in patients with HS, including smoking cessation and weight loss, as well as decreasing pressure/friction on lesions, using warm compresses, and modifying diet. “This generally involves a low-inflammatory diet: Low carbohydrate, low dairy, and higher protein content, but there is much work needed to understand the role of diet in HS,” he said.

“This is a tough disease, but the compassion you offer these patients will be paid back to you a thousandfold. They tend to be some of the happiest and most appreciative patients you will ever have in your practice.”

Dr. Hamzavi disclosed that he has been a clinical investigator for Clinuvel, Incyte, Pfizer, Avita, and Ferndale Labs. He has also been a consultant for Pfizer, AbbVie, Novartis, and Aclaris, and has received a grant from Estee Lauder.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

According to Iltefat H. Hamzavi, MD, the initial clinical assessment for hidradenitis suppurativa (HS) includes posing two questions to patients: Have you had outbreaks of boils during the past 6 months? Where and how many boils have you had?

If the answer to the first question is “yes” and the patient has had at least two boils in intertriginous areas, that person likely has HS, a disease of apocrine gland–bearing skin that occurs in 1%-4% of people, has a higher prevalence in Blacks, compared with Whites, and affects more women than men by a 3:1 ratio.

“Current treatments offer limited efficacy, and the disease is chronic and recurrent,” Dr. Hamzavi, of the department of dermatology at Henry Ford Health System, Detroit, said during MedscapeLive’s annual Las Vegas Dermatology Seminar. “You often see nodules, abscesses, fistulae, and scarring,” with all different skin types represented in the majority of patients.

Typical HS lesions appear as inflamed nodules, abscesses, draining fistulas, and scars as well as double-headed “tombstone” comedones, he said. These are typically located in the axilla, intermammary folds, in the groin, around the genitals, and on the buttocks. Atypical lesions can also occur – often folliculitis and open comedones in locations such as the waistline, the neck, and behind the ears.

The differential diagnosis is wide-ranging and includes bacterial abscess, inflamed cyst, folliculitis, pilonidal sinus, cellulitis, and cutaneous Crohn’s disease. Pain may appear out of proportion to the physical examination.

“There is a window of opportunity to treat HS, early in the disease process,” Dr. Hamzavi said. “There are no definitive cures for HS but lots of treatment options.”

According to clinical management guidelines published by the United States and Canadian Hidradenitis Suppurativa Foundations, options for moderate stage disease include antibiotics, antiandrogens, retinoids, immunosuppression/biologics, deroofing, and limited excision with primary closure. Options for severe disease include radical excision.

“HS requires a mix of medical and procedural treatments based on the number of nodules,” Dr. Hamzavi said. “Because the disease has so many different phases, there is no perfect outcome measure yet, but progress is being made.”

In 2018, an effort to develop a consensus core outcome set of domains regarding what to measure in clinical trials of HS was launched; it is known as the Hidradenitis Suppurativa Core Outcomes Set International Collaboration (HISTORIC). It was formed as a collaboration between the International Dermatology Outcome Measures (IDEOM) initiative, the Cochrane Skin Group – Core Outcome Set Initiative (CSG-COUSIN), and Zealand University Hospital, Roskilde.

HISTORIC is now part of the partnership with CSG-COUSIN and this work continues onward. Core domains as defined by the group include pain, physical signs, HS-specific quality of life, global assessment, and disease progression. “For now, we are mostly using some objective measures and some patient-reported outcomes with the addition of ultrasound in some centers,” Dr. Hamzavi said.

He underscored the importance of lifestyle modifications in patients with HS, including smoking cessation and weight loss, as well as decreasing pressure/friction on lesions, using warm compresses, and modifying diet. “This generally involves a low-inflammatory diet: Low carbohydrate, low dairy, and higher protein content, but there is much work needed to understand the role of diet in HS,” he said.

“This is a tough disease, but the compassion you offer these patients will be paid back to you a thousandfold. They tend to be some of the happiest and most appreciative patients you will ever have in your practice.”

Dr. Hamzavi disclosed that he has been a clinical investigator for Clinuvel, Incyte, Pfizer, Avita, and Ferndale Labs. He has also been a consultant for Pfizer, AbbVie, Novartis, and Aclaris, and has received a grant from Estee Lauder.

MedscapeLive and this news organization are owned by the same parent company.

[email protected]

In clinicians and patients alike, lithium triggers reactions ranging from apprehension and fear about adverse effects and toxicity to confusion over lithium’s usefulness compared with other mood stabilizers that do not require blood monitoring. Research from the 1950s to the 1970s demonstrated that lithium is effective for prophylaxis of mood episodes in patients with bipolar disorder and could reduce the frequency of hospitalization in patients who are depressed.¹ For years, lithium was commonly prescribed to treat bipolar disorder, but in recent years its use has fallen out of favor due to concerns about its risks, and the availability of newer medications. This article reviews lithium’s origins (Box^1-4), pharmacology, risks, and benefits, and makes a case for why it should remain a first-line therapy for bipolar disorder.

Box

How lithium works

Lithium has effects on neurotransmitters implicated in mania, such as glutamate, dopamine, and gamma-aminobutyric acid.⁵ Quiroz et al⁶ provide a detailed description of lithium’s effects, which can be summarized as modulating neuronal signaling pathways, including B-cell lymphoma 2 (BCL2), cAMP-response element binding protein (CREB), and glycogen synthase kinase-3 (GSK-3). Through these signaling cascades, lithium can curtail progression of neuronal apoptosis caused by the biochemical stress commonly seen in bipolar disorder pathogenesis.⁶  

A wide range of potential adverse effects

Lithium can cause adverse effects in several organ systems. Clinicians must be aware of these effects before prescribing lithium or continuing long-term use. The most commonly documented adverse effects and symptoms of toxicity are:

• tremor
• renal dysfunction, including renal insufficiency and polyuria or polydipsia
• hypothyroidism
• hyperparathyroidism (with subsequent hypercalcemia)
• weight gain
• gastrointestinal (GI) symptoms.

These symptoms tend to occur when lithium serum levels are outside the reference range of 0.6 to 1.2 mEq/L, typically once blood levels reach ≥1.5 mEq/L.⁷ However, thyroid and renal abnormalities can occur at levels below this value, and might be related to cumulative lithium exposure.⁷ Adverse effects usually are precipitated by inadequate water intake or inadvertently taking an extra dose. Symptoms of lithium toxicity can be mild, moderate (GI complaints, tremor, weakness, fatigue), or severe (agitation, seizures, autonomic dysregulation, confusion, coma, death).

Lithium adverse effects and toxicity are infrequent. An analysis of 17 years of data in Sweden showed the incidence of moderate to severe lithium intoxication (serum level ≥1.5 mEq/L) was .01 patients per year.⁸ A recently published US analysis found the prevalence rate of lithium toxicity was 2.2%.⁹ Results from both groups show that drug interactions were an important cause of increased lithium levels, and specifically that initiating a medication that could interact with lithium was associated with 30-fold higher risk of needing acute care for lithium toxicity.⁹ Possible drug interactions include nonsteroidal anti-inflammatory drugs, diuretics, and renin-angiotensin-aldosterone system inhibitors.⁹ Because lithium is eliminated exclusively by the kidneys, impaired or altered renal function can increase the risk of lithium retention, leading to intoxication. Other risk factors include older age, alteration of water-salt homeostasis (fever, diarrhea, vomiting), higher number of treated chronic diseases as measured by Chronic Disease Score (range: 0 to 35; higher scores denotes higher number of treated chronic diseases and increased hospitalization risk), and higher total daily lithium dosage.⁹

Presentation of lithium intoxication often is mild or nonspecific, and physicians should have a low threshold for checking lithium blood levels.⁸ Lithium intoxication can be safely managed with volume expansion, forced diuresis, and hemodialysis.

Continue to: Lithium use during pregnancy...

Lithium use during pregnancy

When considering lithium for a woman who is pregnant, it is important to weigh the potential teratogenic risks against the benefit of successful management of the mood disorder. Ebstein’s anomaly (abnormal tricuspid valve leaflets) is the most well-known teratogenic risk associated with lithium, with an estimated absolute risk of 1 in 1,000 in patients treated with lithium compared with 1 in 20,000 in controls.^10,11 The risk of congenital anomalies is increased in infants exposed to lithium in utero (4% to 12% vs 2% to 4% in controls)¹²; exposure during the first trimester of pregnancy is associated with increased risk. Lithium levels must be adjusted during pregnancy. Pregnant patients are at higher risk of relapse to mania because renal lithium clearance increases by 30% to 50% during pregnancy, and normalizes shortly after delivery.¹³

Lithium exposure during pregnancy has been linked to increased risk of miscarriage and preterm delivery; however, more research is needed to define the true risk of noncardiac teratogenicity associated with lithium.¹¹ Because there is a lack of definitive data regarding teratogenicity, and because of lithium’s well-documented effectiveness in mood disorders, lithium should be considered a first-line therapy for pregnant patients with bipolar disorder.¹⁰

Prescribing trends

Despite data showing the efficacy and benefits of lithium, there has been a paradoxical decrease in lithium prescribing. This is the result of multiple factors, including fear of adverse effects and lithium toxicity and a shift toward newer medications, such as anticonvulsants and antipsychotics, for treatment and prophylaxis of mania.

A 2011 study examined prescribing trends for bipolar disorder in the United Kingdom.¹⁴ Overall, it found increased usage of valproate, carbamazepine, and lamotrigine from 1995 to 2009. During that time, lithium prescribing mostly remained steady at approximately 30%, whereas valproate use increased from 0% to 22.7%. Overall, antipsychotic and valproate prescribing increased relative to lithium.¹⁴ A literature review¹⁵ analyzed 6 studies of lithium prescribing trends from 1950 to 2010. Four of these studies (2 in the United States, 1 in Canada, and 1 in German-Swiss-Austrian hospitals) found lithium use was declining. The increased use found in Italy and Spain was attributed to multiple factors, including a broader definition of bipolar disorders and the unavailability of valproate in Spain, lithium’s low cost, and mental health reforms in both countries that resulted in overall increased psychotropic prescribing. Decreased lithium use was attributed to increased use of valproate and second-generation antipsychotics, lack of clinician training in lithium therapy, and aggressive marketing of brand-name medications.¹⁵
 

Reduced suicides, possible protection against dementia

A 2013 meta-analysis of 48 randomized controlled trials (RCTs) that included a total of 6,674 patients with mood disorders indicated that compared with placebo, lithium was more effective in reducing suicides and deaths from any cause.¹⁶

Large retrospective studies have demonstrated that compared with valproate, lithium has superior anti-suicide properties.¹⁷ Researchers found that risk of suicide attempt or completion was 1.5 to 3 times higher during periods of valproate treatment compared with lithium.¹⁸ Both short- and long-term lithium use was associated with decreased non-suicide mortality compared with valproate.¹⁹ In Denmark, compared with valproate, lithium was associated with fewer psychiatric hospital admissions.¹⁹ One RCT, the BALANCE trial, showed that lithium (alone or in combination with valproate) is more likely to prevent relapse in persons with bipolar I disorder than valproate monotherapy.²⁰

Recent research in Denmark suggests that long-term doses of naturally occurring lithium in drinking water might confer some level of protection against dementia.²¹ Researchers examined the Danish National Patient Register to determine where participants lived and their local water supply. Drinking water lithium levels were assessed, and the mean lithium level for each municipality was calculated. This case-control study selected patients with dementia and 10 age- and sex-matched controls.²¹

Researchers found that the incidence rate ratio of Alzheimer disease, vascular dementia, and dementia overall was significantly lower among individuals whose drinking water contained lithium, 15.1 to 27.0 µg/L, compared with those whose water had lithium levels 2.0 to 5.0 µg/L.²¹ Although this study does not prove causality, it opens the door for continued research on lithium as a neuroprotective agent involved in pathways beyond mood stabilization.

Why should you prescribe lithium?

Lithium, which is available in several formulations (Table), should continue to be first-line pharmacotherapy for treating acute mood episodes, prophylaxis, and suicide prevention in bipolar disorder. Although there are many effective medications for treating bipolar disorder—such as second-generation antipsychotics that are available as a long-acting injectable formulation or can be combined with a mood stabilizer—lithium is a thoroughly researched medication with a long history of effectiveness for managing bipolar disorder. As is the case with all psychotropic medications, lithium has adverse effects and necessary precautions, but these are outweighed by its neuroprotective benefits and efficacy. Research has demonstrated that lithium outperforms medications that have largely replaced it, specifically valproate.

Related Resources

• Ali ZA, El-Mallakh RS. Lithium and kidney disease: Understand the risks. Current Psychiatry. 2021;20(6):34- 38,50. doi:10.12788/cp.0130
• Malhi GS, Gessler D, Outhred T. The use of lithium for the treatment of bipolar disorder: recommendations from clinical practice guidelines. J Affect Disord. 2017;217: 266-280. doi:10.1016/j.jad.2017.03.052

Drug Brand Names

Carbamazepine • Tegretol

Lamotrigine • Lamictal

Lithium • Eskalith, Lithobid

Valproate • Depacon, Depakote, Depakene

Bottom Line

Lithium is a well-researched first-line pharmacotherapy for bipolar disorder, with efficacy equivalent to—or superior to—newer pharmacotherapies such as valproate and second-generation antipsychotics. When prescribing lithium, carefully monitor patients for symptoms of adverse effects or toxicity. Despite teratogenic risks, lithium can be considered for pregnant patients with bipolar disorder.

In clinicians and patients alike, lithium triggers reactions ranging from apprehension and fear about adverse effects and toxicity to confusion over lithium’s usefulness compared with other mood stabilizers that do not require blood monitoring. Research from the 1950s to the 1970s demonstrated that lithium is effective for prophylaxis of mood episodes in patients with bipolar disorder and could reduce the frequency of hospitalization in patients who are depressed.¹ For years, lithium was commonly prescribed to treat bipolar disorder, but in recent years its use has fallen out of favor due to concerns about its risks, and the availability of newer medications. This article reviews lithium’s origins (Box^1-4), pharmacology, risks, and benefits, and makes a case for why it should remain a first-line therapy for bipolar disorder.

Box

How lithium works

Lithium has effects on neurotransmitters implicated in mania, such as glutamate, dopamine, and gamma-aminobutyric acid.⁵ Quiroz et al⁶ provide a detailed description of lithium’s effects, which can be summarized as modulating neuronal signaling pathways, including B-cell lymphoma 2 (BCL2), cAMP-response element binding protein (CREB), and glycogen synthase kinase-3 (GSK-3). Through these signaling cascades, lithium can curtail progression of neuronal apoptosis caused by the biochemical stress commonly seen in bipolar disorder pathogenesis.⁶  

A wide range of potential adverse effects

Lithium can cause adverse effects in several organ systems. Clinicians must be aware of these effects before prescribing lithium or continuing long-term use. The most commonly documented adverse effects and symptoms of toxicity are:

• tremor
• renal dysfunction, including renal insufficiency and polyuria or polydipsia
• hypothyroidism
• hyperparathyroidism (with subsequent hypercalcemia)
• weight gain
• gastrointestinal (GI) symptoms.

These symptoms tend to occur when lithium serum levels are outside the reference range of 0.6 to 1.2 mEq/L, typically once blood levels reach ≥1.5 mEq/L.⁷ However, thyroid and renal abnormalities can occur at levels below this value, and might be related to cumulative lithium exposure.⁷ Adverse effects usually are precipitated by inadequate water intake or inadvertently taking an extra dose. Symptoms of lithium toxicity can be mild, moderate (GI complaints, tremor, weakness, fatigue), or severe (agitation, seizures, autonomic dysregulation, confusion, coma, death).

Lithium adverse effects and toxicity are infrequent. An analysis of 17 years of data in Sweden showed the incidence of moderate to severe lithium intoxication (serum level ≥1.5 mEq/L) was .01 patients per year.⁸ A recently published US analysis found the prevalence rate of lithium toxicity was 2.2%.⁹ Results from both groups show that drug interactions were an important cause of increased lithium levels, and specifically that initiating a medication that could interact with lithium was associated with 30-fold higher risk of needing acute care for lithium toxicity.⁹ Possible drug interactions include nonsteroidal anti-inflammatory drugs, diuretics, and renin-angiotensin-aldosterone system inhibitors.⁹ Because lithium is eliminated exclusively by the kidneys, impaired or altered renal function can increase the risk of lithium retention, leading to intoxication. Other risk factors include older age, alteration of water-salt homeostasis (fever, diarrhea, vomiting), higher number of treated chronic diseases as measured by Chronic Disease Score (range: 0 to 35; higher scores denotes higher number of treated chronic diseases and increased hospitalization risk), and higher total daily lithium dosage.⁹

Presentation of lithium intoxication often is mild or nonspecific, and physicians should have a low threshold for checking lithium blood levels.⁸ Lithium intoxication can be safely managed with volume expansion, forced diuresis, and hemodialysis.

Continue to: Lithium use during pregnancy...

Lithium use during pregnancy

When considering lithium for a woman who is pregnant, it is important to weigh the potential teratogenic risks against the benefit of successful management of the mood disorder. Ebstein’s anomaly (abnormal tricuspid valve leaflets) is the most well-known teratogenic risk associated with lithium, with an estimated absolute risk of 1 in 1,000 in patients treated with lithium compared with 1 in 20,000 in controls.^10,11 The risk of congenital anomalies is increased in infants exposed to lithium in utero (4% to 12% vs 2% to 4% in controls)¹²; exposure during the first trimester of pregnancy is associated with increased risk. Lithium levels must be adjusted during pregnancy. Pregnant patients are at higher risk of relapse to mania because renal lithium clearance increases by 30% to 50% during pregnancy, and normalizes shortly after delivery.¹³

Lithium exposure during pregnancy has been linked to increased risk of miscarriage and preterm delivery; however, more research is needed to define the true risk of noncardiac teratogenicity associated with lithium.¹¹ Because there is a lack of definitive data regarding teratogenicity, and because of lithium’s well-documented effectiveness in mood disorders, lithium should be considered a first-line therapy for pregnant patients with bipolar disorder.¹⁰

Prescribing trends

Despite data showing the efficacy and benefits of lithium, there has been a paradoxical decrease in lithium prescribing. This is the result of multiple factors, including fear of adverse effects and lithium toxicity and a shift toward newer medications, such as anticonvulsants and antipsychotics, for treatment and prophylaxis of mania.

A 2011 study examined prescribing trends for bipolar disorder in the United Kingdom.¹⁴ Overall, it found increased usage of valproate, carbamazepine, and lamotrigine from 1995 to 2009. During that time, lithium prescribing mostly remained steady at approximately 30%, whereas valproate use increased from 0% to 22.7%. Overall, antipsychotic and valproate prescribing increased relative to lithium.¹⁴ A literature review¹⁵ analyzed 6 studies of lithium prescribing trends from 1950 to 2010. Four of these studies (2 in the United States, 1 in Canada, and 1 in German-Swiss-Austrian hospitals) found lithium use was declining. The increased use found in Italy and Spain was attributed to multiple factors, including a broader definition of bipolar disorders and the unavailability of valproate in Spain, lithium’s low cost, and mental health reforms in both countries that resulted in overall increased psychotropic prescribing. Decreased lithium use was attributed to increased use of valproate and second-generation antipsychotics, lack of clinician training in lithium therapy, and aggressive marketing of brand-name medications.¹⁵
 

Reduced suicides, possible protection against dementia

A 2013 meta-analysis of 48 randomized controlled trials (RCTs) that included a total of 6,674 patients with mood disorders indicated that compared with placebo, lithium was more effective in reducing suicides and deaths from any cause.¹⁶

Large retrospective studies have demonstrated that compared with valproate, lithium has superior anti-suicide properties.¹⁷ Researchers found that risk of suicide attempt or completion was 1.5 to 3 times higher during periods of valproate treatment compared with lithium.¹⁸ Both short- and long-term lithium use was associated with decreased non-suicide mortality compared with valproate.¹⁹ In Denmark, compared with valproate, lithium was associated with fewer psychiatric hospital admissions.¹⁹ One RCT, the BALANCE trial, showed that lithium (alone or in combination with valproate) is more likely to prevent relapse in persons with bipolar I disorder than valproate monotherapy.²⁰

Recent research in Denmark suggests that long-term doses of naturally occurring lithium in drinking water might confer some level of protection against dementia.²¹ Researchers examined the Danish National Patient Register to determine where participants lived and their local water supply. Drinking water lithium levels were assessed, and the mean lithium level for each municipality was calculated. This case-control study selected patients with dementia and 10 age- and sex-matched controls.²¹

Researchers found that the incidence rate ratio of Alzheimer disease, vascular dementia, and dementia overall was significantly lower among individuals whose drinking water contained lithium, 15.1 to 27.0 µg/L, compared with those whose water had lithium levels 2.0 to 5.0 µg/L.²¹ Although this study does not prove causality, it opens the door for continued research on lithium as a neuroprotective agent involved in pathways beyond mood stabilization.

Why should you prescribe lithium?

Lithium, which is available in several formulations (Table), should continue to be first-line pharmacotherapy for treating acute mood episodes, prophylaxis, and suicide prevention in bipolar disorder. Although there are many effective medications for treating bipolar disorder—such as second-generation antipsychotics that are available as a long-acting injectable formulation or can be combined with a mood stabilizer—lithium is a thoroughly researched medication with a long history of effectiveness for managing bipolar disorder. As is the case with all psychotropic medications, lithium has adverse effects and necessary precautions, but these are outweighed by its neuroprotective benefits and efficacy. Research has demonstrated that lithium outperforms medications that have largely replaced it, specifically valproate.

Related Resources

• Ali ZA, El-Mallakh RS. Lithium and kidney disease: Understand the risks. Current Psychiatry. 2021;20(6):34- 38,50. doi:10.12788/cp.0130
• Malhi GS, Gessler D, Outhred T. The use of lithium for the treatment of bipolar disorder: recommendations from clinical practice guidelines. J Affect Disord. 2017;217: 266-280. doi:10.1016/j.jad.2017.03.052

Drug Brand Names

Carbamazepine • Tegretol

Lamotrigine • Lamictal

Lithium • Eskalith, Lithobid

Valproate • Depacon, Depakote, Depakene

Bottom Line

Lithium is a well-researched first-line pharmacotherapy for bipolar disorder, with efficacy equivalent to—or superior to—newer pharmacotherapies such as valproate and second-generation antipsychotics. When prescribing lithium, carefully monitor patients for symptoms of adverse effects or toxicity. Despite teratogenic risks, lithium can be considered for pregnant patients with bipolar disorder.

In clinicians and patients alike, lithium triggers reactions ranging from apprehension and fear about adverse effects and toxicity to confusion over lithium’s usefulness compared with other mood stabilizers that do not require blood monitoring. Research from the 1950s to the 1970s demonstrated that lithium is effective for prophylaxis of mood episodes in patients with bipolar disorder and could reduce the frequency of hospitalization in patients who are depressed.¹ For years, lithium was commonly prescribed to treat bipolar disorder, but in recent years its use has fallen out of favor due to concerns about its risks, and the availability of newer medications. This article reviews lithium’s origins (Box^1-4), pharmacology, risks, and benefits, and makes a case for why it should remain a first-line therapy for bipolar disorder.

Box

How lithium works

Lithium has effects on neurotransmitters implicated in mania, such as glutamate, dopamine, and gamma-aminobutyric acid.⁵ Quiroz et al⁶ provide a detailed description of lithium’s effects, which can be summarized as modulating neuronal signaling pathways, including B-cell lymphoma 2 (BCL2), cAMP-response element binding protein (CREB), and glycogen synthase kinase-3 (GSK-3). Through these signaling cascades, lithium can curtail progression of neuronal apoptosis caused by the biochemical stress commonly seen in bipolar disorder pathogenesis.⁶  

A wide range of potential adverse effects

Lithium can cause adverse effects in several organ systems. Clinicians must be aware of these effects before prescribing lithium or continuing long-term use. The most commonly documented adverse effects and symptoms of toxicity are:

• tremor
• renal dysfunction, including renal insufficiency and polyuria or polydipsia
• hypothyroidism
• hyperparathyroidism (with subsequent hypercalcemia)
• weight gain
• gastrointestinal (GI) symptoms.

These symptoms tend to occur when lithium serum levels are outside the reference range of 0.6 to 1.2 mEq/L, typically once blood levels reach ≥1.5 mEq/L.⁷ However, thyroid and renal abnormalities can occur at levels below this value, and might be related to cumulative lithium exposure.⁷ Adverse effects usually are precipitated by inadequate water intake or inadvertently taking an extra dose. Symptoms of lithium toxicity can be mild, moderate (GI complaints, tremor, weakness, fatigue), or severe (agitation, seizures, autonomic dysregulation, confusion, coma, death).

Lithium adverse effects and toxicity are infrequent. An analysis of 17 years of data in Sweden showed the incidence of moderate to severe lithium intoxication (serum level ≥1.5 mEq/L) was .01 patients per year.⁸ A recently published US analysis found the prevalence rate of lithium toxicity was 2.2%.⁹ Results from both groups show that drug interactions were an important cause of increased lithium levels, and specifically that initiating a medication that could interact with lithium was associated with 30-fold higher risk of needing acute care for lithium toxicity.⁹ Possible drug interactions include nonsteroidal anti-inflammatory drugs, diuretics, and renin-angiotensin-aldosterone system inhibitors.⁹ Because lithium is eliminated exclusively by the kidneys, impaired or altered renal function can increase the risk of lithium retention, leading to intoxication. Other risk factors include older age, alteration of water-salt homeostasis (fever, diarrhea, vomiting), higher number of treated chronic diseases as measured by Chronic Disease Score (range: 0 to 35; higher scores denotes higher number of treated chronic diseases and increased hospitalization risk), and higher total daily lithium dosage.⁹

Presentation of lithium intoxication often is mild or nonspecific, and physicians should have a low threshold for checking lithium blood levels.⁸ Lithium intoxication can be safely managed with volume expansion, forced diuresis, and hemodialysis.

Continue to: Lithium use during pregnancy...

Lithium use during pregnancy

When considering lithium for a woman who is pregnant, it is important to weigh the potential teratogenic risks against the benefit of successful management of the mood disorder. Ebstein’s anomaly (abnormal tricuspid valve leaflets) is the most well-known teratogenic risk associated with lithium, with an estimated absolute risk of 1 in 1,000 in patients treated with lithium compared with 1 in 20,000 in controls.^10,11 The risk of congenital anomalies is increased in infants exposed to lithium in utero (4% to 12% vs 2% to 4% in controls)¹²; exposure during the first trimester of pregnancy is associated with increased risk. Lithium levels must be adjusted during pregnancy. Pregnant patients are at higher risk of relapse to mania because renal lithium clearance increases by 30% to 50% during pregnancy, and normalizes shortly after delivery.¹³

Lithium exposure during pregnancy has been linked to increased risk of miscarriage and preterm delivery; however, more research is needed to define the true risk of noncardiac teratogenicity associated with lithium.¹¹ Because there is a lack of definitive data regarding teratogenicity, and because of lithium’s well-documented effectiveness in mood disorders, lithium should be considered a first-line therapy for pregnant patients with bipolar disorder.¹⁰

Prescribing trends

Despite data showing the efficacy and benefits of lithium, there has been a paradoxical decrease in lithium prescribing. This is the result of multiple factors, including fear of adverse effects and lithium toxicity and a shift toward newer medications, such as anticonvulsants and antipsychotics, for treatment and prophylaxis of mania.

A 2011 study examined prescribing trends for bipolar disorder in the United Kingdom.¹⁴ Overall, it found increased usage of valproate, carbamazepine, and lamotrigine from 1995 to 2009. During that time, lithium prescribing mostly remained steady at approximately 30%, whereas valproate use increased from 0% to 22.7%. Overall, antipsychotic and valproate prescribing increased relative to lithium.¹⁴ A literature review¹⁵ analyzed 6 studies of lithium prescribing trends from 1950 to 2010. Four of these studies (2 in the United States, 1 in Canada, and 1 in German-Swiss-Austrian hospitals) found lithium use was declining. The increased use found in Italy and Spain was attributed to multiple factors, including a broader definition of bipolar disorders and the unavailability of valproate in Spain, lithium’s low cost, and mental health reforms in both countries that resulted in overall increased psychotropic prescribing. Decreased lithium use was attributed to increased use of valproate and second-generation antipsychotics, lack of clinician training in lithium therapy, and aggressive marketing of brand-name medications.¹⁵
 

Reduced suicides, possible protection against dementia

A 2013 meta-analysis of 48 randomized controlled trials (RCTs) that included a total of 6,674 patients with mood disorders indicated that compared with placebo, lithium was more effective in reducing suicides and deaths from any cause.¹⁶

Large retrospective studies have demonstrated that compared with valproate, lithium has superior anti-suicide properties.¹⁷ Researchers found that risk of suicide attempt or completion was 1.5 to 3 times higher during periods of valproate treatment compared with lithium.¹⁸ Both short- and long-term lithium use was associated with decreased non-suicide mortality compared with valproate.¹⁹ In Denmark, compared with valproate, lithium was associated with fewer psychiatric hospital admissions.¹⁹ One RCT, the BALANCE trial, showed that lithium (alone or in combination with valproate) is more likely to prevent relapse in persons with bipolar I disorder than valproate monotherapy.²⁰

Recent research in Denmark suggests that long-term doses of naturally occurring lithium in drinking water might confer some level of protection against dementia.²¹ Researchers examined the Danish National Patient Register to determine where participants lived and their local water supply. Drinking water lithium levels were assessed, and the mean lithium level for each municipality was calculated. This case-control study selected patients with dementia and 10 age- and sex-matched controls.²¹

Researchers found that the incidence rate ratio of Alzheimer disease, vascular dementia, and dementia overall was significantly lower among individuals whose drinking water contained lithium, 15.1 to 27.0 µg/L, compared with those whose water had lithium levels 2.0 to 5.0 µg/L.²¹ Although this study does not prove causality, it opens the door for continued research on lithium as a neuroprotective agent involved in pathways beyond mood stabilization.

Why should you prescribe lithium?

Lithium, which is available in several formulations (Table), should continue to be first-line pharmacotherapy for treating acute mood episodes, prophylaxis, and suicide prevention in bipolar disorder. Although there are many effective medications for treating bipolar disorder—such as second-generation antipsychotics that are available as a long-acting injectable formulation or can be combined with a mood stabilizer—lithium is a thoroughly researched medication with a long history of effectiveness for managing bipolar disorder. As is the case with all psychotropic medications, lithium has adverse effects and necessary precautions, but these are outweighed by its neuroprotective benefits and efficacy. Research has demonstrated that lithium outperforms medications that have largely replaced it, specifically valproate.

Related Resources

• Ali ZA, El-Mallakh RS. Lithium and kidney disease: Understand the risks. Current Psychiatry. 2021;20(6):34- 38,50. doi:10.12788/cp.0130
• Malhi GS, Gessler D, Outhred T. The use of lithium for the treatment of bipolar disorder: recommendations from clinical practice guidelines. J Affect Disord. 2017;217: 266-280. doi:10.1016/j.jad.2017.03.052

Drug Brand Names

Carbamazepine • Tegretol

Lamotrigine • Lamictal

Lithium • Eskalith, Lithobid

Valproate • Depacon, Depakote, Depakene

Bottom Line

Lithium is a well-researched first-line pharmacotherapy for bipolar disorder, with efficacy equivalent to—or superior to—newer pharmacotherapies such as valproate and second-generation antipsychotics. When prescribing lithium, carefully monitor patients for symptoms of adverse effects or toxicity. Despite teratogenic risks, lithium can be considered for pregnant patients with bipolar disorder.

The patient has probably transitioned to the secondary progressive form of multiple sclerosis (MS). Four phenotypes have been identified in MS, with relapsing-remitting MS (RRMS) representing the most common and secondary progressive MS (SPMS) the second most common. RRMS is thought to begin as an inflammatory disease that over time becomes primarily neurodegenerative. The course of RRMS is marked by episodes of neurologic deficit followed by periods of remission which may be asymptomatic. When symptoms do not resolve — becoming fixed without remission — this is a sign of progression to SPMS. One in two RRMS patients will develop SPMS within 15 years of their diagnosis, leading to a progressive decrease of neurologic function and limitation of daily activities. Risk factors for developing SPMS include older age at onset of RRMS, longer duration of RRMS, and more cortical inflammatory lesions at baseline.

RRMS is diagnosed through clinical findings and laboratory results, the main approaches being MRI of the brain and spinal cord, and examination of cerebrospinal fluid. Neurologic symptoms must be consistent with those typically seen in MS, with deficit lasting for days to weeks. MRI is useful in monitoring disease progression (ie, new lesions that develop during relapses in RRMS). There are no universally accepted diagnostic criteria for SPMS, however. A patient usually can be diagnosed upon meeting these criteria: The patient was previously diagnosed with RRMS; the patient's symptoms are gradually worsening; this worsening is not tied to a relapse; and this worsening has been observed for 6 months or longer. Of note, SPMS' symptom-worsening characteristics can be subtle and difficult for patients to detect, and delays in diagnosis of up to several years are common.

Recognizing the onset of transition to SPMS is critical, as early initiation of therapy is thought to slow disease progression, the primary goal of treatment. In patients with SPMS, adhering to a holistic health program and managing comorbidities, especially vascular risk factors, can help preserve the health and functions of both the central nervous system and brain. Patients with SPMS who experience relapses or demonstrate new lesion formation as captured on MRI are thought to have active SPMS (aSPMS) and generally benefit from disease-modifying therapy (DMT). There is generally a transition period of about 5 years during which SPMS patients will still have a relapsing form of the disease, meaning that DMTs have proven to be effective in managing progressive MS should theoretically be beneficial for SPMS during this period. There are FDA-approved treatments for aSPMS, but off-label use is acceptable of those medications indicated for relapsing MS in those patients with evidence of relapses or new MRI activity.

Krupa Pandey, MD, Director, Multiple Sclerosis Center, Department of Neurology & Neuroscience Institute, Hackensack University Medical Center; Neurologist, Department of Neurology, Hackensack Meridian Health, Hackensack, NJ

Krupa Pandey, MD, has serve(d) as a speaker or a member of a speakers bureau for: Bristol-Myers Squibb; Biogen; Alexion; Genentech; Sanofi-Genzyme

The patient has probably transitioned to the secondary progressive form of multiple sclerosis (MS). Four phenotypes have been identified in MS, with relapsing-remitting MS (RRMS) representing the most common and secondary progressive MS (SPMS) the second most common. RRMS is thought to begin as an inflammatory disease that over time becomes primarily neurodegenerative. The course of RRMS is marked by episodes of neurologic deficit followed by periods of remission which may be asymptomatic. When symptoms do not resolve — becoming fixed without remission — this is a sign of progression to SPMS. One in two RRMS patients will develop SPMS within 15 years of their diagnosis, leading to a progressive decrease of neurologic function and limitation of daily activities. Risk factors for developing SPMS include older age at onset of RRMS, longer duration of RRMS, and more cortical inflammatory lesions at baseline.

RRMS is diagnosed through clinical findings and laboratory results, the main approaches being MRI of the brain and spinal cord, and examination of cerebrospinal fluid. Neurologic symptoms must be consistent with those typically seen in MS, with deficit lasting for days to weeks. MRI is useful in monitoring disease progression (ie, new lesions that develop during relapses in RRMS). There are no universally accepted diagnostic criteria for SPMS, however. A patient usually can be diagnosed upon meeting these criteria: The patient was previously diagnosed with RRMS; the patient's symptoms are gradually worsening; this worsening is not tied to a relapse; and this worsening has been observed for 6 months or longer. Of note, SPMS' symptom-worsening characteristics can be subtle and difficult for patients to detect, and delays in diagnosis of up to several years are common.

Recognizing the onset of transition to SPMS is critical, as early initiation of therapy is thought to slow disease progression, the primary goal of treatment. In patients with SPMS, adhering to a holistic health program and managing comorbidities, especially vascular risk factors, can help preserve the health and functions of both the central nervous system and brain. Patients with SPMS who experience relapses or demonstrate new lesion formation as captured on MRI are thought to have active SPMS (aSPMS) and generally benefit from disease-modifying therapy (DMT). There is generally a transition period of about 5 years during which SPMS patients will still have a relapsing form of the disease, meaning that DMTs have proven to be effective in managing progressive MS should theoretically be beneficial for SPMS during this period. There are FDA-approved treatments for aSPMS, but off-label use is acceptable of those medications indicated for relapsing MS in those patients with evidence of relapses or new MRI activity.

Krupa Pandey, MD, Director, Multiple Sclerosis Center, Department of Neurology & Neuroscience Institute, Hackensack University Medical Center; Neurologist, Department of Neurology, Hackensack Meridian Health, Hackensack, NJ

Krupa Pandey, MD, has serve(d) as a speaker or a member of a speakers bureau for: Bristol-Myers Squibb; Biogen; Alexion; Genentech; Sanofi-Genzyme

The patient has probably transitioned to the secondary progressive form of multiple sclerosis (MS). Four phenotypes have been identified in MS, with relapsing-remitting MS (RRMS) representing the most common and secondary progressive MS (SPMS) the second most common. RRMS is thought to begin as an inflammatory disease that over time becomes primarily neurodegenerative. The course of RRMS is marked by episodes of neurologic deficit followed by periods of remission which may be asymptomatic. When symptoms do not resolve — becoming fixed without remission — this is a sign of progression to SPMS. One in two RRMS patients will develop SPMS within 15 years of their diagnosis, leading to a progressive decrease of neurologic function and limitation of daily activities. Risk factors for developing SPMS include older age at onset of RRMS, longer duration of RRMS, and more cortical inflammatory lesions at baseline.

RRMS is diagnosed through clinical findings and laboratory results, the main approaches being MRI of the brain and spinal cord, and examination of cerebrospinal fluid. Neurologic symptoms must be consistent with those typically seen in MS, with deficit lasting for days to weeks. MRI is useful in monitoring disease progression (ie, new lesions that develop during relapses in RRMS). There are no universally accepted diagnostic criteria for SPMS, however. A patient usually can be diagnosed upon meeting these criteria: The patient was previously diagnosed with RRMS; the patient's symptoms are gradually worsening; this worsening is not tied to a relapse; and this worsening has been observed for 6 months or longer. Of note, SPMS' symptom-worsening characteristics can be subtle and difficult for patients to detect, and delays in diagnosis of up to several years are common.

Recognizing the onset of transition to SPMS is critical, as early initiation of therapy is thought to slow disease progression, the primary goal of treatment. In patients with SPMS, adhering to a holistic health program and managing comorbidities, especially vascular risk factors, can help preserve the health and functions of both the central nervous system and brain. Patients with SPMS who experience relapses or demonstrate new lesion formation as captured on MRI are thought to have active SPMS (aSPMS) and generally benefit from disease-modifying therapy (DMT). There is generally a transition period of about 5 years during which SPMS patients will still have a relapsing form of the disease, meaning that DMTs have proven to be effective in managing progressive MS should theoretically be beneficial for SPMS during this period. There are FDA-approved treatments for aSPMS, but off-label use is acceptable of those medications indicated for relapsing MS in those patients with evidence of relapses or new MRI activity.

Krupa Pandey, MD, Director, Multiple Sclerosis Center, Department of Neurology & Neuroscience Institute, Hackensack University Medical Center; Neurologist, Department of Neurology, Hackensack Meridian Health, Hackensack, NJ

Krupa Pandey, MD, has serve(d) as a speaker or a member of a speakers bureau for: Bristol-Myers Squibb; Biogen; Alexion; Genentech; Sanofi-Genzyme

CASE A long history of suicidality

Mr. X, age 26, who has a history of bipolar II disorder and multiple inpatient admissions, presents to a state hospital after a suicide attempt by gunshot. He reports that throughout his lifetime, he has had >20 suicide attempts, often by overdose.

Mr. X is admitted to the hospital under a temporary detention order. He is initially adherent and cooperative with his psychiatric evaluations.

HISTORY Chronic physical and emotional pain

Mr. X is single, unemployed, and lives with his mother and nephew. He was diagnosed with bipolar II disorder during adolescence and receives sertraline, 50 mg twice a day, and lamotrigine, 100 mg twice a day, to which he reports adherence. He also was taking clonazepam and zolpidem, dosages unknown.

His medical history is significant for severe childhood liver disease and inflammatory bowel disease. He dropped out of school during high school due to his multiple medical conditions, which resulted in a significantly diminished overall childhood experience, interrupted developmental trajectory, and chronic physical and emotional pain. He has never been employed and receives financial support through disability benefits. He spends his days on the internet or watching television. He reports daily cigarette and marijuana use and occasional alcohol use, but no other substance use. His mother helps manage his medical conditions and is his main support. His biological father was abusive towards his mother and absent for most of Mr. X’s life. Beyond his mother and therapist, Mr. X has minimal other interpersonal interactions, and reports feeling isolated, lonely, and frustrated.

EVALUATION Agitated and aggressive while hospitalized

Upon learning that he is being involuntarily committed, Mr. X becomes physically aggressive, makes verbal threats, and throws objects across his room. He is given diphenhydramine, 50 mg, haloperidol, 5 mg, and lorazepam, 2 mg, all of which are ordered on an as-needed basis. Mr. X is placed in an emergency restraint chair and put in seclusion. The episode resolves within an hour with reassurance and attention from the treatment team; the rapid escalation from and return to a calmer state is indicative of situational, stress-induced mood lability and impulsivity. Mr. X is counseled on maintaining safety and appropriate behavior, and is advised to ask for medication if he feels agitated or unable to control his behaviors. To maintain safe and appropriate behavior, he requires daily counseling and expectation management regarding his treatment timeline. No further aggressive incidents are noted throughout his hospitalization, and he requires only minimal use of the as-needed medications.

[polldaddy:10983392]

The authors’ observations

The least appropriate therapy for Mr. X would be exposure and response prevention, which allows patients to face their fears without the need to soothe or relieve related feelings with a compulsive act. It is designed to improve specific behavioral deficits most often associated with obsessive-compulsive disorder, a diagnosis inconsistent with Mr. X’s history and presentation. Trauma-focused CBT could facilitate healing from Mr. X’s childhood trauma/adverse childhood experiences, and DBT might help with his anger, maladaptive coping strategies, and chronic suicidality. Motivational interviewing might help with his substance use and his apparent lack of motivation for other forms of social engagement, including seeking employment.

Based on Mr. X’s history of trauma and chronic physical and emotional pain, the treatment team reevaluated him and reconsidered his original diagnosis.

Continue to: EVALUATION A closer look at the diagnosis...

After meeting with Mr. X, the treatment team begins to piece together a more robust picture of him. They review his childhood trauma involving his biological father, his chronic and limiting medical illnesses, and his restricted and somewhat regressive level of functioning. Further, they consider his >20 suicide attempts, numerous psychiatric hospitalizations, and mood and behavioral lability and reactivity. Based on its review, the treatment team concludes that a diagnosis of bipolar disorder II or major depressive disorder is not fully adequate to describe Mr. X’s clinical picture.

At no point during his hospitalization does Mr. X meet full criteria for a major depressive episode or display mania or hypomania. The treatment team considers posttraumatic stress disorder (PTSD) in the setting of chronic, repetitive trauma given Mr. X’s nightmares, dissociative behavior, anger, negative cognitions, and intrusive symptoms. However, not all his symptoms fall within the diagnostic criteria of PTSD. There are also elements of borderline personality disorder in Mr. X’s history, most notably his multiple suicide attempts, emotional lability, and disrupted interpersonal attachments. In this context, a diagnosis of complex PTSD (CPTSD) seems most appropriate in capturing the array of trauma-related symptoms with which he presents. 

Complex PTSD

Since at least the early to mid-1990s, there has been recognition of a qualitatively distinct clinical picture that can emerge when an individual’s exposure to trauma or adversity is chronic or repetitive, causing not only familiar PTSD symptomatology but also alterations in self-perception, interpersonal functioning, and affective instability. Complex PTSD was first described by Judith Herman, MD, in 1992 as a distinct entity from PTSD.¹ She theorized that PTSD derives primarily from singular traumatic events, while a distinct clinical syndrome might arise after prolonged, repeated trauma.¹ A diagnosis of CPTSD might arise in situations with more chronicity than a classic single circumscribed traumatic event, such as being held in captivity, under the control of perpetrators for extended periods of time, imprisoned, or subject to prolonged sexual abuse. Herman’s description of CPTSD identifies 3 areas of psychopathology that extend beyond PTSD¹:

• symptomatic refers to the complex, diffuse, and tenacious symptom presentation
• characterological focuses on the personality changes in terms of dissociation, ego-fragmentation, and identity complications
• vulnerability describes characteristic repeated harm with respect to self-mutilation or other self-injurious behaviors, and suicidality.

Taxometrics, official recognition, and controversy

Complex PTSD was proposed for inclusion in DSM-IV as “Disorders of Extreme Stress Not Otherwise Specified,” or DESNOS. Reportedly, it was interpreted as a severe presentation of PTSD, and therefore not included in the manual as a separate diagnosis.² In contrast, ICD-10 included a CPTSD-like entity of “Enduring Personality Change After Catastrophic Event” (EPCACE). Although the existence of CPTSD as a categorically distinct diagnosis in the psychiatric mainstream has been debated and discussed for years, with many arguably unaware of its existence, clinicians and researchers specializing in trauma are well-versed in its clinical utility. As such, CPTSD was again discussed during the development of DSM-5. In an apparent attempt to balance this clinical utility with ongoing concerns about its validity as a diagnostically distinct syndrome, DSM-5 did not officially recognize CPTSD, but added several criteria to PTSD referencing changes in self-perception, affective instability, and dysphoria, as well as a dissociative subtype, effectively expanding the scope of a PTSD diagnosis to also include CPTSD symptoms when applicable. ICD-11 has taken a different direction, and officially recognizes CPTSD as a distinct diagnosis.

ICD-11 presents CPTSD as a “sibling” disorder, which it distinguishes from PTSD with high levels of dissociation, depression, and borderline personality disorder traits.³ Within this framework, the diagnosis of CPTSD requires that the PTSD criteria be met in addition to symptoms that fall into a “disturbances of self-organization” category. When parsing the symptoms of the “disturbances of self-organization” category, the overlap with borderline personality disorder symptoms is apparent.⁴ This overlap has given rise to yet another controversy regarding CPTSD’s categorical validity; in addition to its distinctness from PTSD, its distinctness from borderline personality disorder has also been debated. In a study examining the similarity between CPTSD and borderline personality disorder, Jowett et al⁵ concluded that CPTSD was associated with greater exposure to multiple traumas earlier in life and resulted in higher functional impairment than borderline personality disorder, ultimately supporting CPTSD as a separate entity with features that overlap borderline personality disorder.⁵ According to Ford and Courtois⁶ “the evidence ... suggests that a sub-group of BPD patients—who often but not always have comorbid PTSD—may be best understood and treated if CPTSD is explicitly addressed as well—and in some cases, in lieu of—BPD.”

PTSD and CPTSD may therefore both be understood to fall within a spectrum of trauma diagnoses; this paradigm postulates that there exists a wide variety of posttraumatic patient presentations, perhaps on a continuum. On the less severe side of the trauma spectrum, the symptoms traditionally seen and characterized as PTSD (such as hypervigilance, nightmares, and flashbacks) may be found, while, with increasingly severe or prolonged trauma, there may be a tendency to see more complex elements (such as dissociation, personality changes mimicking borderline personality disorder, depression, anxiety, self-injurious behavior, and suicidality).⁷ Nevertheless, controversy about discriminant validity still exists. A review article by Resnick et al⁸ argued that the existing evidence is not strong enough to support CPTSD as a standalone entity. However, Resnick et al⁸ agreed that a singular PTSD diagnosis has limitations, and that there is a need for more research in the field of trauma psychiatry.

Continue to: Utility of the diagnostic conceptualization...

Although the controversy surrounding the distinction of CPTSD demands categorical clarity with respect to PTSD and borderline personality disorder as a means of resolution, the diagnosis has practical applications that should not limit its use in clinical formulation or treatment planning. Comorbid diagnoses do not prevent clinicians from diagnosing and treating patients who present with complicated manifestations of trauma.⁹ In fact, having overlapping diagnoses would highlight the array of patient presentations that can be seen in the posttraumatic condition. Furthermore, in the pursuit of individualized care approaches, the addition of CPTSD as a diagnostic conception would allow for more integrated treatment options using a multi-modular approach.¹⁰

The addition of CPTSD as a diagnosis is helpful in determining the etiology of a patient’s presentation and therefore formulating the most appropriate treatment plan. While the 2-pronged approach of psychopharmacology and therapy is the central dogma of psychiatric care, there are many specific options to consider for each. By viewing such patients through the lens of trauma as opposed to depression and anxiety, there is a clear shift in treatment that has the potential to make more lasting impacts and progress.¹¹

CPTSD may coexist with PTSD, but it extends beyond it to include a pleomorphic symptom picture encompassing personality changes and a high risk for repeated harm. Failure to correctly classify a patient’s presentation as a response to repetitive, prolonged trauma may result in discrimination and inappropriate or ineffective treatment recommendations.

For a comparison of the diagnostic criteria of PTSD, CPTSD, and borderline personality disorder, see Table 1¹², Table 2,^13,14, and Table 3¹².

Patients with CPTSD

One of the authors (NR) has cared for several similar individuals presenting for treatment with vague diagnoses of “chronic depression and anxiety” for years, sometimes with a speculative bipolar disorder diagnosis due to situational mood swings or reactivity, and a generally poor response to both medications and psychotherapy. These patients were frustrated because none of the diagnoses seemed to fully “fit” with their pattern of symptoms or subjective experience, and treatment seemed minimally helpful. Very often, their social history revealed a variety of adversities or traumatic events, such as childhood sexual or physical abuse, a home environment plagued by domestic violence, or being raised by one or both parents with their own history of trauma, or perhaps a personality or substance use disorder. Although many of these patients’ symptom profiles aligned only partially with “typical” PTSD, they were often better captured by CPTSD, with a focus on negative self-perception and impact on close relationships. Helping the patient “connect the dots” to create a more continuous narrative, and consequently reconceptualizing the diagnosis as a complex trauma disorder, has proven effective in a number of these cases, allowing the patient to make sense of their symptoms in the context of their personal history, reducing stigma, and allowing for different avenues with medication, therapy, and self-understanding. It can also help to validate the impact of a patient’s adverse experiences and encourage a patient to view their symptoms as an understandable or even once-adaptive response to traumatic stress, rather than a sign of personal weakness or defectiveness.

TREATMENT A trauma-focused approach

Once the treatment team considersMr. X’s significant childhood trauma and recon­ceptualizes his behaviors through this lens, treatment is adjusted accordingly. His significant reactivity, dissociative symptoms, social impairment, and repeated suicide attempts are better understood and have more significance through a trauma lens, which provides a better explanation than a primary mood disorder.

Therapeutic interventions in the hospital are tailored according to the treatment team’s new insight. Specific DBT skills are practiced, insight-oriented therapy and motivational interviewing are used, and Mr. X and his therapist begin to explore his trauma, both from his biological father and from his intense stressors experienced because of his medical issues.

Mr. X’s mother, who is very involved in his care, is provided with education on this conceptualization and given instruction on trauma-focused therapies in the outpatient setting. While Mr. X’s medication regimen is not changed significantly, for some patients, the reformulation from a primary mood or anxiety disorder to a trauma disorder might require a change in the pharmacotherapy regimen to address behavioral symptoms such as mood reactivity or issues with sleep.

OUTCOME Decreased intensity of suicidal thoughts

By the time of discharge, Mr. X has maintained safety, with no further outbursts, and subjectively reports feeling more understood and validated. Although chronic suicidal ideation can take months or years of treatment to resolve, at the time of discharge Mr. X reports a decreased intensity of these thoughts, and no acute suicidal ideation, plan, or intent. His discharge planning emphasizes ongoing work specifically related to coping with symptoms of traumatic stress, and the involvement of his main social support in facilitating this work.

The authors’ observations

As a caveat, it may be in some cases that chronic negative affect, dysphoria, and self-perception are better understood as a comorbid depressive disorder rather than subsumed into a PTSD/ CPTSD diagnosis. Also, because situational mood instability and impulsivity are often interpreted as bipolar disorder, a history of hypomania and mania should be ruled out. In Mr. X’s case, the diagnostic reformulation did not significantly impact pharmacotherapy because the target symptoms of mood instability, irritability, anxiety, and depression remained, despite the change in diagnosis.

Although the DSM-5 PTSD criteria effectively incorporate many CPTSD elements, we argue that this inclusivity comes at the expense of appreciating CPTSD as a qualitatively distinct condition, and we prefer ICD-11’s recognition of CPTSD as a separate diagnosis that incorporates PTSD criteria but extends the definition to include negative self-concept, affect dysregulation, and interpersonal difficulties.

Related Resources

• US Department of Veterans Affairs. PTSD: National Center for PTSD. Published January 1, 2007. https://www.ptsd.va.gov/ professional/treat/essentials/complex_ptsd.asp
• Jowett S, Karatzias T, Shevlin M, et al. Differentiating symptom profiles of ICD-11 PTSD, complex PTSD, and borderline personality disorder: a latent class analysis in a multiply traumatized sample. Personality disorders: theory, research, and treatment. 2020;11(1):36.

Drug Brand Names

Clonazepam • Klonopin

Haloperidol • Haldol

Lamotrigine • Lamictal

Lorazepam • Ativan

Sertraline • Zoloft

Zolpidem • Ambien

Bottom Line

Consider a diagnosis of complex posttraumatic stress disorder (CPTSD) when providing care for patients with chronic depression and suicidality with a history of trauma or childhood adversity. This reformulation can allow clinicians to understand the contributing factors more holistically; align with the patient more effectively; appreciate past and present interpersonal, psychological, and psychosocial factors that may precipitate and perpetuate symptoms; and allow for treatment recommendations beyond those of mood and anxiety disorders.

CASE A long history of suicidality

Mr. X, age 26, who has a history of bipolar II disorder and multiple inpatient admissions, presents to a state hospital after a suicide attempt by gunshot. He reports that throughout his lifetime, he has had >20 suicide attempts, often by overdose.

Mr. X is admitted to the hospital under a temporary detention order. He is initially adherent and cooperative with his psychiatric evaluations.

HISTORY Chronic physical and emotional pain

Mr. X is single, unemployed, and lives with his mother and nephew. He was diagnosed with bipolar II disorder during adolescence and receives sertraline, 50 mg twice a day, and lamotrigine, 100 mg twice a day, to which he reports adherence. He also was taking clonazepam and zolpidem, dosages unknown.

His medical history is significant for severe childhood liver disease and inflammatory bowel disease. He dropped out of school during high school due to his multiple medical conditions, which resulted in a significantly diminished overall childhood experience, interrupted developmental trajectory, and chronic physical and emotional pain. He has never been employed and receives financial support through disability benefits. He spends his days on the internet or watching television. He reports daily cigarette and marijuana use and occasional alcohol use, but no other substance use. His mother helps manage his medical conditions and is his main support. His biological father was abusive towards his mother and absent for most of Mr. X’s life. Beyond his mother and therapist, Mr. X has minimal other interpersonal interactions, and reports feeling isolated, lonely, and frustrated.

EVALUATION Agitated and aggressive while hospitalized

Upon learning that he is being involuntarily committed, Mr. X becomes physically aggressive, makes verbal threats, and throws objects across his room. He is given diphenhydramine, 50 mg, haloperidol, 5 mg, and lorazepam, 2 mg, all of which are ordered on an as-needed basis. Mr. X is placed in an emergency restraint chair and put in seclusion. The episode resolves within an hour with reassurance and attention from the treatment team; the rapid escalation from and return to a calmer state is indicative of situational, stress-induced mood lability and impulsivity. Mr. X is counseled on maintaining safety and appropriate behavior, and is advised to ask for medication if he feels agitated or unable to control his behaviors. To maintain safe and appropriate behavior, he requires daily counseling and expectation management regarding his treatment timeline. No further aggressive incidents are noted throughout his hospitalization, and he requires only minimal use of the as-needed medications.

[polldaddy:10983392]

The authors’ observations

The least appropriate therapy for Mr. X would be exposure and response prevention, which allows patients to face their fears without the need to soothe or relieve related feelings with a compulsive act. It is designed to improve specific behavioral deficits most often associated with obsessive-compulsive disorder, a diagnosis inconsistent with Mr. X’s history and presentation. Trauma-focused CBT could facilitate healing from Mr. X’s childhood trauma/adverse childhood experiences, and DBT might help with his anger, maladaptive coping strategies, and chronic suicidality. Motivational interviewing might help with his substance use and his apparent lack of motivation for other forms of social engagement, including seeking employment.

Based on Mr. X’s history of trauma and chronic physical and emotional pain, the treatment team reevaluated him and reconsidered his original diagnosis.

Continue to: EVALUATION A closer look at the diagnosis...

After meeting with Mr. X, the treatment team begins to piece together a more robust picture of him. They review his childhood trauma involving his biological father, his chronic and limiting medical illnesses, and his restricted and somewhat regressive level of functioning. Further, they consider his >20 suicide attempts, numerous psychiatric hospitalizations, and mood and behavioral lability and reactivity. Based on its review, the treatment team concludes that a diagnosis of bipolar disorder II or major depressive disorder is not fully adequate to describe Mr. X’s clinical picture.

At no point during his hospitalization does Mr. X meet full criteria for a major depressive episode or display mania or hypomania. The treatment team considers posttraumatic stress disorder (PTSD) in the setting of chronic, repetitive trauma given Mr. X’s nightmares, dissociative behavior, anger, negative cognitions, and intrusive symptoms. However, not all his symptoms fall within the diagnostic criteria of PTSD. There are also elements of borderline personality disorder in Mr. X’s history, most notably his multiple suicide attempts, emotional lability, and disrupted interpersonal attachments. In this context, a diagnosis of complex PTSD (CPTSD) seems most appropriate in capturing the array of trauma-related symptoms with which he presents. 

Complex PTSD

Since at least the early to mid-1990s, there has been recognition of a qualitatively distinct clinical picture that can emerge when an individual’s exposure to trauma or adversity is chronic or repetitive, causing not only familiar PTSD symptomatology but also alterations in self-perception, interpersonal functioning, and affective instability. Complex PTSD was first described by Judith Herman, MD, in 1992 as a distinct entity from PTSD.¹ She theorized that PTSD derives primarily from singular traumatic events, while a distinct clinical syndrome might arise after prolonged, repeated trauma.¹ A diagnosis of CPTSD might arise in situations with more chronicity than a classic single circumscribed traumatic event, such as being held in captivity, under the control of perpetrators for extended periods of time, imprisoned, or subject to prolonged sexual abuse. Herman’s description of CPTSD identifies 3 areas of psychopathology that extend beyond PTSD¹:

• symptomatic refers to the complex, diffuse, and tenacious symptom presentation
• characterological focuses on the personality changes in terms of dissociation, ego-fragmentation, and identity complications
• vulnerability describes characteristic repeated harm with respect to self-mutilation or other self-injurious behaviors, and suicidality.

Taxometrics, official recognition, and controversy

Complex PTSD was proposed for inclusion in DSM-IV as “Disorders of Extreme Stress Not Otherwise Specified,” or DESNOS. Reportedly, it was interpreted as a severe presentation of PTSD, and therefore not included in the manual as a separate diagnosis.² In contrast, ICD-10 included a CPTSD-like entity of “Enduring Personality Change After Catastrophic Event” (EPCACE). Although the existence of CPTSD as a categorically distinct diagnosis in the psychiatric mainstream has been debated and discussed for years, with many arguably unaware of its existence, clinicians and researchers specializing in trauma are well-versed in its clinical utility. As such, CPTSD was again discussed during the development of DSM-5. In an apparent attempt to balance this clinical utility with ongoing concerns about its validity as a diagnostically distinct syndrome, DSM-5 did not officially recognize CPTSD, but added several criteria to PTSD referencing changes in self-perception, affective instability, and dysphoria, as well as a dissociative subtype, effectively expanding the scope of a PTSD diagnosis to also include CPTSD symptoms when applicable. ICD-11 has taken a different direction, and officially recognizes CPTSD as a distinct diagnosis.

ICD-11 presents CPTSD as a “sibling” disorder, which it distinguishes from PTSD with high levels of dissociation, depression, and borderline personality disorder traits.³ Within this framework, the diagnosis of CPTSD requires that the PTSD criteria be met in addition to symptoms that fall into a “disturbances of self-organization” category. When parsing the symptoms of the “disturbances of self-organization” category, the overlap with borderline personality disorder symptoms is apparent.⁴ This overlap has given rise to yet another controversy regarding CPTSD’s categorical validity; in addition to its distinctness from PTSD, its distinctness from borderline personality disorder has also been debated. In a study examining the similarity between CPTSD and borderline personality disorder, Jowett et al⁵ concluded that CPTSD was associated with greater exposure to multiple traumas earlier in life and resulted in higher functional impairment than borderline personality disorder, ultimately supporting CPTSD as a separate entity with features that overlap borderline personality disorder.⁵ According to Ford and Courtois⁶ “the evidence ... suggests that a sub-group of BPD patients—who often but not always have comorbid PTSD—may be best understood and treated if CPTSD is explicitly addressed as well—and in some cases, in lieu of—BPD.”

PTSD and CPTSD may therefore both be understood to fall within a spectrum of trauma diagnoses; this paradigm postulates that there exists a wide variety of posttraumatic patient presentations, perhaps on a continuum. On the less severe side of the trauma spectrum, the symptoms traditionally seen and characterized as PTSD (such as hypervigilance, nightmares, and flashbacks) may be found, while, with increasingly severe or prolonged trauma, there may be a tendency to see more complex elements (such as dissociation, personality changes mimicking borderline personality disorder, depression, anxiety, self-injurious behavior, and suicidality).⁷ Nevertheless, controversy about discriminant validity still exists. A review article by Resnick et al⁸ argued that the existing evidence is not strong enough to support CPTSD as a standalone entity. However, Resnick et al⁸ agreed that a singular PTSD diagnosis has limitations, and that there is a need for more research in the field of trauma psychiatry.

Continue to: Utility of the diagnostic conceptualization...

Although the controversy surrounding the distinction of CPTSD demands categorical clarity with respect to PTSD and borderline personality disorder as a means of resolution, the diagnosis has practical applications that should not limit its use in clinical formulation or treatment planning. Comorbid diagnoses do not prevent clinicians from diagnosing and treating patients who present with complicated manifestations of trauma.⁹ In fact, having overlapping diagnoses would highlight the array of patient presentations that can be seen in the posttraumatic condition. Furthermore, in the pursuit of individualized care approaches, the addition of CPTSD as a diagnostic conception would allow for more integrated treatment options using a multi-modular approach.¹⁰

The addition of CPTSD as a diagnosis is helpful in determining the etiology of a patient’s presentation and therefore formulating the most appropriate treatment plan. While the 2-pronged approach of psychopharmacology and therapy is the central dogma of psychiatric care, there are many specific options to consider for each. By viewing such patients through the lens of trauma as opposed to depression and anxiety, there is a clear shift in treatment that has the potential to make more lasting impacts and progress.¹¹

CPTSD may coexist with PTSD, but it extends beyond it to include a pleomorphic symptom picture encompassing personality changes and a high risk for repeated harm. Failure to correctly classify a patient’s presentation as a response to repetitive, prolonged trauma may result in discrimination and inappropriate or ineffective treatment recommendations.

For a comparison of the diagnostic criteria of PTSD, CPTSD, and borderline personality disorder, see Table 1¹², Table 2,^13,14, and Table 3¹².

Patients with CPTSD

One of the authors (NR) has cared for several similar individuals presenting for treatment with vague diagnoses of “chronic depression and anxiety” for years, sometimes with a speculative bipolar disorder diagnosis due to situational mood swings or reactivity, and a generally poor response to both medications and psychotherapy. These patients were frustrated because none of the diagnoses seemed to fully “fit” with their pattern of symptoms or subjective experience, and treatment seemed minimally helpful. Very often, their social history revealed a variety of adversities or traumatic events, such as childhood sexual or physical abuse, a home environment plagued by domestic violence, or being raised by one or both parents with their own history of trauma, or perhaps a personality or substance use disorder. Although many of these patients’ symptom profiles aligned only partially with “typical” PTSD, they were often better captured by CPTSD, with a focus on negative self-perception and impact on close relationships. Helping the patient “connect the dots” to create a more continuous narrative, and consequently reconceptualizing the diagnosis as a complex trauma disorder, has proven effective in a number of these cases, allowing the patient to make sense of their symptoms in the context of their personal history, reducing stigma, and allowing for different avenues with medication, therapy, and self-understanding. It can also help to validate the impact of a patient’s adverse experiences and encourage a patient to view their symptoms as an understandable or even once-adaptive response to traumatic stress, rather than a sign of personal weakness or defectiveness.

TREATMENT A trauma-focused approach

Once the treatment team considersMr. X’s significant childhood trauma and recon­ceptualizes his behaviors through this lens, treatment is adjusted accordingly. His significant reactivity, dissociative symptoms, social impairment, and repeated suicide attempts are better understood and have more significance through a trauma lens, which provides a better explanation than a primary mood disorder.

Therapeutic interventions in the hospital are tailored according to the treatment team’s new insight. Specific DBT skills are practiced, insight-oriented therapy and motivational interviewing are used, and Mr. X and his therapist begin to explore his trauma, both from his biological father and from his intense stressors experienced because of his medical issues.

Mr. X’s mother, who is very involved in his care, is provided with education on this conceptualization and given instruction on trauma-focused therapies in the outpatient setting. While Mr. X’s medication regimen is not changed significantly, for some patients, the reformulation from a primary mood or anxiety disorder to a trauma disorder might require a change in the pharmacotherapy regimen to address behavioral symptoms such as mood reactivity or issues with sleep.

OUTCOME Decreased intensity of suicidal thoughts

By the time of discharge, Mr. X has maintained safety, with no further outbursts, and subjectively reports feeling more understood and validated. Although chronic suicidal ideation can take months or years of treatment to resolve, at the time of discharge Mr. X reports a decreased intensity of these thoughts, and no acute suicidal ideation, plan, or intent. His discharge planning emphasizes ongoing work specifically related to coping with symptoms of traumatic stress, and the involvement of his main social support in facilitating this work.

The authors’ observations

As a caveat, it may be in some cases that chronic negative affect, dysphoria, and self-perception are better understood as a comorbid depressive disorder rather than subsumed into a PTSD/ CPTSD diagnosis. Also, because situational mood instability and impulsivity are often interpreted as bipolar disorder, a history of hypomania and mania should be ruled out. In Mr. X’s case, the diagnostic reformulation did not significantly impact pharmacotherapy because the target symptoms of mood instability, irritability, anxiety, and depression remained, despite the change in diagnosis.

Although the DSM-5 PTSD criteria effectively incorporate many CPTSD elements, we argue that this inclusivity comes at the expense of appreciating CPTSD as a qualitatively distinct condition, and we prefer ICD-11’s recognition of CPTSD as a separate diagnosis that incorporates PTSD criteria but extends the definition to include negative self-concept, affect dysregulation, and interpersonal difficulties.

Related Resources

• US Department of Veterans Affairs. PTSD: National Center for PTSD. Published January 1, 2007. https://www.ptsd.va.gov/ professional/treat/essentials/complex_ptsd.asp
• Jowett S, Karatzias T, Shevlin M, et al. Differentiating symptom profiles of ICD-11 PTSD, complex PTSD, and borderline personality disorder: a latent class analysis in a multiply traumatized sample. Personality disorders: theory, research, and treatment. 2020;11(1):36.

Drug Brand Names

Clonazepam • Klonopin

Haloperidol • Haldol

Lamotrigine • Lamictal

Lorazepam • Ativan

Sertraline • Zoloft

Zolpidem • Ambien

Bottom Line

Consider a diagnosis of complex posttraumatic stress disorder (CPTSD) when providing care for patients with chronic depression and suicidality with a history of trauma or childhood adversity. This reformulation can allow clinicians to understand the contributing factors more holistically; align with the patient more effectively; appreciate past and present interpersonal, psychological, and psychosocial factors that may precipitate and perpetuate symptoms; and allow for treatment recommendations beyond those of mood and anxiety disorders.

CASE A long history of suicidality

Mr. X, age 26, who has a history of bipolar II disorder and multiple inpatient admissions, presents to a state hospital after a suicide attempt by gunshot. He reports that throughout his lifetime, he has had >20 suicide attempts, often by overdose.

Mr. X is admitted to the hospital under a temporary detention order. He is initially adherent and cooperative with his psychiatric evaluations.

HISTORY Chronic physical and emotional pain

Mr. X is single, unemployed, and lives with his mother and nephew. He was diagnosed with bipolar II disorder during adolescence and receives sertraline, 50 mg twice a day, and lamotrigine, 100 mg twice a day, to which he reports adherence. He also was taking clonazepam and zolpidem, dosages unknown.

His medical history is significant for severe childhood liver disease and inflammatory bowel disease. He dropped out of school during high school due to his multiple medical conditions, which resulted in a significantly diminished overall childhood experience, interrupted developmental trajectory, and chronic physical and emotional pain. He has never been employed and receives financial support through disability benefits. He spends his days on the internet or watching television. He reports daily cigarette and marijuana use and occasional alcohol use, but no other substance use. His mother helps manage his medical conditions and is his main support. His biological father was abusive towards his mother and absent for most of Mr. X’s life. Beyond his mother and therapist, Mr. X has minimal other interpersonal interactions, and reports feeling isolated, lonely, and frustrated.

EVALUATION Agitated and aggressive while hospitalized

Upon learning that he is being involuntarily committed, Mr. X becomes physically aggressive, makes verbal threats, and throws objects across his room. He is given diphenhydramine, 50 mg, haloperidol, 5 mg, and lorazepam, 2 mg, all of which are ordered on an as-needed basis. Mr. X is placed in an emergency restraint chair and put in seclusion. The episode resolves within an hour with reassurance and attention from the treatment team; the rapid escalation from and return to a calmer state is indicative of situational, stress-induced mood lability and impulsivity. Mr. X is counseled on maintaining safety and appropriate behavior, and is advised to ask for medication if he feels agitated or unable to control his behaviors. To maintain safe and appropriate behavior, he requires daily counseling and expectation management regarding his treatment timeline. No further aggressive incidents are noted throughout his hospitalization, and he requires only minimal use of the as-needed medications.

[polldaddy:10983392]

The authors’ observations

The least appropriate therapy for Mr. X would be exposure and response prevention, which allows patients to face their fears without the need to soothe or relieve related feelings with a compulsive act. It is designed to improve specific behavioral deficits most often associated with obsessive-compulsive disorder, a diagnosis inconsistent with Mr. X’s history and presentation. Trauma-focused CBT could facilitate healing from Mr. X’s childhood trauma/adverse childhood experiences, and DBT might help with his anger, maladaptive coping strategies, and chronic suicidality. Motivational interviewing might help with his substance use and his apparent lack of motivation for other forms of social engagement, including seeking employment.

Based on Mr. X’s history of trauma and chronic physical and emotional pain, the treatment team reevaluated him and reconsidered his original diagnosis.

Continue to: EVALUATION A closer look at the diagnosis...

After meeting with Mr. X, the treatment team begins to piece together a more robust picture of him. They review his childhood trauma involving his biological father, his chronic and limiting medical illnesses, and his restricted and somewhat regressive level of functioning. Further, they consider his >20 suicide attempts, numerous psychiatric hospitalizations, and mood and behavioral lability and reactivity. Based on its review, the treatment team concludes that a diagnosis of bipolar disorder II or major depressive disorder is not fully adequate to describe Mr. X’s clinical picture.

At no point during his hospitalization does Mr. X meet full criteria for a major depressive episode or display mania or hypomania. The treatment team considers posttraumatic stress disorder (PTSD) in the setting of chronic, repetitive trauma given Mr. X’s nightmares, dissociative behavior, anger, negative cognitions, and intrusive symptoms. However, not all his symptoms fall within the diagnostic criteria of PTSD. There are also elements of borderline personality disorder in Mr. X’s history, most notably his multiple suicide attempts, emotional lability, and disrupted interpersonal attachments. In this context, a diagnosis of complex PTSD (CPTSD) seems most appropriate in capturing the array of trauma-related symptoms with which he presents. 

Complex PTSD

Since at least the early to mid-1990s, there has been recognition of a qualitatively distinct clinical picture that can emerge when an individual’s exposure to trauma or adversity is chronic or repetitive, causing not only familiar PTSD symptomatology but also alterations in self-perception, interpersonal functioning, and affective instability. Complex PTSD was first described by Judith Herman, MD, in 1992 as a distinct entity from PTSD.¹ She theorized that PTSD derives primarily from singular traumatic events, while a distinct clinical syndrome might arise after prolonged, repeated trauma.¹ A diagnosis of CPTSD might arise in situations with more chronicity than a classic single circumscribed traumatic event, such as being held in captivity, under the control of perpetrators for extended periods of time, imprisoned, or subject to prolonged sexual abuse. Herman’s description of CPTSD identifies 3 areas of psychopathology that extend beyond PTSD¹:

• symptomatic refers to the complex, diffuse, and tenacious symptom presentation
• characterological focuses on the personality changes in terms of dissociation, ego-fragmentation, and identity complications
• vulnerability describes characteristic repeated harm with respect to self-mutilation or other self-injurious behaviors, and suicidality.

Taxometrics, official recognition, and controversy

Complex PTSD was proposed for inclusion in DSM-IV as “Disorders of Extreme Stress Not Otherwise Specified,” or DESNOS. Reportedly, it was interpreted as a severe presentation of PTSD, and therefore not included in the manual as a separate diagnosis.² In contrast, ICD-10 included a CPTSD-like entity of “Enduring Personality Change After Catastrophic Event” (EPCACE). Although the existence of CPTSD as a categorically distinct diagnosis in the psychiatric mainstream has been debated and discussed for years, with many arguably unaware of its existence, clinicians and researchers specializing in trauma are well-versed in its clinical utility. As such, CPTSD was again discussed during the development of DSM-5. In an apparent attempt to balance this clinical utility with ongoing concerns about its validity as a diagnostically distinct syndrome, DSM-5 did not officially recognize CPTSD, but added several criteria to PTSD referencing changes in self-perception, affective instability, and dysphoria, as well as a dissociative subtype, effectively expanding the scope of a PTSD diagnosis to also include CPTSD symptoms when applicable. ICD-11 has taken a different direction, and officially recognizes CPTSD as a distinct diagnosis.

ICD-11 presents CPTSD as a “sibling” disorder, which it distinguishes from PTSD with high levels of dissociation, depression, and borderline personality disorder traits.³ Within this framework, the diagnosis of CPTSD requires that the PTSD criteria be met in addition to symptoms that fall into a “disturbances of self-organization” category. When parsing the symptoms of the “disturbances of self-organization” category, the overlap with borderline personality disorder symptoms is apparent.⁴ This overlap has given rise to yet another controversy regarding CPTSD’s categorical validity; in addition to its distinctness from PTSD, its distinctness from borderline personality disorder has also been debated. In a study examining the similarity between CPTSD and borderline personality disorder, Jowett et al⁵ concluded that CPTSD was associated with greater exposure to multiple traumas earlier in life and resulted in higher functional impairment than borderline personality disorder, ultimately supporting CPTSD as a separate entity with features that overlap borderline personality disorder.⁵ According to Ford and Courtois⁶ “the evidence ... suggests that a sub-group of BPD patients—who often but not always have comorbid PTSD—may be best understood and treated if CPTSD is explicitly addressed as well—and in some cases, in lieu of—BPD.”

PTSD and CPTSD may therefore both be understood to fall within a spectrum of trauma diagnoses; this paradigm postulates that there exists a wide variety of posttraumatic patient presentations, perhaps on a continuum. On the less severe side of the trauma spectrum, the symptoms traditionally seen and characterized as PTSD (such as hypervigilance, nightmares, and flashbacks) may be found, while, with increasingly severe or prolonged trauma, there may be a tendency to see more complex elements (such as dissociation, personality changes mimicking borderline personality disorder, depression, anxiety, self-injurious behavior, and suicidality).⁷ Nevertheless, controversy about discriminant validity still exists. A review article by Resnick et al⁸ argued that the existing evidence is not strong enough to support CPTSD as a standalone entity. However, Resnick et al⁸ agreed that a singular PTSD diagnosis has limitations, and that there is a need for more research in the field of trauma psychiatry.

Continue to: Utility of the diagnostic conceptualization...

Although the controversy surrounding the distinction of CPTSD demands categorical clarity with respect to PTSD and borderline personality disorder as a means of resolution, the diagnosis has practical applications that should not limit its use in clinical formulation or treatment planning. Comorbid diagnoses do not prevent clinicians from diagnosing and treating patients who present with complicated manifestations of trauma.⁹ In fact, having overlapping diagnoses would highlight the array of patient presentations that can be seen in the posttraumatic condition. Furthermore, in the pursuit of individualized care approaches, the addition of CPTSD as a diagnostic conception would allow for more integrated treatment options using a multi-modular approach.¹⁰

The addition of CPTSD as a diagnosis is helpful in determining the etiology of a patient’s presentation and therefore formulating the most appropriate treatment plan. While the 2-pronged approach of psychopharmacology and therapy is the central dogma of psychiatric care, there are many specific options to consider for each. By viewing such patients through the lens of trauma as opposed to depression and anxiety, there is a clear shift in treatment that has the potential to make more lasting impacts and progress.¹¹

CPTSD may coexist with PTSD, but it extends beyond it to include a pleomorphic symptom picture encompassing personality changes and a high risk for repeated harm. Failure to correctly classify a patient’s presentation as a response to repetitive, prolonged trauma may result in discrimination and inappropriate or ineffective treatment recommendations.

For a comparison of the diagnostic criteria of PTSD, CPTSD, and borderline personality disorder, see Table 1¹², Table 2,^13,14, and Table 3¹².

Patients with CPTSD

One of the authors (NR) has cared for several similar individuals presenting for treatment with vague diagnoses of “chronic depression and anxiety” for years, sometimes with a speculative bipolar disorder diagnosis due to situational mood swings or reactivity, and a generally poor response to both medications and psychotherapy. These patients were frustrated because none of the diagnoses seemed to fully “fit” with their pattern of symptoms or subjective experience, and treatment seemed minimally helpful. Very often, their social history revealed a variety of adversities or traumatic events, such as childhood sexual or physical abuse, a home environment plagued by domestic violence, or being raised by one or both parents with their own history of trauma, or perhaps a personality or substance use disorder. Although many of these patients’ symptom profiles aligned only partially with “typical” PTSD, they were often better captured by CPTSD, with a focus on negative self-perception and impact on close relationships. Helping the patient “connect the dots” to create a more continuous narrative, and consequently reconceptualizing the diagnosis as a complex trauma disorder, has proven effective in a number of these cases, allowing the patient to make sense of their symptoms in the context of their personal history, reducing stigma, and allowing for different avenues with medication, therapy, and self-understanding. It can also help to validate the impact of a patient’s adverse experiences and encourage a patient to view their symptoms as an understandable or even once-adaptive response to traumatic stress, rather than a sign of personal weakness or defectiveness.

TREATMENT A trauma-focused approach

Once the treatment team considersMr. X’s significant childhood trauma and recon­ceptualizes his behaviors through this lens, treatment is adjusted accordingly. His significant reactivity, dissociative symptoms, social impairment, and repeated suicide attempts are better understood and have more significance through a trauma lens, which provides a better explanation than a primary mood disorder.

Therapeutic interventions in the hospital are tailored according to the treatment team’s new insight. Specific DBT skills are practiced, insight-oriented therapy and motivational interviewing are used, and Mr. X and his therapist begin to explore his trauma, both from his biological father and from his intense stressors experienced because of his medical issues.

Mr. X’s mother, who is very involved in his care, is provided with education on this conceptualization and given instruction on trauma-focused therapies in the outpatient setting. While Mr. X’s medication regimen is not changed significantly, for some patients, the reformulation from a primary mood or anxiety disorder to a trauma disorder might require a change in the pharmacotherapy regimen to address behavioral symptoms such as mood reactivity or issues with sleep.

OUTCOME Decreased intensity of suicidal thoughts

By the time of discharge, Mr. X has maintained safety, with no further outbursts, and subjectively reports feeling more understood and validated. Although chronic suicidal ideation can take months or years of treatment to resolve, at the time of discharge Mr. X reports a decreased intensity of these thoughts, and no acute suicidal ideation, plan, or intent. His discharge planning emphasizes ongoing work specifically related to coping with symptoms of traumatic stress, and the involvement of his main social support in facilitating this work.

The authors’ observations

As a caveat, it may be in some cases that chronic negative affect, dysphoria, and self-perception are better understood as a comorbid depressive disorder rather than subsumed into a PTSD/ CPTSD diagnosis. Also, because situational mood instability and impulsivity are often interpreted as bipolar disorder, a history of hypomania and mania should be ruled out. In Mr. X’s case, the diagnostic reformulation did not significantly impact pharmacotherapy because the target symptoms of mood instability, irritability, anxiety, and depression remained, despite the change in diagnosis.

Although the DSM-5 PTSD criteria effectively incorporate many CPTSD elements, we argue that this inclusivity comes at the expense of appreciating CPTSD as a qualitatively distinct condition, and we prefer ICD-11’s recognition of CPTSD as a separate diagnosis that incorporates PTSD criteria but extends the definition to include negative self-concept, affect dysregulation, and interpersonal difficulties.

Related Resources

• US Department of Veterans Affairs. PTSD: National Center for PTSD. Published January 1, 2007. https://www.ptsd.va.gov/ professional/treat/essentials/complex_ptsd.asp
• Jowett S, Karatzias T, Shevlin M, et al. Differentiating symptom profiles of ICD-11 PTSD, complex PTSD, and borderline personality disorder: a latent class analysis in a multiply traumatized sample. Personality disorders: theory, research, and treatment. 2020;11(1):36.

Drug Brand Names

Clonazepam • Klonopin

Haloperidol • Haldol

Lamotrigine • Lamictal

Lorazepam • Ativan

Sertraline • Zoloft

Zolpidem • Ambien

Bottom Line

Consider a diagnosis of complex posttraumatic stress disorder (CPTSD) when providing care for patients with chronic depression and suicidality with a history of trauma or childhood adversity. This reformulation can allow clinicians to understand the contributing factors more holistically; align with the patient more effectively; appreciate past and present interpersonal, psychological, and psychosocial factors that may precipitate and perpetuate symptoms; and allow for treatment recommendations beyond those of mood and anxiety disorders.

Pediatric dermatologists who treat infantile hemangioma (IH) can consider nadolol as a noninferior – and possibly a better – alternative to the standard treatment propranolol, according to a study published in JAMA Pediatrics.

“In our experience, nadolol is preferable to propranolol given its observed efficacy and similar safety profile [and] its more predictable metabolism that does not involve the liver,” lead author Elena Pope, MD, told this news organization. “In addition, the fact that nadolol is less lipophilic than propranolol makes it less likely to cross the blood-brain barrier and potentially affect the central nervous system,” added Dr. Pope, who is head of the division of pediatric dermatology at the Hospital for Sick Children, Toronto, and professor of pediatric medicine at the University of Toronto.

The prospective double-blind, randomized noninferiority study was conducted between 2016 and 2020 at two tertiary academic pediatric dermatology clinics in Ontario, Canada. It included 71 infants with a corrected gestational age of 1-6 months whose hemangiomas were greater than 1.5 cm on the face or 3 cm or greater on another body part and had the potential to cause functional impairment or cosmetic disfigurement.

Patients were randomized to either nadolol (oral suspension, 10 mg/mL) or propranolol (oral suspension, 5 mg/mL) beginning at a dose of 0.5 mg/kg per day twice a day and titrated weekly by 0.5 mg/kg per day until the maximum dose of 2 mg/kg per day. The dose was then adjusted until week 24, based on patient weight and clinical response, after which parents could choose to continue the infant on the assigned medication or switch to the other one. Follow-up visits occurred every 2 months after that until week 52.

For the main study outcome, measured by visual analog scale (VAS) scores at week 24, the between-group differences of IH size and color from baseline were 8.8 and 17.1, respectively, in favor of the nadolol group, the researchers report, with similar results seen at week 52. Safety data were similar for both treatments, “demonstrating that nadolol was noninferior to propranolol,” they write.

Additionally, the mean size involution, compared with baseline was 97.9% in the nadolol group and 89.1% in the propranolol group, and the mean color fading was 94.5% in the nadolol group, compared with 80.5% in the propranolol group. During the study, nadolol was also “59% faster in achieving 75% shrinkage of IH, compared with propranolol (P = .02) and 105% faster in achieving 100% shrinkage (P = .07),” they add.

“A considerable portion of patients experienced at least one mild adverse event (77.1% vs. 94.4% at 0-24 weeks and 84.2% vs. 74.2% at 24-52 weeks in the nadolol group vs. the propranolol group, respectively), with a median of two in each intervention group,” they noted, adding that while these numbers are high, they are similar to those in previous clinical trials.

“The efficacy data coupled with a more predictable pharmacokinetic profile and lower chance of crossing the blood-brain barrier may make nadolol a favorable alternative intervention in patients with IHs,” the authors conclude. However, they add that “further studies are needed to prove superiority over propranolol.”

Asked to comment on the results, Ilona J. Frieden, MD, director of the Birthmarks & Vascular Anomalies Center at the University of California, San Francisco, said that while this is a “very interesting study and deserves further consideration,” the findings do not reach the level at which they would change guidelines. “The vast majority of patients being treated with a systemic medication for IH are in fact getting propranolol,” said Dr. Frieden, coauthor of the American Academy of Pediatrics Clinical Practice Guideline for the Management of Infantile Hemangiomas.

“Though this study – designed as a noninferiority study – does seem to show slightly better outcomes from nadolol versus propranolol … it is a relatively small study,” she told this news organization. “Infantile hemangiomas are a very heterogeneous group, and larger studies and longer-term outcome data would be needed to truly compare the two modalities of treatment.”

Concern over the safety of nadolol was raised in a case report published in Pediatrics, which described the death of a 10-week-old girl 7 weeks after starting nadolol for IH. The infant was found to have an elevated postmortem cardiac blood nadolol level of 0.94 mg/L. “Although we debated the conclusion of that report in terms of death attribution to nadolol, one practical pearl is to instruct the parents to discontinue nadolol if the baby has no bowel movements for more than 3 days,” Dr. Pope advised.

The author of that case report, Eric McGillis, MD, program director of clinical pharmacology and toxicology and an emergency physician at Alberta Health Services, in Calgary, Alt., said the conclusion of his report has been taken out of context. “We acknowledge that our case report, like any case report, cannot prove causation,” he told this news organization. “We hypothesized that nadolol may have contributed to the death of the infant based on the limited pharmacokinetic data currently available for nadolol in infants. Nadolol is largely eliminated in the feces and infants may have infrequent stooling based on diet and other factors; therefore, nadolol may accumulate,” he noted.

The infant in the case report did not have a bowel movement for 10 days “and had an elevated postmortem cardiac nadolol concentration in the absence of another obvious cause of death. More pharmacokinetic studies on nadolol in this population are needed to substantiate our hypothesis. However, in the meantime, we agree that having parents monitor stool output for dose adjustments makes practical sense and can potentially reduce harm.”

Dr. Pope presented the results of the study earlier this year at the annual meeting of the Society for Pediatric Dermatology.

The study was supported by Physician Services, Ont. Dr. Pope has reported serving as an advisory board member for Boehringer Ingelheim, Novartis, Sanofi Genzyme, and Timber. Other authors have reported receiving personal fees from Pierre Fabre during the conduct of the study, as well as personal fees from Amgen, Ipsen, Novartis, Pfizer, and Sanofi Genzyme; grants from AbbVie, Clementia, Mayne Pharma, and Sanofi Genzyme; and grants and personal fees from Venthera. One author has a patent for a new topical treatment of IH. Dr. Frieden has reported being a consultant for Pfizer (data safety board), Novartis, and Venthera. Dr. McGillis has reported no relevant financial relationships.

Commentary by Lawrence W. Eichenfield, MD

The treatment of functionally significant and deforming hemangiomas has been revolutionized by propranolol, developed after the observation by Christine Léauté-Labrèze, MD, that a child who developed hypertension as a side effect of systemic steroids for a nasal hemangioma and was prescribed propranolol for the hypertension had rapid shrinkage of the hemangioma. The study by Pope and colleagues assesses nadolol as an alternative to propranolol, showing noninferiority and in some parameters improved outcomes and speed of response. The drug appeared to be fairly well tolerated in the study, though there is a prior published case report of a death from nadolol use for hemangioma treatment from a different Canadian center. Nadolol may be an important alternative to propranolol; however, propranolol remains the only FDA-approved medication for infantile hemangiomas and the generally recommended medication in the American Academy of Pediatrics guidelines for management of infantile hemangiomas.

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children's Hospital-San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. He disclosed that he has served as an investigator and/or consultant to AbbVie, Lilly, Pfizer, Regeneron, Sanofi-Genzyme, and Verrica.

A version of this article first appeared on Medscape.com.

This article was updated 6/18/22.

Pediatric dermatologists who treat infantile hemangioma (IH) can consider nadolol as a noninferior – and possibly a better – alternative to the standard treatment propranolol, according to a study published in JAMA Pediatrics.

“In our experience, nadolol is preferable to propranolol given its observed efficacy and similar safety profile [and] its more predictable metabolism that does not involve the liver,” lead author Elena Pope, MD, told this news organization. “In addition, the fact that nadolol is less lipophilic than propranolol makes it less likely to cross the blood-brain barrier and potentially affect the central nervous system,” added Dr. Pope, who is head of the division of pediatric dermatology at the Hospital for Sick Children, Toronto, and professor of pediatric medicine at the University of Toronto.

The prospective double-blind, randomized noninferiority study was conducted between 2016 and 2020 at two tertiary academic pediatric dermatology clinics in Ontario, Canada. It included 71 infants with a corrected gestational age of 1-6 months whose hemangiomas were greater than 1.5 cm on the face or 3 cm or greater on another body part and had the potential to cause functional impairment or cosmetic disfigurement.

Patients were randomized to either nadolol (oral suspension, 10 mg/mL) or propranolol (oral suspension, 5 mg/mL) beginning at a dose of 0.5 mg/kg per day twice a day and titrated weekly by 0.5 mg/kg per day until the maximum dose of 2 mg/kg per day. The dose was then adjusted until week 24, based on patient weight and clinical response, after which parents could choose to continue the infant on the assigned medication or switch to the other one. Follow-up visits occurred every 2 months after that until week 52.

For the main study outcome, measured by visual analog scale (VAS) scores at week 24, the between-group differences of IH size and color from baseline were 8.8 and 17.1, respectively, in favor of the nadolol group, the researchers report, with similar results seen at week 52. Safety data were similar for both treatments, “demonstrating that nadolol was noninferior to propranolol,” they write.

Additionally, the mean size involution, compared with baseline was 97.9% in the nadolol group and 89.1% in the propranolol group, and the mean color fading was 94.5% in the nadolol group, compared with 80.5% in the propranolol group. During the study, nadolol was also “59% faster in achieving 75% shrinkage of IH, compared with propranolol (P = .02) and 105% faster in achieving 100% shrinkage (P = .07),” they add.

“A considerable portion of patients experienced at least one mild adverse event (77.1% vs. 94.4% at 0-24 weeks and 84.2% vs. 74.2% at 24-52 weeks in the nadolol group vs. the propranolol group, respectively), with a median of two in each intervention group,” they noted, adding that while these numbers are high, they are similar to those in previous clinical trials.

“The efficacy data coupled with a more predictable pharmacokinetic profile and lower chance of crossing the blood-brain barrier may make nadolol a favorable alternative intervention in patients with IHs,” the authors conclude. However, they add that “further studies are needed to prove superiority over propranolol.”

Asked to comment on the results, Ilona J. Frieden, MD, director of the Birthmarks & Vascular Anomalies Center at the University of California, San Francisco, said that while this is a “very interesting study and deserves further consideration,” the findings do not reach the level at which they would change guidelines. “The vast majority of patients being treated with a systemic medication for IH are in fact getting propranolol,” said Dr. Frieden, coauthor of the American Academy of Pediatrics Clinical Practice Guideline for the Management of Infantile Hemangiomas.

“Though this study – designed as a noninferiority study – does seem to show slightly better outcomes from nadolol versus propranolol … it is a relatively small study,” she told this news organization. “Infantile hemangiomas are a very heterogeneous group, and larger studies and longer-term outcome data would be needed to truly compare the two modalities of treatment.”

Concern over the safety of nadolol was raised in a case report published in Pediatrics, which described the death of a 10-week-old girl 7 weeks after starting nadolol for IH. The infant was found to have an elevated postmortem cardiac blood nadolol level of 0.94 mg/L. “Although we debated the conclusion of that report in terms of death attribution to nadolol, one practical pearl is to instruct the parents to discontinue nadolol if the baby has no bowel movements for more than 3 days,” Dr. Pope advised.

The author of that case report, Eric McGillis, MD, program director of clinical pharmacology and toxicology and an emergency physician at Alberta Health Services, in Calgary, Alt., said the conclusion of his report has been taken out of context. “We acknowledge that our case report, like any case report, cannot prove causation,” he told this news organization. “We hypothesized that nadolol may have contributed to the death of the infant based on the limited pharmacokinetic data currently available for nadolol in infants. Nadolol is largely eliminated in the feces and infants may have infrequent stooling based on diet and other factors; therefore, nadolol may accumulate,” he noted.

The infant in the case report did not have a bowel movement for 10 days “and had an elevated postmortem cardiac nadolol concentration in the absence of another obvious cause of death. More pharmacokinetic studies on nadolol in this population are needed to substantiate our hypothesis. However, in the meantime, we agree that having parents monitor stool output for dose adjustments makes practical sense and can potentially reduce harm.”

Dr. Pope presented the results of the study earlier this year at the annual meeting of the Society for Pediatric Dermatology.

The study was supported by Physician Services, Ont. Dr. Pope has reported serving as an advisory board member for Boehringer Ingelheim, Novartis, Sanofi Genzyme, and Timber. Other authors have reported receiving personal fees from Pierre Fabre during the conduct of the study, as well as personal fees from Amgen, Ipsen, Novartis, Pfizer, and Sanofi Genzyme; grants from AbbVie, Clementia, Mayne Pharma, and Sanofi Genzyme; and grants and personal fees from Venthera. One author has a patent for a new topical treatment of IH. Dr. Frieden has reported being a consultant for Pfizer (data safety board), Novartis, and Venthera. Dr. McGillis has reported no relevant financial relationships.

Commentary by Lawrence W. Eichenfield, MD

The treatment of functionally significant and deforming hemangiomas has been revolutionized by propranolol, developed after the observation by Christine Léauté-Labrèze, MD, that a child who developed hypertension as a side effect of systemic steroids for a nasal hemangioma and was prescribed propranolol for the hypertension had rapid shrinkage of the hemangioma. The study by Pope and colleagues assesses nadolol as an alternative to propranolol, showing noninferiority and in some parameters improved outcomes and speed of response. The drug appeared to be fairly well tolerated in the study, though there is a prior published case report of a death from nadolol use for hemangioma treatment from a different Canadian center. Nadolol may be an important alternative to propranolol; however, propranolol remains the only FDA-approved medication for infantile hemangiomas and the generally recommended medication in the American Academy of Pediatrics guidelines for management of infantile hemangiomas.

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children's Hospital-San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. He disclosed that he has served as an investigator and/or consultant to AbbVie, Lilly, Pfizer, Regeneron, Sanofi-Genzyme, and Verrica.

A version of this article first appeared on Medscape.com.

This article was updated 6/18/22.

Pediatric dermatologists who treat infantile hemangioma (IH) can consider nadolol as a noninferior – and possibly a better – alternative to the standard treatment propranolol, according to a study published in JAMA Pediatrics.

“In our experience, nadolol is preferable to propranolol given its observed efficacy and similar safety profile [and] its more predictable metabolism that does not involve the liver,” lead author Elena Pope, MD, told this news organization. “In addition, the fact that nadolol is less lipophilic than propranolol makes it less likely to cross the blood-brain barrier and potentially affect the central nervous system,” added Dr. Pope, who is head of the division of pediatric dermatology at the Hospital for Sick Children, Toronto, and professor of pediatric medicine at the University of Toronto.

The prospective double-blind, randomized noninferiority study was conducted between 2016 and 2020 at two tertiary academic pediatric dermatology clinics in Ontario, Canada. It included 71 infants with a corrected gestational age of 1-6 months whose hemangiomas were greater than 1.5 cm on the face or 3 cm or greater on another body part and had the potential to cause functional impairment or cosmetic disfigurement.

Patients were randomized to either nadolol (oral suspension, 10 mg/mL) or propranolol (oral suspension, 5 mg/mL) beginning at a dose of 0.5 mg/kg per day twice a day and titrated weekly by 0.5 mg/kg per day until the maximum dose of 2 mg/kg per day. The dose was then adjusted until week 24, based on patient weight and clinical response, after which parents could choose to continue the infant on the assigned medication or switch to the other one. Follow-up visits occurred every 2 months after that until week 52.

For the main study outcome, measured by visual analog scale (VAS) scores at week 24, the between-group differences of IH size and color from baseline were 8.8 and 17.1, respectively, in favor of the nadolol group, the researchers report, with similar results seen at week 52. Safety data were similar for both treatments, “demonstrating that nadolol was noninferior to propranolol,” they write.

Additionally, the mean size involution, compared with baseline was 97.9% in the nadolol group and 89.1% in the propranolol group, and the mean color fading was 94.5% in the nadolol group, compared with 80.5% in the propranolol group. During the study, nadolol was also “59% faster in achieving 75% shrinkage of IH, compared with propranolol (P = .02) and 105% faster in achieving 100% shrinkage (P = .07),” they add.

“A considerable portion of patients experienced at least one mild adverse event (77.1% vs. 94.4% at 0-24 weeks and 84.2% vs. 74.2% at 24-52 weeks in the nadolol group vs. the propranolol group, respectively), with a median of two in each intervention group,” they noted, adding that while these numbers are high, they are similar to those in previous clinical trials.

“The efficacy data coupled with a more predictable pharmacokinetic profile and lower chance of crossing the blood-brain barrier may make nadolol a favorable alternative intervention in patients with IHs,” the authors conclude. However, they add that “further studies are needed to prove superiority over propranolol.”

Asked to comment on the results, Ilona J. Frieden, MD, director of the Birthmarks & Vascular Anomalies Center at the University of California, San Francisco, said that while this is a “very interesting study and deserves further consideration,” the findings do not reach the level at which they would change guidelines. “The vast majority of patients being treated with a systemic medication for IH are in fact getting propranolol,” said Dr. Frieden, coauthor of the American Academy of Pediatrics Clinical Practice Guideline for the Management of Infantile Hemangiomas.

“Though this study – designed as a noninferiority study – does seem to show slightly better outcomes from nadolol versus propranolol … it is a relatively small study,” she told this news organization. “Infantile hemangiomas are a very heterogeneous group, and larger studies and longer-term outcome data would be needed to truly compare the two modalities of treatment.”

Concern over the safety of nadolol was raised in a case report published in Pediatrics, which described the death of a 10-week-old girl 7 weeks after starting nadolol for IH. The infant was found to have an elevated postmortem cardiac blood nadolol level of 0.94 mg/L. “Although we debated the conclusion of that report in terms of death attribution to nadolol, one practical pearl is to instruct the parents to discontinue nadolol if the baby has no bowel movements for more than 3 days,” Dr. Pope advised.

The author of that case report, Eric McGillis, MD, program director of clinical pharmacology and toxicology and an emergency physician at Alberta Health Services, in Calgary, Alt., said the conclusion of his report has been taken out of context. “We acknowledge that our case report, like any case report, cannot prove causation,” he told this news organization. “We hypothesized that nadolol may have contributed to the death of the infant based on the limited pharmacokinetic data currently available for nadolol in infants. Nadolol is largely eliminated in the feces and infants may have infrequent stooling based on diet and other factors; therefore, nadolol may accumulate,” he noted.

The infant in the case report did not have a bowel movement for 10 days “and had an elevated postmortem cardiac nadolol concentration in the absence of another obvious cause of death. More pharmacokinetic studies on nadolol in this population are needed to substantiate our hypothesis. However, in the meantime, we agree that having parents monitor stool output for dose adjustments makes practical sense and can potentially reduce harm.”

Dr. Pope presented the results of the study earlier this year at the annual meeting of the Society for Pediatric Dermatology.

The study was supported by Physician Services, Ont. Dr. Pope has reported serving as an advisory board member for Boehringer Ingelheim, Novartis, Sanofi Genzyme, and Timber. Other authors have reported receiving personal fees from Pierre Fabre during the conduct of the study, as well as personal fees from Amgen, Ipsen, Novartis, Pfizer, and Sanofi Genzyme; grants from AbbVie, Clementia, Mayne Pharma, and Sanofi Genzyme; and grants and personal fees from Venthera. One author has a patent for a new topical treatment of IH. Dr. Frieden has reported being a consultant for Pfizer (data safety board), Novartis, and Venthera. Dr. McGillis has reported no relevant financial relationships.

Commentary by Lawrence W. Eichenfield, MD

The treatment of functionally significant and deforming hemangiomas has been revolutionized by propranolol, developed after the observation by Christine Léauté-Labrèze, MD, that a child who developed hypertension as a side effect of systemic steroids for a nasal hemangioma and was prescribed propranolol for the hypertension had rapid shrinkage of the hemangioma. The study by Pope and colleagues assesses nadolol as an alternative to propranolol, showing noninferiority and in some parameters improved outcomes and speed of response. The drug appeared to be fairly well tolerated in the study, though there is a prior published case report of a death from nadolol use for hemangioma treatment from a different Canadian center. Nadolol may be an important alternative to propranolol; however, propranolol remains the only FDA-approved medication for infantile hemangiomas and the generally recommended medication in the American Academy of Pediatrics guidelines for management of infantile hemangiomas.

Dr. Eichenfield is chief of pediatric and adolescent dermatology at Rady Children's Hospital-San Diego. He is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego. He disclosed that he has served as an investigator and/or consultant to AbbVie, Lilly, Pfizer, Regeneron, Sanofi-Genzyme, and Verrica.

A version of this article first appeared on Medscape.com.

This article was updated 6/18/22.

It was supper time in the Whittier, California, home of Air Force veteran Danyelle Clark-Gutierrez, and eagerly awaiting a bowl of kibble and canned dog food was Lisa, a 3-year-old yellow Labrador retriever.

Her nails clicking on the kitchen floor as she danced about, Lisa looked more like an exuberant puppy than the highly trained service animal that helps Clark-Gutierrez manage the symptoms of post-traumatic stress disorder.

“Having her now, it’s like I can go anywhere,” Clark-Gutierrez said. “And, yes, if somebody did come at me, I’d have warning — I could run.”

A growing body of research into PTSD and service animals paved the way for President Joe Biden to sign into law the Puppies Assisting Wounded Servicemembers (PAWS) for Veterans Therapy Act. The legislation, enacted in August, requires the Department of Veterans Affairs to open its service dog referral program to veterans with PTSD and to launch a five-year pilot program in which veterans with PTSD train service dogs for other veterans.

Clark-Gutierrez, 33, is among the 25 percent of female veterans who have reported experiencing military sexual trauma while serving in the U.S. armed services.

Military sexual trauma, combat violence and brain injuries are some of the experiences that increase the risk that service members will develop PTSD. Symptoms include flashbacks to the traumatic event, severe anxiety, nightmares and hypervigilance — all normal reactions to experiencing or witnessing violence, according to psychologists. Someone receives a PTSD diagnosis when symptoms worsen or remain for months or years.

That’s what Clark-Gutierrez said happened to her after ongoing sexual harassment by a fellow airman escalated to a physical attack about a decade ago. A lawyer with three children, she said that to feel safe leaving her home she needed her husband by her side. After diagnosing Clark-Gutierrez with PTSD, doctors at VA hospitals prescribed a cascade of medications for her. At one point, Clark-Gutierrez said, her prescriptions added up to more than a dozen pills a day.

“I had medication, and then I had medication for the two or three side effects for each medication,” she said. “And every time they gave me a new med, they had to give me three more. I just couldn’t do it anymore. I was just getting so tired. So we started looking at other therapies.”

And that’s how she got her service dog, Lisa. Clark-Gutierrez’s husband, also an Air Force veteran, discovered the nonprofit group K9s for Warriors, which rescues dogs — many from kill shelters — and trains them to be service animals for veterans with PTSD. Lisa is one of about 700 dogs the group has paired with veterans dealing with symptoms caused by traumatic experiences.

“Now with Lisa we take bike rides, we go down to the park, we go to Home Depot,” said Clark-Gutierrez. “I go grocery shopping — normal-people things that I get to do that I didn’t get to do before Lisa.”

That comes as no surprise to Maggie O’Haire, an associate professor of human-animal interaction at Purdue University. Her research suggests that while service dogs aren’t necessarily a cure for PTSD, they do ease its symptoms. Among her published studies is one showing that veterans partnered with these dogs experience less anger and anxiety and get better sleep than those without a service dog. Another of her studies suggests that service dogs lower cortisol levels in veterans who have been traumatized.

“We actually saw patterns of that stress hormone that were more similar to healthy adults who don’t have post-traumatic stress disorder,” O’Haire said.

A congressionally mandated VA study that focuses on service dogs’ impact on veterans with PTSD and was published this year suggests that those partnered with the animals experience less suicidal ideation and more improvement to their symptoms than those without them.

Until now, the federal dog referral program — which relies on nonprofit service dog organizations to pay for the dogs and to provide them to veterans for free — required that participating veterans have a physical mobility issue, such as a lost limb, paralysis or blindness. Veterans like Clark-Gutierrez who have PTSD but no physical disability were on their own in arranging for a service dog.

The pilot program created by the new federal law will give veterans with PTSD the chance to train mental health service dogs for other veterans. It’s modeled on a program at the VA hospital in Palo Alto, California, and will be offered at five VA medical centers nationwide in partnership with accredited service dog training organizations.

“This bill is really about therapeutic, on-the-job training, or ‘training the trainer,’” said Adam Webb, a spokesperson for Sen. Thom Tillis (R-N.C.), who introduced the legislation in the Senate. “We don’t anticipate VA will start prescribing PTSD service dogs, but the data we generate from this pilot program will likely be useful in making that case in the future.”

The Congressional Budget Office estimates the pilot program will cost the VA about $19 million. The law stops short of requiring the VA to pay for the dogs. Instead, the agency will partner with accredited service dog organizations that use private money to cover the cost of adopting, training and pairing the dogs with veterans.

Still, the law represents a welcome about-face in VA policy, said Rory Diamond, CEO of K9s for Warriors.

“For the last 10 years, the VA has essentially told us that they don’t recognize service dogs as helping a veteran with post-traumatic stress,” Diamond said.

PTSD service dogs are often confused with emotional support dogs, Diamond said. The latter provide companionship and are not trained to support someone with a disability. PTSD service dogs cost about $25,000 to adopt and train, he said.

Diamond explained that the command “cover” means “the dog will sit next to the warrior, look behind them and alert them if someone comes up from behind.” The command “block” means the dog will “stand perpendicular and give them some space from whatever’s in front of them.”

Retired Army Master Sgt. David Crenshaw of Kearny, New Jersey, said his service dog, Doc, has changed his life.

“We teach in the military to have a battle buddy,” Crenshaw said. “And these service animals act as a battle buddy.”

A few months ago, Crenshaw experienced this firsthand. He had generally avoided large gatherings because persistent hypervigilance is one symptom of his combat-caused PTSD. But this summer, Doc, a pointer and Labrador mix, helped Crenshaw navigate the crowds at Disney World — a significant first for Crenshaw and his family of five.

“I was not agitated. I was not anxious. I was not upset,” said Crenshaw, 39. “It was truly, truly amazing and so much so that I didn’t even have to even stop to think about it in the moment. It just happened naturally.”

Thanks to Doc, Crenshaw said, he no longer takes PTSD drugs or self-medicates with alcohol. Clark-Gutierrez said Lisa, too, has helped her quit using alcohol and stop taking VA-prescribed medications for panic attacks, nightmares and periods of disassociation.

The dogs actually save the VA money over time, Diamond said. “Our warriors are far less likely to be on expensive prescription drugs, are far less likely to use other VA services and far more likely to go to school or go to work. So it’s a win-win-win across the board.”

It was supper time in the Whittier, California, home of Air Force veteran Danyelle Clark-Gutierrez, and eagerly awaiting a bowl of kibble and canned dog food was Lisa, a 3-year-old yellow Labrador retriever.

Her nails clicking on the kitchen floor as she danced about, Lisa looked more like an exuberant puppy than the highly trained service animal that helps Clark-Gutierrez manage the symptoms of post-traumatic stress disorder.

“Having her now, it’s like I can go anywhere,” Clark-Gutierrez said. “And, yes, if somebody did come at me, I’d have warning — I could run.”

A growing body of research into PTSD and service animals paved the way for President Joe Biden to sign into law the Puppies Assisting Wounded Servicemembers (PAWS) for Veterans Therapy Act. The legislation, enacted in August, requires the Department of Veterans Affairs to open its service dog referral program to veterans with PTSD and to launch a five-year pilot program in which veterans with PTSD train service dogs for other veterans.

Clark-Gutierrez, 33, is among the 25 percent of female veterans who have reported experiencing military sexual trauma while serving in the U.S. armed services.

Military sexual trauma, combat violence and brain injuries are some of the experiences that increase the risk that service members will develop PTSD. Symptoms include flashbacks to the traumatic event, severe anxiety, nightmares and hypervigilance — all normal reactions to experiencing or witnessing violence, according to psychologists. Someone receives a PTSD diagnosis when symptoms worsen or remain for months or years.

That’s what Clark-Gutierrez said happened to her after ongoing sexual harassment by a fellow airman escalated to a physical attack about a decade ago. A lawyer with three children, she said that to feel safe leaving her home she needed her husband by her side. After diagnosing Clark-Gutierrez with PTSD, doctors at VA hospitals prescribed a cascade of medications for her. At one point, Clark-Gutierrez said, her prescriptions added up to more than a dozen pills a day.

“I had medication, and then I had medication for the two or three side effects for each medication,” she said. “And every time they gave me a new med, they had to give me three more. I just couldn’t do it anymore. I was just getting so tired. So we started looking at other therapies.”

And that’s how she got her service dog, Lisa. Clark-Gutierrez’s husband, also an Air Force veteran, discovered the nonprofit group K9s for Warriors, which rescues dogs — many from kill shelters — and trains them to be service animals for veterans with PTSD. Lisa is one of about 700 dogs the group has paired with veterans dealing with symptoms caused by traumatic experiences.

“Now with Lisa we take bike rides, we go down to the park, we go to Home Depot,” said Clark-Gutierrez. “I go grocery shopping — normal-people things that I get to do that I didn’t get to do before Lisa.”

That comes as no surprise to Maggie O’Haire, an associate professor of human-animal interaction at Purdue University. Her research suggests that while service dogs aren’t necessarily a cure for PTSD, they do ease its symptoms. Among her published studies is one showing that veterans partnered with these dogs experience less anger and anxiety and get better sleep than those without a service dog. Another of her studies suggests that service dogs lower cortisol levels in veterans who have been traumatized.

“We actually saw patterns of that stress hormone that were more similar to healthy adults who don’t have post-traumatic stress disorder,” O’Haire said.

A congressionally mandated VA study that focuses on service dogs’ impact on veterans with PTSD and was published this year suggests that those partnered with the animals experience less suicidal ideation and more improvement to their symptoms than those without them.

Until now, the federal dog referral program — which relies on nonprofit service dog organizations to pay for the dogs and to provide them to veterans for free — required that participating veterans have a physical mobility issue, such as a lost limb, paralysis or blindness. Veterans like Clark-Gutierrez who have PTSD but no physical disability were on their own in arranging for a service dog.

The pilot program created by the new federal law will give veterans with PTSD the chance to train mental health service dogs for other veterans. It’s modeled on a program at the VA hospital in Palo Alto, California, and will be offered at five VA medical centers nationwide in partnership with accredited service dog training organizations.

“This bill is really about therapeutic, on-the-job training, or ‘training the trainer,’” said Adam Webb, a spokesperson for Sen. Thom Tillis (R-N.C.), who introduced the legislation in the Senate. “We don’t anticipate VA will start prescribing PTSD service dogs, but the data we generate from this pilot program will likely be useful in making that case in the future.”

The Congressional Budget Office estimates the pilot program will cost the VA about $19 million. The law stops short of requiring the VA to pay for the dogs. Instead, the agency will partner with accredited service dog organizations that use private money to cover the cost of adopting, training and pairing the dogs with veterans.

Still, the law represents a welcome about-face in VA policy, said Rory Diamond, CEO of K9s for Warriors.

“For the last 10 years, the VA has essentially told us that they don’t recognize service dogs as helping a veteran with post-traumatic stress,” Diamond said.

PTSD service dogs are often confused with emotional support dogs, Diamond said. The latter provide companionship and are not trained to support someone with a disability. PTSD service dogs cost about $25,000 to adopt and train, he said.

Diamond explained that the command “cover” means “the dog will sit next to the warrior, look behind them and alert them if someone comes up from behind.” The command “block” means the dog will “stand perpendicular and give them some space from whatever’s in front of them.”

Retired Army Master Sgt. David Crenshaw of Kearny, New Jersey, said his service dog, Doc, has changed his life.

“We teach in the military to have a battle buddy,” Crenshaw said. “And these service animals act as a battle buddy.”

A few months ago, Crenshaw experienced this firsthand. He had generally avoided large gatherings because persistent hypervigilance is one symptom of his combat-caused PTSD. But this summer, Doc, a pointer and Labrador mix, helped Crenshaw navigate the crowds at Disney World — a significant first for Crenshaw and his family of five.

“I was not agitated. I was not anxious. I was not upset,” said Crenshaw, 39. “It was truly, truly amazing and so much so that I didn’t even have to even stop to think about it in the moment. It just happened naturally.”

Thanks to Doc, Crenshaw said, he no longer takes PTSD drugs or self-medicates with alcohol. Clark-Gutierrez said Lisa, too, has helped her quit using alcohol and stop taking VA-prescribed medications for panic attacks, nightmares and periods of disassociation.

The dogs actually save the VA money over time, Diamond said. “Our warriors are far less likely to be on expensive prescription drugs, are far less likely to use other VA services and far more likely to go to school or go to work. So it’s a win-win-win across the board.”

It was supper time in the Whittier, California, home of Air Force veteran Danyelle Clark-Gutierrez, and eagerly awaiting a bowl of kibble and canned dog food was Lisa, a 3-year-old yellow Labrador retriever.

Her nails clicking on the kitchen floor as she danced about, Lisa looked more like an exuberant puppy than the highly trained service animal that helps Clark-Gutierrez manage the symptoms of post-traumatic stress disorder.

“Having her now, it’s like I can go anywhere,” Clark-Gutierrez said. “And, yes, if somebody did come at me, I’d have warning — I could run.”

A growing body of research into PTSD and service animals paved the way for President Joe Biden to sign into law the Puppies Assisting Wounded Servicemembers (PAWS) for Veterans Therapy Act. The legislation, enacted in August, requires the Department of Veterans Affairs to open its service dog referral program to veterans with PTSD and to launch a five-year pilot program in which veterans with PTSD train service dogs for other veterans.

Clark-Gutierrez, 33, is among the 25 percent of female veterans who have reported experiencing military sexual trauma while serving in the U.S. armed services.

Military sexual trauma, combat violence and brain injuries are some of the experiences that increase the risk that service members will develop PTSD. Symptoms include flashbacks to the traumatic event, severe anxiety, nightmares and hypervigilance — all normal reactions to experiencing or witnessing violence, according to psychologists. Someone receives a PTSD diagnosis when symptoms worsen or remain for months or years.

That’s what Clark-Gutierrez said happened to her after ongoing sexual harassment by a fellow airman escalated to a physical attack about a decade ago. A lawyer with three children, she said that to feel safe leaving her home she needed her husband by her side. After diagnosing Clark-Gutierrez with PTSD, doctors at VA hospitals prescribed a cascade of medications for her. At one point, Clark-Gutierrez said, her prescriptions added up to more than a dozen pills a day.

“I had medication, and then I had medication for the two or three side effects for each medication,” she said. “And every time they gave me a new med, they had to give me three more. I just couldn’t do it anymore. I was just getting so tired. So we started looking at other therapies.”

And that’s how she got her service dog, Lisa. Clark-Gutierrez’s husband, also an Air Force veteran, discovered the nonprofit group K9s for Warriors, which rescues dogs — many from kill shelters — and trains them to be service animals for veterans with PTSD. Lisa is one of about 700 dogs the group has paired with veterans dealing with symptoms caused by traumatic experiences.

“Now with Lisa we take bike rides, we go down to the park, we go to Home Depot,” said Clark-Gutierrez. “I go grocery shopping — normal-people things that I get to do that I didn’t get to do before Lisa.”

That comes as no surprise to Maggie O’Haire, an associate professor of human-animal interaction at Purdue University. Her research suggests that while service dogs aren’t necessarily a cure for PTSD, they do ease its symptoms. Among her published studies is one showing that veterans partnered with these dogs experience less anger and anxiety and get better sleep than those without a service dog. Another of her studies suggests that service dogs lower cortisol levels in veterans who have been traumatized.

“We actually saw patterns of that stress hormone that were more similar to healthy adults who don’t have post-traumatic stress disorder,” O’Haire said.

A congressionally mandated VA study that focuses on service dogs’ impact on veterans with PTSD and was published this year suggests that those partnered with the animals experience less suicidal ideation and more improvement to their symptoms than those without them.

Until now, the federal dog referral program — which relies on nonprofit service dog organizations to pay for the dogs and to provide them to veterans for free — required that participating veterans have a physical mobility issue, such as a lost limb, paralysis or blindness. Veterans like Clark-Gutierrez who have PTSD but no physical disability were on their own in arranging for a service dog.

The pilot program created by the new federal law will give veterans with PTSD the chance to train mental health service dogs for other veterans. It’s modeled on a program at the VA hospital in Palo Alto, California, and will be offered at five VA medical centers nationwide in partnership with accredited service dog training organizations.

“This bill is really about therapeutic, on-the-job training, or ‘training the trainer,’” said Adam Webb, a spokesperson for Sen. Thom Tillis (R-N.C.), who introduced the legislation in the Senate. “We don’t anticipate VA will start prescribing PTSD service dogs, but the data we generate from this pilot program will likely be useful in making that case in the future.”

The Congressional Budget Office estimates the pilot program will cost the VA about $19 million. The law stops short of requiring the VA to pay for the dogs. Instead, the agency will partner with accredited service dog organizations that use private money to cover the cost of adopting, training and pairing the dogs with veterans.

Still, the law represents a welcome about-face in VA policy, said Rory Diamond, CEO of K9s for Warriors.

“For the last 10 years, the VA has essentially told us that they don’t recognize service dogs as helping a veteran with post-traumatic stress,” Diamond said.

PTSD service dogs are often confused with emotional support dogs, Diamond said. The latter provide companionship and are not trained to support someone with a disability. PTSD service dogs cost about $25,000 to adopt and train, he said.

Diamond explained that the command “cover” means “the dog will sit next to the warrior, look behind them and alert them if someone comes up from behind.” The command “block” means the dog will “stand perpendicular and give them some space from whatever’s in front of them.”

Retired Army Master Sgt. David Crenshaw of Kearny, New Jersey, said his service dog, Doc, has changed his life.

“We teach in the military to have a battle buddy,” Crenshaw said. “And these service animals act as a battle buddy.”

A few months ago, Crenshaw experienced this firsthand. He had generally avoided large gatherings because persistent hypervigilance is one symptom of his combat-caused PTSD. But this summer, Doc, a pointer and Labrador mix, helped Crenshaw navigate the crowds at Disney World — a significant first for Crenshaw and his family of five.

“I was not agitated. I was not anxious. I was not upset,” said Crenshaw, 39. “It was truly, truly amazing and so much so that I didn’t even have to even stop to think about it in the moment. It just happened naturally.”

Thanks to Doc, Crenshaw said, he no longer takes PTSD drugs or self-medicates with alcohol. Clark-Gutierrez said Lisa, too, has helped her quit using alcohol and stop taking VA-prescribed medications for panic attacks, nightmares and periods of disassociation.

The dogs actually save the VA money over time, Diamond said. “Our warriors are far less likely to be on expensive prescription drugs, are far less likely to use other VA services and far more likely to go to school or go to work. So it’s a win-win-win across the board.”

The diagnosis is squamous cell carcinoma. A central or hilar mass is most likely to be a squamous cell carcinoma or a small cell tumor and less commonly an adenocarcinoma. Histologically, when there is lack of cohesion among the epithelial cells due to malignant changes, the cells get arranged in a concentric manner. The fate of a squamous cell is to form keratin, so these cells lay down keratin in a concentric manner and then appear as keratin pearls. 

This patient's tumor is found to have programmed cell death–ligand 1 ≥ 1% and has no actionable molecular markers. The patient has a performance status score of 1. In a patient with advanced or metastatic squamous cell carcinoma with a performance status score of 1, the National Comprehensive Cancer Network recommends pembrolizumab/carboplatin/paclitaxel or pembrolizumab/carboplatin/albumin-bound paclitaxel as preferred regimens. The pembrolizumab component is based on the results of the KEYNOTE-407 trial. In patients with previously untreated metastatic, squamous non-small cell lung cancer, the addition of pembrolizumab to chemotherapy with carboplatin plus paclitaxel or nab-paclitaxel resulted in significantly longer overall survival and progression-free survival than chemotherapy alone.

Maurie Markman, MD, President, Department of Medical Oncology, Cancer Treatment Centers of America.

Maurie Markman, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Merck
Serve(d) as a speaker or a member of a speakers bureau for: AstraZeneca; Novis; Glaxo Smith Kline
Received research grant from: AstraZeneca; Novis; GSK; Merck

The diagnosis is squamous cell carcinoma. A central or hilar mass is most likely to be a squamous cell carcinoma or a small cell tumor and less commonly an adenocarcinoma. Histologically, when there is lack of cohesion among the epithelial cells due to malignant changes, the cells get arranged in a concentric manner. The fate of a squamous cell is to form keratin, so these cells lay down keratin in a concentric manner and then appear as keratin pearls. 

This patient's tumor is found to have programmed cell death–ligand 1 ≥ 1% and has no actionable molecular markers. The patient has a performance status score of 1. In a patient with advanced or metastatic squamous cell carcinoma with a performance status score of 1, the National Comprehensive Cancer Network recommends pembrolizumab/carboplatin/paclitaxel or pembrolizumab/carboplatin/albumin-bound paclitaxel as preferred regimens. The pembrolizumab component is based on the results of the KEYNOTE-407 trial. In patients with previously untreated metastatic, squamous non-small cell lung cancer, the addition of pembrolizumab to chemotherapy with carboplatin plus paclitaxel or nab-paclitaxel resulted in significantly longer overall survival and progression-free survival than chemotherapy alone.

Maurie Markman, MD, President, Department of Medical Oncology, Cancer Treatment Centers of America.

Maurie Markman, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Merck
Serve(d) as a speaker or a member of a speakers bureau for: AstraZeneca; Novis; Glaxo Smith Kline
Received research grant from: AstraZeneca; Novis; GSK; Merck

The diagnosis is squamous cell carcinoma. A central or hilar mass is most likely to be a squamous cell carcinoma or a small cell tumor and less commonly an adenocarcinoma. Histologically, when there is lack of cohesion among the epithelial cells due to malignant changes, the cells get arranged in a concentric manner. The fate of a squamous cell is to form keratin, so these cells lay down keratin in a concentric manner and then appear as keratin pearls. 

This patient's tumor is found to have programmed cell death–ligand 1 ≥ 1% and has no actionable molecular markers. The patient has a performance status score of 1. In a patient with advanced or metastatic squamous cell carcinoma with a performance status score of 1, the National Comprehensive Cancer Network recommends pembrolizumab/carboplatin/paclitaxel or pembrolizumab/carboplatin/albumin-bound paclitaxel as preferred regimens. The pembrolizumab component is based on the results of the KEYNOTE-407 trial. In patients with previously untreated metastatic, squamous non-small cell lung cancer, the addition of pembrolizumab to chemotherapy with carboplatin plus paclitaxel or nab-paclitaxel resulted in significantly longer overall survival and progression-free survival than chemotherapy alone.

Maurie Markman, MD, President, Department of Medical Oncology, Cancer Treatment Centers of America.

Maurie Markman, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Merck
Serve(d) as a speaker or a member of a speakers bureau for: AstraZeneca; Novis; Glaxo Smith Kline
Received research grant from: AstraZeneca; Novis; GSK; Merck

Dr. April Lockley’s commentary marks the final special article Family Practice News is publishing to celebrate its 50th Anniversary. While this is the last piece in a series, my intention is for it to read more like the opening of a new book on family medicine, rather than an ending to a story about the specialty.

April Lockley, DO, represents a new generation of family physicians who began their careers in the 21st century, and she is hopeful that the experiences of practicing family medicine and being the patient of a family physician will change in several ways.

Among her desires for the future, is to be able to write a prescription for a medication or physical therapy to a patient who is able “to fill the prescription without having to worry about the financial implications of paying for it,” she writes. She also hopes “patients can seek out care without the fear of discrimination or racism through an increasingly diverse work force.”

In her article, Dr. Lockley both expresses how she wants family medicine to change and what she already finds satisfying about being a family physician.

I hope you enjoyed reading about the professional journeys of Dr. Lockley and other family physicians who have written commentaries or interviewed for articles in Family Practice News’ 50th Anniversary series this year.

To revisit any of these articles, go to the 50th Anniversary bucket on mdedge.com/familymedicine.

Thank you for continuing to read Family Practice News, and I hope to celebrate more milestones with you in the future.

[email protected]

Dr. April Lockley’s commentary marks the final special article Family Practice News is publishing to celebrate its 50th Anniversary. While this is the last piece in a series, my intention is for it to read more like the opening of a new book on family medicine, rather than an ending to a story about the specialty.

April Lockley, DO, represents a new generation of family physicians who began their careers in the 21st century, and she is hopeful that the experiences of practicing family medicine and being the patient of a family physician will change in several ways.

Among her desires for the future, is to be able to write a prescription for a medication or physical therapy to a patient who is able “to fill the prescription without having to worry about the financial implications of paying for it,” she writes. She also hopes “patients can seek out care without the fear of discrimination or racism through an increasingly diverse work force.”

In her article, Dr. Lockley both expresses how she wants family medicine to change and what she already finds satisfying about being a family physician.

I hope you enjoyed reading about the professional journeys of Dr. Lockley and other family physicians who have written commentaries or interviewed for articles in Family Practice News’ 50th Anniversary series this year.

To revisit any of these articles, go to the 50th Anniversary bucket on mdedge.com/familymedicine.

Thank you for continuing to read Family Practice News, and I hope to celebrate more milestones with you in the future.

[email protected]

Dr. April Lockley’s commentary marks the final special article Family Practice News is publishing to celebrate its 50th Anniversary. While this is the last piece in a series, my intention is for it to read more like the opening of a new book on family medicine, rather than an ending to a story about the specialty.

April Lockley, DO, represents a new generation of family physicians who began their careers in the 21st century, and she is hopeful that the experiences of practicing family medicine and being the patient of a family physician will change in several ways.

Among her desires for the future, is to be able to write a prescription for a medication or physical therapy to a patient who is able “to fill the prescription without having to worry about the financial implications of paying for it,” she writes. She also hopes “patients can seek out care without the fear of discrimination or racism through an increasingly diverse work force.”

In her article, Dr. Lockley both expresses how she wants family medicine to change and what she already finds satisfying about being a family physician.

I hope you enjoyed reading about the professional journeys of Dr. Lockley and other family physicians who have written commentaries or interviewed for articles in Family Practice News’ 50th Anniversary series this year.

To revisit any of these articles, go to the 50th Anniversary bucket on mdedge.com/familymedicine.

Thank you for continuing to read Family Practice News, and I hope to celebrate more milestones with you in the future.

[email protected]

Background: There are extensive publications regarding preoperative risk assessment and optimization of risk management. This article is a review of current aggregate data from various meta-analyses and observational studies. It explores a systematic approach to preoperative risk assessment.

Dr. Young is a hospitalist at Northwestern Memorial Hospital and instructor of medicine, Feinberg School of Medicine, both in Chicago.

Background: There are extensive publications regarding preoperative risk assessment and optimization of risk management. This article is a review of current aggregate data from various meta-analyses and observational studies. It explores a systematic approach to preoperative risk assessment.

Dr. Young is a hospitalist at Northwestern Memorial Hospital and instructor of medicine, Feinberg School of Medicine, both in Chicago.

Background: There are extensive publications regarding preoperative risk assessment and optimization of risk management. This article is a review of current aggregate data from various meta-analyses and observational studies. It explores a systematic approach to preoperative risk assessment.

Dr. Young is a hospitalist at Northwestern Memorial Hospital and instructor of medicine, Feinberg School of Medicine, both in Chicago.