Article

THE CASE

Juana*, a 10-year-old who identifies as a cisgender, Hispanic female, was referred to our integrated behavioral health program by her primary care physician. Her mother was concerned because Juana had been refusing to attend school due to complaints of gastrointestinal upset. This concern began when Juana was in first grade but had increased in severity over the past few months.

Upon further questioning, the patient reported that she initially did not want to attend school due to academic difficulties and bullying. However, since COVID-19, her fears of attending school had significantly worsened. Juana’s mother’s primary language was Spanish and she had limited English proficiency; she reported difficulty communicating with school personnel about Juana’s poor attendance.

Juana had recently had a complete medical work-up for her gastrointestinal concerns, with negative results. Since the negative work-up, Juana’s mother had told her daughter that she would be punished if she didn’t go to school.

● How would you proceed with this patient?

* The patient’s name has been changed to protect her identity.

School avoidance, also referred to as school refusal, is a symptom of an emotional condition that manifests as a child refusing to go to school or having difficulty going to school or remaining in the classroom for the entire day. School avoidance is not a clinical diagnosis but often is related to an underlying disorder.¹

School avoidance is common, affecting 5% to 28% of youth sometime in their school career.² Available data are not specific to school avoidance but focus on chronic absenteeism (missing ≥ 15 days per school year). Rates of chronic absenteeism are high in elementary and middle school (about 14% each) and tend to increase in high school (about 21%).³ Students with disabilities are 1.5 times more likely to be chronically absent than students without disabilities.³ Compared to White students, American Indian and Pacific Islander students are > 50% more likely, Black students 40% more likely, and Hispanic students 17% more likely to miss ≥ 3 weeks of school.³ Rates of chronic absenteeism are similar (about 16%) for males and females.³

Absenteeism can have immediate and long-term negative effects.⁴ School attendance issues are correlated to negative life outcomes, such as delinquency, teen pregnancy, substance use, and poor academic achievement.⁵ According to the US Department of Education, individuals who chronically miss school are less likely to achieve educational milestones (particularly in younger years) and may be more likely to drop out of school.³

What school avoidance is (and what it isn’t)

It is important to distinguish school avoidance from truancy. Truancy often is associated with antisocial behavior such as lying and stealing, while school avoidance occurs in the absence of significant antisocial disorders.⁶ With truancy, the absence usually is hidden from the parent. In contrast, with school avoidance, the parents usually know where their child is; the child often spends the day secluded in their bedroom. Students who engage in truancy do not demonstrate excessive anxiety about attending school but may have decreased interest in schoolwork and academic performance.⁶ With school avoidance, the child exhibits severe emotional distress about attending school but is willing to complete schoolwork at home.

Why children may avoid school

School avoidance is a biopsychosocial condition with a multitude of underlying causes.⁴ It is associated most commonly with anxiety disorders and neurodevelopmental disorders, including but not limited to learning disabilities and attention-deficit/hyperactivity disorder.¹ Depressive disorders also have been associated with school avoidance.⁷ Social concerns related to changes with school personnel or classes, academic challenges, bullying, health emergencies, and family stressors also can result in symptoms of school avoidance.¹

Continue to: A child seeking to avoid...

A child seeking to avoid school may be motivated by potential negative and/or positive effects of doing so. Kearney and Silverman⁸ identified 4 primary functions of school refusal behaviors:

• avoiding stimuli at school that lend to negative affect (depression, anxiety)
• escaping the social interactions and/or situations for evaluation that occur at school
• gaining more attention from caregivers, and
• obtaining tangible rewards or benefits outside the school environment.

How school avoidance manifests

School avoidance has attributes of internalizing (depression, anxiety, somatic complaints) and externalizing (aggression, tantrums, running away, clinginess) behaviors. It can cause distress for the student, parents and caregivers, and school personnel.

With school avoidance, the child exhibits severe emotional distress about attending school but is willing to complete schoolwork at home.

The avoidance may manifest with behaviors such as crying, hiding, emotional outbursts, and refusing to move prior to the start of the school day. Additionally, the child may beg their parents not to make them go to school or, when at school, they may leave the classroom to go to a safe place such as the nurse’s or counselor’s office.

The avoidance may occur abruptly, such as after a break in the school schedule or a change of school. Or it may be the final result of the student’s gradual inability to cope with the underlying issue.

How to assess for school avoidance

Due to the multifactorial nature of this presenting concern, a comprehensive evaluation is recommended when school avoidance is reported.⁴ Often the child will present with physical symptoms, such as abdominal pain, nausea, vomiting, diarrhea, headaches, shortness of breath, dizziness, chest pain, and palpitations. A thorough medical examination should be performed to rule out a physiological cause. The medical visit should include clinical interviews with the patient and family members or guardians.

Continue to: To identify school avoidance...

To identify school avoidance in pediatric and adolescent populations, medical history and physical ­examination—along with social history to better understand familial, social, and academic concerns—should be a regular part of the medical encounter. The School Refusal Assessment Scale-Revised (SRAS-R) for both parents and their children was developed to assess for school avoidance and can be utilized within the primary care setting. Additional psychiatric history for both the family and patient may be beneficial, due to associations between parental mental health concerns and school avoidance in their children.^9,10

More than onethird of children with behavioral problems, such as school avoidance, have been diagnosed with anxiety.

Assessment for an underlying mental health condition, such as an anxiety or depressive disorder, should be completed when a patient presents with school avoidance.⁴ More than one-third of children with behavioral problems, such as school avoidance, have been diagnosed with anxiety.¹¹ The 2020 National Survey of Children’s Health found that 7.8% of children and adolescents ages 3 to 17 years had a current anxiety disorder, leading the US Preventive Services Task Force to recommend screening for anxiety in children and adolescents ages 8 to 18 years.^12,13 Furthermore, if academic achievement is of concern, then consideration of further assessment for neurodevelopmental disorders is warranted.¹

Treatment is multimodal and multidisciplinary

Treatment for school avoidance is often multimodal and may involve interdisciplinary, team-based care including the medical provider, school system (eg, Child Study Team), family, and mental health care provider.^1,4

Cognitive behavioral therapy (CBT) is the most-studied intervention for school avoidance, with behavioral, exposure-based interventions often central to therapeutic gains in treatment.^1,14,15 The goals of treatment are to increase school attendance while decreasing emotional distress through various strategies, including exposure-based interventions, contingency management with parents and school staff, relaxation training, and/or social skills training.^14,16 Collaborative involvement between the medical provider and the school system is key to successful treatment.

Medication may be considered alone or in combination with CBT when comorbid mental health conditions have been identified. Selective serotonin reuptake inhibitors (SSRIs)—including fluoxetine, sertraline, and escitalopram—are considered first-line treatment for anxiety in children and adolescents.¹⁷ Serotonin-norepinephrine reuptake inhibitors (SNRIs), such as duloxetine and venlafaxine, also have been shown to be effective. Duloxetine is the only medication approved by the US Food and Drug Administration (FDA) for treatment of generalized anxiety disorder in children ages 7 years and older.¹⁷

Continue to: SSRIs and SNRIs have a boxed warning...

SSRIs and SNRIs have a boxed warning from the FDA for increased suicidal thoughts and behaviors in children and adolescents. Although this risk is rare, it should be discussed with the patient and parent/guardian in order to obtain informed consent prior to treatment initiation.

Medication should be started at the lowest possible dose and increased gradually. Patients should remain on the medication for 6 to 12 months after symptom resolution and should be tapered during a nonstressful time, such as the summer break.

THE CASE

Based on the concerns of continued school refusal after negative gastrointestinal work-up, Juana’s physician screened her for anxiety and conducted a clinical interview to better understand any psychosocial concerns. Juana’s score of 10 on the General Anxiety Disorder-7 scale indicated moderate anxiety. She reported symptoms consistent with social anxiety disorder contributing to school avoidance.

The physician consulted with the clinic’s behavioral health consultant (BHC) to confirm the multimodal treatment plan, which was then discussed with Juana and her mother. The physician discussed medication options (SSRIs) and provided documentation (in both English and Spanish) from the visit to Juana’s mother so she could initiate a school-based intervention with the Child Study Team at Juana’s school. A plan for CBT—including a collaborative contingency management plan between the patient and her parent (eg, a reward chart for attending school) and exposure interventions (eg, a graduated plan to participate in school-based activities with the end goal to resume full school attendance)—was developed with the BHC. Biweekly follow-up appointments were scheduled with the BHC and monthly appointments were scheduled with the physician to reinforce the interventions.

CORRESPONDENCE
Meredith L. C. Williamson, PhD, 2900 East 29th Street, Suite 100, Bryan, TX 77840; [email protected]

THE CASE

Juana*, a 10-year-old who identifies as a cisgender, Hispanic female, was referred to our integrated behavioral health program by her primary care physician. Her mother was concerned because Juana had been refusing to attend school due to complaints of gastrointestinal upset. This concern began when Juana was in first grade but had increased in severity over the past few months.

Upon further questioning, the patient reported that she initially did not want to attend school due to academic difficulties and bullying. However, since COVID-19, her fears of attending school had significantly worsened. Juana’s mother’s primary language was Spanish and she had limited English proficiency; she reported difficulty communicating with school personnel about Juana’s poor attendance.

Juana had recently had a complete medical work-up for her gastrointestinal concerns, with negative results. Since the negative work-up, Juana’s mother had told her daughter that she would be punished if she didn’t go to school.

● How would you proceed with this patient?

* The patient’s name has been changed to protect her identity.

School avoidance, also referred to as school refusal, is a symptom of an emotional condition that manifests as a child refusing to go to school or having difficulty going to school or remaining in the classroom for the entire day. School avoidance is not a clinical diagnosis but often is related to an underlying disorder.¹

School avoidance is common, affecting 5% to 28% of youth sometime in their school career.² Available data are not specific to school avoidance but focus on chronic absenteeism (missing ≥ 15 days per school year). Rates of chronic absenteeism are high in elementary and middle school (about 14% each) and tend to increase in high school (about 21%).³ Students with disabilities are 1.5 times more likely to be chronically absent than students without disabilities.³ Compared to White students, American Indian and Pacific Islander students are > 50% more likely, Black students 40% more likely, and Hispanic students 17% more likely to miss ≥ 3 weeks of school.³ Rates of chronic absenteeism are similar (about 16%) for males and females.³

Absenteeism can have immediate and long-term negative effects.⁴ School attendance issues are correlated to negative life outcomes, such as delinquency, teen pregnancy, substance use, and poor academic achievement.⁵ According to the US Department of Education, individuals who chronically miss school are less likely to achieve educational milestones (particularly in younger years) and may be more likely to drop out of school.³

What school avoidance is (and what it isn’t)

It is important to distinguish school avoidance from truancy. Truancy often is associated with antisocial behavior such as lying and stealing, while school avoidance occurs in the absence of significant antisocial disorders.⁶ With truancy, the absence usually is hidden from the parent. In contrast, with school avoidance, the parents usually know where their child is; the child often spends the day secluded in their bedroom. Students who engage in truancy do not demonstrate excessive anxiety about attending school but may have decreased interest in schoolwork and academic performance.⁶ With school avoidance, the child exhibits severe emotional distress about attending school but is willing to complete schoolwork at home.

Why children may avoid school

School avoidance is a biopsychosocial condition with a multitude of underlying causes.⁴ It is associated most commonly with anxiety disorders and neurodevelopmental disorders, including but not limited to learning disabilities and attention-deficit/hyperactivity disorder.¹ Depressive disorders also have been associated with school avoidance.⁷ Social concerns related to changes with school personnel or classes, academic challenges, bullying, health emergencies, and family stressors also can result in symptoms of school avoidance.¹

Continue to: A child seeking to avoid...

A child seeking to avoid school may be motivated by potential negative and/or positive effects of doing so. Kearney and Silverman⁸ identified 4 primary functions of school refusal behaviors:

• avoiding stimuli at school that lend to negative affect (depression, anxiety)
• escaping the social interactions and/or situations for evaluation that occur at school
• gaining more attention from caregivers, and
• obtaining tangible rewards or benefits outside the school environment.

How school avoidance manifests

School avoidance has attributes of internalizing (depression, anxiety, somatic complaints) and externalizing (aggression, tantrums, running away, clinginess) behaviors. It can cause distress for the student, parents and caregivers, and school personnel.

With school avoidance, the child exhibits severe emotional distress about attending school but is willing to complete schoolwork at home.

The avoidance may manifest with behaviors such as crying, hiding, emotional outbursts, and refusing to move prior to the start of the school day. Additionally, the child may beg their parents not to make them go to school or, when at school, they may leave the classroom to go to a safe place such as the nurse’s or counselor’s office.

The avoidance may occur abruptly, such as after a break in the school schedule or a change of school. Or it may be the final result of the student’s gradual inability to cope with the underlying issue.

How to assess for school avoidance

Due to the multifactorial nature of this presenting concern, a comprehensive evaluation is recommended when school avoidance is reported.⁴ Often the child will present with physical symptoms, such as abdominal pain, nausea, vomiting, diarrhea, headaches, shortness of breath, dizziness, chest pain, and palpitations. A thorough medical examination should be performed to rule out a physiological cause. The medical visit should include clinical interviews with the patient and family members or guardians.

Continue to: To identify school avoidance...

To identify school avoidance in pediatric and adolescent populations, medical history and physical ­examination—along with social history to better understand familial, social, and academic concerns—should be a regular part of the medical encounter. The School Refusal Assessment Scale-Revised (SRAS-R) for both parents and their children was developed to assess for school avoidance and can be utilized within the primary care setting. Additional psychiatric history for both the family and patient may be beneficial, due to associations between parental mental health concerns and school avoidance in their children.^9,10

More than onethird of children with behavioral problems, such as school avoidance, have been diagnosed with anxiety.

Assessment for an underlying mental health condition, such as an anxiety or depressive disorder, should be completed when a patient presents with school avoidance.⁴ More than one-third of children with behavioral problems, such as school avoidance, have been diagnosed with anxiety.¹¹ The 2020 National Survey of Children’s Health found that 7.8% of children and adolescents ages 3 to 17 years had a current anxiety disorder, leading the US Preventive Services Task Force to recommend screening for anxiety in children and adolescents ages 8 to 18 years.^12,13 Furthermore, if academic achievement is of concern, then consideration of further assessment for neurodevelopmental disorders is warranted.¹

Treatment is multimodal and multidisciplinary

Treatment for school avoidance is often multimodal and may involve interdisciplinary, team-based care including the medical provider, school system (eg, Child Study Team), family, and mental health care provider.^1,4

Cognitive behavioral therapy (CBT) is the most-studied intervention for school avoidance, with behavioral, exposure-based interventions often central to therapeutic gains in treatment.^1,14,15 The goals of treatment are to increase school attendance while decreasing emotional distress through various strategies, including exposure-based interventions, contingency management with parents and school staff, relaxation training, and/or social skills training.^14,16 Collaborative involvement between the medical provider and the school system is key to successful treatment.

Medication may be considered alone or in combination with CBT when comorbid mental health conditions have been identified. Selective serotonin reuptake inhibitors (SSRIs)—including fluoxetine, sertraline, and escitalopram—are considered first-line treatment for anxiety in children and adolescents.¹⁷ Serotonin-norepinephrine reuptake inhibitors (SNRIs), such as duloxetine and venlafaxine, also have been shown to be effective. Duloxetine is the only medication approved by the US Food and Drug Administration (FDA) for treatment of generalized anxiety disorder in children ages 7 years and older.¹⁷

Continue to: SSRIs and SNRIs have a boxed warning...

SSRIs and SNRIs have a boxed warning from the FDA for increased suicidal thoughts and behaviors in children and adolescents. Although this risk is rare, it should be discussed with the patient and parent/guardian in order to obtain informed consent prior to treatment initiation.

Medication should be started at the lowest possible dose and increased gradually. Patients should remain on the medication for 6 to 12 months after symptom resolution and should be tapered during a nonstressful time, such as the summer break.

THE CASE

Based on the concerns of continued school refusal after negative gastrointestinal work-up, Juana’s physician screened her for anxiety and conducted a clinical interview to better understand any psychosocial concerns. Juana’s score of 10 on the General Anxiety Disorder-7 scale indicated moderate anxiety. She reported symptoms consistent with social anxiety disorder contributing to school avoidance.

The physician consulted with the clinic’s behavioral health consultant (BHC) to confirm the multimodal treatment plan, which was then discussed with Juana and her mother. The physician discussed medication options (SSRIs) and provided documentation (in both English and Spanish) from the visit to Juana’s mother so she could initiate a school-based intervention with the Child Study Team at Juana’s school. A plan for CBT—including a collaborative contingency management plan between the patient and her parent (eg, a reward chart for attending school) and exposure interventions (eg, a graduated plan to participate in school-based activities with the end goal to resume full school attendance)—was developed with the BHC. Biweekly follow-up appointments were scheduled with the BHC and monthly appointments were scheduled with the physician to reinforce the interventions.

CORRESPONDENCE
Meredith L. C. Williamson, PhD, 2900 East 29th Street, Suite 100, Bryan, TX 77840; [email protected]

THE CASE

Juana*, a 10-year-old who identifies as a cisgender, Hispanic female, was referred to our integrated behavioral health program by her primary care physician. Her mother was concerned because Juana had been refusing to attend school due to complaints of gastrointestinal upset. This concern began when Juana was in first grade but had increased in severity over the past few months.

Upon further questioning, the patient reported that she initially did not want to attend school due to academic difficulties and bullying. However, since COVID-19, her fears of attending school had significantly worsened. Juana’s mother’s primary language was Spanish and she had limited English proficiency; she reported difficulty communicating with school personnel about Juana’s poor attendance.

Juana had recently had a complete medical work-up for her gastrointestinal concerns, with negative results. Since the negative work-up, Juana’s mother had told her daughter that she would be punished if she didn’t go to school.

● How would you proceed with this patient?

* The patient’s name has been changed to protect her identity.

School avoidance, also referred to as school refusal, is a symptom of an emotional condition that manifests as a child refusing to go to school or having difficulty going to school or remaining in the classroom for the entire day. School avoidance is not a clinical diagnosis but often is related to an underlying disorder.¹

School avoidance is common, affecting 5% to 28% of youth sometime in their school career.² Available data are not specific to school avoidance but focus on chronic absenteeism (missing ≥ 15 days per school year). Rates of chronic absenteeism are high in elementary and middle school (about 14% each) and tend to increase in high school (about 21%).³ Students with disabilities are 1.5 times more likely to be chronically absent than students without disabilities.³ Compared to White students, American Indian and Pacific Islander students are > 50% more likely, Black students 40% more likely, and Hispanic students 17% more likely to miss ≥ 3 weeks of school.³ Rates of chronic absenteeism are similar (about 16%) for males and females.³

Absenteeism can have immediate and long-term negative effects.⁴ School attendance issues are correlated to negative life outcomes, such as delinquency, teen pregnancy, substance use, and poor academic achievement.⁵ According to the US Department of Education, individuals who chronically miss school are less likely to achieve educational milestones (particularly in younger years) and may be more likely to drop out of school.³

What school avoidance is (and what it isn’t)

It is important to distinguish school avoidance from truancy. Truancy often is associated with antisocial behavior such as lying and stealing, while school avoidance occurs in the absence of significant antisocial disorders.⁶ With truancy, the absence usually is hidden from the parent. In contrast, with school avoidance, the parents usually know where their child is; the child often spends the day secluded in their bedroom. Students who engage in truancy do not demonstrate excessive anxiety about attending school but may have decreased interest in schoolwork and academic performance.⁶ With school avoidance, the child exhibits severe emotional distress about attending school but is willing to complete schoolwork at home.

Why children may avoid school

School avoidance is a biopsychosocial condition with a multitude of underlying causes.⁴ It is associated most commonly with anxiety disorders and neurodevelopmental disorders, including but not limited to learning disabilities and attention-deficit/hyperactivity disorder.¹ Depressive disorders also have been associated with school avoidance.⁷ Social concerns related to changes with school personnel or classes, academic challenges, bullying, health emergencies, and family stressors also can result in symptoms of school avoidance.¹

Continue to: A child seeking to avoid...

A child seeking to avoid school may be motivated by potential negative and/or positive effects of doing so. Kearney and Silverman⁸ identified 4 primary functions of school refusal behaviors:

• avoiding stimuli at school that lend to negative affect (depression, anxiety)
• escaping the social interactions and/or situations for evaluation that occur at school
• gaining more attention from caregivers, and
• obtaining tangible rewards or benefits outside the school environment.

How school avoidance manifests

School avoidance has attributes of internalizing (depression, anxiety, somatic complaints) and externalizing (aggression, tantrums, running away, clinginess) behaviors. It can cause distress for the student, parents and caregivers, and school personnel.

With school avoidance, the child exhibits severe emotional distress about attending school but is willing to complete schoolwork at home.

The avoidance may manifest with behaviors such as crying, hiding, emotional outbursts, and refusing to move prior to the start of the school day. Additionally, the child may beg their parents not to make them go to school or, when at school, they may leave the classroom to go to a safe place such as the nurse’s or counselor’s office.

The avoidance may occur abruptly, such as after a break in the school schedule or a change of school. Or it may be the final result of the student’s gradual inability to cope with the underlying issue.

How to assess for school avoidance

Due to the multifactorial nature of this presenting concern, a comprehensive evaluation is recommended when school avoidance is reported.⁴ Often the child will present with physical symptoms, such as abdominal pain, nausea, vomiting, diarrhea, headaches, shortness of breath, dizziness, chest pain, and palpitations. A thorough medical examination should be performed to rule out a physiological cause. The medical visit should include clinical interviews with the patient and family members or guardians.

Continue to: To identify school avoidance...

To identify school avoidance in pediatric and adolescent populations, medical history and physical ­examination—along with social history to better understand familial, social, and academic concerns—should be a regular part of the medical encounter. The School Refusal Assessment Scale-Revised (SRAS-R) for both parents and their children was developed to assess for school avoidance and can be utilized within the primary care setting. Additional psychiatric history for both the family and patient may be beneficial, due to associations between parental mental health concerns and school avoidance in their children.^9,10

More than onethird of children with behavioral problems, such as school avoidance, have been diagnosed with anxiety.

Assessment for an underlying mental health condition, such as an anxiety or depressive disorder, should be completed when a patient presents with school avoidance.⁴ More than one-third of children with behavioral problems, such as school avoidance, have been diagnosed with anxiety.¹¹ The 2020 National Survey of Children’s Health found that 7.8% of children and adolescents ages 3 to 17 years had a current anxiety disorder, leading the US Preventive Services Task Force to recommend screening for anxiety in children and adolescents ages 8 to 18 years.^12,13 Furthermore, if academic achievement is of concern, then consideration of further assessment for neurodevelopmental disorders is warranted.¹

Treatment is multimodal and multidisciplinary

Treatment for school avoidance is often multimodal and may involve interdisciplinary, team-based care including the medical provider, school system (eg, Child Study Team), family, and mental health care provider.^1,4

Cognitive behavioral therapy (CBT) is the most-studied intervention for school avoidance, with behavioral, exposure-based interventions often central to therapeutic gains in treatment.^1,14,15 The goals of treatment are to increase school attendance while decreasing emotional distress through various strategies, including exposure-based interventions, contingency management with parents and school staff, relaxation training, and/or social skills training.^14,16 Collaborative involvement between the medical provider and the school system is key to successful treatment.

Medication may be considered alone or in combination with CBT when comorbid mental health conditions have been identified. Selective serotonin reuptake inhibitors (SSRIs)—including fluoxetine, sertraline, and escitalopram—are considered first-line treatment for anxiety in children and adolescents.¹⁷ Serotonin-norepinephrine reuptake inhibitors (SNRIs), such as duloxetine and venlafaxine, also have been shown to be effective. Duloxetine is the only medication approved by the US Food and Drug Administration (FDA) for treatment of generalized anxiety disorder in children ages 7 years and older.¹⁷

Continue to: SSRIs and SNRIs have a boxed warning...

SSRIs and SNRIs have a boxed warning from the FDA for increased suicidal thoughts and behaviors in children and adolescents. Although this risk is rare, it should be discussed with the patient and parent/guardian in order to obtain informed consent prior to treatment initiation.

Medication should be started at the lowest possible dose and increased gradually. Patients should remain on the medication for 6 to 12 months after symptom resolution and should be tapered during a nonstressful time, such as the summer break.

THE CASE

Based on the concerns of continued school refusal after negative gastrointestinal work-up, Juana’s physician screened her for anxiety and conducted a clinical interview to better understand any psychosocial concerns. Juana’s score of 10 on the General Anxiety Disorder-7 scale indicated moderate anxiety. She reported symptoms consistent with social anxiety disorder contributing to school avoidance.

The physician consulted with the clinic’s behavioral health consultant (BHC) to confirm the multimodal treatment plan, which was then discussed with Juana and her mother. The physician discussed medication options (SSRIs) and provided documentation (in both English and Spanish) from the visit to Juana’s mother so she could initiate a school-based intervention with the Child Study Team at Juana’s school. A plan for CBT—including a collaborative contingency management plan between the patient and her parent (eg, a reward chart for attending school) and exposure interventions (eg, a graduated plan to participate in school-based activities with the end goal to resume full school attendance)—was developed with the BHC. Biweekly follow-up appointments were scheduled with the BHC and monthly appointments were scheduled with the physician to reinforce the interventions.

CORRESPONDENCE
Meredith L. C. Williamson, PhD, 2900 East 29th Street, Suite 100, Bryan, TX 77840; [email protected]

ABSTRACT

Background: The Altman Rule, a simple tool for consumers seeking to make healthier packaged food choices at the point of sale, applies to packaged carbohydrates. According to the Altman Rule, a food is a healthier option if it has at least 3 g of fiber per serving and the grams of fiber plus the grams of protein exceed the grams of sugar per serving. This study sought to evaluate whether the Altman Rule is a valid proxy for glycemic load (GL).

Methods: We compared the binary outcome of whether a food item meets the Altman Rule with the GL of all foods categorized as cereals, chips, crackers, and granola bars in the Nutrition Data System for Research Database (University of Minnesota, Version 2010). We examined the percentage of foods in low-, medium-, and high-GL categories that met the Altman Rule.

Results: There were 1235 foods (342 cereals, 305 chips, 379 crackers, and 209 granola bars) in this analysis. There was a significant relationship between the GL of foods and the Altman Rule (P < .001) in that most low-GL (68%), almost half of medium-GL (48%), and very few high-GL (7%) foods met the criteria of the rule.

Conclusions: The Altman Rule is a reasonable proxy for GL and can be a useful and accessible tool for consumers interested in buying healthier packaged carbohydrate foods.

Nutrition can be complicated for consumers interested in making healthier choices at the grocery store. Consumers may have difficulty identifying more nutritious options, especially when food labels are adorned with claims such as “Good Source of Fiber” or “Heart Healthy.”¹ In addition, when reading food labels, consumers may find it difficult to decipher which data to prioritize when carbohydrates, total sugars, added sugars, total dietary fiber, soluble fiber, and insoluble fiber are all listed.

The concept of glycemic load (GL) is an important consideration, especially for people with diabetes. GL approximates the blood sugar response to different foods. A food with a high GL is digested quickly, and its carbohydrates are taken into the bloodstream rapidly. This leads to a spike and subsequent drop in blood sugars, which can cause symptoms of hyperglycemia and hypoglycemia in a person with diabetes.^2,3 Despite its usefulness, GL may be too complicated for a consumer to understand, and it does not appear anywhere on the food label. Since GL is calculated using pooled blood sugar response from individuals after the ingestion of the particular food, estimation of the GL is not intuitable.⁴

Point-of-sale tools. People seeking to lose weight, control diabetes, improve dyslipidemia and/or blood pressure, and/or decrease their risk for heart disease may benefit from point-of-sale tools such as the Altman Rule, which simplifies and encourages the selection of more nutritious foods.¹ Other tools—such as Guiding Stars (https://guidingstars.com), NuVal (www.nuval.com), and different variations of traffic lights—have been created to help consumers make more informed and healthier food choices.^5-8 However, Guiding Stars and NuVal are based on complicated algorithms that are not entirely transparent and not accessible to the average consumer.^6,7 Evaluations of these nutrition tools indicate that consumers tend to underrate the healthiness of some foods, such as raw almonds and salmon, and overrate the healthiness of others, such as fruit punch and diet soda, when using traffic light systems.⁶ Furthermore, these nutrition tools are not available in many supermarkets. Previous research suggests that the use of point-of-sale nutrition apps decreases with the time and effort involved in using an app.⁹

Continue to: The Altman Rule

The Altman Rule was developed by a family physician (author WA) to provide a more accessible tool for people interested in choosing healthier prepackaged carbohydrate foods while shopping. Since the user does not need to have a smartphone, and they are not required to download or understand an app for each purchase, the Altman Rule may be more usable compared with more complicated alternatives.

The Altman Rule can be used with nutrition labels that feature serving information and calories in enlarged and bold type, in compliance with the most recent US Food and Drug Administration (FDA) guideline from 2016. Many foods with high fiber also have high amounts of sugar, so the criteria of the Altman Rule includes a 2-step process requiring (1) a minimum of 3 g of total dietary fiber per serving and (2) the sum of the grams of fiber plus the grams of protein per serving to be greater than the total grams of sugar (not grams of added sugar or grams of carbohydrate) per serving (FIGURE 1A). Unlike the relatively complicated formula related to GL, this 2-part rule can be applied in seconds while shopping (FIGURE 1B).

The rule is intended only to be used for packaged carbohydrate products, such as bread, muffins, bagels, pasta, rice, oatmeal, cereals, snack bars, chips, and crackers. It does not apply to whole foods, such as meat, dairy, fruits, or vegetables. These foods are excluded to prevent any consumer confusion related to the nutritional content of whole foods (eg, an apple may have more sugar than fiber and protein combined, but it is still a nutritious option).

Since the user does not need to have a smartphone, the Altman Rule may be more usable compared with more complicated alternatives.

This study aimed to determine if the Altman Rule is a reasonable proxy for the more complicated concept of GL. We calculated the relationship between the GL of commercially available packaged carbohydrate foods and whether those foods met the Altman Rule.

METHODS

The Altman Rule was tested by comparing the binary outcome of the rule (meets/does not meet) with data on all foods categorized as cereals, chips, crackers, and granola bars in the Nutrition Data System for Research (NDSR) Database (University of Minnesota, Version 2010).

Continue to: To account for differences...

To account for differences in serving size, we used the standard of 50 g for each product as 1 serving. We used 50 g (about 1.7 oz) to help compare the different foods and between foods within the same group. Additionally, 50 g is close to 1 serving for most foods in these groups; it is about the size of a typical granola bar, three-quarters to 2 cups of cereal, 10 to 12 crackers, and 15 to 25 chips. We determined the GL for each product by multiplying the number of available carbohydrates (total carbohydrate – dietary fiber) by the product’s glycemic index/100. In general, GL is categorized as low (≤ 10), medium (11-19), or high (≥ 20).

We applied the Altman Rule to categorize each product as meeting or not meeting the rule. We compared the proportion of foods meeting the Altman Rule, stratified by GL and by specific foods, and used chi-square to determine if differences were statistically significant. These data were collected and analyzed in the summer of 2019.

RESULTS

There were 1235 foods (342 breakfast cereals, 305 chips, 379 crackers, and 209 granola bars) used for this analysis. There is a significant relationship between the GL of foods and the Altman Rule in that most low-GL (68%), almost half of medium-GL (48%), and only a few high-GL foods (7%) met the rule (P < .001) (TABLE 1). There was also a significant relationship between “meeting the ­Altman Rule” and GL within each food type (P < .001) (TABLE 2).

The medium-GL foods were the second largest category of foods we calculated; thus we further broke them into binary categories of low-medium GL (values 11-14) and high-medium GL (values 15-19) to explore the results of the Altman Rule. About half of the foods in medium-GL category met the Altman Rule. About eighty-five percent of the foods with low-medium GL passed the Altman Rule, while only 39% of the foods with high-medium GL did.

Foods that met the rule were more likely to be low GL and foods that did not pass the rule were more likely high GL. Within the medium-GL category, foods that met the rule were more likely to be low-medium GL. 

Continue to: The findings within food categories...

The findings within food categories showed that very few cereals, chips, crackers, and granola bars were low GL. For every food category, except granola bars, far more low-GL foods met the Altman Rule than those that did not. At the same time, very few high-GL foods met the Altman Rule. The category with the most individual high-GL food items meeting the Altman Rule was cereal. This was also the subcategory with the largest percentage of high-GL food items meeting the Altman Rule. Thirty-nine cereals that were high GL met the rule, but more than 4 times as many high-GL cereals did not (n = 190).

DISCUSSION

Marketing and nutrition messaging create consumer confusion that makes it challenging to identify packaged food items that are more nutrient dense. The Altman Rule simplifies food choices that have become unnecessarily complex. Our findings suggest this 2-step rule is a reasonable proxy for the more complicated and less accessible GL for packaged carbohydrates, such as cereals, chips, crackers, and snack bars. Foods that meet the rule are likely low or low-medium GL and thus are foods that are likely to be healthier choices.

Our findings suggest this 2-step rule is a reasonable proxy for the more complicated and less accessible glycemic load for packaged carbohydrates.

Of note, only 9% of chips (n = 27) passed the Altman Rule, likely due to their low dietary fiber content, which was typical of chips. If a food item does not have at least 3 grams of total dietary fiber per serving, it does not pass the Altman Rule, regardless of how much protein or sugar is in the product. This may be considered a strength or a weakness of the Altman Rule. Few nutrition-dense foods are low in fiber, but some foods could be nutritious but do not meet the Altman Rule due to having < 3 g of fiber.

With the high prevalence of chronic diseases such as hypertension, diabetes, hyperlipidemia, and cardiovascular disease, it is essential to help consumers prevent chronic disease altogether or manage their chronic disease by providing tools to identify healthier food choices. The tool also has a place in clinical medicine for use by physicians and other health care professionals. Research shows that physicians find both time and lack of ­knowledge/resources to be a barrier to providing nutritional counseling to patients.¹⁰ Since the Altman Rule can be shared and explained with very little time and without extensive nutritional knowledge, it meets these needs.

Limitations

Glycemic load. We acknowledge that the Altman Rule is not foolproof and that assessing this rule based on GL has some limitations. GL is not a perfect or comprehensive way to measure the nutritional value of a food. For example, fruits such as watermelon and grapes are nutritionally dense. However, they contain high amounts of natural sugars—and as such, their GL is relatively high, which could lead a consumer to perceive them as unhealthy. Nevertheless, GL is both a useful and accepted tool and a reasonable way to assess the validity of the rule, specifically when assessing packaged carbohydrates. The simplicity of the Altman Rule and its relationship with GL makes it such that consumers are more likely to make a healthier food choice using it.⁹

Continue to: Specificity and sensitivity

Specificity and sensitivity. There are other limitations to the Altman Rule, given that a small number of high-GL foods meet the rule. For example, some granola bars had high dietary protein, which offset a high sugar content just enough to pass the rule despite a higher GL. As such, concluding that a snack bar is a healthier choice because it meets the Altman Rule when it has high amounts of sugar may not be appropriate. This limitation could be considered a lack of specificity (the rule includes food it ought not to include). Another limitation to consider would be a lack of sensitivity, given that only 68% of low-GL foods passed the Altman Rule. Since GL is associated with carbohydrate content, foods with a low carbohydrate count often have little to no fiber and thus would fall into the category of foods that did not meet the Altman Rule but had low GL. In this case, however, the low amount of fiber may render the Altman Rule a better indicator of a healthier food choice than the GL.

Hidden sugars. Foods with sugar alcohols and artificial sweeteners may be as deleterious as caloric alternatives while not being accounted for when reporting the grams of sugar per serving on the nutrition label.⁷ This may represent an exception to the Altman Rule, as foods that are not healthier choices may pass the rule because the sugar content on the nutrition label is, in a sense, artificially lowered. Future research may investigate the hypothesis that these foods are nutritionally inferior despite meeting the Altman Rule.

The sample. Our study also was limited to working only with foods that were included in the NDSR database up to 2010. This limitation is mitigated by the fact that the sample size was large (> 1000 packaged food items were included in our analyses). The study also could be limited by the food categories that were analyzed; food categories such as bread, rice, pasta, and bagels were not included.

The objective of this research was to investigate the relationship between GL and the Altman Rule, rather than to conduct an exhaustive analysis of the Altman Rule for every possible food category. Studying the relationship between the Altman Rule and GL in other categories of food is an objective for future research. The data so far support a relationship between these entities. The likelihood of the nutrition facts of foods changing without the GL changing (or vice versa) is very low. As such, the Altman Rule still seems to be a reasonable proxy of GL.

CONCLUSIONS

Research indicates that point-of-sale tools, such as Guiding Stars, NuVal, and other stoplight tools, can successfully alter consumers’ behaviors.⁹ These tools can be helpful but are not available in many supermarkets. Despite the limitations, the Altman Rule is a useful decision aid that is accessible to all consumers no matter where they live or shop and is easy to use and remember.

The Altman rule can be used in clinical practice by health care professionals, such as physicians, nurse practitioners, physician assistants, dietitians, and health coaches. It also has the potential to be used in commercial settings, such as grocery stores, to help consumers easily identify healthier convenience foods. This has public health implications, as the rule can both empower consumers and potentially incentivize food manufacturers to upgrade their products nutritionally.

Additional research would be useful to evaluate consumers’ preferences and perceptions about how user-friendly the Altman Rule is at the point of sale with packaged carbohydrate foods. This would help to further understand how the use of information on food packaging can motivate healthier decisions—thereby helping to alleviate the burden of chronic disease.

CORRESPONDENCE
Kimberly R. Dong, DrPH, MS, RDN, Tufts University School of Medicine, Department of Public Health and Community Medicine, 136 Harrison Avenue, MV Building, Boston, MA 02111; [email protected]

ABSTRACT

Background: The Altman Rule, a simple tool for consumers seeking to make healthier packaged food choices at the point of sale, applies to packaged carbohydrates. According to the Altman Rule, a food is a healthier option if it has at least 3 g of fiber per serving and the grams of fiber plus the grams of protein exceed the grams of sugar per serving. This study sought to evaluate whether the Altman Rule is a valid proxy for glycemic load (GL).

Methods: We compared the binary outcome of whether a food item meets the Altman Rule with the GL of all foods categorized as cereals, chips, crackers, and granola bars in the Nutrition Data System for Research Database (University of Minnesota, Version 2010). We examined the percentage of foods in low-, medium-, and high-GL categories that met the Altman Rule.

Results: There were 1235 foods (342 cereals, 305 chips, 379 crackers, and 209 granola bars) in this analysis. There was a significant relationship between the GL of foods and the Altman Rule (P < .001) in that most low-GL (68%), almost half of medium-GL (48%), and very few high-GL (7%) foods met the criteria of the rule.

Conclusions: The Altman Rule is a reasonable proxy for GL and can be a useful and accessible tool for consumers interested in buying healthier packaged carbohydrate foods.

Nutrition can be complicated for consumers interested in making healthier choices at the grocery store. Consumers may have difficulty identifying more nutritious options, especially when food labels are adorned with claims such as “Good Source of Fiber” or “Heart Healthy.”¹ In addition, when reading food labels, consumers may find it difficult to decipher which data to prioritize when carbohydrates, total sugars, added sugars, total dietary fiber, soluble fiber, and insoluble fiber are all listed.

The concept of glycemic load (GL) is an important consideration, especially for people with diabetes. GL approximates the blood sugar response to different foods. A food with a high GL is digested quickly, and its carbohydrates are taken into the bloodstream rapidly. This leads to a spike and subsequent drop in blood sugars, which can cause symptoms of hyperglycemia and hypoglycemia in a person with diabetes.^2,3 Despite its usefulness, GL may be too complicated for a consumer to understand, and it does not appear anywhere on the food label. Since GL is calculated using pooled blood sugar response from individuals after the ingestion of the particular food, estimation of the GL is not intuitable.⁴

Point-of-sale tools. People seeking to lose weight, control diabetes, improve dyslipidemia and/or blood pressure, and/or decrease their risk for heart disease may benefit from point-of-sale tools such as the Altman Rule, which simplifies and encourages the selection of more nutritious foods.¹ Other tools—such as Guiding Stars (https://guidingstars.com), NuVal (www.nuval.com), and different variations of traffic lights—have been created to help consumers make more informed and healthier food choices.^5-8 However, Guiding Stars and NuVal are based on complicated algorithms that are not entirely transparent and not accessible to the average consumer.^6,7 Evaluations of these nutrition tools indicate that consumers tend to underrate the healthiness of some foods, such as raw almonds and salmon, and overrate the healthiness of others, such as fruit punch and diet soda, when using traffic light systems.⁶ Furthermore, these nutrition tools are not available in many supermarkets. Previous research suggests that the use of point-of-sale nutrition apps decreases with the time and effort involved in using an app.⁹

Continue to: The Altman Rule

The Altman Rule was developed by a family physician (author WA) to provide a more accessible tool for people interested in choosing healthier prepackaged carbohydrate foods while shopping. Since the user does not need to have a smartphone, and they are not required to download or understand an app for each purchase, the Altman Rule may be more usable compared with more complicated alternatives.

The Altman Rule can be used with nutrition labels that feature serving information and calories in enlarged and bold type, in compliance with the most recent US Food and Drug Administration (FDA) guideline from 2016. Many foods with high fiber also have high amounts of sugar, so the criteria of the Altman Rule includes a 2-step process requiring (1) a minimum of 3 g of total dietary fiber per serving and (2) the sum of the grams of fiber plus the grams of protein per serving to be greater than the total grams of sugar (not grams of added sugar or grams of carbohydrate) per serving (FIGURE 1A). Unlike the relatively complicated formula related to GL, this 2-part rule can be applied in seconds while shopping (FIGURE 1B).

The rule is intended only to be used for packaged carbohydrate products, such as bread, muffins, bagels, pasta, rice, oatmeal, cereals, snack bars, chips, and crackers. It does not apply to whole foods, such as meat, dairy, fruits, or vegetables. These foods are excluded to prevent any consumer confusion related to the nutritional content of whole foods (eg, an apple may have more sugar than fiber and protein combined, but it is still a nutritious option).

Since the user does not need to have a smartphone, the Altman Rule may be more usable compared with more complicated alternatives.

This study aimed to determine if the Altman Rule is a reasonable proxy for the more complicated concept of GL. We calculated the relationship between the GL of commercially available packaged carbohydrate foods and whether those foods met the Altman Rule.

METHODS

The Altman Rule was tested by comparing the binary outcome of the rule (meets/does not meet) with data on all foods categorized as cereals, chips, crackers, and granola bars in the Nutrition Data System for Research (NDSR) Database (University of Minnesota, Version 2010).

Continue to: To account for differences...

To account for differences in serving size, we used the standard of 50 g for each product as 1 serving. We used 50 g (about 1.7 oz) to help compare the different foods and between foods within the same group. Additionally, 50 g is close to 1 serving for most foods in these groups; it is about the size of a typical granola bar, three-quarters to 2 cups of cereal, 10 to 12 crackers, and 15 to 25 chips. We determined the GL for each product by multiplying the number of available carbohydrates (total carbohydrate – dietary fiber) by the product’s glycemic index/100. In general, GL is categorized as low (≤ 10), medium (11-19), or high (≥ 20).

We applied the Altman Rule to categorize each product as meeting or not meeting the rule. We compared the proportion of foods meeting the Altman Rule, stratified by GL and by specific foods, and used chi-square to determine if differences were statistically significant. These data were collected and analyzed in the summer of 2019.

RESULTS

There were 1235 foods (342 breakfast cereals, 305 chips, 379 crackers, and 209 granola bars) used for this analysis. There is a significant relationship between the GL of foods and the Altman Rule in that most low-GL (68%), almost half of medium-GL (48%), and only a few high-GL foods (7%) met the rule (P < .001) (TABLE 1). There was also a significant relationship between “meeting the ­Altman Rule” and GL within each food type (P < .001) (TABLE 2).

The medium-GL foods were the second largest category of foods we calculated; thus we further broke them into binary categories of low-medium GL (values 11-14) and high-medium GL (values 15-19) to explore the results of the Altman Rule. About half of the foods in medium-GL category met the Altman Rule. About eighty-five percent of the foods with low-medium GL passed the Altman Rule, while only 39% of the foods with high-medium GL did.

Foods that met the rule were more likely to be low GL and foods that did not pass the rule were more likely high GL. Within the medium-GL category, foods that met the rule were more likely to be low-medium GL. 

Continue to: The findings within food categories...

The findings within food categories showed that very few cereals, chips, crackers, and granola bars were low GL. For every food category, except granola bars, far more low-GL foods met the Altman Rule than those that did not. At the same time, very few high-GL foods met the Altman Rule. The category with the most individual high-GL food items meeting the Altman Rule was cereal. This was also the subcategory with the largest percentage of high-GL food items meeting the Altman Rule. Thirty-nine cereals that were high GL met the rule, but more than 4 times as many high-GL cereals did not (n = 190).

DISCUSSION

Marketing and nutrition messaging create consumer confusion that makes it challenging to identify packaged food items that are more nutrient dense. The Altman Rule simplifies food choices that have become unnecessarily complex. Our findings suggest this 2-step rule is a reasonable proxy for the more complicated and less accessible GL for packaged carbohydrates, such as cereals, chips, crackers, and snack bars. Foods that meet the rule are likely low or low-medium GL and thus are foods that are likely to be healthier choices.

Our findings suggest this 2-step rule is a reasonable proxy for the more complicated and less accessible glycemic load for packaged carbohydrates.

Of note, only 9% of chips (n = 27) passed the Altman Rule, likely due to their low dietary fiber content, which was typical of chips. If a food item does not have at least 3 grams of total dietary fiber per serving, it does not pass the Altman Rule, regardless of how much protein or sugar is in the product. This may be considered a strength or a weakness of the Altman Rule. Few nutrition-dense foods are low in fiber, but some foods could be nutritious but do not meet the Altman Rule due to having < 3 g of fiber.

With the high prevalence of chronic diseases such as hypertension, diabetes, hyperlipidemia, and cardiovascular disease, it is essential to help consumers prevent chronic disease altogether or manage their chronic disease by providing tools to identify healthier food choices. The tool also has a place in clinical medicine for use by physicians and other health care professionals. Research shows that physicians find both time and lack of ­knowledge/resources to be a barrier to providing nutritional counseling to patients.¹⁰ Since the Altman Rule can be shared and explained with very little time and without extensive nutritional knowledge, it meets these needs.

Limitations

Glycemic load. We acknowledge that the Altman Rule is not foolproof and that assessing this rule based on GL has some limitations. GL is not a perfect or comprehensive way to measure the nutritional value of a food. For example, fruits such as watermelon and grapes are nutritionally dense. However, they contain high amounts of natural sugars—and as such, their GL is relatively high, which could lead a consumer to perceive them as unhealthy. Nevertheless, GL is both a useful and accepted tool and a reasonable way to assess the validity of the rule, specifically when assessing packaged carbohydrates. The simplicity of the Altman Rule and its relationship with GL makes it such that consumers are more likely to make a healthier food choice using it.⁹

Continue to: Specificity and sensitivity

Specificity and sensitivity. There are other limitations to the Altman Rule, given that a small number of high-GL foods meet the rule. For example, some granola bars had high dietary protein, which offset a high sugar content just enough to pass the rule despite a higher GL. As such, concluding that a snack bar is a healthier choice because it meets the Altman Rule when it has high amounts of sugar may not be appropriate. This limitation could be considered a lack of specificity (the rule includes food it ought not to include). Another limitation to consider would be a lack of sensitivity, given that only 68% of low-GL foods passed the Altman Rule. Since GL is associated with carbohydrate content, foods with a low carbohydrate count often have little to no fiber and thus would fall into the category of foods that did not meet the Altman Rule but had low GL. In this case, however, the low amount of fiber may render the Altman Rule a better indicator of a healthier food choice than the GL.

Hidden sugars. Foods with sugar alcohols and artificial sweeteners may be as deleterious as caloric alternatives while not being accounted for when reporting the grams of sugar per serving on the nutrition label.⁷ This may represent an exception to the Altman Rule, as foods that are not healthier choices may pass the rule because the sugar content on the nutrition label is, in a sense, artificially lowered. Future research may investigate the hypothesis that these foods are nutritionally inferior despite meeting the Altman Rule.

The sample. Our study also was limited to working only with foods that were included in the NDSR database up to 2010. This limitation is mitigated by the fact that the sample size was large (> 1000 packaged food items were included in our analyses). The study also could be limited by the food categories that were analyzed; food categories such as bread, rice, pasta, and bagels were not included.

The objective of this research was to investigate the relationship between GL and the Altman Rule, rather than to conduct an exhaustive analysis of the Altman Rule for every possible food category. Studying the relationship between the Altman Rule and GL in other categories of food is an objective for future research. The data so far support a relationship between these entities. The likelihood of the nutrition facts of foods changing without the GL changing (or vice versa) is very low. As such, the Altman Rule still seems to be a reasonable proxy of GL.

CONCLUSIONS

Research indicates that point-of-sale tools, such as Guiding Stars, NuVal, and other stoplight tools, can successfully alter consumers’ behaviors.⁹ These tools can be helpful but are not available in many supermarkets. Despite the limitations, the Altman Rule is a useful decision aid that is accessible to all consumers no matter where they live or shop and is easy to use and remember.

The Altman rule can be used in clinical practice by health care professionals, such as physicians, nurse practitioners, physician assistants, dietitians, and health coaches. It also has the potential to be used in commercial settings, such as grocery stores, to help consumers easily identify healthier convenience foods. This has public health implications, as the rule can both empower consumers and potentially incentivize food manufacturers to upgrade their products nutritionally.

Additional research would be useful to evaluate consumers’ preferences and perceptions about how user-friendly the Altman Rule is at the point of sale with packaged carbohydrate foods. This would help to further understand how the use of information on food packaging can motivate healthier decisions—thereby helping to alleviate the burden of chronic disease.

CORRESPONDENCE
Kimberly R. Dong, DrPH, MS, RDN, Tufts University School of Medicine, Department of Public Health and Community Medicine, 136 Harrison Avenue, MV Building, Boston, MA 02111; [email protected]

ABSTRACT

Background: The Altman Rule, a simple tool for consumers seeking to make healthier packaged food choices at the point of sale, applies to packaged carbohydrates. According to the Altman Rule, a food is a healthier option if it has at least 3 g of fiber per serving and the grams of fiber plus the grams of protein exceed the grams of sugar per serving. This study sought to evaluate whether the Altman Rule is a valid proxy for glycemic load (GL).

Methods: We compared the binary outcome of whether a food item meets the Altman Rule with the GL of all foods categorized as cereals, chips, crackers, and granola bars in the Nutrition Data System for Research Database (University of Minnesota, Version 2010). We examined the percentage of foods in low-, medium-, and high-GL categories that met the Altman Rule.

Results: There were 1235 foods (342 cereals, 305 chips, 379 crackers, and 209 granola bars) in this analysis. There was a significant relationship between the GL of foods and the Altman Rule (P < .001) in that most low-GL (68%), almost half of medium-GL (48%), and very few high-GL (7%) foods met the criteria of the rule.

Conclusions: The Altman Rule is a reasonable proxy for GL and can be a useful and accessible tool for consumers interested in buying healthier packaged carbohydrate foods.

Nutrition can be complicated for consumers interested in making healthier choices at the grocery store. Consumers may have difficulty identifying more nutritious options, especially when food labels are adorned with claims such as “Good Source of Fiber” or “Heart Healthy.”¹ In addition, when reading food labels, consumers may find it difficult to decipher which data to prioritize when carbohydrates, total sugars, added sugars, total dietary fiber, soluble fiber, and insoluble fiber are all listed.

The concept of glycemic load (GL) is an important consideration, especially for people with diabetes. GL approximates the blood sugar response to different foods. A food with a high GL is digested quickly, and its carbohydrates are taken into the bloodstream rapidly. This leads to a spike and subsequent drop in blood sugars, which can cause symptoms of hyperglycemia and hypoglycemia in a person with diabetes.^2,3 Despite its usefulness, GL may be too complicated for a consumer to understand, and it does not appear anywhere on the food label. Since GL is calculated using pooled blood sugar response from individuals after the ingestion of the particular food, estimation of the GL is not intuitable.⁴

Point-of-sale tools. People seeking to lose weight, control diabetes, improve dyslipidemia and/or blood pressure, and/or decrease their risk for heart disease may benefit from point-of-sale tools such as the Altman Rule, which simplifies and encourages the selection of more nutritious foods.¹ Other tools—such as Guiding Stars (https://guidingstars.com), NuVal (www.nuval.com), and different variations of traffic lights—have been created to help consumers make more informed and healthier food choices.^5-8 However, Guiding Stars and NuVal are based on complicated algorithms that are not entirely transparent and not accessible to the average consumer.^6,7 Evaluations of these nutrition tools indicate that consumers tend to underrate the healthiness of some foods, such as raw almonds and salmon, and overrate the healthiness of others, such as fruit punch and diet soda, when using traffic light systems.⁶ Furthermore, these nutrition tools are not available in many supermarkets. Previous research suggests that the use of point-of-sale nutrition apps decreases with the time and effort involved in using an app.⁹

Continue to: The Altman Rule

The Altman Rule was developed by a family physician (author WA) to provide a more accessible tool for people interested in choosing healthier prepackaged carbohydrate foods while shopping. Since the user does not need to have a smartphone, and they are not required to download or understand an app for each purchase, the Altman Rule may be more usable compared with more complicated alternatives.

The Altman Rule can be used with nutrition labels that feature serving information and calories in enlarged and bold type, in compliance with the most recent US Food and Drug Administration (FDA) guideline from 2016. Many foods with high fiber also have high amounts of sugar, so the criteria of the Altman Rule includes a 2-step process requiring (1) a minimum of 3 g of total dietary fiber per serving and (2) the sum of the grams of fiber plus the grams of protein per serving to be greater than the total grams of sugar (not grams of added sugar or grams of carbohydrate) per serving (FIGURE 1A). Unlike the relatively complicated formula related to GL, this 2-part rule can be applied in seconds while shopping (FIGURE 1B).

The rule is intended only to be used for packaged carbohydrate products, such as bread, muffins, bagels, pasta, rice, oatmeal, cereals, snack bars, chips, and crackers. It does not apply to whole foods, such as meat, dairy, fruits, or vegetables. These foods are excluded to prevent any consumer confusion related to the nutritional content of whole foods (eg, an apple may have more sugar than fiber and protein combined, but it is still a nutritious option).

Since the user does not need to have a smartphone, the Altman Rule may be more usable compared with more complicated alternatives.

This study aimed to determine if the Altman Rule is a reasonable proxy for the more complicated concept of GL. We calculated the relationship between the GL of commercially available packaged carbohydrate foods and whether those foods met the Altman Rule.

METHODS

The Altman Rule was tested by comparing the binary outcome of the rule (meets/does not meet) with data on all foods categorized as cereals, chips, crackers, and granola bars in the Nutrition Data System for Research (NDSR) Database (University of Minnesota, Version 2010).

Continue to: To account for differences...

To account for differences in serving size, we used the standard of 50 g for each product as 1 serving. We used 50 g (about 1.7 oz) to help compare the different foods and between foods within the same group. Additionally, 50 g is close to 1 serving for most foods in these groups; it is about the size of a typical granola bar, three-quarters to 2 cups of cereal, 10 to 12 crackers, and 15 to 25 chips. We determined the GL for each product by multiplying the number of available carbohydrates (total carbohydrate – dietary fiber) by the product’s glycemic index/100. In general, GL is categorized as low (≤ 10), medium (11-19), or high (≥ 20).

We applied the Altman Rule to categorize each product as meeting or not meeting the rule. We compared the proportion of foods meeting the Altman Rule, stratified by GL and by specific foods, and used chi-square to determine if differences were statistically significant. These data were collected and analyzed in the summer of 2019.

RESULTS

There were 1235 foods (342 breakfast cereals, 305 chips, 379 crackers, and 209 granola bars) used for this analysis. There is a significant relationship between the GL of foods and the Altman Rule in that most low-GL (68%), almost half of medium-GL (48%), and only a few high-GL foods (7%) met the rule (P < .001) (TABLE 1). There was also a significant relationship between “meeting the ­Altman Rule” and GL within each food type (P < .001) (TABLE 2).

The medium-GL foods were the second largest category of foods we calculated; thus we further broke them into binary categories of low-medium GL (values 11-14) and high-medium GL (values 15-19) to explore the results of the Altman Rule. About half of the foods in medium-GL category met the Altman Rule. About eighty-five percent of the foods with low-medium GL passed the Altman Rule, while only 39% of the foods with high-medium GL did.

Foods that met the rule were more likely to be low GL and foods that did not pass the rule were more likely high GL. Within the medium-GL category, foods that met the rule were more likely to be low-medium GL. 

Continue to: The findings within food categories...

The findings within food categories showed that very few cereals, chips, crackers, and granola bars were low GL. For every food category, except granola bars, far more low-GL foods met the Altman Rule than those that did not. At the same time, very few high-GL foods met the Altman Rule. The category with the most individual high-GL food items meeting the Altman Rule was cereal. This was also the subcategory with the largest percentage of high-GL food items meeting the Altman Rule. Thirty-nine cereals that were high GL met the rule, but more than 4 times as many high-GL cereals did not (n = 190).

DISCUSSION

Marketing and nutrition messaging create consumer confusion that makes it challenging to identify packaged food items that are more nutrient dense. The Altman Rule simplifies food choices that have become unnecessarily complex. Our findings suggest this 2-step rule is a reasonable proxy for the more complicated and less accessible GL for packaged carbohydrates, such as cereals, chips, crackers, and snack bars. Foods that meet the rule are likely low or low-medium GL and thus are foods that are likely to be healthier choices.

Our findings suggest this 2-step rule is a reasonable proxy for the more complicated and less accessible glycemic load for packaged carbohydrates.

Of note, only 9% of chips (n = 27) passed the Altman Rule, likely due to their low dietary fiber content, which was typical of chips. If a food item does not have at least 3 grams of total dietary fiber per serving, it does not pass the Altman Rule, regardless of how much protein or sugar is in the product. This may be considered a strength or a weakness of the Altman Rule. Few nutrition-dense foods are low in fiber, but some foods could be nutritious but do not meet the Altman Rule due to having < 3 g of fiber.

With the high prevalence of chronic diseases such as hypertension, diabetes, hyperlipidemia, and cardiovascular disease, it is essential to help consumers prevent chronic disease altogether or manage their chronic disease by providing tools to identify healthier food choices. The tool also has a place in clinical medicine for use by physicians and other health care professionals. Research shows that physicians find both time and lack of ­knowledge/resources to be a barrier to providing nutritional counseling to patients.¹⁰ Since the Altman Rule can be shared and explained with very little time and without extensive nutritional knowledge, it meets these needs.

Limitations

Glycemic load. We acknowledge that the Altman Rule is not foolproof and that assessing this rule based on GL has some limitations. GL is not a perfect or comprehensive way to measure the nutritional value of a food. For example, fruits such as watermelon and grapes are nutritionally dense. However, they contain high amounts of natural sugars—and as such, their GL is relatively high, which could lead a consumer to perceive them as unhealthy. Nevertheless, GL is both a useful and accepted tool and a reasonable way to assess the validity of the rule, specifically when assessing packaged carbohydrates. The simplicity of the Altman Rule and its relationship with GL makes it such that consumers are more likely to make a healthier food choice using it.⁹

Continue to: Specificity and sensitivity

Specificity and sensitivity. There are other limitations to the Altman Rule, given that a small number of high-GL foods meet the rule. For example, some granola bars had high dietary protein, which offset a high sugar content just enough to pass the rule despite a higher GL. As such, concluding that a snack bar is a healthier choice because it meets the Altman Rule when it has high amounts of sugar may not be appropriate. This limitation could be considered a lack of specificity (the rule includes food it ought not to include). Another limitation to consider would be a lack of sensitivity, given that only 68% of low-GL foods passed the Altman Rule. Since GL is associated with carbohydrate content, foods with a low carbohydrate count often have little to no fiber and thus would fall into the category of foods that did not meet the Altman Rule but had low GL. In this case, however, the low amount of fiber may render the Altman Rule a better indicator of a healthier food choice than the GL.

Hidden sugars. Foods with sugar alcohols and artificial sweeteners may be as deleterious as caloric alternatives while not being accounted for when reporting the grams of sugar per serving on the nutrition label.⁷ This may represent an exception to the Altman Rule, as foods that are not healthier choices may pass the rule because the sugar content on the nutrition label is, in a sense, artificially lowered. Future research may investigate the hypothesis that these foods are nutritionally inferior despite meeting the Altman Rule.

The sample. Our study also was limited to working only with foods that were included in the NDSR database up to 2010. This limitation is mitigated by the fact that the sample size was large (> 1000 packaged food items were included in our analyses). The study also could be limited by the food categories that were analyzed; food categories such as bread, rice, pasta, and bagels were not included.

The objective of this research was to investigate the relationship between GL and the Altman Rule, rather than to conduct an exhaustive analysis of the Altman Rule for every possible food category. Studying the relationship between the Altman Rule and GL in other categories of food is an objective for future research. The data so far support a relationship between these entities. The likelihood of the nutrition facts of foods changing without the GL changing (or vice versa) is very low. As such, the Altman Rule still seems to be a reasonable proxy of GL.

CONCLUSIONS

Research indicates that point-of-sale tools, such as Guiding Stars, NuVal, and other stoplight tools, can successfully alter consumers’ behaviors.⁹ These tools can be helpful but are not available in many supermarkets. Despite the limitations, the Altman Rule is a useful decision aid that is accessible to all consumers no matter where they live or shop and is easy to use and remember.

The Altman rule can be used in clinical practice by health care professionals, such as physicians, nurse practitioners, physician assistants, dietitians, and health coaches. It also has the potential to be used in commercial settings, such as grocery stores, to help consumers easily identify healthier convenience foods. This has public health implications, as the rule can both empower consumers and potentially incentivize food manufacturers to upgrade their products nutritionally.

Additional research would be useful to evaluate consumers’ preferences and perceptions about how user-friendly the Altman Rule is at the point of sale with packaged carbohydrate foods. This would help to further understand how the use of information on food packaging can motivate healthier decisions—thereby helping to alleviate the burden of chronic disease.

CORRESPONDENCE
Kimberly R. Dong, DrPH, MS, RDN, Tufts University School of Medicine, Department of Public Health and Community Medicine, 136 Harrison Avenue, MV Building, Boston, MA 02111; [email protected]

Migraine is a headache disorder that often causes unilateral pain, photophobia, phonophobia, nausea, and vomiting. More than 70% of office visits for migraine are made to primary care physicians.¹ Recent data suggest migraine may be caused primarily by neuronal dysfunction and only secondarily by vasodilation.² Although there are numerous classes of drugs used for migraine prevention and treatment, their success has been limited by inadequate efficacy, tolerability, and patient adherence.³ The discovery of pro-inflammatory markers such as calcitonin gene-related peptide (CGRP) has led to the development of new medications to prevent and treat migraine.⁴

IMAGE: © SCOTT BODELL

Pathophysiology, Dx and triggers, indications for pharmacotherapy

Pathophysiology. A migraine is thought to be caused by cortical spreading depression (CSD), a depolarization of glial and neuronal cell membranes.⁵This results in increased cortical excitability, central trigeminal-thalamic sensitization, and defective descending pain modulatory activity.⁶The activation of the trigeminal sensory pathways, primarily the ophthalmic branch, sends nociceptive signals to second-order neurons mediated by the release of neurotransmitters, such as CGRPs.⁵ This activation explains in part the primary location for a migraine, which is around the eye and the neighboring cranial regions. The pain perceived by the patient is caused by these second-order neurons.

It has been theorized that gepants bind to calcitonin gene-related peptide receptors, resulting in decreased blood flow to the brain, inhibition of neurogenic inflammation, and reduced pain signaling.

Dx and triggers. In 2018, the International Headache Society revised its guidelines for the diagnosis of migraine.⁷ According to the 3rd edition of The International Classification of Headache Disorders (ICHD-3), the diagnosis of migraine is made when a patient has at least 5 headache attacks that last 4 to 72 hours and have at least 2 of the following characteristics: (1) unilateral location, (2) pulsating quality, (3) moderate-to-severe pain intensity, and (4) aggravated by or causing avoidance of routine physical activity.⁷ The headache attacks also should have (1) associated nausea or vomiting or (2) photophobia and phonophobia.⁷ The presence of atypical signs or symptoms as indicated by the SNNOOP10 mnemonic raises concerns for secondary headaches and the need for further investigation into the cause of the headache (TABLE 1).⁸ It is not possible to detect every secondary headache with standard neuroimaging, but the SNNOOP10 red flags can help determine when imaging may be indicated.⁸ Potential triggers for migraine can be found in TABLE 2.⁹

Indications for pharmacotherapy. All patients receiving a diagnosis of migraine should be offered acute pharmacologic treatment. Consider preventive therapy anytime there are ≥ 4 headache days per month, debilitating attacks despite acute therapy, overuse of acute medication (> 2 d/wk), difficulty tolerating acute medication, patient preference, or presence of certain migraine subtypes.^7,10

Acute treatments

Abortive therapies for migraine include analgesics such as nonsteroidal anti-­inflammatory drugs (NSAIDs) and acetaminophen, and ergot alkaloids, triptans, or small-molecule CGRP receptor antagonists (gepants). Prompt administration increases the chance of success with acute therapy. Medications with the highest levels of efficacy based on the 2015 guidelines from the American Headache Society (AHS) are given in TABLE 3.¹¹ Lasmiditan (Reyvow) is not included in the 2015 guidelines, as it was approved after publication of the guidelines.

Non-CGRP first-line therapies

NSAIDs and acetaminophen. NSAIDs such as aspirin, diclofenac, ibuprofen, and naproxen have a high level of evidence to support their use as first-line treatments for mild-to-moderate migraine attacks. Trials consistently demonstrate their superiority to placebo in headache relief and complete pain relief at 2 hours. There is no recommendation for selecting one NSAID over another; however, consider their frequency of dosing and ­adverse effect profiles. The number needed to treat for complete pain relief at 2 hours ranges from 7 to 10 for most NSAIDs.^11,12 In some placebo-controlled studies, acetaminophen was less effective than NSAIDs, but was safer because it did not cause gastric irritation or antiplatelet effects.¹²

Triptans inhibit 5-HT_1B/1D receptors. Consider formulation, route of administration, cost, and pharmacokinetics when selecting a triptan. Patients who do not respond well to one triptan may respond favorably to another. A meta-analysis of the effectiveness of the 7 available agents found that triptans at standard doses provided pain relief within 2 hours in 42% to 76% of patients, and sustained freedom from pain for 2 hours in 18% to 50% of patients.¹³ Lasmiditan is a selective serotonin receptor (5-HT_1F) agonist that lacks vasoconstrictor activity. This is an option for patients with relative contraindications to triptans due to cardiovascular risk factors.¹⁰

Continue to: Second-line therapies

Intranasal dihydroergotamine has a favorable adverse event profile and greater evidence for efficacy compared with ergotamine. Compared with triptans, intranasal dihydroergotamine has a high level of efficacy but causes more adverse effects.¹⁴ Severe nausea is common, and dihydroergotamine often is used in combination with an antiemetic drug. Dihydroergotamine should not be used within 24 hours of taking a triptan, and it is contraindicated for patients who have hypertension or ischemic heart disease or who are pregnant or breastfeeding. There is also the potential for adverse drug interactions.¹⁵

A meta-analysis found that triptans at standard doses provided pain relief within 2 hours in 42% to 76% of patients, and sustained freedom from pain for 2 hours in 18% to 50% of patients.

Antiemetics may be helpful for migraine associated with severe nausea or vomiting. The dopamine antagonists metoclopramide, prochlorperazine, and chlorpromazine have demonstrated benefit in randomized ­placebo-controlled trials.¹¹ Ondansetron has not been studied extensively, but sometimes is used in clinical practice. Nonoral routes of administration may be useful in patients having trouble swallowing medications or in those experiencing significant nausea or vomiting early during migraine attacks.

Due to the high potential for abuse, opioids should not be used routinely for the treatment of migraine.¹² There is no high-quality evidence supporting the efficacy of barbiturates (ie, butalbital-containing compounds) for acute migraine treatment.¹¹ Moreover, use of these agents may increase the likelihood of progression from episodic to chronic migraine.¹⁶

Gepants for acute migraine treatment

Neuropeptide CGRP is released from trigeminal nerves and is a potent dilator of cerebral and dural vessels, playing a key role in regulating blood flow to the brain. Other roles of CGRP include the release of inflammatory agents from mast cells and the transmission of painful stimuli from intracranial vessels.¹⁷ The CGRP receptor or ligand can be targeted by small-molecule receptor antagonists for acute and preventive migraine treatment (and by monoclonal antibodies solely for prevention, discussed later). It has been theorized that gepants bind to CGRP receptors, resulting in decreased blood flow to the brain, inhibition of neurogenic inflammation, and reduced pain signaling.¹⁷ Unlike triptans and ergotamine derivatives, these novel treatments do not constrict blood vessels and may have a unique role in patients with contraindications to triptans.

The 3 gepants approved for acute treatment—ubrogepant (Ubrelvy),¹⁸ rimegepant (Nurtec),¹⁹ and zavegepant (Zavzpret)²⁰—were compared with placebo in clinical trials and were shown to increase the number of patients who were completely pain free at 2 hours, were free of the most bothersome associated symptom (photophobia, phonophobia, or nausea) at 2 hours, and remained pain free at 24 hours (TABLE 4^18-24).

Continue to: Ubrogrepant

Ubrogepant, in 2 Phase 3 trials (ACHIEVE I and ACHIEVE II) demonstrated effectiveness compared with placebo.^21,22 The most common adverse effects reported were nausea and somnolence at very low rates. Pain-relief rates at 2 hours post dose (> 60% of participants) were higher than pain-free rates, and a significantly higher percentage (> 40%) of ubrogepant-treated participants reported ability to function normally on the Functional Disability Scale.²⁵

Rimegepant was also superior to placebo (59% vs 43%) in pain relief at 2 hours post dose and other secondary endpoints.²³ Rimegepant also has potential drug interactions and dose adjustments (TABLE 4^18-24).

Zavegepant, approved in March 2023, is administered once daily as a 10-mg nasal spray. In its Phase 3 trial, zavegepant was significantly superior to placebo at 2 hours post dose in freedom from pain (24% v 15%), and in freedom from the most bothersome symptom (40% v 31%).²⁴ Dosage modifications are not needed with mild-to-moderate renal or hepatic disease.²⁰

Worth noting. The safety of using ubrogepant to treat more than 8 migraine episodes in a 30-day period has not been established. The safety of using more than 18 doses of zavegepant in a 30-day period also has not been established. With ubrogepant and rimegepant, there are dosing modifications for concomitant use with specific drugs (CYP3A4 inhibitors and inducers) due to potential interactions and in patients with hepatic or renal impairment.^18,19

There are no trials comparing efficacy of CGRP antagonists to triptans. Recognizing that these newer medications would be costly, the AHS position statement released in 2019 recommends that gepants be considered for those with contraindications to triptans or for whom at least 2 oral triptans have failed (as determined by a validated patient outcome questionnaire).¹⁰ Step therapy with documentation of previous trials and therapy failures is often required by insurance companies prior to gepant coverage.

Continue to: Preventive therapies

Preventive therapies

Preventive migraine therapies are used to reduce duration, frequency, and severity of attacks, the need for acute treatment, and overall headache disability.²⁶ Medications typically are chosen based on efficacy, adverse effect profile, and patient comorbidities. Barriers to successful use include poor patient adherence and tolerability, the need for slow dose titration, and long-term use (minimum of 2 months) at maximum tolerated or minimum effective doses. Medications with established efficacy (Level A^a) based on the 2012 guidelines from the American Academy of Neurology (AAN) and the AHS are given in TABLE 5.^27-29

Drugs having received the strongest level of evidence for migraine prevention are metoprolol, propranolol, timolol, topiramate, valproate sodium, divalproex sodium, and onabotulinumtoxinA (Botox), and frovatriptan for menstrual migraine prevention. Because these guidelines were last updated in 2012, they did not cover gepants (which will be discussed shortly). The AHS released a position statement in 2019 supporting the use of anti-CGRP monoclonal antibodies (mAbs) in those who cannot tolerate or have had an inadequate response to a 6-week trial of at least 2 AAN/AHA Level A or B^b treatments.¹⁰ No head-to-head trials exist between non-CGRP preventive therapies and the CGRP antagonists.

CGRP-targeted prevention

Four anti-CGRP mAbs and 2 gepants have been approved for migraine prevention in the United States. Differences between products include targets (ligand vs receptor), antibody IgG subtype, bioavailability, route of administration, and frequency of administration.²⁸ As noted in the Phase 3 studies (TABLE 6^19,30-47), these therapies are highly efficacious, safe, and tolerable.

Gepants. Rimegepant, discussed earlier for migraine treatment, is one of the CGRP receptor antagonists approved for prevention. The other is atogepant (Qulipta), approved only for prevention. Ubrogepant is not approved for prevention.

Anti-CGRP mAb is the only medication class specifically created for migraine prevention.^10,26 As already noted, several efficacious non-CGRP treatment options are available for migraine prevention. However, higher doses of those agents, if needed, can lead to intolerable adverse effects for some patients, thereby limiting overall efficacy. ­Anti-CGRP mAbs, a targeted, highly efficacious treatment option, offer efficacy comparable to non-CGRP agents with a more favorable adverse effect profile for those who cannot tolerate or achieve only minimal efficacy with traditional preventive therapies.¹⁰

Continue to: The targeted anti-CGRP approach...

The targeted anti-CGRP approach, which can be used by patients with liver or kidney disease, results in decreased toxicity and minimal drug interactions. Long half-lives allow for monthly or quarterly injections, possibly resulting in increased compliance.²⁸ Dose titration is not needed, allowing for more rapid symptom management. The large molecular size of a mAb limits its transfer across the blood-brain barrier, making central nervous system adverse effects unlikely.²⁸ Despite the compelling mAb pharmacologic properties, their use may be limited by a lack of long-term safety data and the need for parenteral administration. Although ­immunogenicity—the development of neutralizing antibodies—can limit long-term tolerability or efficacy of mAbs generally,^26,28 anti-CGRP mAbs were engineered to minimally activate the immune system and have not been associated with immune suppression, opportunistic infections, malignancies, or decreased efficacy.²⁸

Unlike triptans and ergotamine derivatives, gepants do not constrict blood vessels and may have a unique role in patients with contraindications to triptans.

A pooled meta-analysis including 4 trials (3166 patients) found that CGRP mAbs compared with placebo significantly improved patient response rates, defined as at least a 50% and 75% reduction in monthly ­headache/migraine days from baseline to Weeks 9 to 12.⁴⁸ Another meta-analysis including 8 trials (2292 patients) found a significant reduction from baseline in monthly migraine days and monthly acute migraine medication consumption among patients taking CGRP mAbs compared with those taking placebo.⁴⁹ Open-label extension studies have shown progressive and cumulative benefits in individuals who respond to anti-CGRP mAbs. Therefore, several treatment cycles may be necessary to determine overall efficacy of therapy.^10,28

Cost initially can be a barrier. Insurance companies often require step therapy before agreeing to cover mAb therapy, which aligns with the 2019 AHS position statement.¹⁰Due to differences in insurance coverage, out-of-pocket expenses can vary greatly. However, options are available through online manufacturer assistance to reduce cost, making it comparable to other migraine treatments. Safety and efficacy studies of anti-CGRP mAbs use in pregnant individuals are limited. At this time, they should not be prescribed for those who are pregnant, planning to become pregnant, or breastfeeding. Counsel nonpregnant patients on appropriate contraception while using a mAb due to possible teratogenicity and negative pregnancy outcomes.^28,50

When combination treatment may be appropriate

Monotherapy is the usual approach to preventing migraine due to advantages of efficacy, simplified regimens, lower cost, and reduced adverse effects.⁵¹ However, if a patient does not benefit from monotherapy even after trying dose titrations as tolerated or switching therapies, trying complementary combination therapy is appropriate. Despite a shortage of clinical trials supporting the use of 2 or more preventive medications with different mechanisms of action, this strategy is used clinically.¹⁰ Consider combination therapy in those with refractory disease, partial responses, or intolerance to recommended doses.⁵² Articles reporting on case study reviews have rationalized the combined use of onabotulinumtoxinA and anti-CGRP mAbs, noting better migraine control.^51,53 The 2019 AHS position statement recommends adding a mAb to an existing preventive treatment regimen with no other changes until mAb effectiveness is determined, as the risk for drug interactions on dual therapy is low.¹⁰ Safety and efficacy also have been demonstrated with the combination of preventive anti-CGRP mAbs and acute treatment with gepants as needed.⁵⁴

Monoclonal antibodies are highly efficacious options for those who cannot tolerate or achieve only minimal efficacy with traditional preventive therapies.

Overall, gepants and mAbs are as effective as traditional acute and preventive treatments for migraine, and they cause fewer adverse effects and often allow a more simplified regimen. Gepants and mAbs are viable options in the primary care setting. Due to limited long-term data and high cost, however, they routinely are used for refractory migraine rather than as first-line agents. These therapies are especially favorable options for patients when traditional migraine therapies yield inadequate efficacy, cause intolerable adverse effects, are contraindicated, or introduce the risk for medication interactions.

CORRESPONDENCE
Emily Peterson, PharmD, BCACP, 3640 Middlebury Road, Iowa City, IA 52242; [email protected]

Migraine is a headache disorder that often causes unilateral pain, photophobia, phonophobia, nausea, and vomiting. More than 70% of office visits for migraine are made to primary care physicians.¹ Recent data suggest migraine may be caused primarily by neuronal dysfunction and only secondarily by vasodilation.² Although there are numerous classes of drugs used for migraine prevention and treatment, their success has been limited by inadequate efficacy, tolerability, and patient adherence.³ The discovery of pro-inflammatory markers such as calcitonin gene-related peptide (CGRP) has led to the development of new medications to prevent and treat migraine.⁴

IMAGE: © SCOTT BODELL

Pathophysiology, Dx and triggers, indications for pharmacotherapy

Pathophysiology. A migraine is thought to be caused by cortical spreading depression (CSD), a depolarization of glial and neuronal cell membranes.⁵This results in increased cortical excitability, central trigeminal-thalamic sensitization, and defective descending pain modulatory activity.⁶The activation of the trigeminal sensory pathways, primarily the ophthalmic branch, sends nociceptive signals to second-order neurons mediated by the release of neurotransmitters, such as CGRPs.⁵ This activation explains in part the primary location for a migraine, which is around the eye and the neighboring cranial regions. The pain perceived by the patient is caused by these second-order neurons.

It has been theorized that gepants bind to calcitonin gene-related peptide receptors, resulting in decreased blood flow to the brain, inhibition of neurogenic inflammation, and reduced pain signaling.

Dx and triggers. In 2018, the International Headache Society revised its guidelines for the diagnosis of migraine.⁷ According to the 3rd edition of The International Classification of Headache Disorders (ICHD-3), the diagnosis of migraine is made when a patient has at least 5 headache attacks that last 4 to 72 hours and have at least 2 of the following characteristics: (1) unilateral location, (2) pulsating quality, (3) moderate-to-severe pain intensity, and (4) aggravated by or causing avoidance of routine physical activity.⁷ The headache attacks also should have (1) associated nausea or vomiting or (2) photophobia and phonophobia.⁷ The presence of atypical signs or symptoms as indicated by the SNNOOP10 mnemonic raises concerns for secondary headaches and the need for further investigation into the cause of the headache (TABLE 1).⁸ It is not possible to detect every secondary headache with standard neuroimaging, but the SNNOOP10 red flags can help determine when imaging may be indicated.⁸ Potential triggers for migraine can be found in TABLE 2.⁹

Indications for pharmacotherapy. All patients receiving a diagnosis of migraine should be offered acute pharmacologic treatment. Consider preventive therapy anytime there are ≥ 4 headache days per month, debilitating attacks despite acute therapy, overuse of acute medication (> 2 d/wk), difficulty tolerating acute medication, patient preference, or presence of certain migraine subtypes.^7,10

Acute treatments

Abortive therapies for migraine include analgesics such as nonsteroidal anti-­inflammatory drugs (NSAIDs) and acetaminophen, and ergot alkaloids, triptans, or small-molecule CGRP receptor antagonists (gepants). Prompt administration increases the chance of success with acute therapy. Medications with the highest levels of efficacy based on the 2015 guidelines from the American Headache Society (AHS) are given in TABLE 3.¹¹ Lasmiditan (Reyvow) is not included in the 2015 guidelines, as it was approved after publication of the guidelines.

Non-CGRP first-line therapies

NSAIDs and acetaminophen. NSAIDs such as aspirin, diclofenac, ibuprofen, and naproxen have a high level of evidence to support their use as first-line treatments for mild-to-moderate migraine attacks. Trials consistently demonstrate their superiority to placebo in headache relief and complete pain relief at 2 hours. There is no recommendation for selecting one NSAID over another; however, consider their frequency of dosing and ­adverse effect profiles. The number needed to treat for complete pain relief at 2 hours ranges from 7 to 10 for most NSAIDs.^11,12 In some placebo-controlled studies, acetaminophen was less effective than NSAIDs, but was safer because it did not cause gastric irritation or antiplatelet effects.¹²

Triptans inhibit 5-HT_1B/1D receptors. Consider formulation, route of administration, cost, and pharmacokinetics when selecting a triptan. Patients who do not respond well to one triptan may respond favorably to another. A meta-analysis of the effectiveness of the 7 available agents found that triptans at standard doses provided pain relief within 2 hours in 42% to 76% of patients, and sustained freedom from pain for 2 hours in 18% to 50% of patients.¹³ Lasmiditan is a selective serotonin receptor (5-HT_1F) agonist that lacks vasoconstrictor activity. This is an option for patients with relative contraindications to triptans due to cardiovascular risk factors.¹⁰

Continue to: Second-line therapies

Intranasal dihydroergotamine has a favorable adverse event profile and greater evidence for efficacy compared with ergotamine. Compared with triptans, intranasal dihydroergotamine has a high level of efficacy but causes more adverse effects.¹⁴ Severe nausea is common, and dihydroergotamine often is used in combination with an antiemetic drug. Dihydroergotamine should not be used within 24 hours of taking a triptan, and it is contraindicated for patients who have hypertension or ischemic heart disease or who are pregnant or breastfeeding. There is also the potential for adverse drug interactions.¹⁵

A meta-analysis found that triptans at standard doses provided pain relief within 2 hours in 42% to 76% of patients, and sustained freedom from pain for 2 hours in 18% to 50% of patients.

Antiemetics may be helpful for migraine associated with severe nausea or vomiting. The dopamine antagonists metoclopramide, prochlorperazine, and chlorpromazine have demonstrated benefit in randomized ­placebo-controlled trials.¹¹ Ondansetron has not been studied extensively, but sometimes is used in clinical practice. Nonoral routes of administration may be useful in patients having trouble swallowing medications or in those experiencing significant nausea or vomiting early during migraine attacks.

Due to the high potential for abuse, opioids should not be used routinely for the treatment of migraine.¹² There is no high-quality evidence supporting the efficacy of barbiturates (ie, butalbital-containing compounds) for acute migraine treatment.¹¹ Moreover, use of these agents may increase the likelihood of progression from episodic to chronic migraine.¹⁶

Gepants for acute migraine treatment

Neuropeptide CGRP is released from trigeminal nerves and is a potent dilator of cerebral and dural vessels, playing a key role in regulating blood flow to the brain. Other roles of CGRP include the release of inflammatory agents from mast cells and the transmission of painful stimuli from intracranial vessels.¹⁷ The CGRP receptor or ligand can be targeted by small-molecule receptor antagonists for acute and preventive migraine treatment (and by monoclonal antibodies solely for prevention, discussed later). It has been theorized that gepants bind to CGRP receptors, resulting in decreased blood flow to the brain, inhibition of neurogenic inflammation, and reduced pain signaling.¹⁷ Unlike triptans and ergotamine derivatives, these novel treatments do not constrict blood vessels and may have a unique role in patients with contraindications to triptans.

The 3 gepants approved for acute treatment—ubrogepant (Ubrelvy),¹⁸ rimegepant (Nurtec),¹⁹ and zavegepant (Zavzpret)²⁰—were compared with placebo in clinical trials and were shown to increase the number of patients who were completely pain free at 2 hours, were free of the most bothersome associated symptom (photophobia, phonophobia, or nausea) at 2 hours, and remained pain free at 24 hours (TABLE 4^18-24).

Continue to: Ubrogrepant

Ubrogepant, in 2 Phase 3 trials (ACHIEVE I and ACHIEVE II) demonstrated effectiveness compared with placebo.^21,22 The most common adverse effects reported were nausea and somnolence at very low rates. Pain-relief rates at 2 hours post dose (> 60% of participants) were higher than pain-free rates, and a significantly higher percentage (> 40%) of ubrogepant-treated participants reported ability to function normally on the Functional Disability Scale.²⁵

Rimegepant was also superior to placebo (59% vs 43%) in pain relief at 2 hours post dose and other secondary endpoints.²³ Rimegepant also has potential drug interactions and dose adjustments (TABLE 4^18-24).

Zavegepant, approved in March 2023, is administered once daily as a 10-mg nasal spray. In its Phase 3 trial, zavegepant was significantly superior to placebo at 2 hours post dose in freedom from pain (24% v 15%), and in freedom from the most bothersome symptom (40% v 31%).²⁴ Dosage modifications are not needed with mild-to-moderate renal or hepatic disease.²⁰

Worth noting. The safety of using ubrogepant to treat more than 8 migraine episodes in a 30-day period has not been established. The safety of using more than 18 doses of zavegepant in a 30-day period also has not been established. With ubrogepant and rimegepant, there are dosing modifications for concomitant use with specific drugs (CYP3A4 inhibitors and inducers) due to potential interactions and in patients with hepatic or renal impairment.^18,19

There are no trials comparing efficacy of CGRP antagonists to triptans. Recognizing that these newer medications would be costly, the AHS position statement released in 2019 recommends that gepants be considered for those with contraindications to triptans or for whom at least 2 oral triptans have failed (as determined by a validated patient outcome questionnaire).¹⁰ Step therapy with documentation of previous trials and therapy failures is often required by insurance companies prior to gepant coverage.

Continue to: Preventive therapies

Preventive therapies

Preventive migraine therapies are used to reduce duration, frequency, and severity of attacks, the need for acute treatment, and overall headache disability.²⁶ Medications typically are chosen based on efficacy, adverse effect profile, and patient comorbidities. Barriers to successful use include poor patient adherence and tolerability, the need for slow dose titration, and long-term use (minimum of 2 months) at maximum tolerated or minimum effective doses. Medications with established efficacy (Level A^a) based on the 2012 guidelines from the American Academy of Neurology (AAN) and the AHS are given in TABLE 5.^27-29

Drugs having received the strongest level of evidence for migraine prevention are metoprolol, propranolol, timolol, topiramate, valproate sodium, divalproex sodium, and onabotulinumtoxinA (Botox), and frovatriptan for menstrual migraine prevention. Because these guidelines were last updated in 2012, they did not cover gepants (which will be discussed shortly). The AHS released a position statement in 2019 supporting the use of anti-CGRP monoclonal antibodies (mAbs) in those who cannot tolerate or have had an inadequate response to a 6-week trial of at least 2 AAN/AHA Level A or B^b treatments.¹⁰ No head-to-head trials exist between non-CGRP preventive therapies and the CGRP antagonists.

CGRP-targeted prevention

Four anti-CGRP mAbs and 2 gepants have been approved for migraine prevention in the United States. Differences between products include targets (ligand vs receptor), antibody IgG subtype, bioavailability, route of administration, and frequency of administration.²⁸ As noted in the Phase 3 studies (TABLE 6^19,30-47), these therapies are highly efficacious, safe, and tolerable.

Gepants. Rimegepant, discussed earlier for migraine treatment, is one of the CGRP receptor antagonists approved for prevention. The other is atogepant (Qulipta), approved only for prevention. Ubrogepant is not approved for prevention.

Anti-CGRP mAb is the only medication class specifically created for migraine prevention.^10,26 As already noted, several efficacious non-CGRP treatment options are available for migraine prevention. However, higher doses of those agents, if needed, can lead to intolerable adverse effects for some patients, thereby limiting overall efficacy. ­Anti-CGRP mAbs, a targeted, highly efficacious treatment option, offer efficacy comparable to non-CGRP agents with a more favorable adverse effect profile for those who cannot tolerate or achieve only minimal efficacy with traditional preventive therapies.¹⁰

Continue to: The targeted anti-CGRP approach...

The targeted anti-CGRP approach, which can be used by patients with liver or kidney disease, results in decreased toxicity and minimal drug interactions. Long half-lives allow for monthly or quarterly injections, possibly resulting in increased compliance.²⁸ Dose titration is not needed, allowing for more rapid symptom management. The large molecular size of a mAb limits its transfer across the blood-brain barrier, making central nervous system adverse effects unlikely.²⁸ Despite the compelling mAb pharmacologic properties, their use may be limited by a lack of long-term safety data and the need for parenteral administration. Although ­immunogenicity—the development of neutralizing antibodies—can limit long-term tolerability or efficacy of mAbs generally,^26,28 anti-CGRP mAbs were engineered to minimally activate the immune system and have not been associated with immune suppression, opportunistic infections, malignancies, or decreased efficacy.²⁸

Unlike triptans and ergotamine derivatives, gepants do not constrict blood vessels and may have a unique role in patients with contraindications to triptans.

A pooled meta-analysis including 4 trials (3166 patients) found that CGRP mAbs compared with placebo significantly improved patient response rates, defined as at least a 50% and 75% reduction in monthly ­headache/migraine days from baseline to Weeks 9 to 12.⁴⁸ Another meta-analysis including 8 trials (2292 patients) found a significant reduction from baseline in monthly migraine days and monthly acute migraine medication consumption among patients taking CGRP mAbs compared with those taking placebo.⁴⁹ Open-label extension studies have shown progressive and cumulative benefits in individuals who respond to anti-CGRP mAbs. Therefore, several treatment cycles may be necessary to determine overall efficacy of therapy.^10,28

Cost initially can be a barrier. Insurance companies often require step therapy before agreeing to cover mAb therapy, which aligns with the 2019 AHS position statement.¹⁰Due to differences in insurance coverage, out-of-pocket expenses can vary greatly. However, options are available through online manufacturer assistance to reduce cost, making it comparable to other migraine treatments. Safety and efficacy studies of anti-CGRP mAbs use in pregnant individuals are limited. At this time, they should not be prescribed for those who are pregnant, planning to become pregnant, or breastfeeding. Counsel nonpregnant patients on appropriate contraception while using a mAb due to possible teratogenicity and negative pregnancy outcomes.^28,50

When combination treatment may be appropriate

Monotherapy is the usual approach to preventing migraine due to advantages of efficacy, simplified regimens, lower cost, and reduced adverse effects.⁵¹ However, if a patient does not benefit from monotherapy even after trying dose titrations as tolerated or switching therapies, trying complementary combination therapy is appropriate. Despite a shortage of clinical trials supporting the use of 2 or more preventive medications with different mechanisms of action, this strategy is used clinically.¹⁰ Consider combination therapy in those with refractory disease, partial responses, or intolerance to recommended doses.⁵² Articles reporting on case study reviews have rationalized the combined use of onabotulinumtoxinA and anti-CGRP mAbs, noting better migraine control.^51,53 The 2019 AHS position statement recommends adding a mAb to an existing preventive treatment regimen with no other changes until mAb effectiveness is determined, as the risk for drug interactions on dual therapy is low.¹⁰ Safety and efficacy also have been demonstrated with the combination of preventive anti-CGRP mAbs and acute treatment with gepants as needed.⁵⁴

Monoclonal antibodies are highly efficacious options for those who cannot tolerate or achieve only minimal efficacy with traditional preventive therapies.

Overall, gepants and mAbs are as effective as traditional acute and preventive treatments for migraine, and they cause fewer adverse effects and often allow a more simplified regimen. Gepants and mAbs are viable options in the primary care setting. Due to limited long-term data and high cost, however, they routinely are used for refractory migraine rather than as first-line agents. These therapies are especially favorable options for patients when traditional migraine therapies yield inadequate efficacy, cause intolerable adverse effects, are contraindicated, or introduce the risk for medication interactions.

CORRESPONDENCE
Emily Peterson, PharmD, BCACP, 3640 Middlebury Road, Iowa City, IA 52242; [email protected]

Migraine is a headache disorder that often causes unilateral pain, photophobia, phonophobia, nausea, and vomiting. More than 70% of office visits for migraine are made to primary care physicians.¹ Recent data suggest migraine may be caused primarily by neuronal dysfunction and only secondarily by vasodilation.² Although there are numerous classes of drugs used for migraine prevention and treatment, their success has been limited by inadequate efficacy, tolerability, and patient adherence.³ The discovery of pro-inflammatory markers such as calcitonin gene-related peptide (CGRP) has led to the development of new medications to prevent and treat migraine.⁴

IMAGE: © SCOTT BODELL

Pathophysiology, Dx and triggers, indications for pharmacotherapy

Pathophysiology. A migraine is thought to be caused by cortical spreading depression (CSD), a depolarization of glial and neuronal cell membranes.⁵This results in increased cortical excitability, central trigeminal-thalamic sensitization, and defective descending pain modulatory activity.⁶The activation of the trigeminal sensory pathways, primarily the ophthalmic branch, sends nociceptive signals to second-order neurons mediated by the release of neurotransmitters, such as CGRPs.⁵ This activation explains in part the primary location for a migraine, which is around the eye and the neighboring cranial regions. The pain perceived by the patient is caused by these second-order neurons.

It has been theorized that gepants bind to calcitonin gene-related peptide receptors, resulting in decreased blood flow to the brain, inhibition of neurogenic inflammation, and reduced pain signaling.

Dx and triggers. In 2018, the International Headache Society revised its guidelines for the diagnosis of migraine.⁷ According to the 3rd edition of The International Classification of Headache Disorders (ICHD-3), the diagnosis of migraine is made when a patient has at least 5 headache attacks that last 4 to 72 hours and have at least 2 of the following characteristics: (1) unilateral location, (2) pulsating quality, (3) moderate-to-severe pain intensity, and (4) aggravated by or causing avoidance of routine physical activity.⁷ The headache attacks also should have (1) associated nausea or vomiting or (2) photophobia and phonophobia.⁷ The presence of atypical signs or symptoms as indicated by the SNNOOP10 mnemonic raises concerns for secondary headaches and the need for further investigation into the cause of the headache (TABLE 1).⁸ It is not possible to detect every secondary headache with standard neuroimaging, but the SNNOOP10 red flags can help determine when imaging may be indicated.⁸ Potential triggers for migraine can be found in TABLE 2.⁹

Indications for pharmacotherapy. All patients receiving a diagnosis of migraine should be offered acute pharmacologic treatment. Consider preventive therapy anytime there are ≥ 4 headache days per month, debilitating attacks despite acute therapy, overuse of acute medication (> 2 d/wk), difficulty tolerating acute medication, patient preference, or presence of certain migraine subtypes.^7,10

Acute treatments

Abortive therapies for migraine include analgesics such as nonsteroidal anti-­inflammatory drugs (NSAIDs) and acetaminophen, and ergot alkaloids, triptans, or small-molecule CGRP receptor antagonists (gepants). Prompt administration increases the chance of success with acute therapy. Medications with the highest levels of efficacy based on the 2015 guidelines from the American Headache Society (AHS) are given in TABLE 3.¹¹ Lasmiditan (Reyvow) is not included in the 2015 guidelines, as it was approved after publication of the guidelines.

Non-CGRP first-line therapies

NSAIDs and acetaminophen. NSAIDs such as aspirin, diclofenac, ibuprofen, and naproxen have a high level of evidence to support their use as first-line treatments for mild-to-moderate migraine attacks. Trials consistently demonstrate their superiority to placebo in headache relief and complete pain relief at 2 hours. There is no recommendation for selecting one NSAID over another; however, consider their frequency of dosing and ­adverse effect profiles. The number needed to treat for complete pain relief at 2 hours ranges from 7 to 10 for most NSAIDs.^11,12 In some placebo-controlled studies, acetaminophen was less effective than NSAIDs, but was safer because it did not cause gastric irritation or antiplatelet effects.¹²

Triptans inhibit 5-HT_1B/1D receptors. Consider formulation, route of administration, cost, and pharmacokinetics when selecting a triptan. Patients who do not respond well to one triptan may respond favorably to another. A meta-analysis of the effectiveness of the 7 available agents found that triptans at standard doses provided pain relief within 2 hours in 42% to 76% of patients, and sustained freedom from pain for 2 hours in 18% to 50% of patients.¹³ Lasmiditan is a selective serotonin receptor (5-HT_1F) agonist that lacks vasoconstrictor activity. This is an option for patients with relative contraindications to triptans due to cardiovascular risk factors.¹⁰

Continue to: Second-line therapies

Intranasal dihydroergotamine has a favorable adverse event profile and greater evidence for efficacy compared with ergotamine. Compared with triptans, intranasal dihydroergotamine has a high level of efficacy but causes more adverse effects.¹⁴ Severe nausea is common, and dihydroergotamine often is used in combination with an antiemetic drug. Dihydroergotamine should not be used within 24 hours of taking a triptan, and it is contraindicated for patients who have hypertension or ischemic heart disease or who are pregnant or breastfeeding. There is also the potential for adverse drug interactions.¹⁵

A meta-analysis found that triptans at standard doses provided pain relief within 2 hours in 42% to 76% of patients, and sustained freedom from pain for 2 hours in 18% to 50% of patients.

Antiemetics may be helpful for migraine associated with severe nausea or vomiting. The dopamine antagonists metoclopramide, prochlorperazine, and chlorpromazine have demonstrated benefit in randomized ­placebo-controlled trials.¹¹ Ondansetron has not been studied extensively, but sometimes is used in clinical practice. Nonoral routes of administration may be useful in patients having trouble swallowing medications or in those experiencing significant nausea or vomiting early during migraine attacks.

Due to the high potential for abuse, opioids should not be used routinely for the treatment of migraine.¹² There is no high-quality evidence supporting the efficacy of barbiturates (ie, butalbital-containing compounds) for acute migraine treatment.¹¹ Moreover, use of these agents may increase the likelihood of progression from episodic to chronic migraine.¹⁶

Gepants for acute migraine treatment

Neuropeptide CGRP is released from trigeminal nerves and is a potent dilator of cerebral and dural vessels, playing a key role in regulating blood flow to the brain. Other roles of CGRP include the release of inflammatory agents from mast cells and the transmission of painful stimuli from intracranial vessels.¹⁷ The CGRP receptor or ligand can be targeted by small-molecule receptor antagonists for acute and preventive migraine treatment (and by monoclonal antibodies solely for prevention, discussed later). It has been theorized that gepants bind to CGRP receptors, resulting in decreased blood flow to the brain, inhibition of neurogenic inflammation, and reduced pain signaling.¹⁷ Unlike triptans and ergotamine derivatives, these novel treatments do not constrict blood vessels and may have a unique role in patients with contraindications to triptans.

The 3 gepants approved for acute treatment—ubrogepant (Ubrelvy),¹⁸ rimegepant (Nurtec),¹⁹ and zavegepant (Zavzpret)²⁰—were compared with placebo in clinical trials and were shown to increase the number of patients who were completely pain free at 2 hours, were free of the most bothersome associated symptom (photophobia, phonophobia, or nausea) at 2 hours, and remained pain free at 24 hours (TABLE 4^18-24).

Continue to: Ubrogrepant

Ubrogepant, in 2 Phase 3 trials (ACHIEVE I and ACHIEVE II) demonstrated effectiveness compared with placebo.^21,22 The most common adverse effects reported were nausea and somnolence at very low rates. Pain-relief rates at 2 hours post dose (> 60% of participants) were higher than pain-free rates, and a significantly higher percentage (> 40%) of ubrogepant-treated participants reported ability to function normally on the Functional Disability Scale.²⁵

Rimegepant was also superior to placebo (59% vs 43%) in pain relief at 2 hours post dose and other secondary endpoints.²³ Rimegepant also has potential drug interactions and dose adjustments (TABLE 4^18-24).

Zavegepant, approved in March 2023, is administered once daily as a 10-mg nasal spray. In its Phase 3 trial, zavegepant was significantly superior to placebo at 2 hours post dose in freedom from pain (24% v 15%), and in freedom from the most bothersome symptom (40% v 31%).²⁴ Dosage modifications are not needed with mild-to-moderate renal or hepatic disease.²⁰

Worth noting. The safety of using ubrogepant to treat more than 8 migraine episodes in a 30-day period has not been established. The safety of using more than 18 doses of zavegepant in a 30-day period also has not been established. With ubrogepant and rimegepant, there are dosing modifications for concomitant use with specific drugs (CYP3A4 inhibitors and inducers) due to potential interactions and in patients with hepatic or renal impairment.^18,19

There are no trials comparing efficacy of CGRP antagonists to triptans. Recognizing that these newer medications would be costly, the AHS position statement released in 2019 recommends that gepants be considered for those with contraindications to triptans or for whom at least 2 oral triptans have failed (as determined by a validated patient outcome questionnaire).¹⁰ Step therapy with documentation of previous trials and therapy failures is often required by insurance companies prior to gepant coverage.

Continue to: Preventive therapies

Preventive therapies

Preventive migraine therapies are used to reduce duration, frequency, and severity of attacks, the need for acute treatment, and overall headache disability.²⁶ Medications typically are chosen based on efficacy, adverse effect profile, and patient comorbidities. Barriers to successful use include poor patient adherence and tolerability, the need for slow dose titration, and long-term use (minimum of 2 months) at maximum tolerated or minimum effective doses. Medications with established efficacy (Level A^a) based on the 2012 guidelines from the American Academy of Neurology (AAN) and the AHS are given in TABLE 5.^27-29

Drugs having received the strongest level of evidence for migraine prevention are metoprolol, propranolol, timolol, topiramate, valproate sodium, divalproex sodium, and onabotulinumtoxinA (Botox), and frovatriptan for menstrual migraine prevention. Because these guidelines were last updated in 2012, they did not cover gepants (which will be discussed shortly). The AHS released a position statement in 2019 supporting the use of anti-CGRP monoclonal antibodies (mAbs) in those who cannot tolerate or have had an inadequate response to a 6-week trial of at least 2 AAN/AHA Level A or B^b treatments.¹⁰ No head-to-head trials exist between non-CGRP preventive therapies and the CGRP antagonists.

CGRP-targeted prevention

Four anti-CGRP mAbs and 2 gepants have been approved for migraine prevention in the United States. Differences between products include targets (ligand vs receptor), antibody IgG subtype, bioavailability, route of administration, and frequency of administration.²⁸ As noted in the Phase 3 studies (TABLE 6^19,30-47), these therapies are highly efficacious, safe, and tolerable.

Gepants. Rimegepant, discussed earlier for migraine treatment, is one of the CGRP receptor antagonists approved for prevention. The other is atogepant (Qulipta), approved only for prevention. Ubrogepant is not approved for prevention.

Anti-CGRP mAb is the only medication class specifically created for migraine prevention.^10,26 As already noted, several efficacious non-CGRP treatment options are available for migraine prevention. However, higher doses of those agents, if needed, can lead to intolerable adverse effects for some patients, thereby limiting overall efficacy. ­Anti-CGRP mAbs, a targeted, highly efficacious treatment option, offer efficacy comparable to non-CGRP agents with a more favorable adverse effect profile for those who cannot tolerate or achieve only minimal efficacy with traditional preventive therapies.¹⁰

Continue to: The targeted anti-CGRP approach...

The targeted anti-CGRP approach, which can be used by patients with liver or kidney disease, results in decreased toxicity and minimal drug interactions. Long half-lives allow for monthly or quarterly injections, possibly resulting in increased compliance.²⁸ Dose titration is not needed, allowing for more rapid symptom management. The large molecular size of a mAb limits its transfer across the blood-brain barrier, making central nervous system adverse effects unlikely.²⁸ Despite the compelling mAb pharmacologic properties, their use may be limited by a lack of long-term safety data and the need for parenteral administration. Although ­immunogenicity—the development of neutralizing antibodies—can limit long-term tolerability or efficacy of mAbs generally,^26,28 anti-CGRP mAbs were engineered to minimally activate the immune system and have not been associated with immune suppression, opportunistic infections, malignancies, or decreased efficacy.²⁸

Unlike triptans and ergotamine derivatives, gepants do not constrict blood vessels and may have a unique role in patients with contraindications to triptans.

A pooled meta-analysis including 4 trials (3166 patients) found that CGRP mAbs compared with placebo significantly improved patient response rates, defined as at least a 50% and 75% reduction in monthly ­headache/migraine days from baseline to Weeks 9 to 12.⁴⁸ Another meta-analysis including 8 trials (2292 patients) found a significant reduction from baseline in monthly migraine days and monthly acute migraine medication consumption among patients taking CGRP mAbs compared with those taking placebo.⁴⁹ Open-label extension studies have shown progressive and cumulative benefits in individuals who respond to anti-CGRP mAbs. Therefore, several treatment cycles may be necessary to determine overall efficacy of therapy.^10,28

Cost initially can be a barrier. Insurance companies often require step therapy before agreeing to cover mAb therapy, which aligns with the 2019 AHS position statement.¹⁰Due to differences in insurance coverage, out-of-pocket expenses can vary greatly. However, options are available through online manufacturer assistance to reduce cost, making it comparable to other migraine treatments. Safety and efficacy studies of anti-CGRP mAbs use in pregnant individuals are limited. At this time, they should not be prescribed for those who are pregnant, planning to become pregnant, or breastfeeding. Counsel nonpregnant patients on appropriate contraception while using a mAb due to possible teratogenicity and negative pregnancy outcomes.^28,50

When combination treatment may be appropriate

Monotherapy is the usual approach to preventing migraine due to advantages of efficacy, simplified regimens, lower cost, and reduced adverse effects.⁵¹ However, if a patient does not benefit from monotherapy even after trying dose titrations as tolerated or switching therapies, trying complementary combination therapy is appropriate. Despite a shortage of clinical trials supporting the use of 2 or more preventive medications with different mechanisms of action, this strategy is used clinically.¹⁰ Consider combination therapy in those with refractory disease, partial responses, or intolerance to recommended doses.⁵² Articles reporting on case study reviews have rationalized the combined use of onabotulinumtoxinA and anti-CGRP mAbs, noting better migraine control.^51,53 The 2019 AHS position statement recommends adding a mAb to an existing preventive treatment regimen with no other changes until mAb effectiveness is determined, as the risk for drug interactions on dual therapy is low.¹⁰ Safety and efficacy also have been demonstrated with the combination of preventive anti-CGRP mAbs and acute treatment with gepants as needed.⁵⁴

Monoclonal antibodies are highly efficacious options for those who cannot tolerate or achieve only minimal efficacy with traditional preventive therapies.

Overall, gepants and mAbs are as effective as traditional acute and preventive treatments for migraine, and they cause fewer adverse effects and often allow a more simplified regimen. Gepants and mAbs are viable options in the primary care setting. Due to limited long-term data and high cost, however, they routinely are used for refractory migraine rather than as first-line agents. These therapies are especially favorable options for patients when traditional migraine therapies yield inadequate efficacy, cause intolerable adverse effects, are contraindicated, or introduce the risk for medication interactions.

CORRESPONDENCE
Emily Peterson, PharmD, BCACP, 3640 Middlebury Road, Iowa City, IA 52242; [email protected]

Hirshberg A, Zhu Y, Smith-McLallen A, et al. Association of a remote blood pressure monitoring program with postpartum adverse outcomes. Obstet Gynecol. 2023;141:1163-1170. doi:10.1097/AOG.0000000000005197. 

EXPERT COMMENTARY

Courtney Bisson, MD, is a Maternal-Fetal Medicine Fellow, University of Chicago/NorthShore University HealthSystem, Chicago, Illinois.

Sarosh Rana, MD, MPH, is Professor of Obstetrics and Gynecology and Section Chief, Maternal-Fetal Medicine, University of Chicago.

Hypertensive disorders of pregnancy account for a significant amount of morbidity during pregnancy and postpartum. In the pregnant population, data have shown that the implementation of a standardized blood pressure education program, provision of a blood pressure cuff, and assistance with postpartum follow-up result in improved blood pressures and postpartum follow-up for up to 6 weeks. In the nonpregnant population, literature suggests that RBPM in patients with hypertension results in improved outcomes, although the long-term impact of RBPM in the postpartum population remains unclear.

Recently, Hirshberg and colleagues published the results of a retrospective cohort study that assessed the impact of RBPM with text message reminders for 10 days postpartum on a composite of adverse maternal outcomes, readmissions, and follow-up within 1 year postpartum.¹

PHOTO: MICROGEN/SHUTTERSTOCK

Details of the study

The retrospective cohort study was conducted during 2017–2021 based on insurance claims of patients with hypertensive disorders of pregnancy who were enrolled in a twice-daily text message–based RBPM program for 10 days postpartum.

Data from 1,700 patients enrolled in RBPM were compared with that of propensity score matched controls that included 2,297 women not enrolled in RBPM. Of these controls, 1,276 patients (cohort C) simultaneously received care at other institutions without RBPM, and 1,021 patients (cohort A) received care at the same institution prior to implementation of RBPM.

Results. Patients in the RBPM group were found to have a significantly lower rate of composite adverse maternal outcomes compared with their matched cohorts in the year after delivery. (Individual adverse outcomes included stroke, disseminated intravascular coagulation, eclampsia, pulmonary edema, renal injury or liver failure, HELLP [hemolysis, elevated liver enzymes, low platelet count] syndrome, myocardial infarction, and cardiomyopathy.) Rates were 2.9% versus 4.7% (odds ratio [OR], 0.61; 95% confidence interval [CI], 0.40–0.98) in the RBPM group compared with cohort A; rates in the RBPM group compared with cohort C were 3.2% versus 4.5% (OR, 0.71; 95% CI, 0.47–1.07).

Although not statistically significant, rates of emergency department visits and readmissions also were lower in the RBPM patients. Those enrolled in the RBPM program were more likely to have follow-up with cardiologists or specialist visits within 6 months postpartum. Fewer emergency department visits and readmissions resulted in lower health care utilization costs.

Study strengths and limitations

This study’s strength lies in its design and implementation of standardized protocols that allowed assessment of clinically meaningful outcomes postpartum. Although the program for RBPM was for only 10 days postpartum, it showed effects beyond the timeframe of the direct care. No such prior data exist evaluating a program’s effectiveness in improving postpartum clinical outcomes and costs through 1 year postdelivery.

Study limitations include residual bias from unobserved confounders, analysis of only 1 payer type, lack of patient level data, and evaluation of disparity. ●

Hirshberg A, Zhu Y, Smith-McLallen A, et al. Association of a remote blood pressure monitoring program with postpartum adverse outcomes. Obstet Gynecol. 2023;141:1163-1170. doi:10.1097/AOG.0000000000005197. 

EXPERT COMMENTARY

Courtney Bisson, MD, is a Maternal-Fetal Medicine Fellow, University of Chicago/NorthShore University HealthSystem, Chicago, Illinois.

Sarosh Rana, MD, MPH, is Professor of Obstetrics and Gynecology and Section Chief, Maternal-Fetal Medicine, University of Chicago.

Hypertensive disorders of pregnancy account for a significant amount of morbidity during pregnancy and postpartum. In the pregnant population, data have shown that the implementation of a standardized blood pressure education program, provision of a blood pressure cuff, and assistance with postpartum follow-up result in improved blood pressures and postpartum follow-up for up to 6 weeks. In the nonpregnant population, literature suggests that RBPM in patients with hypertension results in improved outcomes, although the long-term impact of RBPM in the postpartum population remains unclear.

Recently, Hirshberg and colleagues published the results of a retrospective cohort study that assessed the impact of RBPM with text message reminders for 10 days postpartum on a composite of adverse maternal outcomes, readmissions, and follow-up within 1 year postpartum.¹

PHOTO: MICROGEN/SHUTTERSTOCK

Details of the study

The retrospective cohort study was conducted during 2017–2021 based on insurance claims of patients with hypertensive disorders of pregnancy who were enrolled in a twice-daily text message–based RBPM program for 10 days postpartum.

Data from 1,700 patients enrolled in RBPM were compared with that of propensity score matched controls that included 2,297 women not enrolled in RBPM. Of these controls, 1,276 patients (cohort C) simultaneously received care at other institutions without RBPM, and 1,021 patients (cohort A) received care at the same institution prior to implementation of RBPM.

Results. Patients in the RBPM group were found to have a significantly lower rate of composite adverse maternal outcomes compared with their matched cohorts in the year after delivery. (Individual adverse outcomes included stroke, disseminated intravascular coagulation, eclampsia, pulmonary edema, renal injury or liver failure, HELLP [hemolysis, elevated liver enzymes, low platelet count] syndrome, myocardial infarction, and cardiomyopathy.) Rates were 2.9% versus 4.7% (odds ratio [OR], 0.61; 95% confidence interval [CI], 0.40–0.98) in the RBPM group compared with cohort A; rates in the RBPM group compared with cohort C were 3.2% versus 4.5% (OR, 0.71; 95% CI, 0.47–1.07).

Although not statistically significant, rates of emergency department visits and readmissions also were lower in the RBPM patients. Those enrolled in the RBPM program were more likely to have follow-up with cardiologists or specialist visits within 6 months postpartum. Fewer emergency department visits and readmissions resulted in lower health care utilization costs.

Study strengths and limitations

This study’s strength lies in its design and implementation of standardized protocols that allowed assessment of clinically meaningful outcomes postpartum. Although the program for RBPM was for only 10 days postpartum, it showed effects beyond the timeframe of the direct care. No such prior data exist evaluating a program’s effectiveness in improving postpartum clinical outcomes and costs through 1 year postdelivery.

Study limitations include residual bias from unobserved confounders, analysis of only 1 payer type, lack of patient level data, and evaluation of disparity. ●

Hirshberg A, Zhu Y, Smith-McLallen A, et al. Association of a remote blood pressure monitoring program with postpartum adverse outcomes. Obstet Gynecol. 2023;141:1163-1170. doi:10.1097/AOG.0000000000005197. 

EXPERT COMMENTARY

Courtney Bisson, MD, is a Maternal-Fetal Medicine Fellow, University of Chicago/NorthShore University HealthSystem, Chicago, Illinois.

Sarosh Rana, MD, MPH, is Professor of Obstetrics and Gynecology and Section Chief, Maternal-Fetal Medicine, University of Chicago.

Hypertensive disorders of pregnancy account for a significant amount of morbidity during pregnancy and postpartum. In the pregnant population, data have shown that the implementation of a standardized blood pressure education program, provision of a blood pressure cuff, and assistance with postpartum follow-up result in improved blood pressures and postpartum follow-up for up to 6 weeks. In the nonpregnant population, literature suggests that RBPM in patients with hypertension results in improved outcomes, although the long-term impact of RBPM in the postpartum population remains unclear.

Recently, Hirshberg and colleagues published the results of a retrospective cohort study that assessed the impact of RBPM with text message reminders for 10 days postpartum on a composite of adverse maternal outcomes, readmissions, and follow-up within 1 year postpartum.¹

PHOTO: MICROGEN/SHUTTERSTOCK

Details of the study

The retrospective cohort study was conducted during 2017–2021 based on insurance claims of patients with hypertensive disorders of pregnancy who were enrolled in a twice-daily text message–based RBPM program for 10 days postpartum.

Data from 1,700 patients enrolled in RBPM were compared with that of propensity score matched controls that included 2,297 women not enrolled in RBPM. Of these controls, 1,276 patients (cohort C) simultaneously received care at other institutions without RBPM, and 1,021 patients (cohort A) received care at the same institution prior to implementation of RBPM.

Results. Patients in the RBPM group were found to have a significantly lower rate of composite adverse maternal outcomes compared with their matched cohorts in the year after delivery. (Individual adverse outcomes included stroke, disseminated intravascular coagulation, eclampsia, pulmonary edema, renal injury or liver failure, HELLP [hemolysis, elevated liver enzymes, low platelet count] syndrome, myocardial infarction, and cardiomyopathy.) Rates were 2.9% versus 4.7% (odds ratio [OR], 0.61; 95% confidence interval [CI], 0.40–0.98) in the RBPM group compared with cohort A; rates in the RBPM group compared with cohort C were 3.2% versus 4.5% (OR, 0.71; 95% CI, 0.47–1.07).

Although not statistically significant, rates of emergency department visits and readmissions also were lower in the RBPM patients. Those enrolled in the RBPM program were more likely to have follow-up with cardiologists or specialist visits within 6 months postpartum. Fewer emergency department visits and readmissions resulted in lower health care utilization costs.

Study strengths and limitations

This study’s strength lies in its design and implementation of standardized protocols that allowed assessment of clinically meaningful outcomes postpartum. Although the program for RBPM was for only 10 days postpartum, it showed effects beyond the timeframe of the direct care. No such prior data exist evaluating a program’s effectiveness in improving postpartum clinical outcomes and costs through 1 year postdelivery.

Study limitations include residual bias from unobserved confounders, analysis of only 1 payer type, lack of patient level data, and evaluation of disparity. ●

The Centers for Disease Control and Prevention (CDC) reported 106,699 deaths in 2021 from drug overdose, with the majority being linked to synthetic opioids, including fentanyl and tramadol.¹ This number compares with 42,795 deaths due to motor vehicle accidents and 48,183 deaths due to suicide in 2021.^2,3 Most of the opioid overdose deaths occurred among people aged 25 to 64 years, the peak age of patients cared for by obstetrician-gynecologists. Among pregnant and postpartum persons, mortality due to drug overdose has increased by 81% between 2017 and 2020.⁴

Among pregnant and postpartum patients, drug overdose death is more common than suicide, and the risk for drug overdose death appears to be greatest in the year following delivery.^5,6 In many cases, postpartum patients with OUD have had multiple contacts with the health care system prior to their death, showing that there is an opportunity for therapeutic intervention before the death occurred.⁷ Medication-assisted recovery for OUD involves a comprehensive array of interventions including medication, counseling, and social support. Medication treatment of OUD with BUP or methadone reduces the risk for death but is underutilized among patients with OUD.^6,8 Recent federal legislation has removed restrictions on the use of BUP, increasing the opportunity for primary care clinicians to prescribe it for the treatment of OUD.⁹

Screening and diagnosis of OUD

Screening for OUD is recommended for patients who are at risk for opioid misuse (ie, those who are taking/have taken opioid medications). The OWLS (Overuse, Worrying, Losing interest, and feeling Slowed down, sluggish, or sedated) screening tool is used to detect prescription medication OUD and has 4 questions¹⁰:

1. In the past 3 months did you use your opioid medicines for other purposes—for example, to help you sleep or to help with stress or worry?

2. In the past 3 months did opioid medicines cause you to feel slowed down, sluggish, or sedated?

3. In the past 3 months did opioid medicines cause you to lose interest in your usual activities?

4. In the past 3 months did you worry about your use of opioid medicines? 

Patient agreement with 3 or 4 questions indicates a positive screening test.

If the patient has a positive screening test, a formal diagnosis of OUD can be made using the 11 symptoms outlined in the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.¹¹ The diagnosis of mild (2 to 3 symptoms), moderate (4 to 5 symptoms), or severe OUD (6 or more symptoms) is made based on the number of symptoms the patient reports.

Buprenorphine treatment of OUD in primary care

The role of primary care clinicians in the medication treatment of OUD is increasing. Using a nationwide system that tracks prescription medications, investigators reported that, in 2004, psychiatrists wrote 32.2% of all BUP prescriptions; in 2021, however, only 10% of such prescriptions were provided by psychiatrists, with most prescriptions written by non-psychiatrist physicians, nurse practitioners, and physician assistants that year.¹² Innovative telehealth approaches to consultation and medication treatment of OUD are now available—one example is QuickMD.¹³ Such sites are designed to remove barriers to initiating medication treatment of OUD.

The role of primary care clinicians in the management of OUD using BUP and buprenorphine-naloxone (BUP-NAL) has increased due to many factors, including:

• the removal of US Food and Drug Administration (FDA) barriers to prescribing BUP
• the epidemic of OUD and the small size of the addiction specialist workforce, necessitating that primary care clinicians become engaged in the treatment of OUD
• an increase in unobserved initiation of BUP among ambulatory patients, and a parallel decrease in cases of observed initiation in addiction center settings
• the reframing of OUD as a chronic medical problem, with many similarities to diabetes, obesity, dyslipidemia, and hypertension.

Similar to other diseases managed by primary care clinicians, OUD requires long-term chronic treatment with a medicine that, if taken as directed, provides excellent outcomes. Primary care clinicians who prescribe BUP also can optimize longitudinal care for comorbid disorders such as hypertension and diabetes, which are prevalent in people with OUD.

In 2019, New Jersey implemented new guidelines for the treatment of OUD, removing prior authorization barriers, increasing reimbursement for office-based OUD treatment, and establishing regional centers of excellence. The implementation of the new guidelines was followed by a marked increase in BUP prescribers among primary care clinicians, emergency medicine physicians, and advanced practice clinicians.¹⁴

To estimate the public health impact of BUP prescribing by primary care clinicians, investigators simulated patient outcomes in 3 scenarios¹⁵:

1. primary care clinicians refer patients to addiction specialists for OUD treatment

2. primary care clinicians provide BUP services in their practice

3. primary care clinicians provide BUP and harm reduction kits containing syringes and wound care supplies in their practice. 

Strategies 2 and 3 resulted in 14% fewer deaths due to opioid overdose, an increased life expectancy of approximately 2.7 years, and reduced hospital costs. For strategy 3, the incremental cost per life-year saved was $34,400. The investigators noted that prescribing BUP in primary care practice increases practice costs.¹⁵

Treatment with BUP reduces death from opioid overdose, improves patient health, decreases use of illicit opioids, and reduces patient cravings for opioids. BUP is a safe medication and is associated with fewer adverse effects than insulin or warfarin.¹⁶

Continue to: Methadone treatment of OUD...

Methadone is a full opioid agonist approved by the FDA for the treatment of severe pain or OUD. Methadone treatment of OUD is strictly regulated and typically is ordered and administered at an opioid treatment program that is federally licensed. Methadone for OUD treatment cannot be prescribed by a physician to a pharmacy, limiting its use in primary care practice. Methadone used to treat OUD is ordered and dispensed at opioid-treatment programs. Take-home doses of methadone may be available to patients after adherence to the regimen has been established. When used long-term, higher doses of methadone are associated with better adherence, but these higher doses can cause respiratory depression. In a study of 189 pregnant patients taking methadone to treat OUD, daily doses of 60 mg or greater were associated with better treatment retention at delivery and 60 days postpartum, as well as less use of nonprescription opioids.¹⁷ Under limited circumstances methadone can be ordered and dispensed for hospitalized patients with OUD.

Medication treatment of OUD in obstetrics

In the United States, the prevalence of OUD among pregnant patients hospitalized for delivery more than quadrupled from 1999 through 2014.¹⁸ BUP and methadone commonly are used to treat OUD during pregnancy.¹⁹ Among pregnant patients about 5% of buprenorphine prescriptions are written by obstetricians.²⁰ An innovative approach to initiating BUP for pregnant patients with OUD is to use unobserved initiation, which involves outpatient discontinuation of nonprescription opioids to induce mild to moderate withdrawal symptoms followed by initiation of BUP treatment. In one cohort study, 55 pregnant patients used an unobserved outpatient protocol to initiate BUP treatment; 80% of the patients previously had used methadone or BUP. No patient experienced a precipitated withdrawal and 96% of patients returned for their office visit 1 week after initiation of treatment. Eighty-six percent of patients remained in treatment 3 months following initiation of BUP.²¹

Compared with methadone, BUP treatment during pregnancy may result in lower rates of neonatal abstinence syndrome. In one study of pregnant patients who were using methadone (n = 5,056) or BUP (n = 11,272) in late pregnancy, neonatal abstinence syndrome was diagnosed in 69.2% and 52.0% of newborns, respectively (adjusted relative risk, 0.73; 95% confidence interval, 0.71–0.75).²² In addition, compared with methadone, the use of BUP was associated with a reduced risk for low birth weight (14.9% vs 8.3%) and a lower risk for preterm birth (24.9% vs 14.4%). In this study, there were no differences in maternal obstetric outcomes when comparing BUP versus methadone treatment. Similar results have been reported in a meta-analysis analyzing the use of methadone and BUP during pregnancy.²³ Studies performed to date have not shown an increased risk of congenital anomalies with the use of BUP-NAL during pregnancy.^24,25

Although there may be differences in newborn outcomes with BUP and methadone, the American College of Obstetricians and Gynecologists does not recommend switching from methadone to BUP during pregnancy because precipitated withdrawal may occur.²⁶ Based on recent studies, the American Society of Addiction Medicine has advised that it is safe to prescribe pregnant patients either BUP or BUP-NAL.^27,28

Medication treatment of OUD with or without intensive counseling

The FDA recently reviewed literature related to the advantages and challenges of combining intensive counseling with medication treatment of OUD.²⁹ The FDA noted that treatment saves lives and encouraged clinicians to initiate medication treatment of OUD or refer the patient to an appropriate clinician or treatment center. Combining medication treatment of OUD with intensive counseling is associated with greater treatment adherence and reduced health care costs. For example, in one study of 4,987 patients with OUD, initiation of counseling within 8 weeks of the start of medication treatment and a BUP dose of 16 mg or greater daily were associated with increased adherence to treatment.³⁰ For patients receiving a BUP dose of less than 16 mg daily, treatment adherence with and without counseling was approximately 325 and 230 days, respectively. When the dose of BUP was 16 mg or greater, treatment adherence with and without counseling was approximately 405 and 320 days, respectively.³⁰

Counseling should always be offered to patients initiating medication treatment of OUD. It should be noted that counseling alone is not a highly effective treatment for OUD.³¹ The FDA recently advised that the lack of availability of intensive counseling should not prevent clinicians from initiating BUP for the treatment of OUD.²⁹ OUD is associated with a high mortalityrate and if counseling is not possible, medication treatment should be initiated. Substantial evidence demonstrates that medication treatment of OUD is associated with many benefits.¹⁶ The FDA advisory committee concluded that OUD treatment decisions should use shared decision making and be supportive and patient centered.²⁹

The opportunities for medication treatment of OUD in primary care practice have expanded due to the recent FDA removal of restrictions on the use of BUP and heightened awareness of the positive public health impact of medication treatment. Challenges to the medication treatment of OUD remain, including stigmatization of OUD, barriers to insurance coverage for BUP, practice costs of treating OUD, and gaps in clinical education. For many pregnant patients, their main point of contact with health care is their obstetrician. By incorporating OUD treatment in pregnancy care, obstetricians will improve the health of the mother and newborn, contributing to the well-being of current and future generations. ●

The Centers for Disease Control and Prevention (CDC) reported 106,699 deaths in 2021 from drug overdose, with the majority being linked to synthetic opioids, including fentanyl and tramadol.¹ This number compares with 42,795 deaths due to motor vehicle accidents and 48,183 deaths due to suicide in 2021.^2,3 Most of the opioid overdose deaths occurred among people aged 25 to 64 years, the peak age of patients cared for by obstetrician-gynecologists. Among pregnant and postpartum persons, mortality due to drug overdose has increased by 81% between 2017 and 2020.⁴

Among pregnant and postpartum patients, drug overdose death is more common than suicide, and the risk for drug overdose death appears to be greatest in the year following delivery.^5,6 In many cases, postpartum patients with OUD have had multiple contacts with the health care system prior to their death, showing that there is an opportunity for therapeutic intervention before the death occurred.⁷ Medication-assisted recovery for OUD involves a comprehensive array of interventions including medication, counseling, and social support. Medication treatment of OUD with BUP or methadone reduces the risk for death but is underutilized among patients with OUD.^6,8 Recent federal legislation has removed restrictions on the use of BUP, increasing the opportunity for primary care clinicians to prescribe it for the treatment of OUD.⁹

Screening and diagnosis of OUD

Screening for OUD is recommended for patients who are at risk for opioid misuse (ie, those who are taking/have taken opioid medications). The OWLS (Overuse, Worrying, Losing interest, and feeling Slowed down, sluggish, or sedated) screening tool is used to detect prescription medication OUD and has 4 questions¹⁰:

1. In the past 3 months did you use your opioid medicines for other purposes—for example, to help you sleep or to help with stress or worry?

2. In the past 3 months did opioid medicines cause you to feel slowed down, sluggish, or sedated?

3. In the past 3 months did opioid medicines cause you to lose interest in your usual activities?

4. In the past 3 months did you worry about your use of opioid medicines? 

Patient agreement with 3 or 4 questions indicates a positive screening test.

If the patient has a positive screening test, a formal diagnosis of OUD can be made using the 11 symptoms outlined in the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.¹¹ The diagnosis of mild (2 to 3 symptoms), moderate (4 to 5 symptoms), or severe OUD (6 or more symptoms) is made based on the number of symptoms the patient reports.

Buprenorphine treatment of OUD in primary care

The role of primary care clinicians in the medication treatment of OUD is increasing. Using a nationwide system that tracks prescription medications, investigators reported that, in 2004, psychiatrists wrote 32.2% of all BUP prescriptions; in 2021, however, only 10% of such prescriptions were provided by psychiatrists, with most prescriptions written by non-psychiatrist physicians, nurse practitioners, and physician assistants that year.¹² Innovative telehealth approaches to consultation and medication treatment of OUD are now available—one example is QuickMD.¹³ Such sites are designed to remove barriers to initiating medication treatment of OUD.

The role of primary care clinicians in the management of OUD using BUP and buprenorphine-naloxone (BUP-NAL) has increased due to many factors, including:

• the removal of US Food and Drug Administration (FDA) barriers to prescribing BUP
• the epidemic of OUD and the small size of the addiction specialist workforce, necessitating that primary care clinicians become engaged in the treatment of OUD
• an increase in unobserved initiation of BUP among ambulatory patients, and a parallel decrease in cases of observed initiation in addiction center settings
• the reframing of OUD as a chronic medical problem, with many similarities to diabetes, obesity, dyslipidemia, and hypertension.

Similar to other diseases managed by primary care clinicians, OUD requires long-term chronic treatment with a medicine that, if taken as directed, provides excellent outcomes. Primary care clinicians who prescribe BUP also can optimize longitudinal care for comorbid disorders such as hypertension and diabetes, which are prevalent in people with OUD.

In 2019, New Jersey implemented new guidelines for the treatment of OUD, removing prior authorization barriers, increasing reimbursement for office-based OUD treatment, and establishing regional centers of excellence. The implementation of the new guidelines was followed by a marked increase in BUP prescribers among primary care clinicians, emergency medicine physicians, and advanced practice clinicians.¹⁴

To estimate the public health impact of BUP prescribing by primary care clinicians, investigators simulated patient outcomes in 3 scenarios¹⁵:

1. primary care clinicians refer patients to addiction specialists for OUD treatment

2. primary care clinicians provide BUP services in their practice

3. primary care clinicians provide BUP and harm reduction kits containing syringes and wound care supplies in their practice. 

Strategies 2 and 3 resulted in 14% fewer deaths due to opioid overdose, an increased life expectancy of approximately 2.7 years, and reduced hospital costs. For strategy 3, the incremental cost per life-year saved was $34,400. The investigators noted that prescribing BUP in primary care practice increases practice costs.¹⁵

Treatment with BUP reduces death from opioid overdose, improves patient health, decreases use of illicit opioids, and reduces patient cravings for opioids. BUP is a safe medication and is associated with fewer adverse effects than insulin or warfarin.¹⁶

Continue to: Methadone treatment of OUD...

Methadone is a full opioid agonist approved by the FDA for the treatment of severe pain or OUD. Methadone treatment of OUD is strictly regulated and typically is ordered and administered at an opioid treatment program that is federally licensed. Methadone for OUD treatment cannot be prescribed by a physician to a pharmacy, limiting its use in primary care practice. Methadone used to treat OUD is ordered and dispensed at opioid-treatment programs. Take-home doses of methadone may be available to patients after adherence to the regimen has been established. When used long-term, higher doses of methadone are associated with better adherence, but these higher doses can cause respiratory depression. In a study of 189 pregnant patients taking methadone to treat OUD, daily doses of 60 mg or greater were associated with better treatment retention at delivery and 60 days postpartum, as well as less use of nonprescription opioids.¹⁷ Under limited circumstances methadone can be ordered and dispensed for hospitalized patients with OUD.

Medication treatment of OUD in obstetrics

In the United States, the prevalence of OUD among pregnant patients hospitalized for delivery more than quadrupled from 1999 through 2014.¹⁸ BUP and methadone commonly are used to treat OUD during pregnancy.¹⁹ Among pregnant patients about 5% of buprenorphine prescriptions are written by obstetricians.²⁰ An innovative approach to initiating BUP for pregnant patients with OUD is to use unobserved initiation, which involves outpatient discontinuation of nonprescription opioids to induce mild to moderate withdrawal symptoms followed by initiation of BUP treatment. In one cohort study, 55 pregnant patients used an unobserved outpatient protocol to initiate BUP treatment; 80% of the patients previously had used methadone or BUP. No patient experienced a precipitated withdrawal and 96% of patients returned for their office visit 1 week after initiation of treatment. Eighty-six percent of patients remained in treatment 3 months following initiation of BUP.²¹

Compared with methadone, BUP treatment during pregnancy may result in lower rates of neonatal abstinence syndrome. In one study of pregnant patients who were using methadone (n = 5,056) or BUP (n = 11,272) in late pregnancy, neonatal abstinence syndrome was diagnosed in 69.2% and 52.0% of newborns, respectively (adjusted relative risk, 0.73; 95% confidence interval, 0.71–0.75).²² In addition, compared with methadone, the use of BUP was associated with a reduced risk for low birth weight (14.9% vs 8.3%) and a lower risk for preterm birth (24.9% vs 14.4%). In this study, there were no differences in maternal obstetric outcomes when comparing BUP versus methadone treatment. Similar results have been reported in a meta-analysis analyzing the use of methadone and BUP during pregnancy.²³ Studies performed to date have not shown an increased risk of congenital anomalies with the use of BUP-NAL during pregnancy.^24,25

Although there may be differences in newborn outcomes with BUP and methadone, the American College of Obstetricians and Gynecologists does not recommend switching from methadone to BUP during pregnancy because precipitated withdrawal may occur.²⁶ Based on recent studies, the American Society of Addiction Medicine has advised that it is safe to prescribe pregnant patients either BUP or BUP-NAL.^27,28

Medication treatment of OUD with or without intensive counseling

The FDA recently reviewed literature related to the advantages and challenges of combining intensive counseling with medication treatment of OUD.²⁹ The FDA noted that treatment saves lives and encouraged clinicians to initiate medication treatment of OUD or refer the patient to an appropriate clinician or treatment center. Combining medication treatment of OUD with intensive counseling is associated with greater treatment adherence and reduced health care costs. For example, in one study of 4,987 patients with OUD, initiation of counseling within 8 weeks of the start of medication treatment and a BUP dose of 16 mg or greater daily were associated with increased adherence to treatment.³⁰ For patients receiving a BUP dose of less than 16 mg daily, treatment adherence with and without counseling was approximately 325 and 230 days, respectively. When the dose of BUP was 16 mg or greater, treatment adherence with and without counseling was approximately 405 and 320 days, respectively.³⁰

Counseling should always be offered to patients initiating medication treatment of OUD. It should be noted that counseling alone is not a highly effective treatment for OUD.³¹ The FDA recently advised that the lack of availability of intensive counseling should not prevent clinicians from initiating BUP for the treatment of OUD.²⁹ OUD is associated with a high mortalityrate and if counseling is not possible, medication treatment should be initiated. Substantial evidence demonstrates that medication treatment of OUD is associated with many benefits.¹⁶ The FDA advisory committee concluded that OUD treatment decisions should use shared decision making and be supportive and patient centered.²⁹

The opportunities for medication treatment of OUD in primary care practice have expanded due to the recent FDA removal of restrictions on the use of BUP and heightened awareness of the positive public health impact of medication treatment. Challenges to the medication treatment of OUD remain, including stigmatization of OUD, barriers to insurance coverage for BUP, practice costs of treating OUD, and gaps in clinical education. For many pregnant patients, their main point of contact with health care is their obstetrician. By incorporating OUD treatment in pregnancy care, obstetricians will improve the health of the mother and newborn, contributing to the well-being of current and future generations. ●

The Centers for Disease Control and Prevention (CDC) reported 106,699 deaths in 2021 from drug overdose, with the majority being linked to synthetic opioids, including fentanyl and tramadol.¹ This number compares with 42,795 deaths due to motor vehicle accidents and 48,183 deaths due to suicide in 2021.^2,3 Most of the opioid overdose deaths occurred among people aged 25 to 64 years, the peak age of patients cared for by obstetrician-gynecologists. Among pregnant and postpartum persons, mortality due to drug overdose has increased by 81% between 2017 and 2020.⁴

Among pregnant and postpartum patients, drug overdose death is more common than suicide, and the risk for drug overdose death appears to be greatest in the year following delivery.^5,6 In many cases, postpartum patients with OUD have had multiple contacts with the health care system prior to their death, showing that there is an opportunity for therapeutic intervention before the death occurred.⁷ Medication-assisted recovery for OUD involves a comprehensive array of interventions including medication, counseling, and social support. Medication treatment of OUD with BUP or methadone reduces the risk for death but is underutilized among patients with OUD.^6,8 Recent federal legislation has removed restrictions on the use of BUP, increasing the opportunity for primary care clinicians to prescribe it for the treatment of OUD.⁹

Screening and diagnosis of OUD

Screening for OUD is recommended for patients who are at risk for opioid misuse (ie, those who are taking/have taken opioid medications). The OWLS (Overuse, Worrying, Losing interest, and feeling Slowed down, sluggish, or sedated) screening tool is used to detect prescription medication OUD and has 4 questions¹⁰:

1. In the past 3 months did you use your opioid medicines for other purposes—for example, to help you sleep or to help with stress or worry?

2. In the past 3 months did opioid medicines cause you to feel slowed down, sluggish, or sedated?

3. In the past 3 months did opioid medicines cause you to lose interest in your usual activities?

4. In the past 3 months did you worry about your use of opioid medicines? 

Patient agreement with 3 or 4 questions indicates a positive screening test.

If the patient has a positive screening test, a formal diagnosis of OUD can be made using the 11 symptoms outlined in the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.¹¹ The diagnosis of mild (2 to 3 symptoms), moderate (4 to 5 symptoms), or severe OUD (6 or more symptoms) is made based on the number of symptoms the patient reports.

Buprenorphine treatment of OUD in primary care

The role of primary care clinicians in the medication treatment of OUD is increasing. Using a nationwide system that tracks prescription medications, investigators reported that, in 2004, psychiatrists wrote 32.2% of all BUP prescriptions; in 2021, however, only 10% of such prescriptions were provided by psychiatrists, with most prescriptions written by non-psychiatrist physicians, nurse practitioners, and physician assistants that year.¹² Innovative telehealth approaches to consultation and medication treatment of OUD are now available—one example is QuickMD.¹³ Such sites are designed to remove barriers to initiating medication treatment of OUD.

The role of primary care clinicians in the management of OUD using BUP and buprenorphine-naloxone (BUP-NAL) has increased due to many factors, including:

• the removal of US Food and Drug Administration (FDA) barriers to prescribing BUP
• the epidemic of OUD and the small size of the addiction specialist workforce, necessitating that primary care clinicians become engaged in the treatment of OUD
• an increase in unobserved initiation of BUP among ambulatory patients, and a parallel decrease in cases of observed initiation in addiction center settings
• the reframing of OUD as a chronic medical problem, with many similarities to diabetes, obesity, dyslipidemia, and hypertension.

Similar to other diseases managed by primary care clinicians, OUD requires long-term chronic treatment with a medicine that, if taken as directed, provides excellent outcomes. Primary care clinicians who prescribe BUP also can optimize longitudinal care for comorbid disorders such as hypertension and diabetes, which are prevalent in people with OUD.

In 2019, New Jersey implemented new guidelines for the treatment of OUD, removing prior authorization barriers, increasing reimbursement for office-based OUD treatment, and establishing regional centers of excellence. The implementation of the new guidelines was followed by a marked increase in BUP prescribers among primary care clinicians, emergency medicine physicians, and advanced practice clinicians.¹⁴

To estimate the public health impact of BUP prescribing by primary care clinicians, investigators simulated patient outcomes in 3 scenarios¹⁵:

1. primary care clinicians refer patients to addiction specialists for OUD treatment

2. primary care clinicians provide BUP services in their practice

3. primary care clinicians provide BUP and harm reduction kits containing syringes and wound care supplies in their practice. 

Strategies 2 and 3 resulted in 14% fewer deaths due to opioid overdose, an increased life expectancy of approximately 2.7 years, and reduced hospital costs. For strategy 3, the incremental cost per life-year saved was $34,400. The investigators noted that prescribing BUP in primary care practice increases practice costs.¹⁵

Treatment with BUP reduces death from opioid overdose, improves patient health, decreases use of illicit opioids, and reduces patient cravings for opioids. BUP is a safe medication and is associated with fewer adverse effects than insulin or warfarin.¹⁶

Continue to: Methadone treatment of OUD...

Methadone is a full opioid agonist approved by the FDA for the treatment of severe pain or OUD. Methadone treatment of OUD is strictly regulated and typically is ordered and administered at an opioid treatment program that is federally licensed. Methadone for OUD treatment cannot be prescribed by a physician to a pharmacy, limiting its use in primary care practice. Methadone used to treat OUD is ordered and dispensed at opioid-treatment programs. Take-home doses of methadone may be available to patients after adherence to the regimen has been established. When used long-term, higher doses of methadone are associated with better adherence, but these higher doses can cause respiratory depression. In a study of 189 pregnant patients taking methadone to treat OUD, daily doses of 60 mg or greater were associated with better treatment retention at delivery and 60 days postpartum, as well as less use of nonprescription opioids.¹⁷ Under limited circumstances methadone can be ordered and dispensed for hospitalized patients with OUD.

Medication treatment of OUD in obstetrics

In the United States, the prevalence of OUD among pregnant patients hospitalized for delivery more than quadrupled from 1999 through 2014.¹⁸ BUP and methadone commonly are used to treat OUD during pregnancy.¹⁹ Among pregnant patients about 5% of buprenorphine prescriptions are written by obstetricians.²⁰ An innovative approach to initiating BUP for pregnant patients with OUD is to use unobserved initiation, which involves outpatient discontinuation of nonprescription opioids to induce mild to moderate withdrawal symptoms followed by initiation of BUP treatment. In one cohort study, 55 pregnant patients used an unobserved outpatient protocol to initiate BUP treatment; 80% of the patients previously had used methadone or BUP. No patient experienced a precipitated withdrawal and 96% of patients returned for their office visit 1 week after initiation of treatment. Eighty-six percent of patients remained in treatment 3 months following initiation of BUP.²¹

Compared with methadone, BUP treatment during pregnancy may result in lower rates of neonatal abstinence syndrome. In one study of pregnant patients who were using methadone (n = 5,056) or BUP (n = 11,272) in late pregnancy, neonatal abstinence syndrome was diagnosed in 69.2% and 52.0% of newborns, respectively (adjusted relative risk, 0.73; 95% confidence interval, 0.71–0.75).²² In addition, compared with methadone, the use of BUP was associated with a reduced risk for low birth weight (14.9% vs 8.3%) and a lower risk for preterm birth (24.9% vs 14.4%). In this study, there were no differences in maternal obstetric outcomes when comparing BUP versus methadone treatment. Similar results have been reported in a meta-analysis analyzing the use of methadone and BUP during pregnancy.²³ Studies performed to date have not shown an increased risk of congenital anomalies with the use of BUP-NAL during pregnancy.^24,25

Although there may be differences in newborn outcomes with BUP and methadone, the American College of Obstetricians and Gynecologists does not recommend switching from methadone to BUP during pregnancy because precipitated withdrawal may occur.²⁶ Based on recent studies, the American Society of Addiction Medicine has advised that it is safe to prescribe pregnant patients either BUP or BUP-NAL.^27,28

Medication treatment of OUD with or without intensive counseling

The FDA recently reviewed literature related to the advantages and challenges of combining intensive counseling with medication treatment of OUD.²⁹ The FDA noted that treatment saves lives and encouraged clinicians to initiate medication treatment of OUD or refer the patient to an appropriate clinician or treatment center. Combining medication treatment of OUD with intensive counseling is associated with greater treatment adherence and reduced health care costs. For example, in one study of 4,987 patients with OUD, initiation of counseling within 8 weeks of the start of medication treatment and a BUP dose of 16 mg or greater daily were associated with increased adherence to treatment.³⁰ For patients receiving a BUP dose of less than 16 mg daily, treatment adherence with and without counseling was approximately 325 and 230 days, respectively. When the dose of BUP was 16 mg or greater, treatment adherence with and without counseling was approximately 405 and 320 days, respectively.³⁰

Counseling should always be offered to patients initiating medication treatment of OUD. It should be noted that counseling alone is not a highly effective treatment for OUD.³¹ The FDA recently advised that the lack of availability of intensive counseling should not prevent clinicians from initiating BUP for the treatment of OUD.²⁹ OUD is associated with a high mortalityrate and if counseling is not possible, medication treatment should be initiated. Substantial evidence demonstrates that medication treatment of OUD is associated with many benefits.¹⁶ The FDA advisory committee concluded that OUD treatment decisions should use shared decision making and be supportive and patient centered.²⁹

The opportunities for medication treatment of OUD in primary care practice have expanded due to the recent FDA removal of restrictions on the use of BUP and heightened awareness of the positive public health impact of medication treatment. Challenges to the medication treatment of OUD remain, including stigmatization of OUD, barriers to insurance coverage for BUP, practice costs of treating OUD, and gaps in clinical education. For many pregnant patients, their main point of contact with health care is their obstetrician. By incorporating OUD treatment in pregnancy care, obstetricians will improve the health of the mother and newborn, contributing to the well-being of current and future generations. ●

PURPOSE

This project aims to describe the demographics of Veterans diagnosed with breast and gynecologic cancers and assess differences compared to the general population.

BACKGROUND

With an increasing number of women Veterans enrolling in the VA, it is crucial for oncologists to be prepared to provide care for VeterS32 • SEPTEMBER 2023 www.mdedge.com/fedprac/avaho NOTES ans diagnosed with breast and gynecologic cancers. Despite the rising incidence of these cancers among Veterans, there is limited characterization of the demographic profile of this population. Understanding the unique characteristics of Veterans with these malignancies, distinct from the general population, is essential for the Veterans Administration (VA) to develop programs and enhance care for these patients.

METHODS/DATA ANALYSIS

Consult records from the VA Corporate Data Warehouse between January 1, 2021, and December 31, 2022, were analyzed to identify Veterans with newly diagnosed breast, uterine, ovarian, cervical, and vulvovaginal cancer. Demographic were evaluated. Data on the general population were obtained data from SEER (Surveillance, Epidemiology, and End Results) 19 database for 2020.

RESULTS

A total of 3,304 Veterans diagnosed with breast cancer and 918 Veterans with gynecologic cancers were identified (uterine, n = 365; cervical, n = 344, ovarian, n = 177; vulvovaginal, n = 32). Veterans were found to be younger than the general population, with a mean age at diagnosis of 59 for Veterans with breast cancer to 63 for non-veterans. Among those with gynecologic cancers, the mean age at diagnosis for Veterans was 55 compared to 61 for non-veterans. Male breast cancer cases were more prevalent among Veterans, accounting for 11% in the VA compared to 1% in SEER. The Veteran cohort also displayed a higher proportion of Black patients, with 30% of breast cancer cases in the VA being Black compared to 12% in SEER.

CONCLUSIONS/IMPLICATIONS

Veterans diagnosed with breast and gynecologic cancers exhibit unique demographic characteristics compared to the general population. They tend to be younger and have a higher representation of Black patients. The incidence of male breast cancer is notably higher among Veterans. As the prevalence of these cancer types continue to rise among Veterans, it is vital for oncologists to be aware of and adequately address the unique health needs of this population. These findings emphasize the importance of tailored strategies and programs to provide optimal care for Veterans with breast and gynecologic cancers.

PURPOSE

This project aims to describe the demographics of Veterans diagnosed with breast and gynecologic cancers and assess differences compared to the general population.

BACKGROUND

With an increasing number of women Veterans enrolling in the VA, it is crucial for oncologists to be prepared to provide care for VeterS32 • SEPTEMBER 2023 www.mdedge.com/fedprac/avaho NOTES ans diagnosed with breast and gynecologic cancers. Despite the rising incidence of these cancers among Veterans, there is limited characterization of the demographic profile of this population. Understanding the unique characteristics of Veterans with these malignancies, distinct from the general population, is essential for the Veterans Administration (VA) to develop programs and enhance care for these patients.

METHODS/DATA ANALYSIS

Consult records from the VA Corporate Data Warehouse between January 1, 2021, and December 31, 2022, were analyzed to identify Veterans with newly diagnosed breast, uterine, ovarian, cervical, and vulvovaginal cancer. Demographic were evaluated. Data on the general population were obtained data from SEER (Surveillance, Epidemiology, and End Results) 19 database for 2020.

RESULTS

A total of 3,304 Veterans diagnosed with breast cancer and 918 Veterans with gynecologic cancers were identified (uterine, n = 365; cervical, n = 344, ovarian, n = 177; vulvovaginal, n = 32). Veterans were found to be younger than the general population, with a mean age at diagnosis of 59 for Veterans with breast cancer to 63 for non-veterans. Among those with gynecologic cancers, the mean age at diagnosis for Veterans was 55 compared to 61 for non-veterans. Male breast cancer cases were more prevalent among Veterans, accounting for 11% in the VA compared to 1% in SEER. The Veteran cohort also displayed a higher proportion of Black patients, with 30% of breast cancer cases in the VA being Black compared to 12% in SEER.

CONCLUSIONS/IMPLICATIONS

Veterans diagnosed with breast and gynecologic cancers exhibit unique demographic characteristics compared to the general population. They tend to be younger and have a higher representation of Black patients. The incidence of male breast cancer is notably higher among Veterans. As the prevalence of these cancer types continue to rise among Veterans, it is vital for oncologists to be aware of and adequately address the unique health needs of this population. These findings emphasize the importance of tailored strategies and programs to provide optimal care for Veterans with breast and gynecologic cancers.

PURPOSE

This project aims to describe the demographics of Veterans diagnosed with breast and gynecologic cancers and assess differences compared to the general population.

BACKGROUND

With an increasing number of women Veterans enrolling in the VA, it is crucial for oncologists to be prepared to provide care for VeterS32 • SEPTEMBER 2023 www.mdedge.com/fedprac/avaho NOTES ans diagnosed with breast and gynecologic cancers. Despite the rising incidence of these cancers among Veterans, there is limited characterization of the demographic profile of this population. Understanding the unique characteristics of Veterans with these malignancies, distinct from the general population, is essential for the Veterans Administration (VA) to develop programs and enhance care for these patients.

METHODS/DATA ANALYSIS

Consult records from the VA Corporate Data Warehouse between January 1, 2021, and December 31, 2022, were analyzed to identify Veterans with newly diagnosed breast, uterine, ovarian, cervical, and vulvovaginal cancer. Demographic were evaluated. Data on the general population were obtained data from SEER (Surveillance, Epidemiology, and End Results) 19 database for 2020.

RESULTS

A total of 3,304 Veterans diagnosed with breast cancer and 918 Veterans with gynecologic cancers were identified (uterine, n = 365; cervical, n = 344, ovarian, n = 177; vulvovaginal, n = 32). Veterans were found to be younger than the general population, with a mean age at diagnosis of 59 for Veterans with breast cancer to 63 for non-veterans. Among those with gynecologic cancers, the mean age at diagnosis for Veterans was 55 compared to 61 for non-veterans. Male breast cancer cases were more prevalent among Veterans, accounting for 11% in the VA compared to 1% in SEER. The Veteran cohort also displayed a higher proportion of Black patients, with 30% of breast cancer cases in the VA being Black compared to 12% in SEER.

CONCLUSIONS/IMPLICATIONS

Veterans diagnosed with breast and gynecologic cancers exhibit unique demographic characteristics compared to the general population. They tend to be younger and have a higher representation of Black patients. The incidence of male breast cancer is notably higher among Veterans. As the prevalence of these cancer types continue to rise among Veterans, it is vital for oncologists to be aware of and adequately address the unique health needs of this population. These findings emphasize the importance of tailored strategies and programs to provide optimal care for Veterans with breast and gynecologic cancers.

BACKGROUND

There are 5 germline mutations that lead to hypercoagulability in the general population including: Factor V Leiden (FVL), Prothrombin G20210A (F2A), Protein C Deficiency (PCD), Protein S Deficiency (PSD), and Antithrombin Deficiency (ATD). Typical guidance is to defer testing, as it is thought not to change management.

CASE REPORT

We present a case of a patient who was found to be compound heterozygous mutations for FVL and F2A, who presented with two episodes of arterial thromboembolism resulting in cerebrovascular accident (CVA). A 63-year-old male with past medical history of hypertension, a CVA four years prior, and medication non-compliance presents with new onset left sided hemiparesis after an episode of convulsions. MRI and CT imaging of the head revealed ischemic CVA secondary to thromboembolism in the right posterior cerebral artery’s (PCA), P1 branch. Following administration of tissue plasminogen activator (tPA) he had rapid symptom improvement. This second ischemic CVA prompted a workup which was notable for: negative echocardiogram, negative 30-day cardiac monitor, CT chest negative for malignancy, no significant vascular findings, negative for antiphospholipid syndrome, but genetic testing revealed the patient to be heterozygous for FVL and F2A mutations. He was started on apixaban 5 mg twice daily for ongoing secondary prevention. Though medication compliance continues to be difficult, after being placed on direct anticoagulant (DOAC), he has not had recurrent venous or arterial thrombotic events. A small case series found double heterozygosity for FVL and F2A further increases the risk of venous thromboembolism up to 17% or more in a lifetime.

CONCLUSIONS

Although current recommendations advocate against testing for specific mutations in most cases as it is likely not to change management1, this case suggests that it may be of some benefit in patients that have a workup that does not yield a clear etiology, especially in cryptogenic stroke which is typically managed with aspirin rather than direct oral anticoagulant.

BACKGROUND

There are 5 germline mutations that lead to hypercoagulability in the general population including: Factor V Leiden (FVL), Prothrombin G20210A (F2A), Protein C Deficiency (PCD), Protein S Deficiency (PSD), and Antithrombin Deficiency (ATD). Typical guidance is to defer testing, as it is thought not to change management.

CASE REPORT

We present a case of a patient who was found to be compound heterozygous mutations for FVL and F2A, who presented with two episodes of arterial thromboembolism resulting in cerebrovascular accident (CVA). A 63-year-old male with past medical history of hypertension, a CVA four years prior, and medication non-compliance presents with new onset left sided hemiparesis after an episode of convulsions. MRI and CT imaging of the head revealed ischemic CVA secondary to thromboembolism in the right posterior cerebral artery’s (PCA), P1 branch. Following administration of tissue plasminogen activator (tPA) he had rapid symptom improvement. This second ischemic CVA prompted a workup which was notable for: negative echocardiogram, negative 30-day cardiac monitor, CT chest negative for malignancy, no significant vascular findings, negative for antiphospholipid syndrome, but genetic testing revealed the patient to be heterozygous for FVL and F2A mutations. He was started on apixaban 5 mg twice daily for ongoing secondary prevention. Though medication compliance continues to be difficult, after being placed on direct anticoagulant (DOAC), he has not had recurrent venous or arterial thrombotic events. A small case series found double heterozygosity for FVL and F2A further increases the risk of venous thromboembolism up to 17% or more in a lifetime.

CONCLUSIONS

Although current recommendations advocate against testing for specific mutations in most cases as it is likely not to change management1, this case suggests that it may be of some benefit in patients that have a workup that does not yield a clear etiology, especially in cryptogenic stroke which is typically managed with aspirin rather than direct oral anticoagulant.

BACKGROUND

There are 5 germline mutations that lead to hypercoagulability in the general population including: Factor V Leiden (FVL), Prothrombin G20210A (F2A), Protein C Deficiency (PCD), Protein S Deficiency (PSD), and Antithrombin Deficiency (ATD). Typical guidance is to defer testing, as it is thought not to change management.

CASE REPORT

We present a case of a patient who was found to be compound heterozygous mutations for FVL and F2A, who presented with two episodes of arterial thromboembolism resulting in cerebrovascular accident (CVA). A 63-year-old male with past medical history of hypertension, a CVA four years prior, and medication non-compliance presents with new onset left sided hemiparesis after an episode of convulsions. MRI and CT imaging of the head revealed ischemic CVA secondary to thromboembolism in the right posterior cerebral artery’s (PCA), P1 branch. Following administration of tissue plasminogen activator (tPA) he had rapid symptom improvement. This second ischemic CVA prompted a workup which was notable for: negative echocardiogram, negative 30-day cardiac monitor, CT chest negative for malignancy, no significant vascular findings, negative for antiphospholipid syndrome, but genetic testing revealed the patient to be heterozygous for FVL and F2A mutations. He was started on apixaban 5 mg twice daily for ongoing secondary prevention. Though medication compliance continues to be difficult, after being placed on direct anticoagulant (DOAC), he has not had recurrent venous or arterial thrombotic events. A small case series found double heterozygosity for FVL and F2A further increases the risk of venous thromboembolism up to 17% or more in a lifetime.

CONCLUSIONS

Although current recommendations advocate against testing for specific mutations in most cases as it is likely not to change management1, this case suggests that it may be of some benefit in patients that have a workup that does not yield a clear etiology, especially in cryptogenic stroke which is typically managed with aspirin rather than direct oral anticoagulant.

PURPOSE

This study addresses a gap in knowledge regarding socioeconomic factors, facility type, and overall survival in stage I vs stage IV Amelanotic Melanoma.

BACKGROUND

Amelanotic Melanoma (AM) is a rare form of melanoma that lacks pigment and accounts for approximately 5% of melanomas. Light skin color and increasing age are important risk factors. Although curable when diagnosed early, it is often missed or mistaken for other benign conditions. A study investigating the impact of facility type on overall survival between stage I vs stage IV AM has yet to be done.

METHODS

This is a retrospective study of patients diagnosed with Amelanotic Melanoma (ICD-8730) between 2004 and 2020 in the National Cancer Database (NCDB) to compare demographic features and overall survival (n = 2147). Exclusion criteria included missing data.

DATA ANALYSIS

Descriptive statistics for all AM patients were collected. Median household income and facility type were compared between patients diagnosed with stage I and stage IV AM using Pearson Chi- Square test. Breslow thickness and overall survival between stage I and stage IV were evaluated using independent t-test and Kaplan-Meier test, respectively. All variables were evaluated for a significance of P < .05.

RESULTS

Most cases analyzed were White (98.1%), male (58.6%), and had Medicare as the primary payor at diagnosis (51.1%). Of 2147 cases, 497 were stage I (23.1%) and 164 were stage IV AM (7.6%) with a mean age at diagnosis of 66.05 and 63.72 years, respectively. There was a significant difference in overall survival between stage I (mean = 118.7 months) and stage 4 (mean = 42.4 months, P < 0.001). The average Breslow thickness was 1.17mm in stage I and 2.59mm in stage IV (P<0.05). More patients diagnosed at stage I used academic facilities than those diagnosed at stage IV (43.9% vs 33.8%, P<0.05). Most patients diagnosed at stage I were high income compared to patients diagnosed at stage IV (55% vs 43.2%, P<0.05).

CONCLUSIONS

With the overall survival of stage IV AM being significantly worse, we hope this study can provide a starting point in the study and prevention of disparities in the early diagnosis of AM.

PURPOSE

This study addresses a gap in knowledge regarding socioeconomic factors, facility type, and overall survival in stage I vs stage IV Amelanotic Melanoma.

BACKGROUND

Amelanotic Melanoma (AM) is a rare form of melanoma that lacks pigment and accounts for approximately 5% of melanomas. Light skin color and increasing age are important risk factors. Although curable when diagnosed early, it is often missed or mistaken for other benign conditions. A study investigating the impact of facility type on overall survival between stage I vs stage IV AM has yet to be done.

METHODS

This is a retrospective study of patients diagnosed with Amelanotic Melanoma (ICD-8730) between 2004 and 2020 in the National Cancer Database (NCDB) to compare demographic features and overall survival (n = 2147). Exclusion criteria included missing data.

DATA ANALYSIS

Descriptive statistics for all AM patients were collected. Median household income and facility type were compared between patients diagnosed with stage I and stage IV AM using Pearson Chi- Square test. Breslow thickness and overall survival between stage I and stage IV were evaluated using independent t-test and Kaplan-Meier test, respectively. All variables were evaluated for a significance of P < .05.

RESULTS

Most cases analyzed were White (98.1%), male (58.6%), and had Medicare as the primary payor at diagnosis (51.1%). Of 2147 cases, 497 were stage I (23.1%) and 164 were stage IV AM (7.6%) with a mean age at diagnosis of 66.05 and 63.72 years, respectively. There was a significant difference in overall survival between stage I (mean = 118.7 months) and stage 4 (mean = 42.4 months, P < 0.001). The average Breslow thickness was 1.17mm in stage I and 2.59mm in stage IV (P<0.05). More patients diagnosed at stage I used academic facilities than those diagnosed at stage IV (43.9% vs 33.8%, P<0.05). Most patients diagnosed at stage I were high income compared to patients diagnosed at stage IV (55% vs 43.2%, P<0.05).

CONCLUSIONS

With the overall survival of stage IV AM being significantly worse, we hope this study can provide a starting point in the study and prevention of disparities in the early diagnosis of AM.

PURPOSE

This study addresses a gap in knowledge regarding socioeconomic factors, facility type, and overall survival in stage I vs stage IV Amelanotic Melanoma.

BACKGROUND

Amelanotic Melanoma (AM) is a rare form of melanoma that lacks pigment and accounts for approximately 5% of melanomas. Light skin color and increasing age are important risk factors. Although curable when diagnosed early, it is often missed or mistaken for other benign conditions. A study investigating the impact of facility type on overall survival between stage I vs stage IV AM has yet to be done.

METHODS

This is a retrospective study of patients diagnosed with Amelanotic Melanoma (ICD-8730) between 2004 and 2020 in the National Cancer Database (NCDB) to compare demographic features and overall survival (n = 2147). Exclusion criteria included missing data.

DATA ANALYSIS

Descriptive statistics for all AM patients were collected. Median household income and facility type were compared between patients diagnosed with stage I and stage IV AM using Pearson Chi- Square test. Breslow thickness and overall survival between stage I and stage IV were evaluated using independent t-test and Kaplan-Meier test, respectively. All variables were evaluated for a significance of P < .05.

RESULTS

Most cases analyzed were White (98.1%), male (58.6%), and had Medicare as the primary payor at diagnosis (51.1%). Of 2147 cases, 497 were stage I (23.1%) and 164 were stage IV AM (7.6%) with a mean age at diagnosis of 66.05 and 63.72 years, respectively. There was a significant difference in overall survival between stage I (mean = 118.7 months) and stage 4 (mean = 42.4 months, P < 0.001). The average Breslow thickness was 1.17mm in stage I and 2.59mm in stage IV (P<0.05). More patients diagnosed at stage I used academic facilities than those diagnosed at stage IV (43.9% vs 33.8%, P<0.05). Most patients diagnosed at stage I were high income compared to patients diagnosed at stage IV (55% vs 43.2%, P<0.05).

CONCLUSIONS

With the overall survival of stage IV AM being significantly worse, we hope this study can provide a starting point in the study and prevention of disparities in the early diagnosis of AM.

INTRODUCTION

Follicular thyroid cancer (FTC) is a common endocrine malignancy that is mainly treated with surgical resection. Few prior studies have investigated the optimal type of surgery for this FTC, particularly at a national registry level. The aim of this study is to examine the differences between surgical subtypes in the management of FTC.

METHODS

Patients from the Surveillance, Epidemiology, and End Results (SEER) database who were diagnosed with FTC between 2000-2020 were selected. The surgeries were categorized into sublobectomy, lobectomy, subtotal thyroidectomy, or thyroidectomy groups based on the surgical procedure performed. Additional variables were collected including age, sex, race, stage, radiation status, time to treatment, household income, and population size. Kaplan-Meier, Chi-square and logistic regression analyses were performed.

RESULTS

A total of 9,983 patients were included. Using Kaplan-Meier, there was improved survival for patients that received surgery (p<0.001). Patients who underwent lobectomy had greater survival than all groups (p<0.001) while thyroidectomy had greater survival compared to sub-lobectomy (p=0.015). On Chi-square, differences at one- and five-year survival were present between surgical groups (p=0.022 and p<0.001, respectively). However, logistic regression showed no survival difference between surgery type at one- and five-years. Additional findings include regional and distal staging having worse survival at one- and five-years (p’s<0.001) while median household income >$75,000 and receipt of radiation improved survival at one-year (p’s<0.05). Household income >$75,000 and radiation status no longer improved survival at five-years. Patients living outside metropolitan areas showed an improved survival at fiveyears (p=0.036).

CONCLUSIONS

The results of the preliminary Kaplan- Meier and Chi-square analysis showed that there are significant differences in survival between different surgery subtypes. However, after controlling for multiple variables, no survival differences were observed between surgical types. Despite minimal differences in FTC survival based on the type of surgical intervention, clinical factors like stage and radiation and socioeconomic factors like household income and population size may influence FTC survival. Identifying and controlling for these variables should be considered in future research on FTC.

INTRODUCTION

Follicular thyroid cancer (FTC) is a common endocrine malignancy that is mainly treated with surgical resection. Few prior studies have investigated the optimal type of surgery for this FTC, particularly at a national registry level. The aim of this study is to examine the differences between surgical subtypes in the management of FTC.

METHODS

Patients from the Surveillance, Epidemiology, and End Results (SEER) database who were diagnosed with FTC between 2000-2020 were selected. The surgeries were categorized into sublobectomy, lobectomy, subtotal thyroidectomy, or thyroidectomy groups based on the surgical procedure performed. Additional variables were collected including age, sex, race, stage, radiation status, time to treatment, household income, and population size. Kaplan-Meier, Chi-square and logistic regression analyses were performed.

RESULTS

A total of 9,983 patients were included. Using Kaplan-Meier, there was improved survival for patients that received surgery (p<0.001). Patients who underwent lobectomy had greater survival than all groups (p<0.001) while thyroidectomy had greater survival compared to sub-lobectomy (p=0.015). On Chi-square, differences at one- and five-year survival were present between surgical groups (p=0.022 and p<0.001, respectively). However, logistic regression showed no survival difference between surgery type at one- and five-years. Additional findings include regional and distal staging having worse survival at one- and five-years (p’s<0.001) while median household income >$75,000 and receipt of radiation improved survival at one-year (p’s<0.05). Household income >$75,000 and radiation status no longer improved survival at five-years. Patients living outside metropolitan areas showed an improved survival at fiveyears (p=0.036).

CONCLUSIONS

The results of the preliminary Kaplan- Meier and Chi-square analysis showed that there are significant differences in survival between different surgery subtypes. However, after controlling for multiple variables, no survival differences were observed between surgical types. Despite minimal differences in FTC survival based on the type of surgical intervention, clinical factors like stage and radiation and socioeconomic factors like household income and population size may influence FTC survival. Identifying and controlling for these variables should be considered in future research on FTC.

INTRODUCTION

Follicular thyroid cancer (FTC) is a common endocrine malignancy that is mainly treated with surgical resection. Few prior studies have investigated the optimal type of surgery for this FTC, particularly at a national registry level. The aim of this study is to examine the differences between surgical subtypes in the management of FTC.

METHODS

Patients from the Surveillance, Epidemiology, and End Results (SEER) database who were diagnosed with FTC between 2000-2020 were selected. The surgeries were categorized into sublobectomy, lobectomy, subtotal thyroidectomy, or thyroidectomy groups based on the surgical procedure performed. Additional variables were collected including age, sex, race, stage, radiation status, time to treatment, household income, and population size. Kaplan-Meier, Chi-square and logistic regression analyses were performed.

RESULTS

A total of 9,983 patients were included. Using Kaplan-Meier, there was improved survival for patients that received surgery (p<0.001). Patients who underwent lobectomy had greater survival than all groups (p<0.001) while thyroidectomy had greater survival compared to sub-lobectomy (p=0.015). On Chi-square, differences at one- and five-year survival were present between surgical groups (p=0.022 and p<0.001, respectively). However, logistic regression showed no survival difference between surgery type at one- and five-years. Additional findings include regional and distal staging having worse survival at one- and five-years (p’s<0.001) while median household income >$75,000 and receipt of radiation improved survival at one-year (p’s<0.05). Household income >$75,000 and radiation status no longer improved survival at five-years. Patients living outside metropolitan areas showed an improved survival at fiveyears (p=0.036).

CONCLUSIONS

The results of the preliminary Kaplan- Meier and Chi-square analysis showed that there are significant differences in survival between different surgery subtypes. However, after controlling for multiple variables, no survival differences were observed between surgical types. Despite minimal differences in FTC survival based on the type of surgical intervention, clinical factors like stage and radiation and socioeconomic factors like household income and population size may influence FTC survival. Identifying and controlling for these variables should be considered in future research on FTC.