Mr. B, age 37, presents to a community mental health center for an appointment following a recent emergency department visit. He is diagnosed with schizophrenia, and has been treated for approximately 1 year. Six months ago, Mr. B stopped taking his antipsychotic due to its adverse effects. Despite compliance with another agent, he has become increasingly disorganized and paranoid.

He now believes that his mother, with whom he has lived all his life and who serves as his guardian, is poisoning his food and trying to kill him. She is an employee at a local grocery store, and Mr. B has expressed concern that her coworkers are assisting her in the plot to kill him.

Following a home visit, Mr. B’s case manager indicates that the patient showed them the collection of weapons he is amassing to “defend” himself. This leads to a concern for the safety of the patient, his mother, and others.

Although parricide—killing one’s parent—is a relatively rare event, its sensationalistic nature has long captured the attention of headline writers and the general public. This article discusses the diagnostic and demographic factors that may be seen among individuals who kill their parents, with an emphasis on those who commit matricide (murder of one’s mother) and associated spree killings, where an individual kills multiple people within a single brief but contiguous time period. Understanding these characteristics can help clinicians identify and more safely manage patients who may be at risk of harming their parents in addition to others.

Characteristics of perpetrators of parricide

Worldwide, approximately 2% to 4% of homicides involve parricide, or killing one’s parent.^1,2 Most offenders are men in early adulthood, though a proportion are adolescents and some are women.^1,3 They are often single, unemployed, and live with the parent prior to the killing.¹ Patricide occurs more frequently than matricide.⁴ In the United States, approximately 150 fathers and 100 mothers are killed by their child each year.⁵

In a study of all homicides in England and Wales between 1997 and 2014, two-thirds of parricide offenders had previously been diagnosed with a mental disorder.¹ One-third were diagnosed with schizophrenia.¹ In a Canadian study focusing on 43 adult perpetrators found not criminally responsible,⁶ most were experiencing psychotic symptoms at the time of parricide; symptoms of a personality disorder were the second-most prevalent symptoms. Similarly, Bourget et al⁴ studied Canadian coroner records for 64 parents killed by their children. Of the children involved in those parricides, 15% attempted suicide after the killing. Two-thirds of the male offenders evidenced delusional thinking, and/or excessive violence (overkill) was common. Some cases (16%) followed an argument, and some of those perpetrators were intoxicated or psychotic. From our clinical experience, when there are identifiable nonpsychotic triggers, they often can be small things such as an argument over food, smoking, or video games. Often, the perpetrator was financially dependent on their parents and were “trapped in a difficult/hostile/dependence/love relationship” with that parent.⁶ Adolescent males who kill their parents may not have psychosis⁷; however, they may be victims of longstanding serious abuse at the hands of their parents. These perpetrators often express relief rather than remorse after committing murder.

Three categories to classify the perpetrators of parricide have been proposed: severely abused, severely mentally ill, and “dangerously antisocial.”³ While severe mental illness was most common in adult defendants, severe abuse was most common in adolescent offenders. There may be significant commonalities between adolescent and adult perpetrators. A more recent latent class analysis by Bojanic et al¹ indicated 3 unique types of parricide offenders (Table 1).

Continue to: Matricide: A closer look...

Though multiple studies have found a higher rate of psychosis among perpetrators of matricide, it is important to note that most people with psychotic disorders would never kill their mother. These events, however, tend to grab headlines and may be highly focused upon by the general population. In addition, matricide may be part of a larger crime that draws additional attention. For example, the 1966 University of Texas Bell Tower shooter and the 2012 Sandy Hook Elementary school shooter both killed their mothers before engaging in mass homicide. Often in cases of matricide, a longer-term dysfunctional relationship existed between the mother and the child. The mother is frequently described as controlling and intrusive and the (often adult) child as overly dependent, while the father may be absent or ineffectual. Hostility and mutual dependence are usual hallmarks of these relationships.⁸

However, in some cases where an individual with a psychotic disorder kills their mother, there may have been a traditional nurturing relationship.⁸ Alternative motivations unrelated to psychosis must be considered, including crimes motivated by money/inheritance or those perpetrated out of nonpsychotic anger. Green⁸ described motive categories for matricide that include paranoid and persecutory, altruistic, and other. In the “paranoid and persecutory” group, delusional beliefs about the mother occur; for example, the perpetrator may believe their mother was the devil. Sexual elements are found in some cases.⁸ Alternatively, the “altruistic” group demonstrated rather selfless reasons for killing, such as altruistic infanticide cases, or killing out of love.⁹ The altruistic matricide perpetrator may believe their mother is unwell, which may be a delusion or actually true. Finally, the “other” category contains cases related to jealousy, rage, and impulsivity.

In a study of 15 matricidal men in New York conducted by Campion et al,¹⁰ individuals seen by forensic psychiatric services for the crime of matricide included those with schizophrenia, substance-induced psychosis, and impulse control disorders. The authors noted there was often “a serious chronic derangement in the relationships of most matricidal men and their mothers.” Psychometric testing in these cases indicated feelings of dependency, weakness, and difficulty accepting an adult role separate from their mother. Some had conceptualized their mothers as a threat to their masculinity, while others had become enraged at their mothers.

Prevention requires addressing underlying issues

As described above, several factors are common among individuals who commit parricide, and these can be used to develop prevention strategies that focus on addressing underlying issues (Table 2). It is important to consider the relationship dynamics between the potential victim and perpetrator, as well as the motive, rather than focusing solely on mental illness or substance misuse.²

Spree killings that start as parricide

Although spree killing is a relatively rare event, a subset of spree killings involve parricide. One infamous recent event occurred in 2012 at Sandy Hook Elementary School, where the gunman killed his mother before going to the school and killing 26 additional people, many of whom were children.^11,12 Because such events are rare, and because in these cases there is a high likelihood that the perpetrator is deceased (eg, died by suicide or killed by the police), much remains unknown about specific motivations and causative factors.

Information is often pieced together from postmortem reviews, which can be hampered by hindsight/recall bias and lack of contemporaneous documentation. Even worse, when these events occur, they may lead to a bias that all parricides or mass murders follow the pattern of the most recent case. This can result in overgeneralization of an individual’s history as being actionable risk violence factors for all potential parricide cases both by the public (eg, “My sister’s son has autism, and the Sandy Hook shooter was reported to have autism—should I be worried for my sister?”) and professionals (eg, “Will I be blamed for the next Sandy Hook by not taking more aggressive action even though I am not sure it is clinically warranted?”).

To identify trends for individuals committing parricide who engage in mass murder events (such as spree killing), we reviewed the 2000-2019 FBI active shooter list.¹² Of the 333 events identified, 46 could be classified as domestic violence situations (eg, the perpetrator was in a romantic or familial relationship/former relationship and engaged in an active shooting incident involving at least 1 person from that relationship). We classified 11 of those 46 cases as parricide. Ten of those 11 parricides involved a child killing a parent (Table 3), and the other involved a grandchild killing a grandfather who served as their primary caregiver. Of the 11 incidents, mothers were involved (killed or wounded) in 4, and father figures (including the grandfather serving as a father and a stepfather) were killed in 9, with 2 incidents involving both parents. In 4 of the 11 parricides, other family members were killed in addition to the parent (including siblings, grandparents, or extended family). When considering spree shooters who committed parricide, 4 alleged perpetrators died by suicide, 1 was killed at the scene, and the rest were apprehended. The most common active shooting site endangering the public was an educational location (5), followed by commerce locations (4), with 2 involving open spaces. Eight of the 11 parricides occurred before the event was designated as an active shooting. The mean age for a parricide plus spree shooter was 23, once the oldest (age 61) and youngest (age 14) were removed from the calculation. The majority of the cases fell into the age range of 16 to 25 (n = 6), followed by 3 individuals who were age 26 to 31 (n = 3). All suspected individuals were male.

Continue to: Parricide and society...

Parricide and society

For centuries, mothers and fathers have been honored and revered. Therefore, it is not surprising that killing of one’s mother or father attracts a great deal of macabre interest. Examples of parricide are present throughout popular culture, in mythology, comic books, movies, and television. As all psychiatrists know, Oedipus killed his father and married his mother. Other popular culture examples include: Grant Morrison’s Arkham Asylum: A Serious House on Serious Earth, Alfred Hitchcock’s Psycho, Oliver Stone’s Natural Born Killers, Peter Jackson’s Heavenly Creatures, The Affair drama series, and Star Wars: The Force Awakens.^13,14

CASE CONTINUED

In Mr. B’s case, it is imperative for the treatment team to inquire about his history of violence, paying particular attention to prior violent acts towards his mother. His clinicians should consider hospitalization with the guardian’s consent if the danger appears imminent, especially considering the presence of weapons at home. They should attempt to stabilize Mr. B on effective, tolerable medications to ameliorate his psychosis, and to refer him for long-term psychotherapy to address difficult dynamic issues in the family relationship and encourage compliance with treatment. These steps may help avert a tragedy.

Bottom Line

Individuals who commit parricide often have a history of psychosis, a mood disorder, childhood abuse, and/or difficult relationship dynamics with the parent they kill. Some go on a spree killing in the community. Through careful consideration of individual risk factors, psychiatrists may help prevent some cases of parent murder by a child and possibly more tragedy in the community.

Mr. B, age 37, presents to a community mental health center for an appointment following a recent emergency department visit. He is diagnosed with schizophrenia, and has been treated for approximately 1 year. Six months ago, Mr. B stopped taking his antipsychotic due to its adverse effects. Despite compliance with another agent, he has become increasingly disorganized and paranoid.

He now believes that his mother, with whom he has lived all his life and who serves as his guardian, is poisoning his food and trying to kill him. She is an employee at a local grocery store, and Mr. B has expressed concern that her coworkers are assisting her in the plot to kill him.

Following a home visit, Mr. B’s case manager indicates that the patient showed them the collection of weapons he is amassing to “defend” himself. This leads to a concern for the safety of the patient, his mother, and others.

Although parricide—killing one’s parent—is a relatively rare event, its sensationalistic nature has long captured the attention of headline writers and the general public. This article discusses the diagnostic and demographic factors that may be seen among individuals who kill their parents, with an emphasis on those who commit matricide (murder of one’s mother) and associated spree killings, where an individual kills multiple people within a single brief but contiguous time period. Understanding these characteristics can help clinicians identify and more safely manage patients who may be at risk of harming their parents in addition to others.

Characteristics of perpetrators of parricide

Worldwide, approximately 2% to 4% of homicides involve parricide, or killing one’s parent.^1,2 Most offenders are men in early adulthood, though a proportion are adolescents and some are women.^1,3 They are often single, unemployed, and live with the parent prior to the killing.¹ Patricide occurs more frequently than matricide.⁴ In the United States, approximately 150 fathers and 100 mothers are killed by their child each year.⁵

In a study of all homicides in England and Wales between 1997 and 2014, two-thirds of parricide offenders had previously been diagnosed with a mental disorder.¹ One-third were diagnosed with schizophrenia.¹ In a Canadian study focusing on 43 adult perpetrators found not criminally responsible,⁶ most were experiencing psychotic symptoms at the time of parricide; symptoms of a personality disorder were the second-most prevalent symptoms. Similarly, Bourget et al⁴ studied Canadian coroner records for 64 parents killed by their children. Of the children involved in those parricides, 15% attempted suicide after the killing. Two-thirds of the male offenders evidenced delusional thinking, and/or excessive violence (overkill) was common. Some cases (16%) followed an argument, and some of those perpetrators were intoxicated or psychotic. From our clinical experience, when there are identifiable nonpsychotic triggers, they often can be small things such as an argument over food, smoking, or video games. Often, the perpetrator was financially dependent on their parents and were “trapped in a difficult/hostile/dependence/love relationship” with that parent.⁶ Adolescent males who kill their parents may not have psychosis⁷; however, they may be victims of longstanding serious abuse at the hands of their parents. These perpetrators often express relief rather than remorse after committing murder.

Three categories to classify the perpetrators of parricide have been proposed: severely abused, severely mentally ill, and “dangerously antisocial.”³ While severe mental illness was most common in adult defendants, severe abuse was most common in adolescent offenders. There may be significant commonalities between adolescent and adult perpetrators. A more recent latent class analysis by Bojanic et al¹ indicated 3 unique types of parricide offenders (Table 1).

Continue to: Matricide: A closer look...

Though multiple studies have found a higher rate of psychosis among perpetrators of matricide, it is important to note that most people with psychotic disorders would never kill their mother. These events, however, tend to grab headlines and may be highly focused upon by the general population. In addition, matricide may be part of a larger crime that draws additional attention. For example, the 1966 University of Texas Bell Tower shooter and the 2012 Sandy Hook Elementary school shooter both killed their mothers before engaging in mass homicide. Often in cases of matricide, a longer-term dysfunctional relationship existed between the mother and the child. The mother is frequently described as controlling and intrusive and the (often adult) child as overly dependent, while the father may be absent or ineffectual. Hostility and mutual dependence are usual hallmarks of these relationships.⁸

However, in some cases where an individual with a psychotic disorder kills their mother, there may have been a traditional nurturing relationship.⁸ Alternative motivations unrelated to psychosis must be considered, including crimes motivated by money/inheritance or those perpetrated out of nonpsychotic anger. Green⁸ described motive categories for matricide that include paranoid and persecutory, altruistic, and other. In the “paranoid and persecutory” group, delusional beliefs about the mother occur; for example, the perpetrator may believe their mother was the devil. Sexual elements are found in some cases.⁸ Alternatively, the “altruistic” group demonstrated rather selfless reasons for killing, such as altruistic infanticide cases, or killing out of love.⁹ The altruistic matricide perpetrator may believe their mother is unwell, which may be a delusion or actually true. Finally, the “other” category contains cases related to jealousy, rage, and impulsivity.

In a study of 15 matricidal men in New York conducted by Campion et al,¹⁰ individuals seen by forensic psychiatric services for the crime of matricide included those with schizophrenia, substance-induced psychosis, and impulse control disorders. The authors noted there was often “a serious chronic derangement in the relationships of most matricidal men and their mothers.” Psychometric testing in these cases indicated feelings of dependency, weakness, and difficulty accepting an adult role separate from their mother. Some had conceptualized their mothers as a threat to their masculinity, while others had become enraged at their mothers.

Prevention requires addressing underlying issues

As described above, several factors are common among individuals who commit parricide, and these can be used to develop prevention strategies that focus on addressing underlying issues (Table 2). It is important to consider the relationship dynamics between the potential victim and perpetrator, as well as the motive, rather than focusing solely on mental illness or substance misuse.²

Spree killings that start as parricide

Although spree killing is a relatively rare event, a subset of spree killings involve parricide. One infamous recent event occurred in 2012 at Sandy Hook Elementary School, where the gunman killed his mother before going to the school and killing 26 additional people, many of whom were children.^11,12 Because such events are rare, and because in these cases there is a high likelihood that the perpetrator is deceased (eg, died by suicide or killed by the police), much remains unknown about specific motivations and causative factors.

Information is often pieced together from postmortem reviews, which can be hampered by hindsight/recall bias and lack of contemporaneous documentation. Even worse, when these events occur, they may lead to a bias that all parricides or mass murders follow the pattern of the most recent case. This can result in overgeneralization of an individual’s history as being actionable risk violence factors for all potential parricide cases both by the public (eg, “My sister’s son has autism, and the Sandy Hook shooter was reported to have autism—should I be worried for my sister?”) and professionals (eg, “Will I be blamed for the next Sandy Hook by not taking more aggressive action even though I am not sure it is clinically warranted?”).

To identify trends for individuals committing parricide who engage in mass murder events (such as spree killing), we reviewed the 2000-2019 FBI active shooter list.¹² Of the 333 events identified, 46 could be classified as domestic violence situations (eg, the perpetrator was in a romantic or familial relationship/former relationship and engaged in an active shooting incident involving at least 1 person from that relationship). We classified 11 of those 46 cases as parricide. Ten of those 11 parricides involved a child killing a parent (Table 3), and the other involved a grandchild killing a grandfather who served as their primary caregiver. Of the 11 incidents, mothers were involved (killed or wounded) in 4, and father figures (including the grandfather serving as a father and a stepfather) were killed in 9, with 2 incidents involving both parents. In 4 of the 11 parricides, other family members were killed in addition to the parent (including siblings, grandparents, or extended family). When considering spree shooters who committed parricide, 4 alleged perpetrators died by suicide, 1 was killed at the scene, and the rest were apprehended. The most common active shooting site endangering the public was an educational location (5), followed by commerce locations (4), with 2 involving open spaces. Eight of the 11 parricides occurred before the event was designated as an active shooting. The mean age for a parricide plus spree shooter was 23, once the oldest (age 61) and youngest (age 14) were removed from the calculation. The majority of the cases fell into the age range of 16 to 25 (n = 6), followed by 3 individuals who were age 26 to 31 (n = 3). All suspected individuals were male.

Continue to: Parricide and society...

Parricide and society

For centuries, mothers and fathers have been honored and revered. Therefore, it is not surprising that killing of one’s mother or father attracts a great deal of macabre interest. Examples of parricide are present throughout popular culture, in mythology, comic books, movies, and television. As all psychiatrists know, Oedipus killed his father and married his mother. Other popular culture examples include: Grant Morrison’s Arkham Asylum: A Serious House on Serious Earth, Alfred Hitchcock’s Psycho, Oliver Stone’s Natural Born Killers, Peter Jackson’s Heavenly Creatures, The Affair drama series, and Star Wars: The Force Awakens.^13,14

CASE CONTINUED

In Mr. B’s case, it is imperative for the treatment team to inquire about his history of violence, paying particular attention to prior violent acts towards his mother. His clinicians should consider hospitalization with the guardian’s consent if the danger appears imminent, especially considering the presence of weapons at home. They should attempt to stabilize Mr. B on effective, tolerable medications to ameliorate his psychosis, and to refer him for long-term psychotherapy to address difficult dynamic issues in the family relationship and encourage compliance with treatment. These steps may help avert a tragedy.

Bottom Line

Individuals who commit parricide often have a history of psychosis, a mood disorder, childhood abuse, and/or difficult relationship dynamics with the parent they kill. Some go on a spree killing in the community. Through careful consideration of individual risk factors, psychiatrists may help prevent some cases of parent murder by a child and possibly more tragedy in the community.

Mr. B, age 37, presents to a community mental health center for an appointment following a recent emergency department visit. He is diagnosed with schizophrenia, and has been treated for approximately 1 year. Six months ago, Mr. B stopped taking his antipsychotic due to its adverse effects. Despite compliance with another agent, he has become increasingly disorganized and paranoid.

He now believes that his mother, with whom he has lived all his life and who serves as his guardian, is poisoning his food and trying to kill him. She is an employee at a local grocery store, and Mr. B has expressed concern that her coworkers are assisting her in the plot to kill him.

Following a home visit, Mr. B’s case manager indicates that the patient showed them the collection of weapons he is amassing to “defend” himself. This leads to a concern for the safety of the patient, his mother, and others.

Although parricide—killing one’s parent—is a relatively rare event, its sensationalistic nature has long captured the attention of headline writers and the general public. This article discusses the diagnostic and demographic factors that may be seen among individuals who kill their parents, with an emphasis on those who commit matricide (murder of one’s mother) and associated spree killings, where an individual kills multiple people within a single brief but contiguous time period. Understanding these characteristics can help clinicians identify and more safely manage patients who may be at risk of harming their parents in addition to others.

Characteristics of perpetrators of parricide

Worldwide, approximately 2% to 4% of homicides involve parricide, or killing one’s parent.^1,2 Most offenders are men in early adulthood, though a proportion are adolescents and some are women.^1,3 They are often single, unemployed, and live with the parent prior to the killing.¹ Patricide occurs more frequently than matricide.⁴ In the United States, approximately 150 fathers and 100 mothers are killed by their child each year.⁵

In a study of all homicides in England and Wales between 1997 and 2014, two-thirds of parricide offenders had previously been diagnosed with a mental disorder.¹ One-third were diagnosed with schizophrenia.¹ In a Canadian study focusing on 43 adult perpetrators found not criminally responsible,⁶ most were experiencing psychotic symptoms at the time of parricide; symptoms of a personality disorder were the second-most prevalent symptoms. Similarly, Bourget et al⁴ studied Canadian coroner records for 64 parents killed by their children. Of the children involved in those parricides, 15% attempted suicide after the killing. Two-thirds of the male offenders evidenced delusional thinking, and/or excessive violence (overkill) was common. Some cases (16%) followed an argument, and some of those perpetrators were intoxicated or psychotic. From our clinical experience, when there are identifiable nonpsychotic triggers, they often can be small things such as an argument over food, smoking, or video games. Often, the perpetrator was financially dependent on their parents and were “trapped in a difficult/hostile/dependence/love relationship” with that parent.⁶ Adolescent males who kill their parents may not have psychosis⁷; however, they may be victims of longstanding serious abuse at the hands of their parents. These perpetrators often express relief rather than remorse after committing murder.

Three categories to classify the perpetrators of parricide have been proposed: severely abused, severely mentally ill, and “dangerously antisocial.”³ While severe mental illness was most common in adult defendants, severe abuse was most common in adolescent offenders. There may be significant commonalities between adolescent and adult perpetrators. A more recent latent class analysis by Bojanic et al¹ indicated 3 unique types of parricide offenders (Table 1).

Continue to: Matricide: A closer look...

Though multiple studies have found a higher rate of psychosis among perpetrators of matricide, it is important to note that most people with psychotic disorders would never kill their mother. These events, however, tend to grab headlines and may be highly focused upon by the general population. In addition, matricide may be part of a larger crime that draws additional attention. For example, the 1966 University of Texas Bell Tower shooter and the 2012 Sandy Hook Elementary school shooter both killed their mothers before engaging in mass homicide. Often in cases of matricide, a longer-term dysfunctional relationship existed between the mother and the child. The mother is frequently described as controlling and intrusive and the (often adult) child as overly dependent, while the father may be absent or ineffectual. Hostility and mutual dependence are usual hallmarks of these relationships.⁸

However, in some cases where an individual with a psychotic disorder kills their mother, there may have been a traditional nurturing relationship.⁸ Alternative motivations unrelated to psychosis must be considered, including crimes motivated by money/inheritance or those perpetrated out of nonpsychotic anger. Green⁸ described motive categories for matricide that include paranoid and persecutory, altruistic, and other. In the “paranoid and persecutory” group, delusional beliefs about the mother occur; for example, the perpetrator may believe their mother was the devil. Sexual elements are found in some cases.⁸ Alternatively, the “altruistic” group demonstrated rather selfless reasons for killing, such as altruistic infanticide cases, or killing out of love.⁹ The altruistic matricide perpetrator may believe their mother is unwell, which may be a delusion or actually true. Finally, the “other” category contains cases related to jealousy, rage, and impulsivity.

In a study of 15 matricidal men in New York conducted by Campion et al,¹⁰ individuals seen by forensic psychiatric services for the crime of matricide included those with schizophrenia, substance-induced psychosis, and impulse control disorders. The authors noted there was often “a serious chronic derangement in the relationships of most matricidal men and their mothers.” Psychometric testing in these cases indicated feelings of dependency, weakness, and difficulty accepting an adult role separate from their mother. Some had conceptualized their mothers as a threat to their masculinity, while others had become enraged at their mothers.

Prevention requires addressing underlying issues

As described above, several factors are common among individuals who commit parricide, and these can be used to develop prevention strategies that focus on addressing underlying issues (Table 2). It is important to consider the relationship dynamics between the potential victim and perpetrator, as well as the motive, rather than focusing solely on mental illness or substance misuse.²

Spree killings that start as parricide

Although spree killing is a relatively rare event, a subset of spree killings involve parricide. One infamous recent event occurred in 2012 at Sandy Hook Elementary School, where the gunman killed his mother before going to the school and killing 26 additional people, many of whom were children.^11,12 Because such events are rare, and because in these cases there is a high likelihood that the perpetrator is deceased (eg, died by suicide or killed by the police), much remains unknown about specific motivations and causative factors.

Information is often pieced together from postmortem reviews, which can be hampered by hindsight/recall bias and lack of contemporaneous documentation. Even worse, when these events occur, they may lead to a bias that all parricides or mass murders follow the pattern of the most recent case. This can result in overgeneralization of an individual’s history as being actionable risk violence factors for all potential parricide cases both by the public (eg, “My sister’s son has autism, and the Sandy Hook shooter was reported to have autism—should I be worried for my sister?”) and professionals (eg, “Will I be blamed for the next Sandy Hook by not taking more aggressive action even though I am not sure it is clinically warranted?”).

To identify trends for individuals committing parricide who engage in mass murder events (such as spree killing), we reviewed the 2000-2019 FBI active shooter list.¹² Of the 333 events identified, 46 could be classified as domestic violence situations (eg, the perpetrator was in a romantic or familial relationship/former relationship and engaged in an active shooting incident involving at least 1 person from that relationship). We classified 11 of those 46 cases as parricide. Ten of those 11 parricides involved a child killing a parent (Table 3), and the other involved a grandchild killing a grandfather who served as their primary caregiver. Of the 11 incidents, mothers were involved (killed or wounded) in 4, and father figures (including the grandfather serving as a father and a stepfather) were killed in 9, with 2 incidents involving both parents. In 4 of the 11 parricides, other family members were killed in addition to the parent (including siblings, grandparents, or extended family). When considering spree shooters who committed parricide, 4 alleged perpetrators died by suicide, 1 was killed at the scene, and the rest were apprehended. The most common active shooting site endangering the public was an educational location (5), followed by commerce locations (4), with 2 involving open spaces. Eight of the 11 parricides occurred before the event was designated as an active shooting. The mean age for a parricide plus spree shooter was 23, once the oldest (age 61) and youngest (age 14) were removed from the calculation. The majority of the cases fell into the age range of 16 to 25 (n = 6), followed by 3 individuals who were age 26 to 31 (n = 3). All suspected individuals were male.

Continue to: Parricide and society...

Parricide and society

For centuries, mothers and fathers have been honored and revered. Therefore, it is not surprising that killing of one’s mother or father attracts a great deal of macabre interest. Examples of parricide are present throughout popular culture, in mythology, comic books, movies, and television. As all psychiatrists know, Oedipus killed his father and married his mother. Other popular culture examples include: Grant Morrison’s Arkham Asylum: A Serious House on Serious Earth, Alfred Hitchcock’s Psycho, Oliver Stone’s Natural Born Killers, Peter Jackson’s Heavenly Creatures, The Affair drama series, and Star Wars: The Force Awakens.^13,14

CASE CONTINUED

In Mr. B’s case, it is imperative for the treatment team to inquire about his history of violence, paying particular attention to prior violent acts towards his mother. His clinicians should consider hospitalization with the guardian’s consent if the danger appears imminent, especially considering the presence of weapons at home. They should attempt to stabilize Mr. B on effective, tolerable medications to ameliorate his psychosis, and to refer him for long-term psychotherapy to address difficult dynamic issues in the family relationship and encourage compliance with treatment. These steps may help avert a tragedy.

Bottom Line

Individuals who commit parricide often have a history of psychosis, a mood disorder, childhood abuse, and/or difficult relationship dynamics with the parent they kill. Some go on a spree killing in the community. Through careful consideration of individual risk factors, psychiatrists may help prevent some cases of parent murder by a child and possibly more tragedy in the community.

Mr. J, age 35, is brought to the hospital from prison due to priapism that does not improve with treatment. He says he has had priapism 5 times previously, with the first incidence occurring “years ago” due to trazodone.

Recently, he has been receiving risperidone, which the treatment team believes is the cause of his current priapism. His medical history includes asthma, schizophrenia, hypertension, seizures, and sickle cell trait. Mr. J is experiencing auditory hallucinations, which he describes as “continuous, neutral voices that are annoying.” He would like relief from his auditory hallucinations and is willing to change his antipsychotic, but does not want additional treatment for his priapism. His present medications include risperidone, 1 mg twice a day, escitalopram, 10 mg/d, benztropine, 1 mg twice a day, and phenytoin, 500 mg/d at bedtime.

Priapism is a prolonged, persistent, and often painful erection that occurs without sexual stimulation. Although relatively rare, it can result in potentially serious long-term complications, including impotence and gangrene, and requires immediate evaluation and management.

There are 2 types of priapism: nonischemic, or “high-flow,” priapism, and ischemic, or “low-flow,” priapism (Table 1). While nonischemic priapism is typically caused by penile or perineal trauma, ischemic priapism can occur as a result of medications, including antipsychotics, antidepressants, anxiolytics, and antihypertensives, or hematological conditions such as sickle cell disease.¹ Other risk factors associated with priapism include substance abuse, hyperprolactinemia, diabetes, and liver disease.⁴

Antipsychotic-induced priapism

Medication-induced priapism is a rare adverse drug reaction (ADR). Of the medication classes associated with priapism, antipsychotics have the highest incidence and account for approximately 20% of all cases.¹

The mechanism of priapism associated with antipsychotics is thought to be related to alpha-1 blockade in the corpora cavernosa of the penis. Although antipsychotics within each class share common characteristics, each agent has a unique profile of receptor affinities. As such, antipsychotics have varying affinities for the alpha-adrenergic receptor (Table 2). Agents such as ziprasidone, chlorpromazine, and risperidone—which have the highest affinity for the alpha-1 adrenoceptors—may be more likely to cause priapism compared with agents with lower affinity, such as olanzapine. Priapism may occur at any time during antipsychotic treatment, and does not appear to be dose-related.

Continue to: Antipsychotic drug interactions and priapism...

Patients who are receiving multiple medications as treatment for chronic medical or psychiatric conditions have an increased likelihood of experiencing drug-drug interactions (DDIs) that lead to adverse effects.

Various case reports have described priapism as a result of DDIs related to antipsychotic agents combined with other psychotropic or nonpsychotropic medications.³ Most of these DDIs have been attributed to the cytochrome P450 (CYP) family of enzymes, including CYP2D6, CYP1A2, and CYP3A4/5, which are major enzymes implicated in the metabolism of antipsychotics (Table 3).

Mitigating the risk of priapism

Although there are associated risk factors for priapism, there are no concrete indicators to predict the onset or development of the condition. The best predictor may be a history of prolonged and painless erections.³

As such, when choosing an antipsychotic, it is critical to screen the patient for the previously mentioned risk factors, including the presence of medications with strong alpha-1 receptor affinity and CYP interactions, especially to minimize the risk of recurrence of priapism in those with prior or similar episodes. Management of patients with priapism due to antipsychotics has involved reducing the dose of the offending agent and/or changing the medication to one with a lower alpha-adrenergic affinity (Table 2²).

Similar to most situations, management is patient-specific and depends on several factors, including the severity of the patient’s psychiatric disease, history/severity of priapism and treatment, concurrent medication list, etc. For example, although clozapine is considered to have relatively high affinity for the alpha-1 receptor, it is also the agent of choice for treatment-refractory schizophrenia. Risks and benefits must be weighed on a individualized basis. Case reports have described symptom improvement via lowering the dose of clozapine and adding on or switching to an antipsychotic agent with minimal alpha-1 receptor affinity.⁴

After considering Mr. J’s history, risk factors, and preferences, the treatment team discontinues risperidone and initiates haloperidol, 5 mg twice a day. Soon after, Mr. J no longer experiences priapism.

Mr. J, age 35, is brought to the hospital from prison due to priapism that does not improve with treatment. He says he has had priapism 5 times previously, with the first incidence occurring “years ago” due to trazodone.

Recently, he has been receiving risperidone, which the treatment team believes is the cause of his current priapism. His medical history includes asthma, schizophrenia, hypertension, seizures, and sickle cell trait. Mr. J is experiencing auditory hallucinations, which he describes as “continuous, neutral voices that are annoying.” He would like relief from his auditory hallucinations and is willing to change his antipsychotic, but does not want additional treatment for his priapism. His present medications include risperidone, 1 mg twice a day, escitalopram, 10 mg/d, benztropine, 1 mg twice a day, and phenytoin, 500 mg/d at bedtime.

Priapism is a prolonged, persistent, and often painful erection that occurs without sexual stimulation. Although relatively rare, it can result in potentially serious long-term complications, including impotence and gangrene, and requires immediate evaluation and management.

There are 2 types of priapism: nonischemic, or “high-flow,” priapism, and ischemic, or “low-flow,” priapism (Table 1). While nonischemic priapism is typically caused by penile or perineal trauma, ischemic priapism can occur as a result of medications, including antipsychotics, antidepressants, anxiolytics, and antihypertensives, or hematological conditions such as sickle cell disease.¹ Other risk factors associated with priapism include substance abuse, hyperprolactinemia, diabetes, and liver disease.⁴

Antipsychotic-induced priapism

Medication-induced priapism is a rare adverse drug reaction (ADR). Of the medication classes associated with priapism, antipsychotics have the highest incidence and account for approximately 20% of all cases.¹

The mechanism of priapism associated with antipsychotics is thought to be related to alpha-1 blockade in the corpora cavernosa of the penis. Although antipsychotics within each class share common characteristics, each agent has a unique profile of receptor affinities. As such, antipsychotics have varying affinities for the alpha-adrenergic receptor (Table 2). Agents such as ziprasidone, chlorpromazine, and risperidone—which have the highest affinity for the alpha-1 adrenoceptors—may be more likely to cause priapism compared with agents with lower affinity, such as olanzapine. Priapism may occur at any time during antipsychotic treatment, and does not appear to be dose-related.

Continue to: Antipsychotic drug interactions and priapism...

Patients who are receiving multiple medications as treatment for chronic medical or psychiatric conditions have an increased likelihood of experiencing drug-drug interactions (DDIs) that lead to adverse effects.

Various case reports have described priapism as a result of DDIs related to antipsychotic agents combined with other psychotropic or nonpsychotropic medications.³ Most of these DDIs have been attributed to the cytochrome P450 (CYP) family of enzymes, including CYP2D6, CYP1A2, and CYP3A4/5, which are major enzymes implicated in the metabolism of antipsychotics (Table 3).

Mitigating the risk of priapism

Although there are associated risk factors for priapism, there are no concrete indicators to predict the onset or development of the condition. The best predictor may be a history of prolonged and painless erections.³

As such, when choosing an antipsychotic, it is critical to screen the patient for the previously mentioned risk factors, including the presence of medications with strong alpha-1 receptor affinity and CYP interactions, especially to minimize the risk of recurrence of priapism in those with prior or similar episodes. Management of patients with priapism due to antipsychotics has involved reducing the dose of the offending agent and/or changing the medication to one with a lower alpha-adrenergic affinity (Table 2²).

Similar to most situations, management is patient-specific and depends on several factors, including the severity of the patient’s psychiatric disease, history/severity of priapism and treatment, concurrent medication list, etc. For example, although clozapine is considered to have relatively high affinity for the alpha-1 receptor, it is also the agent of choice for treatment-refractory schizophrenia. Risks and benefits must be weighed on a individualized basis. Case reports have described symptom improvement via lowering the dose of clozapine and adding on or switching to an antipsychotic agent with minimal alpha-1 receptor affinity.⁴

After considering Mr. J’s history, risk factors, and preferences, the treatment team discontinues risperidone and initiates haloperidol, 5 mg twice a day. Soon after, Mr. J no longer experiences priapism.

Mr. J, age 35, is brought to the hospital from prison due to priapism that does not improve with treatment. He says he has had priapism 5 times previously, with the first incidence occurring “years ago” due to trazodone.

Recently, he has been receiving risperidone, which the treatment team believes is the cause of his current priapism. His medical history includes asthma, schizophrenia, hypertension, seizures, and sickle cell trait. Mr. J is experiencing auditory hallucinations, which he describes as “continuous, neutral voices that are annoying.” He would like relief from his auditory hallucinations and is willing to change his antipsychotic, but does not want additional treatment for his priapism. His present medications include risperidone, 1 mg twice a day, escitalopram, 10 mg/d, benztropine, 1 mg twice a day, and phenytoin, 500 mg/d at bedtime.

Priapism is a prolonged, persistent, and often painful erection that occurs without sexual stimulation. Although relatively rare, it can result in potentially serious long-term complications, including impotence and gangrene, and requires immediate evaluation and management.

There are 2 types of priapism: nonischemic, or “high-flow,” priapism, and ischemic, or “low-flow,” priapism (Table 1). While nonischemic priapism is typically caused by penile or perineal trauma, ischemic priapism can occur as a result of medications, including antipsychotics, antidepressants, anxiolytics, and antihypertensives, or hematological conditions such as sickle cell disease.¹ Other risk factors associated with priapism include substance abuse, hyperprolactinemia, diabetes, and liver disease.⁴

Antipsychotic-induced priapism

Medication-induced priapism is a rare adverse drug reaction (ADR). Of the medication classes associated with priapism, antipsychotics have the highest incidence and account for approximately 20% of all cases.¹

The mechanism of priapism associated with antipsychotics is thought to be related to alpha-1 blockade in the corpora cavernosa of the penis. Although antipsychotics within each class share common characteristics, each agent has a unique profile of receptor affinities. As such, antipsychotics have varying affinities for the alpha-adrenergic receptor (Table 2). Agents such as ziprasidone, chlorpromazine, and risperidone—which have the highest affinity for the alpha-1 adrenoceptors—may be more likely to cause priapism compared with agents with lower affinity, such as olanzapine. Priapism may occur at any time during antipsychotic treatment, and does not appear to be dose-related.

Continue to: Antipsychotic drug interactions and priapism...

Patients who are receiving multiple medications as treatment for chronic medical or psychiatric conditions have an increased likelihood of experiencing drug-drug interactions (DDIs) that lead to adverse effects.

Various case reports have described priapism as a result of DDIs related to antipsychotic agents combined with other psychotropic or nonpsychotropic medications.³ Most of these DDIs have been attributed to the cytochrome P450 (CYP) family of enzymes, including CYP2D6, CYP1A2, and CYP3A4/5, which are major enzymes implicated in the metabolism of antipsychotics (Table 3).

Mitigating the risk of priapism

Although there are associated risk factors for priapism, there are no concrete indicators to predict the onset or development of the condition. The best predictor may be a history of prolonged and painless erections.³

As such, when choosing an antipsychotic, it is critical to screen the patient for the previously mentioned risk factors, including the presence of medications with strong alpha-1 receptor affinity and CYP interactions, especially to minimize the risk of recurrence of priapism in those with prior or similar episodes. Management of patients with priapism due to antipsychotics has involved reducing the dose of the offending agent and/or changing the medication to one with a lower alpha-adrenergic affinity (Table 2²).

Similar to most situations, management is patient-specific and depends on several factors, including the severity of the patient’s psychiatric disease, history/severity of priapism and treatment, concurrent medication list, etc. For example, although clozapine is considered to have relatively high affinity for the alpha-1 receptor, it is also the agent of choice for treatment-refractory schizophrenia. Risks and benefits must be weighed on a individualized basis. Case reports have described symptom improvement via lowering the dose of clozapine and adding on or switching to an antipsychotic agent with minimal alpha-1 receptor affinity.⁴

After considering Mr. J’s history, risk factors, and preferences, the treatment team discontinues risperidone and initiates haloperidol, 5 mg twice a day. Soon after, Mr. J no longer experiences priapism.

CASE Treatment-resistant MDD

Ms. P, age 21, presents to the outpatient clinic. She has diagnoses of treatment-resistant major depressive disorder (MDD) and schizoid personality disorder (SPD). Ms. P was diagnosed with MDD 3 years ago after reporting symptoms of prevailing sadness for approximately 8 years, described as feelings of worthlessness, anhedonia, social withdrawal, and decreased hygiene and self-care behaviors, as well as suicidal ideation and self-harm. SPD was diagnosed 1 year earlier based on her “odd” behaviors and disheveled appearance following observation and in collateral with her family. Her odd behaviors are described as spending most of her time alone, preferring solitary activities, and having little contact with people other than her parents.

Ms. P reports that she was previously treated with citalopram, 20 mg/d, bupropion, 150 mg/d, aripiprazole, 3.75 mg/d, topiramate, 100 mg twice daily, and melatonin, 9 mg/d at bedtime, but discontinued follow-up appointments and medications after no significant improvement in symptoms.

[polldaddy:11027942]

The authors’ observations

The term “schizoid” first made its debut in the medical community to describe the prodromal social withdrawal and isolation observed in schizophrenia.¹ The use of schizoid to describe a personality type first occurred in DSM-III in 1980.² SPD is a Cluster A personality disorder that groups personalities characterized by common traits that are “odd” or “eccentric” and may resemble the positive and/or negative symptoms of schizophrenia.^3,4 Relatively uncommon in clinical settings, SPD includes individuals who do not desire or enjoy close relationships. Those afflicted with SPD will be described as isolated, aloof, and detached from social relationships with others, even immediate family members. Individuals with SPD may appear indifferent to criticism and praise, and may take pleasure in only a few activities. They may exhibit a general absence of affective range, which contributes to their characterization as flat, blunted, or emotionally vacant. SPD is more commonly diagnosed in males and may be present in childhood and adolescence. These children are typified by solitariness, poor peer relationships, and underachievement in school. SPD impacts 3.1% to 4.9% of the United States population and approximately 1% of community populations.^5,6

EVALUATION Persistent depressive symptoms

Ms. P is accompanied by her parents for the examination. She reports a chronic, persistent sad mood, hopelessness, anergia, insomnia, anhedonia, and decreased concentration and appetite. She says she experiences episodes of intense worry, along with tension, restlessness, feelings of being on the edge, irritability, and difficulty relaxing. Socially, she is withdrawn, preferring to stay alone in her room most of the day watching YouTube or trying to write stories. She has 2 friends with whom she does not interact with in person, but rather through digital means. Ms. P has never enjoyed attending school and feels “nervous” when she is around people. She has difficulty expressing her thoughts and often looks to her parents for help. Her parents add that getting Ms. P to attend school was a struggle, which resulted in periods of home schooling throughout high school.

The treating team prescribes citalopram, 10 mg/d, and aripiprazole, 2 mg/d. On subsequent follow-up visits, Ms. P’s depression improves with an increase in citalopram to 40 mg/d. Psychotherapy is added to her treatment plan to help address the persistent social deficits, odd behavior, and anxieties.

Continue to: Evaluation Psychological assessment...

At her psychotherapy intake appointment with the clinical neuropsychologist, Ms. P is dressed in purple from head to toe and sits clutching her purse and looking at the ground. She is overweight with clean, fitting clothing. Ms. P takes a secondary role during most of the interview, allowing her parents to answer most questions. When asked why she is starting therapy, Ms. P replies, “Well, I’ve been using the bathroom a lot.” She describes a feeling of comfort and calmness while in the restroom. Suddenly, she asks her parents to exit the exam room for a moment. Once they leave, she leans in and whispers, “Have you ever heard of self-sabotage? I think that’s what I’m doing.”

Her mood is euthymic, with a blunted affect. She scores 2 on the Patient Health Questionnaire-9 (PHQ-9) and 10 on the Generalized Anxiety Disorder 7-item scale (GAD-7), which indicates the positive impact of medication on her depressive symptoms but continuing moderate anxious distress. She endorses fear of the night, insomnia, and suicidal ideation. She reports an unusual “constant itching sensation,” resulting in hours of repetitive excoriation. Physical examination reveals several significant scars and scabs covering her bilateral upper and lower extremities. Her vocational history is brief; she had held 2 entry-level customer service positions that lasted <1 year. She was fired due to excessive bathroom use.

As the interview progresses, the intake clinician’s background in neuropsychological assessment facilitates screening for possible developmental disorders. Given the nature of the referral and psychotherapy intake, a full neuropsychological assessment is not conducted. The clinician emphasizes verbal abstraction and theory of mind. Ms. P’s IQ was estimated to be average by Wide Range Achievement Test 4 word reading and interview questions about her academic history. Questions are abstracted from the Autism Diagnostic Observation Schedule, Module 4, to assess for conversation ability, emotional insight, awareness and expression, relationships, and areas of functioning in daily living. Developmental history questions, such as those found on the Adaptive Behavior Assessment System, 3rd edition, help guide developmental information provided by parents in the areas of communication, emotion and eye-gaze, gestures, sensory function, language, social functioning, hygiene behavior, and specific interests.

Ms. P’s mother describes a normal pregnancy and delivery; however, she states that Ms. P was “born with problems,” including difficulty with rooting and sucking, and required gastrointestinal intubation until age 3. Cyclical vomiting followed normal food consumption. Ambulation, language acquisition, toilet training, and hygiene behavior were delayed. Ms. P experienced improvements with early intervention in intensive physical and occupational therapy.

Ms. P’s hygiene is well below average, and she requires cueing from her parents. She attended general education until she reached high school, when she began special education. She was sensitive to sensory stimulation from infancy, with sensory sensitivity to textures. Ms. P continues to report sensory sensitivity and lapses in hygiene.

She has difficulty establishing and maintaining relationships with her peers, and prefers solitary activities. Ms. P has no history of romantic relationships, although she does desire one. When asked about her understanding of various relationships, Ms. P’s responses are stereotyped, such as “I know someone is my friend because they are nice to me” and “People get married because they love each other.” She struggles to offer greater insight into the nuances that form lasting relationships and bonds. Ms. P struggles to imitate and describe the physical and internal cues of several basic emotions (eg, fear, joy, anger).

Her conversational and social skills are assessed by asking her to engage in a conversation with the examiner as if meeting for the first time. Her speech is reciprocal, aprosodic, and delayed. The conversation is one-sided, and the examiner fills in several awkward pauses. Ms. P’s gaze at times is intense and prolonged, especially when responding to questions. She tends to use descriptive statements (eg, “I like your purple pen, I like your shirt”) to engage in conversation, rather than gathering more information through reflective statements, questions, or expressing a shared interest.

Ms. P’s verbal abstraction is screened using questions from the Wechsler Adult Intelligence Scale, 4th edition Similarities subtest, to which she provides several responses within normal limits. Her understanding of colloquial speech is assessed by asking her the meaning of common phrases (eg, “Get knocked down 9 times, get up 10,” “Jack and Jill are 2 peas in a pod”). On many occasions, she is able to limit her response to 1 word, (eg, “resiliency”), demonstrating intact ability to decipher idioms.

[polldaddy:11027971]

The authors’ observations

Upon reflection of Ms. P’s clinical presentation and history of developmental delays, social deficits, sensory sensitivity since infancy, and repetitive behaviors (all which continue to impact her), the clinical team concluded that the diagnosis of autism spectrum disorder (ASD) helps explain the patient’s “odd” behaviors, more so than SPD.

ASD is a heterogenous, complex neuropsychiatric disorder characterized by a persistent deficit in social reciprocity, verbal, and nonverbal communication, and includes a pattern of restricted, repetitive and/or stereotyped behaviors and/or interests.⁵ The term “autismus” is Greek meaning “self,” and was first used to classify the qualities of “morbid self-admiration” observed in prodromal schizophrenia.⁷Due to disorganized, odd behaviors and speech, adults with ASD are sometimes misdiagnosed with schizophrenia and schizophrenia-related disorders, such as SPD.⁸ Ms. P is an example of this phenomenon. In a prospective study looking at the continuity of ASD and SPD traits, Cook et al⁹ found that higher severity levels of ASD symptoms in childhood were associated with a higher level of reported SPD traits in adolescence. Although ASD and SPD are usually diagnosed at opposite ends of the age spectrum, they do have characteristics that overlap, such as limited range of affect and tendency to be described as loners. Table 1^5,8,9 highlights some of these similarities.

Continue to: Treatment...

TREATMENT Adding CBT

At an interdisciplinary session several weeks later that includes Ms. P and her parents, the treatment team discusses the revised diagnoses of ASD and MDD, a treatment recommendation for cognitive-behavioral therapy (CBT), and continued use of medication. At this session, Ms. P discloses that she has not been consistent with her medication regimen since her last appointment, which helps explain the increase in her PHQ-9 score from 2 to 14 and GAD-7 score from 10 to 15 as noted at this interdisciplinary session.

[polldaddy:11027990]

The authors’ observations

CBT can be helpful in improving medication adherence, developing coping skills, and modifying maladaptive behaviors.^16,17Table 2^16,17 provides examples of behavioral interventions that CBT can implement. The evidence for the benefits of psychosocial interventions for adults with ASD is growing. A small systemic review of psychosocial interventions for adults with ASD found that social cognition training, social skills training, and applied behavior analysis had positive benefits.¹⁸

OUTCOME Improvement with psychotherapy

Ms. P and family agree with the team’s recommendations. The aims of Ms. P’s psychotherapy are to maintain medication compliance; implement behavioral modification, vocational rehabilitation, and community engagement; develop social skills; increase functional independence; and develop coping skills for depression and anxiety.

Once her medication is augmented with psychotherapy, Ms. P exhibits a steady decline in PHQ-9 and GAD-7 scores, consistent with an overall reduction of subjective anxiety and depression. In 5 months, her PHQ-9 score decreases from 14 to 2 and her GAD-7 score decreases from 15 to 3. Ms. P is treatment-compliant, more active around the home, and spends more time engaging with friends face-to-face. Overall, the psychotherapy interventions most helpful to her are the development of social skills and coping skills. She reports improved mood, energy levels, concentration, interests, and appetite. Suicidal ideation lessens, and she has not engaged in self-harm since beginning treatment. Worries, tension, and difficulty relaxing also have lessened, though restlessness persists. Excoriation has also decreased significantly, and Ms. P spends less time in the bathroom. Sheenrolls in college courses, plans to start a volleyball team, and is excited about the future.

Bottom Line

The prevalence of schizoid personality disorder (SPD) is low, and its symptoms overlap with those of autism spectrum disorder. Therefore, before diagnosing SPD in an adult patient, it is important to obtain a detailed developmental history and include an interdisciplinary team to assess for autism spectrum disorder.

CASE Treatment-resistant MDD

Ms. P, age 21, presents to the outpatient clinic. She has diagnoses of treatment-resistant major depressive disorder (MDD) and schizoid personality disorder (SPD). Ms. P was diagnosed with MDD 3 years ago after reporting symptoms of prevailing sadness for approximately 8 years, described as feelings of worthlessness, anhedonia, social withdrawal, and decreased hygiene and self-care behaviors, as well as suicidal ideation and self-harm. SPD was diagnosed 1 year earlier based on her “odd” behaviors and disheveled appearance following observation and in collateral with her family. Her odd behaviors are described as spending most of her time alone, preferring solitary activities, and having little contact with people other than her parents.

Ms. P reports that she was previously treated with citalopram, 20 mg/d, bupropion, 150 mg/d, aripiprazole, 3.75 mg/d, topiramate, 100 mg twice daily, and melatonin, 9 mg/d at bedtime, but discontinued follow-up appointments and medications after no significant improvement in symptoms.

[polldaddy:11027942]

The authors’ observations

The term “schizoid” first made its debut in the medical community to describe the prodromal social withdrawal and isolation observed in schizophrenia.¹ The use of schizoid to describe a personality type first occurred in DSM-III in 1980.² SPD is a Cluster A personality disorder that groups personalities characterized by common traits that are “odd” or “eccentric” and may resemble the positive and/or negative symptoms of schizophrenia.^3,4 Relatively uncommon in clinical settings, SPD includes individuals who do not desire or enjoy close relationships. Those afflicted with SPD will be described as isolated, aloof, and detached from social relationships with others, even immediate family members. Individuals with SPD may appear indifferent to criticism and praise, and may take pleasure in only a few activities. They may exhibit a general absence of affective range, which contributes to their characterization as flat, blunted, or emotionally vacant. SPD is more commonly diagnosed in males and may be present in childhood and adolescence. These children are typified by solitariness, poor peer relationships, and underachievement in school. SPD impacts 3.1% to 4.9% of the United States population and approximately 1% of community populations.^5,6

EVALUATION Persistent depressive symptoms

Ms. P is accompanied by her parents for the examination. She reports a chronic, persistent sad mood, hopelessness, anergia, insomnia, anhedonia, and decreased concentration and appetite. She says she experiences episodes of intense worry, along with tension, restlessness, feelings of being on the edge, irritability, and difficulty relaxing. Socially, she is withdrawn, preferring to stay alone in her room most of the day watching YouTube or trying to write stories. She has 2 friends with whom she does not interact with in person, but rather through digital means. Ms. P has never enjoyed attending school and feels “nervous” when she is around people. She has difficulty expressing her thoughts and often looks to her parents for help. Her parents add that getting Ms. P to attend school was a struggle, which resulted in periods of home schooling throughout high school.

The treating team prescribes citalopram, 10 mg/d, and aripiprazole, 2 mg/d. On subsequent follow-up visits, Ms. P’s depression improves with an increase in citalopram to 40 mg/d. Psychotherapy is added to her treatment plan to help address the persistent social deficits, odd behavior, and anxieties.

Continue to: Evaluation Psychological assessment...

At her psychotherapy intake appointment with the clinical neuropsychologist, Ms. P is dressed in purple from head to toe and sits clutching her purse and looking at the ground. She is overweight with clean, fitting clothing. Ms. P takes a secondary role during most of the interview, allowing her parents to answer most questions. When asked why she is starting therapy, Ms. P replies, “Well, I’ve been using the bathroom a lot.” She describes a feeling of comfort and calmness while in the restroom. Suddenly, she asks her parents to exit the exam room for a moment. Once they leave, she leans in and whispers, “Have you ever heard of self-sabotage? I think that’s what I’m doing.”

Her mood is euthymic, with a blunted affect. She scores 2 on the Patient Health Questionnaire-9 (PHQ-9) and 10 on the Generalized Anxiety Disorder 7-item scale (GAD-7), which indicates the positive impact of medication on her depressive symptoms but continuing moderate anxious distress. She endorses fear of the night, insomnia, and suicidal ideation. She reports an unusual “constant itching sensation,” resulting in hours of repetitive excoriation. Physical examination reveals several significant scars and scabs covering her bilateral upper and lower extremities. Her vocational history is brief; she had held 2 entry-level customer service positions that lasted <1 year. She was fired due to excessive bathroom use.

As the interview progresses, the intake clinician’s background in neuropsychological assessment facilitates screening for possible developmental disorders. Given the nature of the referral and psychotherapy intake, a full neuropsychological assessment is not conducted. The clinician emphasizes verbal abstraction and theory of mind. Ms. P’s IQ was estimated to be average by Wide Range Achievement Test 4 word reading and interview questions about her academic history. Questions are abstracted from the Autism Diagnostic Observation Schedule, Module 4, to assess for conversation ability, emotional insight, awareness and expression, relationships, and areas of functioning in daily living. Developmental history questions, such as those found on the Adaptive Behavior Assessment System, 3rd edition, help guide developmental information provided by parents in the areas of communication, emotion and eye-gaze, gestures, sensory function, language, social functioning, hygiene behavior, and specific interests.

Ms. P’s mother describes a normal pregnancy and delivery; however, she states that Ms. P was “born with problems,” including difficulty with rooting and sucking, and required gastrointestinal intubation until age 3. Cyclical vomiting followed normal food consumption. Ambulation, language acquisition, toilet training, and hygiene behavior were delayed. Ms. P experienced improvements with early intervention in intensive physical and occupational therapy.

Ms. P’s hygiene is well below average, and she requires cueing from her parents. She attended general education until she reached high school, when she began special education. She was sensitive to sensory stimulation from infancy, with sensory sensitivity to textures. Ms. P continues to report sensory sensitivity and lapses in hygiene.

She has difficulty establishing and maintaining relationships with her peers, and prefers solitary activities. Ms. P has no history of romantic relationships, although she does desire one. When asked about her understanding of various relationships, Ms. P’s responses are stereotyped, such as “I know someone is my friend because they are nice to me” and “People get married because they love each other.” She struggles to offer greater insight into the nuances that form lasting relationships and bonds. Ms. P struggles to imitate and describe the physical and internal cues of several basic emotions (eg, fear, joy, anger).

Her conversational and social skills are assessed by asking her to engage in a conversation with the examiner as if meeting for the first time. Her speech is reciprocal, aprosodic, and delayed. The conversation is one-sided, and the examiner fills in several awkward pauses. Ms. P’s gaze at times is intense and prolonged, especially when responding to questions. She tends to use descriptive statements (eg, “I like your purple pen, I like your shirt”) to engage in conversation, rather than gathering more information through reflective statements, questions, or expressing a shared interest.

Ms. P’s verbal abstraction is screened using questions from the Wechsler Adult Intelligence Scale, 4th edition Similarities subtest, to which she provides several responses within normal limits. Her understanding of colloquial speech is assessed by asking her the meaning of common phrases (eg, “Get knocked down 9 times, get up 10,” “Jack and Jill are 2 peas in a pod”). On many occasions, she is able to limit her response to 1 word, (eg, “resiliency”), demonstrating intact ability to decipher idioms.

[polldaddy:11027971]

The authors’ observations

Upon reflection of Ms. P’s clinical presentation and history of developmental delays, social deficits, sensory sensitivity since infancy, and repetitive behaviors (all which continue to impact her), the clinical team concluded that the diagnosis of autism spectrum disorder (ASD) helps explain the patient’s “odd” behaviors, more so than SPD.

ASD is a heterogenous, complex neuropsychiatric disorder characterized by a persistent deficit in social reciprocity, verbal, and nonverbal communication, and includes a pattern of restricted, repetitive and/or stereotyped behaviors and/or interests.⁵ The term “autismus” is Greek meaning “self,” and was first used to classify the qualities of “morbid self-admiration” observed in prodromal schizophrenia.⁷Due to disorganized, odd behaviors and speech, adults with ASD are sometimes misdiagnosed with schizophrenia and schizophrenia-related disorders, such as SPD.⁸ Ms. P is an example of this phenomenon. In a prospective study looking at the continuity of ASD and SPD traits, Cook et al⁹ found that higher severity levels of ASD symptoms in childhood were associated with a higher level of reported SPD traits in adolescence. Although ASD and SPD are usually diagnosed at opposite ends of the age spectrum, they do have characteristics that overlap, such as limited range of affect and tendency to be described as loners. Table 1^5,8,9 highlights some of these similarities.

Continue to: Treatment...

TREATMENT Adding CBT

At an interdisciplinary session several weeks later that includes Ms. P and her parents, the treatment team discusses the revised diagnoses of ASD and MDD, a treatment recommendation for cognitive-behavioral therapy (CBT), and continued use of medication. At this session, Ms. P discloses that she has not been consistent with her medication regimen since her last appointment, which helps explain the increase in her PHQ-9 score from 2 to 14 and GAD-7 score from 10 to 15 as noted at this interdisciplinary session.

[polldaddy:11027990]

The authors’ observations

CBT can be helpful in improving medication adherence, developing coping skills, and modifying maladaptive behaviors.^16,17Table 2^16,17 provides examples of behavioral interventions that CBT can implement. The evidence for the benefits of psychosocial interventions for adults with ASD is growing. A small systemic review of psychosocial interventions for adults with ASD found that social cognition training, social skills training, and applied behavior analysis had positive benefits.¹⁸

OUTCOME Improvement with psychotherapy

Ms. P and family agree with the team’s recommendations. The aims of Ms. P’s psychotherapy are to maintain medication compliance; implement behavioral modification, vocational rehabilitation, and community engagement; develop social skills; increase functional independence; and develop coping skills for depression and anxiety.

Once her medication is augmented with psychotherapy, Ms. P exhibits a steady decline in PHQ-9 and GAD-7 scores, consistent with an overall reduction of subjective anxiety and depression. In 5 months, her PHQ-9 score decreases from 14 to 2 and her GAD-7 score decreases from 15 to 3. Ms. P is treatment-compliant, more active around the home, and spends more time engaging with friends face-to-face. Overall, the psychotherapy interventions most helpful to her are the development of social skills and coping skills. She reports improved mood, energy levels, concentration, interests, and appetite. Suicidal ideation lessens, and she has not engaged in self-harm since beginning treatment. Worries, tension, and difficulty relaxing also have lessened, though restlessness persists. Excoriation has also decreased significantly, and Ms. P spends less time in the bathroom. Sheenrolls in college courses, plans to start a volleyball team, and is excited about the future.

Bottom Line

The prevalence of schizoid personality disorder (SPD) is low, and its symptoms overlap with those of autism spectrum disorder. Therefore, before diagnosing SPD in an adult patient, it is important to obtain a detailed developmental history and include an interdisciplinary team to assess for autism spectrum disorder.

CASE Treatment-resistant MDD

Ms. P, age 21, presents to the outpatient clinic. She has diagnoses of treatment-resistant major depressive disorder (MDD) and schizoid personality disorder (SPD). Ms. P was diagnosed with MDD 3 years ago after reporting symptoms of prevailing sadness for approximately 8 years, described as feelings of worthlessness, anhedonia, social withdrawal, and decreased hygiene and self-care behaviors, as well as suicidal ideation and self-harm. SPD was diagnosed 1 year earlier based on her “odd” behaviors and disheveled appearance following observation and in collateral with her family. Her odd behaviors are described as spending most of her time alone, preferring solitary activities, and having little contact with people other than her parents.

Ms. P reports that she was previously treated with citalopram, 20 mg/d, bupropion, 150 mg/d, aripiprazole, 3.75 mg/d, topiramate, 100 mg twice daily, and melatonin, 9 mg/d at bedtime, but discontinued follow-up appointments and medications after no significant improvement in symptoms.

[polldaddy:11027942]

The authors’ observations

The term “schizoid” first made its debut in the medical community to describe the prodromal social withdrawal and isolation observed in schizophrenia.¹ The use of schizoid to describe a personality type first occurred in DSM-III in 1980.² SPD is a Cluster A personality disorder that groups personalities characterized by common traits that are “odd” or “eccentric” and may resemble the positive and/or negative symptoms of schizophrenia.^3,4 Relatively uncommon in clinical settings, SPD includes individuals who do not desire or enjoy close relationships. Those afflicted with SPD will be described as isolated, aloof, and detached from social relationships with others, even immediate family members. Individuals with SPD may appear indifferent to criticism and praise, and may take pleasure in only a few activities. They may exhibit a general absence of affective range, which contributes to their characterization as flat, blunted, or emotionally vacant. SPD is more commonly diagnosed in males and may be present in childhood and adolescence. These children are typified by solitariness, poor peer relationships, and underachievement in school. SPD impacts 3.1% to 4.9% of the United States population and approximately 1% of community populations.^5,6

EVALUATION Persistent depressive symptoms

Ms. P is accompanied by her parents for the examination. She reports a chronic, persistent sad mood, hopelessness, anergia, insomnia, anhedonia, and decreased concentration and appetite. She says she experiences episodes of intense worry, along with tension, restlessness, feelings of being on the edge, irritability, and difficulty relaxing. Socially, she is withdrawn, preferring to stay alone in her room most of the day watching YouTube or trying to write stories. She has 2 friends with whom she does not interact with in person, but rather through digital means. Ms. P has never enjoyed attending school and feels “nervous” when she is around people. She has difficulty expressing her thoughts and often looks to her parents for help. Her parents add that getting Ms. P to attend school was a struggle, which resulted in periods of home schooling throughout high school.

The treating team prescribes citalopram, 10 mg/d, and aripiprazole, 2 mg/d. On subsequent follow-up visits, Ms. P’s depression improves with an increase in citalopram to 40 mg/d. Psychotherapy is added to her treatment plan to help address the persistent social deficits, odd behavior, and anxieties.

Continue to: Evaluation Psychological assessment...

At her psychotherapy intake appointment with the clinical neuropsychologist, Ms. P is dressed in purple from head to toe and sits clutching her purse and looking at the ground. She is overweight with clean, fitting clothing. Ms. P takes a secondary role during most of the interview, allowing her parents to answer most questions. When asked why she is starting therapy, Ms. P replies, “Well, I’ve been using the bathroom a lot.” She describes a feeling of comfort and calmness while in the restroom. Suddenly, she asks her parents to exit the exam room for a moment. Once they leave, she leans in and whispers, “Have you ever heard of self-sabotage? I think that’s what I’m doing.”

Her mood is euthymic, with a blunted affect. She scores 2 on the Patient Health Questionnaire-9 (PHQ-9) and 10 on the Generalized Anxiety Disorder 7-item scale (GAD-7), which indicates the positive impact of medication on her depressive symptoms but continuing moderate anxious distress. She endorses fear of the night, insomnia, and suicidal ideation. She reports an unusual “constant itching sensation,” resulting in hours of repetitive excoriation. Physical examination reveals several significant scars and scabs covering her bilateral upper and lower extremities. Her vocational history is brief; she had held 2 entry-level customer service positions that lasted <1 year. She was fired due to excessive bathroom use.

As the interview progresses, the intake clinician’s background in neuropsychological assessment facilitates screening for possible developmental disorders. Given the nature of the referral and psychotherapy intake, a full neuropsychological assessment is not conducted. The clinician emphasizes verbal abstraction and theory of mind. Ms. P’s IQ was estimated to be average by Wide Range Achievement Test 4 word reading and interview questions about her academic history. Questions are abstracted from the Autism Diagnostic Observation Schedule, Module 4, to assess for conversation ability, emotional insight, awareness and expression, relationships, and areas of functioning in daily living. Developmental history questions, such as those found on the Adaptive Behavior Assessment System, 3rd edition, help guide developmental information provided by parents in the areas of communication, emotion and eye-gaze, gestures, sensory function, language, social functioning, hygiene behavior, and specific interests.

Ms. P’s mother describes a normal pregnancy and delivery; however, she states that Ms. P was “born with problems,” including difficulty with rooting and sucking, and required gastrointestinal intubation until age 3. Cyclical vomiting followed normal food consumption. Ambulation, language acquisition, toilet training, and hygiene behavior were delayed. Ms. P experienced improvements with early intervention in intensive physical and occupational therapy.

Ms. P’s hygiene is well below average, and she requires cueing from her parents. She attended general education until she reached high school, when she began special education. She was sensitive to sensory stimulation from infancy, with sensory sensitivity to textures. Ms. P continues to report sensory sensitivity and lapses in hygiene.

She has difficulty establishing and maintaining relationships with her peers, and prefers solitary activities. Ms. P has no history of romantic relationships, although she does desire one. When asked about her understanding of various relationships, Ms. P’s responses are stereotyped, such as “I know someone is my friend because they are nice to me” and “People get married because they love each other.” She struggles to offer greater insight into the nuances that form lasting relationships and bonds. Ms. P struggles to imitate and describe the physical and internal cues of several basic emotions (eg, fear, joy, anger).

Her conversational and social skills are assessed by asking her to engage in a conversation with the examiner as if meeting for the first time. Her speech is reciprocal, aprosodic, and delayed. The conversation is one-sided, and the examiner fills in several awkward pauses. Ms. P’s gaze at times is intense and prolonged, especially when responding to questions. She tends to use descriptive statements (eg, “I like your purple pen, I like your shirt”) to engage in conversation, rather than gathering more information through reflective statements, questions, or expressing a shared interest.

Ms. P’s verbal abstraction is screened using questions from the Wechsler Adult Intelligence Scale, 4th edition Similarities subtest, to which she provides several responses within normal limits. Her understanding of colloquial speech is assessed by asking her the meaning of common phrases (eg, “Get knocked down 9 times, get up 10,” “Jack and Jill are 2 peas in a pod”). On many occasions, she is able to limit her response to 1 word, (eg, “resiliency”), demonstrating intact ability to decipher idioms.

[polldaddy:11027971]

The authors’ observations

Upon reflection of Ms. P’s clinical presentation and history of developmental delays, social deficits, sensory sensitivity since infancy, and repetitive behaviors (all which continue to impact her), the clinical team concluded that the diagnosis of autism spectrum disorder (ASD) helps explain the patient’s “odd” behaviors, more so than SPD.

ASD is a heterogenous, complex neuropsychiatric disorder characterized by a persistent deficit in social reciprocity, verbal, and nonverbal communication, and includes a pattern of restricted, repetitive and/or stereotyped behaviors and/or interests.⁵ The term “autismus” is Greek meaning “self,” and was first used to classify the qualities of “morbid self-admiration” observed in prodromal schizophrenia.⁷Due to disorganized, odd behaviors and speech, adults with ASD are sometimes misdiagnosed with schizophrenia and schizophrenia-related disorders, such as SPD.⁸ Ms. P is an example of this phenomenon. In a prospective study looking at the continuity of ASD and SPD traits, Cook et al⁹ found that higher severity levels of ASD symptoms in childhood were associated with a higher level of reported SPD traits in adolescence. Although ASD and SPD are usually diagnosed at opposite ends of the age spectrum, they do have characteristics that overlap, such as limited range of affect and tendency to be described as loners. Table 1^5,8,9 highlights some of these similarities.

Continue to: Treatment...

TREATMENT Adding CBT

At an interdisciplinary session several weeks later that includes Ms. P and her parents, the treatment team discusses the revised diagnoses of ASD and MDD, a treatment recommendation for cognitive-behavioral therapy (CBT), and continued use of medication. At this session, Ms. P discloses that she has not been consistent with her medication regimen since her last appointment, which helps explain the increase in her PHQ-9 score from 2 to 14 and GAD-7 score from 10 to 15 as noted at this interdisciplinary session.

[polldaddy:11027990]

The authors’ observations

CBT can be helpful in improving medication adherence, developing coping skills, and modifying maladaptive behaviors.^16,17Table 2^16,17 provides examples of behavioral interventions that CBT can implement. The evidence for the benefits of psychosocial interventions for adults with ASD is growing. A small systemic review of psychosocial interventions for adults with ASD found that social cognition training, social skills training, and applied behavior analysis had positive benefits.¹⁸

OUTCOME Improvement with psychotherapy

Ms. P and family agree with the team’s recommendations. The aims of Ms. P’s psychotherapy are to maintain medication compliance; implement behavioral modification, vocational rehabilitation, and community engagement; develop social skills; increase functional independence; and develop coping skills for depression and anxiety.

Once her medication is augmented with psychotherapy, Ms. P exhibits a steady decline in PHQ-9 and GAD-7 scores, consistent with an overall reduction of subjective anxiety and depression. In 5 months, her PHQ-9 score decreases from 14 to 2 and her GAD-7 score decreases from 15 to 3. Ms. P is treatment-compliant, more active around the home, and spends more time engaging with friends face-to-face. Overall, the psychotherapy interventions most helpful to her are the development of social skills and coping skills. She reports improved mood, energy levels, concentration, interests, and appetite. Suicidal ideation lessens, and she has not engaged in self-harm since beginning treatment. Worries, tension, and difficulty relaxing also have lessened, though restlessness persists. Excoriation has also decreased significantly, and Ms. P spends less time in the bathroom. Sheenrolls in college courses, plans to start a volleyball team, and is excited about the future.

Bottom Line

The prevalence of schizoid personality disorder (SPD) is low, and its symptoms overlap with those of autism spectrum disorder. Therefore, before diagnosing SPD in an adult patient, it is important to obtain a detailed developmental history and include an interdisciplinary team to assess for autism spectrum disorder.

The intramuscular (IM) route is commonly used to administer medication in various clinical settings. Even when an IM medication is administered appropriately, patient factors such as high subcutaneous tissue, greater body mass index, and gender can lower the success rate of injections.¹ A key but infrequently discussed issue is the skill of the individual administering the IM medication. Incorrectly administering an IM medication can lead to complications, such as abscesses, nerve injury, and skeletal muscle fibrosis.² Poor IM injection technique can impact patient care and safety.¹ For example, a poorly administered antipsychotic medication might lead to the patient receiving a subtherapeutic dose, and could prompt a clinician to ask, “Does this agitated patient need more emergent medication because the medication being given is not effective, or because the medication is not being administered properly?”

This article offers 3 questions to ask when clinicians are evaluating how IM medications are being administered in their clinical setting.

1. Who is administering the medication?

Is the person a registered nurse, licensed psychiatric technician, certified nursing assistant, licensed vocational nurse, or medical assistant? What a specific clinician is permitted to do in one state may not be permitted in another state. For example, in the state of Washington, under certain conditions a medical assistant is allowed to administer an IM medication.³

2. What is the individual’s training in administering IM medications?

Has the person been trained in the proper technique, depending on the body location? Is the injection being properly prepared? Is the correct needle gauge being used?

3. What is the individual’s comfort level with administering IM medications?

Is the person comfortable administering medication only when a patient is calm? Or are they comfortable administering medication when a patient is agitated and being physically held or in 4-point restraints, such as in inpatient psychiatric units or emergency departments?

The intramuscular (IM) route is commonly used to administer medication in various clinical settings. Even when an IM medication is administered appropriately, patient factors such as high subcutaneous tissue, greater body mass index, and gender can lower the success rate of injections.¹ A key but infrequently discussed issue is the skill of the individual administering the IM medication. Incorrectly administering an IM medication can lead to complications, such as abscesses, nerve injury, and skeletal muscle fibrosis.² Poor IM injection technique can impact patient care and safety.¹ For example, a poorly administered antipsychotic medication might lead to the patient receiving a subtherapeutic dose, and could prompt a clinician to ask, “Does this agitated patient need more emergent medication because the medication being given is not effective, or because the medication is not being administered properly?”

This article offers 3 questions to ask when clinicians are evaluating how IM medications are being administered in their clinical setting.

1. Who is administering the medication?

Is the person a registered nurse, licensed psychiatric technician, certified nursing assistant, licensed vocational nurse, or medical assistant? What a specific clinician is permitted to do in one state may not be permitted in another state. For example, in the state of Washington, under certain conditions a medical assistant is allowed to administer an IM medication.³

2. What is the individual’s training in administering IM medications?

Has the person been trained in the proper technique, depending on the body location? Is the injection being properly prepared? Is the correct needle gauge being used?

3. What is the individual’s comfort level with administering IM medications?

Is the person comfortable administering medication only when a patient is calm? Or are they comfortable administering medication when a patient is agitated and being physically held or in 4-point restraints, such as in inpatient psychiatric units or emergency departments?

The intramuscular (IM) route is commonly used to administer medication in various clinical settings. Even when an IM medication is administered appropriately, patient factors such as high subcutaneous tissue, greater body mass index, and gender can lower the success rate of injections.¹ A key but infrequently discussed issue is the skill of the individual administering the IM medication. Incorrectly administering an IM medication can lead to complications, such as abscesses, nerve injury, and skeletal muscle fibrosis.² Poor IM injection technique can impact patient care and safety.¹ For example, a poorly administered antipsychotic medication might lead to the patient receiving a subtherapeutic dose, and could prompt a clinician to ask, “Does this agitated patient need more emergent medication because the medication being given is not effective, or because the medication is not being administered properly?”

This article offers 3 questions to ask when clinicians are evaluating how IM medications are being administered in their clinical setting.

1. Who is administering the medication?

Is the person a registered nurse, licensed psychiatric technician, certified nursing assistant, licensed vocational nurse, or medical assistant? What a specific clinician is permitted to do in one state may not be permitted in another state. For example, in the state of Washington, under certain conditions a medical assistant is allowed to administer an IM medication.³

2. What is the individual’s training in administering IM medications?

Has the person been trained in the proper technique, depending on the body location? Is the injection being properly prepared? Is the correct needle gauge being used?

3. What is the individual’s comfort level with administering IM medications?

Is the person comfortable administering medication only when a patient is calm? Or are they comfortable administering medication when a patient is agitated and being physically held or in 4-point restraints, such as in inpatient psychiatric units or emergency departments?

Intermittent fasting is the purposeful, restricted intake of food (and sometimes water), usually for health or religious reasons. Common forms are alternative-day fasting or time-restricted fasting, with variable ratios of days or hours for fasting and eating/drinking.¹ For example, fasting during Ramadan, the ninth month of the Islamic calendar, occurs from dawn to sunset, for a variable duration due to latitude and seasonal shifts.² Clinicians are likely to care for a patient who occasionally fasts. While there are potential benefits of fasting, clinicians need to consider the implications for patients who fast, particularly those receiving psychotropic medications.

Potential benefits for weight loss, mood

Some research suggests fasting is popular and may have benefits for an individual’s physical and mental health. In a 2020 online poll (N = 1,241), 24% of respondents said they had tried intermittent fasting, and 87% said the practice was very effective (50%) or somewhat effective (37%) in helping them lose weight.³ While more randomized control trials are needed to examine the practice’s effectiveness in promoting and maintaining weight loss, fasting has been linked to better glucose control in both humans and animals, and patients may have better adherence with fasting compared to caloric restriction alone.¹ Improved mood, alertness, tranquility, and sometimes euphoria have been documented among individuals who fast, but these benefits may not be sustained.⁴ A prospective study of 462 participants who fasted during Ramadan found the practice reduced depression in patients with diabetes, possibly due to mindfulness, decreased inflammation from improved insulin sensitivity, and/or social cohesion.⁵

Be aware of the potential risks

Fasting may either improve or destabilize mood in people with bipolar disorder by disrupting circadian rhythm and sleep.² Fasting might exacerbate underlying eating disorders.² Increased dehydration escalates the risk for orthostatic hypotension, which might require discontinuing clozapine.⁶ Hypotension and toxicity might arise during lithium pharmacotherapy. The Table⁴ summarizes things to consider when caring for a patient who fasts while receiving pharmacotherapy.

Provide patients with guidance

Advise patients not to fast if you believe it might exacerbate their mental illness, and encourage them to discuss with their primary care physicians any potential worsening of physical illnesses.² When caring for a patient who fasts for religious reasons, consider consulting with the patient’s religious leaders.² If patients choose to fast, monitor them for mood destabilization and/or medication adverse effects. If possible, avoid altering drug treatment regimens during fasting, and carefully monitor whenever a pharmaceutical change is necessary. When appropriate, the use of long-acting injectable medications may minimize adverse effects while maintaining mood stability. Encourage patients who fast to ensure they remain hydrated and practice sleep hygiene while they fast.⁷

Intermittent fasting is the purposeful, restricted intake of food (and sometimes water), usually for health or religious reasons. Common forms are alternative-day fasting or time-restricted fasting, with variable ratios of days or hours for fasting and eating/drinking.¹ For example, fasting during Ramadan, the ninth month of the Islamic calendar, occurs from dawn to sunset, for a variable duration due to latitude and seasonal shifts.² Clinicians are likely to care for a patient who occasionally fasts. While there are potential benefits of fasting, clinicians need to consider the implications for patients who fast, particularly those receiving psychotropic medications.

Potential benefits for weight loss, mood

Some research suggests fasting is popular and may have benefits for an individual’s physical and mental health. In a 2020 online poll (N = 1,241), 24% of respondents said they had tried intermittent fasting, and 87% said the practice was very effective (50%) or somewhat effective (37%) in helping them lose weight.³ While more randomized control trials are needed to examine the practice’s effectiveness in promoting and maintaining weight loss, fasting has been linked to better glucose control in both humans and animals, and patients may have better adherence with fasting compared to caloric restriction alone.¹ Improved mood, alertness, tranquility, and sometimes euphoria have been documented among individuals who fast, but these benefits may not be sustained.⁴ A prospective study of 462 participants who fasted during Ramadan found the practice reduced depression in patients with diabetes, possibly due to mindfulness, decreased inflammation from improved insulin sensitivity, and/or social cohesion.⁵

Be aware of the potential risks

Fasting may either improve or destabilize mood in people with bipolar disorder by disrupting circadian rhythm and sleep.² Fasting might exacerbate underlying eating disorders.² Increased dehydration escalates the risk for orthostatic hypotension, which might require discontinuing clozapine.⁶ Hypotension and toxicity might arise during lithium pharmacotherapy. The Table⁴ summarizes things to consider when caring for a patient who fasts while receiving pharmacotherapy.

Provide patients with guidance

Advise patients not to fast if you believe it might exacerbate their mental illness, and encourage them to discuss with their primary care physicians any potential worsening of physical illnesses.² When caring for a patient who fasts for religious reasons, consider consulting with the patient’s religious leaders.² If patients choose to fast, monitor them for mood destabilization and/or medication adverse effects. If possible, avoid altering drug treatment regimens during fasting, and carefully monitor whenever a pharmaceutical change is necessary. When appropriate, the use of long-acting injectable medications may minimize adverse effects while maintaining mood stability. Encourage patients who fast to ensure they remain hydrated and practice sleep hygiene while they fast.⁷

Intermittent fasting is the purposeful, restricted intake of food (and sometimes water), usually for health or religious reasons. Common forms are alternative-day fasting or time-restricted fasting, with variable ratios of days or hours for fasting and eating/drinking.¹ For example, fasting during Ramadan, the ninth month of the Islamic calendar, occurs from dawn to sunset, for a variable duration due to latitude and seasonal shifts.² Clinicians are likely to care for a patient who occasionally fasts. While there are potential benefits of fasting, clinicians need to consider the implications for patients who fast, particularly those receiving psychotropic medications.

Potential benefits for weight loss, mood

Some research suggests fasting is popular and may have benefits for an individual’s physical and mental health. In a 2020 online poll (N = 1,241), 24% of respondents said they had tried intermittent fasting, and 87% said the practice was very effective (50%) or somewhat effective (37%) in helping them lose weight.³ While more randomized control trials are needed to examine the practice’s effectiveness in promoting and maintaining weight loss, fasting has been linked to better glucose control in both humans and animals, and patients may have better adherence with fasting compared to caloric restriction alone.¹ Improved mood, alertness, tranquility, and sometimes euphoria have been documented among individuals who fast, but these benefits may not be sustained.⁴ A prospective study of 462 participants who fasted during Ramadan found the practice reduced depression in patients with diabetes, possibly due to mindfulness, decreased inflammation from improved insulin sensitivity, and/or social cohesion.⁵

Be aware of the potential risks

Fasting may either improve or destabilize mood in people with bipolar disorder by disrupting circadian rhythm and sleep.² Fasting might exacerbate underlying eating disorders.² Increased dehydration escalates the risk for orthostatic hypotension, which might require discontinuing clozapine.⁶ Hypotension and toxicity might arise during lithium pharmacotherapy. The Table⁴ summarizes things to consider when caring for a patient who fasts while receiving pharmacotherapy.

Provide patients with guidance

Advise patients not to fast if you believe it might exacerbate their mental illness, and encourage them to discuss with their primary care physicians any potential worsening of physical illnesses.² When caring for a patient who fasts for religious reasons, consider consulting with the patient’s religious leaders.² If patients choose to fast, monitor them for mood destabilization and/or medication adverse effects. If possible, avoid altering drug treatment regimens during fasting, and carefully monitor whenever a pharmaceutical change is necessary. When appropriate, the use of long-acting injectable medications may minimize adverse effects while maintaining mood stability. Encourage patients who fast to ensure they remain hydrated and practice sleep hygiene while they fast.⁷

As Rheumatology News celebrates 20 years of publication in 2022, we’ll be taking a look back at rheumatology’s past and ahead to its future throughout the year. This time around, we’ll examine the first issue of Rheumatology News, which was published in February 2002. You can read the first-ever issue at the "PDF Download" link above.

In that premiere issue, information about early treatment of rheumatoid arthritis with tumor necrosis factor inhibitors and other disease-modifying antirheumatic drugs (DMARDs) featured prominently. A front-page story described new findings showing that early treatment of RA with DMARDs could reduce disease-related disability by one-third or more. A second article described quantitative improvement in MRI-detected synovitis in patients with early RA who were treated with infliximab for 14 weeks, while another reported on clinically relevant responses seen in 66% of patients treated with adalimumab plus methotrexate in a trial of patients with an inadequate response to methotrexate alone.

In other RA news, a report focused on low rates of preventive health care services and screening for other disorders in women, including Pap smears, mammograms, and influenza vaccinations. Another story suggested the possibility that methotrexate may elevate cancer risk in patients with RA. An analysis of two separate prospective studies indicated that women who regularly drink decaffeinated coffee may be at higher risk for developing RA.

Another page 1 story examined the potential of new drugs bosentan and epoprostenol for treating pulmonary arterial hypertension associated with various forms of connective tissue disease.

Etanercept was the focus of two articles, one announcing its approval for psoriatic arthritis, and another describing a small trial of the biologic in treating moderate to severe ankylosing spondylitis.

In osteoarthritis news, a front-page report described two placebo-controlled studies of oral glucosamine sulfate supplementation that suggested the formulation might slow the progression of joint space narrowing in postmenopausal women, and another article noted how a combined formulation of tramadol and acetaminophen reduced OA pain flares.

Readers were also treated to a pro and con editorial debate between Frederick Wolfe, MD, and Thomas J. Romano, MD, on whether trauma causes fibromyalgia.

Looking ahead

Throughout 2022, look for articles examining the past and future of rheumatology, including:

• The rise of women in the field;
• the rise of biologic and targeted synthetic disease-modifying antirheumatic drugs;
• the history and ongoing influence of OMERACT (Outcome Measures in Rheumatology);
• the growth and future of ACR-EULAR collaborations;
• progress and future directions of pediatric rheumatology; and
• the growth in understanding how sociodemographics and racial/ethnic identity affect access to and acceptance and receipt of rheumatologic care.

Are there any topics you think would be valuable to cover in light of Rheumatology News’ 20th anniversary? The editorial staff welcomes your suggestions. Please share them by emailing us at [email protected].

As Rheumatology News celebrates 20 years of publication in 2022, we’ll be taking a look back at rheumatology’s past and ahead to its future throughout the year. This time around, we’ll examine the first issue of Rheumatology News, which was published in February 2002. You can read the first-ever issue at the "PDF Download" link above.

In that premiere issue, information about early treatment of rheumatoid arthritis with tumor necrosis factor inhibitors and other disease-modifying antirheumatic drugs (DMARDs) featured prominently. A front-page story described new findings showing that early treatment of RA with DMARDs could reduce disease-related disability by one-third or more. A second article described quantitative improvement in MRI-detected synovitis in patients with early RA who were treated with infliximab for 14 weeks, while another reported on clinically relevant responses seen in 66% of patients treated with adalimumab plus methotrexate in a trial of patients with an inadequate response to methotrexate alone.

In other RA news, a report focused on low rates of preventive health care services and screening for other disorders in women, including Pap smears, mammograms, and influenza vaccinations. Another story suggested the possibility that methotrexate may elevate cancer risk in patients with RA. An analysis of two separate prospective studies indicated that women who regularly drink decaffeinated coffee may be at higher risk for developing RA.

Another page 1 story examined the potential of new drugs bosentan and epoprostenol for treating pulmonary arterial hypertension associated with various forms of connective tissue disease.

Etanercept was the focus of two articles, one announcing its approval for psoriatic arthritis, and another describing a small trial of the biologic in treating moderate to severe ankylosing spondylitis.

In osteoarthritis news, a front-page report described two placebo-controlled studies of oral glucosamine sulfate supplementation that suggested the formulation might slow the progression of joint space narrowing in postmenopausal women, and another article noted how a combined formulation of tramadol and acetaminophen reduced OA pain flares.

Readers were also treated to a pro and con editorial debate between Frederick Wolfe, MD, and Thomas J. Romano, MD, on whether trauma causes fibromyalgia.

Looking ahead

Throughout 2022, look for articles examining the past and future of rheumatology, including:

• The rise of women in the field;
• the rise of biologic and targeted synthetic disease-modifying antirheumatic drugs;
• the history and ongoing influence of OMERACT (Outcome Measures in Rheumatology);
• the growth and future of ACR-EULAR collaborations;
• progress and future directions of pediatric rheumatology; and
• the growth in understanding how sociodemographics and racial/ethnic identity affect access to and acceptance and receipt of rheumatologic care.

Are there any topics you think would be valuable to cover in light of Rheumatology News’ 20th anniversary? The editorial staff welcomes your suggestions. Please share them by emailing us at [email protected].

As Rheumatology News celebrates 20 years of publication in 2022, we’ll be taking a look back at rheumatology’s past and ahead to its future throughout the year. This time around, we’ll examine the first issue of Rheumatology News, which was published in February 2002. You can read the first-ever issue at the "PDF Download" link above.

In that premiere issue, information about early treatment of rheumatoid arthritis with tumor necrosis factor inhibitors and other disease-modifying antirheumatic drugs (DMARDs) featured prominently. A front-page story described new findings showing that early treatment of RA with DMARDs could reduce disease-related disability by one-third or more. A second article described quantitative improvement in MRI-detected synovitis in patients with early RA who were treated with infliximab for 14 weeks, while another reported on clinically relevant responses seen in 66% of patients treated with adalimumab plus methotrexate in a trial of patients with an inadequate response to methotrexate alone.

In other RA news, a report focused on low rates of preventive health care services and screening for other disorders in women, including Pap smears, mammograms, and influenza vaccinations. Another story suggested the possibility that methotrexate may elevate cancer risk in patients with RA. An analysis of two separate prospective studies indicated that women who regularly drink decaffeinated coffee may be at higher risk for developing RA.

Another page 1 story examined the potential of new drugs bosentan and epoprostenol for treating pulmonary arterial hypertension associated with various forms of connective tissue disease.

Etanercept was the focus of two articles, one announcing its approval for psoriatic arthritis, and another describing a small trial of the biologic in treating moderate to severe ankylosing spondylitis.

In osteoarthritis news, a front-page report described two placebo-controlled studies of oral glucosamine sulfate supplementation that suggested the formulation might slow the progression of joint space narrowing in postmenopausal women, and another article noted how a combined formulation of tramadol and acetaminophen reduced OA pain flares.

Readers were also treated to a pro and con editorial debate between Frederick Wolfe, MD, and Thomas J. Romano, MD, on whether trauma causes fibromyalgia.

Looking ahead

Throughout 2022, look for articles examining the past and future of rheumatology, including:

• The rise of women in the field;
• the rise of biologic and targeted synthetic disease-modifying antirheumatic drugs;
• the history and ongoing influence of OMERACT (Outcome Measures in Rheumatology);
• the growth and future of ACR-EULAR collaborations;
• progress and future directions of pediatric rheumatology; and
• the growth in understanding how sociodemographics and racial/ethnic identity affect access to and acceptance and receipt of rheumatologic care.

Are there any topics you think would be valuable to cover in light of Rheumatology News’ 20th anniversary? The editorial staff welcomes your suggestions. Please share them by emailing us at [email protected].

Inflammatory bowel disease (IBD) incidence is rising globally.^1-3 In the United States, we have seen a 123% increase in prevalence of IBD among adults and a 133% increase among children from 2007 to 2016, with an annual percentage change of 9.9%.¹ The rise of IBD in young people, and the overall higher prevalence in women compared with men, make pregnancy and IBD a topic of increasing importance for gastroenterologists.¹ Here, we will discuss management and expectations in women with IBD before conception, during pregnancy, and post partum.

Preconception

Disease activity
 

Achieving both clinical and endoscopic remission of disease prior to conception is the key to ensuring the best maternal and fetal outcomes. Patients with IBD who conceive while in remission remain in remission 80% of the time.^4,5 On the other hand, those who conceive while their disease is active may continue to have active or worsening disease in nearly 70% of cases.⁴ Active disease has been associated with an increased incidence of preterm birth, low birth weight, and small-for-gestational-age birth.^6-8 Active disease can also exacerbate malnutrition and result in poor maternal weight gain, which is associated with intrauterine growth restriction.^9,7 Pregnancy outcomes in patients with IBD and quiescent disease are similar to those in the general population.^10,11

Health care maintenance

Optimizing maternal health prior to conception is critical. Alcohol, tobacco, recreational drugs, and marijuana should all be avoided. Opioids should be tapered off prior to conception, as continued use may result in neonatal opioid withdrawal syndrome and long-term neurodevelopmental consequences.^12,13 In addition, aiming for a healthy body mass index between 18 and 25 months prior to conception allows for better overall pregnancy outcomes.¹³ Appropriate cancer screening includes colon cancer screening in those with more than 8 years of colitis, regular pap smear for cervical cancer, and annual total body skin cancer examinations for patients on thiopurines and biologic therapies.¹⁴

UCSF

Nutrition

Folic acid supplementation with at least 400 micrograms (mcg) daily is necessary for all women planning pregnancy. Patients with small bowel involvement or history of small bowel resection should have a folate intake of a minimum of 2 grams per day. Adequate vitamin D levels (at least 20 ng/mL) are recommended in all women with IBD. Those with malabsorption should be screened for deficiencies in vitamin B12, folate, and iron.¹³ These nutritional markers should be evaluated prepregnancy, during the first trimester, and thereafter as needed.^15-18

Preconception counseling

Steroid-free remission for at least 3 months prior to conception is recommended and is associated with reduced risk of flare during pregnancy.^16,19 IBD medications needed to control disease activity are generally safe preconception and during pregnancy, with some exception (Table).

Pregnancy

Coordinated care

A complete team of specialists with coordinated care among all providers is needed for optimal maternal and fetal outcomes.^23,24 A gastroenterologist, ideally an IBD specialist, should follow the patient throughout pregnancy, seeing the patient at least once during the first or second trimester and as needed during pregnancy.¹⁶ A high-risk obstetrician or maternal-fetal medicine specialist should be involved early in pregnancy, as well. Open communication among all disciplines ensures that a common message is conveyed to the patient.^16,24 A nutritionist, mental health provider, and lactation specialist knowledgeable about IBD drugs may be of assistance, as well.¹⁶

Disease activity

While women with IBD are at increased risk of spontaneous abortion, preterm birth, and labor complications, this risk is mitigated by controlling disease activity.²⁵ The risk of preterm birth, small-for-gestational-age birth, and delivery via C-section is much higher in women with moderate-to-high disease activity, compared with those with low disease activity.²⁶ The presence of active perianal disease mandates C-section over vaginal delivery. Fourth-degree lacerations following vaginal delivery are most common among those patients with perianal disease.^26,27 Stillbirths were shown to be increased only in those with active IBD when compared with non-IBD comparators and inactive IBD.^28-31;11

Noninvasive methods for disease monitoring are preferred in pregnancy, but serum markers such as erythrocyte sedimentation rate and C-reactive protein may not be reliable in the pregnant patient (Figure).³² Fecal calprotectin does rise in correlation with disease activity, but exact thresholds have not been validated in pregnancy.^33,34

Medication use and safety

IBD medications are a priority topic of concern among pregnant patients or those considering conception.³⁸ Comprehensive data from the PIANO (Pregnancy in Inflammatory Bowel Disease and Neonatal Outcomes) registry has shown that most IBD drugs do not result in adverse pregnancy outcomes and should be continued.³⁹ The use of biologics and thiopurines, either in combination or alone, is not related to an increased risk of congenital malformations, spontaneous abortion, preterm birth, low birth weight, or infections during the child’s first year of life.^7,39 Developmental milestones also remain unaffected.³⁹ Here, we will discuss safety considerations during pregnancy (see Table).

5-aminosalycylic acid. 5-aminosalicylic acid (5-ASA) agents are generally low risk during pregnancy and should be continued.^40-41 Sulfasalazine does interfere with folate metabolism, but by increasing folic acid supplementation to 2 grams per day, sulfasalazine can be continued throughout pregnancy, as well.⁴²



Corticosteroids. Intrapartum corticosteroid use is associated with an increased risk of gestational diabetes and adrenal insufficiency when used long term.^43-45 Short-term use may, however, be necessary to control an acute flare. The lowest dose for the shortest duration possible is recommended. Because of its high first-pass metabolism, budesonide is considered low risk in pregnancy.



Methotrexate. Methotrexate needs to be stopped at least 3 months prior to conception and should be avoided throughout pregnancy. Use during pregnancy can result in spontaneous abortions, as well as embryotoxicity.⁴⁶



Thiopurines (6-mercaptopurine and azathioprine). Patients who are taking thiopurines prior to conception to maintain remission can continue to do so. Data on thiopurines from the PIANO registry has shown no increase in spontaneous abortions, congenital malformations, low birth weight, preterm birth, rates of infection in the child, or developmental delays.^47-51



Calcineurin inhibitors (cyclosporine and tacrolimus). Calcineurin inhibitors are reserved for the management of acute severe UC. Safety data on calcineurin inhibitors is conflicting, and there is not enough information at this time to identify risk during pregnancy. Cyclosporine can be used for salvage therapy if absolutely needed, and there are case reports of its successful using during pregnancy.^16,52



Biologic therapies. With the exception of certolizumab, all of the currently used biologics are actively transported across the placenta.^39,53,54 Intrapartum use of biologic therapies does not worsen pregnancy or neonatal outcomes, including the risk for intensive care unit admission, infections, and developmental milestones.^39,47

While drug concentrations may vary slightly during pregnancy, these changes are not substantial enough to warrant more frequent monitoring or dose adjustments, and prepregnancy weight should be used for dosing.^55,56

Antitumor necrosis factor agents used in IBD include infliximab, adalimumab, certolizumab, and golimumab.⁵⁷ All are low risk for pregnant patients and their offspring. Dosage timings can be adjusted, but not stopped, to minimize exposure to the child; however, it cannot be adjusted for certolizumab pegol because of its lack of placental transfer.^58-59

Natalizumab and vedolizumab are integrin receptor antagonists and are also low risk in pregnancy.^57;60-62;39

Ustekinumab, an interleukin-12/23 antagonist, can be found in infant serum and cord blood, as well. Health outcomes are similar in the exposed mother and child, however, compared with those of the general population.^39;63-64



Small molecule drugs. Unlike monoclonal antibodies, which do not cross the placenta in large amounts until early in the second trimester, small molecules can cross in the first trimester during the critical period of organogenesis.

The two small molecule agents currently approved for use in UC are tofacitinib, a janus kinase inhibitor, and ozanimod, a sphingosine-1-phosphate receptor agonist.^65-66 Further data are still needed to make recommendations on the use of tofacitinib and ozanimod in pregnancy. At this time, we recommend weighing the risks (unknown risk to human pregnancy) vs. benefits (controlled disease activity with clear risk of harm to mother and baby from flare) in the individual patient before counseling on use in pregnancy.
 

Delivery

Mode of delivery

The mode of delivery should be determined by the obstetrician. C-section is recommended for patients with active perianal disease or, in some cases, a history of ileal pouch anal anastomosis (IPAA).^67-68 Vaginal delivery in the setting of perianal disease has been shown to increase the risk of fourth-degree laceration and anal sphincter dysfunction in the future.^26-27 Anorectal motility may be impacted by IPAA construction and vaginal delivery independently of each other. It is therefore suggested that vaginal delivery be avoided in patients with a history of IPAA to avoid compounding the risk. Some studies do not show clear harm from vaginal delivery in the setting of IPAA, however, and informed decision making among all stakeholders should be had.^27;69-70

Anticoagulation

The incidence of venous thromboembolism (VTE) is elevated in patients with IBD during pregnancy, and up to 12 weeks postpartum, compared with pregnant patients without IBD.^71-72 VTE for prophylaxis is indicated in the pregnant patient while hospitalized and potentially thereafter depending on the patient’s risk factors, which may include obesity, prior personal history of VTE, heart failure, and prolonged immobility. Unfractionated heparin, low molecular weight heparin, and warfarin are safe for breastfeeding women.^16,73

Postpartum care of mother

There is a risk of postpartum flare, occurring in about one third of patients in the first 6 months postpartum.^74-75 De-escalating therapy during delivery or immediately postpartum is a predictor of a postpartum flare.⁷⁵ If no infection is present and the timing interval is appropriate, biologic therapies should be continued and can be resumed 24 hours after a vaginal delivery and 48 hours after a C-section.^16,76

NSAIDs and opioids can be used for pain relief but should be avoided in the long-term to prevent flares (NSAIDs) and infant sedation (associated with opioids) when used while breastfeeding.⁷⁷ The LactMed database is an excellent resource for clarification on risk of medication use while breastfeeding.⁷⁸

In particular, contraception should be addressed postpartum. Exogenous estrogen use increases the risk of VTE, which is already increased in IBD; nonestrogen containing, long-acting reversible contraception is preferred.^79-80 Progestin-only implants or intrauterine devices may be used first line. The efficacy of oral contraceptives is theoretically reduced in those with rapid bowel transit, active small bowel inflammation, and prior small bowel resection, so adding another form of contraception is recommended.^16,81

Source: American Gastroenterological Association

Postdelivery care of baby

Breastfeeding

Guidelines regarding medication use during breastfeeding are similar to those in pregnancy (see Table). Breastfeeding on biologics and thiopurines can continue without interruption in the child. Thiopurine concentrations in breast milk are low or undetectable.^82,78 TNF receptor antagonists, anti-integrin therapies, and ustekinumab are found in low to undetectable levels in breast milk, as well.⁷⁸

On the other hand, the active metabolite of methotrexate is detectable in breast milk and most sources recommend not breastfeeding on methotrexate. At doses used in IBD (15-25 milligrams per week), some experts have suggested avoiding breastfeeding for 24 hours following a dose.^57,78 It is the practice of this author to recommend not breastfeeding at all on methotrexate.

5-ASA therapies are low risk for breastfeeding, but alternatives to sulfasalazine are preferred. The sulfapyridine metabolite transfers to breast milk and may cause hemolysis in infants born with a glucose-6-phosphate dehydrogenase deficiency.⁷⁸

With regards to calcineurin inhibitors, tacrolimus appears in breast milk in low quantities, while cyclosporine levels are variable. Data from the National Transplantation Pregnancy Registry suggest that these medications can be used at the time of breastfeeding with close monitoring.⁷⁸

There is not enough data on small molecule therapies at this time to support breastfeeding safety, and it is our practice to not recommend breastfeeding in this scenario.

The transfer of steroids to the child via breast milk does occur but at subtherapeutic levels.¹⁶ Budesonide has high first pass metabolism and is low risk during breastfeeding.^83-84 As far as is known, IBD maintenance medications do not suppress lactation. The use of intravenous corticosteroids can, however, temporarily decrease milk production.^16,85
 

Vaccines

Vaccination of infants can proceed as indicated by the Center for Disease Control and Prevention guidelines, with one exception. If the child’s mother was exposed to any biologic agents (not including certolizumab) during the third trimester, any live vaccines should be withheld in the first 6 months of life. In the United States, this restriction currently only applies to the rotavirus vaccine, which is administered starting at the age of 2 months.^16,86 Notably, inadvertent administration of the rotavirus vaccine in the biologic-exposed child does not appear to result in any adverse effects.⁸⁷ Immunity is achieved even if the child is exposed to IBD therapies through breast milk.⁸⁸

Developmental milestones

Infant exposure to biologics and thiopurines has not been shown to result in any developmental delays. The PIANO study measured developmental milestones at 48 months from birth and found no differences when compared with validated population norms.³⁹ A separate study observing childhood development up to 7 years of age in patients born to mothers with IBD found similar cognitive scores and motor development when compared with those born to mothers without IBD.⁸⁹

Conclusion

Women considering conception should be optimized prior to pregnancy and maintained on appropriate medications throughout pregnancy and lactation to achieve a healthy pregnancy for both mother and baby. To date, biologics and thiopurines are not associated with adverse pregnancy outcomes. More data are needed for small molecules.

Dr. Chugh is an advanced inflammatory bowel disease fellow in the division of gastroenterology at the University of California San Francisco. Dr. Mahadevan is professor of medicine and codirector at the Center for Colitis and Crohn’s Disease in the division of gastroenterology at the University of California San Francisco. Dr. Mahadevan has potential conflicts related to AbbVie, Janssen, BMS, Takeda, Pfizer, Lilly, Gilead, Arena, and Prometheus Biosciences.

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10. Lee HH et al. Aliment Pharmacol Ther. 2020;51:861-9.

11. Kim MA et al. J Crohns Colitis. 2021;15:719-32.

12. Conradt E et al. Pediatrics. 2019;144.

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14. Farraye FA et al. Am J Gastroenterol. 2017;112:241-58.

15. Lee S et al. J Crohns Colitis. 2018;12:702-9.

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20. Annese V. Pharmacol Res. 2020;159:104892.

21. Bennett RA et al. Gastroenterology. 1991;100:1638-43.

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23. de Lima A et al. Clin Gastroenterol Hepatol. 2016;14:1285-92 e1.

24. Selinger C et al. Frontline Gastroenterol. 2021;12:182-7.

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27. Foulon A et al. Inflamm Bowel Dis. 2017;23:712-20.

28. Norgard B et al. Am J Gastroenterol. 2007;102:1947-54.

29. Broms G et al. Scand J Gastroenterol 2016;51:1462-9.

30. Meyer A et al. Aliment Pharmacol Ther. 2020;52:1480-90.

31. Kammerlander H et al. Inflamm Bowel Dis. 2017;23:1011-8.

32. Tandon P et al. J Clin Gastroenterol. 2019;53:574-81.

33. Kammerlander H et al. Inflamm Bowel Dis. 2018;24:839-48.

34. Julsgaard M et al. Inflamm Bowel Dis. 2017;23:1240-6.

35. Ko MS et al. Dig Dis Sci. 2020;65:2979-85.

36. Cappell MS et al. J Reprod Med. 2010;55:115-23.

37. Committee ASoP et al. Gastrointest Endosc. 2012;76:18-24.

38. Aboubakr A et al. Dig Dis Sci. 2021;66:1829-35.

39. Mahadevan U et al. Gastroenterology. 2021;160:1131-9.

40. Diav-Citrin O et al. Gastroenterology. 1998;114:23-8.

41. Rahimi R et al. Reprod Toxicol. 2008;25:271-5.

42. Norgard B et al. Aliment Pharmacol Ther. 2001;15:483-6.

43. Leung YP et al. J Crohns Colitis. 2015;9:223-30.

44. Schulze H et al. Aliment Pharmacol Ther. 2014;40:991-1008.

45. Szymanska E et al. J Gynecol Obstet Hum Reprod. 2021;50:101777.

46. Weber-Schoendorfer C et al. Arthritis Rheumatol. 2014;66:1101-10.

47. Nielsen OH et al. Clin Gastroenterol Hepatol. 2022 Jan;20(1):74-87.e3.

48. Coelho J et al. Gut. 2011;60:198-203.

49. Sheikh M et al. J Crohns Colitis. 2015;9:680-4.

50. Kanis SL et al. Clin Gastroenterol Hepatol. 2017;15:1232-41 e1.

51. Mahadevan U et al. Inflamm Bowel Dis. 2018;24:2494-500.

52. Rosen MH et al. Inflamm Bowel Dis. 2020;26:971-3.

53. Porter C et al. J Reprod Immunol. 2016;116:7-12.

54. Mahadevan U et al. Clin Gastroenterol Hepatol. 2013;11:286-92; quiz e24.

55. Picardo S and Seow CH. Best Pract Res Clin Gastroenterol. 2020;44-5:101670.

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57. Singh S et al. Gastroenterology. 2021;160:2512-56 e9.

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64. Matro R et al. Gastroenterology. 2018;155:696-704.

65. Feuerstein JD et al. Gastroenterology. 2020;158:1450-61.

66. Sandborn WJ et al. J Crohns Colitis. 2021 Jul 5;15(7):1120-1129.

67. Lamb CA et al. Gut. 2019;68:s1-s106.

68. Nguyen GC et al. Gastroenterology. 2016;150:734-57 e1.

69. Ravid A et al. Dis Colon Rectum. 2002;45:1283-8.

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72. Hansen AT et al. J Thromb Haemost. 2017;15:702-8.

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89. Friedman S et al. J Crohns Colitis. 2020 Dec 2;14(12):1709-1716.

Inflammatory bowel disease (IBD) incidence is rising globally.^1-3 In the United States, we have seen a 123% increase in prevalence of IBD among adults and a 133% increase among children from 2007 to 2016, with an annual percentage change of 9.9%.¹ The rise of IBD in young people, and the overall higher prevalence in women compared with men, make pregnancy and IBD a topic of increasing importance for gastroenterologists.¹ Here, we will discuss management and expectations in women with IBD before conception, during pregnancy, and post partum.

Preconception

Disease activity
 

Achieving both clinical and endoscopic remission of disease prior to conception is the key to ensuring the best maternal and fetal outcomes. Patients with IBD who conceive while in remission remain in remission 80% of the time.^4,5 On the other hand, those who conceive while their disease is active may continue to have active or worsening disease in nearly 70% of cases.⁴ Active disease has been associated with an increased incidence of preterm birth, low birth weight, and small-for-gestational-age birth.^6-8 Active disease can also exacerbate malnutrition and result in poor maternal weight gain, which is associated with intrauterine growth restriction.^9,7 Pregnancy outcomes in patients with IBD and quiescent disease are similar to those in the general population.^10,11

Health care maintenance

Optimizing maternal health prior to conception is critical. Alcohol, tobacco, recreational drugs, and marijuana should all be avoided. Opioids should be tapered off prior to conception, as continued use may result in neonatal opioid withdrawal syndrome and long-term neurodevelopmental consequences.^12,13 In addition, aiming for a healthy body mass index between 18 and 25 months prior to conception allows for better overall pregnancy outcomes.¹³ Appropriate cancer screening includes colon cancer screening in those with more than 8 years of colitis, regular pap smear for cervical cancer, and annual total body skin cancer examinations for patients on thiopurines and biologic therapies.¹⁴

UCSF

Nutrition

Folic acid supplementation with at least 400 micrograms (mcg) daily is necessary for all women planning pregnancy. Patients with small bowel involvement or history of small bowel resection should have a folate intake of a minimum of 2 grams per day. Adequate vitamin D levels (at least 20 ng/mL) are recommended in all women with IBD. Those with malabsorption should be screened for deficiencies in vitamin B12, folate, and iron.¹³ These nutritional markers should be evaluated prepregnancy, during the first trimester, and thereafter as needed.^15-18

Preconception counseling

Steroid-free remission for at least 3 months prior to conception is recommended and is associated with reduced risk of flare during pregnancy.^16,19 IBD medications needed to control disease activity are generally safe preconception and during pregnancy, with some exception (Table).

Pregnancy

Coordinated care

A complete team of specialists with coordinated care among all providers is needed for optimal maternal and fetal outcomes.^23,24 A gastroenterologist, ideally an IBD specialist, should follow the patient throughout pregnancy, seeing the patient at least once during the first or second trimester and as needed during pregnancy.¹⁶ A high-risk obstetrician or maternal-fetal medicine specialist should be involved early in pregnancy, as well. Open communication among all disciplines ensures that a common message is conveyed to the patient.^16,24 A nutritionist, mental health provider, and lactation specialist knowledgeable about IBD drugs may be of assistance, as well.¹⁶

Disease activity

While women with IBD are at increased risk of spontaneous abortion, preterm birth, and labor complications, this risk is mitigated by controlling disease activity.²⁵ The risk of preterm birth, small-for-gestational-age birth, and delivery via C-section is much higher in women with moderate-to-high disease activity, compared with those with low disease activity.²⁶ The presence of active perianal disease mandates C-section over vaginal delivery. Fourth-degree lacerations following vaginal delivery are most common among those patients with perianal disease.^26,27 Stillbirths were shown to be increased only in those with active IBD when compared with non-IBD comparators and inactive IBD.^28-31;11

Noninvasive methods for disease monitoring are preferred in pregnancy, but serum markers such as erythrocyte sedimentation rate and C-reactive protein may not be reliable in the pregnant patient (Figure).³² Fecal calprotectin does rise in correlation with disease activity, but exact thresholds have not been validated in pregnancy.^33,34

Medication use and safety

IBD medications are a priority topic of concern among pregnant patients or those considering conception.³⁸ Comprehensive data from the PIANO (Pregnancy in Inflammatory Bowel Disease and Neonatal Outcomes) registry has shown that most IBD drugs do not result in adverse pregnancy outcomes and should be continued.³⁹ The use of biologics and thiopurines, either in combination or alone, is not related to an increased risk of congenital malformations, spontaneous abortion, preterm birth, low birth weight, or infections during the child’s first year of life.^7,39 Developmental milestones also remain unaffected.³⁹ Here, we will discuss safety considerations during pregnancy (see Table).

5-aminosalycylic acid. 5-aminosalicylic acid (5-ASA) agents are generally low risk during pregnancy and should be continued.^40-41 Sulfasalazine does interfere with folate metabolism, but by increasing folic acid supplementation to 2 grams per day, sulfasalazine can be continued throughout pregnancy, as well.⁴²



Corticosteroids. Intrapartum corticosteroid use is associated with an increased risk of gestational diabetes and adrenal insufficiency when used long term.^43-45 Short-term use may, however, be necessary to control an acute flare. The lowest dose for the shortest duration possible is recommended. Because of its high first-pass metabolism, budesonide is considered low risk in pregnancy.



Methotrexate. Methotrexate needs to be stopped at least 3 months prior to conception and should be avoided throughout pregnancy. Use during pregnancy can result in spontaneous abortions, as well as embryotoxicity.⁴⁶



Thiopurines (6-mercaptopurine and azathioprine). Patients who are taking thiopurines prior to conception to maintain remission can continue to do so. Data on thiopurines from the PIANO registry has shown no increase in spontaneous abortions, congenital malformations, low birth weight, preterm birth, rates of infection in the child, or developmental delays.^47-51



Calcineurin inhibitors (cyclosporine and tacrolimus). Calcineurin inhibitors are reserved for the management of acute severe UC. Safety data on calcineurin inhibitors is conflicting, and there is not enough information at this time to identify risk during pregnancy. Cyclosporine can be used for salvage therapy if absolutely needed, and there are case reports of its successful using during pregnancy.^16,52



Biologic therapies. With the exception of certolizumab, all of the currently used biologics are actively transported across the placenta.^39,53,54 Intrapartum use of biologic therapies does not worsen pregnancy or neonatal outcomes, including the risk for intensive care unit admission, infections, and developmental milestones.^39,47

While drug concentrations may vary slightly during pregnancy, these changes are not substantial enough to warrant more frequent monitoring or dose adjustments, and prepregnancy weight should be used for dosing.^55,56

Antitumor necrosis factor agents used in IBD include infliximab, adalimumab, certolizumab, and golimumab.⁵⁷ All are low risk for pregnant patients and their offspring. Dosage timings can be adjusted, but not stopped, to minimize exposure to the child; however, it cannot be adjusted for certolizumab pegol because of its lack of placental transfer.^58-59

Natalizumab and vedolizumab are integrin receptor antagonists and are also low risk in pregnancy.^57;60-62;39

Ustekinumab, an interleukin-12/23 antagonist, can be found in infant serum and cord blood, as well. Health outcomes are similar in the exposed mother and child, however, compared with those of the general population.^39;63-64



Small molecule drugs. Unlike monoclonal antibodies, which do not cross the placenta in large amounts until early in the second trimester, small molecules can cross in the first trimester during the critical period of organogenesis.

The two small molecule agents currently approved for use in UC are tofacitinib, a janus kinase inhibitor, and ozanimod, a sphingosine-1-phosphate receptor agonist.^65-66 Further data are still needed to make recommendations on the use of tofacitinib and ozanimod in pregnancy. At this time, we recommend weighing the risks (unknown risk to human pregnancy) vs. benefits (controlled disease activity with clear risk of harm to mother and baby from flare) in the individual patient before counseling on use in pregnancy.
 

Delivery

Mode of delivery

The mode of delivery should be determined by the obstetrician. C-section is recommended for patients with active perianal disease or, in some cases, a history of ileal pouch anal anastomosis (IPAA).^67-68 Vaginal delivery in the setting of perianal disease has been shown to increase the risk of fourth-degree laceration and anal sphincter dysfunction in the future.^26-27 Anorectal motility may be impacted by IPAA construction and vaginal delivery independently of each other. It is therefore suggested that vaginal delivery be avoided in patients with a history of IPAA to avoid compounding the risk. Some studies do not show clear harm from vaginal delivery in the setting of IPAA, however, and informed decision making among all stakeholders should be had.^27;69-70

Anticoagulation

The incidence of venous thromboembolism (VTE) is elevated in patients with IBD during pregnancy, and up to 12 weeks postpartum, compared with pregnant patients without IBD.^71-72 VTE for prophylaxis is indicated in the pregnant patient while hospitalized and potentially thereafter depending on the patient’s risk factors, which may include obesity, prior personal history of VTE, heart failure, and prolonged immobility. Unfractionated heparin, low molecular weight heparin, and warfarin are safe for breastfeeding women.^16,73

Postpartum care of mother

There is a risk of postpartum flare, occurring in about one third of patients in the first 6 months postpartum.^74-75 De-escalating therapy during delivery or immediately postpartum is a predictor of a postpartum flare.⁷⁵ If no infection is present and the timing interval is appropriate, biologic therapies should be continued and can be resumed 24 hours after a vaginal delivery and 48 hours after a C-section.^16,76

NSAIDs and opioids can be used for pain relief but should be avoided in the long-term to prevent flares (NSAIDs) and infant sedation (associated with opioids) when used while breastfeeding.⁷⁷ The LactMed database is an excellent resource for clarification on risk of medication use while breastfeeding.⁷⁸

In particular, contraception should be addressed postpartum. Exogenous estrogen use increases the risk of VTE, which is already increased in IBD; nonestrogen containing, long-acting reversible contraception is preferred.^79-80 Progestin-only implants or intrauterine devices may be used first line. The efficacy of oral contraceptives is theoretically reduced in those with rapid bowel transit, active small bowel inflammation, and prior small bowel resection, so adding another form of contraception is recommended.^16,81

Source: American Gastroenterological Association

Postdelivery care of baby

Breastfeeding

Guidelines regarding medication use during breastfeeding are similar to those in pregnancy (see Table). Breastfeeding on biologics and thiopurines can continue without interruption in the child. Thiopurine concentrations in breast milk are low or undetectable.^82,78 TNF receptor antagonists, anti-integrin therapies, and ustekinumab are found in low to undetectable levels in breast milk, as well.⁷⁸

On the other hand, the active metabolite of methotrexate is detectable in breast milk and most sources recommend not breastfeeding on methotrexate. At doses used in IBD (15-25 milligrams per week), some experts have suggested avoiding breastfeeding for 24 hours following a dose.^57,78 It is the practice of this author to recommend not breastfeeding at all on methotrexate.

5-ASA therapies are low risk for breastfeeding, but alternatives to sulfasalazine are preferred. The sulfapyridine metabolite transfers to breast milk and may cause hemolysis in infants born with a glucose-6-phosphate dehydrogenase deficiency.⁷⁸

With regards to calcineurin inhibitors, tacrolimus appears in breast milk in low quantities, while cyclosporine levels are variable. Data from the National Transplantation Pregnancy Registry suggest that these medications can be used at the time of breastfeeding with close monitoring.⁷⁸

There is not enough data on small molecule therapies at this time to support breastfeeding safety, and it is our practice to not recommend breastfeeding in this scenario.

The transfer of steroids to the child via breast milk does occur but at subtherapeutic levels.¹⁶ Budesonide has high first pass metabolism and is low risk during breastfeeding.^83-84 As far as is known, IBD maintenance medications do not suppress lactation. The use of intravenous corticosteroids can, however, temporarily decrease milk production.^16,85
 

Vaccines

Vaccination of infants can proceed as indicated by the Center for Disease Control and Prevention guidelines, with one exception. If the child’s mother was exposed to any biologic agents (not including certolizumab) during the third trimester, any live vaccines should be withheld in the first 6 months of life. In the United States, this restriction currently only applies to the rotavirus vaccine, which is administered starting at the age of 2 months.^16,86 Notably, inadvertent administration of the rotavirus vaccine in the biologic-exposed child does not appear to result in any adverse effects.⁸⁷ Immunity is achieved even if the child is exposed to IBD therapies through breast milk.⁸⁸

Developmental milestones

Infant exposure to biologics and thiopurines has not been shown to result in any developmental delays. The PIANO study measured developmental milestones at 48 months from birth and found no differences when compared with validated population norms.³⁹ A separate study observing childhood development up to 7 years of age in patients born to mothers with IBD found similar cognitive scores and motor development when compared with those born to mothers without IBD.⁸⁹

Conclusion

Women considering conception should be optimized prior to pregnancy and maintained on appropriate medications throughout pregnancy and lactation to achieve a healthy pregnancy for both mother and baby. To date, biologics and thiopurines are not associated with adverse pregnancy outcomes. More data are needed for small molecules.

Dr. Chugh is an advanced inflammatory bowel disease fellow in the division of gastroenterology at the University of California San Francisco. Dr. Mahadevan is professor of medicine and codirector at the Center for Colitis and Crohn’s Disease in the division of gastroenterology at the University of California San Francisco. Dr. Mahadevan has potential conflicts related to AbbVie, Janssen, BMS, Takeda, Pfizer, Lilly, Gilead, Arena, and Prometheus Biosciences.

References

1. Ye Y et al. Inflamm Bowel Dis. 2020;26:619-25.

2. Sykora J et al. World J Gastroenterol. 2018;24:2741-63.

3. Murakami Y et al. J Gastroenterol 2019;54:1070-7.

4. Hashash JG and Kane S. Gastroenterol Hepatol. (N Y) 2015;11:96-102.

5. Miller JP. J R Soc Med. 1986;79:221-5.

6. Cornish J et al. Gut. 2007;56:830-7.

7. Leung KK et al. Inflamm Bowel Dis. 2021;27:550-62.

8. O’Toole A et al. Dig Dis Sci. 2015;60:2750-61.

9. Nguyen GC et al. Inflamm Bowel Dis. 2008;14:1105-11.

10. Lee HH et al. Aliment Pharmacol Ther. 2020;51:861-9.

11. Kim MA et al. J Crohns Colitis. 2021;15:719-32.

12. Conradt E et al. Pediatrics. 2019;144.

13. ACOG Committee Opinion No. 762: Prepregnancy Counseling. Obstet Gynecol. 2019;133:e78-e89.

14. Farraye FA et al. Am J Gastroenterol. 2017;112:241-58.

15. Lee S et al. J Crohns Colitis. 2018;12:702-9.

16. Mahadevan U et al. Inflamm Bowel Dis. 2019;25:627-41.

17. Ward MG et al. Inflamm. Bowel Dis 2015;21:2839-47.

18. Battat R et al. Inflamm Bowel Dis. 2014;20:1120-8.

19. Pedersen N et al. Aliment Pharmacol Ther. 2013;38:501-12.

20. Annese V. Pharmacol Res. 2020;159:104892.

21. Bennett RA et al. Gastroenterology. 1991;100:1638-43.

22. Turpin W et al. Inflamm Bowel Dis. 2018;24:1133-48.

23. de Lima A et al. Clin Gastroenterol Hepatol. 2016;14:1285-92 e1.

24. Selinger C et al. Frontline Gastroenterol. 2021;12:182-7.

25. Mahadevan U et al. Gastroenterology. 2007;133:1106-12.

26. Hatch Q et al. Dis Colon Rectum. 2014;57:174-8.

27. Foulon A et al. Inflamm Bowel Dis. 2017;23:712-20.

28. Norgard B et al. Am J Gastroenterol. 2007;102:1947-54.

29. Broms G et al. Scand J Gastroenterol 2016;51:1462-9.

30. Meyer A et al. Aliment Pharmacol Ther. 2020;52:1480-90.

31. Kammerlander H et al. Inflamm Bowel Dis. 2017;23:1011-8.

32. Tandon P et al. J Clin Gastroenterol. 2019;53:574-81.

33. Kammerlander H et al. Inflamm Bowel Dis. 2018;24:839-48.

34. Julsgaard M et al. Inflamm Bowel Dis. 2017;23:1240-6.

35. Ko MS et al. Dig Dis Sci. 2020;65:2979-85.

36. Cappell MS et al. J Reprod Med. 2010;55:115-23.

37. Committee ASoP et al. Gastrointest Endosc. 2012;76:18-24.

38. Aboubakr A et al. Dig Dis Sci. 2021;66:1829-35.

39. Mahadevan U et al. Gastroenterology. 2021;160:1131-9.

40. Diav-Citrin O et al. Gastroenterology. 1998;114:23-8.

41. Rahimi R et al. Reprod Toxicol. 2008;25:271-5.

42. Norgard B et al. Aliment Pharmacol Ther. 2001;15:483-6.

43. Leung YP et al. J Crohns Colitis. 2015;9:223-30.

44. Schulze H et al. Aliment Pharmacol Ther. 2014;40:991-1008.

45. Szymanska E et al. J Gynecol Obstet Hum Reprod. 2021;50:101777.

46. Weber-Schoendorfer C et al. Arthritis Rheumatol. 2014;66:1101-10.

47. Nielsen OH et al. Clin Gastroenterol Hepatol. 2022 Jan;20(1):74-87.e3.

48. Coelho J et al. Gut. 2011;60:198-203.

49. Sheikh M et al. J Crohns Colitis. 2015;9:680-4.

50. Kanis SL et al. Clin Gastroenterol Hepatol. 2017;15:1232-41 e1.

51. Mahadevan U et al. Inflamm Bowel Dis. 2018;24:2494-500.

52. Rosen MH et al. Inflamm Bowel Dis. 2020;26:971-3.

53. Porter C et al. J Reprod Immunol. 2016;116:7-12.

54. Mahadevan U et al. Clin Gastroenterol Hepatol. 2013;11:286-92; quiz e24.

55. Picardo S and Seow CH. Best Pract Res Clin Gastroenterol. 2020;44-5:101670.

56. Flanagan E et al. Aliment Pharmacol Ther. 2020;52:1551-62.

57. Singh S et al. Gastroenterology. 2021;160:2512-56 e9.

58. de Lima A et al. Gut. 2016;65:1261-8.

59. Julsgaard M et al. Inflamm Bowel Dis. 2020;26:93-102.

60. Wils P et al. Aliment Pharmacol Ther. 2021;53:460-70.

61. Mahadevan U et al. Aliment Pharmacol Ther. 2017;45:941-50.

62. Bar-Gil Shitrit A et al. Am J Gastroenterol. 2019;114:1172-5.

63. Klenske E et al. J Crohns Colitis. 2019;13:267-9.

64. Matro R et al. Gastroenterology. 2018;155:696-704.

65. Feuerstein JD et al. Gastroenterology. 2020;158:1450-61.

66. Sandborn WJ et al. J Crohns Colitis. 2021 Jul 5;15(7):1120-1129.

67. Lamb CA et al. Gut. 2019;68:s1-s106.

68. Nguyen GC et al. Gastroenterology. 2016;150:734-57 e1.

69. Ravid A et al. Dis Colon Rectum. 2002;45:1283-8.

70. Seligman NS et al. J Matern Fetal Neonatal Med. 2011;24:525-30.

71. Kim YH et al. Medicine (Baltimore). 2019;98:e17309.

72. Hansen AT et al. J Thromb Haemost. 2017;15:702-8.

73. Bates SM et al. J Thromb Thrombolysis. 2016;41:92-128.

74. Bennett A et al. Inflamm Bowel Dis. 2021 May 17;izab104.

75. Yu A et al. Inflamm Bowel Dis. 2020;26:1926-32.

76. Mahadevan U et al. Gastroenterology. 2017;152:451-62 e2.

77. Long MD et al. J Clin Gastroenterol. 2016;50:152-6.

78. Drugs and Lactation Database (LactMed). 2006 ed. Bethesda, MD: National Library of Medicine (US), 2006-2021.

79. Khalili H et al. Gut. 2013;62:1153-9.

80. Long MD and Hutfless S. Gastroenterology. 2016;150:1518-20.

81. Centers for Disease Control and Prevention. U S. Medical Eligibility Criteria for Contraceptive Use, 2010. MMWR Recomm Rep. 2010;59:1-86.

82. Angelberger S et al. J Crohns Colitis. 2011;5:95-100.

83. Vestergaard T et al. Scand J Gastroenterol. 2018;53:1459-62.

84. Beaulieu DB et al. Inflamm Bowel Dis. 2009;15:25-8.

85. Anderson PO. Breastfeed Med. 2017;12:199-201.

86. Wodi AP et al. MMWR Morb Mortal Wkly Rep. 2021;70:189-92.

87. Chiarella-Redfern H et al. Inflamm Bowel Dis. 2022 Jan 5;28(1):79-86.

88. Beaulieu DB et al. Clin Gastroenterol Hepatol. 2018;16:99-105.

89. Friedman S et al. J Crohns Colitis. 2020 Dec 2;14(12):1709-1716.

Inflammatory bowel disease (IBD) incidence is rising globally.^1-3 In the United States, we have seen a 123% increase in prevalence of IBD among adults and a 133% increase among children from 2007 to 2016, with an annual percentage change of 9.9%.¹ The rise of IBD in young people, and the overall higher prevalence in women compared with men, make pregnancy and IBD a topic of increasing importance for gastroenterologists.¹ Here, we will discuss management and expectations in women with IBD before conception, during pregnancy, and post partum.

Preconception

Disease activity
 

Achieving both clinical and endoscopic remission of disease prior to conception is the key to ensuring the best maternal and fetal outcomes. Patients with IBD who conceive while in remission remain in remission 80% of the time.^4,5 On the other hand, those who conceive while their disease is active may continue to have active or worsening disease in nearly 70% of cases.⁴ Active disease has been associated with an increased incidence of preterm birth, low birth weight, and small-for-gestational-age birth.^6-8 Active disease can also exacerbate malnutrition and result in poor maternal weight gain, which is associated with intrauterine growth restriction.^9,7 Pregnancy outcomes in patients with IBD and quiescent disease are similar to those in the general population.^10,11

Health care maintenance

Optimizing maternal health prior to conception is critical. Alcohol, tobacco, recreational drugs, and marijuana should all be avoided. Opioids should be tapered off prior to conception, as continued use may result in neonatal opioid withdrawal syndrome and long-term neurodevelopmental consequences.^12,13 In addition, aiming for a healthy body mass index between 18 and 25 months prior to conception allows for better overall pregnancy outcomes.¹³ Appropriate cancer screening includes colon cancer screening in those with more than 8 years of colitis, regular pap smear for cervical cancer, and annual total body skin cancer examinations for patients on thiopurines and biologic therapies.¹⁴

UCSF

Nutrition

Folic acid supplementation with at least 400 micrograms (mcg) daily is necessary for all women planning pregnancy. Patients with small bowel involvement or history of small bowel resection should have a folate intake of a minimum of 2 grams per day. Adequate vitamin D levels (at least 20 ng/mL) are recommended in all women with IBD. Those with malabsorption should be screened for deficiencies in vitamin B12, folate, and iron.¹³ These nutritional markers should be evaluated prepregnancy, during the first trimester, and thereafter as needed.^15-18

Preconception counseling

Steroid-free remission for at least 3 months prior to conception is recommended and is associated with reduced risk of flare during pregnancy.^16,19 IBD medications needed to control disease activity are generally safe preconception and during pregnancy, with some exception (Table).

Pregnancy

Coordinated care

A complete team of specialists with coordinated care among all providers is needed for optimal maternal and fetal outcomes.^23,24 A gastroenterologist, ideally an IBD specialist, should follow the patient throughout pregnancy, seeing the patient at least once during the first or second trimester and as needed during pregnancy.¹⁶ A high-risk obstetrician or maternal-fetal medicine specialist should be involved early in pregnancy, as well. Open communication among all disciplines ensures that a common message is conveyed to the patient.^16,24 A nutritionist, mental health provider, and lactation specialist knowledgeable about IBD drugs may be of assistance, as well.¹⁶

Disease activity

While women with IBD are at increased risk of spontaneous abortion, preterm birth, and labor complications, this risk is mitigated by controlling disease activity.²⁵ The risk of preterm birth, small-for-gestational-age birth, and delivery via C-section is much higher in women with moderate-to-high disease activity, compared with those with low disease activity.²⁶ The presence of active perianal disease mandates C-section over vaginal delivery. Fourth-degree lacerations following vaginal delivery are most common among those patients with perianal disease.^26,27 Stillbirths were shown to be increased only in those with active IBD when compared with non-IBD comparators and inactive IBD.^28-31;11

Noninvasive methods for disease monitoring are preferred in pregnancy, but serum markers such as erythrocyte sedimentation rate and C-reactive protein may not be reliable in the pregnant patient (Figure).³² Fecal calprotectin does rise in correlation with disease activity, but exact thresholds have not been validated in pregnancy.^33,34

Medication use and safety

IBD medications are a priority topic of concern among pregnant patients or those considering conception.³⁸ Comprehensive data from the PIANO (Pregnancy in Inflammatory Bowel Disease and Neonatal Outcomes) registry has shown that most IBD drugs do not result in adverse pregnancy outcomes and should be continued.³⁹ The use of biologics and thiopurines, either in combination or alone, is not related to an increased risk of congenital malformations, spontaneous abortion, preterm birth, low birth weight, or infections during the child’s first year of life.^7,39 Developmental milestones also remain unaffected.³⁹ Here, we will discuss safety considerations during pregnancy (see Table).

5-aminosalycylic acid. 5-aminosalicylic acid (5-ASA) agents are generally low risk during pregnancy and should be continued.^40-41 Sulfasalazine does interfere with folate metabolism, but by increasing folic acid supplementation to 2 grams per day, sulfasalazine can be continued throughout pregnancy, as well.⁴²



Corticosteroids. Intrapartum corticosteroid use is associated with an increased risk of gestational diabetes and adrenal insufficiency when used long term.^43-45 Short-term use may, however, be necessary to control an acute flare. The lowest dose for the shortest duration possible is recommended. Because of its high first-pass metabolism, budesonide is considered low risk in pregnancy.



Methotrexate. Methotrexate needs to be stopped at least 3 months prior to conception and should be avoided throughout pregnancy. Use during pregnancy can result in spontaneous abortions, as well as embryotoxicity.⁴⁶



Thiopurines (6-mercaptopurine and azathioprine). Patients who are taking thiopurines prior to conception to maintain remission can continue to do so. Data on thiopurines from the PIANO registry has shown no increase in spontaneous abortions, congenital malformations, low birth weight, preterm birth, rates of infection in the child, or developmental delays.^47-51



Calcineurin inhibitors (cyclosporine and tacrolimus). Calcineurin inhibitors are reserved for the management of acute severe UC. Safety data on calcineurin inhibitors is conflicting, and there is not enough information at this time to identify risk during pregnancy. Cyclosporine can be used for salvage therapy if absolutely needed, and there are case reports of its successful using during pregnancy.^16,52



Biologic therapies. With the exception of certolizumab, all of the currently used biologics are actively transported across the placenta.^39,53,54 Intrapartum use of biologic therapies does not worsen pregnancy or neonatal outcomes, including the risk for intensive care unit admission, infections, and developmental milestones.^39,47

While drug concentrations may vary slightly during pregnancy, these changes are not substantial enough to warrant more frequent monitoring or dose adjustments, and prepregnancy weight should be used for dosing.^55,56

Antitumor necrosis factor agents used in IBD include infliximab, adalimumab, certolizumab, and golimumab.⁵⁷ All are low risk for pregnant patients and their offspring. Dosage timings can be adjusted, but not stopped, to minimize exposure to the child; however, it cannot be adjusted for certolizumab pegol because of its lack of placental transfer.^58-59

Natalizumab and vedolizumab are integrin receptor antagonists and are also low risk in pregnancy.^57;60-62;39

Ustekinumab, an interleukin-12/23 antagonist, can be found in infant serum and cord blood, as well. Health outcomes are similar in the exposed mother and child, however, compared with those of the general population.^39;63-64



Small molecule drugs. Unlike monoclonal antibodies, which do not cross the placenta in large amounts until early in the second trimester, small molecules can cross in the first trimester during the critical period of organogenesis.

The two small molecule agents currently approved for use in UC are tofacitinib, a janus kinase inhibitor, and ozanimod, a sphingosine-1-phosphate receptor agonist.^65-66 Further data are still needed to make recommendations on the use of tofacitinib and ozanimod in pregnancy. At this time, we recommend weighing the risks (unknown risk to human pregnancy) vs. benefits (controlled disease activity with clear risk of harm to mother and baby from flare) in the individual patient before counseling on use in pregnancy.
 

Delivery

Mode of delivery

The mode of delivery should be determined by the obstetrician. C-section is recommended for patients with active perianal disease or, in some cases, a history of ileal pouch anal anastomosis (IPAA).^67-68 Vaginal delivery in the setting of perianal disease has been shown to increase the risk of fourth-degree laceration and anal sphincter dysfunction in the future.^26-27 Anorectal motility may be impacted by IPAA construction and vaginal delivery independently of each other. It is therefore suggested that vaginal delivery be avoided in patients with a history of IPAA to avoid compounding the risk. Some studies do not show clear harm from vaginal delivery in the setting of IPAA, however, and informed decision making among all stakeholders should be had.^27;69-70

Anticoagulation

The incidence of venous thromboembolism (VTE) is elevated in patients with IBD during pregnancy, and up to 12 weeks postpartum, compared with pregnant patients without IBD.^71-72 VTE for prophylaxis is indicated in the pregnant patient while hospitalized and potentially thereafter depending on the patient’s risk factors, which may include obesity, prior personal history of VTE, heart failure, and prolonged immobility. Unfractionated heparin, low molecular weight heparin, and warfarin are safe for breastfeeding women.^16,73

Postpartum care of mother

There is a risk of postpartum flare, occurring in about one third of patients in the first 6 months postpartum.^74-75 De-escalating therapy during delivery or immediately postpartum is a predictor of a postpartum flare.⁷⁵ If no infection is present and the timing interval is appropriate, biologic therapies should be continued and can be resumed 24 hours after a vaginal delivery and 48 hours after a C-section.^16,76

NSAIDs and opioids can be used for pain relief but should be avoided in the long-term to prevent flares (NSAIDs) and infant sedation (associated with opioids) when used while breastfeeding.⁷⁷ The LactMed database is an excellent resource for clarification on risk of medication use while breastfeeding.⁷⁸

In particular, contraception should be addressed postpartum. Exogenous estrogen use increases the risk of VTE, which is already increased in IBD; nonestrogen containing, long-acting reversible contraception is preferred.^79-80 Progestin-only implants or intrauterine devices may be used first line. The efficacy of oral contraceptives is theoretically reduced in those with rapid bowel transit, active small bowel inflammation, and prior small bowel resection, so adding another form of contraception is recommended.^16,81

Source: American Gastroenterological Association

Postdelivery care of baby

Breastfeeding

Guidelines regarding medication use during breastfeeding are similar to those in pregnancy (see Table). Breastfeeding on biologics and thiopurines can continue without interruption in the child. Thiopurine concentrations in breast milk are low or undetectable.^82,78 TNF receptor antagonists, anti-integrin therapies, and ustekinumab are found in low to undetectable levels in breast milk, as well.⁷⁸

On the other hand, the active metabolite of methotrexate is detectable in breast milk and most sources recommend not breastfeeding on methotrexate. At doses used in IBD (15-25 milligrams per week), some experts have suggested avoiding breastfeeding for 24 hours following a dose.^57,78 It is the practice of this author to recommend not breastfeeding at all on methotrexate.

5-ASA therapies are low risk for breastfeeding, but alternatives to sulfasalazine are preferred. The sulfapyridine metabolite transfers to breast milk and may cause hemolysis in infants born with a glucose-6-phosphate dehydrogenase deficiency.⁷⁸

With regards to calcineurin inhibitors, tacrolimus appears in breast milk in low quantities, while cyclosporine levels are variable. Data from the National Transplantation Pregnancy Registry suggest that these medications can be used at the time of breastfeeding with close monitoring.⁷⁸

There is not enough data on small molecule therapies at this time to support breastfeeding safety, and it is our practice to not recommend breastfeeding in this scenario.

The transfer of steroids to the child via breast milk does occur but at subtherapeutic levels.¹⁶ Budesonide has high first pass metabolism and is low risk during breastfeeding.^83-84 As far as is known, IBD maintenance medications do not suppress lactation. The use of intravenous corticosteroids can, however, temporarily decrease milk production.^16,85
 

Vaccines

Vaccination of infants can proceed as indicated by the Center for Disease Control and Prevention guidelines, with one exception. If the child’s mother was exposed to any biologic agents (not including certolizumab) during the third trimester, any live vaccines should be withheld in the first 6 months of life. In the United States, this restriction currently only applies to the rotavirus vaccine, which is administered starting at the age of 2 months.^16,86 Notably, inadvertent administration of the rotavirus vaccine in the biologic-exposed child does not appear to result in any adverse effects.⁸⁷ Immunity is achieved even if the child is exposed to IBD therapies through breast milk.⁸⁸

Developmental milestones

Infant exposure to biologics and thiopurines has not been shown to result in any developmental delays. The PIANO study measured developmental milestones at 48 months from birth and found no differences when compared with validated population norms.³⁹ A separate study observing childhood development up to 7 years of age in patients born to mothers with IBD found similar cognitive scores and motor development when compared with those born to mothers without IBD.⁸⁹

Conclusion

Women considering conception should be optimized prior to pregnancy and maintained on appropriate medications throughout pregnancy and lactation to achieve a healthy pregnancy for both mother and baby. To date, biologics and thiopurines are not associated with adverse pregnancy outcomes. More data are needed for small molecules.

Dr. Chugh is an advanced inflammatory bowel disease fellow in the division of gastroenterology at the University of California San Francisco. Dr. Mahadevan is professor of medicine and codirector at the Center for Colitis and Crohn’s Disease in the division of gastroenterology at the University of California San Francisco. Dr. Mahadevan has potential conflicts related to AbbVie, Janssen, BMS, Takeda, Pfizer, Lilly, Gilead, Arena, and Prometheus Biosciences.

References

1. Ye Y et al. Inflamm Bowel Dis. 2020;26:619-25.

2. Sykora J et al. World J Gastroenterol. 2018;24:2741-63.

3. Murakami Y et al. J Gastroenterol 2019;54:1070-7.

4. Hashash JG and Kane S. Gastroenterol Hepatol. (N Y) 2015;11:96-102.

5. Miller JP. J R Soc Med. 1986;79:221-5.

6. Cornish J et al. Gut. 2007;56:830-7.

7. Leung KK et al. Inflamm Bowel Dis. 2021;27:550-62.

8. O’Toole A et al. Dig Dis Sci. 2015;60:2750-61.

9. Nguyen GC et al. Inflamm Bowel Dis. 2008;14:1105-11.

10. Lee HH et al. Aliment Pharmacol Ther. 2020;51:861-9.

11. Kim MA et al. J Crohns Colitis. 2021;15:719-32.

12. Conradt E et al. Pediatrics. 2019;144.

13. ACOG Committee Opinion No. 762: Prepregnancy Counseling. Obstet Gynecol. 2019;133:e78-e89.

14. Farraye FA et al. Am J Gastroenterol. 2017;112:241-58.

15. Lee S et al. J Crohns Colitis. 2018;12:702-9.

16. Mahadevan U et al. Inflamm Bowel Dis. 2019;25:627-41.

17. Ward MG et al. Inflamm. Bowel Dis 2015;21:2839-47.

18. Battat R et al. Inflamm Bowel Dis. 2014;20:1120-8.

19. Pedersen N et al. Aliment Pharmacol Ther. 2013;38:501-12.

20. Annese V. Pharmacol Res. 2020;159:104892.

21. Bennett RA et al. Gastroenterology. 1991;100:1638-43.

22. Turpin W et al. Inflamm Bowel Dis. 2018;24:1133-48.

23. de Lima A et al. Clin Gastroenterol Hepatol. 2016;14:1285-92 e1.

24. Selinger C et al. Frontline Gastroenterol. 2021;12:182-7.

25. Mahadevan U et al. Gastroenterology. 2007;133:1106-12.

26. Hatch Q et al. Dis Colon Rectum. 2014;57:174-8.

27. Foulon A et al. Inflamm Bowel Dis. 2017;23:712-20.

28. Norgard B et al. Am J Gastroenterol. 2007;102:1947-54.

29. Broms G et al. Scand J Gastroenterol 2016;51:1462-9.

30. Meyer A et al. Aliment Pharmacol Ther. 2020;52:1480-90.

31. Kammerlander H et al. Inflamm Bowel Dis. 2017;23:1011-8.

32. Tandon P et al. J Clin Gastroenterol. 2019;53:574-81.

33. Kammerlander H et al. Inflamm Bowel Dis. 2018;24:839-48.

34. Julsgaard M et al. Inflamm Bowel Dis. 2017;23:1240-6.

35. Ko MS et al. Dig Dis Sci. 2020;65:2979-85.

36. Cappell MS et al. J Reprod Med. 2010;55:115-23.

37. Committee ASoP et al. Gastrointest Endosc. 2012;76:18-24.

38. Aboubakr A et al. Dig Dis Sci. 2021;66:1829-35.

39. Mahadevan U et al. Gastroenterology. 2021;160:1131-9.

40. Diav-Citrin O et al. Gastroenterology. 1998;114:23-8.

41. Rahimi R et al. Reprod Toxicol. 2008;25:271-5.

42. Norgard B et al. Aliment Pharmacol Ther. 2001;15:483-6.

43. Leung YP et al. J Crohns Colitis. 2015;9:223-30.

44. Schulze H et al. Aliment Pharmacol Ther. 2014;40:991-1008.

45. Szymanska E et al. J Gynecol Obstet Hum Reprod. 2021;50:101777.

46. Weber-Schoendorfer C et al. Arthritis Rheumatol. 2014;66:1101-10.

47. Nielsen OH et al. Clin Gastroenterol Hepatol. 2022 Jan;20(1):74-87.e3.

48. Coelho J et al. Gut. 2011;60:198-203.

49. Sheikh M et al. J Crohns Colitis. 2015;9:680-4.

50. Kanis SL et al. Clin Gastroenterol Hepatol. 2017;15:1232-41 e1.

51. Mahadevan U et al. Inflamm Bowel Dis. 2018;24:2494-500.

52. Rosen MH et al. Inflamm Bowel Dis. 2020;26:971-3.

53. Porter C et al. J Reprod Immunol. 2016;116:7-12.

54. Mahadevan U et al. Clin Gastroenterol Hepatol. 2013;11:286-92; quiz e24.

55. Picardo S and Seow CH. Best Pract Res Clin Gastroenterol. 2020;44-5:101670.

56. Flanagan E et al. Aliment Pharmacol Ther. 2020;52:1551-62.

57. Singh S et al. Gastroenterology. 2021;160:2512-56 e9.

58. de Lima A et al. Gut. 2016;65:1261-8.

59. Julsgaard M et al. Inflamm Bowel Dis. 2020;26:93-102.

60. Wils P et al. Aliment Pharmacol Ther. 2021;53:460-70.

61. Mahadevan U et al. Aliment Pharmacol Ther. 2017;45:941-50.

62. Bar-Gil Shitrit A et al. Am J Gastroenterol. 2019;114:1172-5.

63. Klenske E et al. J Crohns Colitis. 2019;13:267-9.

64. Matro R et al. Gastroenterology. 2018;155:696-704.

65. Feuerstein JD et al. Gastroenterology. 2020;158:1450-61.

66. Sandborn WJ et al. J Crohns Colitis. 2021 Jul 5;15(7):1120-1129.

67. Lamb CA et al. Gut. 2019;68:s1-s106.

68. Nguyen GC et al. Gastroenterology. 2016;150:734-57 e1.

69. Ravid A et al. Dis Colon Rectum. 2002;45:1283-8.

70. Seligman NS et al. J Matern Fetal Neonatal Med. 2011;24:525-30.

71. Kim YH et al. Medicine (Baltimore). 2019;98:e17309.

72. Hansen AT et al. J Thromb Haemost. 2017;15:702-8.

73. Bates SM et al. J Thromb Thrombolysis. 2016;41:92-128.

74. Bennett A et al. Inflamm Bowel Dis. 2021 May 17;izab104.

75. Yu A et al. Inflamm Bowel Dis. 2020;26:1926-32.

76. Mahadevan U et al. Gastroenterology. 2017;152:451-62 e2.

77. Long MD et al. J Clin Gastroenterol. 2016;50:152-6.

78. Drugs and Lactation Database (LactMed). 2006 ed. Bethesda, MD: National Library of Medicine (US), 2006-2021.

79. Khalili H et al. Gut. 2013;62:1153-9.

80. Long MD and Hutfless S. Gastroenterology. 2016;150:1518-20.

81. Centers for Disease Control and Prevention. U S. Medical Eligibility Criteria for Contraceptive Use, 2010. MMWR Recomm Rep. 2010;59:1-86.

82. Angelberger S et al. J Crohns Colitis. 2011;5:95-100.

83. Vestergaard T et al. Scand J Gastroenterol. 2018;53:1459-62.

84. Beaulieu DB et al. Inflamm Bowel Dis. 2009;15:25-8.

85. Anderson PO. Breastfeed Med. 2017;12:199-201.

86. Wodi AP et al. MMWR Morb Mortal Wkly Rep. 2021;70:189-92.

87. Chiarella-Redfern H et al. Inflamm Bowel Dis. 2022 Jan 5;28(1):79-86.

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89. Friedman S et al. J Crohns Colitis. 2020 Dec 2;14(12):1709-1716.

February is National Cancer Prevention Month. With approximately 4.8 million new cases and 3.4 million deaths worldwide annually, GI cancers represent roughly a quarter of the global cancer incidence and over a third of all cancer-related deaths, according to one study.

In this month’s issue of GI & Hepatology News, we feature timely content relevant to prevention and early detection of GI cancers, which remains a central focus of our clinical and endoscopic practice as gastroenterologists. This includes important studies that demonstrate the value of upper endoscopy in reducing GI cancer mortality, illustrate the potential promise of artificial intelligence in improving early detection of gastric cancer, and link adenoma detection rate to long-term survival in patients who undergo CRC screening with flexible sigmoidoscopy. We also report on a focused update from the U.S. Multi-Society Task Force on colorectal cancer, which thoughtfully reviews the data supporting a shift in the age of initiation of average-risk CRC screening from 50 to 45 years.

On the policy front, AGA and its partners have worked tirelessly for many years to eliminate financial barriers to colorectal cancer (CRC) screening through national advocacy efforts. These efforts resulted in closure of the so-called Medicare “colonoscopy loophole” through legislation included in the COVID-19 relief bill – as a result, out-of-pocket costs for patients undergoing a screening colonoscopy that results in polypectomy are disallowed as of January 2022. The Biden Administration recently issued guidance in January in response to multisociety advocacy efforts: Private insurers must provide coverage without cost sharing for a follow-up colonoscopy after a positive stool-based CRC screening test for plan or policy years starting on or after May 31, 2022. Removing these financial barriers to care is particularly critical to efforts to improve CRC screening rates among medically underserved communities.

These achievements highlight the power of physician advocacy in inspiring policy changes that directly improve the health and well-being of our patients. I encourage you to visit the AGA website to learn how you can contribute to ongoing advocacy efforts.

Megan A. Adams, MD, JD, MSc
Editor in Chief

February is National Cancer Prevention Month. With approximately 4.8 million new cases and 3.4 million deaths worldwide annually, GI cancers represent roughly a quarter of the global cancer incidence and over a third of all cancer-related deaths, according to one study.

In this month’s issue of GI & Hepatology News, we feature timely content relevant to prevention and early detection of GI cancers, which remains a central focus of our clinical and endoscopic practice as gastroenterologists. This includes important studies that demonstrate the value of upper endoscopy in reducing GI cancer mortality, illustrate the potential promise of artificial intelligence in improving early detection of gastric cancer, and link adenoma detection rate to long-term survival in patients who undergo CRC screening with flexible sigmoidoscopy. We also report on a focused update from the U.S. Multi-Society Task Force on colorectal cancer, which thoughtfully reviews the data supporting a shift in the age of initiation of average-risk CRC screening from 50 to 45 years.

On the policy front, AGA and its partners have worked tirelessly for many years to eliminate financial barriers to colorectal cancer (CRC) screening through national advocacy efforts. These efforts resulted in closure of the so-called Medicare “colonoscopy loophole” through legislation included in the COVID-19 relief bill – as a result, out-of-pocket costs for patients undergoing a screening colonoscopy that results in polypectomy are disallowed as of January 2022. The Biden Administration recently issued guidance in January in response to multisociety advocacy efforts: Private insurers must provide coverage without cost sharing for a follow-up colonoscopy after a positive stool-based CRC screening test for plan or policy years starting on or after May 31, 2022. Removing these financial barriers to care is particularly critical to efforts to improve CRC screening rates among medically underserved communities.

These achievements highlight the power of physician advocacy in inspiring policy changes that directly improve the health and well-being of our patients. I encourage you to visit the AGA website to learn how you can contribute to ongoing advocacy efforts.

Megan A. Adams, MD, JD, MSc
Editor in Chief

February is National Cancer Prevention Month. With approximately 4.8 million new cases and 3.4 million deaths worldwide annually, GI cancers represent roughly a quarter of the global cancer incidence and over a third of all cancer-related deaths, according to one study.

In this month’s issue of GI & Hepatology News, we feature timely content relevant to prevention and early detection of GI cancers, which remains a central focus of our clinical and endoscopic practice as gastroenterologists. This includes important studies that demonstrate the value of upper endoscopy in reducing GI cancer mortality, illustrate the potential promise of artificial intelligence in improving early detection of gastric cancer, and link adenoma detection rate to long-term survival in patients who undergo CRC screening with flexible sigmoidoscopy. We also report on a focused update from the U.S. Multi-Society Task Force on colorectal cancer, which thoughtfully reviews the data supporting a shift in the age of initiation of average-risk CRC screening from 50 to 45 years.

On the policy front, AGA and its partners have worked tirelessly for many years to eliminate financial barriers to colorectal cancer (CRC) screening through national advocacy efforts. These efforts resulted in closure of the so-called Medicare “colonoscopy loophole” through legislation included in the COVID-19 relief bill – as a result, out-of-pocket costs for patients undergoing a screening colonoscopy that results in polypectomy are disallowed as of January 2022. The Biden Administration recently issued guidance in January in response to multisociety advocacy efforts: Private insurers must provide coverage without cost sharing for a follow-up colonoscopy after a positive stool-based CRC screening test for plan or policy years starting on or after May 31, 2022. Removing these financial barriers to care is particularly critical to efforts to improve CRC screening rates among medically underserved communities.

These achievements highlight the power of physician advocacy in inspiring policy changes that directly improve the health and well-being of our patients. I encourage you to visit the AGA website to learn how you can contribute to ongoing advocacy efforts.

Megan A. Adams, MD, JD, MSc
Editor in Chief

Dear colleagues,

I’m thrilled to introduce the first edition of The New Gastroenterologist in 2022! The onslaught of the COVID-19 pandemic continues, and as physicians, we are exhausted. The past year brought glimpses of normalcy, but these were ultimately eclipsed by the precipitous surge of the very contagious Omicron variant, once again overwhelming health systems and threatening our daily routines. We will keep on, doing our best to protect our patients and our families, with the hope for an eventual transition ‘from pandemic to endemic.’

Due to the pandemic, telemedicine has now been firmly cemented as a cornerstone of clinical care, which Dr. Naresh Gunaratnam (Huron Gastroenterology, Ann Arbor, Mich.) discusses in our DHPA Private Practice Perspectives article for the quarter. Telemedicine boasts many benefits and while it will never be adopted entirely in lieu of in-person visits, it is a tool that should remain an option for years to come in the appropriate subset of patients.

Dear colleagues,

I’m thrilled to introduce the first edition of The New Gastroenterologist in 2022! The onslaught of the COVID-19 pandemic continues, and as physicians, we are exhausted. The past year brought glimpses of normalcy, but these were ultimately eclipsed by the precipitous surge of the very contagious Omicron variant, once again overwhelming health systems and threatening our daily routines. We will keep on, doing our best to protect our patients and our families, with the hope for an eventual transition ‘from pandemic to endemic.’

Due to the pandemic, telemedicine has now been firmly cemented as a cornerstone of clinical care, which Dr. Naresh Gunaratnam (Huron Gastroenterology, Ann Arbor, Mich.) discusses in our DHPA Private Practice Perspectives article for the quarter. Telemedicine boasts many benefits and while it will never be adopted entirely in lieu of in-person visits, it is a tool that should remain an option for years to come in the appropriate subset of patients.

Dear colleagues,

I’m thrilled to introduce the first edition of The New Gastroenterologist in 2022! The onslaught of the COVID-19 pandemic continues, and as physicians, we are exhausted. The past year brought glimpses of normalcy, but these were ultimately eclipsed by the precipitous surge of the very contagious Omicron variant, once again overwhelming health systems and threatening our daily routines. We will keep on, doing our best to protect our patients and our families, with the hope for an eventual transition ‘from pandemic to endemic.’

Due to the pandemic, telemedicine has now been firmly cemented as a cornerstone of clinical care, which Dr. Naresh Gunaratnam (Huron Gastroenterology, Ann Arbor, Mich.) discusses in our DHPA Private Practice Perspectives article for the quarter. Telemedicine boasts many benefits and while it will never be adopted entirely in lieu of in-person visits, it is a tool that should remain an option for years to come in the appropriate subset of patients.

The COVID-19 pandemic is now associated with the highest number of excess deaths worldwide since the 1918 flu pandemic, sometimes known as the “Spanish flu.”

Excess mortality is a way of quantifying the impact of a pandemic, based on overall mortality from nonpandemic periods. Mortality data over long periods of time are not available for many countries, but Switzerland, Sweden, and Spain have accumulated death count data for an uninterrupted period of more than 100 years.

In a study published in the Annals of Internal Medicine, Kaspar Staub, PhD, of the University of Zurich led a team of researchers in reviewing data on monthly excess deaths from all causes for Switzerland, Sweden, and Spain for 2020 to 2021. Dr. Staub and colleagues also compared these numbers to other pandemic and nonpandemic periods since the end of the 19th century. The starting years were 1877 for Switzerland, 1851 for Sweden, and 1908 for Spain.

The researchers collected data for monthly all-cause deaths from the statistical offices of each country and determined excess mortality by comparing these numbers to population size and age structure.

They found that 2020 showed the highest number of excess deaths since 1918, with relative excess of deaths of 12.5% in Switzerland, 8.5% in Sweden, and 17.3 % in Spain.

To put it another way, the number of excess deaths per 100,000 people was 100 for Switzerland, 75 for Sweden, and 155 for Spain.

“Our findings suggest that the pandemic led to the second-largest mortality disaster driven by a viral infection in more than 100 years in the three countries we studied, second only to the 1918 influenza pandemic,” the researchers wrote.

They explained that the excess mortality for the year 1918 was six to seven times higher than the 2020 numbers, but that the 2020 numbers might have been higher without the strong public health interventions taken worldwide to mitigate the impact of the COVID-19 pandemic.

“Early estimates suggest that vaccination prevented approximately 470,000 deaths in persons aged 60 years or older across 33 European countries between December 2019 and November 2021,” they wrote. However, because the COVID-19 pandemic is ongoing, “a more conclusive assessment will have to wait,” they added.

The 2020 numbers also were higher than most mortality rates since 1918, including peak years of previous influenza pandemics that occurred in 1957, 1968, 1977, and, most recently, the swine flu pandemic of 2009 which was caused by a novel strain of the H1N1 influenza virus.

The study findings had some limitations. For example, only three countries were included. Also, monthly death numbers according to sex, age, and cause of death were available only for the past 60 years, and data from years before the 20th century may not be reliable, the researchers said.

The new study does not account for the long-term effects of patients suffering from long COVID, they noted.

Study findings support strong public health response

“With the COVID-19 pandemic ongoing, this study reinforces the historic magnitude of the problem in terms of mortality and could add to the justification for ongoing public health measures such as vaccination drives and vaccine mandates to curb deaths,” said Suman Pal, MD, an internal medicine physician at the University of New Mexico, Albuquerque, in an interview.

“The results are surprising because when we view the rapid advancement in medical science over the last few decades, which have led to a decline in mortality from many previously fatal diseases, the scale of excess mortality from COVID-19 seems to have offset many such gains in the past 2 years.”

Prior studies of United States mortality data have estimated that excess deaths in the United States in 2020 exceeded the deaths attributed to COVID-19, said Dr. Pal. “The findings of this study could help clinicians in their discussion of the need for COVID-19 prevention measures with their patients” and inform discussions between doctors and patients about prevention strategies, he explained.

“Emphasizing that this pandemic is the second-largest cause of death due to a viral infection in a century could help patients understand the need for public health measures that may be viewed as unprecedented, such as government-imposed lockdowns, contact tracing, mask requirements, restrictions on travel, and vaccine mandates,” Dr. Pal noted. Better understanding of the evidence behind such measures may decrease the public’s resistance to following them, he added.As for additional research, “region-specific analysis of excess deaths may help estimate the impact of COVID-19 better, especially in regions where data reporting may be unreliable.”

Dr. F. Perry Wilson's take on study

“All-cause mortality is a key metric to assess the impact of the pandemic, because each death is treated equally,” said F. Perry Wilson, MD, of Yale University, in an interview. “With this type of analysis, there is no vague definition of a death from COVID or with COVID,” he explained. “A death is a death, and more deaths than expected is, of course, a bad thing. These analyses give a high-level view of the true human cost of the pandemic,” he said.

Yale School of Medicine

Dr. Wilson said he was not surprised by the findings. “There have been multiple studies, across multiple countries including the United States, which show similar findings—that observed deaths during this pandemic are substantially higher than expected,” he said. The current study findings are unique in that they compare the current pandemic to death rates in a nearly unbroken chain into the last century using data that only a few countries can provide, he noted. 

The mortality data are “quite similar to what we see in the United States, with the exception that Spain was particularly hard-hit in the first COVID-19 wave in April 2020, said Dr. Wilson. By contrast, “the U.S. had substantially more excess deaths in the recent Delta wave, presumably due to lower vaccination uptake,” he added.

The current study is important for clinicians and their patients, said Dr. Wilson. “Data like these can help cut through some of the misinformation, such as the idea that only people who would have died anyway die of COVID, or that COVID is not severe,” he emphasized. “Overall death data are quite clear that far more people, millions more people, died over the last 22 months than could possibly be explained except by a global-level mortality event,” he said. 

“One thing this study reminds us of is the value of high-quality data,” said Dr. Wilson. “Few countries have near complete vital statistics records on their entire populations and these can be so crucial to understand the true impact of pandemics and other disasters,” he explained. Of course, mortality data also serve as a reminder “that COVID is a serious disease: a once-in-a-century (we hope) pandemic,” he added.

The current study showed that excess death rates were similar, but not the same, from country to country, Dr. Wilson noted. “Moving forward, we need to learn what factors, from vaccination to social distancing strategies,” saved lives around the world,” he said. 

The study was supported by the Foundation for Research in Science and the Humanities at the University of Zurich, the Swiss National Science Foundation, and the U.S. National Institute of Allergy and Infectious Diseases. The researchers, Dr. Pal, and Dr. Wilson had no financial conflicts.

*This article was updated on 2/1/2022.

The COVID-19 pandemic is now associated with the highest number of excess deaths worldwide since the 1918 flu pandemic, sometimes known as the “Spanish flu.”

Excess mortality is a way of quantifying the impact of a pandemic, based on overall mortality from nonpandemic periods. Mortality data over long periods of time are not available for many countries, but Switzerland, Sweden, and Spain have accumulated death count data for an uninterrupted period of more than 100 years.

In a study published in the Annals of Internal Medicine, Kaspar Staub, PhD, of the University of Zurich led a team of researchers in reviewing data on monthly excess deaths from all causes for Switzerland, Sweden, and Spain for 2020 to 2021. Dr. Staub and colleagues also compared these numbers to other pandemic and nonpandemic periods since the end of the 19th century. The starting years were 1877 for Switzerland, 1851 for Sweden, and 1908 for Spain.

The researchers collected data for monthly all-cause deaths from the statistical offices of each country and determined excess mortality by comparing these numbers to population size and age structure.

They found that 2020 showed the highest number of excess deaths since 1918, with relative excess of deaths of 12.5% in Switzerland, 8.5% in Sweden, and 17.3 % in Spain.

To put it another way, the number of excess deaths per 100,000 people was 100 for Switzerland, 75 for Sweden, and 155 for Spain.

“Our findings suggest that the pandemic led to the second-largest mortality disaster driven by a viral infection in more than 100 years in the three countries we studied, second only to the 1918 influenza pandemic,” the researchers wrote.

They explained that the excess mortality for the year 1918 was six to seven times higher than the 2020 numbers, but that the 2020 numbers might have been higher without the strong public health interventions taken worldwide to mitigate the impact of the COVID-19 pandemic.

“Early estimates suggest that vaccination prevented approximately 470,000 deaths in persons aged 60 years or older across 33 European countries between December 2019 and November 2021,” they wrote. However, because the COVID-19 pandemic is ongoing, “a more conclusive assessment will have to wait,” they added.

The 2020 numbers also were higher than most mortality rates since 1918, including peak years of previous influenza pandemics that occurred in 1957, 1968, 1977, and, most recently, the swine flu pandemic of 2009 which was caused by a novel strain of the H1N1 influenza virus.

The study findings had some limitations. For example, only three countries were included. Also, monthly death numbers according to sex, age, and cause of death were available only for the past 60 years, and data from years before the 20th century may not be reliable, the researchers said.

The new study does not account for the long-term effects of patients suffering from long COVID, they noted.

Study findings support strong public health response

“With the COVID-19 pandemic ongoing, this study reinforces the historic magnitude of the problem in terms of mortality and could add to the justification for ongoing public health measures such as vaccination drives and vaccine mandates to curb deaths,” said Suman Pal, MD, an internal medicine physician at the University of New Mexico, Albuquerque, in an interview.

“The results are surprising because when we view the rapid advancement in medical science over the last few decades, which have led to a decline in mortality from many previously fatal diseases, the scale of excess mortality from COVID-19 seems to have offset many such gains in the past 2 years.”

Prior studies of United States mortality data have estimated that excess deaths in the United States in 2020 exceeded the deaths attributed to COVID-19, said Dr. Pal. “The findings of this study could help clinicians in their discussion of the need for COVID-19 prevention measures with their patients” and inform discussions between doctors and patients about prevention strategies, he explained.

“Emphasizing that this pandemic is the second-largest cause of death due to a viral infection in a century could help patients understand the need for public health measures that may be viewed as unprecedented, such as government-imposed lockdowns, contact tracing, mask requirements, restrictions on travel, and vaccine mandates,” Dr. Pal noted. Better understanding of the evidence behind such measures may decrease the public’s resistance to following them, he added.As for additional research, “region-specific analysis of excess deaths may help estimate the impact of COVID-19 better, especially in regions where data reporting may be unreliable.”

Dr. F. Perry Wilson's take on study

“All-cause mortality is a key metric to assess the impact of the pandemic, because each death is treated equally,” said F. Perry Wilson, MD, of Yale University, in an interview. “With this type of analysis, there is no vague definition of a death from COVID or with COVID,” he explained. “A death is a death, and more deaths than expected is, of course, a bad thing. These analyses give a high-level view of the true human cost of the pandemic,” he said.

Yale School of Medicine

Dr. Wilson said he was not surprised by the findings. “There have been multiple studies, across multiple countries including the United States, which show similar findings—that observed deaths during this pandemic are substantially higher than expected,” he said. The current study findings are unique in that they compare the current pandemic to death rates in a nearly unbroken chain into the last century using data that only a few countries can provide, he noted. 

The mortality data are “quite similar to what we see in the United States, with the exception that Spain was particularly hard-hit in the first COVID-19 wave in April 2020, said Dr. Wilson. By contrast, “the U.S. had substantially more excess deaths in the recent Delta wave, presumably due to lower vaccination uptake,” he added.

The current study is important for clinicians and their patients, said Dr. Wilson. “Data like these can help cut through some of the misinformation, such as the idea that only people who would have died anyway die of COVID, or that COVID is not severe,” he emphasized. “Overall death data are quite clear that far more people, millions more people, died over the last 22 months than could possibly be explained except by a global-level mortality event,” he said. 

“One thing this study reminds us of is the value of high-quality data,” said Dr. Wilson. “Few countries have near complete vital statistics records on their entire populations and these can be so crucial to understand the true impact of pandemics and other disasters,” he explained. Of course, mortality data also serve as a reminder “that COVID is a serious disease: a once-in-a-century (we hope) pandemic,” he added.

The current study showed that excess death rates were similar, but not the same, from country to country, Dr. Wilson noted. “Moving forward, we need to learn what factors, from vaccination to social distancing strategies,” saved lives around the world,” he said. 

The study was supported by the Foundation for Research in Science and the Humanities at the University of Zurich, the Swiss National Science Foundation, and the U.S. National Institute of Allergy and Infectious Diseases. The researchers, Dr. Pal, and Dr. Wilson had no financial conflicts.

*This article was updated on 2/1/2022.

The COVID-19 pandemic is now associated with the highest number of excess deaths worldwide since the 1918 flu pandemic, sometimes known as the “Spanish flu.”

Excess mortality is a way of quantifying the impact of a pandemic, based on overall mortality from nonpandemic periods. Mortality data over long periods of time are not available for many countries, but Switzerland, Sweden, and Spain have accumulated death count data for an uninterrupted period of more than 100 years.

In a study published in the Annals of Internal Medicine, Kaspar Staub, PhD, of the University of Zurich led a team of researchers in reviewing data on monthly excess deaths from all causes for Switzerland, Sweden, and Spain for 2020 to 2021. Dr. Staub and colleagues also compared these numbers to other pandemic and nonpandemic periods since the end of the 19th century. The starting years were 1877 for Switzerland, 1851 for Sweden, and 1908 for Spain.

The researchers collected data for monthly all-cause deaths from the statistical offices of each country and determined excess mortality by comparing these numbers to population size and age structure.

They found that 2020 showed the highest number of excess deaths since 1918, with relative excess of deaths of 12.5% in Switzerland, 8.5% in Sweden, and 17.3 % in Spain.

To put it another way, the number of excess deaths per 100,000 people was 100 for Switzerland, 75 for Sweden, and 155 for Spain.

“Our findings suggest that the pandemic led to the second-largest mortality disaster driven by a viral infection in more than 100 years in the three countries we studied, second only to the 1918 influenza pandemic,” the researchers wrote.

They explained that the excess mortality for the year 1918 was six to seven times higher than the 2020 numbers, but that the 2020 numbers might have been higher without the strong public health interventions taken worldwide to mitigate the impact of the COVID-19 pandemic.

“Early estimates suggest that vaccination prevented approximately 470,000 deaths in persons aged 60 years or older across 33 European countries between December 2019 and November 2021,” they wrote. However, because the COVID-19 pandemic is ongoing, “a more conclusive assessment will have to wait,” they added.

The 2020 numbers also were higher than most mortality rates since 1918, including peak years of previous influenza pandemics that occurred in 1957, 1968, 1977, and, most recently, the swine flu pandemic of 2009 which was caused by a novel strain of the H1N1 influenza virus.

The study findings had some limitations. For example, only three countries were included. Also, monthly death numbers according to sex, age, and cause of death were available only for the past 60 years, and data from years before the 20th century may not be reliable, the researchers said.

The new study does not account for the long-term effects of patients suffering from long COVID, they noted.

Study findings support strong public health response

“With the COVID-19 pandemic ongoing, this study reinforces the historic magnitude of the problem in terms of mortality and could add to the justification for ongoing public health measures such as vaccination drives and vaccine mandates to curb deaths,” said Suman Pal, MD, an internal medicine physician at the University of New Mexico, Albuquerque, in an interview.

“The results are surprising because when we view the rapid advancement in medical science over the last few decades, which have led to a decline in mortality from many previously fatal diseases, the scale of excess mortality from COVID-19 seems to have offset many such gains in the past 2 years.”

Prior studies of United States mortality data have estimated that excess deaths in the United States in 2020 exceeded the deaths attributed to COVID-19, said Dr. Pal. “The findings of this study could help clinicians in their discussion of the need for COVID-19 prevention measures with their patients” and inform discussions between doctors and patients about prevention strategies, he explained.

“Emphasizing that this pandemic is the second-largest cause of death due to a viral infection in a century could help patients understand the need for public health measures that may be viewed as unprecedented, such as government-imposed lockdowns, contact tracing, mask requirements, restrictions on travel, and vaccine mandates,” Dr. Pal noted. Better understanding of the evidence behind such measures may decrease the public’s resistance to following them, he added.As for additional research, “region-specific analysis of excess deaths may help estimate the impact of COVID-19 better, especially in regions where data reporting may be unreliable.”

Dr. F. Perry Wilson's take on study

“All-cause mortality is a key metric to assess the impact of the pandemic, because each death is treated equally,” said F. Perry Wilson, MD, of Yale University, in an interview. “With this type of analysis, there is no vague definition of a death from COVID or with COVID,” he explained. “A death is a death, and more deaths than expected is, of course, a bad thing. These analyses give a high-level view of the true human cost of the pandemic,” he said.

Yale School of Medicine

Dr. Wilson said he was not surprised by the findings. “There have been multiple studies, across multiple countries including the United States, which show similar findings—that observed deaths during this pandemic are substantially higher than expected,” he said. The current study findings are unique in that they compare the current pandemic to death rates in a nearly unbroken chain into the last century using data that only a few countries can provide, he noted. 

The mortality data are “quite similar to what we see in the United States, with the exception that Spain was particularly hard-hit in the first COVID-19 wave in April 2020, said Dr. Wilson. By contrast, “the U.S. had substantially more excess deaths in the recent Delta wave, presumably due to lower vaccination uptake,” he added.

The current study is important for clinicians and their patients, said Dr. Wilson. “Data like these can help cut through some of the misinformation, such as the idea that only people who would have died anyway die of COVID, or that COVID is not severe,” he emphasized. “Overall death data are quite clear that far more people, millions more people, died over the last 22 months than could possibly be explained except by a global-level mortality event,” he said. 

“One thing this study reminds us of is the value of high-quality data,” said Dr. Wilson. “Few countries have near complete vital statistics records on their entire populations and these can be so crucial to understand the true impact of pandemics and other disasters,” he explained. Of course, mortality data also serve as a reminder “that COVID is a serious disease: a once-in-a-century (we hope) pandemic,” he added.

The current study showed that excess death rates were similar, but not the same, from country to country, Dr. Wilson noted. “Moving forward, we need to learn what factors, from vaccination to social distancing strategies,” saved lives around the world,” he said. 

The study was supported by the Foundation for Research in Science and the Humanities at the University of Zurich, the Swiss National Science Foundation, and the U.S. National Institute of Allergy and Infectious Diseases. The researchers, Dr. Pal, and Dr. Wilson had no financial conflicts.

*This article was updated on 2/1/2022.