Commentary

Introduction

In the last 20 years there has been a marked rise in the number of children and adolescents receiving the diagnosis of bipolar disorder (BD) – a mood disorder that, classically, involves cycling between episodes of elevated mood and episodes of low mood (Arch. Gen. Psychiatry 2207;64:1032-9). The increase in diagnosis is partly explained by the inclusion of children with chronic irritability being diagnosed with BD. This has led to concern about the subsequent use of approved second-generation antipsychotics for chronically irritable children, with the resultant side effects.

A new diagnosis called disruptive mood dysregulation disorder (DMDD) was introduced into the DSM-5 to describe these chronically irritable children and, in part, to reduce the number of children receiving a bipolar diagnosis. So, how does one know whether a child has BD, DMDD, or something else? The two brief cases that follow distinguish the difference between BD and DMDD.

Case 1 summary

Joseph is a 15-year-old boy with a history of childhood depression. About 1 year ago, he began to appear more irritable and anxious. Despite his parents’ prohibition, he was going out at night and was intoxicated on several occasions when he came home – something he had never done before. After about 2 weeks of this, he began going to bed at midnight, but would be up again by 4 a.m. talking to himself, playing music, or exercising. He was hanging out with a different crowd. He began to talk about the possibility of becoming part of a motorcycle gang – at some point perhaps the leader of Hells Angels. Slowly, this resolved. However, these symptoms recurred about 1 month ago with progressive worsening, again, and 2 days ago he stopped sleeping at all. He has been locking himself in his room, talking rapidly and excessively about motorcycles, complaining that he “just needed to get his thoughts together.” He was very distractible and was not eating. His mother called his primary care clinician who advised her to bring him to the ED, which she could do only by police because he refused to leave the home, complaining of the “noises” outside.

Case 1 discussion

Joseph most likely has bipolar I disorder, although a substance-induced mania will have to be ruled out. His symptoms are classic for what we think of as “narrow phenotypic” mania – elated and irritable mood, grandiosity, flight of ideas, decreased need for sleep, hypertalkativeness, increase in goal-directed activity, severe distractibility, and excessive involvement in activities that are likely to have painful consequences. These episodes are a clear change from baseline. Here, Joseph has been previously depressed, but never had symptoms like this that came, went, and then returned. If these manic symptoms continue for 1 week or longer, or are so severe as to require him to be hospitalized, these are a manic episode, which, essentially, makes the diagnosis of bipolar I disorder. Most clinicians have seen mania in late adolescence and early adulthood and can distinguish when these episodes occur in childhood. There is less ambiguity about this diagnosis when it occurs with frank mania.

Case 2 summary

Henry is a 12-year-old boy. His parents say that he’s been difficult since he was “in the womb.” Starting at about the age of 4 years, they started to notice that he would frequently become moody – lasting almost all day in a way that was noticed by everyone. He remains almost constantly irritable. He responds extremely to negative emotional stimuli, like when he got so upset about striking out at a Little League game last year that he had a 15-minute temper outburst that couldn’t be stopped. When his father removed him from the field to the car, he kicked out a window. These types of events are not uncommon, occurring four to five times per week, and are associated with verbal and physical aggression. There have been no symptom-free periods since age 4 years. There have been no clear episodes, and nothing that could be described as elation.

Case 2 discussion

Henry would very likely meet the criteria for the DSM-5 diagnosis of disruptive mood dysregulation disorder. DMDD requires that there be severe and recurrent temper outbursts that can be verbal or physical and are grossly out of proportion to the situation, happening at least three times a week for the past year. In between these outbursts, the child’s mood is angry or irritable, most of the day, nearly every day with no time longer than 3 months in the last year without symptoms. There cannot be symptoms of mania or hypomania. DMDD should be distinguished from oppositional-defiant disorder (ODD), which cannot be diagnosed concurrently. ODD has similar characteristics, but the temper outbursts are not as severe, frequent, or chronic. The mood symptoms in DMDD predominate, while oppositionality predominates in ODD. Note the chronicity of irritable mood in DMDD. This is the distinguishing characteristic of the disorder – chronic, nonepisodic irritability.

General discussion

The distinction between BD and DMDD does matter, but it is sometimes quite hard to draw a clear line – even for the experts. It can be easy to be frustrated with yourself as a clinician when you’re unable to come to a clear decision about the diagnosis. With mood disorders in children, however, it’s important not to attribute the field’s lack of clarity to your own lack of knowledge. In these difficult cases, it’s highly likely that even the experts would disagree. Making the distinction between bipolar disorder and DMDD becomes even more complex in the situation of “other specified bipolar and related disorders,” which allows for short or subsyndromal hypomanic episodes with major depression, hypomania without depression, or short-duration cyclothymia. These cases, formerly called “bipolar, not otherwise specified,” are more likely to progress to adult bipolar disorder I or II. DMDD, on the other hand, is more likely to progress to adult depression (Biol. Psychiatry 2006;60:991-7).

Why does the distinction matter? Because the treatment for bipolar disorder is likely to involve one of the traditional mood stabilizers or the second-generation antipsychotics that are Food and Drug Administration–approved for bipolar disorder along with family education and cognitive-behavioral therapy. However, there is no evidence at this time that the management of DMDD should consist of these same treatments. In fact, a trial of lithium for DMDD (actually, its research predecessor severe mood dysregulation) was negative (J. Child. Adolesc. Psychopharmacol. 2009;19:61-73). While we are still working out how to help children with DMDD, the current trials being done are examining the use of antidepressants and psychostimulants (either serially or in combination) along with family-based interventions similar to those used for ODD. These are tough cases, and frequently a consult with a child psychiatrist or psychologist will be helpful.

Dr. Althoff is an associate professor of psychiatry, psychology, and pediatrics at the University of Vermont, Burlington. He is director of the division of behavioral genetics and conducts research on the development of self-regulation in children. Dr. Althoff has received grants/research support from the National Institute of Mental Health, the National Institute of General Medical Sciences, the Research Center for Children, Youth, and Families, and the Klingenstein Third Generation Foundation, and honoraria from the Oakstone General Publishing for CME presentations. E-mail him at [email protected].

Introduction

In the last 20 years there has been a marked rise in the number of children and adolescents receiving the diagnosis of bipolar disorder (BD) – a mood disorder that, classically, involves cycling between episodes of elevated mood and episodes of low mood (Arch. Gen. Psychiatry 2207;64:1032-9). The increase in diagnosis is partly explained by the inclusion of children with chronic irritability being diagnosed with BD. This has led to concern about the subsequent use of approved second-generation antipsychotics for chronically irritable children, with the resultant side effects.

A new diagnosis called disruptive mood dysregulation disorder (DMDD) was introduced into the DSM-5 to describe these chronically irritable children and, in part, to reduce the number of children receiving a bipolar diagnosis. So, how does one know whether a child has BD, DMDD, or something else? The two brief cases that follow distinguish the difference between BD and DMDD.

Case 1 summary

Joseph is a 15-year-old boy with a history of childhood depression. About 1 year ago, he began to appear more irritable and anxious. Despite his parents’ prohibition, he was going out at night and was intoxicated on several occasions when he came home – something he had never done before. After about 2 weeks of this, he began going to bed at midnight, but would be up again by 4 a.m. talking to himself, playing music, or exercising. He was hanging out with a different crowd. He began to talk about the possibility of becoming part of a motorcycle gang – at some point perhaps the leader of Hells Angels. Slowly, this resolved. However, these symptoms recurred about 1 month ago with progressive worsening, again, and 2 days ago he stopped sleeping at all. He has been locking himself in his room, talking rapidly and excessively about motorcycles, complaining that he “just needed to get his thoughts together.” He was very distractible and was not eating. His mother called his primary care clinician who advised her to bring him to the ED, which she could do only by police because he refused to leave the home, complaining of the “noises” outside.

Case 1 discussion

Joseph most likely has bipolar I disorder, although a substance-induced mania will have to be ruled out. His symptoms are classic for what we think of as “narrow phenotypic” mania – elated and irritable mood, grandiosity, flight of ideas, decreased need for sleep, hypertalkativeness, increase in goal-directed activity, severe distractibility, and excessive involvement in activities that are likely to have painful consequences. These episodes are a clear change from baseline. Here, Joseph has been previously depressed, but never had symptoms like this that came, went, and then returned. If these manic symptoms continue for 1 week or longer, or are so severe as to require him to be hospitalized, these are a manic episode, which, essentially, makes the diagnosis of bipolar I disorder. Most clinicians have seen mania in late adolescence and early adulthood and can distinguish when these episodes occur in childhood. There is less ambiguity about this diagnosis when it occurs with frank mania.

Case 2 summary

Henry is a 12-year-old boy. His parents say that he’s been difficult since he was “in the womb.” Starting at about the age of 4 years, they started to notice that he would frequently become moody – lasting almost all day in a way that was noticed by everyone. He remains almost constantly irritable. He responds extremely to negative emotional stimuli, like when he got so upset about striking out at a Little League game last year that he had a 15-minute temper outburst that couldn’t be stopped. When his father removed him from the field to the car, he kicked out a window. These types of events are not uncommon, occurring four to five times per week, and are associated with verbal and physical aggression. There have been no symptom-free periods since age 4 years. There have been no clear episodes, and nothing that could be described as elation.

Case 2 discussion

Henry would very likely meet the criteria for the DSM-5 diagnosis of disruptive mood dysregulation disorder. DMDD requires that there be severe and recurrent temper outbursts that can be verbal or physical and are grossly out of proportion to the situation, happening at least three times a week for the past year. In between these outbursts, the child’s mood is angry or irritable, most of the day, nearly every day with no time longer than 3 months in the last year without symptoms. There cannot be symptoms of mania or hypomania. DMDD should be distinguished from oppositional-defiant disorder (ODD), which cannot be diagnosed concurrently. ODD has similar characteristics, but the temper outbursts are not as severe, frequent, or chronic. The mood symptoms in DMDD predominate, while oppositionality predominates in ODD. Note the chronicity of irritable mood in DMDD. This is the distinguishing characteristic of the disorder – chronic, nonepisodic irritability.

General discussion

The distinction between BD and DMDD does matter, but it is sometimes quite hard to draw a clear line – even for the experts. It can be easy to be frustrated with yourself as a clinician when you’re unable to come to a clear decision about the diagnosis. With mood disorders in children, however, it’s important not to attribute the field’s lack of clarity to your own lack of knowledge. In these difficult cases, it’s highly likely that even the experts would disagree. Making the distinction between bipolar disorder and DMDD becomes even more complex in the situation of “other specified bipolar and related disorders,” which allows for short or subsyndromal hypomanic episodes with major depression, hypomania without depression, or short-duration cyclothymia. These cases, formerly called “bipolar, not otherwise specified,” are more likely to progress to adult bipolar disorder I or II. DMDD, on the other hand, is more likely to progress to adult depression (Biol. Psychiatry 2006;60:991-7).

Why does the distinction matter? Because the treatment for bipolar disorder is likely to involve one of the traditional mood stabilizers or the second-generation antipsychotics that are Food and Drug Administration–approved for bipolar disorder along with family education and cognitive-behavioral therapy. However, there is no evidence at this time that the management of DMDD should consist of these same treatments. In fact, a trial of lithium for DMDD (actually, its research predecessor severe mood dysregulation) was negative (J. Child. Adolesc. Psychopharmacol. 2009;19:61-73). While we are still working out how to help children with DMDD, the current trials being done are examining the use of antidepressants and psychostimulants (either serially or in combination) along with family-based interventions similar to those used for ODD. These are tough cases, and frequently a consult with a child psychiatrist or psychologist will be helpful.

Dr. Althoff is an associate professor of psychiatry, psychology, and pediatrics at the University of Vermont, Burlington. He is director of the division of behavioral genetics and conducts research on the development of self-regulation in children. Dr. Althoff has received grants/research support from the National Institute of Mental Health, the National Institute of General Medical Sciences, the Research Center for Children, Youth, and Families, and the Klingenstein Third Generation Foundation, and honoraria from the Oakstone General Publishing for CME presentations. E-mail him at [email protected].

Introduction

In the last 20 years there has been a marked rise in the number of children and adolescents receiving the diagnosis of bipolar disorder (BD) – a mood disorder that, classically, involves cycling between episodes of elevated mood and episodes of low mood (Arch. Gen. Psychiatry 2207;64:1032-9). The increase in diagnosis is partly explained by the inclusion of children with chronic irritability being diagnosed with BD. This has led to concern about the subsequent use of approved second-generation antipsychotics for chronically irritable children, with the resultant side effects.

A new diagnosis called disruptive mood dysregulation disorder (DMDD) was introduced into the DSM-5 to describe these chronically irritable children and, in part, to reduce the number of children receiving a bipolar diagnosis. So, how does one know whether a child has BD, DMDD, or something else? The two brief cases that follow distinguish the difference between BD and DMDD.

Case 1 summary

Joseph is a 15-year-old boy with a history of childhood depression. About 1 year ago, he began to appear more irritable and anxious. Despite his parents’ prohibition, he was going out at night and was intoxicated on several occasions when he came home – something he had never done before. After about 2 weeks of this, he began going to bed at midnight, but would be up again by 4 a.m. talking to himself, playing music, or exercising. He was hanging out with a different crowd. He began to talk about the possibility of becoming part of a motorcycle gang – at some point perhaps the leader of Hells Angels. Slowly, this resolved. However, these symptoms recurred about 1 month ago with progressive worsening, again, and 2 days ago he stopped sleeping at all. He has been locking himself in his room, talking rapidly and excessively about motorcycles, complaining that he “just needed to get his thoughts together.” He was very distractible and was not eating. His mother called his primary care clinician who advised her to bring him to the ED, which she could do only by police because he refused to leave the home, complaining of the “noises” outside.

Case 1 discussion

Joseph most likely has bipolar I disorder, although a substance-induced mania will have to be ruled out. His symptoms are classic for what we think of as “narrow phenotypic” mania – elated and irritable mood, grandiosity, flight of ideas, decreased need for sleep, hypertalkativeness, increase in goal-directed activity, severe distractibility, and excessive involvement in activities that are likely to have painful consequences. These episodes are a clear change from baseline. Here, Joseph has been previously depressed, but never had symptoms like this that came, went, and then returned. If these manic symptoms continue for 1 week or longer, or are so severe as to require him to be hospitalized, these are a manic episode, which, essentially, makes the diagnosis of bipolar I disorder. Most clinicians have seen mania in late adolescence and early adulthood and can distinguish when these episodes occur in childhood. There is less ambiguity about this diagnosis when it occurs with frank mania.

Case 2 summary

Henry is a 12-year-old boy. His parents say that he’s been difficult since he was “in the womb.” Starting at about the age of 4 years, they started to notice that he would frequently become moody – lasting almost all day in a way that was noticed by everyone. He remains almost constantly irritable. He responds extremely to negative emotional stimuli, like when he got so upset about striking out at a Little League game last year that he had a 15-minute temper outburst that couldn’t be stopped. When his father removed him from the field to the car, he kicked out a window. These types of events are not uncommon, occurring four to five times per week, and are associated with verbal and physical aggression. There have been no symptom-free periods since age 4 years. There have been no clear episodes, and nothing that could be described as elation.

Case 2 discussion

Henry would very likely meet the criteria for the DSM-5 diagnosis of disruptive mood dysregulation disorder. DMDD requires that there be severe and recurrent temper outbursts that can be verbal or physical and are grossly out of proportion to the situation, happening at least three times a week for the past year. In between these outbursts, the child’s mood is angry or irritable, most of the day, nearly every day with no time longer than 3 months in the last year without symptoms. There cannot be symptoms of mania or hypomania. DMDD should be distinguished from oppositional-defiant disorder (ODD), which cannot be diagnosed concurrently. ODD has similar characteristics, but the temper outbursts are not as severe, frequent, or chronic. The mood symptoms in DMDD predominate, while oppositionality predominates in ODD. Note the chronicity of irritable mood in DMDD. This is the distinguishing characteristic of the disorder – chronic, nonepisodic irritability.

General discussion

The distinction between BD and DMDD does matter, but it is sometimes quite hard to draw a clear line – even for the experts. It can be easy to be frustrated with yourself as a clinician when you’re unable to come to a clear decision about the diagnosis. With mood disorders in children, however, it’s important not to attribute the field’s lack of clarity to your own lack of knowledge. In these difficult cases, it’s highly likely that even the experts would disagree. Making the distinction between bipolar disorder and DMDD becomes even more complex in the situation of “other specified bipolar and related disorders,” which allows for short or subsyndromal hypomanic episodes with major depression, hypomania without depression, or short-duration cyclothymia. These cases, formerly called “bipolar, not otherwise specified,” are more likely to progress to adult bipolar disorder I or II. DMDD, on the other hand, is more likely to progress to adult depression (Biol. Psychiatry 2006;60:991-7).

Why does the distinction matter? Because the treatment for bipolar disorder is likely to involve one of the traditional mood stabilizers or the second-generation antipsychotics that are Food and Drug Administration–approved for bipolar disorder along with family education and cognitive-behavioral therapy. However, there is no evidence at this time that the management of DMDD should consist of these same treatments. In fact, a trial of lithium for DMDD (actually, its research predecessor severe mood dysregulation) was negative (J. Child. Adolesc. Psychopharmacol. 2009;19:61-73). While we are still working out how to help children with DMDD, the current trials being done are examining the use of antidepressants and psychostimulants (either serially or in combination) along with family-based interventions similar to those used for ODD. These are tough cases, and frequently a consult with a child psychiatrist or psychologist will be helpful.

Dr. Althoff is an associate professor of psychiatry, psychology, and pediatrics at the University of Vermont, Burlington. He is director of the division of behavioral genetics and conducts research on the development of self-regulation in children. Dr. Althoff has received grants/research support from the National Institute of Mental Health, the National Institute of General Medical Sciences, the Research Center for Children, Youth, and Families, and the Klingenstein Third Generation Foundation, and honoraria from the Oakstone General Publishing for CME presentations. E-mail him at [email protected].

Like many groups, our practice shares backup call on a rotational basis. This week-long pleasure cruise is characterized by phone calls throughout the night (“Why are we checking a temperature on a comfortably sleeping 85-year-old at 2 a.m. again?”), dubious requests (“I am still unclear why you were cleaning out your medicine cabinet at 4 a.m. Even so, I cannot refill the oxycodone you just flushed down the toilet.”), and fragmented sleep associated with clinically significant carbohydrate cravings.

In the old days, this indispensable community service could be handled without the need for remoting into the practice. But most calls these days require that our computers be close at hand. As such, we find ourselves in the wee hours of morning staring at computer screens that, we are increasingly aware, emit melatonin-killing blue wavelengths of light. This makes it that much harder to go back to sleep after triaging colonoscopy-preps-gone-wrong calls.

Several months ago, one of my patients gave me orange-tinted, blue light–blocking (BB) glasses as a gift. These glasses are designed to filter out the blue wavelength (480 nm), which most strongly impacts alertness, cognitive performance, and circadian physiology.

They have collected dust on my desk. … until last week while on call.

In a recently published study, Stéphanie van der Lely of the University of Basel, Switzerland, and colleagues evaluated the impact of blue-blocker glasses as a countermeasure to evening computer screen time among adolescents (J. Adolesc. Health 2015;56:113-9). Thirteen adolescents with a mean age of 16 years participated in this crossover study over 16 days. Blue blockers were provided from 6 p.m. to sleep onset. Glasses reduced the blue light transmission to 30%.

Compared with clear lenses, BB significantly attenuated LED-induced melatonin suppression in the evening. BB glasses also decreased vigilant attention and subjective alertness before bedtime.

This article would suggest that my melatonin is not being suppressed while I wear the glasses as I do my evening article writing and answer phone calls. The color shifts take some getting used to, but the glasses are comfortable. In addition to sleeping in the attic, my backup call routine will include these glasses.

Now, if we can just find something to filter out midnight acetaminophen requests. At least I’ll fall back asleep quickly after telling them to take two and call me in the morning.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author. The opinions expressed in this article should not be used to diagnose or treat any medical condition nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician.

Like many groups, our practice shares backup call on a rotational basis. This week-long pleasure cruise is characterized by phone calls throughout the night (“Why are we checking a temperature on a comfortably sleeping 85-year-old at 2 a.m. again?”), dubious requests (“I am still unclear why you were cleaning out your medicine cabinet at 4 a.m. Even so, I cannot refill the oxycodone you just flushed down the toilet.”), and fragmented sleep associated with clinically significant carbohydrate cravings.

In the old days, this indispensable community service could be handled without the need for remoting into the practice. But most calls these days require that our computers be close at hand. As such, we find ourselves in the wee hours of morning staring at computer screens that, we are increasingly aware, emit melatonin-killing blue wavelengths of light. This makes it that much harder to go back to sleep after triaging colonoscopy-preps-gone-wrong calls.

Several months ago, one of my patients gave me orange-tinted, blue light–blocking (BB) glasses as a gift. These glasses are designed to filter out the blue wavelength (480 nm), which most strongly impacts alertness, cognitive performance, and circadian physiology.

They have collected dust on my desk. … until last week while on call.

In a recently published study, Stéphanie van der Lely of the University of Basel, Switzerland, and colleagues evaluated the impact of blue-blocker glasses as a countermeasure to evening computer screen time among adolescents (J. Adolesc. Health 2015;56:113-9). Thirteen adolescents with a mean age of 16 years participated in this crossover study over 16 days. Blue blockers were provided from 6 p.m. to sleep onset. Glasses reduced the blue light transmission to 30%.

Compared with clear lenses, BB significantly attenuated LED-induced melatonin suppression in the evening. BB glasses also decreased vigilant attention and subjective alertness before bedtime.

This article would suggest that my melatonin is not being suppressed while I wear the glasses as I do my evening article writing and answer phone calls. The color shifts take some getting used to, but the glasses are comfortable. In addition to sleeping in the attic, my backup call routine will include these glasses.

Now, if we can just find something to filter out midnight acetaminophen requests. At least I’ll fall back asleep quickly after telling them to take two and call me in the morning.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author. The opinions expressed in this article should not be used to diagnose or treat any medical condition nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician.

Like many groups, our practice shares backup call on a rotational basis. This week-long pleasure cruise is characterized by phone calls throughout the night (“Why are we checking a temperature on a comfortably sleeping 85-year-old at 2 a.m. again?”), dubious requests (“I am still unclear why you were cleaning out your medicine cabinet at 4 a.m. Even so, I cannot refill the oxycodone you just flushed down the toilet.”), and fragmented sleep associated with clinically significant carbohydrate cravings.

In the old days, this indispensable community service could be handled without the need for remoting into the practice. But most calls these days require that our computers be close at hand. As such, we find ourselves in the wee hours of morning staring at computer screens that, we are increasingly aware, emit melatonin-killing blue wavelengths of light. This makes it that much harder to go back to sleep after triaging colonoscopy-preps-gone-wrong calls.

Several months ago, one of my patients gave me orange-tinted, blue light–blocking (BB) glasses as a gift. These glasses are designed to filter out the blue wavelength (480 nm), which most strongly impacts alertness, cognitive performance, and circadian physiology.

They have collected dust on my desk. … until last week while on call.

In a recently published study, Stéphanie van der Lely of the University of Basel, Switzerland, and colleagues evaluated the impact of blue-blocker glasses as a countermeasure to evening computer screen time among adolescents (J. Adolesc. Health 2015;56:113-9). Thirteen adolescents with a mean age of 16 years participated in this crossover study over 16 days. Blue blockers were provided from 6 p.m. to sleep onset. Glasses reduced the blue light transmission to 30%.

Compared with clear lenses, BB significantly attenuated LED-induced melatonin suppression in the evening. BB glasses also decreased vigilant attention and subjective alertness before bedtime.

This article would suggest that my melatonin is not being suppressed while I wear the glasses as I do my evening article writing and answer phone calls. The color shifts take some getting used to, but the glasses are comfortable. In addition to sleeping in the attic, my backup call routine will include these glasses.

Now, if we can just find something to filter out midnight acetaminophen requests. At least I’ll fall back asleep quickly after telling them to take two and call me in the morning.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author. The opinions expressed in this article should not be used to diagnose or treat any medical condition nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician.

As reviewed in a previous column, in December 2014, the Food and Drug Administration released the Pregnancy and Lactation Labeling Rule (PLLR), which will go into effect on June 30, 2015. This replaces and addresses the limitations of the system that has been in place for more than 30 years, which ascribed a pregnancy risk category of A,B,C,D, or X to drugs, with the purpose of informing the clinician and patient about the reproductive safety of medications during pregnancy. Though well intentioned, criticisms of this system have been abundant.

The system certainly simplified the interaction between physicians and patients, who presumably would be reassured that the risk of a certain medicine had been quantified by a regulatory body and therefore could be used as a basis for making a decision about whether or not to take a medicine during pregnancy. While the purpose of the labeling system was to provide some overarching guidance about available reproductive safety information of a medicine, it was ultimately used by clinicians and patients either to somehow garner reassurance about a medicine, or to heighten concern about a medicine.

From the outset, the system could not take into account the accruing reproductive safety information regarding compounds across therapeutic categories, and as a result, the risk category could be inadvertently reassuring or even misleading to patients with respect to medicines they might decide to stop or to continue.

With the older labeling system, some medicines are in the same category, despite very different amounts of reproductive safety information available on the drugs. In the 1990s, there were more reproductive safety data available on certain selective serotonin reuptake inhibitors (SSRIs), compared with others, but now the amount of such data available across SSRIs is fairly consistent. Yet SSRI labels have not been updated with the abundance of new reproductive safety information that has become available.

Almost 10 years ago, paroxetine (Paxil) was switched from a category C to D, when first-trimester exposure was linked to an increased risk of birth defects, particularly heart defects. But it was not switched back to category C when data became available that did not support that level of concern. Because of some of its side effects, paroxetine may not be considered by many to be a first-line treatment for major depression, but it certainly would not be absolutely contraindicated during pregnancy as might be presumed by the assignment of a category D label.

Lithium and sodium valproate provide another example of the limitations of the old system, which will be addressed in the new system. While the teratogenicity of both agents has been well described, the absolute risk of malformations with fetal exposure to lithium is approximately 0.05%- 0.1%, but the risk of neural tube defects with sodium valproate is estimated at 8%. Complicating the issue further, in 2013, the FDA announced that sodium valproate had been changed from a category D to X for migraine prevention, but retained the category D classification for other indications.

Placing lithium in category D suggests a relative contraindication and yet discontinuing that medication during pregnancy can put the mother and her baby at risk, given the data supporting the rapid onset of relapse in women who stop mood stabilizers during pregnancy.

For women maintained on lithium for recurrent or brittle bipolar disorder, the drug would certainly not be contraindicated and may afford critical emotional well-being and protection from relapse during pregnancy; the clinical scenario of discontinuation of lithium proximate to or during pregnancy and subsequent relapse of underlying illness is a serious clinical matter frequently demanding urgent intervention.

Still another example of the incomplete informative value of the older system is found in the assignment of atypical antipsychotics into different risk categories. Lurasidone (Latuda), approved in 2010, is in category B, but other atypical antipsychotics are in category C. One might assume that this implies that there are more reproductive safety data available on lurasidone supporting safety, but in fact, reproductive safety data for this molecule are extremely limited, and the absence of adverse event information resulted in a category B. This is a great example of the clinical maxim that incomplete or sparse data is just that; it does not imply safety, it implies that we do not know a lot about the safety of a medication.

If the old system of pregnancy labeling was arbitrary, the PLLR will be more descriptive. Safety information during pregnancy and lactation in the drug label will appear in a section on pregnancy, reformatted to include a risk summary, clinical considerations, and data subsections, as well as a section on lactation, and a section on females and males of reproductive potential.

Ongoing revision of the label as information becomes outdated is a requirement, and manufacturers will be obligated to include information on whether there is a pregnancy registry for the given drug. The goal of the PLLR is thus to provide the patient and clinician with information which addresses both sides of the risk-benefit decision for a given medicine – risks of fetal drug exposure and the risk of untreated illness for the woman and baby, a factor that is not addressed at all with the current system.

Certainly, the new label system will be a charge to industry to establish, support, and encourage enrollment in well-designed pregnancy registries across therapeutic areas to provide ample amounts of good quality data that can then be used by patients along with their physicians to make the most appropriate clinical decisions.

Much of the currently available reproductive safety information on drugs is derived from spontaneous reports, where there has been inconsistent information and variable levels of scrutiny with respect to outcomes assessment, and from small, underpowered cohort studies or large administrative databases. Postmarketing surveillance efforts have been rather modest and have not been a priority for manufacturers in most cases. Hopefully, this will change as pregnancy registries become part of routine postmarketing surveillance.

The new system will not be a panacea, and I expect there will be growing pains, considering the huge challenge of reducing the available data of varying quality into distinct paragraphs. It may also be difficult to synthesize the volume of data and the nuanced differences between certain studies into a paragraph on risk assessment. The task will be simpler for some agents and more challenging for others where the data are less consistent. Questions also remain as to how data will be revised over time.

But despite these challenges, the new system represents a monumental change, and in my mind, will bring a focus to the importance of the issue of quantifying reproductive safety of medications used by women either planning to get pregnant or who are pregnant or breastfeeding, across therapeutic areas. Of particular importance, the new system will hopefully lead to more discussion between physician and patient about what is and is not known about the reproductive safety of a medication, versus a cursory reference to some previously assigned category label.

Our group has shown that when it comes to making decisions about using medication during pregnancy, even when given the same information, women will make different decisions. This is critical since people make personal decisions about the use of these medications in collaboration with their doctors on a case-by-case basis, based on personal preference, available information, and clinical conditions across a spectrum of severity.

As the FDA requirements shift from the arbitrary category label assignment to a more descriptive explanation of risk, based on available data, an important question will be what mechanism will be used by regulators collaborating with industry to update labels with the growing amounts of information on reproductive safety, particularly if there is a commitment from industry to enhance postmarketing surveillance with more pregnancy registries.

Better data can catalyze thoughtful discussions between doctor and patient regarding decisions to use or defer treatment with a given medicine. One might wonder if the new system will open a Pandora’s box. But I believe in this case, opening Pandora’s box would be welcome because it will hopefully lead to a more careful examination of the available information regarding reproductive safety and more informed decisions on the part of patients.

Dr. Cohen is the director of the Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information about reproductive mental health. He has been a consultant to manufacturers of antidepressant medications and is the principal investigator of the National Pregnancy Registry for Atypical Antipsychotics, which receives support from the manufacturers of those drugs. To comment, e-mail him at [email protected]. Scan this QR code or go to obgynnews.com to view similar columns.

As reviewed in a previous column, in December 2014, the Food and Drug Administration released the Pregnancy and Lactation Labeling Rule (PLLR), which will go into effect on June 30, 2015. This replaces and addresses the limitations of the system that has been in place for more than 30 years, which ascribed a pregnancy risk category of A,B,C,D, or X to drugs, with the purpose of informing the clinician and patient about the reproductive safety of medications during pregnancy. Though well intentioned, criticisms of this system have been abundant.

The system certainly simplified the interaction between physicians and patients, who presumably would be reassured that the risk of a certain medicine had been quantified by a regulatory body and therefore could be used as a basis for making a decision about whether or not to take a medicine during pregnancy. While the purpose of the labeling system was to provide some overarching guidance about available reproductive safety information of a medicine, it was ultimately used by clinicians and patients either to somehow garner reassurance about a medicine, or to heighten concern about a medicine.

From the outset, the system could not take into account the accruing reproductive safety information regarding compounds across therapeutic categories, and as a result, the risk category could be inadvertently reassuring or even misleading to patients with respect to medicines they might decide to stop or to continue.

With the older labeling system, some medicines are in the same category, despite very different amounts of reproductive safety information available on the drugs. In the 1990s, there were more reproductive safety data available on certain selective serotonin reuptake inhibitors (SSRIs), compared with others, but now the amount of such data available across SSRIs is fairly consistent. Yet SSRI labels have not been updated with the abundance of new reproductive safety information that has become available.

Almost 10 years ago, paroxetine (Paxil) was switched from a category C to D, when first-trimester exposure was linked to an increased risk of birth defects, particularly heart defects. But it was not switched back to category C when data became available that did not support that level of concern. Because of some of its side effects, paroxetine may not be considered by many to be a first-line treatment for major depression, but it certainly would not be absolutely contraindicated during pregnancy as might be presumed by the assignment of a category D label.

Lithium and sodium valproate provide another example of the limitations of the old system, which will be addressed in the new system. While the teratogenicity of both agents has been well described, the absolute risk of malformations with fetal exposure to lithium is approximately 0.05%- 0.1%, but the risk of neural tube defects with sodium valproate is estimated at 8%. Complicating the issue further, in 2013, the FDA announced that sodium valproate had been changed from a category D to X for migraine prevention, but retained the category D classification for other indications.

Placing lithium in category D suggests a relative contraindication and yet discontinuing that medication during pregnancy can put the mother and her baby at risk, given the data supporting the rapid onset of relapse in women who stop mood stabilizers during pregnancy.

For women maintained on lithium for recurrent or brittle bipolar disorder, the drug would certainly not be contraindicated and may afford critical emotional well-being and protection from relapse during pregnancy; the clinical scenario of discontinuation of lithium proximate to or during pregnancy and subsequent relapse of underlying illness is a serious clinical matter frequently demanding urgent intervention.

Still another example of the incomplete informative value of the older system is found in the assignment of atypical antipsychotics into different risk categories. Lurasidone (Latuda), approved in 2010, is in category B, but other atypical antipsychotics are in category C. One might assume that this implies that there are more reproductive safety data available on lurasidone supporting safety, but in fact, reproductive safety data for this molecule are extremely limited, and the absence of adverse event information resulted in a category B. This is a great example of the clinical maxim that incomplete or sparse data is just that; it does not imply safety, it implies that we do not know a lot about the safety of a medication.

If the old system of pregnancy labeling was arbitrary, the PLLR will be more descriptive. Safety information during pregnancy and lactation in the drug label will appear in a section on pregnancy, reformatted to include a risk summary, clinical considerations, and data subsections, as well as a section on lactation, and a section on females and males of reproductive potential.

Ongoing revision of the label as information becomes outdated is a requirement, and manufacturers will be obligated to include information on whether there is a pregnancy registry for the given drug. The goal of the PLLR is thus to provide the patient and clinician with information which addresses both sides of the risk-benefit decision for a given medicine – risks of fetal drug exposure and the risk of untreated illness for the woman and baby, a factor that is not addressed at all with the current system.

Certainly, the new label system will be a charge to industry to establish, support, and encourage enrollment in well-designed pregnancy registries across therapeutic areas to provide ample amounts of good quality data that can then be used by patients along with their physicians to make the most appropriate clinical decisions.

Much of the currently available reproductive safety information on drugs is derived from spontaneous reports, where there has been inconsistent information and variable levels of scrutiny with respect to outcomes assessment, and from small, underpowered cohort studies or large administrative databases. Postmarketing surveillance efforts have been rather modest and have not been a priority for manufacturers in most cases. Hopefully, this will change as pregnancy registries become part of routine postmarketing surveillance.

The new system will not be a panacea, and I expect there will be growing pains, considering the huge challenge of reducing the available data of varying quality into distinct paragraphs. It may also be difficult to synthesize the volume of data and the nuanced differences between certain studies into a paragraph on risk assessment. The task will be simpler for some agents and more challenging for others where the data are less consistent. Questions also remain as to how data will be revised over time.

But despite these challenges, the new system represents a monumental change, and in my mind, will bring a focus to the importance of the issue of quantifying reproductive safety of medications used by women either planning to get pregnant or who are pregnant or breastfeeding, across therapeutic areas. Of particular importance, the new system will hopefully lead to more discussion between physician and patient about what is and is not known about the reproductive safety of a medication, versus a cursory reference to some previously assigned category label.

Our group has shown that when it comes to making decisions about using medication during pregnancy, even when given the same information, women will make different decisions. This is critical since people make personal decisions about the use of these medications in collaboration with their doctors on a case-by-case basis, based on personal preference, available information, and clinical conditions across a spectrum of severity.

As the FDA requirements shift from the arbitrary category label assignment to a more descriptive explanation of risk, based on available data, an important question will be what mechanism will be used by regulators collaborating with industry to update labels with the growing amounts of information on reproductive safety, particularly if there is a commitment from industry to enhance postmarketing surveillance with more pregnancy registries.

Better data can catalyze thoughtful discussions between doctor and patient regarding decisions to use or defer treatment with a given medicine. One might wonder if the new system will open a Pandora’s box. But I believe in this case, opening Pandora’s box would be welcome because it will hopefully lead to a more careful examination of the available information regarding reproductive safety and more informed decisions on the part of patients.

Dr. Cohen is the director of the Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information about reproductive mental health. He has been a consultant to manufacturers of antidepressant medications and is the principal investigator of the National Pregnancy Registry for Atypical Antipsychotics, which receives support from the manufacturers of those drugs. To comment, e-mail him at [email protected]. Scan this QR code or go to obgynnews.com to view similar columns.

As reviewed in a previous column, in December 2014, the Food and Drug Administration released the Pregnancy and Lactation Labeling Rule (PLLR), which will go into effect on June 30, 2015. This replaces and addresses the limitations of the system that has been in place for more than 30 years, which ascribed a pregnancy risk category of A,B,C,D, or X to drugs, with the purpose of informing the clinician and patient about the reproductive safety of medications during pregnancy. Though well intentioned, criticisms of this system have been abundant.

The system certainly simplified the interaction between physicians and patients, who presumably would be reassured that the risk of a certain medicine had been quantified by a regulatory body and therefore could be used as a basis for making a decision about whether or not to take a medicine during pregnancy. While the purpose of the labeling system was to provide some overarching guidance about available reproductive safety information of a medicine, it was ultimately used by clinicians and patients either to somehow garner reassurance about a medicine, or to heighten concern about a medicine.

From the outset, the system could not take into account the accruing reproductive safety information regarding compounds across therapeutic categories, and as a result, the risk category could be inadvertently reassuring or even misleading to patients with respect to medicines they might decide to stop or to continue.

With the older labeling system, some medicines are in the same category, despite very different amounts of reproductive safety information available on the drugs. In the 1990s, there were more reproductive safety data available on certain selective serotonin reuptake inhibitors (SSRIs), compared with others, but now the amount of such data available across SSRIs is fairly consistent. Yet SSRI labels have not been updated with the abundance of new reproductive safety information that has become available.

Almost 10 years ago, paroxetine (Paxil) was switched from a category C to D, when first-trimester exposure was linked to an increased risk of birth defects, particularly heart defects. But it was not switched back to category C when data became available that did not support that level of concern. Because of some of its side effects, paroxetine may not be considered by many to be a first-line treatment for major depression, but it certainly would not be absolutely contraindicated during pregnancy as might be presumed by the assignment of a category D label.

Lithium and sodium valproate provide another example of the limitations of the old system, which will be addressed in the new system. While the teratogenicity of both agents has been well described, the absolute risk of malformations with fetal exposure to lithium is approximately 0.05%- 0.1%, but the risk of neural tube defects with sodium valproate is estimated at 8%. Complicating the issue further, in 2013, the FDA announced that sodium valproate had been changed from a category D to X for migraine prevention, but retained the category D classification for other indications.

Placing lithium in category D suggests a relative contraindication and yet discontinuing that medication during pregnancy can put the mother and her baby at risk, given the data supporting the rapid onset of relapse in women who stop mood stabilizers during pregnancy.

For women maintained on lithium for recurrent or brittle bipolar disorder, the drug would certainly not be contraindicated and may afford critical emotional well-being and protection from relapse during pregnancy; the clinical scenario of discontinuation of lithium proximate to or during pregnancy and subsequent relapse of underlying illness is a serious clinical matter frequently demanding urgent intervention.

Still another example of the incomplete informative value of the older system is found in the assignment of atypical antipsychotics into different risk categories. Lurasidone (Latuda), approved in 2010, is in category B, but other atypical antipsychotics are in category C. One might assume that this implies that there are more reproductive safety data available on lurasidone supporting safety, but in fact, reproductive safety data for this molecule are extremely limited, and the absence of adverse event information resulted in a category B. This is a great example of the clinical maxim that incomplete or sparse data is just that; it does not imply safety, it implies that we do not know a lot about the safety of a medication.

If the old system of pregnancy labeling was arbitrary, the PLLR will be more descriptive. Safety information during pregnancy and lactation in the drug label will appear in a section on pregnancy, reformatted to include a risk summary, clinical considerations, and data subsections, as well as a section on lactation, and a section on females and males of reproductive potential.

Ongoing revision of the label as information becomes outdated is a requirement, and manufacturers will be obligated to include information on whether there is a pregnancy registry for the given drug. The goal of the PLLR is thus to provide the patient and clinician with information which addresses both sides of the risk-benefit decision for a given medicine – risks of fetal drug exposure and the risk of untreated illness for the woman and baby, a factor that is not addressed at all with the current system.

Certainly, the new label system will be a charge to industry to establish, support, and encourage enrollment in well-designed pregnancy registries across therapeutic areas to provide ample amounts of good quality data that can then be used by patients along with their physicians to make the most appropriate clinical decisions.

Much of the currently available reproductive safety information on drugs is derived from spontaneous reports, where there has been inconsistent information and variable levels of scrutiny with respect to outcomes assessment, and from small, underpowered cohort studies or large administrative databases. Postmarketing surveillance efforts have been rather modest and have not been a priority for manufacturers in most cases. Hopefully, this will change as pregnancy registries become part of routine postmarketing surveillance.

The new system will not be a panacea, and I expect there will be growing pains, considering the huge challenge of reducing the available data of varying quality into distinct paragraphs. It may also be difficult to synthesize the volume of data and the nuanced differences between certain studies into a paragraph on risk assessment. The task will be simpler for some agents and more challenging for others where the data are less consistent. Questions also remain as to how data will be revised over time.

But despite these challenges, the new system represents a monumental change, and in my mind, will bring a focus to the importance of the issue of quantifying reproductive safety of medications used by women either planning to get pregnant or who are pregnant or breastfeeding, across therapeutic areas. Of particular importance, the new system will hopefully lead to more discussion between physician and patient about what is and is not known about the reproductive safety of a medication, versus a cursory reference to some previously assigned category label.

Our group has shown that when it comes to making decisions about using medication during pregnancy, even when given the same information, women will make different decisions. This is critical since people make personal decisions about the use of these medications in collaboration with their doctors on a case-by-case basis, based on personal preference, available information, and clinical conditions across a spectrum of severity.

As the FDA requirements shift from the arbitrary category label assignment to a more descriptive explanation of risk, based on available data, an important question will be what mechanism will be used by regulators collaborating with industry to update labels with the growing amounts of information on reproductive safety, particularly if there is a commitment from industry to enhance postmarketing surveillance with more pregnancy registries.

Better data can catalyze thoughtful discussions between doctor and patient regarding decisions to use or defer treatment with a given medicine. One might wonder if the new system will open a Pandora’s box. But I believe in this case, opening Pandora’s box would be welcome because it will hopefully lead to a more careful examination of the available information regarding reproductive safety and more informed decisions on the part of patients.

Dr. Cohen is the director of the Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information about reproductive mental health. He has been a consultant to manufacturers of antidepressant medications and is the principal investigator of the National Pregnancy Registry for Atypical Antipsychotics, which receives support from the manufacturers of those drugs. To comment, e-mail him at [email protected]. Scan this QR code or go to obgynnews.com to view similar columns.

As an experienced clinician who has seen tics and habits in your patients come and go, you may be surprised by the amount of concern parents express about them. At times, it seems, and may be, that the parent’s attention to the habit actually keeps it going! This does not always mean that the child keeps doing the habit to aggravate the parent, as parental correction may amp up the child’s anxiety, which may make the habit worse.

As with other parent concerns, both empathizing with their worry and providing evidence-based information is helpful in relieving their distress.

Habits are complex behaviors done the same way repeatedly. Habits can have a strong protective effect on our lives and be a foundation for success when they ensure that we wash our hands (protection from infection), help us know where the keys are (efficiency), or soothe us to sleep (bedtime routines).

Tics are “involuntary” (meaning often, but not always, suppressible), brief, abrupt, repeated movements usually of the face, head, or neck. More complex, apparently meaningless movements may fall into the category of stereotypies. If they last more than 4 weeks, are driven, and cause marked dysfunction or significant self-injury, they may even qualify as stereotypic movement disorder.

It is good to know that repeated behaviors such as thumb sucking, nail/lip biting, hair twirling, body rocking, self biting, and head banging are relatively common in childhood, and often (but not mostly) disappear after age 4. I like to set the expectation that one habit or tic often evolves to another to reduce panic when this happens. Thumb and hand sucking at a younger developmental age may be replaced by body rocking and head banging, and later by nail biting and finger and foot tapping.

Even in college, habits are common and stress-related such as touching the face; playing with hair, pens, or jewelry; shaking a leg; tapping fingers; or scratching the head. Parents may connect some of these to acne or poor hygiene (a good opening for coaching!) but more importantly they may be accompanied by general distress, anxiety, obsessive-compulsive symptoms, and impulsive aggressive symptoms, which need to be looked for and addressed.

Stereotypies occur in about 20% of typically developing children (called “primary”) and are classified into:

• Common behaviors (such as, rocking, head banging, finger drumming, pencil tapping, hair twisting),

• Head nodding.

• Complex motor movements (such as hand and arm flapping/waving).

Habits – including nail biting, lip chewing, and nose picking – also may be diagnosed as stereotypic movement disorders, although ICD-10 lists includes them as “other specified behavioral and emotional disorders.”

For both conditions, the behavior must not be better accounted for by a compulsion, a tic disorder, part of autism, hair pulling (trichotillomania), or paroxysmal dyskinesias.

So what is the difference between motor stereotypies and tics (and why do you care)? Motor stereotypies begin before 3 years in more than 60%, whereas tics appear later (mean 5-7 years). Stereotypies are more fixed in their pattern, compared with tics that keep shifting form, disappearing, and reappearing. Stereotypies frequently involve the arms, hands, or the entire body, while tics involve the eyes, face, head, and shoulders. Stereotypies are more fixed, rhythmic, and prolonged (most more than 10 seconds) than tics, which are mostly brief, rapid, random, and fluctuating.

One key distinguishing factor is that tics have a premonitory urge and result in a sense of relief after the tic is performed. This also means that they can be suppressed to some extent when the situation requires. While both may occur more during anxiety, excitement, or fatigue, stereotypic movements, unlike tics, also are common when the child is engrossed.

Tics can occur as a side effect of medications such as stimulants and may decrease by lowering the dose, but tics also come and go, so the impact of a medication can be hard to sort out.

One vocal or multiple motor tics occurring many times per day starting before age 18 years and lasting more than 1 year are considered chronic; those occurring less than 1 year are transient. Chronic multiple motor tics accompanied by vocalizations, even sniffing or throat clearing, qualify as Tourette syndrome. The feared component of Tourette of coprolalia (saying bad words or gestures) is fortunately rare. These diagnoses can only be made after ruling out the effects of medication or another neurological condition such as Sydenham’s chorea (resulting from infection via group A beta-hemolytic streptococcus, the bacterium that causes rheumatic fever) or PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections).

The importance of distinguishing tics from stereotypies is in the treatment options, differential diagnosis, and prognosis. Some families (and certainly the kids themselves) do not even notice that they are moving abnormally even though 25% have at least one family member with a similar behavior. But many parents are upset about the potential for teasing and stigmatization. When you ask them directly what they are afraid of, they often admit fearing an underlying diagnosis such as intellectual disability, autism, or Tourette syndrome. The first two are straightforward to rule in or out, but Tourette can be subtle. If parents don’t bring up the possibilities, it is worth telling them directly which underlying conditions can be ruled out.

There are many conditions comorbid with tics including attention-deficit/hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD), learning disorder (LD), behavioral, developmental or social problems, and mood or anxiety disorders. This clearly means that a comprehensive evaluation looking specifically for these conditions is needed when a child has chronic tics. Typically developing children with complex arm or hand movements also are more likely to have ADHD (30%), LD (20%), obsessive-compulsive behaviors (10%), or tics (18%).

Tics and stereotypies may be annoying, but generally are not harmful or progressive, although repeated movements such as skin or nose picking may result in scars or infections, and severe head banging can lead to eye injuries. Frequently repeated motor acts can cause significant muscle pain and fatigue. The most common problems are probably injury to self-esteem or oppositional behavior as a result of repeated (and fruitless) nagging or punishment by parents, even if well-meaning.

Since they occur so often along with comorbid conditions, our job includes determining the most problematic aspect before advising on a treatment. Both tics and stereotypies may be reduced by distraction, but the effect on stereotypies is faster and more certain. You can make this intervention in the office by simply asking how the child can tell when they make the movement and have them plan out what they could do instead. An example might be to shift a hand flapping movement (that makes peers think of autism) into more acceptable fist clenching. Habit reversal training or differential reinforcement based on a functional analysis can be taught by psychologists when this simple suggestion is not effective. When tics are severe, teacher education and school accommodations (504 Plan with extended time, scribe, private location for tic breaks) may be needed.

Medication is not indicated for most tics because most are mild. If ADHD is present, tics may actually be reduced by stimulants or atomoxetine rather than worsened. If the tic is severe and habit reversal training has not been successful, alpha agonists such as clonidine or guanfacine, or typical or atypical neuroleptics may be helpful. Even baclofen, benzodiazepines, anticonvulsants, nicotine, and Botox have been used. These require consultation with a specialist.

As for other chronic medical conditions, tics and persisting stereotypies deserve a comprehensive approach, including repeated education of the parent and child, evaluation for comorbidity, school accommodations, building other strengths and social support, and only rarely pulling out your prescription pad.

Dr. Howard is an assistant professor of pediatrics at The Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She has no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to Frontline. E-mail her at [email protected].

As an experienced clinician who has seen tics and habits in your patients come and go, you may be surprised by the amount of concern parents express about them. At times, it seems, and may be, that the parent’s attention to the habit actually keeps it going! This does not always mean that the child keeps doing the habit to aggravate the parent, as parental correction may amp up the child’s anxiety, which may make the habit worse.

As with other parent concerns, both empathizing with their worry and providing evidence-based information is helpful in relieving their distress.

Habits are complex behaviors done the same way repeatedly. Habits can have a strong protective effect on our lives and be a foundation for success when they ensure that we wash our hands (protection from infection), help us know where the keys are (efficiency), or soothe us to sleep (bedtime routines).

Tics are “involuntary” (meaning often, but not always, suppressible), brief, abrupt, repeated movements usually of the face, head, or neck. More complex, apparently meaningless movements may fall into the category of stereotypies. If they last more than 4 weeks, are driven, and cause marked dysfunction or significant self-injury, they may even qualify as stereotypic movement disorder.

It is good to know that repeated behaviors such as thumb sucking, nail/lip biting, hair twirling, body rocking, self biting, and head banging are relatively common in childhood, and often (but not mostly) disappear after age 4. I like to set the expectation that one habit or tic often evolves to another to reduce panic when this happens. Thumb and hand sucking at a younger developmental age may be replaced by body rocking and head banging, and later by nail biting and finger and foot tapping.

Even in college, habits are common and stress-related such as touching the face; playing with hair, pens, or jewelry; shaking a leg; tapping fingers; or scratching the head. Parents may connect some of these to acne or poor hygiene (a good opening for coaching!) but more importantly they may be accompanied by general distress, anxiety, obsessive-compulsive symptoms, and impulsive aggressive symptoms, which need to be looked for and addressed.

Stereotypies occur in about 20% of typically developing children (called “primary”) and are classified into:

• Common behaviors (such as, rocking, head banging, finger drumming, pencil tapping, hair twisting),

• Head nodding.

• Complex motor movements (such as hand and arm flapping/waving).

Habits – including nail biting, lip chewing, and nose picking – also may be diagnosed as stereotypic movement disorders, although ICD-10 lists includes them as “other specified behavioral and emotional disorders.”

For both conditions, the behavior must not be better accounted for by a compulsion, a tic disorder, part of autism, hair pulling (trichotillomania), or paroxysmal dyskinesias.

So what is the difference between motor stereotypies and tics (and why do you care)? Motor stereotypies begin before 3 years in more than 60%, whereas tics appear later (mean 5-7 years). Stereotypies are more fixed in their pattern, compared with tics that keep shifting form, disappearing, and reappearing. Stereotypies frequently involve the arms, hands, or the entire body, while tics involve the eyes, face, head, and shoulders. Stereotypies are more fixed, rhythmic, and prolonged (most more than 10 seconds) than tics, which are mostly brief, rapid, random, and fluctuating.

One key distinguishing factor is that tics have a premonitory urge and result in a sense of relief after the tic is performed. This also means that they can be suppressed to some extent when the situation requires. While both may occur more during anxiety, excitement, or fatigue, stereotypic movements, unlike tics, also are common when the child is engrossed.

Tics can occur as a side effect of medications such as stimulants and may decrease by lowering the dose, but tics also come and go, so the impact of a medication can be hard to sort out.

One vocal or multiple motor tics occurring many times per day starting before age 18 years and lasting more than 1 year are considered chronic; those occurring less than 1 year are transient. Chronic multiple motor tics accompanied by vocalizations, even sniffing or throat clearing, qualify as Tourette syndrome. The feared component of Tourette of coprolalia (saying bad words or gestures) is fortunately rare. These diagnoses can only be made after ruling out the effects of medication or another neurological condition such as Sydenham’s chorea (resulting from infection via group A beta-hemolytic streptococcus, the bacterium that causes rheumatic fever) or PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections).

The importance of distinguishing tics from stereotypies is in the treatment options, differential diagnosis, and prognosis. Some families (and certainly the kids themselves) do not even notice that they are moving abnormally even though 25% have at least one family member with a similar behavior. But many parents are upset about the potential for teasing and stigmatization. When you ask them directly what they are afraid of, they often admit fearing an underlying diagnosis such as intellectual disability, autism, or Tourette syndrome. The first two are straightforward to rule in or out, but Tourette can be subtle. If parents don’t bring up the possibilities, it is worth telling them directly which underlying conditions can be ruled out.

There are many conditions comorbid with tics including attention-deficit/hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD), learning disorder (LD), behavioral, developmental or social problems, and mood or anxiety disorders. This clearly means that a comprehensive evaluation looking specifically for these conditions is needed when a child has chronic tics. Typically developing children with complex arm or hand movements also are more likely to have ADHD (30%), LD (20%), obsessive-compulsive behaviors (10%), or tics (18%).

Tics and stereotypies may be annoying, but generally are not harmful or progressive, although repeated movements such as skin or nose picking may result in scars or infections, and severe head banging can lead to eye injuries. Frequently repeated motor acts can cause significant muscle pain and fatigue. The most common problems are probably injury to self-esteem or oppositional behavior as a result of repeated (and fruitless) nagging or punishment by parents, even if well-meaning.

Since they occur so often along with comorbid conditions, our job includes determining the most problematic aspect before advising on a treatment. Both tics and stereotypies may be reduced by distraction, but the effect on stereotypies is faster and more certain. You can make this intervention in the office by simply asking how the child can tell when they make the movement and have them plan out what they could do instead. An example might be to shift a hand flapping movement (that makes peers think of autism) into more acceptable fist clenching. Habit reversal training or differential reinforcement based on a functional analysis can be taught by psychologists when this simple suggestion is not effective. When tics are severe, teacher education and school accommodations (504 Plan with extended time, scribe, private location for tic breaks) may be needed.

Medication is not indicated for most tics because most are mild. If ADHD is present, tics may actually be reduced by stimulants or atomoxetine rather than worsened. If the tic is severe and habit reversal training has not been successful, alpha agonists such as clonidine or guanfacine, or typical or atypical neuroleptics may be helpful. Even baclofen, benzodiazepines, anticonvulsants, nicotine, and Botox have been used. These require consultation with a specialist.

As for other chronic medical conditions, tics and persisting stereotypies deserve a comprehensive approach, including repeated education of the parent and child, evaluation for comorbidity, school accommodations, building other strengths and social support, and only rarely pulling out your prescription pad.

Dr. Howard is an assistant professor of pediatrics at The Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She has no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to Frontline. E-mail her at [email protected].

As an experienced clinician who has seen tics and habits in your patients come and go, you may be surprised by the amount of concern parents express about them. At times, it seems, and may be, that the parent’s attention to the habit actually keeps it going! This does not always mean that the child keeps doing the habit to aggravate the parent, as parental correction may amp up the child’s anxiety, which may make the habit worse.

As with other parent concerns, both empathizing with their worry and providing evidence-based information is helpful in relieving their distress.

Habits are complex behaviors done the same way repeatedly. Habits can have a strong protective effect on our lives and be a foundation for success when they ensure that we wash our hands (protection from infection), help us know where the keys are (efficiency), or soothe us to sleep (bedtime routines).

Tics are “involuntary” (meaning often, but not always, suppressible), brief, abrupt, repeated movements usually of the face, head, or neck. More complex, apparently meaningless movements may fall into the category of stereotypies. If they last more than 4 weeks, are driven, and cause marked dysfunction or significant self-injury, they may even qualify as stereotypic movement disorder.

It is good to know that repeated behaviors such as thumb sucking, nail/lip biting, hair twirling, body rocking, self biting, and head banging are relatively common in childhood, and often (but not mostly) disappear after age 4. I like to set the expectation that one habit or tic often evolves to another to reduce panic when this happens. Thumb and hand sucking at a younger developmental age may be replaced by body rocking and head banging, and later by nail biting and finger and foot tapping.

Even in college, habits are common and stress-related such as touching the face; playing with hair, pens, or jewelry; shaking a leg; tapping fingers; or scratching the head. Parents may connect some of these to acne or poor hygiene (a good opening for coaching!) but more importantly they may be accompanied by general distress, anxiety, obsessive-compulsive symptoms, and impulsive aggressive symptoms, which need to be looked for and addressed.

Stereotypies occur in about 20% of typically developing children (called “primary”) and are classified into:

• Common behaviors (such as, rocking, head banging, finger drumming, pencil tapping, hair twisting),

• Head nodding.

• Complex motor movements (such as hand and arm flapping/waving).

Habits – including nail biting, lip chewing, and nose picking – also may be diagnosed as stereotypic movement disorders, although ICD-10 lists includes them as “other specified behavioral and emotional disorders.”

For both conditions, the behavior must not be better accounted for by a compulsion, a tic disorder, part of autism, hair pulling (trichotillomania), or paroxysmal dyskinesias.

So what is the difference between motor stereotypies and tics (and why do you care)? Motor stereotypies begin before 3 years in more than 60%, whereas tics appear later (mean 5-7 years). Stereotypies are more fixed in their pattern, compared with tics that keep shifting form, disappearing, and reappearing. Stereotypies frequently involve the arms, hands, or the entire body, while tics involve the eyes, face, head, and shoulders. Stereotypies are more fixed, rhythmic, and prolonged (most more than 10 seconds) than tics, which are mostly brief, rapid, random, and fluctuating.

One key distinguishing factor is that tics have a premonitory urge and result in a sense of relief after the tic is performed. This also means that they can be suppressed to some extent when the situation requires. While both may occur more during anxiety, excitement, or fatigue, stereotypic movements, unlike tics, also are common when the child is engrossed.

Tics can occur as a side effect of medications such as stimulants and may decrease by lowering the dose, but tics also come and go, so the impact of a medication can be hard to sort out.

One vocal or multiple motor tics occurring many times per day starting before age 18 years and lasting more than 1 year are considered chronic; those occurring less than 1 year are transient. Chronic multiple motor tics accompanied by vocalizations, even sniffing or throat clearing, qualify as Tourette syndrome. The feared component of Tourette of coprolalia (saying bad words or gestures) is fortunately rare. These diagnoses can only be made after ruling out the effects of medication or another neurological condition such as Sydenham’s chorea (resulting from infection via group A beta-hemolytic streptococcus, the bacterium that causes rheumatic fever) or PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections).

The importance of distinguishing tics from stereotypies is in the treatment options, differential diagnosis, and prognosis. Some families (and certainly the kids themselves) do not even notice that they are moving abnormally even though 25% have at least one family member with a similar behavior. But many parents are upset about the potential for teasing and stigmatization. When you ask them directly what they are afraid of, they often admit fearing an underlying diagnosis such as intellectual disability, autism, or Tourette syndrome. The first two are straightforward to rule in or out, but Tourette can be subtle. If parents don’t bring up the possibilities, it is worth telling them directly which underlying conditions can be ruled out.

There are many conditions comorbid with tics including attention-deficit/hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD), learning disorder (LD), behavioral, developmental or social problems, and mood or anxiety disorders. This clearly means that a comprehensive evaluation looking specifically for these conditions is needed when a child has chronic tics. Typically developing children with complex arm or hand movements also are more likely to have ADHD (30%), LD (20%), obsessive-compulsive behaviors (10%), or tics (18%).

Tics and stereotypies may be annoying, but generally are not harmful or progressive, although repeated movements such as skin or nose picking may result in scars or infections, and severe head banging can lead to eye injuries. Frequently repeated motor acts can cause significant muscle pain and fatigue. The most common problems are probably injury to self-esteem or oppositional behavior as a result of repeated (and fruitless) nagging or punishment by parents, even if well-meaning.

Since they occur so often along with comorbid conditions, our job includes determining the most problematic aspect before advising on a treatment. Both tics and stereotypies may be reduced by distraction, but the effect on stereotypies is faster and more certain. You can make this intervention in the office by simply asking how the child can tell when they make the movement and have them plan out what they could do instead. An example might be to shift a hand flapping movement (that makes peers think of autism) into more acceptable fist clenching. Habit reversal training or differential reinforcement based on a functional analysis can be taught by psychologists when this simple suggestion is not effective. When tics are severe, teacher education and school accommodations (504 Plan with extended time, scribe, private location for tic breaks) may be needed.

Medication is not indicated for most tics because most are mild. If ADHD is present, tics may actually be reduced by stimulants or atomoxetine rather than worsened. If the tic is severe and habit reversal training has not been successful, alpha agonists such as clonidine or guanfacine, or typical or atypical neuroleptics may be helpful. Even baclofen, benzodiazepines, anticonvulsants, nicotine, and Botox have been used. These require consultation with a specialist.

As for other chronic medical conditions, tics and persisting stereotypies deserve a comprehensive approach, including repeated education of the parent and child, evaluation for comorbidity, school accommodations, building other strengths and social support, and only rarely pulling out your prescription pad.

Dr. Howard is an assistant professor of pediatrics at The Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She has no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to Frontline. E-mail her at [email protected].

More than 500,000 women of reproductive age (20-49) are diagnosed with cancer each year. Fortunately, given advances in timely detection and effective therapy, more than 83% of these women will survive at least 5 years (SEER Cancer Statistics Review, 1975-2011). As a result, more women are concerned about their child-bearing potential after undergoing chemotherapy or radiation, and as reproductive technology advances, the issue of fertility preservation becomes even more salient.

Potential candidates for fertility preservation

The importance of considering fertility preservation for any reproductive-aged woman with a new cancer diagnosis cannot be overemphasized. This is especially true for women who may be receiving gonadotoxic therapies, such as alkylating agents or abdominal/pelvic radiation.

To assess the risk of various cancer treatments to fertility, patients and providers can access the Fertility Risk Tool at www.livestrong.org. The Fertility Risk Tool compiles known data about the risk of amenorrhea from specific cancers, chemotherapy agents, and radiation treatments, based on the woman’s age. The risk for infertility is likely higher than the stated incidence of amenorrhea, but the chart provides an initial counseling tool for health care providers and an overview for patients.

Discussions regarding fertility preservation are essential for any woman from menarche through mid-40s. However, as technological advances are rapidly occurring in reproductive medicine, options such as ovarian tissue cryopreservation are becoming available for prepubescent girls. Counseling these young patients with a new cancer diagnosis should not be overlooked.

Fertility preservation options

In vitro fertilization (IVF) with embryo banking is currently the most successful fertility preservation option and the standard of care. The process involves an IVF cycle, including monitored ovarian stimulation, transvaginal oocyte retrieval, fertilization of the oocytes, and cryopreservation of embryos.

The entire process takes a minimum of 12 days, and usually starts shortly after the onset of menses. The embryos can survive for years in liquid nitrogen and the survival rate of frozen embryos is greater than 95%. The pregnancy rate per embryo transfer cycle depends on the age of the woman when the embryos were created, with women under age 35 having higher live-birth rates compared with women older than 42 (live-birth rates 42.4% versus 17.8%, respectively, according to national summary data from the Society for Assisted Reproductive Technology).

Another option, which may be more attractive for women without a committed male partner, involves egg banking. This process also involves ovarian stimulation and egg retrieval, but fertilization is not performed. Instead the oocytes are cryopreserved, often by way of a vitrification technique shown to have a higher percentage of oocytes that survive the thaw (Fertil. Steril. 2011;96:277-85).

While the data regarding live birth after egg banking are limited, studies have shown reassuring birth outcomes for more than 900 babies from this technology (Reprod. Biomed. Online 2009;18:769-76).

Timing of treatment must be coordinated with the help of an oncologist. For example, many women with breast cancer opt to have their oncological surgery and undergo ovarian stimulation during the 4-6 week recovery period before initiating chemotherapy.

Ovarian tissue banking is considered experimental, but may be the only option available for women who must initiate treatment immediately, or for prepubescent girls. This technology involves surgical removal of part of an ovary, which is divided into small sections and frozen. The options for reproductive potential may include in vitro maturation of the immature oocytes in the strips of ovarian tissue with subsequent fertilization in the laboratory versus transplantation of the segments of ovarian tissue with the goal of some restoration of ovarian function (Hum. Reprod. 2014;29:1931-40).

Another option is the use of a gonadotropin-releasing hormone (GnRH) agonist during therapy to induce a prepubertal state, with the hypothetical goal to decrease damage to immature oocytes. A recent meta-analysis of randomized trials found that suppression with a GnRH agonist during chemotherapy significantly decreased premature ovarian failure in young women (Cancer Treat. Rev. 2014;40:675-83).

To date, the available literature does not address the effect of GnRH agonist use on rates of infertility in cancer survivors.

Special considerations for hormone sensitive cancers

Women with hormone sensitive cancers, such as breast cancer, often have understandable concerns about preserving their fertility and the impact that ovarian stimulation and future pregnancy may have on their prognosis.

For breast cancer patients, an effective adjuvant treatment during ovarian stimulation is an aromatase inhibitor, which lowers the peak estrogen levels compared to a standard ovarian stimulation cycle, with a similar oocyte yield (J. Clin. Endocrinol. Metab. 2006;91:3885-90).

There does not appear to be a difference in recurrence of breast cancer in women who pursued egg or embryo banking versus those who did not (J. Clin. Oncol. 2008;26:2630-5). Even after subsequent successful pregnancies, recurrence risk in hormone sensitive cancers, including breast cancer, is not increased (Cancer 2004;100:465-9). It is important to note that many women with breast cancer are placed on tamoxifen for many years. These women may consider a surrogate or a “tamoxifen break” after consultation with their oncologists.

When to refer

In any pediatric or reproductive-aged woman with a new cancer diagnosis, it is important to have a conversation exploring fertility options as soon as possible after the diagnosis is made. An early referral yields more options prior to initiating treatment and more time for the woman to discuss and consider all approaches to preserving her fertility.

Dr. Mersereau is an associate professor at the University of North Carolina at Chapel Hill, and director of UNC’s Fertility Preservation Program. Dr. Hoff is a clinical instructor and a fellow in reproductive endocrinology and infertility at UNC-Chapel Hill.

More than 500,000 women of reproductive age (20-49) are diagnosed with cancer each year. Fortunately, given advances in timely detection and effective therapy, more than 83% of these women will survive at least 5 years (SEER Cancer Statistics Review, 1975-2011). As a result, more women are concerned about their child-bearing potential after undergoing chemotherapy or radiation, and as reproductive technology advances, the issue of fertility preservation becomes even more salient.

Potential candidates for fertility preservation

The importance of considering fertility preservation for any reproductive-aged woman with a new cancer diagnosis cannot be overemphasized. This is especially true for women who may be receiving gonadotoxic therapies, such as alkylating agents or abdominal/pelvic radiation.

To assess the risk of various cancer treatments to fertility, patients and providers can access the Fertility Risk Tool at www.livestrong.org. The Fertility Risk Tool compiles known data about the risk of amenorrhea from specific cancers, chemotherapy agents, and radiation treatments, based on the woman’s age. The risk for infertility is likely higher than the stated incidence of amenorrhea, but the chart provides an initial counseling tool for health care providers and an overview for patients.

Discussions regarding fertility preservation are essential for any woman from menarche through mid-40s. However, as technological advances are rapidly occurring in reproductive medicine, options such as ovarian tissue cryopreservation are becoming available for prepubescent girls. Counseling these young patients with a new cancer diagnosis should not be overlooked.

Fertility preservation options

In vitro fertilization (IVF) with embryo banking is currently the most successful fertility preservation option and the standard of care. The process involves an IVF cycle, including monitored ovarian stimulation, transvaginal oocyte retrieval, fertilization of the oocytes, and cryopreservation of embryos.

The entire process takes a minimum of 12 days, and usually starts shortly after the onset of menses. The embryos can survive for years in liquid nitrogen and the survival rate of frozen embryos is greater than 95%. The pregnancy rate per embryo transfer cycle depends on the age of the woman when the embryos were created, with women under age 35 having higher live-birth rates compared with women older than 42 (live-birth rates 42.4% versus 17.8%, respectively, according to national summary data from the Society for Assisted Reproductive Technology).

Another option, which may be more attractive for women without a committed male partner, involves egg banking. This process also involves ovarian stimulation and egg retrieval, but fertilization is not performed. Instead the oocytes are cryopreserved, often by way of a vitrification technique shown to have a higher percentage of oocytes that survive the thaw (Fertil. Steril. 2011;96:277-85).

While the data regarding live birth after egg banking are limited, studies have shown reassuring birth outcomes for more than 900 babies from this technology (Reprod. Biomed. Online 2009;18:769-76).

Timing of treatment must be coordinated with the help of an oncologist. For example, many women with breast cancer opt to have their oncological surgery and undergo ovarian stimulation during the 4-6 week recovery period before initiating chemotherapy.

Ovarian tissue banking is considered experimental, but may be the only option available for women who must initiate treatment immediately, or for prepubescent girls. This technology involves surgical removal of part of an ovary, which is divided into small sections and frozen. The options for reproductive potential may include in vitro maturation of the immature oocytes in the strips of ovarian tissue with subsequent fertilization in the laboratory versus transplantation of the segments of ovarian tissue with the goal of some restoration of ovarian function (Hum. Reprod. 2014;29:1931-40).

Another option is the use of a gonadotropin-releasing hormone (GnRH) agonist during therapy to induce a prepubertal state, with the hypothetical goal to decrease damage to immature oocytes. A recent meta-analysis of randomized trials found that suppression with a GnRH agonist during chemotherapy significantly decreased premature ovarian failure in young women (Cancer Treat. Rev. 2014;40:675-83).

To date, the available literature does not address the effect of GnRH agonist use on rates of infertility in cancer survivors.

Special considerations for hormone sensitive cancers

Women with hormone sensitive cancers, such as breast cancer, often have understandable concerns about preserving their fertility and the impact that ovarian stimulation and future pregnancy may have on their prognosis.

For breast cancer patients, an effective adjuvant treatment during ovarian stimulation is an aromatase inhibitor, which lowers the peak estrogen levels compared to a standard ovarian stimulation cycle, with a similar oocyte yield (J. Clin. Endocrinol. Metab. 2006;91:3885-90).

There does not appear to be a difference in recurrence of breast cancer in women who pursued egg or embryo banking versus those who did not (J. Clin. Oncol. 2008;26:2630-5). Even after subsequent successful pregnancies, recurrence risk in hormone sensitive cancers, including breast cancer, is not increased (Cancer 2004;100:465-9). It is important to note that many women with breast cancer are placed on tamoxifen for many years. These women may consider a surrogate or a “tamoxifen break” after consultation with their oncologists.

When to refer

In any pediatric or reproductive-aged woman with a new cancer diagnosis, it is important to have a conversation exploring fertility options as soon as possible after the diagnosis is made. An early referral yields more options prior to initiating treatment and more time for the woman to discuss and consider all approaches to preserving her fertility.

Dr. Mersereau is an associate professor at the University of North Carolina at Chapel Hill, and director of UNC’s Fertility Preservation Program. Dr. Hoff is a clinical instructor and a fellow in reproductive endocrinology and infertility at UNC-Chapel Hill.

More than 500,000 women of reproductive age (20-49) are diagnosed with cancer each year. Fortunately, given advances in timely detection and effective therapy, more than 83% of these women will survive at least 5 years (SEER Cancer Statistics Review, 1975-2011). As a result, more women are concerned about their child-bearing potential after undergoing chemotherapy or radiation, and as reproductive technology advances, the issue of fertility preservation becomes even more salient.

Potential candidates for fertility preservation

The importance of considering fertility preservation for any reproductive-aged woman with a new cancer diagnosis cannot be overemphasized. This is especially true for women who may be receiving gonadotoxic therapies, such as alkylating agents or abdominal/pelvic radiation.

To assess the risk of various cancer treatments to fertility, patients and providers can access the Fertility Risk Tool at www.livestrong.org. The Fertility Risk Tool compiles known data about the risk of amenorrhea from specific cancers, chemotherapy agents, and radiation treatments, based on the woman’s age. The risk for infertility is likely higher than the stated incidence of amenorrhea, but the chart provides an initial counseling tool for health care providers and an overview for patients.

Discussions regarding fertility preservation are essential for any woman from menarche through mid-40s. However, as technological advances are rapidly occurring in reproductive medicine, options such as ovarian tissue cryopreservation are becoming available for prepubescent girls. Counseling these young patients with a new cancer diagnosis should not be overlooked.

Fertility preservation options

In vitro fertilization (IVF) with embryo banking is currently the most successful fertility preservation option and the standard of care. The process involves an IVF cycle, including monitored ovarian stimulation, transvaginal oocyte retrieval, fertilization of the oocytes, and cryopreservation of embryos.

The entire process takes a minimum of 12 days, and usually starts shortly after the onset of menses. The embryos can survive for years in liquid nitrogen and the survival rate of frozen embryos is greater than 95%. The pregnancy rate per embryo transfer cycle depends on the age of the woman when the embryos were created, with women under age 35 having higher live-birth rates compared with women older than 42 (live-birth rates 42.4% versus 17.8%, respectively, according to national summary data from the Society for Assisted Reproductive Technology).

Another option, which may be more attractive for women without a committed male partner, involves egg banking. This process also involves ovarian stimulation and egg retrieval, but fertilization is not performed. Instead the oocytes are cryopreserved, often by way of a vitrification technique shown to have a higher percentage of oocytes that survive the thaw (Fertil. Steril. 2011;96:277-85).

While the data regarding live birth after egg banking are limited, studies have shown reassuring birth outcomes for more than 900 babies from this technology (Reprod. Biomed. Online 2009;18:769-76).

Timing of treatment must be coordinated with the help of an oncologist. For example, many women with breast cancer opt to have their oncological surgery and undergo ovarian stimulation during the 4-6 week recovery period before initiating chemotherapy.

Ovarian tissue banking is considered experimental, but may be the only option available for women who must initiate treatment immediately, or for prepubescent girls. This technology involves surgical removal of part of an ovary, which is divided into small sections and frozen. The options for reproductive potential may include in vitro maturation of the immature oocytes in the strips of ovarian tissue with subsequent fertilization in the laboratory versus transplantation of the segments of ovarian tissue with the goal of some restoration of ovarian function (Hum. Reprod. 2014;29:1931-40).

Another option is the use of a gonadotropin-releasing hormone (GnRH) agonist during therapy to induce a prepubertal state, with the hypothetical goal to decrease damage to immature oocytes. A recent meta-analysis of randomized trials found that suppression with a GnRH agonist during chemotherapy significantly decreased premature ovarian failure in young women (Cancer Treat. Rev. 2014;40:675-83).

To date, the available literature does not address the effect of GnRH agonist use on rates of infertility in cancer survivors.

Special considerations for hormone sensitive cancers

Women with hormone sensitive cancers, such as breast cancer, often have understandable concerns about preserving their fertility and the impact that ovarian stimulation and future pregnancy may have on their prognosis.

For breast cancer patients, an effective adjuvant treatment during ovarian stimulation is an aromatase inhibitor, which lowers the peak estrogen levels compared to a standard ovarian stimulation cycle, with a similar oocyte yield (J. Clin. Endocrinol. Metab. 2006;91:3885-90).

There does not appear to be a difference in recurrence of breast cancer in women who pursued egg or embryo banking versus those who did not (J. Clin. Oncol. 2008;26:2630-5). Even after subsequent successful pregnancies, recurrence risk in hormone sensitive cancers, including breast cancer, is not increased (Cancer 2004;100:465-9). It is important to note that many women with breast cancer are placed on tamoxifen for many years. These women may consider a surrogate or a “tamoxifen break” after consultation with their oncologists.

When to refer

In any pediatric or reproductive-aged woman with a new cancer diagnosis, it is important to have a conversation exploring fertility options as soon as possible after the diagnosis is made. An early referral yields more options prior to initiating treatment and more time for the woman to discuss and consider all approaches to preserving her fertility.

Dr. Mersereau is an associate professor at the University of North Carolina at Chapel Hill, and director of UNC’s Fertility Preservation Program. Dr. Hoff is a clinical instructor and a fellow in reproductive endocrinology and infertility at UNC-Chapel Hill.

Buried under news of the terrible Charlie Hebdo terrorism murders was another serious attack. A doctor was shot and killed by an angry patient at a Texas VA hospital, who then took his own life.

I’m not trying to belittle the tragedy in Paris, but instead point out that medicine can be more hazardous than many realize.

We don’t intentionally try to offend, but in a field like this, it’s impossible to please everyone. People get upset that I can’t cure them or find a cause for their (medically unexplainable) symptoms, or won’t give them as many narcotics as they want. The unhappy ones never come back, or post an angry review on Yelp, or send a nasty letter, or some combination of the above.

But, occasionally, we get threats. They’re rare in an office practice, though I suspect surprisingly common in emergency department work. Most are empty threats to sue, but occasionally my staff and I get threatened with physical harm. While most are simply words, there’s really no easy way of knowing who will or won’t actually snap and carry them out.

We live in a society where guns are common, easily obtained, and affordable. So anyone might have one. Unless your office has a metal detector or does pat downs, you’re at risk (at least hypothetically). Putting up a sign that says “no guns allowed” isn’t going to stop anyone. Neither do laws to protect health professionals. Those who have decided to harm others don’t worry about such things.

For that matter, I have several patients who usually have a gun on them. Sometimes concealed, sometimes obvious. Does it bother me? Not at all. They’re all polite and pleasant, and I understand their reason for keeping one on hand.

But doctors, unfortunately, are easy targets for the irrational and armed. The shooting in El Paso occurred in a government hospital with armed security, and that certainly didn’t make a difference. We generally keep predictable hours, park in the same spaces, and our offices aren’t locked up. We do a job where trust is assumed, because people are coming to us for help and we’re here for their benefit.

Is there an answer? I know doctors who keep a handgun under their coats, or in their desks. In a perfect world, they wouldn’t need it, but our world is far from it. Being a doctor, whether you’re on the front line in the emergency department or hidden in a nameless medical plaza, can still be a dangerous business.

Medicine is a surprising field to think of as a hazardous one, but these days, sadly, it is.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Buried under news of the terrible Charlie Hebdo terrorism murders was another serious attack. A doctor was shot and killed by an angry patient at a Texas VA hospital, who then took his own life.

I’m not trying to belittle the tragedy in Paris, but instead point out that medicine can be more hazardous than many realize.

We don’t intentionally try to offend, but in a field like this, it’s impossible to please everyone. People get upset that I can’t cure them or find a cause for their (medically unexplainable) symptoms, or won’t give them as many narcotics as they want. The unhappy ones never come back, or post an angry review on Yelp, or send a nasty letter, or some combination of the above.

But, occasionally, we get threats. They’re rare in an office practice, though I suspect surprisingly common in emergency department work. Most are empty threats to sue, but occasionally my staff and I get threatened with physical harm. While most are simply words, there’s really no easy way of knowing who will or won’t actually snap and carry them out.

We live in a society where guns are common, easily obtained, and affordable. So anyone might have one. Unless your office has a metal detector or does pat downs, you’re at risk (at least hypothetically). Putting up a sign that says “no guns allowed” isn’t going to stop anyone. Neither do laws to protect health professionals. Those who have decided to harm others don’t worry about such things.

For that matter, I have several patients who usually have a gun on them. Sometimes concealed, sometimes obvious. Does it bother me? Not at all. They’re all polite and pleasant, and I understand their reason for keeping one on hand.

But doctors, unfortunately, are easy targets for the irrational and armed. The shooting in El Paso occurred in a government hospital with armed security, and that certainly didn’t make a difference. We generally keep predictable hours, park in the same spaces, and our offices aren’t locked up. We do a job where trust is assumed, because people are coming to us for help and we’re here for their benefit.

Is there an answer? I know doctors who keep a handgun under their coats, or in their desks. In a perfect world, they wouldn’t need it, but our world is far from it. Being a doctor, whether you’re on the front line in the emergency department or hidden in a nameless medical plaza, can still be a dangerous business.

Medicine is a surprising field to think of as a hazardous one, but these days, sadly, it is.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Buried under news of the terrible Charlie Hebdo terrorism murders was another serious attack. A doctor was shot and killed by an angry patient at a Texas VA hospital, who then took his own life.

I’m not trying to belittle the tragedy in Paris, but instead point out that medicine can be more hazardous than many realize.

We don’t intentionally try to offend, but in a field like this, it’s impossible to please everyone. People get upset that I can’t cure them or find a cause for their (medically unexplainable) symptoms, or won’t give them as many narcotics as they want. The unhappy ones never come back, or post an angry review on Yelp, or send a nasty letter, or some combination of the above.

But, occasionally, we get threats. They’re rare in an office practice, though I suspect surprisingly common in emergency department work. Most are empty threats to sue, but occasionally my staff and I get threatened with physical harm. While most are simply words, there’s really no easy way of knowing who will or won’t actually snap and carry them out.

We live in a society where guns are common, easily obtained, and affordable. So anyone might have one. Unless your office has a metal detector or does pat downs, you’re at risk (at least hypothetically). Putting up a sign that says “no guns allowed” isn’t going to stop anyone. Neither do laws to protect health professionals. Those who have decided to harm others don’t worry about such things.

For that matter, I have several patients who usually have a gun on them. Sometimes concealed, sometimes obvious. Does it bother me? Not at all. They’re all polite and pleasant, and I understand their reason for keeping one on hand.

But doctors, unfortunately, are easy targets for the irrational and armed. The shooting in El Paso occurred in a government hospital with armed security, and that certainly didn’t make a difference. We generally keep predictable hours, park in the same spaces, and our offices aren’t locked up. We do a job where trust is assumed, because people are coming to us for help and we’re here for their benefit.

Is there an answer? I know doctors who keep a handgun under their coats, or in their desks. In a perfect world, they wouldn’t need it, but our world is far from it. Being a doctor, whether you’re on the front line in the emergency department or hidden in a nameless medical plaza, can still be a dangerous business.

Medicine is a surprising field to think of as a hazardous one, but these days, sadly, it is.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.