Bipolar Disorder

PHILADELPHIA – Seeking to address issues of stigma surrounding bipolar disorder among patients and health care providers, a group of Canadian researchers and patient advocates commissioned a play aimed at giving a human face to someone who has succeeded at living with bipolar disorder.

The result was “That’s Just Crazy Talk,” an hour-long, one-woman performance by actor and playwright Victoria Maxwell, which premiered in performances in Vancouver and Toronto last July, was reprised several more times last year and this year, and is now available on DVD.

Courtesy Collaborative Research Team to Study Bipolar Disorder

The show’s development also was part of a research project that measured the impact that seeing a performance had on stigmatized feelings among people with bipolar disorder, the health care providers who deal with bipolar patients, and people with relatives or friends with bipolar disorder.

Survey results showed that seeing the show reduced stigma, especially among health care professionals, Dr. Sagar V. Parikh said at the annual meeting of the American Psychiatric Association.

The researchers surveyed 84 health care providers who deal with bipolar patients, both before and after the providers saw a performance. The providers’ average scores, as measured on a standard inventory known as the Day’s Mental Illness Stigma Scale (J. Applied Social Psych. 2007;37:2191-219), fell significantly in several categories, including treatability, relationship disturbance, and hygiene. The magnitude of the average effect size in these domains was comparable to the effect of “8 weeks of treatment with a mildly or moderately effective intervention, such as an antidepressant, or psychotherapy,” said Dr. Parikh, a professor of psychiatry at the University of Toronto.

Photo Mitchel L. Zoler/IMNG Medical Media

The responses of patients with bipolar disorder and those of their family members or friends were not as robust, but their stigma levels also seemed to be reduced when they saw the play.

“People said that the play made them think again about decisions they had made about treatment, how to handle treatment at work or in relationships, and how to deal with stigmatizing comments,” he said in an interview. “We think we have an intervention that works.”

“That’s Just Crazy Talk” was commissioned by Dr. Parikh and his associates using funds provided by the Canadian Institutes of Health Research, and with the participation of the Collaborative Research Team to Study Bipolar Disorder, and the Canadian Network for Mood and Anxiety Treatments. The project grew out of a desire to address the stigmas surrounding bipolar disorder, and a hunch that this could be done through a patient’s story told in a comedic and dramatic way. Victoria Maxwell’s prior work served as a catalyst for the concept. Ms. Maxwell is a bipolar disorder patient who had, for several years, incorporated stories about her illness and dealing with it into her performances.

“We knew of her and her work, which made us think of this project,” Dr. Parikh said. Plus, “we had the idea that a personal story could have an impact. Someone’s individual story is often very compelling. We have seen a number of shows and movies where mental illness is portrayed in various ways.

“We were struck that something via theater might be a powerful way to tell this story, and we had the happy circumstance of knowing of Victoria Maxwell. We approached her about creating a play centered on her struggles. For artistic reasons, we deliberately did not give her a list of things to say, but after her play was written we compared it with the key issues. We were prepared to say that some things might need strengthening, but that wasn’t necessary. She dealt with relationships, job discrimination, treatment, [and] adverse effects, and she models how a patient can negotiate a treatment plan that works. She talks about how she deals with life.”

A discussion period between the audience and Ms. Maxwell has followed each performance.

After the initial performances and Dr. Parikh’s assessments last summer, Ms. Maxwell performed her show several more times last year, and this year in Toronto and Vancouver, with additional performances scheduled for later this year and in other sites such as Ottawa and Boston. Also, in April the Collaborative Research Team to Study Bipolar Disorder began making available a DVD of the performance; the first public screening of the DVD occurred in Toronto in early May. The DVD comes with an associated discussion guide, and a future edition of the DVD will include a separate video of a postperformance discussion session.

Dr. Parikh said he had no disclosures.

PHILADELPHIA – Seeking to address issues of stigma surrounding bipolar disorder among patients and health care providers, a group of Canadian researchers and patient advocates commissioned a play aimed at giving a human face to someone who has succeeded at living with bipolar disorder.

The result was “That’s Just Crazy Talk,” an hour-long, one-woman performance by actor and playwright Victoria Maxwell, which premiered in performances in Vancouver and Toronto last July, was reprised several more times last year and this year, and is now available on DVD.

Courtesy Collaborative Research Team to Study Bipolar Disorder

The show’s development also was part of a research project that measured the impact that seeing a performance had on stigmatized feelings among people with bipolar disorder, the health care providers who deal with bipolar patients, and people with relatives or friends with bipolar disorder.

Survey results showed that seeing the show reduced stigma, especially among health care professionals, Dr. Sagar V. Parikh said at the annual meeting of the American Psychiatric Association.

The researchers surveyed 84 health care providers who deal with bipolar patients, both before and after the providers saw a performance. The providers’ average scores, as measured on a standard inventory known as the Day’s Mental Illness Stigma Scale (J. Applied Social Psych. 2007;37:2191-219), fell significantly in several categories, including treatability, relationship disturbance, and hygiene. The magnitude of the average effect size in these domains was comparable to the effect of “8 weeks of treatment with a mildly or moderately effective intervention, such as an antidepressant, or psychotherapy,” said Dr. Parikh, a professor of psychiatry at the University of Toronto.

Photo Mitchel L. Zoler/IMNG Medical Media

The responses of patients with bipolar disorder and those of their family members or friends were not as robust, but their stigma levels also seemed to be reduced when they saw the play.

“People said that the play made them think again about decisions they had made about treatment, how to handle treatment at work or in relationships, and how to deal with stigmatizing comments,” he said in an interview. “We think we have an intervention that works.”

“That’s Just Crazy Talk” was commissioned by Dr. Parikh and his associates using funds provided by the Canadian Institutes of Health Research, and with the participation of the Collaborative Research Team to Study Bipolar Disorder, and the Canadian Network for Mood and Anxiety Treatments. The project grew out of a desire to address the stigmas surrounding bipolar disorder, and a hunch that this could be done through a patient’s story told in a comedic and dramatic way. Victoria Maxwell’s prior work served as a catalyst for the concept. Ms. Maxwell is a bipolar disorder patient who had, for several years, incorporated stories about her illness and dealing with it into her performances.

“We knew of her and her work, which made us think of this project,” Dr. Parikh said. Plus, “we had the idea that a personal story could have an impact. Someone’s individual story is often very compelling. We have seen a number of shows and movies where mental illness is portrayed in various ways.

“We were struck that something via theater might be a powerful way to tell this story, and we had the happy circumstance of knowing of Victoria Maxwell. We approached her about creating a play centered on her struggles. For artistic reasons, we deliberately did not give her a list of things to say, but after her play was written we compared it with the key issues. We were prepared to say that some things might need strengthening, but that wasn’t necessary. She dealt with relationships, job discrimination, treatment, [and] adverse effects, and she models how a patient can negotiate a treatment plan that works. She talks about how she deals with life.”

A discussion period between the audience and Ms. Maxwell has followed each performance.

After the initial performances and Dr. Parikh’s assessments last summer, Ms. Maxwell performed her show several more times last year, and this year in Toronto and Vancouver, with additional performances scheduled for later this year and in other sites such as Ottawa and Boston. Also, in April the Collaborative Research Team to Study Bipolar Disorder began making available a DVD of the performance; the first public screening of the DVD occurred in Toronto in early May. The DVD comes with an associated discussion guide, and a future edition of the DVD will include a separate video of a postperformance discussion session.

Dr. Parikh said he had no disclosures.

PHILADELPHIA – Seeking to address issues of stigma surrounding bipolar disorder among patients and health care providers, a group of Canadian researchers and patient advocates commissioned a play aimed at giving a human face to someone who has succeeded at living with bipolar disorder.

The result was “That’s Just Crazy Talk,” an hour-long, one-woman performance by actor and playwright Victoria Maxwell, which premiered in performances in Vancouver and Toronto last July, was reprised several more times last year and this year, and is now available on DVD.

Courtesy Collaborative Research Team to Study Bipolar Disorder

The show’s development also was part of a research project that measured the impact that seeing a performance had on stigmatized feelings among people with bipolar disorder, the health care providers who deal with bipolar patients, and people with relatives or friends with bipolar disorder.

Survey results showed that seeing the show reduced stigma, especially among health care professionals, Dr. Sagar V. Parikh said at the annual meeting of the American Psychiatric Association.

The researchers surveyed 84 health care providers who deal with bipolar patients, both before and after the providers saw a performance. The providers’ average scores, as measured on a standard inventory known as the Day’s Mental Illness Stigma Scale (J. Applied Social Psych. 2007;37:2191-219), fell significantly in several categories, including treatability, relationship disturbance, and hygiene. The magnitude of the average effect size in these domains was comparable to the effect of “8 weeks of treatment with a mildly or moderately effective intervention, such as an antidepressant, or psychotherapy,” said Dr. Parikh, a professor of psychiatry at the University of Toronto.

Photo Mitchel L. Zoler/IMNG Medical Media

The responses of patients with bipolar disorder and those of their family members or friends were not as robust, but their stigma levels also seemed to be reduced when they saw the play.

“People said that the play made them think again about decisions they had made about treatment, how to handle treatment at work or in relationships, and how to deal with stigmatizing comments,” he said in an interview. “We think we have an intervention that works.”

“That’s Just Crazy Talk” was commissioned by Dr. Parikh and his associates using funds provided by the Canadian Institutes of Health Research, and with the participation of the Collaborative Research Team to Study Bipolar Disorder, and the Canadian Network for Mood and Anxiety Treatments. The project grew out of a desire to address the stigmas surrounding bipolar disorder, and a hunch that this could be done through a patient’s story told in a comedic and dramatic way. Victoria Maxwell’s prior work served as a catalyst for the concept. Ms. Maxwell is a bipolar disorder patient who had, for several years, incorporated stories about her illness and dealing with it into her performances.

“We knew of her and her work, which made us think of this project,” Dr. Parikh said. Plus, “we had the idea that a personal story could have an impact. Someone’s individual story is often very compelling. We have seen a number of shows and movies where mental illness is portrayed in various ways.

“We were struck that something via theater might be a powerful way to tell this story, and we had the happy circumstance of knowing of Victoria Maxwell. We approached her about creating a play centered on her struggles. For artistic reasons, we deliberately did not give her a list of things to say, but after her play was written we compared it with the key issues. We were prepared to say that some things might need strengthening, but that wasn’t necessary. She dealt with relationships, job discrimination, treatment, [and] adverse effects, and she models how a patient can negotiate a treatment plan that works. She talks about how she deals with life.”

A discussion period between the audience and Ms. Maxwell has followed each performance.

After the initial performances and Dr. Parikh’s assessments last summer, Ms. Maxwell performed her show several more times last year, and this year in Toronto and Vancouver, with additional performances scheduled for later this year and in other sites such as Ottawa and Boston. Also, in April the Collaborative Research Team to Study Bipolar Disorder began making available a DVD of the performance; the first public screening of the DVD occurred in Toronto in early May. The DVD comes with an associated discussion guide, and a future edition of the DVD will include a separate video of a postperformance discussion session.

Dr. Parikh said he had no disclosures.

We all understand that bipolar disorder is a mood disorder, characterized by periods of depression and mania, that many of us have seen in adults.

That manic component can include euphoric mood, pressured speech, hypersexual behavior, grandiosity, excessive spending, delusions, and diminished need for sleep. The degree of mania can sometimes reach a psychotic level, meaning its scale is disconnected from reality. For example, a manic adult’s delusions might include his ability to solve the energy crisis or move the world toward peace.

The manic adult is driven in a very active and pressured way. In fact, it’s not uncommon for them to end up in an emergency department. They might, for example, get on a plane as part of some grandiose delusion. When they land, they are alone, in a different city, and acting psychotic. This bizarre behavior gets them transferred to the nearest hospital. We all understand that that happens.

But are there any kinds of behaviors in childhood and adolescence that mimic, parallel, or predict this kind of adult behavior? Pediatric patients certainly experience depression, but are there behaviors that cycle and look like something we call "mania"?

The differential diagnosis is really essential, but it’s not easy. The pediatricians’ job with these children is to recognize a potential mood disorder in terms of depressive symptoms, agitation, and irritability. Consider the symptoms, the age, and the context.

Assess your patient for behaviors that are intense and outside the range of what you typically see in the primary care setting. A mood disorder that has become a daily, dominant feature in the family is telling. Look for a persistent, chronic pattern of agitation and irritability – with frequent explosive and sometimes violent outbursts – to move your diagnosis more solidly in the direction of potential bipolar disorder. A very strong family history of bipolar disorder or mood disorders can support this direction in your diagnosis.

Even child and adolescent psychiatrists have not reached a consensus on whether these behaviors reflect a childhood form of bipolar disorder, or instead a distinct proposed disorder in the DSM-5 (5th edition of the Diagnostic and Statistical Manual of Mental Disorders) called disruptive mood dysregulation disorder (DMDD). This is an area of active controversy in our field (more on that later).

There is enough behavior in childhood and adolescence that reflects dysregulation in temper and agitation about different things, so proceed slowly before you label your patient with a mood disorder. Be careful not to overlap your diagnosis with behaviors that might be related to a child’s temperament or social circumstances (in which the behaviors could be understood as coming from environmental/family factors rather than from an internal mood state). For example, abuse from a parent or older sibling can lead to a miserable life, and a child’s irritable, angry, and moody tantrum behaviors might be completely unrelated to bipolar disorder or temper dysregulation.

That being said, when you meet one of these kids or talk to people who live with them, it’s very clear there is something wrong. Although the term "bipolar disorder" could be overextended among children and adolescents, it does not mean that there is not a group of kids who are very, very difficult to manage because of their chronic mood state.

In your differential diagnosis, distinguish these behaviors from those associated with substance use, oppositional defiant disorder, and/or attention-deficit/hyperactive disorder that is unresponsive to treatment.

Substance use is certainly associated with moodiness and dysregulated behavior. If I told you that an adolescent was using cocaine or was a young alcoholic, you would not be surprised to find out that she also was depressed, irritable, and agitated with a labile mood.

The pattern of behaviors can be a clue as well. You might see similar behaviors in a child with oppositional defiant disorder, but the parents will report that the behaviors emerge in specific situations. For example, a child might throw a tantrum when he objects to something, but not spontaneously or as a matter of essentially daily routine.

Once a diagnosis of severe mood disorder is suspected (and when bipolar or DMDD is considered likely), the management of one of these kids is probably beyond the scope of a typical primary care practice. Pediatricians have a great role to play in child and family mental health, but the severity of these behaviors indicates the need to refer to a child and adolescent psychiatrist.

Part of the reason for the controversy in this area is that we’re at an early point of differentiating kids with these behaviors. In the absence of genetic or biochemical markers, we’re trying to figure this out through observation, interviews, family histories, and follow-up. Maybe there are two, three, or more subtypes of these mood states, and we’re lumping them together without a valid basis. Maybe there are threads in childhood that we can follow to adult bipolar disorder, or threads we can follow to the proposed DMDD. We just don’t know yet.

Currently, there are camps debating this dilemma within child psychiatry. Some of the roots of this controversy began with the identification of a subset of children with ADHD who also had additional comorbidity related to their mood. Some were comorbid with depression and did not respond well to their ADHD medication. Clinicians began to wonder – especially as they looked more closely – whether these children really did have ADHD, or did they have a mood disorder that included depression and behaviors that included irritability and agitation? This generated more questions: Did the behaviors come and go? Were their hyperactive symptoms really part of a manic mood? Is this an early form of bipolar disorder in childhood or early adolescence, especially with a relevant positive family history?

Clearly, these children were miserable. They were very difficult to raise because of their mood swings. Some displayed quite agitated temper tantrums that did not seem to make sense; they got upset over something minor or even out of the blue without explanation (again, an internally generated irritability and agitation).

In an effort to help these patients and their families, some child psychiatrists tried medication that was not typical for ADHD. They wanted to determine, for example, if medication that was indicated for mood disorders and even bipolar disorders in adults could stabilize these childhood behaviors. The ultimate goal was to help these children function better at home and school, and to live more happily.

In fact, some of the children responded to medications that were not for their original diagnosis of hyperactivity. Some people began calling those children "bipolar."

As often happens in medicine, some may have expanded the use of that term beyond its initial precision. These children didn’t have the family history, their depression was not as severe, or maybe their irritability could be explained through a more thorough evaluation.

As the number of children who were being diagnosed as bipolar increased, their age range went younger and many of them received powerful medications.

Others clinicians felt that this adult diagnosis was being inappropriately stretched to apply to children. They agreed that there are children who seem to have irritability, agitation, and violent temper tantrums, and to be very disruptive and difficult to manage at home and school. But they didn’t want to use an adult term to describe this behavior, or to call these children ADHD because they didn’t fit that diagnosis. The clinicians began using the term DMDD: These children were "dysregulated" because their moods were not regulated in the developmentally expected manner, and because temper and irritability were among the manifestations.

Additional guidance may come from the working groups for the DSM-5. As they prepare for it, experts are debating that we shouldn’t call kids with these symptoms bipolar, but rather DMDD, and that we should try to study them within that framework. But that view is not unanimous and the answer is not yet final.

Dr. Michael Jellinek is a professor of psychiatry and pediatrics at Harvard Medical School, Boston. He is also president of Newton (Mass.)–Wellesley Hospital and chief of clinical affairs, Partners HealthCare. He said he has no relevant disclosures.

We all understand that bipolar disorder is a mood disorder, characterized by periods of depression and mania, that many of us have seen in adults.

That manic component can include euphoric mood, pressured speech, hypersexual behavior, grandiosity, excessive spending, delusions, and diminished need for sleep. The degree of mania can sometimes reach a psychotic level, meaning its scale is disconnected from reality. For example, a manic adult’s delusions might include his ability to solve the energy crisis or move the world toward peace.

The manic adult is driven in a very active and pressured way. In fact, it’s not uncommon for them to end up in an emergency department. They might, for example, get on a plane as part of some grandiose delusion. When they land, they are alone, in a different city, and acting psychotic. This bizarre behavior gets them transferred to the nearest hospital. We all understand that that happens.

But are there any kinds of behaviors in childhood and adolescence that mimic, parallel, or predict this kind of adult behavior? Pediatric patients certainly experience depression, but are there behaviors that cycle and look like something we call "mania"?

The differential diagnosis is really essential, but it’s not easy. The pediatricians’ job with these children is to recognize a potential mood disorder in terms of depressive symptoms, agitation, and irritability. Consider the symptoms, the age, and the context.

Assess your patient for behaviors that are intense and outside the range of what you typically see in the primary care setting. A mood disorder that has become a daily, dominant feature in the family is telling. Look for a persistent, chronic pattern of agitation and irritability – with frequent explosive and sometimes violent outbursts – to move your diagnosis more solidly in the direction of potential bipolar disorder. A very strong family history of bipolar disorder or mood disorders can support this direction in your diagnosis.

Even child and adolescent psychiatrists have not reached a consensus on whether these behaviors reflect a childhood form of bipolar disorder, or instead a distinct proposed disorder in the DSM-5 (5th edition of the Diagnostic and Statistical Manual of Mental Disorders) called disruptive mood dysregulation disorder (DMDD). This is an area of active controversy in our field (more on that later).

There is enough behavior in childhood and adolescence that reflects dysregulation in temper and agitation about different things, so proceed slowly before you label your patient with a mood disorder. Be careful not to overlap your diagnosis with behaviors that might be related to a child’s temperament or social circumstances (in which the behaviors could be understood as coming from environmental/family factors rather than from an internal mood state). For example, abuse from a parent or older sibling can lead to a miserable life, and a child’s irritable, angry, and moody tantrum behaviors might be completely unrelated to bipolar disorder or temper dysregulation.

That being said, when you meet one of these kids or talk to people who live with them, it’s very clear there is something wrong. Although the term "bipolar disorder" could be overextended among children and adolescents, it does not mean that there is not a group of kids who are very, very difficult to manage because of their chronic mood state.

In your differential diagnosis, distinguish these behaviors from those associated with substance use, oppositional defiant disorder, and/or attention-deficit/hyperactive disorder that is unresponsive to treatment.

Substance use is certainly associated with moodiness and dysregulated behavior. If I told you that an adolescent was using cocaine or was a young alcoholic, you would not be surprised to find out that she also was depressed, irritable, and agitated with a labile mood.

The pattern of behaviors can be a clue as well. You might see similar behaviors in a child with oppositional defiant disorder, but the parents will report that the behaviors emerge in specific situations. For example, a child might throw a tantrum when he objects to something, but not spontaneously or as a matter of essentially daily routine.

Once a diagnosis of severe mood disorder is suspected (and when bipolar or DMDD is considered likely), the management of one of these kids is probably beyond the scope of a typical primary care practice. Pediatricians have a great role to play in child and family mental health, but the severity of these behaviors indicates the need to refer to a child and adolescent psychiatrist.

Part of the reason for the controversy in this area is that we’re at an early point of differentiating kids with these behaviors. In the absence of genetic or biochemical markers, we’re trying to figure this out through observation, interviews, family histories, and follow-up. Maybe there are two, three, or more subtypes of these mood states, and we’re lumping them together without a valid basis. Maybe there are threads in childhood that we can follow to adult bipolar disorder, or threads we can follow to the proposed DMDD. We just don’t know yet.

Currently, there are camps debating this dilemma within child psychiatry. Some of the roots of this controversy began with the identification of a subset of children with ADHD who also had additional comorbidity related to their mood. Some were comorbid with depression and did not respond well to their ADHD medication. Clinicians began to wonder – especially as they looked more closely – whether these children really did have ADHD, or did they have a mood disorder that included depression and behaviors that included irritability and agitation? This generated more questions: Did the behaviors come and go? Were their hyperactive symptoms really part of a manic mood? Is this an early form of bipolar disorder in childhood or early adolescence, especially with a relevant positive family history?

Clearly, these children were miserable. They were very difficult to raise because of their mood swings. Some displayed quite agitated temper tantrums that did not seem to make sense; they got upset over something minor or even out of the blue without explanation (again, an internally generated irritability and agitation).

In an effort to help these patients and their families, some child psychiatrists tried medication that was not typical for ADHD. They wanted to determine, for example, if medication that was indicated for mood disorders and even bipolar disorders in adults could stabilize these childhood behaviors. The ultimate goal was to help these children function better at home and school, and to live more happily.

In fact, some of the children responded to medications that were not for their original diagnosis of hyperactivity. Some people began calling those children "bipolar."

As often happens in medicine, some may have expanded the use of that term beyond its initial precision. These children didn’t have the family history, their depression was not as severe, or maybe their irritability could be explained through a more thorough evaluation.

As the number of children who were being diagnosed as bipolar increased, their age range went younger and many of them received powerful medications.

Others clinicians felt that this adult diagnosis was being inappropriately stretched to apply to children. They agreed that there are children who seem to have irritability, agitation, and violent temper tantrums, and to be very disruptive and difficult to manage at home and school. But they didn’t want to use an adult term to describe this behavior, or to call these children ADHD because they didn’t fit that diagnosis. The clinicians began using the term DMDD: These children were "dysregulated" because their moods were not regulated in the developmentally expected manner, and because temper and irritability were among the manifestations.

Additional guidance may come from the working groups for the DSM-5. As they prepare for it, experts are debating that we shouldn’t call kids with these symptoms bipolar, but rather DMDD, and that we should try to study them within that framework. But that view is not unanimous and the answer is not yet final.

Dr. Michael Jellinek is a professor of psychiatry and pediatrics at Harvard Medical School, Boston. He is also president of Newton (Mass.)–Wellesley Hospital and chief of clinical affairs, Partners HealthCare. He said he has no relevant disclosures.

We all understand that bipolar disorder is a mood disorder, characterized by periods of depression and mania, that many of us have seen in adults.

That manic component can include euphoric mood, pressured speech, hypersexual behavior, grandiosity, excessive spending, delusions, and diminished need for sleep. The degree of mania can sometimes reach a psychotic level, meaning its scale is disconnected from reality. For example, a manic adult’s delusions might include his ability to solve the energy crisis or move the world toward peace.

The manic adult is driven in a very active and pressured way. In fact, it’s not uncommon for them to end up in an emergency department. They might, for example, get on a plane as part of some grandiose delusion. When they land, they are alone, in a different city, and acting psychotic. This bizarre behavior gets them transferred to the nearest hospital. We all understand that that happens.

But are there any kinds of behaviors in childhood and adolescence that mimic, parallel, or predict this kind of adult behavior? Pediatric patients certainly experience depression, but are there behaviors that cycle and look like something we call "mania"?

The differential diagnosis is really essential, but it’s not easy. The pediatricians’ job with these children is to recognize a potential mood disorder in terms of depressive symptoms, agitation, and irritability. Consider the symptoms, the age, and the context.

Assess your patient for behaviors that are intense and outside the range of what you typically see in the primary care setting. A mood disorder that has become a daily, dominant feature in the family is telling. Look for a persistent, chronic pattern of agitation and irritability – with frequent explosive and sometimes violent outbursts – to move your diagnosis more solidly in the direction of potential bipolar disorder. A very strong family history of bipolar disorder or mood disorders can support this direction in your diagnosis.

Even child and adolescent psychiatrists have not reached a consensus on whether these behaviors reflect a childhood form of bipolar disorder, or instead a distinct proposed disorder in the DSM-5 (5th edition of the Diagnostic and Statistical Manual of Mental Disorders) called disruptive mood dysregulation disorder (DMDD). This is an area of active controversy in our field (more on that later).

There is enough behavior in childhood and adolescence that reflects dysregulation in temper and agitation about different things, so proceed slowly before you label your patient with a mood disorder. Be careful not to overlap your diagnosis with behaviors that might be related to a child’s temperament or social circumstances (in which the behaviors could be understood as coming from environmental/family factors rather than from an internal mood state). For example, abuse from a parent or older sibling can lead to a miserable life, and a child’s irritable, angry, and moody tantrum behaviors might be completely unrelated to bipolar disorder or temper dysregulation.

That being said, when you meet one of these kids or talk to people who live with them, it’s very clear there is something wrong. Although the term "bipolar disorder" could be overextended among children and adolescents, it does not mean that there is not a group of kids who are very, very difficult to manage because of their chronic mood state.

In your differential diagnosis, distinguish these behaviors from those associated with substance use, oppositional defiant disorder, and/or attention-deficit/hyperactive disorder that is unresponsive to treatment.

Substance use is certainly associated with moodiness and dysregulated behavior. If I told you that an adolescent was using cocaine or was a young alcoholic, you would not be surprised to find out that she also was depressed, irritable, and agitated with a labile mood.

The pattern of behaviors can be a clue as well. You might see similar behaviors in a child with oppositional defiant disorder, but the parents will report that the behaviors emerge in specific situations. For example, a child might throw a tantrum when he objects to something, but not spontaneously or as a matter of essentially daily routine.

Once a diagnosis of severe mood disorder is suspected (and when bipolar or DMDD is considered likely), the management of one of these kids is probably beyond the scope of a typical primary care practice. Pediatricians have a great role to play in child and family mental health, but the severity of these behaviors indicates the need to refer to a child and adolescent psychiatrist.

Part of the reason for the controversy in this area is that we’re at an early point of differentiating kids with these behaviors. In the absence of genetic or biochemical markers, we’re trying to figure this out through observation, interviews, family histories, and follow-up. Maybe there are two, three, or more subtypes of these mood states, and we’re lumping them together without a valid basis. Maybe there are threads in childhood that we can follow to adult bipolar disorder, or threads we can follow to the proposed DMDD. We just don’t know yet.

Currently, there are camps debating this dilemma within child psychiatry. Some of the roots of this controversy began with the identification of a subset of children with ADHD who also had additional comorbidity related to their mood. Some were comorbid with depression and did not respond well to their ADHD medication. Clinicians began to wonder – especially as they looked more closely – whether these children really did have ADHD, or did they have a mood disorder that included depression and behaviors that included irritability and agitation? This generated more questions: Did the behaviors come and go? Were their hyperactive symptoms really part of a manic mood? Is this an early form of bipolar disorder in childhood or early adolescence, especially with a relevant positive family history?

Clearly, these children were miserable. They were very difficult to raise because of their mood swings. Some displayed quite agitated temper tantrums that did not seem to make sense; they got upset over something minor or even out of the blue without explanation (again, an internally generated irritability and agitation).

In an effort to help these patients and their families, some child psychiatrists tried medication that was not typical for ADHD. They wanted to determine, for example, if medication that was indicated for mood disorders and even bipolar disorders in adults could stabilize these childhood behaviors. The ultimate goal was to help these children function better at home and school, and to live more happily.

In fact, some of the children responded to medications that were not for their original diagnosis of hyperactivity. Some people began calling those children "bipolar."

As often happens in medicine, some may have expanded the use of that term beyond its initial precision. These children didn’t have the family history, their depression was not as severe, or maybe their irritability could be explained through a more thorough evaluation.

As the number of children who were being diagnosed as bipolar increased, their age range went younger and many of them received powerful medications.

Others clinicians felt that this adult diagnosis was being inappropriately stretched to apply to children. They agreed that there are children who seem to have irritability, agitation, and violent temper tantrums, and to be very disruptive and difficult to manage at home and school. But they didn’t want to use an adult term to describe this behavior, or to call these children ADHD because they didn’t fit that diagnosis. The clinicians began using the term DMDD: These children were "dysregulated" because their moods were not regulated in the developmentally expected manner, and because temper and irritability were among the manifestations.

Additional guidance may come from the working groups for the DSM-5. As they prepare for it, experts are debating that we shouldn’t call kids with these symptoms bipolar, but rather DMDD, and that we should try to study them within that framework. But that view is not unanimous and the answer is not yet final.

Dr. Michael Jellinek is a professor of psychiatry and pediatrics at Harvard Medical School, Boston. He is also president of Newton (Mass.)–Wellesley Hospital and chief of clinical affairs, Partners HealthCare. He said he has no relevant disclosures.

A $75 million demonstration project aims to see if Medicaid patients with a psychiatric emergency would get better, more efficient care from a psychiatric hospital.

Under current law, Medicaid cannot pay for care provided in psychiatric hospitals. Patients with a psychiatric emergency – those expressing homicidal or suicidal thoughts or actions – generally are treated in the emergency department, which may not be staffed or equipped provide adequate care for them, officials from the Centers for Medicare and Medicaid Services said in announcing the demonstration March 13.

"This new demonstration will help ensure patients receive appropriate, high quality care when they need it most and save states money," acting CMS administrator Marilyn Tavenner said in a statement.

The three-year project – funded under the Affordable Care Act – covers Medicaid enrollees aged 21-64 years in 11 states and the District of Columbia. The project was designed based on proposals from the participating states: Alabama, California, Connecticut, Illinois, Maine, Maryland, Missouri, North Carolina, Rhode Island, Washington, and West Virginia.

Medicaid programs in participating states will receive federal matching funds to help pay for services needed by Medicaid patients being treated at private psychiatric hospitals. They'll also be required to match nearly 45% of federal dollars, resulting in $115 million to $120 million in total spending, said Mark Covall, president and CEO of the National Association of Psychiatric Health Systems. Following the demonstration, Medicaid programs will participate in a survey to evaluate changes in quality of care and program costs.

The American Psychiatric Association has opposed the Medicaid exclusion of private psychiatric hospitals since long before passage of the Affordable Care Act, Nicholas Meyers, APA director of government relations, said in an interview. He added that the organization is relieved that CMS is listening.

"We’re delighted to see that CMS has moved forward with this," Mr. Meyers said. "It will test what happened when a contradiction in federal law is eliminated and thus it will help insure that patients get the appropriate treatment and hospitals get reimbursed for the services they’re required to be providing."

Mr. Covall said the demonstration was approved because of both the increased awareness of the need for inpatient psychiatric care and the burden on the emergency care system. Since most emergency rooms don’t have enough beds to meet the demand, Mr. Covall said patients are often forced to stay in emergency rooms for hours, days, and sometimes even weeks. He added that the demonstration will help address barriers to access as well as cost implications.

"This will allow those patients that are in these emergency departments to be quickly triaged and sent over to the freestanding psychiatric hospital where they will be able to be fully assessed and then admitted to an impatient psychiatric unit," Mr. Covall said in an interview.

In addition to testing the affect of Medicaid reimbursement on the quality of care at psychiatric emergency facilities, the demonstration is also test whether expanded coverage will reduce the burden on general acute care hospital emergency departments.

A $75 million demonstration project aims to see if Medicaid patients with a psychiatric emergency would get better, more efficient care from a psychiatric hospital.

Under current law, Medicaid cannot pay for care provided in psychiatric hospitals. Patients with a psychiatric emergency – those expressing homicidal or suicidal thoughts or actions – generally are treated in the emergency department, which may not be staffed or equipped provide adequate care for them, officials from the Centers for Medicare and Medicaid Services said in announcing the demonstration March 13.

"This new demonstration will help ensure patients receive appropriate, high quality care when they need it most and save states money," acting CMS administrator Marilyn Tavenner said in a statement.

The three-year project – funded under the Affordable Care Act – covers Medicaid enrollees aged 21-64 years in 11 states and the District of Columbia. The project was designed based on proposals from the participating states: Alabama, California, Connecticut, Illinois, Maine, Maryland, Missouri, North Carolina, Rhode Island, Washington, and West Virginia.

Medicaid programs in participating states will receive federal matching funds to help pay for services needed by Medicaid patients being treated at private psychiatric hospitals. They'll also be required to match nearly 45% of federal dollars, resulting in $115 million to $120 million in total spending, said Mark Covall, president and CEO of the National Association of Psychiatric Health Systems. Following the demonstration, Medicaid programs will participate in a survey to evaluate changes in quality of care and program costs.

The American Psychiatric Association has opposed the Medicaid exclusion of private psychiatric hospitals since long before passage of the Affordable Care Act, Nicholas Meyers, APA director of government relations, said in an interview. He added that the organization is relieved that CMS is listening.

"We’re delighted to see that CMS has moved forward with this," Mr. Meyers said. "It will test what happened when a contradiction in federal law is eliminated and thus it will help insure that patients get the appropriate treatment and hospitals get reimbursed for the services they’re required to be providing."

Mr. Covall said the demonstration was approved because of both the increased awareness of the need for inpatient psychiatric care and the burden on the emergency care system. Since most emergency rooms don’t have enough beds to meet the demand, Mr. Covall said patients are often forced to stay in emergency rooms for hours, days, and sometimes even weeks. He added that the demonstration will help address barriers to access as well as cost implications.

"This will allow those patients that are in these emergency departments to be quickly triaged and sent over to the freestanding psychiatric hospital where they will be able to be fully assessed and then admitted to an impatient psychiatric unit," Mr. Covall said in an interview.

In addition to testing the affect of Medicaid reimbursement on the quality of care at psychiatric emergency facilities, the demonstration is also test whether expanded coverage will reduce the burden on general acute care hospital emergency departments.

A $75 million demonstration project aims to see if Medicaid patients with a psychiatric emergency would get better, more efficient care from a psychiatric hospital.

Under current law, Medicaid cannot pay for care provided in psychiatric hospitals. Patients with a psychiatric emergency – those expressing homicidal or suicidal thoughts or actions – generally are treated in the emergency department, which may not be staffed or equipped provide adequate care for them, officials from the Centers for Medicare and Medicaid Services said in announcing the demonstration March 13.

"This new demonstration will help ensure patients receive appropriate, high quality care when they need it most and save states money," acting CMS administrator Marilyn Tavenner said in a statement.

The three-year project – funded under the Affordable Care Act – covers Medicaid enrollees aged 21-64 years in 11 states and the District of Columbia. The project was designed based on proposals from the participating states: Alabama, California, Connecticut, Illinois, Maine, Maryland, Missouri, North Carolina, Rhode Island, Washington, and West Virginia.

Medicaid programs in participating states will receive federal matching funds to help pay for services needed by Medicaid patients being treated at private psychiatric hospitals. They'll also be required to match nearly 45% of federal dollars, resulting in $115 million to $120 million in total spending, said Mark Covall, president and CEO of the National Association of Psychiatric Health Systems. Following the demonstration, Medicaid programs will participate in a survey to evaluate changes in quality of care and program costs.

The American Psychiatric Association has opposed the Medicaid exclusion of private psychiatric hospitals since long before passage of the Affordable Care Act, Nicholas Meyers, APA director of government relations, said in an interview. He added that the organization is relieved that CMS is listening.

"We’re delighted to see that CMS has moved forward with this," Mr. Meyers said. "It will test what happened when a contradiction in federal law is eliminated and thus it will help insure that patients get the appropriate treatment and hospitals get reimbursed for the services they’re required to be providing."

Mr. Covall said the demonstration was approved because of both the increased awareness of the need for inpatient psychiatric care and the burden on the emergency care system. Since most emergency rooms don’t have enough beds to meet the demand, Mr. Covall said patients are often forced to stay in emergency rooms for hours, days, and sometimes even weeks. He added that the demonstration will help address barriers to access as well as cost implications.

"This will allow those patients that are in these emergency departments to be quickly triaged and sent over to the freestanding psychiatric hospital where they will be able to be fully assessed and then admitted to an impatient psychiatric unit," Mr. Covall said in an interview.

In addition to testing the affect of Medicaid reimbursement on the quality of care at psychiatric emergency facilities, the demonstration is also test whether expanded coverage will reduce the burden on general acute care hospital emergency departments.

LAS VEGAS – In a 6-month study, the use of adjunctive moderately dosed lithium to optimized treatment in patients with bipolar disorder was well tolerated yet did not lead to improved outcomes or decreased suicidality. However, use of adjunctive lithium resulted in a significant reduction in the use of second-generation antipsychotics.

Those are key findings from the Bipolar Trials Network Lithium Treatment Moderate Dose Study, a randomized trial that compared the use of lithium plus optimized treatment with optimized treatment alone.

Doug Brunk/Elsevier Global Medical News

"Currently, only about one-third of bipolar patients take lithium," Dr. Michael E. Thase said during a psychopharmacology conference sponsored by the Nevada Psychiatric Association. "And outpatients uncommonly take lithium in higher, well-established doses. Today it’s more commonly used in moderate doses in combination with newer generation therapies. However, the value of lower dose, combination strategies has not been well-studied."

For the outpatient study, known as the Lithium treatment – moderate dose use study, or LiTMUS, and led by Dr. Andrew A. Nierenberg at the Massachusetts General Hospital, investigators at six clinical sites enrolled 283 patients with bipolar I or bipolar II disorder with a Clinical Global Impressions-Bipolar Scale (CGI-BP-S) score of 3 or greater to assess whether lithium, in moderate doses, "could be a useful platform upon which other newer treatments could be evaluated," said Dr. Thase, professor of psychiatry at the University of Pennsylvania, Philadelphia.

"We were working in partnership with colleagues at the National Institute of Mental Health to do this study in a real-world, relevant way, meaning that it must be inclusive so that people with common comorbidities needed to be in the study, that it needed to be administered in an open way so that the results would be generalizable," said Dr. Thase, who also pointed out that there was no placebo control group.

The investigators compared lithium plus optimized treatment or optimized treatment without lithium. Patients in the lithium arm were started on 300 mg b.i.d. and sustained on 600 mg/day for 8 weeks, adjusted as needed thereafter. The Texas Implementation of Medication Algorithms for bipolar disorder informed care.

The two main outcomes assessed at 6 months were the CGI-BP-S and the number of Necessary Clinical Adjustments (NCAs), a measure of how difficult treatment was to implement. "This takes into account how many times you had to change the treatment in response to side effects or in response to the treatment not working," Dr. Thase explained. "The higher the NCA count, the stormier the treatment course."

A secondary measure was side effect burden as measured by the Frequency and Intensity of Side Effects Ratings, "which provides composite ratings of tolerability rather than focusing on specific side effects," he said. "These were completed at each study visit by the treating psychiatrist."

Dr. Thase reported that 84% of patients completed the 6 months of treatment. The attrition rate was not significantly different among those who received lithium, compared with those who did not receive the drug. The modal dose of lithium was 600 mg/day, and the average lithium levels ranged between 0.5-0.6 mEq/L.

Patients who received lithium did not have better outcomes compared with those who did not in terms of overall change in the CGI-BP-S (–1.5 vs. –1.2, respectively). "The average level of improvement for all of our patients was only about a 30% reduction in symptom burden," Dr. Thase said. "Thus, despite using guideline-based treatment algorithms, more patients remained ill than got better."

No statistically significant differences were found between groups in terms of depression and manic symptom severity based on the CGI-BP-S, the Quick Inventory of Depressive Symptoms Score, the Quality of Life Enjoyment and Satisfaction Questionnaire Score, and the Modified Scale for Suicidal Ideation Score.

One significant difference in the study was noted at week 2, when patients who received adjunctive lithium required fewer NCAs, compared with those who did not receive the drug. "Keep in mind, however, that the lithium dose was set at 300 b.i.d. for the first 8 weeks, so unless you were deviating from the protocol you couldn’t adjust the lithium dose," Dr. Thase said. "As a result, the fact that there are fewer adjustments of lithium in the first few weeks of treatment is determined by the [study] protocol. Across the whole 6 months there were no fewer necessary clinical adjustments in the lithium-treated group than in those who received optimized treatment without lithium."

Another significant finding was that patients who received lithium carried a slightly greater side effect burden during the initial 2 months of treatment (P less than .05), "but it was not different after that time period," he said. "The intensity of side effects was also greater in the lithium group during the first two months but was not different [than the optimized treatment without lithium group] after that time period."

There were no serious adverse events specifically related to lithium therapy, but two events (one case of dehydration and one case of acute renal failure) involved medical considerations related to lithium therapy.

The only significant difference in medication use between the two groups pertained to second-generation antipsychotics. Patients who received adjunctive lithium were 15-20% less likely to receive a second-generation antipsychotic (SGA) over the course of the study. "Put another way, if you don’t use lithium in your practice, you are going to be 15-20% more likely to be prescribing SGAs," Dr. Thase noted.

He acknowledged certain limitations of LiTMUS, including the study’s silence on "the utility of higher doses of lithium or the merits of lithium at higher doses in patients taking simpler psychopharmacology regimens."

While LiTMUS found that the use of lithium as an adjunct "did not improve the simplicity of the treatment regiment, it didn’t increase it, either," Dr. Thase said. "So if you know doctors who say ‘I don’t use lithium because it’s too complicated,’ remind them that we did not find lithium complicated in this study.

"In fact ... lithium was associated with a clinically meaningful reduction in the use of SGAs, "which means that using it lead to less patient exposure to the newer generation antipsychotics.

Dr. Thase disclosed that he has received research funding from the Agency for Healthcare Research and Quality, Eli Lilly, Forest Pharmaceuticals, GlaxoSmithKline, the National Institute of Mental Health, Otsuka Pharmaceuticals, and Sepracor. He also has received honoraria or is on the scientific board of several pharmaceutical companies.

LAS VEGAS – In a 6-month study, the use of adjunctive moderately dosed lithium to optimized treatment in patients with bipolar disorder was well tolerated yet did not lead to improved outcomes or decreased suicidality. However, use of adjunctive lithium resulted in a significant reduction in the use of second-generation antipsychotics.

Those are key findings from the Bipolar Trials Network Lithium Treatment Moderate Dose Study, a randomized trial that compared the use of lithium plus optimized treatment with optimized treatment alone.

Doug Brunk/Elsevier Global Medical News

"Currently, only about one-third of bipolar patients take lithium," Dr. Michael E. Thase said during a psychopharmacology conference sponsored by the Nevada Psychiatric Association. "And outpatients uncommonly take lithium in higher, well-established doses. Today it’s more commonly used in moderate doses in combination with newer generation therapies. However, the value of lower dose, combination strategies has not been well-studied."

For the outpatient study, known as the Lithium treatment – moderate dose use study, or LiTMUS, and led by Dr. Andrew A. Nierenberg at the Massachusetts General Hospital, investigators at six clinical sites enrolled 283 patients with bipolar I or bipolar II disorder with a Clinical Global Impressions-Bipolar Scale (CGI-BP-S) score of 3 or greater to assess whether lithium, in moderate doses, "could be a useful platform upon which other newer treatments could be evaluated," said Dr. Thase, professor of psychiatry at the University of Pennsylvania, Philadelphia.

"We were working in partnership with colleagues at the National Institute of Mental Health to do this study in a real-world, relevant way, meaning that it must be inclusive so that people with common comorbidities needed to be in the study, that it needed to be administered in an open way so that the results would be generalizable," said Dr. Thase, who also pointed out that there was no placebo control group.

The investigators compared lithium plus optimized treatment or optimized treatment without lithium. Patients in the lithium arm were started on 300 mg b.i.d. and sustained on 600 mg/day for 8 weeks, adjusted as needed thereafter. The Texas Implementation of Medication Algorithms for bipolar disorder informed care.

The two main outcomes assessed at 6 months were the CGI-BP-S and the number of Necessary Clinical Adjustments (NCAs), a measure of how difficult treatment was to implement. "This takes into account how many times you had to change the treatment in response to side effects or in response to the treatment not working," Dr. Thase explained. "The higher the NCA count, the stormier the treatment course."

A secondary measure was side effect burden as measured by the Frequency and Intensity of Side Effects Ratings, "which provides composite ratings of tolerability rather than focusing on specific side effects," he said. "These were completed at each study visit by the treating psychiatrist."

Dr. Thase reported that 84% of patients completed the 6 months of treatment. The attrition rate was not significantly different among those who received lithium, compared with those who did not receive the drug. The modal dose of lithium was 600 mg/day, and the average lithium levels ranged between 0.5-0.6 mEq/L.

Patients who received lithium did not have better outcomes compared with those who did not in terms of overall change in the CGI-BP-S (–1.5 vs. –1.2, respectively). "The average level of improvement for all of our patients was only about a 30% reduction in symptom burden," Dr. Thase said. "Thus, despite using guideline-based treatment algorithms, more patients remained ill than got better."

No statistically significant differences were found between groups in terms of depression and manic symptom severity based on the CGI-BP-S, the Quick Inventory of Depressive Symptoms Score, the Quality of Life Enjoyment and Satisfaction Questionnaire Score, and the Modified Scale for Suicidal Ideation Score.

One significant difference in the study was noted at week 2, when patients who received adjunctive lithium required fewer NCAs, compared with those who did not receive the drug. "Keep in mind, however, that the lithium dose was set at 300 b.i.d. for the first 8 weeks, so unless you were deviating from the protocol you couldn’t adjust the lithium dose," Dr. Thase said. "As a result, the fact that there are fewer adjustments of lithium in the first few weeks of treatment is determined by the [study] protocol. Across the whole 6 months there were no fewer necessary clinical adjustments in the lithium-treated group than in those who received optimized treatment without lithium."

Another significant finding was that patients who received lithium carried a slightly greater side effect burden during the initial 2 months of treatment (P less than .05), "but it was not different after that time period," he said. "The intensity of side effects was also greater in the lithium group during the first two months but was not different [than the optimized treatment without lithium group] after that time period."

There were no serious adverse events specifically related to lithium therapy, but two events (one case of dehydration and one case of acute renal failure) involved medical considerations related to lithium therapy.

The only significant difference in medication use between the two groups pertained to second-generation antipsychotics. Patients who received adjunctive lithium were 15-20% less likely to receive a second-generation antipsychotic (SGA) over the course of the study. "Put another way, if you don’t use lithium in your practice, you are going to be 15-20% more likely to be prescribing SGAs," Dr. Thase noted.

He acknowledged certain limitations of LiTMUS, including the study’s silence on "the utility of higher doses of lithium or the merits of lithium at higher doses in patients taking simpler psychopharmacology regimens."

While LiTMUS found that the use of lithium as an adjunct "did not improve the simplicity of the treatment regiment, it didn’t increase it, either," Dr. Thase said. "So if you know doctors who say ‘I don’t use lithium because it’s too complicated,’ remind them that we did not find lithium complicated in this study.

"In fact ... lithium was associated with a clinically meaningful reduction in the use of SGAs, "which means that using it lead to less patient exposure to the newer generation antipsychotics.

Dr. Thase disclosed that he has received research funding from the Agency for Healthcare Research and Quality, Eli Lilly, Forest Pharmaceuticals, GlaxoSmithKline, the National Institute of Mental Health, Otsuka Pharmaceuticals, and Sepracor. He also has received honoraria or is on the scientific board of several pharmaceutical companies.

LAS VEGAS – In a 6-month study, the use of adjunctive moderately dosed lithium to optimized treatment in patients with bipolar disorder was well tolerated yet did not lead to improved outcomes or decreased suicidality. However, use of adjunctive lithium resulted in a significant reduction in the use of second-generation antipsychotics.

Those are key findings from the Bipolar Trials Network Lithium Treatment Moderate Dose Study, a randomized trial that compared the use of lithium plus optimized treatment with optimized treatment alone.

Doug Brunk/Elsevier Global Medical News

"Currently, only about one-third of bipolar patients take lithium," Dr. Michael E. Thase said during a psychopharmacology conference sponsored by the Nevada Psychiatric Association. "And outpatients uncommonly take lithium in higher, well-established doses. Today it’s more commonly used in moderate doses in combination with newer generation therapies. However, the value of lower dose, combination strategies has not been well-studied."

For the outpatient study, known as the Lithium treatment – moderate dose use study, or LiTMUS, and led by Dr. Andrew A. Nierenberg at the Massachusetts General Hospital, investigators at six clinical sites enrolled 283 patients with bipolar I or bipolar II disorder with a Clinical Global Impressions-Bipolar Scale (CGI-BP-S) score of 3 or greater to assess whether lithium, in moderate doses, "could be a useful platform upon which other newer treatments could be evaluated," said Dr. Thase, professor of psychiatry at the University of Pennsylvania, Philadelphia.

"We were working in partnership with colleagues at the National Institute of Mental Health to do this study in a real-world, relevant way, meaning that it must be inclusive so that people with common comorbidities needed to be in the study, that it needed to be administered in an open way so that the results would be generalizable," said Dr. Thase, who also pointed out that there was no placebo control group.

The investigators compared lithium plus optimized treatment or optimized treatment without lithium. Patients in the lithium arm were started on 300 mg b.i.d. and sustained on 600 mg/day for 8 weeks, adjusted as needed thereafter. The Texas Implementation of Medication Algorithms for bipolar disorder informed care.

The two main outcomes assessed at 6 months were the CGI-BP-S and the number of Necessary Clinical Adjustments (NCAs), a measure of how difficult treatment was to implement. "This takes into account how many times you had to change the treatment in response to side effects or in response to the treatment not working," Dr. Thase explained. "The higher the NCA count, the stormier the treatment course."

A secondary measure was side effect burden as measured by the Frequency and Intensity of Side Effects Ratings, "which provides composite ratings of tolerability rather than focusing on specific side effects," he said. "These were completed at each study visit by the treating psychiatrist."

Dr. Thase reported that 84% of patients completed the 6 months of treatment. The attrition rate was not significantly different among those who received lithium, compared with those who did not receive the drug. The modal dose of lithium was 600 mg/day, and the average lithium levels ranged between 0.5-0.6 mEq/L.

Patients who received lithium did not have better outcomes compared with those who did not in terms of overall change in the CGI-BP-S (–1.5 vs. –1.2, respectively). "The average level of improvement for all of our patients was only about a 30% reduction in symptom burden," Dr. Thase said. "Thus, despite using guideline-based treatment algorithms, more patients remained ill than got better."

No statistically significant differences were found between groups in terms of depression and manic symptom severity based on the CGI-BP-S, the Quick Inventory of Depressive Symptoms Score, the Quality of Life Enjoyment and Satisfaction Questionnaire Score, and the Modified Scale for Suicidal Ideation Score.

One significant difference in the study was noted at week 2, when patients who received adjunctive lithium required fewer NCAs, compared with those who did not receive the drug. "Keep in mind, however, that the lithium dose was set at 300 b.i.d. for the first 8 weeks, so unless you were deviating from the protocol you couldn’t adjust the lithium dose," Dr. Thase said. "As a result, the fact that there are fewer adjustments of lithium in the first few weeks of treatment is determined by the [study] protocol. Across the whole 6 months there were no fewer necessary clinical adjustments in the lithium-treated group than in those who received optimized treatment without lithium."

Another significant finding was that patients who received lithium carried a slightly greater side effect burden during the initial 2 months of treatment (P less than .05), "but it was not different after that time period," he said. "The intensity of side effects was also greater in the lithium group during the first two months but was not different [than the optimized treatment without lithium group] after that time period."

There were no serious adverse events specifically related to lithium therapy, but two events (one case of dehydration and one case of acute renal failure) involved medical considerations related to lithium therapy.

The only significant difference in medication use between the two groups pertained to second-generation antipsychotics. Patients who received adjunctive lithium were 15-20% less likely to receive a second-generation antipsychotic (SGA) over the course of the study. "Put another way, if you don’t use lithium in your practice, you are going to be 15-20% more likely to be prescribing SGAs," Dr. Thase noted.

He acknowledged certain limitations of LiTMUS, including the study’s silence on "the utility of higher doses of lithium or the merits of lithium at higher doses in patients taking simpler psychopharmacology regimens."

While LiTMUS found that the use of lithium as an adjunct "did not improve the simplicity of the treatment regiment, it didn’t increase it, either," Dr. Thase said. "So if you know doctors who say ‘I don’t use lithium because it’s too complicated,’ remind them that we did not find lithium complicated in this study.

"In fact ... lithium was associated with a clinically meaningful reduction in the use of SGAs, "which means that using it lead to less patient exposure to the newer generation antipsychotics.

Dr. Thase disclosed that he has received research funding from the Agency for Healthcare Research and Quality, Eli Lilly, Forest Pharmaceuticals, GlaxoSmithKline, the National Institute of Mental Health, Otsuka Pharmaceuticals, and Sepracor. He also has received honoraria or is on the scientific board of several pharmaceutical companies.

I feel Dr. Goldberg’s article addressing ultra-rapid cycling (URC) bipolar disorder (BD) (“Ultra-rapid cycling bipolar disorder: A critical look,” Current Psychiatry, December 2011, p. 42-52), fell short in 2 critical regards. First, I believe evidence would have supported much stronger or less ambiguous conclusions. Although URC clearly is an observable symptomatic phenomenon, it’s not a valid construct within the BD spectrum, per se. To include it as such would only detract from the homogeneity that has been achieved with the resolution of that group to date, thereby dissipating the usefulness of the group from both a clinical and research standpoint. Even the Bottom Line stated that URC “has not been validated as a distinct clinical entity,” but “careful evaluation” is recommended “to differentiate URC from affective lability seen in other conditions,” thus implicitly validating using the term as a diagnostic entity.

Second, I am disturbed by the article’s absence of adult attention-deficit/hyperactivity disorder (ADHD), the secondary features of which easily rival BD in accounting for a significant proportion of symptoms commonly attributed to URC, if not the preponderance thereof. Notably, ADHD shares the “trait feature” status the article cites as unique to BD. A commonly cited figure places the prevalence of adult ADHD at 4.4% (using DSM-IV criteria) with 75% to 80% of those patients untreated and undiagnosed.^{Ultra-rapid cycling bipolar disorder: A critical look” (Current Psychiatry, December 2011, p. 42-52).}

However, there was 1 significant diagnostic omission. Patients with adult attention-deficit/hyperactivity disorder (ADHD) can present with an unremarkable mental status exam, yet can give a history of abrupt episodes of dyscontrol, often in interpersonal situations. As opposed to children manifesting ADHD, where comorbidity with BD is substantial, adults may primarily display impulsivity rather than hyperactivity or inattention. By ignoring this diagnostic consideration, important pharmacotherapeutic options have been discarded, although cognitive-behavioral therapy and dialectical behavior therapy for “borderline” patients are always relevant. Regardless of diagnostic terms and the fate of DSM-5, our treatment approach serves to strengthen prefrontal cortex inhibitory activity and block limbic system reactivity.

Robert Barris, MD
Attending Psychiatrist
Nassau University Medical Center
East Meadow, NY

Dr. Goldberg responds

Drs. Bunt and Barris each raise the clinically and theoretically interesting observation that in patients whose childhood attention-deficit/hyperactivity disorder (ADHD) persists into adulthood, affective instability may be a prominent feature. Consequently, they advise that complaints of frequent mood swings within 1 day should alert clinicians to consider ADHD in their differential diagnosis.

Importantly, emotional dysregulation is not an established criterion for ADHD, although investigators have begun to study impaired emotional processing in adults with ADHD.¹ Because observational research examining emotional dysregulation in adult ADHD is preliminary, I cannot concur with Dr. Bunt’s assertion that “an omission of this sort does a disservice to the field.”

To the contrary, it would seem premature to counsel practitioners to look for mood instability as a red flag for adult ADHD. In fact, given the nontrivial rates of comorbid mood disorders with ADHD as cited by Dr. Bunt, it’s plausible that mood instability co-occurring with ADHD simply may be the epiphenomenon of a psychiatric comorbidity such as borderline personality disorder,² a disruptive behavior disorder,³ or substance abuse.³

Moreover, endophenotype studies suggest that emotional lability and ADHD do not cosegregate in families.³ Further research is needed to determine whether moment-to-moment mood fluctuations are an intrinsic feature of ADHD that is not better accounted for by another accompanying condition.

Dr. Bunt appears to have misconstrued my use of the term “validation” with respect to ultra-rapid cycling (URC) as if I had been referring to validation of URC as a diagnosis—which I never suggested—rather than as a putative course modifier or specifier in an otherwise-diagnosed bipolar disorder patient—as was the case when researchers empirically validated rapid cycling (RC) as a bipolar course specifier, leading to its inclusion in DSM-IV.⁴ To my knowledge there’s no movement to consider URC as a bipolar course specifier in DSM-5, which would be a difficult undertaking in the absence of field trials such as those conducted for bipolar RC.

Drs. Barris, Bunt, and I seem to agree that mood shifts occurring on a daily or more frequent basis constitute a non-pathognomonic phenomenon for which “careful evaluation” is necessary to discern the broader psychopathologic condition and context in which it arises.

Joseph F. Goldberg, MD
Associate Clinical Professor of Psychiatry
Mt. Sinai School of Medicine
New York, NY

I feel Dr. Goldberg’s article addressing ultra-rapid cycling (URC) bipolar disorder (BD) (“Ultra-rapid cycling bipolar disorder: A critical look,” Current Psychiatry, December 2011, p. 42-52), fell short in 2 critical regards. First, I believe evidence would have supported much stronger or less ambiguous conclusions. Although URC clearly is an observable symptomatic phenomenon, it’s not a valid construct within the BD spectrum, per se. To include it as such would only detract from the homogeneity that has been achieved with the resolution of that group to date, thereby dissipating the usefulness of the group from both a clinical and research standpoint. Even the Bottom Line stated that URC “has not been validated as a distinct clinical entity,” but “careful evaluation” is recommended “to differentiate URC from affective lability seen in other conditions,” thus implicitly validating using the term as a diagnostic entity.

Second, I am disturbed by the article’s absence of adult attention-deficit/hyperactivity disorder (ADHD), the secondary features of which easily rival BD in accounting for a significant proportion of symptoms commonly attributed to URC, if not the preponderance thereof. Notably, ADHD shares the “trait feature” status the article cites as unique to BD. A commonly cited figure places the prevalence of adult ADHD at 4.4% (using DSM-IV criteria) with 75% to 80% of those patients untreated and undiagnosed.^{Ultra-rapid cycling bipolar disorder: A critical look” (Current Psychiatry, December 2011, p. 42-52).}

However, there was 1 significant diagnostic omission. Patients with adult attention-deficit/hyperactivity disorder (ADHD) can present with an unremarkable mental status exam, yet can give a history of abrupt episodes of dyscontrol, often in interpersonal situations. As opposed to children manifesting ADHD, where comorbidity with BD is substantial, adults may primarily display impulsivity rather than hyperactivity or inattention. By ignoring this diagnostic consideration, important pharmacotherapeutic options have been discarded, although cognitive-behavioral therapy and dialectical behavior therapy for “borderline” patients are always relevant. Regardless of diagnostic terms and the fate of DSM-5, our treatment approach serves to strengthen prefrontal cortex inhibitory activity and block limbic system reactivity.

Robert Barris, MD
Attending Psychiatrist
Nassau University Medical Center
East Meadow, NY

Dr. Goldberg responds

Drs. Bunt and Barris each raise the clinically and theoretically interesting observation that in patients whose childhood attention-deficit/hyperactivity disorder (ADHD) persists into adulthood, affective instability may be a prominent feature. Consequently, they advise that complaints of frequent mood swings within 1 day should alert clinicians to consider ADHD in their differential diagnosis.

Importantly, emotional dysregulation is not an established criterion for ADHD, although investigators have begun to study impaired emotional processing in adults with ADHD.¹ Because observational research examining emotional dysregulation in adult ADHD is preliminary, I cannot concur with Dr. Bunt’s assertion that “an omission of this sort does a disservice to the field.”

To the contrary, it would seem premature to counsel practitioners to look for mood instability as a red flag for adult ADHD. In fact, given the nontrivial rates of comorbid mood disorders with ADHD as cited by Dr. Bunt, it’s plausible that mood instability co-occurring with ADHD simply may be the epiphenomenon of a psychiatric comorbidity such as borderline personality disorder,² a disruptive behavior disorder,³ or substance abuse.³

Moreover, endophenotype studies suggest that emotional lability and ADHD do not cosegregate in families.³ Further research is needed to determine whether moment-to-moment mood fluctuations are an intrinsic feature of ADHD that is not better accounted for by another accompanying condition.

Dr. Bunt appears to have misconstrued my use of the term “validation” with respect to ultra-rapid cycling (URC) as if I had been referring to validation of URC as a diagnosis—which I never suggested—rather than as a putative course modifier or specifier in an otherwise-diagnosed bipolar disorder patient—as was the case when researchers empirically validated rapid cycling (RC) as a bipolar course specifier, leading to its inclusion in DSM-IV.⁴ To my knowledge there’s no movement to consider URC as a bipolar course specifier in DSM-5, which would be a difficult undertaking in the absence of field trials such as those conducted for bipolar RC.

Drs. Barris, Bunt, and I seem to agree that mood shifts occurring on a daily or more frequent basis constitute a non-pathognomonic phenomenon for which “careful evaluation” is necessary to discern the broader psychopathologic condition and context in which it arises.

Joseph F. Goldberg, MD
Associate Clinical Professor of Psychiatry
Mt. Sinai School of Medicine
New York, NY

I feel Dr. Goldberg’s article addressing ultra-rapid cycling (URC) bipolar disorder (BD) (“Ultra-rapid cycling bipolar disorder: A critical look,” Current Psychiatry, December 2011, p. 42-52), fell short in 2 critical regards. First, I believe evidence would have supported much stronger or less ambiguous conclusions. Although URC clearly is an observable symptomatic phenomenon, it’s not a valid construct within the BD spectrum, per se. To include it as such would only detract from the homogeneity that has been achieved with the resolution of that group to date, thereby dissipating the usefulness of the group from both a clinical and research standpoint. Even the Bottom Line stated that URC “has not been validated as a distinct clinical entity,” but “careful evaluation” is recommended “to differentiate URC from affective lability seen in other conditions,” thus implicitly validating using the term as a diagnostic entity.

Second, I am disturbed by the article’s absence of adult attention-deficit/hyperactivity disorder (ADHD), the secondary features of which easily rival BD in accounting for a significant proportion of symptoms commonly attributed to URC, if not the preponderance thereof. Notably, ADHD shares the “trait feature” status the article cites as unique to BD. A commonly cited figure places the prevalence of adult ADHD at 4.4% (using DSM-IV criteria) with 75% to 80% of those patients untreated and undiagnosed.^{Ultra-rapid cycling bipolar disorder: A critical look” (Current Psychiatry, December 2011, p. 42-52).}

However, there was 1 significant diagnostic omission. Patients with adult attention-deficit/hyperactivity disorder (ADHD) can present with an unremarkable mental status exam, yet can give a history of abrupt episodes of dyscontrol, often in interpersonal situations. As opposed to children manifesting ADHD, where comorbidity with BD is substantial, adults may primarily display impulsivity rather than hyperactivity or inattention. By ignoring this diagnostic consideration, important pharmacotherapeutic options have been discarded, although cognitive-behavioral therapy and dialectical behavior therapy for “borderline” patients are always relevant. Regardless of diagnostic terms and the fate of DSM-5, our treatment approach serves to strengthen prefrontal cortex inhibitory activity and block limbic system reactivity.

Robert Barris, MD
Attending Psychiatrist
Nassau University Medical Center
East Meadow, NY

Dr. Goldberg responds

Drs. Bunt and Barris each raise the clinically and theoretically interesting observation that in patients whose childhood attention-deficit/hyperactivity disorder (ADHD) persists into adulthood, affective instability may be a prominent feature. Consequently, they advise that complaints of frequent mood swings within 1 day should alert clinicians to consider ADHD in their differential diagnosis.

Importantly, emotional dysregulation is not an established criterion for ADHD, although investigators have begun to study impaired emotional processing in adults with ADHD.¹ Because observational research examining emotional dysregulation in adult ADHD is preliminary, I cannot concur with Dr. Bunt’s assertion that “an omission of this sort does a disservice to the field.”

To the contrary, it would seem premature to counsel practitioners to look for mood instability as a red flag for adult ADHD. In fact, given the nontrivial rates of comorbid mood disorders with ADHD as cited by Dr. Bunt, it’s plausible that mood instability co-occurring with ADHD simply may be the epiphenomenon of a psychiatric comorbidity such as borderline personality disorder,² a disruptive behavior disorder,³ or substance abuse.³

Moreover, endophenotype studies suggest that emotional lability and ADHD do not cosegregate in families.³ Further research is needed to determine whether moment-to-moment mood fluctuations are an intrinsic feature of ADHD that is not better accounted for by another accompanying condition.

Dr. Bunt appears to have misconstrued my use of the term “validation” with respect to ultra-rapid cycling (URC) as if I had been referring to validation of URC as a diagnosis—which I never suggested—rather than as a putative course modifier or specifier in an otherwise-diagnosed bipolar disorder patient—as was the case when researchers empirically validated rapid cycling (RC) as a bipolar course specifier, leading to its inclusion in DSM-IV.⁴ To my knowledge there’s no movement to consider URC as a bipolar course specifier in DSM-5, which would be a difficult undertaking in the absence of field trials such as those conducted for bipolar RC.

Drs. Barris, Bunt, and I seem to agree that mood shifts occurring on a daily or more frequent basis constitute a non-pathognomonic phenomenon for which “careful evaluation” is necessary to discern the broader psychopathologic condition and context in which it arises.

Joseph F. Goldberg, MD
Associate Clinical Professor of Psychiatry
Mt. Sinai School of Medicine
New York, NY

The rival protagonists of Showtime’s hit series "Homeland" both suffer from exuberant Axis I psychopathology.

Ace Marine sergeant Nicholas Brody (Damien Lewis) returns from 8 years of horrific imprisonment by jihadists to a hero’s welcome. Outwardly the same stalwart patriot, he’s in fact a posttraumatic stress disorder poster boy. Ace CIA officer Carrie Mathison (Claire Danes) believes Brody also is a turncoat dispatched by his former captors to wreak havoc upon the Great Satan. Carrie herself is haunted by traumatic memories – of a bungled Iraq covert mission. She’s also covertly bipolar.

During Homeland’s first season Carrie and Brody briefly became lovers, Brody’s true-false colors were revealed, and Carrie’s mood swings grew as volatile as her conviction about Brody’s sinister intentions. In the penultimate episode, Brody took Carrie off the board by revealing her illness to the agency. Now he could proceed unhindered with the plan to suicide-bomb a hawkish vice president as the latter announced his presidential candidacy, together with top military and defense officials.

Homeland’s creators now faced a dilemma brought on precisely by the powerful, complex narrative so responsible for its popularity. Lame cliff-hangers are the traditional bane of a successful second season. With viewer expectations running so high, how to bring off a final episode that could somehow allow Brody to outlive impending martyrdom and enable disgraced, still-smitten Carrie to resume her dogged pursuit?

The series’ writers turned to electroconvulsive therapy (ECT) for a cunning, literal deus ex machina. Brody, tormented about again abandoning his wife and children – this time to their certain humiliation – opted out of martyrdom at the last moment. He chose instead to dwell in the chambers of power by running for office. Carrie, now convinced her suspicions about Brody were spinning out of paranoid despair, committed herself to a course of inpatient ECT. Hovering in anesthetized twilight on the brink of her first treatment, a memory from the affair with Brody surfaced that incontestably established his villainy. But would ECT stop her from remembering it?

The last episode’s jolting conclusion pleased viewers terrifically. Mental health professionals also praised the show for mounting a reasonable account of ECT. The treatment’s actual depiction seemed blessedly untainted by the gross shake-rattle-and-rolling so dear to the makers of mental health movies since "The Snake Pit."

However, ECT-knowledgeable psychiatrists found Homeland’s take on ECT far from balanced. They believed Carrie’s treatment was unwarranted – her depression largely reactive, symptoms not grave enough, etc. They were chiefly concerned that desperately ill patients would be frightened away from a long-established, potent, and safe remedy. Heavily emphasizing ECT’s dire threat to Carrie’s crucial recollection overrode the brief passing statement that ECT poses no danger of permanent memory loss. The stark closing shots of Carrie’s subconvulsive twitching, her jaw agonizingly clenched around a baby-blue bite plate, only served up a gentler, kinder version of Hollywood’s standard ECT epileptoid extravaganza.

Courtesy Showtime

Such protests ignore the central purpose of mainstream film-making, for most movie and film dramas are not crafted to educate us about anything – not ECT, or veterinary medicine, or moose stalking. They are made to garner great profits by gratifying our ancient appetite for great stories.

Not necessarily a bad thing. Should demonstrating how to stalk a moose or give ECT keep us glued to our Sixplex seats, so much the better. But if viewer pleasure commands sacrificing clinical accuracy, depend upon it, that price will be paid. Whatever its impact upon hapless Carrie’s noggin, ECT as a pure narrative device was instrumental in bringing home Homeland’s first season, leaving the viewer just unsatisfied enough to crave next season’s fix. A handsome achievement, doubtless with handsome rewards to follow.

Dr. Greenberg is clinical professor of psychiatry at the Albert Einstein College of Medicine, New York. He has written several hundred reviews and essays; two books on cinema, media, and popular culture; and numerous articles on adolescent and general psychiatry. For more information, visit http://www.doctorgreenberg.net/.

The rival protagonists of Showtime’s hit series "Homeland" both suffer from exuberant Axis I psychopathology.

Ace Marine sergeant Nicholas Brody (Damien Lewis) returns from 8 years of horrific imprisonment by jihadists to a hero’s welcome. Outwardly the same stalwart patriot, he’s in fact a posttraumatic stress disorder poster boy. Ace CIA officer Carrie Mathison (Claire Danes) believes Brody also is a turncoat dispatched by his former captors to wreak havoc upon the Great Satan. Carrie herself is haunted by traumatic memories – of a bungled Iraq covert mission. She’s also covertly bipolar.

During Homeland’s first season Carrie and Brody briefly became lovers, Brody’s true-false colors were revealed, and Carrie’s mood swings grew as volatile as her conviction about Brody’s sinister intentions. In the penultimate episode, Brody took Carrie off the board by revealing her illness to the agency. Now he could proceed unhindered with the plan to suicide-bomb a hawkish vice president as the latter announced his presidential candidacy, together with top military and defense officials.

Homeland’s creators now faced a dilemma brought on precisely by the powerful, complex narrative so responsible for its popularity. Lame cliff-hangers are the traditional bane of a successful second season. With viewer expectations running so high, how to bring off a final episode that could somehow allow Brody to outlive impending martyrdom and enable disgraced, still-smitten Carrie to resume her dogged pursuit?

The series’ writers turned to electroconvulsive therapy (ECT) for a cunning, literal deus ex machina. Brody, tormented about again abandoning his wife and children – this time to their certain humiliation – opted out of martyrdom at the last moment. He chose instead to dwell in the chambers of power by running for office. Carrie, now convinced her suspicions about Brody were spinning out of paranoid despair, committed herself to a course of inpatient ECT. Hovering in anesthetized twilight on the brink of her first treatment, a memory from the affair with Brody surfaced that incontestably established his villainy. But would ECT stop her from remembering it?

The last episode’s jolting conclusion pleased viewers terrifically. Mental health professionals also praised the show for mounting a reasonable account of ECT. The treatment’s actual depiction seemed blessedly untainted by the gross shake-rattle-and-rolling so dear to the makers of mental health movies since "The Snake Pit."

However, ECT-knowledgeable psychiatrists found Homeland’s take on ECT far from balanced. They believed Carrie’s treatment was unwarranted – her depression largely reactive, symptoms not grave enough, etc. They were chiefly concerned that desperately ill patients would be frightened away from a long-established, potent, and safe remedy. Heavily emphasizing ECT’s dire threat to Carrie’s crucial recollection overrode the brief passing statement that ECT poses no danger of permanent memory loss. The stark closing shots of Carrie’s subconvulsive twitching, her jaw agonizingly clenched around a baby-blue bite plate, only served up a gentler, kinder version of Hollywood’s standard ECT epileptoid extravaganza.

Courtesy Showtime

Such protests ignore the central purpose of mainstream film-making, for most movie and film dramas are not crafted to educate us about anything – not ECT, or veterinary medicine, or moose stalking. They are made to garner great profits by gratifying our ancient appetite for great stories.

Not necessarily a bad thing. Should demonstrating how to stalk a moose or give ECT keep us glued to our Sixplex seats, so much the better. But if viewer pleasure commands sacrificing clinical accuracy, depend upon it, that price will be paid. Whatever its impact upon hapless Carrie’s noggin, ECT as a pure narrative device was instrumental in bringing home Homeland’s first season, leaving the viewer just unsatisfied enough to crave next season’s fix. A handsome achievement, doubtless with handsome rewards to follow.

Dr. Greenberg is clinical professor of psychiatry at the Albert Einstein College of Medicine, New York. He has written several hundred reviews and essays; two books on cinema, media, and popular culture; and numerous articles on adolescent and general psychiatry. For more information, visit http://www.doctorgreenberg.net/.

The rival protagonists of Showtime’s hit series "Homeland" both suffer from exuberant Axis I psychopathology.

Ace Marine sergeant Nicholas Brody (Damien Lewis) returns from 8 years of horrific imprisonment by jihadists to a hero’s welcome. Outwardly the same stalwart patriot, he’s in fact a posttraumatic stress disorder poster boy. Ace CIA officer Carrie Mathison (Claire Danes) believes Brody also is a turncoat dispatched by his former captors to wreak havoc upon the Great Satan. Carrie herself is haunted by traumatic memories – of a bungled Iraq covert mission. She’s also covertly bipolar.

During Homeland’s first season Carrie and Brody briefly became lovers, Brody’s true-false colors were revealed, and Carrie’s mood swings grew as volatile as her conviction about Brody’s sinister intentions. In the penultimate episode, Brody took Carrie off the board by revealing her illness to the agency. Now he could proceed unhindered with the plan to suicide-bomb a hawkish vice president as the latter announced his presidential candidacy, together with top military and defense officials.

Homeland’s creators now faced a dilemma brought on precisely by the powerful, complex narrative so responsible for its popularity. Lame cliff-hangers are the traditional bane of a successful second season. With viewer expectations running so high, how to bring off a final episode that could somehow allow Brody to outlive impending martyrdom and enable disgraced, still-smitten Carrie to resume her dogged pursuit?

The series’ writers turned to electroconvulsive therapy (ECT) for a cunning, literal deus ex machina. Brody, tormented about again abandoning his wife and children – this time to their certain humiliation – opted out of martyrdom at the last moment. He chose instead to dwell in the chambers of power by running for office. Carrie, now convinced her suspicions about Brody were spinning out of paranoid despair, committed herself to a course of inpatient ECT. Hovering in anesthetized twilight on the brink of her first treatment, a memory from the affair with Brody surfaced that incontestably established his villainy. But would ECT stop her from remembering it?

The last episode’s jolting conclusion pleased viewers terrifically. Mental health professionals also praised the show for mounting a reasonable account of ECT. The treatment’s actual depiction seemed blessedly untainted by the gross shake-rattle-and-rolling so dear to the makers of mental health movies since "The Snake Pit."

However, ECT-knowledgeable psychiatrists found Homeland’s take on ECT far from balanced. They believed Carrie’s treatment was unwarranted – her depression largely reactive, symptoms not grave enough, etc. They were chiefly concerned that desperately ill patients would be frightened away from a long-established, potent, and safe remedy. Heavily emphasizing ECT’s dire threat to Carrie’s crucial recollection overrode the brief passing statement that ECT poses no danger of permanent memory loss. The stark closing shots of Carrie’s subconvulsive twitching, her jaw agonizingly clenched around a baby-blue bite plate, only served up a gentler, kinder version of Hollywood’s standard ECT epileptoid extravaganza.

Courtesy Showtime

Such protests ignore the central purpose of mainstream film-making, for most movie and film dramas are not crafted to educate us about anything – not ECT, or veterinary medicine, or moose stalking. They are made to garner great profits by gratifying our ancient appetite for great stories.

Not necessarily a bad thing. Should demonstrating how to stalk a moose or give ECT keep us glued to our Sixplex seats, so much the better. But if viewer pleasure commands sacrificing clinical accuracy, depend upon it, that price will be paid. Whatever its impact upon hapless Carrie’s noggin, ECT as a pure narrative device was instrumental in bringing home Homeland’s first season, leaving the viewer just unsatisfied enough to crave next season’s fix. A handsome achievement, doubtless with handsome rewards to follow.

Dr. Greenberg is clinical professor of psychiatry at the Albert Einstein College of Medicine, New York. He has written several hundred reviews and essays; two books on cinema, media, and popular culture; and numerous articles on adolescent and general psychiatry. For more information, visit http://www.doctorgreenberg.net/.

Lithium is associated with an increased risk of reduced urinary concentrating ability, hypothyroidism, hyperparathyroidism, and weight gain, but, despite widespread belief to the contrary, it may not be associated with congenital malformations, alopecia, skin disorders, or clinically significant reductions in renal function, according to findings from a systematic review and meta-analysis of data from 385 studies.

The review was undertaken in part because new evidence confirming the efficacy of lithium in bipolar disorder has led to suggestions that it be used more widely. Although it is considered an effective long-term therapy for bipolar disorder, its use has declined in recent years as new, more commercially promoted – but not always equally or more effective – drugs have become available. Concerns about potential teratogenic and other adverse effects, particularly on renal function, and have also contributed to declining use, Dr. Rebecca F. McKnight of the University of Oxford (England) and her colleagues reported online in the Jan. 20 issue of the Lancet.

To provide clinicians and patients with accurate evidence of lithium’s harms and benefits, the investigators set out to provide "a clinically informative systematic toxicity profile for lithium" they said (Lancet 2012 Jan. 20 [doi: 10.1016/S0140-6736(11)61516-X]).

Based on a hierarchy of evidence from the 22 randomized controlled trials, 197 cohort studies and case-control studies, and 166 case reports included in the review and meta-analysis, the investigators found that overall, glomerular filtration was reduced by –6.22 mL/min and urinary concentrating ability was reduced by 15% of normal maximum in patients receiving lithium, compared with controls.

"Data for the most clinically important outcome, renal failure, were scarce," the investigators said, noting that the only substantial cohort study showed that only 0.5% of patients receiving lithium were treated with renal replacement therapy.

As for clinical hypothyroidism, those taking lithium were significantly more likely than those on a placebo to develop the condition (odds ratio, 5.78), and based on a meta-analysis of the case-control studies, thyroid-stimulating hormone (TSH) concentrations were also significantly greater in those taking lithium (weighted mean difference, 4.00 IU/mL). Also, based on findings from 60 studies, blood calcium and parathyroid hormone levels were increased by about 10% over normal values in those taking lithium.

Clinically significant weight gain was also more frequent among those taking lithium than in controls (OR, 1.89), the investigators noted.

The evidence indicated, however, that lithium has little effect on hair or skin, with no significant difference seen in the incidence of alopecia in 24 publications reporting on the condition, and with no significant difference found in the prevalence of skin disorders between those taking lithium and controls in a meta-analysis of 77 publications.

Of note, six case-control studies that measured the association between Ebstein’s anomaly and lithium exposure found no link between the two. Although those estimates are unstable because of the low number of events, a case-control study of nearly 10,700 infants with a major congenital abnormality and more than 21,500 healthy controls also showed no significant association between lithium and congenital abnormalities.

Though limited by the quality and quantity of the primary evidence used in this study, which involved the screening of nearly 6,000 abstracts, the findings represent a "reasonable amount of evidence that allows cautious conclusions to be drawn about the safety of lithium," according to the investigators.

"This review provides a comprehensive synthesis of the evidence of harm that should inform clinical decision and draw attention to key questions in urgent need of further clarification," they said.

Based on their findings, the investigators developed the following recommendations for monitoring of lithium in clinical practice:

Before the start of lithium therapy, the risk of major adverse events should be discussed with the patient, a serum calcium level should be added to baseline blood tests, and uncertainty about the risk of congenital malformations to women of childbearing age should be explained. The latter two of these recommendations mark a change from current U.K. guidelines, the authors noted.

Also, during lithium therapy, renal, parathyroid, and thyroid function (at least glomerular filtration rate, TSH, and calcium) should be repeated at least every 12 months – and more frequently if an abnormal result is found or if the patient has a family history of endocrine disease; blood tests should all be repeated immediately in the event of a change in mood state; the occurrence of adverse effects should be routinely recorded; and women who would like to conceive or who have become pregnant during therapy should be advised that the increased risk of congenital malformation is uncertain, and the balance of risks between harm to the baby and maternal mood instability should be discussed before making a decision to discontinue lithium. All but the recommendation regarding repeat blood tests in the setting of mood state changes mark a change from current U.K. guidelines.

This study was funded by the National Institute for Health Research Programme Grant for Applied Research. The authors had no disclosures to report.

Lithium is associated with an increased risk of reduced urinary concentrating ability, hypothyroidism, hyperparathyroidism, and weight gain, but, despite widespread belief to the contrary, it may not be associated with congenital malformations, alopecia, skin disorders, or clinically significant reductions in renal function, according to findings from a systematic review and meta-analysis of data from 385 studies.

The review was undertaken in part because new evidence confirming the efficacy of lithium in bipolar disorder has led to suggestions that it be used more widely. Although it is considered an effective long-term therapy for bipolar disorder, its use has declined in recent years as new, more commercially promoted – but not always equally or more effective – drugs have become available. Concerns about potential teratogenic and other adverse effects, particularly on renal function, and have also contributed to declining use, Dr. Rebecca F. McKnight of the University of Oxford (England) and her colleagues reported online in the Jan. 20 issue of the Lancet.

To provide clinicians and patients with accurate evidence of lithium’s harms and benefits, the investigators set out to provide "a clinically informative systematic toxicity profile for lithium" they said (Lancet 2012 Jan. 20 [doi: 10.1016/S0140-6736(11)61516-X]).

Based on a hierarchy of evidence from the 22 randomized controlled trials, 197 cohort studies and case-control studies, and 166 case reports included in the review and meta-analysis, the investigators found that overall, glomerular filtration was reduced by –6.22 mL/min and urinary concentrating ability was reduced by 15% of normal maximum in patients receiving lithium, compared with controls.

"Data for the most clinically important outcome, renal failure, were scarce," the investigators said, noting that the only substantial cohort study showed that only 0.5% of patients receiving lithium were treated with renal replacement therapy.

As for clinical hypothyroidism, those taking lithium were significantly more likely than those on a placebo to develop the condition (odds ratio, 5.78), and based on a meta-analysis of the case-control studies, thyroid-stimulating hormone (TSH) concentrations were also significantly greater in those taking lithium (weighted mean difference, 4.00 IU/mL). Also, based on findings from 60 studies, blood calcium and parathyroid hormone levels were increased by about 10% over normal values in those taking lithium.

Clinically significant weight gain was also more frequent among those taking lithium than in controls (OR, 1.89), the investigators noted.

The evidence indicated, however, that lithium has little effect on hair or skin, with no significant difference seen in the incidence of alopecia in 24 publications reporting on the condition, and with no significant difference found in the prevalence of skin disorders between those taking lithium and controls in a meta-analysis of 77 publications.

Of note, six case-control studies that measured the association between Ebstein’s anomaly and lithium exposure found no link between the two. Although those estimates are unstable because of the low number of events, a case-control study of nearly 10,700 infants with a major congenital abnormality and more than 21,500 healthy controls also showed no significant association between lithium and congenital abnormalities.

Though limited by the quality and quantity of the primary evidence used in this study, which involved the screening of nearly 6,000 abstracts, the findings represent a "reasonable amount of evidence that allows cautious conclusions to be drawn about the safety of lithium," according to the investigators.

"This review provides a comprehensive synthesis of the evidence of harm that should inform clinical decision and draw attention to key questions in urgent need of further clarification," they said.

Based on their findings, the investigators developed the following recommendations for monitoring of lithium in clinical practice:

Before the start of lithium therapy, the risk of major adverse events should be discussed with the patient, a serum calcium level should be added to baseline blood tests, and uncertainty about the risk of congenital malformations to women of childbearing age should be explained. The latter two of these recommendations mark a change from current U.K. guidelines, the authors noted.

Also, during lithium therapy, renal, parathyroid, and thyroid function (at least glomerular filtration rate, TSH, and calcium) should be repeated at least every 12 months – and more frequently if an abnormal result is found or if the patient has a family history of endocrine disease; blood tests should all be repeated immediately in the event of a change in mood state; the occurrence of adverse effects should be routinely recorded; and women who would like to conceive or who have become pregnant during therapy should be advised that the increased risk of congenital malformation is uncertain, and the balance of risks between harm to the baby and maternal mood instability should be discussed before making a decision to discontinue lithium. All but the recommendation regarding repeat blood tests in the setting of mood state changes mark a change from current U.K. guidelines.

This study was funded by the National Institute for Health Research Programme Grant for Applied Research. The authors had no disclosures to report.

Lithium is associated with an increased risk of reduced urinary concentrating ability, hypothyroidism, hyperparathyroidism, and weight gain, but, despite widespread belief to the contrary, it may not be associated with congenital malformations, alopecia, skin disorders, or clinically significant reductions in renal function, according to findings from a systematic review and meta-analysis of data from 385 studies.

The review was undertaken in part because new evidence confirming the efficacy of lithium in bipolar disorder has led to suggestions that it be used more widely. Although it is considered an effective long-term therapy for bipolar disorder, its use has declined in recent years as new, more commercially promoted – but not always equally or more effective – drugs have become available. Concerns about potential teratogenic and other adverse effects, particularly on renal function, and have also contributed to declining use, Dr. Rebecca F. McKnight of the University of Oxford (England) and her colleagues reported online in the Jan. 20 issue of the Lancet.

To provide clinicians and patients with accurate evidence of lithium’s harms and benefits, the investigators set out to provide "a clinically informative systematic toxicity profile for lithium" they said (Lancet 2012 Jan. 20 [doi: 10.1016/S0140-6736(11)61516-X]).

Based on a hierarchy of evidence from the 22 randomized controlled trials, 197 cohort studies and case-control studies, and 166 case reports included in the review and meta-analysis, the investigators found that overall, glomerular filtration was reduced by –6.22 mL/min and urinary concentrating ability was reduced by 15% of normal maximum in patients receiving lithium, compared with controls.

"Data for the most clinically important outcome, renal failure, were scarce," the investigators said, noting that the only substantial cohort study showed that only 0.5% of patients receiving lithium were treated with renal replacement therapy.

As for clinical hypothyroidism, those taking lithium were significantly more likely than those on a placebo to develop the condition (odds ratio, 5.78), and based on a meta-analysis of the case-control studies, thyroid-stimulating hormone (TSH) concentrations were also significantly greater in those taking lithium (weighted mean difference, 4.00 IU/mL). Also, based on findings from 60 studies, blood calcium and parathyroid hormone levels were increased by about 10% over normal values in those taking lithium.

Clinically significant weight gain was also more frequent among those taking lithium than in controls (OR, 1.89), the investigators noted.

The evidence indicated, however, that lithium has little effect on hair or skin, with no significant difference seen in the incidence of alopecia in 24 publications reporting on the condition, and with no significant difference found in the prevalence of skin disorders between those taking lithium and controls in a meta-analysis of 77 publications.

Of note, six case-control studies that measured the association between Ebstein’s anomaly and lithium exposure found no link between the two. Although those estimates are unstable because of the low number of events, a case-control study of nearly 10,700 infants with a major congenital abnormality and more than 21,500 healthy controls also showed no significant association between lithium and congenital abnormalities.

Though limited by the quality and quantity of the primary evidence used in this study, which involved the screening of nearly 6,000 abstracts, the findings represent a "reasonable amount of evidence that allows cautious conclusions to be drawn about the safety of lithium," according to the investigators.

"This review provides a comprehensive synthesis of the evidence of harm that should inform clinical decision and draw attention to key questions in urgent need of further clarification," they said.

Based on their findings, the investigators developed the following recommendations for monitoring of lithium in clinical practice:

Before the start of lithium therapy, the risk of major adverse events should be discussed with the patient, a serum calcium level should be added to baseline blood tests, and uncertainty about the risk of congenital malformations to women of childbearing age should be explained. The latter two of these recommendations mark a change from current U.K. guidelines, the authors noted.

Also, during lithium therapy, renal, parathyroid, and thyroid function (at least glomerular filtration rate, TSH, and calcium) should be repeated at least every 12 months – and more frequently if an abnormal result is found or if the patient has a family history of endocrine disease; blood tests should all be repeated immediately in the event of a change in mood state; the occurrence of adverse effects should be routinely recorded; and women who would like to conceive or who have become pregnant during therapy should be advised that the increased risk of congenital malformation is uncertain, and the balance of risks between harm to the baby and maternal mood instability should be discussed before making a decision to discontinue lithium. All but the recommendation regarding repeat blood tests in the setting of mood state changes mark a change from current U.K. guidelines.

This study was funded by the National Institute for Health Research Programme Grant for Applied Research. The authors had no disclosures to report.

Concerns about valproate

I read Dr. Jain and Ms. Beste’s Pearl on treating alopecia developing during valproate use ("Valproate-induced hair loss: What to tell patients," Current Psychiatry, November 2011, p. 74) with some dismay.

Valproate is a valuable drug that has demonstrated efficacy in treating bipolar disorder; however, valproate use is associated with substantial side effects for women and developing fetuses.

I take no issue with any of the points made in the article, but I am concerned about the failure to mention critical side effects associated with valproate, including:

• weight gain and metabolic side effects
• for women, polycystic ovary syndrome—a serious and difficult-to-treat complication
• danger to fetuses—recent research suggests marked reductions in intelligence quotient in babies exposed to valproate in utero.¹

We would be wise to remind ourselves of these issues whenever considering initiating or continuing valproate therapy.

Edward Pontius, MD, DFAPA
Private Practice
Brunswick, ME

The authors respond

The concerns expressed by Dr. Pontius regarding clinical use of valproate are genuine and worthy. The purpose of our article was to call attention to a lesser-known side effect of valproate and how to intervene. We assumed that clinicians would discuss with patients the teratogenicity of valproate, along with other common side effects—weight gain, pancreatitis, effect on liver function tests, thrombocytopenia, and polycystic ovary syndrome—before initiating the drug. Such discussion about valproate was beyond the scope of our article, but we thank Dr. Pontius for bringing these concerns to our attention.

Shailesh Jain, MD, MPH, ABDA
Regional Chair
Associate Professor
Department of Psychiatry

Beth Beste, MS
Fourth-Year Medical Student
Texas Tech University Health Sciences Center, Permian Basin
Odessa, TX

Domains of excellence

I want to thank Dr. Nasrallah, whose monthly comments I find interesting and provocative, for his first-of-its-kind description of the “ideal” psychiatrist’s role and identity (“The model psychiatrist: 7 domains of excellence,” From the Editor, Current Psychiatry, November 2011, p. 5-6). This article should be mandatory reading and discussion material for every psychiatry residency program. For this elder psychiatrist, it was a thoughtful review of where I have been and where I am going in my field.

Ronald Blank, MD
Private Practice
Easthampton, MA

Additional traits

I find Current Psychiatry to be exceedingly useful for myself and the physician assistant students I teach. I agree with the 7 domains in Dr. Nasrallah’s editorial (“The model psychiatrist: 7 domains of excellence,” From the Editor, Current Psychiatry, November 2011, p. 5-6). However, I would like to add 2 more traits:

• The role that a psychiatrist plays in his or her family, especially with their children, because ignoring one’s family in the pursuit of clinical sainthood is not a mark of greatness
• The psychiatrist today is more of a team member than team leader. Failure to recognize this role creates intolerable stresses on the treatment environment in which the psychiatrist works. This does not minimize the need for personal excellence, but it certainly helps decrease destructive narcissism.

Kim J. Masters, MD
Medical Director
Three Rivers Midlands Campus Residential Treatment Center
West Columbia, SC

Concerns about valproate

I read Dr. Jain and Ms. Beste’s Pearl on treating alopecia developing during valproate use ("Valproate-induced hair loss: What to tell patients," Current Psychiatry, November 2011, p. 74) with some dismay.

Valproate is a valuable drug that has demonstrated efficacy in treating bipolar disorder; however, valproate use is associated with substantial side effects for women and developing fetuses.

I take no issue with any of the points made in the article, but I am concerned about the failure to mention critical side effects associated with valproate, including:

• weight gain and metabolic side effects
• for women, polycystic ovary syndrome—a serious and difficult-to-treat complication
• danger to fetuses—recent research suggests marked reductions in intelligence quotient in babies exposed to valproate in utero.¹

We would be wise to remind ourselves of these issues whenever considering initiating or continuing valproate therapy.

Edward Pontius, MD, DFAPA
Private Practice
Brunswick, ME

The authors respond

The concerns expressed by Dr. Pontius regarding clinical use of valproate are genuine and worthy. The purpose of our article was to call attention to a lesser-known side effect of valproate and how to intervene. We assumed that clinicians would discuss with patients the teratogenicity of valproate, along with other common side effects—weight gain, pancreatitis, effect on liver function tests, thrombocytopenia, and polycystic ovary syndrome—before initiating the drug. Such discussion about valproate was beyond the scope of our article, but we thank Dr. Pontius for bringing these concerns to our attention.

Shailesh Jain, MD, MPH, ABDA
Regional Chair
Associate Professor
Department of Psychiatry

Beth Beste, MS
Fourth-Year Medical Student
Texas Tech University Health Sciences Center, Permian Basin
Odessa, TX

Domains of excellence

I want to thank Dr. Nasrallah, whose monthly comments I find interesting and provocative, for his first-of-its-kind description of the “ideal” psychiatrist’s role and identity (“The model psychiatrist: 7 domains of excellence,” From the Editor, Current Psychiatry, November 2011, p. 5-6). This article should be mandatory reading and discussion material for every psychiatry residency program. For this elder psychiatrist, it was a thoughtful review of where I have been and where I am going in my field.

Ronald Blank, MD
Private Practice
Easthampton, MA

Additional traits

I find Current Psychiatry to be exceedingly useful for myself and the physician assistant students I teach. I agree with the 7 domains in Dr. Nasrallah’s editorial (“The model psychiatrist: 7 domains of excellence,” From the Editor, Current Psychiatry, November 2011, p. 5-6). However, I would like to add 2 more traits:

• The role that a psychiatrist plays in his or her family, especially with their children, because ignoring one’s family in the pursuit of clinical sainthood is not a mark of greatness
• The psychiatrist today is more of a team member than team leader. Failure to recognize this role creates intolerable stresses on the treatment environment in which the psychiatrist works. This does not minimize the need for personal excellence, but it certainly helps decrease destructive narcissism.

Kim J. Masters, MD
Medical Director
Three Rivers Midlands Campus Residential Treatment Center
West Columbia, SC

Concerns about valproate

I read Dr. Jain and Ms. Beste’s Pearl on treating alopecia developing during valproate use ("Valproate-induced hair loss: What to tell patients," Current Psychiatry, November 2011, p. 74) with some dismay.

Valproate is a valuable drug that has demonstrated efficacy in treating bipolar disorder; however, valproate use is associated with substantial side effects for women and developing fetuses.

I take no issue with any of the points made in the article, but I am concerned about the failure to mention critical side effects associated with valproate, including:

• weight gain and metabolic side effects
• for women, polycystic ovary syndrome—a serious and difficult-to-treat complication
• danger to fetuses—recent research suggests marked reductions in intelligence quotient in babies exposed to valproate in utero.¹

We would be wise to remind ourselves of these issues whenever considering initiating or continuing valproate therapy.

Edward Pontius, MD, DFAPA
Private Practice
Brunswick, ME

The authors respond

The concerns expressed by Dr. Pontius regarding clinical use of valproate are genuine and worthy. The purpose of our article was to call attention to a lesser-known side effect of valproate and how to intervene. We assumed that clinicians would discuss with patients the teratogenicity of valproate, along with other common side effects—weight gain, pancreatitis, effect on liver function tests, thrombocytopenia, and polycystic ovary syndrome—before initiating the drug. Such discussion about valproate was beyond the scope of our article, but we thank Dr. Pontius for bringing these concerns to our attention.

Shailesh Jain, MD, MPH, ABDA
Regional Chair
Associate Professor
Department of Psychiatry

Beth Beste, MS
Fourth-Year Medical Student
Texas Tech University Health Sciences Center, Permian Basin
Odessa, TX

Domains of excellence

I want to thank Dr. Nasrallah, whose monthly comments I find interesting and provocative, for his first-of-its-kind description of the “ideal” psychiatrist’s role and identity (“The model psychiatrist: 7 domains of excellence,” From the Editor, Current Psychiatry, November 2011, p. 5-6). This article should be mandatory reading and discussion material for every psychiatry residency program. For this elder psychiatrist, it was a thoughtful review of where I have been and where I am going in my field.

Ronald Blank, MD
Private Practice
Easthampton, MA

Additional traits

I find Current Psychiatry to be exceedingly useful for myself and the physician assistant students I teach. I agree with the 7 domains in Dr. Nasrallah’s editorial (“The model psychiatrist: 7 domains of excellence,” From the Editor, Current Psychiatry, November 2011, p. 5-6). However, I would like to add 2 more traits:

• The role that a psychiatrist plays in his or her family, especially with their children, because ignoring one’s family in the pursuit of clinical sainthood is not a mark of greatness
• The psychiatrist today is more of a team member than team leader. Failure to recognize this role creates intolerable stresses on the treatment environment in which the psychiatrist works. This does not minimize the need for personal excellence, but it certainly helps decrease destructive narcissism.

Kim J. Masters, MD
Medical Director
Three Rivers Midlands Campus Residential Treatment Center
West Columbia, SC

Ultra-rapid cycling (URC) entered the psychiatric lexicon in the 1990s as a proposed descriptor for manic/hypomanic, mixed, or depressed episodes of bipolar disorder (BD) that occur every few days or weeks. DSM-IV-TR incorporates rapid cycling (RC)—but not URC—as a course specifier that occurs in 10% to 15% of patients with BD who have ≥4 distinct affective episodes per year, each fulfilling duration criteria and separated by identifiable recovery periods (unless an episode directly changes polarity). Since then, the terms RC and URC have seemingly metamorphosed into imprecise, popular colloquialisms meant to loosely describe frequent mood changes rather than distinct episodes over extended time periods, with little regard for the associated signs that define manic or hypomanic episodes.

This article examines the meaning and validity of URC in BD, its relevance and differentiation from rapid mood shifts in patients without BD, and concepts relevant to treatment extrapolated from studies of RC BD.

Imprecise nomenclature

Post et al¹ coined the terms “ultra-rapid cycling” and “ultra-ultra-rapid cycling” (also called “ultradian cycling”) to describe mood episodes that occur monthly (URC) or over the course of as little as 1 day (ultradian cycling). These constructs are controversial because they lack demonstrated content validity and discriminant validity relative to other disorders. (“Content validity” refers to whether the features thought to comprise an entity of interest accurately and meaningfully do so; “discriminant validity” tells researchers and clinicians whether the proposed description of a clinical entity uniquely differentiates it from other disorders—avoiding “false-positive” suspected cases.) Clinicians therefore must pay careful attention to non-bipolar psychiatric problems that can present with rapid mood changes but without the psychomotor and related signs that define bipolar mood episodes. In their looser, nontechnical meanings, “rapid cycling” or “ultra-rapid cycling” may be synonymous with affective lability. RC is neither a diagnosis in itself nor a criterion for diagnosing BD. Rather, it is a course specifier to describe episode frequency in patients with past unambiguous manic or hypomanic episodes.

In children and adolescents, whose presentations often are atypical and can be hard to differentiate from other forms of behavioral or temperamental dysregulation, severe non-episodic mood dysregulation without signs of mania or hypomania may indicate a phenomenon separate from BD.² Geller and colleagues³ proposed using the term “episodes” to frame the duration of a DSM-IV-defined syndrome of mania/hypomania or depression, while reserving the term “cycling” to connote patterns of mood alternation within a given episode. It is not clear whether this concept of “cycling” differs qualitatively from mood lability that arises during a mood episode in children or adults, and notably, this perspective does not account for changes in psychomotor signs in conjunction with changes in mood.

Clinicians also sometimes blur the concept of “mixed episodes” with RC or URC. DSM-IV-TR defines mixed episodes within bipolar I disorder (BD I) based on criteria for a simultaneous manic and depressive episode, rather than on frequent oscillations between affective poles. These and other differential diagnostic considerations for suspected URC are summarized in Table 1.⁴

A further concern regarding nomenclature involves the distinction between cyclicity (ie, successive episodes regardless of pole direction) and changes in polarity (ie, switches from depression to mania/hypomania or vice versa). Some mood disorder patients may have rapid oscillations from euthymia to depression while never changing polarity to mania/hypomania and may be best described as having recurrent brief depression.

Table 1

Differential diagnosis in suspected URC

Duration criteria

Clinicians and researchers have debated the minimum duration criteria for identifying manic or hypomanic episodes, and the extent to which suspected hypomanic periods of short duration constitute distinct illness phases. Although DSM-IV-TR designates 4 days as a minimum time for classifying an episode of hypomania, empirical studies suggest that mood symptoms lasting as few as 2 days may comprise a valid and reliably distinct entity relevant to RC.⁵ More limited data (mainly case observations) identify “affective oscillations” and “mood shifts” occurring faster than once per 24 hours in BD patients without comorbid personality disorders.⁶ Phenomenologic studies that have focused on 24- to 48-hour switch cycles have described new-onset URC arising spontaneously or following closed head injuries.⁷ In children and younger adolescents, reports have identified long index manic episodes (mean durations as long as 80 weeks)⁸ that involve continual (ultradian) mood cycling in as many as 80% of cases.⁹

Is URC a valid construct?

A central controversy surrounding the validity and meaningfulness of URC as a BD subtype involves its sole focus on mood variation rather than the fuller constellation of associated signs and symptoms that define episodes of mania/hypomania or depression. Abrupt, sudden, drastic, or dramatic mood shifts from one moment to the next are nowhere to be found in the DSM-IV-TR definition of BD, and the construct of mood lability or affective instability is neither a cardinal nor defining element of BD. Although individuals with BD I or bipolar II disorder (BD II) may have periods of affective lability, rapid shifts in mood are neither necessary nor sufficient for a BD diagnosis, and may indicate other types of psychopathology when affective instability occurs in the absence of a history of discernible manic or hypomanic episodes.

Studies by our group¹⁰ and others¹¹ have shown that overattention to mood variation without considering associated cognitive, speech-language, chronobiologic, and motor signs of mania/hypomania accounts for substantial overdiagnosis of BD in patients with non-specific mood disturbances, particularly in those with active substance abuse or borderline personality disorder (BPD). Whereas the construct of RC BD attempts to account for changes in energy and psychomotor function as part of recurrent syndromes of mania/hypomania, existing literature on URC does not. Assessing mood changes in <24 hours also precludes assessing associated phenomena that occur over longer periods, such as changes in the sleep-wake cycle.

A rigorous, systematic approach to differential diagnosis for patients with affective instability is essential.

Borderline personality disorder

A common diagnostic debate regarding URC involves how to differentiate it from the chronic mood instability and reactivity inherent to BPD. Although some authors have suggested that RC BD and affective instability in BPD may be the same entity,¹² others object to unifying the 2 conditions without considering their phenomenologic and other clinical differences. For example, affective instability arising from borderline character organization is thought to reflect a patient’s impaired capacity to self-regulate his or her internal state and emotional responses to interpersonal and other environmental stresses, or difficulty managing impulses. By contrast, manic or depressive phases of BD tend not to be “triggered” by interpersonal conflicts or frustrations. Furthermore, reframing intense mood reactions to the environment as bipolar variants carries several pitfalls: doing so wrongly accords patients a passive role in their reactions to life events, inaccurately reinforces a sense of victimization in response to stress, and diverts inquiry away from a patient’s active role in life decisions and circumstances that may be unsatisfying, self-defeating, or volatile.

Two key considerations may be helpful in discriminating rapid mood changes in BD vs BPD. First, some longitudinal studies indicate that RC often is a transient, rather than enduring, phenomenon in BD,¹³ in contrast to the nonvarying, trait feature of affective instability in persons with BPD. It is unknown whether URC is more enduring than transient. Notably, whereas bipolar mood episodes constitute deviations from a baseline state, affective instability in BPD is a baseline characteristic, rather than a deviation from it. Second, by definition, a BPD diagnosis hinges on additional elements unrelated to mood disturbances, such as interpersonal styles or defense mechanisms that involve splitting, projection, and projective identification, feelings of numbness, boredom, or emptiness, identity diffusion, fears of abandonment, and proclivities toward self-mutilation or other self-injurious behaviors as a means to alleviate tension and stress. These characteristics do not overlap with the core elements of BD.

Affective lability in patients with BPD entails prominent oscillations between anger and anxiety, or depression and anxiety, but not depression and elation¹⁴; by contrast, affective instability in BD has been linked with greater oscillations between euthymia and depression, and euthymia and elation, but not euthymia and anger.¹⁵ Moreover, daily mood fluctuations in patients with BD appear to occur in a relatively random fashion,¹⁶ whereas in BPD mood fluctuations are reactions that appear intimately linked to distressing interpersonal experiences.

See the table below, entitled “Rapid cycling and ultra-rapid cycling BD: A comparison,” comparing the phenomenology of RC and URC and a discussion of studies that explored genetic markers or family patterns that may be related to RC or URC.

Treatment considerations

No systematic studies exist for treating URC. Because most clinical trials of BD focus on treatment or prevention of a single episode rather than changes of mood over time, it is difficult to draw inferences about the ability of any treatment to attenuate marked, day-to-day mood variations. Some antimanic drugs, such as carbamazepine, have been suggested to offer better prophylactic efficacy compared with lithium for “non-classical” BD presentations, although the efficacy of carbamazepine has not been studied in URC.

Broadly speaking, treatment for URC, similar to RC, pragmatically involves:

• identifying and eliminating sources of mood destabilization (eg, substance abuse, erratic sleep patterns)
• treating medical comorbidities such as hypothyroidism
• optimizing treatment with mood stabilizing agents
• exercising caution when using antidepressants (see below).

Interestingly, despite frequent allusion to certain medications as “mood stabilizers,” no controlled study has examined mood instability on a day-to-day basis as a primary outcome measure in BD treatment, which limits the ability to surmise that any drug could be expected to diminish mood oscillations that occur over the course of days, or within a single day. However, a post hoc analysis by our group¹⁷ compared randomized treatment with lamotrigine or placebo over 6 months in RC BD I or BD II. Using prospective life charting, we found patients who received lamotrigine were almost twice as likely as those receiving placebo to achieve euthymia from one week to the next, which suggests the possibility that lamotrigine may offer benefit for affective instability in BD I or BD II patients, in addition to preventing discrete mood episodes.

Antidepressant controversy. Concerns that antidepressants might acutely induce mania or accelerate cycling frequency over long time periods have led to a contentious, long-standing debate within psychopharmacology. As noted in the box below, several long-term naturalistic follow-up studies have reported RC as a perceived consequence of antidepressants in most RC patients, although efforts to differentiate cycle acceleration caused by antidepressants (or other iatrogenic factors) from the natural course of illness remains exceedingly difficult without prospective randomized trials. (Antidepressants might cause more affective recurrences, but having multiple episodes may also cause more antidepressant prescriptions.) Some researchers (eg, Schneck et al¹⁸) have reported more frequent episodes among patients taking antidepressants but did not consider that patients with multiple episodes may be more likely to receive antidepressants, which fail to ameliorate acute or recurrent affective episodes. Importantly, a recent multi-site randomized trial by Ghaemi et al¹⁹ found that after a favorable acute response to antidepressants plus mood stabilizers, patients with preexisting RC who were randomized to continue antidepressants for up to 1 year had a 3-fold increased likelihood of developing a new depressive episode, which affirms suggestions that antidepressants do not help—but may exacerbate—cycling in patients with RC. No studies in BD have examined whether URC is more likely to arise as a consequence of antidepressant use.

Mood stabilizers and other biologic therapies. A small body of literature specifically addresses pharmacotherapy of URC in patients with BD (Table 2).^19-26 A limitation of most existing literature is its focus on case reports, small open trials, or anecdotal observations rather than large, randomized controlled trials using systematic outcome measures. Extrapolation from reports focusing on patients with DSM-IV-TR RC is limited because it is uncertain whether URC differs fundamentally from RC and studies of DSM-IV-TR RC typically examine acute response during an index episode or time until relapse during maintenance therapy, rather than impact on mood changes over time.

Psychotherapy. A limited database on the efficacy of adjunctive cognitive-behavioral therapy (CBT) in RC BD describes improvement in depressive symptoms over short-term follow-up.²⁷ No long-term studies of CBT or other structured psychotherapies have focused on RC or URC. Intuitively, one might expect that psychoeducation targeting sleep hygiene, substance use, stress management and coping skills, medication adherence, and prodrome recognition would be of value to patients with BD who experience frequent mood episodes, especially in those who may be unaware of or unfamiliar with basic concepts related to BD. In addition, relevant concepts from dialectical behavior therapy may be beneficial for BD patients with possible URC, such as skills to enhance emotional regulation, distress tolerance, mindfulness, and interpersonal effectiveness.

Table 2

Evidence-based treatments for ultra-rapid cycling BD

Treatment monitoring. Prospective life charting allows patients to systematically record manic/hypomanic and depressive symptoms day-to-day and week-to-week, thus creating a measure that may be particularly relevant for patients whose moods change rapidly. Simple mood charts (see Related Resources) typically take into account the severity of symptoms of either polarity with ratings of mild, moderate, or severe. Such visual records permit simple calculations over the course of a given interval (eg, week-by-week or across months) of several important parameters, including:

• number of days euthymic
• number of days with depression
• number of days with abnormal mood elevation
• number of occasions in which moods of both polarities occur on the same day.

Tracking these parameters during a treatment allows clinicians to make quantitative comparisons over time as a method of determining whether or not meaningful changes are occurring in cyclicity. See the figure below for an example of a completed mood chart and its interpretation.

Additional recommendations for assessing and managing cyclicity in BD are summarized in Table 3.

Table 3

Tips for managing suspected ultra-rapid cycling BD

Table

Rapid cycling and ultra-rapid cycling BD: A comparison

Box

Figure: Example of prospective mood charting to document changes in manic/hypomanic and depressive symptoms across time

In the above example, the prevalence and severity of mood symptoms are identified over 21 days. Note the distinctly separate phases of mood elevation followed by depression, whereas euthymia was present only 6 of 21 days (29% of the time). Symptoms of at least moderate severity were more prominently depressive (5 of 21 days, or 24% of the time) than manic/hypomanic (2 of 21 days, or approximately 10% of the time). Mood charting does not capture associate DSM-IV-TR criteria for a mood episode but instead focuses solely on longitudinal changes in mood elevation or depression

Related Resources

• American Psychiatric Association practice guideline for the treatment of patients with bipolar disorder (revision). Am J Psychiatry. 2002;159(4 suppl):1-50.
• Massachusetts General Hospital Bipolar Clinic and Research Program. Sample mood chart (downloadable). www.manicdepressive.org/moodchart.html.

Drug Brand Names

• Carbamazepine • Equetro, Tegretol
• Divalproex • Depakote
• Lamotrigine • Lamictal
• Levothyroxine • Synthroid
• Lithium • Lithobid
• Nimodipine • Nimotop
• Topiramate • Topamax

Disclosures

Dr. Goldberg is on the speakers’ bureaus for AstraZeneca, Dey Pharmaceuticals, Eli Lilly and Company, Merck, and Sunovion and is a consultant for Axon Advisors, Dey Pharmaceuticals, Eli Lilly and Company, and Grünenthal Group.

Acknowledgment

The author wishes to thank David L. Dunner, MD, for his helpful comments regarding this article.

Ultra-rapid cycling (URC) entered the psychiatric lexicon in the 1990s as a proposed descriptor for manic/hypomanic, mixed, or depressed episodes of bipolar disorder (BD) that occur every few days or weeks. DSM-IV-TR incorporates rapid cycling (RC)—but not URC—as a course specifier that occurs in 10% to 15% of patients with BD who have ≥4 distinct affective episodes per year, each fulfilling duration criteria and separated by identifiable recovery periods (unless an episode directly changes polarity). Since then, the terms RC and URC have seemingly metamorphosed into imprecise, popular colloquialisms meant to loosely describe frequent mood changes rather than distinct episodes over extended time periods, with little regard for the associated signs that define manic or hypomanic episodes.

This article examines the meaning and validity of URC in BD, its relevance and differentiation from rapid mood shifts in patients without BD, and concepts relevant to treatment extrapolated from studies of RC BD.

Imprecise nomenclature

Post et al¹ coined the terms “ultra-rapid cycling” and “ultra-ultra-rapid cycling” (also called “ultradian cycling”) to describe mood episodes that occur monthly (URC) or over the course of as little as 1 day (ultradian cycling). These constructs are controversial because they lack demonstrated content validity and discriminant validity relative to other disorders. (“Content validity” refers to whether the features thought to comprise an entity of interest accurately and meaningfully do so; “discriminant validity” tells researchers and clinicians whether the proposed description of a clinical entity uniquely differentiates it from other disorders—avoiding “false-positive” suspected cases.) Clinicians therefore must pay careful attention to non-bipolar psychiatric problems that can present with rapid mood changes but without the psychomotor and related signs that define bipolar mood episodes. In their looser, nontechnical meanings, “rapid cycling” or “ultra-rapid cycling” may be synonymous with affective lability. RC is neither a diagnosis in itself nor a criterion for diagnosing BD. Rather, it is a course specifier to describe episode frequency in patients with past unambiguous manic or hypomanic episodes.

In children and adolescents, whose presentations often are atypical and can be hard to differentiate from other forms of behavioral or temperamental dysregulation, severe non-episodic mood dysregulation without signs of mania or hypomania may indicate a phenomenon separate from BD.² Geller and colleagues³ proposed using the term “episodes” to frame the duration of a DSM-IV-defined syndrome of mania/hypomania or depression, while reserving the term “cycling” to connote patterns of mood alternation within a given episode. It is not clear whether this concept of “cycling” differs qualitatively from mood lability that arises during a mood episode in children or adults, and notably, this perspective does not account for changes in psychomotor signs in conjunction with changes in mood.

Clinicians also sometimes blur the concept of “mixed episodes” with RC or URC. DSM-IV-TR defines mixed episodes within bipolar I disorder (BD I) based on criteria for a simultaneous manic and depressive episode, rather than on frequent oscillations between affective poles. These and other differential diagnostic considerations for suspected URC are summarized in Table 1.⁴

A further concern regarding nomenclature involves the distinction between cyclicity (ie, successive episodes regardless of pole direction) and changes in polarity (ie, switches from depression to mania/hypomania or vice versa). Some mood disorder patients may have rapid oscillations from euthymia to depression while never changing polarity to mania/hypomania and may be best described as having recurrent brief depression.

Table 1

Differential diagnosis in suspected URC

Duration criteria

Clinicians and researchers have debated the minimum duration criteria for identifying manic or hypomanic episodes, and the extent to which suspected hypomanic periods of short duration constitute distinct illness phases. Although DSM-IV-TR designates 4 days as a minimum time for classifying an episode of hypomania, empirical studies suggest that mood symptoms lasting as few as 2 days may comprise a valid and reliably distinct entity relevant to RC.⁵ More limited data (mainly case observations) identify “affective oscillations” and “mood shifts” occurring faster than once per 24 hours in BD patients without comorbid personality disorders.⁶ Phenomenologic studies that have focused on 24- to 48-hour switch cycles have described new-onset URC arising spontaneously or following closed head injuries.⁷ In children and younger adolescents, reports have identified long index manic episodes (mean durations as long as 80 weeks)⁸ that involve continual (ultradian) mood cycling in as many as 80% of cases.⁹

Is URC a valid construct?

A central controversy surrounding the validity and meaningfulness of URC as a BD subtype involves its sole focus on mood variation rather than the fuller constellation of associated signs and symptoms that define episodes of mania/hypomania or depression. Abrupt, sudden, drastic, or dramatic mood shifts from one moment to the next are nowhere to be found in the DSM-IV-TR definition of BD, and the construct of mood lability or affective instability is neither a cardinal nor defining element of BD. Although individuals with BD I or bipolar II disorder (BD II) may have periods of affective lability, rapid shifts in mood are neither necessary nor sufficient for a BD diagnosis, and may indicate other types of psychopathology when affective instability occurs in the absence of a history of discernible manic or hypomanic episodes.

Studies by our group¹⁰ and others¹¹ have shown that overattention to mood variation without considering associated cognitive, speech-language, chronobiologic, and motor signs of mania/hypomania accounts for substantial overdiagnosis of BD in patients with non-specific mood disturbances, particularly in those with active substance abuse or borderline personality disorder (BPD). Whereas the construct of RC BD attempts to account for changes in energy and psychomotor function as part of recurrent syndromes of mania/hypomania, existing literature on URC does not. Assessing mood changes in <24 hours also precludes assessing associated phenomena that occur over longer periods, such as changes in the sleep-wake cycle.

A rigorous, systematic approach to differential diagnosis for patients with affective instability is essential.

Borderline personality disorder

A common diagnostic debate regarding URC involves how to differentiate it from the chronic mood instability and reactivity inherent to BPD. Although some authors have suggested that RC BD and affective instability in BPD may be the same entity,¹² others object to unifying the 2 conditions without considering their phenomenologic and other clinical differences. For example, affective instability arising from borderline character organization is thought to reflect a patient’s impaired capacity to self-regulate his or her internal state and emotional responses to interpersonal and other environmental stresses, or difficulty managing impulses. By contrast, manic or depressive phases of BD tend not to be “triggered” by interpersonal conflicts or frustrations. Furthermore, reframing intense mood reactions to the environment as bipolar variants carries several pitfalls: doing so wrongly accords patients a passive role in their reactions to life events, inaccurately reinforces a sense of victimization in response to stress, and diverts inquiry away from a patient’s active role in life decisions and circumstances that may be unsatisfying, self-defeating, or volatile.

Two key considerations may be helpful in discriminating rapid mood changes in BD vs BPD. First, some longitudinal studies indicate that RC often is a transient, rather than enduring, phenomenon in BD,¹³ in contrast to the nonvarying, trait feature of affective instability in persons with BPD. It is unknown whether URC is more enduring than transient. Notably, whereas bipolar mood episodes constitute deviations from a baseline state, affective instability in BPD is a baseline characteristic, rather than a deviation from it. Second, by definition, a BPD diagnosis hinges on additional elements unrelated to mood disturbances, such as interpersonal styles or defense mechanisms that involve splitting, projection, and projective identification, feelings of numbness, boredom, or emptiness, identity diffusion, fears of abandonment, and proclivities toward self-mutilation or other self-injurious behaviors as a means to alleviate tension and stress. These characteristics do not overlap with the core elements of BD.

Affective lability in patients with BPD entails prominent oscillations between anger and anxiety, or depression and anxiety, but not depression and elation¹⁴; by contrast, affective instability in BD has been linked with greater oscillations between euthymia and depression, and euthymia and elation, but not euthymia and anger.¹⁵ Moreover, daily mood fluctuations in patients with BD appear to occur in a relatively random fashion,¹⁶ whereas in BPD mood fluctuations are reactions that appear intimately linked to distressing interpersonal experiences.

See the table below, entitled “Rapid cycling and ultra-rapid cycling BD: A comparison,” comparing the phenomenology of RC and URC and a discussion of studies that explored genetic markers or family patterns that may be related to RC or URC.

Treatment considerations

No systematic studies exist for treating URC. Because most clinical trials of BD focus on treatment or prevention of a single episode rather than changes of mood over time, it is difficult to draw inferences about the ability of any treatment to attenuate marked, day-to-day mood variations. Some antimanic drugs, such as carbamazepine, have been suggested to offer better prophylactic efficacy compared with lithium for “non-classical” BD presentations, although the efficacy of carbamazepine has not been studied in URC.

Broadly speaking, treatment for URC, similar to RC, pragmatically involves:

• identifying and eliminating sources of mood destabilization (eg, substance abuse, erratic sleep patterns)
• treating medical comorbidities such as hypothyroidism
• optimizing treatment with mood stabilizing agents
• exercising caution when using antidepressants (see below).

Interestingly, despite frequent allusion to certain medications as “mood stabilizers,” no controlled study has examined mood instability on a day-to-day basis as a primary outcome measure in BD treatment, which limits the ability to surmise that any drug could be expected to diminish mood oscillations that occur over the course of days, or within a single day. However, a post hoc analysis by our group¹⁷ compared randomized treatment with lamotrigine or placebo over 6 months in RC BD I or BD II. Using prospective life charting, we found patients who received lamotrigine were almost twice as likely as those receiving placebo to achieve euthymia from one week to the next, which suggests the possibility that lamotrigine may offer benefit for affective instability in BD I or BD II patients, in addition to preventing discrete mood episodes.

Antidepressant controversy. Concerns that antidepressants might acutely induce mania or accelerate cycling frequency over long time periods have led to a contentious, long-standing debate within psychopharmacology. As noted in the box below, several long-term naturalistic follow-up studies have reported RC as a perceived consequence of antidepressants in most RC patients, although efforts to differentiate cycle acceleration caused by antidepressants (or other iatrogenic factors) from the natural course of illness remains exceedingly difficult without prospective randomized trials. (Antidepressants might cause more affective recurrences, but having multiple episodes may also cause more antidepressant prescriptions.) Some researchers (eg, Schneck et al¹⁸) have reported more frequent episodes among patients taking antidepressants but did not consider that patients with multiple episodes may be more likely to receive antidepressants, which fail to ameliorate acute or recurrent affective episodes. Importantly, a recent multi-site randomized trial by Ghaemi et al¹⁹ found that after a favorable acute response to antidepressants plus mood stabilizers, patients with preexisting RC who were randomized to continue antidepressants for up to 1 year had a 3-fold increased likelihood of developing a new depressive episode, which affirms suggestions that antidepressants do not help—but may exacerbate—cycling in patients with RC. No studies in BD have examined whether URC is more likely to arise as a consequence of antidepressant use.

Mood stabilizers and other biologic therapies. A small body of literature specifically addresses pharmacotherapy of URC in patients with BD (Table 2).^19-26 A limitation of most existing literature is its focus on case reports, small open trials, or anecdotal observations rather than large, randomized controlled trials using systematic outcome measures. Extrapolation from reports focusing on patients with DSM-IV-TR RC is limited because it is uncertain whether URC differs fundamentally from RC and studies of DSM-IV-TR RC typically examine acute response during an index episode or time until relapse during maintenance therapy, rather than impact on mood changes over time.

Psychotherapy. A limited database on the efficacy of adjunctive cognitive-behavioral therapy (CBT) in RC BD describes improvement in depressive symptoms over short-term follow-up.²⁷ No long-term studies of CBT or other structured psychotherapies have focused on RC or URC. Intuitively, one might expect that psychoeducation targeting sleep hygiene, substance use, stress management and coping skills, medication adherence, and prodrome recognition would be of value to patients with BD who experience frequent mood episodes, especially in those who may be unaware of or unfamiliar with basic concepts related to BD. In addition, relevant concepts from dialectical behavior therapy may be beneficial for BD patients with possible URC, such as skills to enhance emotional regulation, distress tolerance, mindfulness, and interpersonal effectiveness.

Table 2

Evidence-based treatments for ultra-rapid cycling BD

Treatment monitoring. Prospective life charting allows patients to systematically record manic/hypomanic and depressive symptoms day-to-day and week-to-week, thus creating a measure that may be particularly relevant for patients whose moods change rapidly. Simple mood charts (see Related Resources) typically take into account the severity of symptoms of either polarity with ratings of mild, moderate, or severe. Such visual records permit simple calculations over the course of a given interval (eg, week-by-week or across months) of several important parameters, including:

• number of days euthymic
• number of days with depression
• number of days with abnormal mood elevation
• number of occasions in which moods of both polarities occur on the same day.

Tracking these parameters during a treatment allows clinicians to make quantitative comparisons over time as a method of determining whether or not meaningful changes are occurring in cyclicity. See the figure below for an example of a completed mood chart and its interpretation.

Additional recommendations for assessing and managing cyclicity in BD are summarized in Table 3.

Table 3

Tips for managing suspected ultra-rapid cycling BD

Table

Rapid cycling and ultra-rapid cycling BD: A comparison

Box

Figure: Example of prospective mood charting to document changes in manic/hypomanic and depressive symptoms across time

In the above example, the prevalence and severity of mood symptoms are identified over 21 days. Note the distinctly separate phases of mood elevation followed by depression, whereas euthymia was present only 6 of 21 days (29% of the time). Symptoms of at least moderate severity were more prominently depressive (5 of 21 days, or 24% of the time) than manic/hypomanic (2 of 21 days, or approximately 10% of the time). Mood charting does not capture associate DSM-IV-TR criteria for a mood episode but instead focuses solely on longitudinal changes in mood elevation or depression

Related Resources

• American Psychiatric Association practice guideline for the treatment of patients with bipolar disorder (revision). Am J Psychiatry. 2002;159(4 suppl):1-50.
• Massachusetts General Hospital Bipolar Clinic and Research Program. Sample mood chart (downloadable). www.manicdepressive.org/moodchart.html.

Drug Brand Names

• Carbamazepine • Equetro, Tegretol
• Divalproex • Depakote
• Lamotrigine • Lamictal
• Levothyroxine • Synthroid
• Lithium • Lithobid
• Nimodipine • Nimotop
• Topiramate • Topamax

Disclosures

Dr. Goldberg is on the speakers’ bureaus for AstraZeneca, Dey Pharmaceuticals, Eli Lilly and Company, Merck, and Sunovion and is a consultant for Axon Advisors, Dey Pharmaceuticals, Eli Lilly and Company, and Grünenthal Group.

Acknowledgment

The author wishes to thank David L. Dunner, MD, for his helpful comments regarding this article.

Ultra-rapid cycling (URC) entered the psychiatric lexicon in the 1990s as a proposed descriptor for manic/hypomanic, mixed, or depressed episodes of bipolar disorder (BD) that occur every few days or weeks. DSM-IV-TR incorporates rapid cycling (RC)—but not URC—as a course specifier that occurs in 10% to 15% of patients with BD who have ≥4 distinct affective episodes per year, each fulfilling duration criteria and separated by identifiable recovery periods (unless an episode directly changes polarity). Since then, the terms RC and URC have seemingly metamorphosed into imprecise, popular colloquialisms meant to loosely describe frequent mood changes rather than distinct episodes over extended time periods, with little regard for the associated signs that define manic or hypomanic episodes.

This article examines the meaning and validity of URC in BD, its relevance and differentiation from rapid mood shifts in patients without BD, and concepts relevant to treatment extrapolated from studies of RC BD.

Imprecise nomenclature

Post et al¹ coined the terms “ultra-rapid cycling” and “ultra-ultra-rapid cycling” (also called “ultradian cycling”) to describe mood episodes that occur monthly (URC) or over the course of as little as 1 day (ultradian cycling). These constructs are controversial because they lack demonstrated content validity and discriminant validity relative to other disorders. (“Content validity” refers to whether the features thought to comprise an entity of interest accurately and meaningfully do so; “discriminant validity” tells researchers and clinicians whether the proposed description of a clinical entity uniquely differentiates it from other disorders—avoiding “false-positive” suspected cases.) Clinicians therefore must pay careful attention to non-bipolar psychiatric problems that can present with rapid mood changes but without the psychomotor and related signs that define bipolar mood episodes. In their looser, nontechnical meanings, “rapid cycling” or “ultra-rapid cycling” may be synonymous with affective lability. RC is neither a diagnosis in itself nor a criterion for diagnosing BD. Rather, it is a course specifier to describe episode frequency in patients with past unambiguous manic or hypomanic episodes.

In children and adolescents, whose presentations often are atypical and can be hard to differentiate from other forms of behavioral or temperamental dysregulation, severe non-episodic mood dysregulation without signs of mania or hypomania may indicate a phenomenon separate from BD.² Geller and colleagues³ proposed using the term “episodes” to frame the duration of a DSM-IV-defined syndrome of mania/hypomania or depression, while reserving the term “cycling” to connote patterns of mood alternation within a given episode. It is not clear whether this concept of “cycling” differs qualitatively from mood lability that arises during a mood episode in children or adults, and notably, this perspective does not account for changes in psychomotor signs in conjunction with changes in mood.

Clinicians also sometimes blur the concept of “mixed episodes” with RC or URC. DSM-IV-TR defines mixed episodes within bipolar I disorder (BD I) based on criteria for a simultaneous manic and depressive episode, rather than on frequent oscillations between affective poles. These and other differential diagnostic considerations for suspected URC are summarized in Table 1.⁴

A further concern regarding nomenclature involves the distinction between cyclicity (ie, successive episodes regardless of pole direction) and changes in polarity (ie, switches from depression to mania/hypomania or vice versa). Some mood disorder patients may have rapid oscillations from euthymia to depression while never changing polarity to mania/hypomania and may be best described as having recurrent brief depression.

Table 1

Differential diagnosis in suspected URC

Duration criteria

Clinicians and researchers have debated the minimum duration criteria for identifying manic or hypomanic episodes, and the extent to which suspected hypomanic periods of short duration constitute distinct illness phases. Although DSM-IV-TR designates 4 days as a minimum time for classifying an episode of hypomania, empirical studies suggest that mood symptoms lasting as few as 2 days may comprise a valid and reliably distinct entity relevant to RC.⁵ More limited data (mainly case observations) identify “affective oscillations” and “mood shifts” occurring faster than once per 24 hours in BD patients without comorbid personality disorders.⁶ Phenomenologic studies that have focused on 24- to 48-hour switch cycles have described new-onset URC arising spontaneously or following closed head injuries.⁷ In children and younger adolescents, reports have identified long index manic episodes (mean durations as long as 80 weeks)⁸ that involve continual (ultradian) mood cycling in as many as 80% of cases.⁹

Is URC a valid construct?

A central controversy surrounding the validity and meaningfulness of URC as a BD subtype involves its sole focus on mood variation rather than the fuller constellation of associated signs and symptoms that define episodes of mania/hypomania or depression. Abrupt, sudden, drastic, or dramatic mood shifts from one moment to the next are nowhere to be found in the DSM-IV-TR definition of BD, and the construct of mood lability or affective instability is neither a cardinal nor defining element of BD. Although individuals with BD I or bipolar II disorder (BD II) may have periods of affective lability, rapid shifts in mood are neither necessary nor sufficient for a BD diagnosis, and may indicate other types of psychopathology when affective instability occurs in the absence of a history of discernible manic or hypomanic episodes.

Studies by our group¹⁰ and others¹¹ have shown that overattention to mood variation without considering associated cognitive, speech-language, chronobiologic, and motor signs of mania/hypomania accounts for substantial overdiagnosis of BD in patients with non-specific mood disturbances, particularly in those with active substance abuse or borderline personality disorder (BPD). Whereas the construct of RC BD attempts to account for changes in energy and psychomotor function as part of recurrent syndromes of mania/hypomania, existing literature on URC does not. Assessing mood changes in <24 hours also precludes assessing associated phenomena that occur over longer periods, such as changes in the sleep-wake cycle.

A rigorous, systematic approach to differential diagnosis for patients with affective instability is essential.

Borderline personality disorder

A common diagnostic debate regarding URC involves how to differentiate it from the chronic mood instability and reactivity inherent to BPD. Although some authors have suggested that RC BD and affective instability in BPD may be the same entity,¹² others object to unifying the 2 conditions without considering their phenomenologic and other clinical differences. For example, affective instability arising from borderline character organization is thought to reflect a patient’s impaired capacity to self-regulate his or her internal state and emotional responses to interpersonal and other environmental stresses, or difficulty managing impulses. By contrast, manic or depressive phases of BD tend not to be “triggered” by interpersonal conflicts or frustrations. Furthermore, reframing intense mood reactions to the environment as bipolar variants carries several pitfalls: doing so wrongly accords patients a passive role in their reactions to life events, inaccurately reinforces a sense of victimization in response to stress, and diverts inquiry away from a patient’s active role in life decisions and circumstances that may be unsatisfying, self-defeating, or volatile.

Two key considerations may be helpful in discriminating rapid mood changes in BD vs BPD. First, some longitudinal studies indicate that RC often is a transient, rather than enduring, phenomenon in BD,¹³ in contrast to the nonvarying, trait feature of affective instability in persons with BPD. It is unknown whether URC is more enduring than transient. Notably, whereas bipolar mood episodes constitute deviations from a baseline state, affective instability in BPD is a baseline characteristic, rather than a deviation from it. Second, by definition, a BPD diagnosis hinges on additional elements unrelated to mood disturbances, such as interpersonal styles or defense mechanisms that involve splitting, projection, and projective identification, feelings of numbness, boredom, or emptiness, identity diffusion, fears of abandonment, and proclivities toward self-mutilation or other self-injurious behaviors as a means to alleviate tension and stress. These characteristics do not overlap with the core elements of BD.

Affective lability in patients with BPD entails prominent oscillations between anger and anxiety, or depression and anxiety, but not depression and elation¹⁴; by contrast, affective instability in BD has been linked with greater oscillations between euthymia and depression, and euthymia and elation, but not euthymia and anger.¹⁵ Moreover, daily mood fluctuations in patients with BD appear to occur in a relatively random fashion,¹⁶ whereas in BPD mood fluctuations are reactions that appear intimately linked to distressing interpersonal experiences.

See the table below, entitled “Rapid cycling and ultra-rapid cycling BD: A comparison,” comparing the phenomenology of RC and URC and a discussion of studies that explored genetic markers or family patterns that may be related to RC or URC.

Treatment considerations

No systematic studies exist for treating URC. Because most clinical trials of BD focus on treatment or prevention of a single episode rather than changes of mood over time, it is difficult to draw inferences about the ability of any treatment to attenuate marked, day-to-day mood variations. Some antimanic drugs, such as carbamazepine, have been suggested to offer better prophylactic efficacy compared with lithium for “non-classical” BD presentations, although the efficacy of carbamazepine has not been studied in URC.

Broadly speaking, treatment for URC, similar to RC, pragmatically involves:

• identifying and eliminating sources of mood destabilization (eg, substance abuse, erratic sleep patterns)
• treating medical comorbidities such as hypothyroidism
• optimizing treatment with mood stabilizing agents
• exercising caution when using antidepressants (see below).

Interestingly, despite frequent allusion to certain medications as “mood stabilizers,” no controlled study has examined mood instability on a day-to-day basis as a primary outcome measure in BD treatment, which limits the ability to surmise that any drug could be expected to diminish mood oscillations that occur over the course of days, or within a single day. However, a post hoc analysis by our group¹⁷ compared randomized treatment with lamotrigine or placebo over 6 months in RC BD I or BD II. Using prospective life charting, we found patients who received lamotrigine were almost twice as likely as those receiving placebo to achieve euthymia from one week to the next, which suggests the possibility that lamotrigine may offer benefit for affective instability in BD I or BD II patients, in addition to preventing discrete mood episodes.

Antidepressant controversy. Concerns that antidepressants might acutely induce mania or accelerate cycling frequency over long time periods have led to a contentious, long-standing debate within psychopharmacology. As noted in the box below, several long-term naturalistic follow-up studies have reported RC as a perceived consequence of antidepressants in most RC patients, although efforts to differentiate cycle acceleration caused by antidepressants (or other iatrogenic factors) from the natural course of illness remains exceedingly difficult without prospective randomized trials. (Antidepressants might cause more affective recurrences, but having multiple episodes may also cause more antidepressant prescriptions.) Some researchers (eg, Schneck et al¹⁸) have reported more frequent episodes among patients taking antidepressants but did not consider that patients with multiple episodes may be more likely to receive antidepressants, which fail to ameliorate acute or recurrent affective episodes. Importantly, a recent multi-site randomized trial by Ghaemi et al¹⁹ found that after a favorable acute response to antidepressants plus mood stabilizers, patients with preexisting RC who were randomized to continue antidepressants for up to 1 year had a 3-fold increased likelihood of developing a new depressive episode, which affirms suggestions that antidepressants do not help—but may exacerbate—cycling in patients with RC. No studies in BD have examined whether URC is more likely to arise as a consequence of antidepressant use.

Mood stabilizers and other biologic therapies. A small body of literature specifically addresses pharmacotherapy of URC in patients with BD (Table 2).^19-26 A limitation of most existing literature is its focus on case reports, small open trials, or anecdotal observations rather than large, randomized controlled trials using systematic outcome measures. Extrapolation from reports focusing on patients with DSM-IV-TR RC is limited because it is uncertain whether URC differs fundamentally from RC and studies of DSM-IV-TR RC typically examine acute response during an index episode or time until relapse during maintenance therapy, rather than impact on mood changes over time.

Psychotherapy. A limited database on the efficacy of adjunctive cognitive-behavioral therapy (CBT) in RC BD describes improvement in depressive symptoms over short-term follow-up.²⁷ No long-term studies of CBT or other structured psychotherapies have focused on RC or URC. Intuitively, one might expect that psychoeducation targeting sleep hygiene, substance use, stress management and coping skills, medication adherence, and prodrome recognition would be of value to patients with BD who experience frequent mood episodes, especially in those who may be unaware of or unfamiliar with basic concepts related to BD. In addition, relevant concepts from dialectical behavior therapy may be beneficial for BD patients with possible URC, such as skills to enhance emotional regulation, distress tolerance, mindfulness, and interpersonal effectiveness.

Table 2

Evidence-based treatments for ultra-rapid cycling BD

Treatment monitoring. Prospective life charting allows patients to systematically record manic/hypomanic and depressive symptoms day-to-day and week-to-week, thus creating a measure that may be particularly relevant for patients whose moods change rapidly. Simple mood charts (see Related Resources) typically take into account the severity of symptoms of either polarity with ratings of mild, moderate, or severe. Such visual records permit simple calculations over the course of a given interval (eg, week-by-week or across months) of several important parameters, including:

• number of days euthymic
• number of days with depression
• number of days with abnormal mood elevation
• number of occasions in which moods of both polarities occur on the same day.

Tracking these parameters during a treatment allows clinicians to make quantitative comparisons over time as a method of determining whether or not meaningful changes are occurring in cyclicity. See the figure below for an example of a completed mood chart and its interpretation.

Additional recommendations for assessing and managing cyclicity in BD are summarized in Table 3.

Table 3

Tips for managing suspected ultra-rapid cycling BD

Table

Rapid cycling and ultra-rapid cycling BD: A comparison

Box

Figure: Example of prospective mood charting to document changes in manic/hypomanic and depressive symptoms across time

In the above example, the prevalence and severity of mood symptoms are identified over 21 days. Note the distinctly separate phases of mood elevation followed by depression, whereas euthymia was present only 6 of 21 days (29% of the time). Symptoms of at least moderate severity were more prominently depressive (5 of 21 days, or 24% of the time) than manic/hypomanic (2 of 21 days, or approximately 10% of the time). Mood charting does not capture associate DSM-IV-TR criteria for a mood episode but instead focuses solely on longitudinal changes in mood elevation or depression

Related Resources

• American Psychiatric Association practice guideline for the treatment of patients with bipolar disorder (revision). Am J Psychiatry. 2002;159(4 suppl):1-50.
• Massachusetts General Hospital Bipolar Clinic and Research Program. Sample mood chart (downloadable). www.manicdepressive.org/moodchart.html.

Drug Brand Names

• Carbamazepine • Equetro, Tegretol
• Divalproex • Depakote
• Lamotrigine • Lamictal
• Levothyroxine • Synthroid
• Lithium • Lithobid
• Nimodipine • Nimotop
• Topiramate • Topamax

Disclosures

Dr. Goldberg is on the speakers’ bureaus for AstraZeneca, Dey Pharmaceuticals, Eli Lilly and Company, Merck, and Sunovion and is a consultant for Axon Advisors, Dey Pharmaceuticals, Eli Lilly and Company, and Grünenthal Group.

Acknowledgment

The author wishes to thank David L. Dunner, MD, for his helpful comments regarding this article.