Damian McNamara

BERLIN – The factors that patients report to be triggers of familial hemiplegic migraine appear to coincide in many instances with the same triggers reported by migraine patients with and without aura, according to findings from a questionnaire-based study.

Mailed questionnaires completed by 75 patients with familial hemiplegic migraine (FHM) indicated that 63% experience between 1 and 12 triggers, whereas the remaining 37% said no environmental triggers precede their attacks, Dr. Jakob Hansen said at the International Headache Congress, which was sponsored by the International Headache Society and the American Headache Society.

At least half of the respondents reported that most commonly acute stress (following a stressful event) triggered FHM, followed in frequency by sunlight and other bright lights; acute stress (during a stressful episode); intense emotional influences; and sleep disturbances (too little or too much sleep).

"If you can identify and avoid these trigger factors, that actually might be helpful in your clinical practice, so talk to your patients about this," said Dr. Hansen, a research fellow at the Danish Headache Center at the University of Copenhagen.

The pattern of trigger factors for FHM and those previously reported for migraine with aura and migraine without aura "seem to match pretty well," he said. For example, acute stress (following a stressful event) topped the list for both FHM and migraine without aura patients.

"Now we have some data that [FHM] does not seem to be so different from the more common types of migraine," Dr. Hansen said. He added that although neurologists consider FHM a distinct headache type, the alignment of triggers suggests some shared etiology or physiology.

The researchers asked the patients to rate 16 possible environmental factors that trigger headaches on the questionnaire using a scale of 0 (never) to 4 (always).

Although patients report some of these same triggers in face-to-face consultations with physicians, "what our patients tell us triggers their headaches [can differ]," Dr. Hansen said. Patients often said these factors include hormones; foods such as cheese, red wine, or chocolate; weather changes; and medication. "Some will say, ‘I get this from my mother,’ which in part could be true, especially if they suffer from familial hemiplegic migraine."

Among the patients who selected at least one trigger for FHM on the questionnaire, 36% reported at least one trigger factor that often or always (questionnaire response of 3 or 4, respectively) precipitated a FHM attack, he said.

A total 76% of patients reported at least one FHM attack within the past year. More members of this group identified at least one trigger factor than did those without a recent attack (76% vs. 11%, respectively).

Only 15 participants reported solely having FHM headaches. Other patients also reported experiencing migraines with and without aura (29), migraines with aura (25), and migraines without aura (6).

A meeting attendee questioned the accuracy of patient self-reports, suggesting that, if asked, patients tend to overreport the number of factors that trigger their migraines. "It’s interesting that one-third of our patients did not report any trigger factors. It seemed they answered truthfully," Dr. Hansen replied.

Dr. Hansen said that he had no relevant financial disclosures.

BERLIN – The factors that patients report to be triggers of familial hemiplegic migraine appear to coincide in many instances with the same triggers reported by migraine patients with and without aura, according to findings from a questionnaire-based study.

Mailed questionnaires completed by 75 patients with familial hemiplegic migraine (FHM) indicated that 63% experience between 1 and 12 triggers, whereas the remaining 37% said no environmental triggers precede their attacks, Dr. Jakob Hansen said at the International Headache Congress, which was sponsored by the International Headache Society and the American Headache Society.

At least half of the respondents reported that most commonly acute stress (following a stressful event) triggered FHM, followed in frequency by sunlight and other bright lights; acute stress (during a stressful episode); intense emotional influences; and sleep disturbances (too little or too much sleep).

"If you can identify and avoid these trigger factors, that actually might be helpful in your clinical practice, so talk to your patients about this," said Dr. Hansen, a research fellow at the Danish Headache Center at the University of Copenhagen.

The pattern of trigger factors for FHM and those previously reported for migraine with aura and migraine without aura "seem to match pretty well," he said. For example, acute stress (following a stressful event) topped the list for both FHM and migraine without aura patients.

"Now we have some data that [FHM] does not seem to be so different from the more common types of migraine," Dr. Hansen said. He added that although neurologists consider FHM a distinct headache type, the alignment of triggers suggests some shared etiology or physiology.

The researchers asked the patients to rate 16 possible environmental factors that trigger headaches on the questionnaire using a scale of 0 (never) to 4 (always).

Although patients report some of these same triggers in face-to-face consultations with physicians, "what our patients tell us triggers their headaches [can differ]," Dr. Hansen said. Patients often said these factors include hormones; foods such as cheese, red wine, or chocolate; weather changes; and medication. "Some will say, ‘I get this from my mother,’ which in part could be true, especially if they suffer from familial hemiplegic migraine."

Among the patients who selected at least one trigger for FHM on the questionnaire, 36% reported at least one trigger factor that often or always (questionnaire response of 3 or 4, respectively) precipitated a FHM attack, he said.

A total 76% of patients reported at least one FHM attack within the past year. More members of this group identified at least one trigger factor than did those without a recent attack (76% vs. 11%, respectively).

Only 15 participants reported solely having FHM headaches. Other patients also reported experiencing migraines with and without aura (29), migraines with aura (25), and migraines without aura (6).

A meeting attendee questioned the accuracy of patient self-reports, suggesting that, if asked, patients tend to overreport the number of factors that trigger their migraines. "It’s interesting that one-third of our patients did not report any trigger factors. It seemed they answered truthfully," Dr. Hansen replied.

Dr. Hansen said that he had no relevant financial disclosures.

BERLIN – The factors that patients report to be triggers of familial hemiplegic migraine appear to coincide in many instances with the same triggers reported by migraine patients with and without aura, according to findings from a questionnaire-based study.

Mailed questionnaires completed by 75 patients with familial hemiplegic migraine (FHM) indicated that 63% experience between 1 and 12 triggers, whereas the remaining 37% said no environmental triggers precede their attacks, Dr. Jakob Hansen said at the International Headache Congress, which was sponsored by the International Headache Society and the American Headache Society.

At least half of the respondents reported that most commonly acute stress (following a stressful event) triggered FHM, followed in frequency by sunlight and other bright lights; acute stress (during a stressful episode); intense emotional influences; and sleep disturbances (too little or too much sleep).

"If you can identify and avoid these trigger factors, that actually might be helpful in your clinical practice, so talk to your patients about this," said Dr. Hansen, a research fellow at the Danish Headache Center at the University of Copenhagen.

The pattern of trigger factors for FHM and those previously reported for migraine with aura and migraine without aura "seem to match pretty well," he said. For example, acute stress (following a stressful event) topped the list for both FHM and migraine without aura patients.

"Now we have some data that [FHM] does not seem to be so different from the more common types of migraine," Dr. Hansen said. He added that although neurologists consider FHM a distinct headache type, the alignment of triggers suggests some shared etiology or physiology.

The researchers asked the patients to rate 16 possible environmental factors that trigger headaches on the questionnaire using a scale of 0 (never) to 4 (always).

Although patients report some of these same triggers in face-to-face consultations with physicians, "what our patients tell us triggers their headaches [can differ]," Dr. Hansen said. Patients often said these factors include hormones; foods such as cheese, red wine, or chocolate; weather changes; and medication. "Some will say, ‘I get this from my mother,’ which in part could be true, especially if they suffer from familial hemiplegic migraine."

Among the patients who selected at least one trigger for FHM on the questionnaire, 36% reported at least one trigger factor that often or always (questionnaire response of 3 or 4, respectively) precipitated a FHM attack, he said.

A total 76% of patients reported at least one FHM attack within the past year. More members of this group identified at least one trigger factor than did those without a recent attack (76% vs. 11%, respectively).

Only 15 participants reported solely having FHM headaches. Other patients also reported experiencing migraines with and without aura (29), migraines with aura (25), and migraines without aura (6).

A meeting attendee questioned the accuracy of patient self-reports, suggesting that, if asked, patients tend to overreport the number of factors that trigger their migraines. "It’s interesting that one-third of our patients did not report any trigger factors. It seemed they answered truthfully," Dr. Hansen replied.

Dr. Hansen said that he had no relevant financial disclosures.

BOCA RATON, FLA.  – Patients with major depressive disorder who provided their primary care physician with monthly ratings of their symptoms were more likely to respond to antidepressant treatment and to achieve remission compared with a usual care group, findings of a prospective, observational cohort study have shown.

In a multivariate analysis that controlled for significant differences in baseline characteristics, patients who provided monthly updates were twice as likely to respond to therapy (odds ratio, 2.02) and 59% more likely to achieve remission (OR, 1.59) compared with the usual care group.

A total of 83 primary care physicians enrolled 915 patients with major depressive disorder in the Clinical Outcomes in Measurement-Based Treatment (COMET) trial. Physicians were alternatively assigned to an intervention group that received monthly patient symptom ratings on the 9-item Patient Health Questionnaire (PHQ-9) or a usual care group, with PHQ-9 feedback only at the 6-month study end. A total of 380 patients in the intervention group and 284 in the usual care group completed all measures and were assessed further.

Usual care may be insufficient to monitor patient response to antidepressant treatment in the primary care setting, Dr. Trina Chang said at the annual meeting of the New Clinical Drug Evaluation Unit, sponsored by the National Institute of Mental Health.

"We found there is not a lot of change going on in this first 6 months in these patients with major depression," Dr. Chang said in an interview. For example, 43% of 253 patients who received usual care had no treatment changes during the study.

"There are a couple of different ways to interpret it. The wishful thinking way ... would be [that] all our patients got better so they didn’t need treatment changes," said Dr. Chang, a psychiatrist at Massachusetts General Hospital and Harvard Medical School in Boston.

"Unfortunately, because the study also found [that] less than half of patients go into remission, probably more of them should have been having changes" to their treatment regimen.

In the usual care group, 58% scored 5 or higher on the PHQ-9 at 6 months and were considered nonremitters.

In a subset of the usual care group that had 6-month PHQ-9 scores, among participants who had less than a 25% improvement at that time compared with baseline, only 15% had a treatment change during the study. The findings "indicate an area where there could be a lot of improvement," she said. If the remaining 85% of patients were to get treatment adjustments, "we could do a lot to improve depression outcomes."

None of the participants had received treatment within 120 days prior to enrollment. The primary care physicians were free to choose any kind of antidepressant therapy. Most patients started monotherapy that included selective serotonin reuptake inhibitors for 63%, selective norepinephrine reuptake inhibitors for 25%, or bupropion for 10%. Only 0.4% of patients received an initial augmentation treatment.

Of the patients who received a change in treatment, 17% switched antidepressants; 16% had a dose titration of their initial medication (up or down); 5% had another type of medication added (for example, a benzodiazepine); 3% received augmentation with an antipsychotic, stimulant, or antiepileptic; and 2% received a second antidepressant. The remaining 57% of patients discontinued treatment.

Mean age was 47 years in the intervention group and 45 years in the usual care patients. Women made up 64% of the intervention group and 67% of the usual care group. There were some baseline differences between groups, including a significantly greater proportion of intervention group patients who had Medicaid insurance, were unemployed, and were black or African American. In contrast, the usual care group had a significantly greater proportion of participants who were employed full time, had a 4-year college degree, were married, and were white, Hispanic, or Latino.

Remission was achieved in 48% of the intervention group versus 43% of the usual care group. Complete response rates were achieved in 67% and 60% of the groups, respectively. At 6 months, partial responses were noted in 16% of the intervention and 18% of the usual care groups.

Potential solutions can involve both providers and patients, Dr. Chang said. "On the provider end, anything that could help them detect symptoms and follow up on patients better ... would help." In addition, symptom reporting coupled with treatment algorithms and/or a collaborative care model with a care manager who could more frequently and closely monitor patient treatment response could help, she said.

"On the patient end, anything that might help them to not discontinue their medications would help," she added. Making patients feel supported and answering their questions could all bolster compliance with treatment and possibly improve outcomes.

Dr. Chang said she has received research funding from AstraZeneca, CeNeRx, Euthymics, Forest Laboratories, GlaxoSmithKline, Johnson & Johnson, and Pfizer. Some of the COMET study coauthors are employees of Bristol-Myers Squibb.

BOCA RATON, FLA.  – Patients with major depressive disorder who provided their primary care physician with monthly ratings of their symptoms were more likely to respond to antidepressant treatment and to achieve remission compared with a usual care group, findings of a prospective, observational cohort study have shown.

In a multivariate analysis that controlled for significant differences in baseline characteristics, patients who provided monthly updates were twice as likely to respond to therapy (odds ratio, 2.02) and 59% more likely to achieve remission (OR, 1.59) compared with the usual care group.

A total of 83 primary care physicians enrolled 915 patients with major depressive disorder in the Clinical Outcomes in Measurement-Based Treatment (COMET) trial. Physicians were alternatively assigned to an intervention group that received monthly patient symptom ratings on the 9-item Patient Health Questionnaire (PHQ-9) or a usual care group, with PHQ-9 feedback only at the 6-month study end. A total of 380 patients in the intervention group and 284 in the usual care group completed all measures and were assessed further.

Usual care may be insufficient to monitor patient response to antidepressant treatment in the primary care setting, Dr. Trina Chang said at the annual meeting of the New Clinical Drug Evaluation Unit, sponsored by the National Institute of Mental Health.

"We found there is not a lot of change going on in this first 6 months in these patients with major depression," Dr. Chang said in an interview. For example, 43% of 253 patients who received usual care had no treatment changes during the study.

"There are a couple of different ways to interpret it. The wishful thinking way ... would be [that] all our patients got better so they didn’t need treatment changes," said Dr. Chang, a psychiatrist at Massachusetts General Hospital and Harvard Medical School in Boston.

"Unfortunately, because the study also found [that] less than half of patients go into remission, probably more of them should have been having changes" to their treatment regimen.

In the usual care group, 58% scored 5 or higher on the PHQ-9 at 6 months and were considered nonremitters.

In a subset of the usual care group that had 6-month PHQ-9 scores, among participants who had less than a 25% improvement at that time compared with baseline, only 15% had a treatment change during the study. The findings "indicate an area where there could be a lot of improvement," she said. If the remaining 85% of patients were to get treatment adjustments, "we could do a lot to improve depression outcomes."

None of the participants had received treatment within 120 days prior to enrollment. The primary care physicians were free to choose any kind of antidepressant therapy. Most patients started monotherapy that included selective serotonin reuptake inhibitors for 63%, selective norepinephrine reuptake inhibitors for 25%, or bupropion for 10%. Only 0.4% of patients received an initial augmentation treatment.

Of the patients who received a change in treatment, 17% switched antidepressants; 16% had a dose titration of their initial medication (up or down); 5% had another type of medication added (for example, a benzodiazepine); 3% received augmentation with an antipsychotic, stimulant, or antiepileptic; and 2% received a second antidepressant. The remaining 57% of patients discontinued treatment.

Mean age was 47 years in the intervention group and 45 years in the usual care patients. Women made up 64% of the intervention group and 67% of the usual care group. There were some baseline differences between groups, including a significantly greater proportion of intervention group patients who had Medicaid insurance, were unemployed, and were black or African American. In contrast, the usual care group had a significantly greater proportion of participants who were employed full time, had a 4-year college degree, were married, and were white, Hispanic, or Latino.

Remission was achieved in 48% of the intervention group versus 43% of the usual care group. Complete response rates were achieved in 67% and 60% of the groups, respectively. At 6 months, partial responses were noted in 16% of the intervention and 18% of the usual care groups.

Potential solutions can involve both providers and patients, Dr. Chang said. "On the provider end, anything that could help them detect symptoms and follow up on patients better ... would help." In addition, symptom reporting coupled with treatment algorithms and/or a collaborative care model with a care manager who could more frequently and closely monitor patient treatment response could help, she said.

"On the patient end, anything that might help them to not discontinue their medications would help," she added. Making patients feel supported and answering their questions could all bolster compliance with treatment and possibly improve outcomes.

Dr. Chang said she has received research funding from AstraZeneca, CeNeRx, Euthymics, Forest Laboratories, GlaxoSmithKline, Johnson & Johnson, and Pfizer. Some of the COMET study coauthors are employees of Bristol-Myers Squibb.

BOCA RATON, FLA.  – Patients with major depressive disorder who provided their primary care physician with monthly ratings of their symptoms were more likely to respond to antidepressant treatment and to achieve remission compared with a usual care group, findings of a prospective, observational cohort study have shown.

In a multivariate analysis that controlled for significant differences in baseline characteristics, patients who provided monthly updates were twice as likely to respond to therapy (odds ratio, 2.02) and 59% more likely to achieve remission (OR, 1.59) compared with the usual care group.

A total of 83 primary care physicians enrolled 915 patients with major depressive disorder in the Clinical Outcomes in Measurement-Based Treatment (COMET) trial. Physicians were alternatively assigned to an intervention group that received monthly patient symptom ratings on the 9-item Patient Health Questionnaire (PHQ-9) or a usual care group, with PHQ-9 feedback only at the 6-month study end. A total of 380 patients in the intervention group and 284 in the usual care group completed all measures and were assessed further.

Usual care may be insufficient to monitor patient response to antidepressant treatment in the primary care setting, Dr. Trina Chang said at the annual meeting of the New Clinical Drug Evaluation Unit, sponsored by the National Institute of Mental Health.

"We found there is not a lot of change going on in this first 6 months in these patients with major depression," Dr. Chang said in an interview. For example, 43% of 253 patients who received usual care had no treatment changes during the study.

"There are a couple of different ways to interpret it. The wishful thinking way ... would be [that] all our patients got better so they didn’t need treatment changes," said Dr. Chang, a psychiatrist at Massachusetts General Hospital and Harvard Medical School in Boston.

"Unfortunately, because the study also found [that] less than half of patients go into remission, probably more of them should have been having changes" to their treatment regimen.

In the usual care group, 58% scored 5 or higher on the PHQ-9 at 6 months and were considered nonremitters.

In a subset of the usual care group that had 6-month PHQ-9 scores, among participants who had less than a 25% improvement at that time compared with baseline, only 15% had a treatment change during the study. The findings "indicate an area where there could be a lot of improvement," she said. If the remaining 85% of patients were to get treatment adjustments, "we could do a lot to improve depression outcomes."

None of the participants had received treatment within 120 days prior to enrollment. The primary care physicians were free to choose any kind of antidepressant therapy. Most patients started monotherapy that included selective serotonin reuptake inhibitors for 63%, selective norepinephrine reuptake inhibitors for 25%, or bupropion for 10%. Only 0.4% of patients received an initial augmentation treatment.

Of the patients who received a change in treatment, 17% switched antidepressants; 16% had a dose titration of their initial medication (up or down); 5% had another type of medication added (for example, a benzodiazepine); 3% received augmentation with an antipsychotic, stimulant, or antiepileptic; and 2% received a second antidepressant. The remaining 57% of patients discontinued treatment.

Mean age was 47 years in the intervention group and 45 years in the usual care patients. Women made up 64% of the intervention group and 67% of the usual care group. There were some baseline differences between groups, including a significantly greater proportion of intervention group patients who had Medicaid insurance, were unemployed, and were black or African American. In contrast, the usual care group had a significantly greater proportion of participants who were employed full time, had a 4-year college degree, were married, and were white, Hispanic, or Latino.

Remission was achieved in 48% of the intervention group versus 43% of the usual care group. Complete response rates were achieved in 67% and 60% of the groups, respectively. At 6 months, partial responses were noted in 16% of the intervention and 18% of the usual care groups.

Potential solutions can involve both providers and patients, Dr. Chang said. "On the provider end, anything that could help them detect symptoms and follow up on patients better ... would help." In addition, symptom reporting coupled with treatment algorithms and/or a collaborative care model with a care manager who could more frequently and closely monitor patient treatment response could help, she said.

"On the patient end, anything that might help them to not discontinue their medications would help," she added. Making patients feel supported and answering their questions could all bolster compliance with treatment and possibly improve outcomes.

Dr. Chang said she has received research funding from AstraZeneca, CeNeRx, Euthymics, Forest Laboratories, GlaxoSmithKline, Johnson & Johnson, and Pfizer. Some of the COMET study coauthors are employees of Bristol-Myers Squibb.

BOCA RATON, FLA.  – Proposed changes for the diagnosis of patients with mixed depressive episodes for the next edition of the Diagnostic and Statistical Manual of Mental Disorders will more closely reflect the patients psychiatrists see in their everyday practice, Ellen Frank, Ph.D., said.

The current DSM-IV-TR definition of a mixed episode requires that a patient meet full criteria for a manic episode and full criteria for a major depressive episode (except for duration) nearly every day for at least a 1-week period. "What did I think was wrong with this definition? As far as I’m concerned, these patients don’t exist," Dr. Frank said at the annual meeting of the New Clinical Drug Evaluation Unit, sponsored by the National Institute of Mental Health.

I would argue that if you really carefully distinguish, for example, agitation from increased goal-directed activity, [and] if you really carefully distinguish the potential overlapping symptoms, these patients are about as rare as unicorns," Dr. Frank said.

"We thought the current criteria too restrictive, and they are rarely adhered to. When we say the patient is mixed, we rarely mean that the patient meets full criteria for both poles," said Dr. Frank, professor of psychiatry and psychology at the University of Pittsburgh. "This results in a lot of confusion, a lack of precision, and fails to identify [those] who are at risk of progression from unipolar to bipolar disorder."

Inappropriate treatment selection is another possibility with the DSM-IV-TR definition, said Dr. Frank, director of the Depression and Manic Depression Prevention Program at the Western Psychiatric Institute and Clinic in Pittsburgh, and a member of the DSM-5 Mood Disorders Work Group. In addition, "the consequence of the current definition in common use is that we underestimate suicide risk, because I do believe these patients are at excessive risk of suicide.

"This is a horrible state to be in, and we need to figure out how to do a better job of treating it."

What Dr. Frank and her collaborators on the working group propose for the DSM-5 is a mixed specifier that indicates the presence of symptoms – not the syndrome – of the opposite pole. The specifier would be applied to both episodes of mania and depression, and would be applicable in the context of both unipolar and bipolar lifetime diagnoses.

The psychiatric history of those who experience mixed states tend to include early onset of illness, multiple previous episodes, suicidal behavior, substance abuse, and other comorbid diagnoses that tend to be associated with bipolar disorder (such as panic).

Under the proposed construct, if a "mixed" patient is predominantly depressed, they meet full criteria for a major depressive episode and have at least three of the following nearly every day during the episode:

• Elevated mood.

• Decreased need for sleep (not insomnia).

• Goal-directed activity.

• Increased energy or visible hyperactivity (again, goal directed).

• Grandiosity.

• Accelerated speech.

• Racing thoughts.

If the patient is predominantly manic or hypomanic, they meet full criteria for the manic or hypomanic episode and feature at least three of the following:

• Subjective depression.

• Worry.

• Self-reproach or guilt.

• Negative evaluation of self.

• Hopelessness.

• Suicidal ideation or behavior.

• Anhedonia.

• Fatigue.

• Psychomotor retardation.

Interestingly, the proposed criteria do not include what the working group considered to be characteristics of both poles: irritability, indecisiveness, and psychomotor agitation (which is distinguished from goal-directed activity). In addition, the proposal does not include distractibility, "which I’ve come to believe is actually a feature of almost every patient anywhere on the bipolar spectrum," Dr. Frank said.

Insomnia or hypersomnia is another shared symptom not included in the specifier. Insomnia "is difficult to distinguish as a manic or depressive symptom," said Dr. Roy H. Perlis, director of the bipolar research program at Massachusetts General Hospital and instructor in psychiatry at Harvard Medical School, both in Boston.

Family aggregation, psychiatric history, concurrent psychiatric symptoms, and, particularly, treatment outcome were used as validators for the proposed specifier, Dr. Frank said. For example, in terms of treatment outcome, she added that a poor response to lithium and hypomanic symptoms during predominantly depressive states are associated with destabilization on antidepressants.

DSM-5 field trials are underway to assess the proposed criteria. The goal is to test the clinical acceptability and utility of the new constructs in both academic and practice settings. In addition, the reliability of diagnosis will be assessed in the academic component of the field trials. The clinics testing the mixed depression specifier include the Mayo Clinic, Rochester, Minn.; University of California,Los Angeles; the University of Texas Health Science Center at San Antonio; and the Veterans Affairs Medical Centers in Dallas and Houston.

Dr. Frank’s disclosures include Guilford Press and Servier International. Dr. Perlis’s disclosures include Concordant Rater Systems, Proteus Biomedical, and RIDVentures.

BOCA RATON, FLA.  – Proposed changes for the diagnosis of patients with mixed depressive episodes for the next edition of the Diagnostic and Statistical Manual of Mental Disorders will more closely reflect the patients psychiatrists see in their everyday practice, Ellen Frank, Ph.D., said.

The current DSM-IV-TR definition of a mixed episode requires that a patient meet full criteria for a manic episode and full criteria for a major depressive episode (except for duration) nearly every day for at least a 1-week period. "What did I think was wrong with this definition? As far as I’m concerned, these patients don’t exist," Dr. Frank said at the annual meeting of the New Clinical Drug Evaluation Unit, sponsored by the National Institute of Mental Health.

I would argue that if you really carefully distinguish, for example, agitation from increased goal-directed activity, [and] if you really carefully distinguish the potential overlapping symptoms, these patients are about as rare as unicorns," Dr. Frank said.

"We thought the current criteria too restrictive, and they are rarely adhered to. When we say the patient is mixed, we rarely mean that the patient meets full criteria for both poles," said Dr. Frank, professor of psychiatry and psychology at the University of Pittsburgh. "This results in a lot of confusion, a lack of precision, and fails to identify [those] who are at risk of progression from unipolar to bipolar disorder."

Inappropriate treatment selection is another possibility with the DSM-IV-TR definition, said Dr. Frank, director of the Depression and Manic Depression Prevention Program at the Western Psychiatric Institute and Clinic in Pittsburgh, and a member of the DSM-5 Mood Disorders Work Group. In addition, "the consequence of the current definition in common use is that we underestimate suicide risk, because I do believe these patients are at excessive risk of suicide.

"This is a horrible state to be in, and we need to figure out how to do a better job of treating it."

What Dr. Frank and her collaborators on the working group propose for the DSM-5 is a mixed specifier that indicates the presence of symptoms – not the syndrome – of the opposite pole. The specifier would be applied to both episodes of mania and depression, and would be applicable in the context of both unipolar and bipolar lifetime diagnoses.

The psychiatric history of those who experience mixed states tend to include early onset of illness, multiple previous episodes, suicidal behavior, substance abuse, and other comorbid diagnoses that tend to be associated with bipolar disorder (such as panic).

Under the proposed construct, if a "mixed" patient is predominantly depressed, they meet full criteria for a major depressive episode and have at least three of the following nearly every day during the episode:

• Elevated mood.

• Decreased need for sleep (not insomnia).

• Goal-directed activity.

• Increased energy or visible hyperactivity (again, goal directed).

• Grandiosity.

• Accelerated speech.

• Racing thoughts.

If the patient is predominantly manic or hypomanic, they meet full criteria for the manic or hypomanic episode and feature at least three of the following:

• Subjective depression.

• Worry.

• Self-reproach or guilt.

• Negative evaluation of self.

• Hopelessness.

• Suicidal ideation or behavior.

• Anhedonia.

• Fatigue.

• Psychomotor retardation.

Interestingly, the proposed criteria do not include what the working group considered to be characteristics of both poles: irritability, indecisiveness, and psychomotor agitation (which is distinguished from goal-directed activity). In addition, the proposal does not include distractibility, "which I’ve come to believe is actually a feature of almost every patient anywhere on the bipolar spectrum," Dr. Frank said.

Insomnia or hypersomnia is another shared symptom not included in the specifier. Insomnia "is difficult to distinguish as a manic or depressive symptom," said Dr. Roy H. Perlis, director of the bipolar research program at Massachusetts General Hospital and instructor in psychiatry at Harvard Medical School, both in Boston.

Family aggregation, psychiatric history, concurrent psychiatric symptoms, and, particularly, treatment outcome were used as validators for the proposed specifier, Dr. Frank said. For example, in terms of treatment outcome, she added that a poor response to lithium and hypomanic symptoms during predominantly depressive states are associated with destabilization on antidepressants.

DSM-5 field trials are underway to assess the proposed criteria. The goal is to test the clinical acceptability and utility of the new constructs in both academic and practice settings. In addition, the reliability of diagnosis will be assessed in the academic component of the field trials. The clinics testing the mixed depression specifier include the Mayo Clinic, Rochester, Minn.; University of California,Los Angeles; the University of Texas Health Science Center at San Antonio; and the Veterans Affairs Medical Centers in Dallas and Houston.

Dr. Frank’s disclosures include Guilford Press and Servier International. Dr. Perlis’s disclosures include Concordant Rater Systems, Proteus Biomedical, and RIDVentures.

BOCA RATON, FLA.  – Proposed changes for the diagnosis of patients with mixed depressive episodes for the next edition of the Diagnostic and Statistical Manual of Mental Disorders will more closely reflect the patients psychiatrists see in their everyday practice, Ellen Frank, Ph.D., said.

The current DSM-IV-TR definition of a mixed episode requires that a patient meet full criteria for a manic episode and full criteria for a major depressive episode (except for duration) nearly every day for at least a 1-week period. "What did I think was wrong with this definition? As far as I’m concerned, these patients don’t exist," Dr. Frank said at the annual meeting of the New Clinical Drug Evaluation Unit, sponsored by the National Institute of Mental Health.

I would argue that if you really carefully distinguish, for example, agitation from increased goal-directed activity, [and] if you really carefully distinguish the potential overlapping symptoms, these patients are about as rare as unicorns," Dr. Frank said.

"We thought the current criteria too restrictive, and they are rarely adhered to. When we say the patient is mixed, we rarely mean that the patient meets full criteria for both poles," said Dr. Frank, professor of psychiatry and psychology at the University of Pittsburgh. "This results in a lot of confusion, a lack of precision, and fails to identify [those] who are at risk of progression from unipolar to bipolar disorder."

Inappropriate treatment selection is another possibility with the DSM-IV-TR definition, said Dr. Frank, director of the Depression and Manic Depression Prevention Program at the Western Psychiatric Institute and Clinic in Pittsburgh, and a member of the DSM-5 Mood Disorders Work Group. In addition, "the consequence of the current definition in common use is that we underestimate suicide risk, because I do believe these patients are at excessive risk of suicide.

"This is a horrible state to be in, and we need to figure out how to do a better job of treating it."

What Dr. Frank and her collaborators on the working group propose for the DSM-5 is a mixed specifier that indicates the presence of symptoms – not the syndrome – of the opposite pole. The specifier would be applied to both episodes of mania and depression, and would be applicable in the context of both unipolar and bipolar lifetime diagnoses.

The psychiatric history of those who experience mixed states tend to include early onset of illness, multiple previous episodes, suicidal behavior, substance abuse, and other comorbid diagnoses that tend to be associated with bipolar disorder (such as panic).

Under the proposed construct, if a "mixed" patient is predominantly depressed, they meet full criteria for a major depressive episode and have at least three of the following nearly every day during the episode:

• Elevated mood.

• Decreased need for sleep (not insomnia).

• Goal-directed activity.

• Increased energy or visible hyperactivity (again, goal directed).

• Grandiosity.

• Accelerated speech.

• Racing thoughts.

If the patient is predominantly manic or hypomanic, they meet full criteria for the manic or hypomanic episode and feature at least three of the following:

• Subjective depression.

• Worry.

• Self-reproach or guilt.

• Negative evaluation of self.

• Hopelessness.

• Suicidal ideation or behavior.

• Anhedonia.

• Fatigue.

• Psychomotor retardation.

Interestingly, the proposed criteria do not include what the working group considered to be characteristics of both poles: irritability, indecisiveness, and psychomotor agitation (which is distinguished from goal-directed activity). In addition, the proposal does not include distractibility, "which I’ve come to believe is actually a feature of almost every patient anywhere on the bipolar spectrum," Dr. Frank said.

Insomnia or hypersomnia is another shared symptom not included in the specifier. Insomnia "is difficult to distinguish as a manic or depressive symptom," said Dr. Roy H. Perlis, director of the bipolar research program at Massachusetts General Hospital and instructor in psychiatry at Harvard Medical School, both in Boston.

Family aggregation, psychiatric history, concurrent psychiatric symptoms, and, particularly, treatment outcome were used as validators for the proposed specifier, Dr. Frank said. For example, in terms of treatment outcome, she added that a poor response to lithium and hypomanic symptoms during predominantly depressive states are associated with destabilization on antidepressants.

DSM-5 field trials are underway to assess the proposed criteria. The goal is to test the clinical acceptability and utility of the new constructs in both academic and practice settings. In addition, the reliability of diagnosis will be assessed in the academic component of the field trials. The clinics testing the mixed depression specifier include the Mayo Clinic, Rochester, Minn.; University of California,Los Angeles; the University of Texas Health Science Center at San Antonio; and the Veterans Affairs Medical Centers in Dallas and Houston.

Dr. Frank’s disclosures include Guilford Press and Servier International. Dr. Perlis’s disclosures include Concordant Rater Systems, Proteus Biomedical, and RIDVentures.

BOCA RATON, FLA.  – Proposed changes for the diagnosis of patients with mixed depressive episodes for the next edition of the Diagnostic and Statistical Manual of Mental Disorders will more closely reflect the patients psychiatrists see in their everyday practice, Ellen Frank, Ph.D., said.

The current DSM-IV-TR definition of a mixed episode requires that a patient meet full criteria for a manic episode and full criteria for a major depressive episode (except for duration) nearly every day for at least a 1-week period. "What did I think was wrong with this definition? As far as I’m concerned, these patients don’t exist," Dr. Frank said at the annual meeting of the New Clinical Drug Evaluation Unit, sponsored by the National Institute of Mental Health.

I would argue that if you really carefully distinguish, for example, agitation from increased goal-directed activity, [and] if you really carefully distinguish the potential overlapping symptoms, these patients are about as rare as unicorns," Dr. Frank said.

"We thought the current criteria too restrictive, and they are rarely adhered to. When we say the patient is mixed, we rarely mean that the patient meets full criteria for both poles," said Dr. Frank, professor of psychiatry and psychology at the University of Pittsburgh. "This results in a lot of confusion, a lack of precision, and fails to identify [those] who are at risk of progression from unipolar to bipolar disorder."

Inappropriate treatment selection is another possibility with the DSM-IV-TR definition, said Dr. Frank, director of the Depression and Manic Depression Prevention Program at the Western Psychiatric Institute and Clinic in Pittsburgh, and a member of the DSM-5 Mood Disorders Work Group. In addition, "the consequence of the current definition in common use is that we underestimate suicide risk, because I do believe these patients are at excessive risk of suicide.

"This is a horrible state to be in, and we need to figure out how to do a better job of treating it."

What Dr. Frank and her collaborators on the working group propose for the DSM-5 is a mixed specifier that indicates the presence of symptoms – not the syndrome – of the opposite pole. The specifier would be applied to both episodes of mania and depression, and would be applicable in the context of both unipolar and bipolar lifetime diagnoses.

The psychiatric history of those who experience mixed states tend to include early onset of illness, multiple previous episodes, suicidal behavior, substance abuse, and other comorbid diagnoses that tend to be associated with bipolar disorder (such as panic).

Under the proposed construct, if a "mixed" patient is predominantly depressed, they meet full criteria for a major depressive episode and have at least three of the following nearly every day during the episode:

• Elevated mood.

• Decreased need for sleep (not insomnia).

• Goal-directed activity.

• Increased energy or visible hyperactivity (again, goal directed).

• Grandiosity.

• Accelerated speech.

• Racing thoughts.

If the patient is predominantly manic or hypomanic, they meet full criteria for the manic or hypomanic episode and feature at least three of the following:

• Subjective depression.

• Worry.

• Self-reproach or guilt.

• Negative evaluation of self.

• Hopelessness.

• Suicidal ideation or behavior.

• Anhedonia.

• Fatigue.

• Psychomotor retardation.

Interestingly, the proposed criteria do not include what the working group considered to be characteristics of both poles: irritability, indecisiveness, and psychomotor agitation (which is distinguished from goal-directed activity). In addition, the proposal does not include distractibility, "which I’ve come to believe is actually a feature of almost every patient anywhere on the bipolar spectrum," Dr. Frank said.

Insomnia or hypersomnia is another shared symptom not included in the specifier. Insomnia "is difficult to distinguish as a manic or depressive symptom," said Dr. Roy H. Perlis, director of the bipolar research program at Massachusetts General Hospital and instructor in psychiatry at Harvard Medical School, both in Boston.

Family aggregation, psychiatric history, concurrent psychiatric symptoms, and, particularly, treatment outcome were used as validators for the proposed specifier, Dr. Frank said. For example, in terms of treatment outcome, she added that a poor response to lithium and hypomanic symptoms during predominantly depressive states are associated with destabilization on antidepressants.

DSM-5 field trials are underway to assess the proposed criteria. The goal is to test the clinical acceptability and utility of the new constructs in both academic and practice settings. In addition, the reliability of diagnosis will be assessed in the academic component of the field trials. The clinics testing the mixed depression specifier include the Mayo Clinic, Rochester, Minn.; University of California,Los Angeles; the University of Texas Health Science Center at San Antonio; and the Veterans Affairs Medical Centers in Dallas and Houston.

Dr. Frank’s disclosures include Guilford Press and Servier International. Dr. Perlis’s disclosures include Concordant Rater Systems, Proteus Biomedical, and RIDVentures.

BOCA RATON, FLA.  – Proposed changes for the diagnosis of patients with mixed depressive episodes for the next edition of the Diagnostic and Statistical Manual of Mental Disorders will more closely reflect the patients psychiatrists see in their everyday practice, Ellen Frank, Ph.D., said.

The current DSM-IV-TR definition of a mixed episode requires that a patient meet full criteria for a manic episode and full criteria for a major depressive episode (except for duration) nearly every day for at least a 1-week period. "What did I think was wrong with this definition? As far as I’m concerned, these patients don’t exist," Dr. Frank said at the annual meeting of the New Clinical Drug Evaluation Unit, sponsored by the National Institute of Mental Health.

I would argue that if you really carefully distinguish, for example, agitation from increased goal-directed activity, [and] if you really carefully distinguish the potential overlapping symptoms, these patients are about as rare as unicorns," Dr. Frank said.

"We thought the current criteria too restrictive, and they are rarely adhered to. When we say the patient is mixed, we rarely mean that the patient meets full criteria for both poles," said Dr. Frank, professor of psychiatry and psychology at the University of Pittsburgh. "This results in a lot of confusion, a lack of precision, and fails to identify [those] who are at risk of progression from unipolar to bipolar disorder."

Inappropriate treatment selection is another possibility with the DSM-IV-TR definition, said Dr. Frank, director of the Depression and Manic Depression Prevention Program at the Western Psychiatric Institute and Clinic in Pittsburgh, and a member of the DSM-5 Mood Disorders Work Group. In addition, "the consequence of the current definition in common use is that we underestimate suicide risk, because I do believe these patients are at excessive risk of suicide.

"This is a horrible state to be in, and we need to figure out how to do a better job of treating it."

What Dr. Frank and her collaborators on the working group propose for the DSM-5 is a mixed specifier that indicates the presence of symptoms – not the syndrome – of the opposite pole. The specifier would be applied to both episodes of mania and depression, and would be applicable in the context of both unipolar and bipolar lifetime diagnoses.

The psychiatric history of those who experience mixed states tend to include early onset of illness, multiple previous episodes, suicidal behavior, substance abuse, and other comorbid diagnoses that tend to be associated with bipolar disorder (such as panic).

Under the proposed construct, if a "mixed" patient is predominantly depressed, they meet full criteria for a major depressive episode and have at least three of the following nearly every day during the episode:

• Elevated mood.

• Decreased need for sleep (not insomnia).

• Goal-directed activity.

• Increased energy or visible hyperactivity (again, goal directed).

• Grandiosity.

• Accelerated speech.

• Racing thoughts.

If the patient is predominantly manic or hypomanic, they meet full criteria for the manic or hypomanic episode and feature at least three of the following:

• Subjective depression.

• Worry.

• Self-reproach or guilt.

• Negative evaluation of self.

• Hopelessness.

• Suicidal ideation or behavior.

• Anhedonia.

• Fatigue.

• Psychomotor retardation.

Interestingly, the proposed criteria do not include what the working group considered to be characteristics of both poles: irritability, indecisiveness, and psychomotor agitation (which is distinguished from goal-directed activity). In addition, the proposal does not include distractibility, "which I’ve come to believe is actually a feature of almost every patient anywhere on the bipolar spectrum," Dr. Frank said.

Insomnia or hypersomnia is another shared symptom not included in the specifier. Insomnia "is difficult to distinguish as a manic or depressive symptom," said Dr. Roy H. Perlis, director of the bipolar research program at Massachusetts General Hospital and instructor in psychiatry at Harvard Medical School, both in Boston.

Family aggregation, psychiatric history, concurrent psychiatric symptoms, and, particularly, treatment outcome were used as validators for the proposed specifier, Dr. Frank said. For example, in terms of treatment outcome, she added that a poor response to lithium and hypomanic symptoms during predominantly depressive states are associated with destabilization on antidepressants.

DSM-5 field trials are underway to assess the proposed criteria. The goal is to test the clinical acceptability and utility of the new constructs in both academic and practice settings. In addition, the reliability of diagnosis will be assessed in the academic component of the field trials. The clinics testing the mixed depression specifier include the Mayo Clinic, Rochester, Minn.; University of California,Los Angeles; the University of Texas Health Science Center at San Antonio; and the Veterans Affairs Medical Centers in Dallas and Houston.

Dr. Frank’s disclosures include Guilford Press and Servier International. Dr. Perlis’s disclosures include Concordant Rater Systems, Proteus Biomedical, and RIDVentures.

BOCA RATON, FLA.  – Proposed changes for the diagnosis of patients with mixed depressive episodes for the next edition of the Diagnostic and Statistical Manual of Mental Disorders will more closely reflect the patients psychiatrists see in their everyday practice, Ellen Frank, Ph.D., said.

The current DSM-IV-TR definition of a mixed episode requires that a patient meet full criteria for a manic episode and full criteria for a major depressive episode (except for duration) nearly every day for at least a 1-week period. "What did I think was wrong with this definition? As far as I’m concerned, these patients don’t exist," Dr. Frank said at the annual meeting of the New Clinical Drug Evaluation Unit, sponsored by the National Institute of Mental Health.

I would argue that if you really carefully distinguish, for example, agitation from increased goal-directed activity, [and] if you really carefully distinguish the potential overlapping symptoms, these patients are about as rare as unicorns," Dr. Frank said.

"We thought the current criteria too restrictive, and they are rarely adhered to. When we say the patient is mixed, we rarely mean that the patient meets full criteria for both poles," said Dr. Frank, professor of psychiatry and psychology at the University of Pittsburgh. "This results in a lot of confusion, a lack of precision, and fails to identify [those] who are at risk of progression from unipolar to bipolar disorder."

Inappropriate treatment selection is another possibility with the DSM-IV-TR definition, said Dr. Frank, director of the Depression and Manic Depression Prevention Program at the Western Psychiatric Institute and Clinic in Pittsburgh, and a member of the DSM-5 Mood Disorders Work Group. In addition, "the consequence of the current definition in common use is that we underestimate suicide risk, because I do believe these patients are at excessive risk of suicide.

"This is a horrible state to be in, and we need to figure out how to do a better job of treating it."

What Dr. Frank and her collaborators on the working group propose for the DSM-5 is a mixed specifier that indicates the presence of symptoms – not the syndrome – of the opposite pole. The specifier would be applied to both episodes of mania and depression, and would be applicable in the context of both unipolar and bipolar lifetime diagnoses.

The psychiatric history of those who experience mixed states tend to include early onset of illness, multiple previous episodes, suicidal behavior, substance abuse, and other comorbid diagnoses that tend to be associated with bipolar disorder (such as panic).

Under the proposed construct, if a "mixed" patient is predominantly depressed, they meet full criteria for a major depressive episode and have at least three of the following nearly every day during the episode:

• Elevated mood.

• Decreased need for sleep (not insomnia).

• Goal-directed activity.

• Increased energy or visible hyperactivity (again, goal directed).

• Grandiosity.

• Accelerated speech.

• Racing thoughts.

If the patient is predominantly manic or hypomanic, they meet full criteria for the manic or hypomanic episode and feature at least three of the following:

• Subjective depression.

• Worry.

• Self-reproach or guilt.

• Negative evaluation of self.

• Hopelessness.

• Suicidal ideation or behavior.

• Anhedonia.

• Fatigue.

• Psychomotor retardation.

Interestingly, the proposed criteria do not include what the working group considered to be characteristics of both poles: irritability, indecisiveness, and psychomotor agitation (which is distinguished from goal-directed activity). In addition, the proposal does not include distractibility, "which I’ve come to believe is actually a feature of almost every patient anywhere on the bipolar spectrum," Dr. Frank said.

Insomnia or hypersomnia is another shared symptom not included in the specifier. Insomnia "is difficult to distinguish as a manic or depressive symptom," said Dr. Roy H. Perlis, director of the bipolar research program at Massachusetts General Hospital and instructor in psychiatry at Harvard Medical School, both in Boston.

Family aggregation, psychiatric history, concurrent psychiatric symptoms, and, particularly, treatment outcome were used as validators for the proposed specifier, Dr. Frank said. For example, in terms of treatment outcome, she added that a poor response to lithium and hypomanic symptoms during predominantly depressive states are associated with destabilization on antidepressants.

DSM-5 field trials are underway to assess the proposed criteria. The goal is to test the clinical acceptability and utility of the new constructs in both academic and practice settings. In addition, the reliability of diagnosis will be assessed in the academic component of the field trials. The clinics testing the mixed depression specifier include the Mayo Clinic, Rochester, Minn.; University of California,Los Angeles; the University of Texas Health Science Center at San Antonio; and the Veterans Affairs Medical Centers in Dallas and Houston.

Dr. Frank’s disclosures include Guilford Press and Servier International. Dr. Perlis’s disclosures include Concordant Rater Systems, Proteus Biomedical, and RIDVentures.

BOCA RATON, FLA.  – Proposed changes for the diagnosis of patients with mixed depressive episodes for the next edition of the Diagnostic and Statistical Manual of Mental Disorders will more closely reflect the patients psychiatrists see in their everyday practice, Ellen Frank, Ph.D., said.

The current DSM-IV-TR definition of a mixed episode requires that a patient meet full criteria for a manic episode and full criteria for a major depressive episode (except for duration) nearly every day for at least a 1-week period. "What did I think was wrong with this definition? As far as I’m concerned, these patients don’t exist," Dr. Frank said at the annual meeting of the New Clinical Drug Evaluation Unit, sponsored by the National Institute of Mental Health.

I would argue that if you really carefully distinguish, for example, agitation from increased goal-directed activity, [and] if you really carefully distinguish the potential overlapping symptoms, these patients are about as rare as unicorns," Dr. Frank said.

"We thought the current criteria too restrictive, and they are rarely adhered to. When we say the patient is mixed, we rarely mean that the patient meets full criteria for both poles," said Dr. Frank, professor of psychiatry and psychology at the University of Pittsburgh. "This results in a lot of confusion, a lack of precision, and fails to identify [those] who are at risk of progression from unipolar to bipolar disorder."

Inappropriate treatment selection is another possibility with the DSM-IV-TR definition, said Dr. Frank, director of the Depression and Manic Depression Prevention Program at the Western Psychiatric Institute and Clinic in Pittsburgh, and a member of the DSM-5 Mood Disorders Work Group. In addition, "the consequence of the current definition in common use is that we underestimate suicide risk, because I do believe these patients are at excessive risk of suicide.

"This is a horrible state to be in, and we need to figure out how to do a better job of treating it."

What Dr. Frank and her collaborators on the working group propose for the DSM-5 is a mixed specifier that indicates the presence of symptoms – not the syndrome – of the opposite pole. The specifier would be applied to both episodes of mania and depression, and would be applicable in the context of both unipolar and bipolar lifetime diagnoses.

The psychiatric history of those who experience mixed states tend to include early onset of illness, multiple previous episodes, suicidal behavior, substance abuse, and other comorbid diagnoses that tend to be associated with bipolar disorder (such as panic).

Under the proposed construct, if a "mixed" patient is predominantly depressed, they meet full criteria for a major depressive episode and have at least three of the following nearly every day during the episode:

• Elevated mood.

• Decreased need for sleep (not insomnia).

• Goal-directed activity.

• Increased energy or visible hyperactivity (again, goal directed).

• Grandiosity.

• Accelerated speech.

• Racing thoughts.

If the patient is predominantly manic or hypomanic, they meet full criteria for the manic or hypomanic episode and feature at least three of the following:

• Subjective depression.

• Worry.

• Self-reproach or guilt.

• Negative evaluation of self.

• Hopelessness.

• Suicidal ideation or behavior.

• Anhedonia.

• Fatigue.

• Psychomotor retardation.

Interestingly, the proposed criteria do not include what the working group considered to be characteristics of both poles: irritability, indecisiveness, and psychomotor agitation (which is distinguished from goal-directed activity). In addition, the proposal does not include distractibility, "which I’ve come to believe is actually a feature of almost every patient anywhere on the bipolar spectrum," Dr. Frank said.

Insomnia or hypersomnia is another shared symptom not included in the specifier. Insomnia "is difficult to distinguish as a manic or depressive symptom," said Dr. Roy H. Perlis, director of the bipolar research program at Massachusetts General Hospital and instructor in psychiatry at Harvard Medical School, both in Boston.

Family aggregation, psychiatric history, concurrent psychiatric symptoms, and, particularly, treatment outcome were used as validators for the proposed specifier, Dr. Frank said. For example, in terms of treatment outcome, she added that a poor response to lithium and hypomanic symptoms during predominantly depressive states are associated with destabilization on antidepressants.

DSM-5 field trials are underway to assess the proposed criteria. The goal is to test the clinical acceptability and utility of the new constructs in both academic and practice settings. In addition, the reliability of diagnosis will be assessed in the academic component of the field trials. The clinics testing the mixed depression specifier include the Mayo Clinic, Rochester, Minn.; University of California,Los Angeles; the University of Texas Health Science Center at San Antonio; and the Veterans Affairs Medical Centers in Dallas and Houston.

Dr. Frank’s disclosures include Guilford Press and Servier International. Dr. Perlis’s disclosures include Concordant Rater Systems, Proteus Biomedical, and RIDVentures.

BOCA RATON, FLA.  – Proposed changes for the diagnosis of patients with mixed depressive episodes for the next edition of the Diagnostic and Statistical Manual of Mental Disorders will more closely reflect the patients psychiatrists see in their everyday practice, Ellen Frank, Ph.D., said.

The current DSM-IV-TR definition of a mixed episode requires that a patient meet full criteria for a manic episode and full criteria for a major depressive episode (except for duration) nearly every day for at least a 1-week period. "What did I think was wrong with this definition? As far as I’m concerned, these patients don’t exist," Dr. Frank said at the annual meeting of the New Clinical Drug Evaluation Unit, sponsored by the National Institute of Mental Health.

I would argue that if you really carefully distinguish, for example, agitation from increased goal-directed activity, [and] if you really carefully distinguish the potential overlapping symptoms, these patients are about as rare as unicorns," Dr. Frank said.

"We thought the current criteria too restrictive, and they are rarely adhered to. When we say the patient is mixed, we rarely mean that the patient meets full criteria for both poles," said Dr. Frank, professor of psychiatry and psychology at the University of Pittsburgh. "This results in a lot of confusion, a lack of precision, and fails to identify [those] who are at risk of progression from unipolar to bipolar disorder."

Inappropriate treatment selection is another possibility with the DSM-IV-TR definition, said Dr. Frank, director of the Depression and Manic Depression Prevention Program at the Western Psychiatric Institute and Clinic in Pittsburgh, and a member of the DSM-5 Mood Disorders Work Group. In addition, "the consequence of the current definition in common use is that we underestimate suicide risk, because I do believe these patients are at excessive risk of suicide.

"This is a horrible state to be in, and we need to figure out how to do a better job of treating it."

What Dr. Frank and her collaborators on the working group propose for the DSM-5 is a mixed specifier that indicates the presence of symptoms – not the syndrome – of the opposite pole. The specifier would be applied to both episodes of mania and depression, and would be applicable in the context of both unipolar and bipolar lifetime diagnoses.

The psychiatric history of those who experience mixed states tend to include early onset of illness, multiple previous episodes, suicidal behavior, substance abuse, and other comorbid diagnoses that tend to be associated with bipolar disorder (such as panic).

Under the proposed construct, if a "mixed" patient is predominantly depressed, they meet full criteria for a major depressive episode and have at least three of the following nearly every day during the episode:

• Elevated mood.

• Decreased need for sleep (not insomnia).

• Goal-directed activity.

• Increased energy or visible hyperactivity (again, goal directed).

• Grandiosity.

• Accelerated speech.

• Racing thoughts.

If the patient is predominantly manic or hypomanic, they meet full criteria for the manic or hypomanic episode and feature at least three of the following:

• Subjective depression.

• Worry.

• Self-reproach or guilt.

• Negative evaluation of self.

• Hopelessness.

• Suicidal ideation or behavior.

• Anhedonia.

• Fatigue.

• Psychomotor retardation.

Interestingly, the proposed criteria do not include what the working group considered to be characteristics of both poles: irritability, indecisiveness, and psychomotor agitation (which is distinguished from goal-directed activity). In addition, the proposal does not include distractibility, "which I’ve come to believe is actually a feature of almost every patient anywhere on the bipolar spectrum," Dr. Frank said.

Insomnia or hypersomnia is another shared symptom not included in the specifier. Insomnia "is difficult to distinguish as a manic or depressive symptom," said Dr. Roy H. Perlis, director of the bipolar research program at Massachusetts General Hospital and instructor in psychiatry at Harvard Medical School, both in Boston.

Family aggregation, psychiatric history, concurrent psychiatric symptoms, and, particularly, treatment outcome were used as validators for the proposed specifier, Dr. Frank said. For example, in terms of treatment outcome, she added that a poor response to lithium and hypomanic symptoms during predominantly depressive states are associated with destabilization on antidepressants.

DSM-5 field trials are underway to assess the proposed criteria. The goal is to test the clinical acceptability and utility of the new constructs in both academic and practice settings. In addition, the reliability of diagnosis will be assessed in the academic component of the field trials. The clinics testing the mixed depression specifier include the Mayo Clinic, Rochester, Minn.; University of California,Los Angeles; the University of Texas Health Science Center at San Antonio; and the Veterans Affairs Medical Centers in Dallas and Houston.

Dr. Frank’s disclosures include Guilford Press and Servier International. Dr. Perlis’s disclosures include Concordant Rater Systems, Proteus Biomedical, and RIDVentures.

BOCA RATON, FLA.  – Proposed changes for the diagnosis of patients with mixed depressive episodes for the next edition of the Diagnostic and Statistical Manual of Mental Disorders will more closely reflect the patients psychiatrists see in their everyday practice, Ellen Frank, Ph.D., said.

The current DSM-IV-TR definition of a mixed episode requires that a patient meet full criteria for a manic episode and full criteria for a major depressive episode (except for duration) nearly every day for at least a 1-week period. "What did I think was wrong with this definition? As far as I’m concerned, these patients don’t exist," Dr. Frank said at the annual meeting of the New Clinical Drug Evaluation Unit, sponsored by the National Institute of Mental Health.

I would argue that if you really carefully distinguish, for example, agitation from increased goal-directed activity, [and] if you really carefully distinguish the potential overlapping symptoms, these patients are about as rare as unicorns," Dr. Frank said.

"We thought the current criteria too restrictive, and they are rarely adhered to. When we say the patient is mixed, we rarely mean that the patient meets full criteria for both poles," said Dr. Frank, professor of psychiatry and psychology at the University of Pittsburgh. "This results in a lot of confusion, a lack of precision, and fails to identify [those] who are at risk of progression from unipolar to bipolar disorder."

Inappropriate treatment selection is another possibility with the DSM-IV-TR definition, said Dr. Frank, director of the Depression and Manic Depression Prevention Program at the Western Psychiatric Institute and Clinic in Pittsburgh, and a member of the DSM-5 Mood Disorders Work Group. In addition, "the consequence of the current definition in common use is that we underestimate suicide risk, because I do believe these patients are at excessive risk of suicide.

"This is a horrible state to be in, and we need to figure out how to do a better job of treating it."

What Dr. Frank and her collaborators on the working group propose for the DSM-5 is a mixed specifier that indicates the presence of symptoms – not the syndrome – of the opposite pole. The specifier would be applied to both episodes of mania and depression, and would be applicable in the context of both unipolar and bipolar lifetime diagnoses.

The psychiatric history of those who experience mixed states tend to include early onset of illness, multiple previous episodes, suicidal behavior, substance abuse, and other comorbid diagnoses that tend to be associated with bipolar disorder (such as panic).

Under the proposed construct, if a "mixed" patient is predominantly depressed, they meet full criteria for a major depressive episode and have at least three of the following nearly every day during the episode:

• Elevated mood.

• Decreased need for sleep (not insomnia).

• Goal-directed activity.

• Increased energy or visible hyperactivity (again, goal directed).

• Grandiosity.

• Accelerated speech.

• Racing thoughts.

If the patient is predominantly manic or hypomanic, they meet full criteria for the manic or hypomanic episode and feature at least three of the following:

• Subjective depression.

• Worry.

• Self-reproach or guilt.

• Negative evaluation of self.

• Hopelessness.

• Suicidal ideation or behavior.

• Anhedonia.

• Fatigue.

• Psychomotor retardation.

Interestingly, the proposed criteria do not include what the working group considered to be characteristics of both poles: irritability, indecisiveness, and psychomotor agitation (which is distinguished from goal-directed activity). In addition, the proposal does not include distractibility, "which I’ve come to believe is actually a feature of almost every patient anywhere on the bipolar spectrum," Dr. Frank said.

Insomnia or hypersomnia is another shared symptom not included in the specifier. Insomnia "is difficult to distinguish as a manic or depressive symptom," said Dr. Roy H. Perlis, director of the bipolar research program at Massachusetts General Hospital and instructor in psychiatry at Harvard Medical School, both in Boston.

Family aggregation, psychiatric history, concurrent psychiatric symptoms, and, particularly, treatment outcome were used as validators for the proposed specifier, Dr. Frank said. For example, in terms of treatment outcome, she added that a poor response to lithium and hypomanic symptoms during predominantly depressive states are associated with destabilization on antidepressants.

DSM-5 field trials are underway to assess the proposed criteria. The goal is to test the clinical acceptability and utility of the new constructs in both academic and practice settings. In addition, the reliability of diagnosis will be assessed in the academic component of the field trials. The clinics testing the mixed depression specifier include the Mayo Clinic, Rochester, Minn.; University of California,Los Angeles; the University of Texas Health Science Center at San Antonio; and the Veterans Affairs Medical Centers in Dallas and Houston.

Dr. Frank’s disclosures include Guilford Press and Servier International. Dr. Perlis’s disclosures include Concordant Rater Systems, Proteus Biomedical, and RIDVentures.

Major Finding: A total of 75% achieved Tanner stage II or greater breast development and 57% achieved Tanner stage II or greater pubic hair development by age 10 years.

Data Source: The 5-year data for 444 healthy girls from the ongoing, longitudinal CYGNET.

Disclosures: Dr. Greenspan said she had no relevant financial disclosures. The investigation is part of a larger study sponsored by the National Institute of Environmental Health Sciences and the National Cancer Institute.

DENVER – A majority of girls start puberty before age 10 years, according to researchers for a longitudinal study who found young ages for onset of breast and pubic hair development.

Tanner stage II breast development ranged from 9% of 7-year-old girls to 91% of 11-year-olds in this ongoing study of 444 healthy girls. Similarly, 10% of the 7-year-olds had Tanner stage II pubic hair development, as did 86% of the 11-year-olds. A total of 75% achieved Tanner stage II or greater breast development and 57% achieved Tanner stage II or greater pubic hair development by age 10 years.

“Observations from this longitudinal cohort study confirm that girls' pubertal development is starting earlier,” Dr. Louise C. Greenspan said at the meeting, where she presented data for the first 5 years. Data from the first 2 years were published previously (Pediatrics 2010;126:e583-90).

A higher body mass index and black ethnicity were associated with earlier onset of puberty, said Dr. Greenspan, a pediatric endocrinologist at the Kaiser Permanente San Francisco Medical Center. Girls were aged 6-8 years in 2005 or 2006 when they were initially enrolled in the Cohort Study of Young Girls' Nutrition, Environment, and Transitions (CYGNET). Participants are 42% white, 24% Hispanic, 22% black, and 12% Asian.

“When we break this down by ethnicity … not surprisingly, the black girls were earlier for all stages of breast development,” Dr. Greenspan said, whereas white girls were the later bloomers at all stages of breast development.

The black girls also were earlier for all stages of pubic hair development. By age 11 years, for example, almost 98% were at Tanner stage II or higher. “The difference here is that the Asian girls were the later girls, basically all the way along, for pubic hair development,” Dr. Greenspan said.

Girls who were below the 85th percentile for BMI were the later bloomers at all stages of pubertal development, Dr. Greenspan said. She added that when girls had a high body-fat percentage on bioelectrical impedance analysis, examiners palpated them to try to distinguish fat from glandular tissue. In a similar fashion, the slimmer girls were the later developers of pubic hair at Tanner stage II.

Breast-development findings in the current study are similar to those reported by investigators for American Academy of Pediatrics' Pediatric Research in Office Settings (PROS) research network. “For breast stage, there were some variations, but it was pretty much on par,” Dr. Greenspan said. However, for pubic hair, CYGNET participants had earlier rates of development versus those in the PROS cross-sectional study (Pediatrics 1997;99:505-12).

In addition to the San Francisco cohort, investigators are prospectively evaluating girls in Cincinnati and New York as part of the larger Breast Cancer and the Environment Research Program. This federally funded study is assessing the effect of early environmental exposures that could potentially trigger earlier pubertal development, and thus increase the risk of breast cancer. “We know that age of menarche is a risk for breast cancer,” Dr. Greenspan said.

“There is growing evidence that timing of exposures may be important to determining breast cancer risk, and puberty may be an important window of susceptibility,” Dr. Greenspan said.

Major Finding: A total of 75% achieved Tanner stage II or greater breast development and 57% achieved Tanner stage II or greater pubic hair development by age 10 years.

Data Source: The 5-year data for 444 healthy girls from the ongoing, longitudinal CYGNET.

Disclosures: Dr. Greenspan said she had no relevant financial disclosures. The investigation is part of a larger study sponsored by the National Institute of Environmental Health Sciences and the National Cancer Institute.

DENVER – A majority of girls start puberty before age 10 years, according to researchers for a longitudinal study who found young ages for onset of breast and pubic hair development.

Tanner stage II breast development ranged from 9% of 7-year-old girls to 91% of 11-year-olds in this ongoing study of 444 healthy girls. Similarly, 10% of the 7-year-olds had Tanner stage II pubic hair development, as did 86% of the 11-year-olds. A total of 75% achieved Tanner stage II or greater breast development and 57% achieved Tanner stage II or greater pubic hair development by age 10 years.

“Observations from this longitudinal cohort study confirm that girls' pubertal development is starting earlier,” Dr. Louise C. Greenspan said at the meeting, where she presented data for the first 5 years. Data from the first 2 years were published previously (Pediatrics 2010;126:e583-90).

A higher body mass index and black ethnicity were associated with earlier onset of puberty, said Dr. Greenspan, a pediatric endocrinologist at the Kaiser Permanente San Francisco Medical Center. Girls were aged 6-8 years in 2005 or 2006 when they were initially enrolled in the Cohort Study of Young Girls' Nutrition, Environment, and Transitions (CYGNET). Participants are 42% white, 24% Hispanic, 22% black, and 12% Asian.

“When we break this down by ethnicity … not surprisingly, the black girls were earlier for all stages of breast development,” Dr. Greenspan said, whereas white girls were the later bloomers at all stages of breast development.

The black girls also were earlier for all stages of pubic hair development. By age 11 years, for example, almost 98% were at Tanner stage II or higher. “The difference here is that the Asian girls were the later girls, basically all the way along, for pubic hair development,” Dr. Greenspan said.

Girls who were below the 85th percentile for BMI were the later bloomers at all stages of pubertal development, Dr. Greenspan said. She added that when girls had a high body-fat percentage on bioelectrical impedance analysis, examiners palpated them to try to distinguish fat from glandular tissue. In a similar fashion, the slimmer girls were the later developers of pubic hair at Tanner stage II.

Breast-development findings in the current study are similar to those reported by investigators for American Academy of Pediatrics' Pediatric Research in Office Settings (PROS) research network. “For breast stage, there were some variations, but it was pretty much on par,” Dr. Greenspan said. However, for pubic hair, CYGNET participants had earlier rates of development versus those in the PROS cross-sectional study (Pediatrics 1997;99:505-12).

In addition to the San Francisco cohort, investigators are prospectively evaluating girls in Cincinnati and New York as part of the larger Breast Cancer and the Environment Research Program. This federally funded study is assessing the effect of early environmental exposures that could potentially trigger earlier pubertal development, and thus increase the risk of breast cancer. “We know that age of menarche is a risk for breast cancer,” Dr. Greenspan said.

“There is growing evidence that timing of exposures may be important to determining breast cancer risk, and puberty may be an important window of susceptibility,” Dr. Greenspan said.

Major Finding: A total of 75% achieved Tanner stage II or greater breast development and 57% achieved Tanner stage II or greater pubic hair development by age 10 years.

Data Source: The 5-year data for 444 healthy girls from the ongoing, longitudinal CYGNET.

Disclosures: Dr. Greenspan said she had no relevant financial disclosures. The investigation is part of a larger study sponsored by the National Institute of Environmental Health Sciences and the National Cancer Institute.

DENVER – A majority of girls start puberty before age 10 years, according to researchers for a longitudinal study who found young ages for onset of breast and pubic hair development.

Tanner stage II breast development ranged from 9% of 7-year-old girls to 91% of 11-year-olds in this ongoing study of 444 healthy girls. Similarly, 10% of the 7-year-olds had Tanner stage II pubic hair development, as did 86% of the 11-year-olds. A total of 75% achieved Tanner stage II or greater breast development and 57% achieved Tanner stage II or greater pubic hair development by age 10 years.

“Observations from this longitudinal cohort study confirm that girls' pubertal development is starting earlier,” Dr. Louise C. Greenspan said at the meeting, where she presented data for the first 5 years. Data from the first 2 years were published previously (Pediatrics 2010;126:e583-90).

A higher body mass index and black ethnicity were associated with earlier onset of puberty, said Dr. Greenspan, a pediatric endocrinologist at the Kaiser Permanente San Francisco Medical Center. Girls were aged 6-8 years in 2005 or 2006 when they were initially enrolled in the Cohort Study of Young Girls' Nutrition, Environment, and Transitions (CYGNET). Participants are 42% white, 24% Hispanic, 22% black, and 12% Asian.

“When we break this down by ethnicity … not surprisingly, the black girls were earlier for all stages of breast development,” Dr. Greenspan said, whereas white girls were the later bloomers at all stages of breast development.

The black girls also were earlier for all stages of pubic hair development. By age 11 years, for example, almost 98% were at Tanner stage II or higher. “The difference here is that the Asian girls were the later girls, basically all the way along, for pubic hair development,” Dr. Greenspan said.

Girls who were below the 85th percentile for BMI were the later bloomers at all stages of pubertal development, Dr. Greenspan said. She added that when girls had a high body-fat percentage on bioelectrical impedance analysis, examiners palpated them to try to distinguish fat from glandular tissue. In a similar fashion, the slimmer girls were the later developers of pubic hair at Tanner stage II.

Breast-development findings in the current study are similar to those reported by investigators for American Academy of Pediatrics' Pediatric Research in Office Settings (PROS) research network. “For breast stage, there were some variations, but it was pretty much on par,” Dr. Greenspan said. However, for pubic hair, CYGNET participants had earlier rates of development versus those in the PROS cross-sectional study (Pediatrics 1997;99:505-12).

In addition to the San Francisco cohort, investigators are prospectively evaluating girls in Cincinnati and New York as part of the larger Breast Cancer and the Environment Research Program. This federally funded study is assessing the effect of early environmental exposures that could potentially trigger earlier pubertal development, and thus increase the risk of breast cancer. “We know that age of menarche is a risk for breast cancer,” Dr. Greenspan said.

“There is growing evidence that timing of exposures may be important to determining breast cancer risk, and puberty may be an important window of susceptibility,” Dr. Greenspan said.

HONOLULU – When it comes to working with patients at risk for suicide in psychotherapy, universal themes apply, according to Barbara Stanley, Ph.D.

Be sure to ask patients explicitly about suicide ideation and collaborate with them on a safety plan and other survival strategies. It also is important to consult with other clinicians, said Dr. Stanley, a clinical psychologist who serves as director of the suicide intervention center at New York State Psychiatric Institute.

At her institute, staff members document this information from patients every time. "If there is any suicidal ideation, they have to document a collaborative plan for managing the suicidality," Dr. Stanley said at the annual meeting of the American Psychiatric Association.

"That is important, no matter what kind of therapy you do."

Patients at greatest risk, in order, are those with bipolar disorder, borderline personality disorder, major depression, schizophrenia, and posttraumatic stress disorder.

Cognitive-behavioral therapy and dialectical behavior therapy have the most support in the literature. However, other therapeutic basics should be used when working with suicidal patients.

Monitor patients for suicidal ideation on an ongoing basis and do not make any assumptions, said Dr. Stanley, also a lecturer in psychiatry at Columbia University, New York. Even if your patient appears well, do not assume that she is not suicidal, particularly if an attempt was made previously. Actively inquire about suicidal ideation and suicidal behavior, because patients might not volunteer the information for various reasons. Some patients say they believe their physician "doesn’t want to hear about it"; others fear they will end up admitted to a facility.

A key goal is to work toward "a collaborative relationship that encourages disclosure."

Keeping an approach that is flexible is important, Dr. Stanley said. "A fixed-treatment model is not such a good idea for people who are suicidal." For example, make some provision for increased contact during periods of suicidal crisis and decreased frequency later – as appropriate. Consider between-session communication either by telephone or e-mail. "This can include the patient checking in without the therapist contacting the patient," she said. "I have someone doing that while I’m here at this meeting."

Group therapy sessions, day programs, and other services can provide therapeutic support between consultations. Also use diary cards (or some variant) to track feedback from the patient.

Communicate with other clinicians, especially experienced, trusted colleagues. "When in doubt, consult. Seek support if you feel you are not on the right track or you are not sure."

Balance your concern without being overly anxious; if you cannot tolerate a frank discussion about suicidality, the patients can become more frightened, Dr. Stanley said. "We use a matter-of-fact tone – with no bold letters or parentheses around this – when we talk to patients about suicidality. It’s like asking about anxiety."

In addition, you have to have some sense when you ask about suicidality that a patient is telling the truth. "I tell patients directly that I need to be able to sleep at night. The deal when you are working with me is, ‘We are going to talk about it.’ My deal in return is I will not automatically throw them in the hospital."

Devise a collaborative strategy with your patient to discuss suicidality in advance. Instead of stating, "When you are suicidal, this is what you do," it is better to say, "Let’s figure out together what will work if you become suicidal again," she said. "Many adolescents will tell me that was a ‘one-time thing.’ I say, ‘Humor me, just in case.’"

No patient should leave a first appointment without a safety plan, Dr. Stanley said. This plan is different from a no-suicide contract, which is popular but not very useful, she said, and is built from a perspective that patients are not simply at the mercy of their suicidal feelings. Also, it acknowledges that suicidal feelings tend to ebb and flow. At her facility, patients are taught how to recognize warning signs and how to employ internal coping strategies, for example.

"When someone has suicidal urges, we [typically] tell them to call 911 or a hotline," Dr. Stanley said. "Do we tell patients with anxiety to call a hotline? No, we teach them how to cope."

A greater structuring of treatment can help suicidal patients as well. Prioritize the therapeutic goals and establish ways to review suicidality with the patient. This will help you to stay on a path of change, she said, versus focusing on crisis after crisis. Set an agenda, conduct a behavioral analysis, and balance validation with problem solving, she added.

"Working with suicidal patients is inevitable," Dr. Stanley said. "Many clinicians are likely to experience a suicide of at least one of their patients." A suicide can take a considerable toll on all survivors, including the therapist. More than one-third of therapists reported extreme distress after a patient suicide in a survey (Suicide Life Threat. Behavior 2010;40:328-36).

Shock, guilt, shame, grief, and fear of blame are among the typical reactions that clinicians feel in the wake of a patient suicide, Dr. Stanley said. "We want to try to avoid this for our own sake as well as for the sake of our patient."

"When young therapists ask me, ‘How can I work with this population?’ I say, ‘I try my best to attend to their suicidality in each and every moment I’m with them,’ " Dr. Stanley said. "And then if something happens, I did my best."

About 90 people per day, or more than 33,000 people each year, die by suicide in the United States. "This is the third-leading cause of death in young people," Dr. Stanley said. "More people die by suicide in the U.S. than by homicide."

These figures are probably an underestimate, Dr. Stanley said. Determination of cause of death, suicide versus accident, can be difficult. Coroners sometimes leave cause of death as "questionable" to protect surviving family members.

In addition, an estimated 3-10 suicide attempts take place for every completed suicide. Many attempts never come to the attention of mental health professionals or physicians, although attempts are a strong predictor of another attempt and of committing suicide.

Researchers found 62% of adults received medical attention after an attempt, "which means almost 40% did not," Dr. Stanley said. The 2009 National Survey on Drug Use and Health, sponsored by the Substance Abuse and Mental Health Services Administration, also showed that young adults, aged 18 to 25 years, are at highest risk for suicidal ideation, making a plan, and attempting suicide, compared with older adults.

Dr. Stanley said she had no relevant disclosures.

HONOLULU – When it comes to working with patients at risk for suicide in psychotherapy, universal themes apply, according to Barbara Stanley, Ph.D.

Be sure to ask patients explicitly about suicide ideation and collaborate with them on a safety plan and other survival strategies. It also is important to consult with other clinicians, said Dr. Stanley, a clinical psychologist who serves as director of the suicide intervention center at New York State Psychiatric Institute.

At her institute, staff members document this information from patients every time. "If there is any suicidal ideation, they have to document a collaborative plan for managing the suicidality," Dr. Stanley said at the annual meeting of the American Psychiatric Association.

"That is important, no matter what kind of therapy you do."

Patients at greatest risk, in order, are those with bipolar disorder, borderline personality disorder, major depression, schizophrenia, and posttraumatic stress disorder.

Cognitive-behavioral therapy and dialectical behavior therapy have the most support in the literature. However, other therapeutic basics should be used when working with suicidal patients.

Monitor patients for suicidal ideation on an ongoing basis and do not make any assumptions, said Dr. Stanley, also a lecturer in psychiatry at Columbia University, New York. Even if your patient appears well, do not assume that she is not suicidal, particularly if an attempt was made previously. Actively inquire about suicidal ideation and suicidal behavior, because patients might not volunteer the information for various reasons. Some patients say they believe their physician "doesn’t want to hear about it"; others fear they will end up admitted to a facility.

A key goal is to work toward "a collaborative relationship that encourages disclosure."

Keeping an approach that is flexible is important, Dr. Stanley said. "A fixed-treatment model is not such a good idea for people who are suicidal." For example, make some provision for increased contact during periods of suicidal crisis and decreased frequency later – as appropriate. Consider between-session communication either by telephone or e-mail. "This can include the patient checking in without the therapist contacting the patient," she said. "I have someone doing that while I’m here at this meeting."

Group therapy sessions, day programs, and other services can provide therapeutic support between consultations. Also use diary cards (or some variant) to track feedback from the patient.

Communicate with other clinicians, especially experienced, trusted colleagues. "When in doubt, consult. Seek support if you feel you are not on the right track or you are not sure."

Balance your concern without being overly anxious; if you cannot tolerate a frank discussion about suicidality, the patients can become more frightened, Dr. Stanley said. "We use a matter-of-fact tone – with no bold letters or parentheses around this – when we talk to patients about suicidality. It’s like asking about anxiety."

In addition, you have to have some sense when you ask about suicidality that a patient is telling the truth. "I tell patients directly that I need to be able to sleep at night. The deal when you are working with me is, ‘We are going to talk about it.’ My deal in return is I will not automatically throw them in the hospital."

Devise a collaborative strategy with your patient to discuss suicidality in advance. Instead of stating, "When you are suicidal, this is what you do," it is better to say, "Let’s figure out together what will work if you become suicidal again," she said. "Many adolescents will tell me that was a ‘one-time thing.’ I say, ‘Humor me, just in case.’"

No patient should leave a first appointment without a safety plan, Dr. Stanley said. This plan is different from a no-suicide contract, which is popular but not very useful, she said, and is built from a perspective that patients are not simply at the mercy of their suicidal feelings. Also, it acknowledges that suicidal feelings tend to ebb and flow. At her facility, patients are taught how to recognize warning signs and how to employ internal coping strategies, for example.

"When someone has suicidal urges, we [typically] tell them to call 911 or a hotline," Dr. Stanley said. "Do we tell patients with anxiety to call a hotline? No, we teach them how to cope."

A greater structuring of treatment can help suicidal patients as well. Prioritize the therapeutic goals and establish ways to review suicidality with the patient. This will help you to stay on a path of change, she said, versus focusing on crisis after crisis. Set an agenda, conduct a behavioral analysis, and balance validation with problem solving, she added.

"Working with suicidal patients is inevitable," Dr. Stanley said. "Many clinicians are likely to experience a suicide of at least one of their patients." A suicide can take a considerable toll on all survivors, including the therapist. More than one-third of therapists reported extreme distress after a patient suicide in a survey (Suicide Life Threat. Behavior 2010;40:328-36).

Shock, guilt, shame, grief, and fear of blame are among the typical reactions that clinicians feel in the wake of a patient suicide, Dr. Stanley said. "We want to try to avoid this for our own sake as well as for the sake of our patient."

"When young therapists ask me, ‘How can I work with this population?’ I say, ‘I try my best to attend to their suicidality in each and every moment I’m with them,’ " Dr. Stanley said. "And then if something happens, I did my best."

About 90 people per day, or more than 33,000 people each year, die by suicide in the United States. "This is the third-leading cause of death in young people," Dr. Stanley said. "More people die by suicide in the U.S. than by homicide."

These figures are probably an underestimate, Dr. Stanley said. Determination of cause of death, suicide versus accident, can be difficult. Coroners sometimes leave cause of death as "questionable" to protect surviving family members.

In addition, an estimated 3-10 suicide attempts take place for every completed suicide. Many attempts never come to the attention of mental health professionals or physicians, although attempts are a strong predictor of another attempt and of committing suicide.

Researchers found 62% of adults received medical attention after an attempt, "which means almost 40% did not," Dr. Stanley said. The 2009 National Survey on Drug Use and Health, sponsored by the Substance Abuse and Mental Health Services Administration, also showed that young adults, aged 18 to 25 years, are at highest risk for suicidal ideation, making a plan, and attempting suicide, compared with older adults.

Dr. Stanley said she had no relevant disclosures.

HONOLULU – When it comes to working with patients at risk for suicide in psychotherapy, universal themes apply, according to Barbara Stanley, Ph.D.

Be sure to ask patients explicitly about suicide ideation and collaborate with them on a safety plan and other survival strategies. It also is important to consult with other clinicians, said Dr. Stanley, a clinical psychologist who serves as director of the suicide intervention center at New York State Psychiatric Institute.

At her institute, staff members document this information from patients every time. "If there is any suicidal ideation, they have to document a collaborative plan for managing the suicidality," Dr. Stanley said at the annual meeting of the American Psychiatric Association.

"That is important, no matter what kind of therapy you do."

Patients at greatest risk, in order, are those with bipolar disorder, borderline personality disorder, major depression, schizophrenia, and posttraumatic stress disorder.

Cognitive-behavioral therapy and dialectical behavior therapy have the most support in the literature. However, other therapeutic basics should be used when working with suicidal patients.

Monitor patients for suicidal ideation on an ongoing basis and do not make any assumptions, said Dr. Stanley, also a lecturer in psychiatry at Columbia University, New York. Even if your patient appears well, do not assume that she is not suicidal, particularly if an attempt was made previously. Actively inquire about suicidal ideation and suicidal behavior, because patients might not volunteer the information for various reasons. Some patients say they believe their physician "doesn’t want to hear about it"; others fear they will end up admitted to a facility.

A key goal is to work toward "a collaborative relationship that encourages disclosure."

Keeping an approach that is flexible is important, Dr. Stanley said. "A fixed-treatment model is not such a good idea for people who are suicidal." For example, make some provision for increased contact during periods of suicidal crisis and decreased frequency later – as appropriate. Consider between-session communication either by telephone or e-mail. "This can include the patient checking in without the therapist contacting the patient," she said. "I have someone doing that while I’m here at this meeting."

Group therapy sessions, day programs, and other services can provide therapeutic support between consultations. Also use diary cards (or some variant) to track feedback from the patient.

Communicate with other clinicians, especially experienced, trusted colleagues. "When in doubt, consult. Seek support if you feel you are not on the right track or you are not sure."

Balance your concern without being overly anxious; if you cannot tolerate a frank discussion about suicidality, the patients can become more frightened, Dr. Stanley said. "We use a matter-of-fact tone – with no bold letters or parentheses around this – when we talk to patients about suicidality. It’s like asking about anxiety."

In addition, you have to have some sense when you ask about suicidality that a patient is telling the truth. "I tell patients directly that I need to be able to sleep at night. The deal when you are working with me is, ‘We are going to talk about it.’ My deal in return is I will not automatically throw them in the hospital."

Devise a collaborative strategy with your patient to discuss suicidality in advance. Instead of stating, "When you are suicidal, this is what you do," it is better to say, "Let’s figure out together what will work if you become suicidal again," she said. "Many adolescents will tell me that was a ‘one-time thing.’ I say, ‘Humor me, just in case.’"

No patient should leave a first appointment without a safety plan, Dr. Stanley said. This plan is different from a no-suicide contract, which is popular but not very useful, she said, and is built from a perspective that patients are not simply at the mercy of their suicidal feelings. Also, it acknowledges that suicidal feelings tend to ebb and flow. At her facility, patients are taught how to recognize warning signs and how to employ internal coping strategies, for example.

"When someone has suicidal urges, we [typically] tell them to call 911 or a hotline," Dr. Stanley said. "Do we tell patients with anxiety to call a hotline? No, we teach them how to cope."

A greater structuring of treatment can help suicidal patients as well. Prioritize the therapeutic goals and establish ways to review suicidality with the patient. This will help you to stay on a path of change, she said, versus focusing on crisis after crisis. Set an agenda, conduct a behavioral analysis, and balance validation with problem solving, she added.

"Working with suicidal patients is inevitable," Dr. Stanley said. "Many clinicians are likely to experience a suicide of at least one of their patients." A suicide can take a considerable toll on all survivors, including the therapist. More than one-third of therapists reported extreme distress after a patient suicide in a survey (Suicide Life Threat. Behavior 2010;40:328-36).

Shock, guilt, shame, grief, and fear of blame are among the typical reactions that clinicians feel in the wake of a patient suicide, Dr. Stanley said. "We want to try to avoid this for our own sake as well as for the sake of our patient."

"When young therapists ask me, ‘How can I work with this population?’ I say, ‘I try my best to attend to their suicidality in each and every moment I’m with them,’ " Dr. Stanley said. "And then if something happens, I did my best."

About 90 people per day, or more than 33,000 people each year, die by suicide in the United States. "This is the third-leading cause of death in young people," Dr. Stanley said. "More people die by suicide in the U.S. than by homicide."

These figures are probably an underestimate, Dr. Stanley said. Determination of cause of death, suicide versus accident, can be difficult. Coroners sometimes leave cause of death as "questionable" to protect surviving family members.

In addition, an estimated 3-10 suicide attempts take place for every completed suicide. Many attempts never come to the attention of mental health professionals or physicians, although attempts are a strong predictor of another attempt and of committing suicide.

Researchers found 62% of adults received medical attention after an attempt, "which means almost 40% did not," Dr. Stanley said. The 2009 National Survey on Drug Use and Health, sponsored by the Substance Abuse and Mental Health Services Administration, also showed that young adults, aged 18 to 25 years, are at highest risk for suicidal ideation, making a plan, and attempting suicide, compared with older adults.

Dr. Stanley said she had no relevant disclosures.

BOCA RATON, FLA. – Significantly more children and adolescents with bipolar disorder mania or mixed episodes responded to 8 weeks of treatment with risperidone vs. lithium or valproate in a multicenter, initial monotherapy comparison trial.

At study end, 69% treated with risperidone achieved an "improved" or "much improved" rating on the primary outcome measure, Clinical Global Impressions- –Improvement scale for Mania (CGI-IM). In contrast, 36% of participants taking lithium saw such improvement, as did 24% of the patients taking valproate.

Dr. Karen D. Wagner

"About two-thirds responded to risperidone, one-third to lithium, and about one-quarter to valproate, with no significant difference between lithium and valproate," Dr. Karen D. Wagner said at a meeting of the New Clinical Drug Evaluation Unit (NCDEU) sponsored by the National Institute of Mental Health.

The 290 children enrolled in the Treatment of Early Age Mania (TEAM) study included 93 randomized to risperidone, 93 to lithium, and 104 to valproate. A total 210 completed the 8-week acute treatment trial.

All participants had a bipolar disorder I manic or mixed state episode of 4 weeks or longer. Participants were aged 6-15 years old, making this a younger cohort than the 10-year cutoff used in other, industry-sponsored studies, Dr. Wagner said. The NIMH funds the ongoing TEAM study.

"This was a very impaired group," Dr. Mark A. Riddle said in a separate presentation at the NCDEU meeting. The mean initial onset for mania was at 5.3 years and the mean duration was 4.9 years at study entry, so "these were kids who had really early disorder and really early problems."

In addition, the mean Children’s Global Assessment Scale (CGAS) score at baseline was 39.2; the mean Clinical Global Impressions Scale for Bipolar Disorder (CGI-BP) severity-mania score was 6.0; and the mean K-SADS Mania Rating Scale (KMRS) score was 43.6.

"Childhood bipolar disorder is a chronic illness and can be very impairing at home, school, and [with] peer functioning," said Dr. Riddle, director of the division of child and adolescent psychiatry at Johns Hopkins University, Baltimore. He added that little is known about effective pharmacologic treatment. "TEAM was deemed essential so we can get some sense of children’s response to treatment, which can be different from adults."

What is the best agent to use for a child who has not been on any medications for bipolar disorder? Answering that question was the primary aim of the acute phase of the TEAM study. Led by principal investigator Dr. Barbara Geller, investigators compared the three most-common agents prescribed for mania at the time of enrollment.

"There was nothing special about selection of risperidone, other than there was the most information about use of risperidone in young children," including safety data from autism spectrum disorder populations, said Dr. Wagner, director of the child and adolescent psychiatry division at University of Texas Medical Branch at Galveston.

Most of the children had comorbidities such as attention-deficit/hyperactivity disorder, 92%, and oppositional defiant disorder, 90%. A total 70% also had an anxiety disorder, and 32% had a sleep disorder.

The agents were titrated up over 6 weeks and maintained at the maximum dose for the final 2 weeks. The mean dose/level at study end was 2.6 mg/day risperidone, 1.1 mEq/L lithium, and 114 mcg/mL valproate. "These were reasonable, upward doses," Dr. Wagner said. This strategy used was aimed at avoiding criticism that any unresponsiveness was attributable to insufficient dosing, she added.

Secondary outcome measures also supported a greater efficacy with risperidone. For example, 48% of the risperidone group achieved a CGAS score more than 60, compared with 27% of the lithium group and 17% of the valproate group. Similarly, the final KRMS score indicated that 16% of the risperidone group had mild to minimal residual symptoms, compared with 26% of the lithium group and 28% of the valproate group.

The investigators looked beyond clinical improvements. "We have to weigh side effects with efficacy," Dr. Wagner said.

"Suicidality is always a concern." Seven participants had suicidal behaviors, including two in the risperidone group, three in the lithium group, and two in the valproate group. There were no suicides during the course of study.

"Interestingly, look at suicidal ideation ... it’s in the direction we like to see this go." From baseline to assessment at 8 weeks, there was a significant decrease in suicidal ideation in all groups, Dr. Wagner said. "Remember, this is a very impaired group of children."

The most common side effects included drowsiness in the risperidone group, which increased from 18% at baseline to 51% at 8 weeks; frequent urination, dry mouth, and excessive thirst in the lithium group; and difficulty arousing in the morning in the valproate group. "It was not a surprise that side effects differed. What was possibly more surprising was we did not see a significant change in extrapyramidal effects," Dr. Wagner said.

The was a "pretty significant" increase in body weight in the risperidone group, a mean 3.3 kg, compared with 1.4 kg in the lithium group and 1.7 kg in the valproate group. "Remember this was an 8-week study, Dr. Wagner said.

Anyone who dropped out of the study prior to week 8 was considered a nonresponder. The discontinuation rates were 16% for the risperidone group, 32% for the lithium group, and 26% for the valproate group, for an overall rate of 25%. "This is probably what we see clinically. About 25% of children are no longer on the medication you want them to take by 8 weeks," Dr. Wagner said.

A change of mind led the reasons for discontinuation, cited by 54%. "I’d like to be more definitive about that," Dr. Wagner said. An additional 22% cited side effects, and 10% withdrew because of symptom worsening.

The drug assignment was open and known by everyone except the blinded rater at 8 weeks, a potential limitation of the study, Dr. Riddle said. The large number of participants and allowing 8 weeks for response to monotherapy were strengths of the study.

Dr. Wagner said the TEAM results are comparable with reports from other major studies in the literature. For example, the valproate response rate of 24% in TEAM was exactly the same that Dr. Wagner and her colleagues reported in a divalproex extended-release trial (J. Am. Acad. Child Adolesc. Psychiatry 2009;48:519-32). In addition, the 69% response rate with risperidone was similar to the 58% mean response rate reported among five second-generation atypical medication trials in pediatric populations (Bipolar Disord. 2010;12:116-41).

The next step for TEAM researchers is to delve more deeply into primary and secondary outcomes, Dr. Wagner said. Data analysis from additional measures such as the Children’s Depression Rating Scale–Revised (CDRS-R), the CGI-BP, and the Caregiver Strain Questionnaire (CSQ) are forthcoming.

In addition, "We need to see in the long term if these response rates will continue," Dr. Wagner said.

A second phase of TEAM involves re-randomizing partial responders to a second study medication (the add-on paradigm) or switching nonresponders to one of the other two agents as monotherapy.

Dr. Wagner said she receives honoraria from CMP Medica, Contemporary Forums, Physicians Postgraduate Press, and Quantia Communications. Dr. Riddle said he had no financial disclosures.

BOCA RATON, FLA. – Significantly more children and adolescents with bipolar disorder mania or mixed episodes responded to 8 weeks of treatment with risperidone vs. lithium or valproate in a multicenter, initial monotherapy comparison trial.

At study end, 69% treated with risperidone achieved an "improved" or "much improved" rating on the primary outcome measure, Clinical Global Impressions- –Improvement scale for Mania (CGI-IM). In contrast, 36% of participants taking lithium saw such improvement, as did 24% of the patients taking valproate.

Dr. Karen D. Wagner

"About two-thirds responded to risperidone, one-third to lithium, and about one-quarter to valproate, with no significant difference between lithium and valproate," Dr. Karen D. Wagner said at a meeting of the New Clinical Drug Evaluation Unit (NCDEU) sponsored by the National Institute of Mental Health.

The 290 children enrolled in the Treatment of Early Age Mania (TEAM) study included 93 randomized to risperidone, 93 to lithium, and 104 to valproate. A total 210 completed the 8-week acute treatment trial.

All participants had a bipolar disorder I manic or mixed state episode of 4 weeks or longer. Participants were aged 6-15 years old, making this a younger cohort than the 10-year cutoff used in other, industry-sponsored studies, Dr. Wagner said. The NIMH funds the ongoing TEAM study.

"This was a very impaired group," Dr. Mark A. Riddle said in a separate presentation at the NCDEU meeting. The mean initial onset for mania was at 5.3 years and the mean duration was 4.9 years at study entry, so "these were kids who had really early disorder and really early problems."

In addition, the mean Children’s Global Assessment Scale (CGAS) score at baseline was 39.2; the mean Clinical Global Impressions Scale for Bipolar Disorder (CGI-BP) severity-mania score was 6.0; and the mean K-SADS Mania Rating Scale (KMRS) score was 43.6.

"Childhood bipolar disorder is a chronic illness and can be very impairing at home, school, and [with] peer functioning," said Dr. Riddle, director of the division of child and adolescent psychiatry at Johns Hopkins University, Baltimore. He added that little is known about effective pharmacologic treatment. "TEAM was deemed essential so we can get some sense of children’s response to treatment, which can be different from adults."

What is the best agent to use for a child who has not been on any medications for bipolar disorder? Answering that question was the primary aim of the acute phase of the TEAM study. Led by principal investigator Dr. Barbara Geller, investigators compared the three most-common agents prescribed for mania at the time of enrollment.

"There was nothing special about selection of risperidone, other than there was the most information about use of risperidone in young children," including safety data from autism spectrum disorder populations, said Dr. Wagner, director of the child and adolescent psychiatry division at University of Texas Medical Branch at Galveston.

Most of the children had comorbidities such as attention-deficit/hyperactivity disorder, 92%, and oppositional defiant disorder, 90%. A total 70% also had an anxiety disorder, and 32% had a sleep disorder.

The agents were titrated up over 6 weeks and maintained at the maximum dose for the final 2 weeks. The mean dose/level at study end was 2.6 mg/day risperidone, 1.1 mEq/L lithium, and 114 mcg/mL valproate. "These were reasonable, upward doses," Dr. Wagner said. This strategy used was aimed at avoiding criticism that any unresponsiveness was attributable to insufficient dosing, she added.

Secondary outcome measures also supported a greater efficacy with risperidone. For example, 48% of the risperidone group achieved a CGAS score more than 60, compared with 27% of the lithium group and 17% of the valproate group. Similarly, the final KRMS score indicated that 16% of the risperidone group had mild to minimal residual symptoms, compared with 26% of the lithium group and 28% of the valproate group.

The investigators looked beyond clinical improvements. "We have to weigh side effects with efficacy," Dr. Wagner said.

"Suicidality is always a concern." Seven participants had suicidal behaviors, including two in the risperidone group, three in the lithium group, and two in the valproate group. There were no suicides during the course of study.

"Interestingly, look at suicidal ideation ... it’s in the direction we like to see this go." From baseline to assessment at 8 weeks, there was a significant decrease in suicidal ideation in all groups, Dr. Wagner said. "Remember, this is a very impaired group of children."

The most common side effects included drowsiness in the risperidone group, which increased from 18% at baseline to 51% at 8 weeks; frequent urination, dry mouth, and excessive thirst in the lithium group; and difficulty arousing in the morning in the valproate group. "It was not a surprise that side effects differed. What was possibly more surprising was we did not see a significant change in extrapyramidal effects," Dr. Wagner said.

The was a "pretty significant" increase in body weight in the risperidone group, a mean 3.3 kg, compared with 1.4 kg in the lithium group and 1.7 kg in the valproate group. "Remember this was an 8-week study, Dr. Wagner said.

Anyone who dropped out of the study prior to week 8 was considered a nonresponder. The discontinuation rates were 16% for the risperidone group, 32% for the lithium group, and 26% for the valproate group, for an overall rate of 25%. "This is probably what we see clinically. About 25% of children are no longer on the medication you want them to take by 8 weeks," Dr. Wagner said.

A change of mind led the reasons for discontinuation, cited by 54%. "I’d like to be more definitive about that," Dr. Wagner said. An additional 22% cited side effects, and 10% withdrew because of symptom worsening.

The drug assignment was open and known by everyone except the blinded rater at 8 weeks, a potential limitation of the study, Dr. Riddle said. The large number of participants and allowing 8 weeks for response to monotherapy were strengths of the study.

Dr. Wagner said the TEAM results are comparable with reports from other major studies in the literature. For example, the valproate response rate of 24% in TEAM was exactly the same that Dr. Wagner and her colleagues reported in a divalproex extended-release trial (J. Am. Acad. Child Adolesc. Psychiatry 2009;48:519-32). In addition, the 69% response rate with risperidone was similar to the 58% mean response rate reported among five second-generation atypical medication trials in pediatric populations (Bipolar Disord. 2010;12:116-41).

The next step for TEAM researchers is to delve more deeply into primary and secondary outcomes, Dr. Wagner said. Data analysis from additional measures such as the Children’s Depression Rating Scale–Revised (CDRS-R), the CGI-BP, and the Caregiver Strain Questionnaire (CSQ) are forthcoming.

In addition, "We need to see in the long term if these response rates will continue," Dr. Wagner said.

A second phase of TEAM involves re-randomizing partial responders to a second study medication (the add-on paradigm) or switching nonresponders to one of the other two agents as monotherapy.

Dr. Wagner said she receives honoraria from CMP Medica, Contemporary Forums, Physicians Postgraduate Press, and Quantia Communications. Dr. Riddle said he had no financial disclosures.

BOCA RATON, FLA. – Significantly more children and adolescents with bipolar disorder mania or mixed episodes responded to 8 weeks of treatment with risperidone vs. lithium or valproate in a multicenter, initial monotherapy comparison trial.

At study end, 69% treated with risperidone achieved an "improved" or "much improved" rating on the primary outcome measure, Clinical Global Impressions- –Improvement scale for Mania (CGI-IM). In contrast, 36% of participants taking lithium saw such improvement, as did 24% of the patients taking valproate.

Dr. Karen D. Wagner

"About two-thirds responded to risperidone, one-third to lithium, and about one-quarter to valproate, with no significant difference between lithium and valproate," Dr. Karen D. Wagner said at a meeting of the New Clinical Drug Evaluation Unit (NCDEU) sponsored by the National Institute of Mental Health.

The 290 children enrolled in the Treatment of Early Age Mania (TEAM) study included 93 randomized to risperidone, 93 to lithium, and 104 to valproate. A total 210 completed the 8-week acute treatment trial.

All participants had a bipolar disorder I manic or mixed state episode of 4 weeks or longer. Participants were aged 6-15 years old, making this a younger cohort than the 10-year cutoff used in other, industry-sponsored studies, Dr. Wagner said. The NIMH funds the ongoing TEAM study.

"This was a very impaired group," Dr. Mark A. Riddle said in a separate presentation at the NCDEU meeting. The mean initial onset for mania was at 5.3 years and the mean duration was 4.9 years at study entry, so "these were kids who had really early disorder and really early problems."

In addition, the mean Children’s Global Assessment Scale (CGAS) score at baseline was 39.2; the mean Clinical Global Impressions Scale for Bipolar Disorder (CGI-BP) severity-mania score was 6.0; and the mean K-SADS Mania Rating Scale (KMRS) score was 43.6.

"Childhood bipolar disorder is a chronic illness and can be very impairing at home, school, and [with] peer functioning," said Dr. Riddle, director of the division of child and adolescent psychiatry at Johns Hopkins University, Baltimore. He added that little is known about effective pharmacologic treatment. "TEAM was deemed essential so we can get some sense of children’s response to treatment, which can be different from adults."

What is the best agent to use for a child who has not been on any medications for bipolar disorder? Answering that question was the primary aim of the acute phase of the TEAM study. Led by principal investigator Dr. Barbara Geller, investigators compared the three most-common agents prescribed for mania at the time of enrollment.

"There was nothing special about selection of risperidone, other than there was the most information about use of risperidone in young children," including safety data from autism spectrum disorder populations, said Dr. Wagner, director of the child and adolescent psychiatry division at University of Texas Medical Branch at Galveston.

Most of the children had comorbidities such as attention-deficit/hyperactivity disorder, 92%, and oppositional defiant disorder, 90%. A total 70% also had an anxiety disorder, and 32% had a sleep disorder.

The agents were titrated up over 6 weeks and maintained at the maximum dose for the final 2 weeks. The mean dose/level at study end was 2.6 mg/day risperidone, 1.1 mEq/L lithium, and 114 mcg/mL valproate. "These were reasonable, upward doses," Dr. Wagner said. This strategy used was aimed at avoiding criticism that any unresponsiveness was attributable to insufficient dosing, she added.

Secondary outcome measures also supported a greater efficacy with risperidone. For example, 48% of the risperidone group achieved a CGAS score more than 60, compared with 27% of the lithium group and 17% of the valproate group. Similarly, the final KRMS score indicated that 16% of the risperidone group had mild to minimal residual symptoms, compared with 26% of the lithium group and 28% of the valproate group.

The investigators looked beyond clinical improvements. "We have to weigh side effects with efficacy," Dr. Wagner said.

"Suicidality is always a concern." Seven participants had suicidal behaviors, including two in the risperidone group, three in the lithium group, and two in the valproate group. There were no suicides during the course of study.

"Interestingly, look at suicidal ideation ... it’s in the direction we like to see this go." From baseline to assessment at 8 weeks, there was a significant decrease in suicidal ideation in all groups, Dr. Wagner said. "Remember, this is a very impaired group of children."

The most common side effects included drowsiness in the risperidone group, which increased from 18% at baseline to 51% at 8 weeks; frequent urination, dry mouth, and excessive thirst in the lithium group; and difficulty arousing in the morning in the valproate group. "It was not a surprise that side effects differed. What was possibly more surprising was we did not see a significant change in extrapyramidal effects," Dr. Wagner said.

The was a "pretty significant" increase in body weight in the risperidone group, a mean 3.3 kg, compared with 1.4 kg in the lithium group and 1.7 kg in the valproate group. "Remember this was an 8-week study, Dr. Wagner said.

Anyone who dropped out of the study prior to week 8 was considered a nonresponder. The discontinuation rates were 16% for the risperidone group, 32% for the lithium group, and 26% for the valproate group, for an overall rate of 25%. "This is probably what we see clinically. About 25% of children are no longer on the medication you want them to take by 8 weeks," Dr. Wagner said.

A change of mind led the reasons for discontinuation, cited by 54%. "I’d like to be more definitive about that," Dr. Wagner said. An additional 22% cited side effects, and 10% withdrew because of symptom worsening.

The drug assignment was open and known by everyone except the blinded rater at 8 weeks, a potential limitation of the study, Dr. Riddle said. The large number of participants and allowing 8 weeks for response to monotherapy were strengths of the study.

Dr. Wagner said the TEAM results are comparable with reports from other major studies in the literature. For example, the valproate response rate of 24% in TEAM was exactly the same that Dr. Wagner and her colleagues reported in a divalproex extended-release trial (J. Am. Acad. Child Adolesc. Psychiatry 2009;48:519-32). In addition, the 69% response rate with risperidone was similar to the 58% mean response rate reported among five second-generation atypical medication trials in pediatric populations (Bipolar Disord. 2010;12:116-41).

The next step for TEAM researchers is to delve more deeply into primary and secondary outcomes, Dr. Wagner said. Data analysis from additional measures such as the Children’s Depression Rating Scale–Revised (CDRS-R), the CGI-BP, and the Caregiver Strain Questionnaire (CSQ) are forthcoming.

In addition, "We need to see in the long term if these response rates will continue," Dr. Wagner said.

A second phase of TEAM involves re-randomizing partial responders to a second study medication (the add-on paradigm) or switching nonresponders to one of the other two agents as monotherapy.

Dr. Wagner said she receives honoraria from CMP Medica, Contemporary Forums, Physicians Postgraduate Press, and Quantia Communications. Dr. Riddle said he had no financial disclosures.

BOCA RATON, FLA. – Significantly more children and adolescents with bipolar disorder mania or mixed episodes responded to 8 weeks of treatment with risperidone vs. lithium or valproate in a multicenter, initial monotherapy comparison trial.

At study end, 69% treated with risperidone achieved an "improved" or "much improved" rating on the primary outcome measure, Clinical Global Impressions- –Improvement scale for Mania (CGI-IM). In contrast, 36% of participants taking lithium saw such improvement, as did 24% of the patients taking valproate.

Dr. Karen D. Wagner

"About two-thirds responded to risperidone, one-third to lithium, and about one-quarter to valproate, with no significant difference between lithium and valproate," Dr. Karen D. Wagner said at a meeting of the New Clinical Drug Evaluation Unit (NCDEU) sponsored by the National Institute of Mental Health.

The 290 children enrolled in the Treatment of Early Age Mania (TEAM) study included 93 randomized to risperidone, 93 to lithium, and 104 to valproate. A total 210 completed the 8-week acute treatment trial.

All participants had a bipolar disorder I manic or mixed state episode of 4 weeks or longer. Participants were aged 6-15 years old, making this a younger cohort than the 10-year cutoff used in other, industry-sponsored studies, Dr. Wagner said. The NIMH funds the ongoing TEAM study.

"This was a very impaired group," Dr. Mark A. Riddle said in a separate presentation at the NCDEU meeting. The mean initial onset for mania was at 5.3 years and the mean duration was 4.9 years at study entry, so "these were kids who had really early disorder and really early problems."

In addition, the mean Children’s Global Assessment Scale (CGAS) score at baseline was 39.2; the mean Clinical Global Impressions Scale for Bipolar Disorder (CGI-BP) severity-mania score was 6.0; and the mean K-SADS Mania Rating Scale (KMRS) score was 43.6.

"Childhood bipolar disorder is a chronic illness and can be very impairing at home, school, and [with] peer functioning," said Dr. Riddle, director of the division of child and adolescent psychiatry at Johns Hopkins University, Baltimore. He added that little is known about effective pharmacologic treatment. "TEAM was deemed essential so we can get some sense of children’s response to treatment, which can be different from adults."

What is the best agent to use for a child who has not been on any medications for bipolar disorder? Answering that question was the primary aim of the acute phase of the TEAM study. Led by principal investigator Dr. Barbara Geller, investigators compared the three most-common agents prescribed for mania at the time of enrollment.

"There was nothing special about selection of risperidone, other than there was the most information about use of risperidone in young children," including safety data from autism spectrum disorder populations, said Dr. Wagner, director of the child and adolescent psychiatry division at University of Texas Medical Branch at Galveston.

Most of the children had comorbidities such as attention-deficit/hyperactivity disorder, 92%, and oppositional defiant disorder, 90%. A total 70% also had an anxiety disorder, and 32% had a sleep disorder.

The agents were titrated up over 6 weeks and maintained at the maximum dose for the final 2 weeks. The mean dose/level at study end was 2.6 mg/day risperidone, 1.1 mEq/L lithium, and 114 mcg/mL valproate. "These were reasonable, upward doses," Dr. Wagner said. This strategy used was aimed at avoiding criticism that any unresponsiveness was attributable to insufficient dosing, she added.

Secondary outcome measures also supported a greater efficacy with risperidone. For example, 48% of the risperidone group achieved a CGAS score more than 60, compared with 27% of the lithium group and 17% of the valproate group. Similarly, the final KRMS score indicated that 16% of the risperidone group had mild to minimal residual symptoms, compared with 26% of the lithium group and 28% of the valproate group.

The investigators looked beyond clinical improvements. "We have to weigh side effects with efficacy," Dr. Wagner said.

"Suicidality is always a concern." Seven participants had suicidal behaviors, including two in the risperidone group, three in the lithium group, and two in the valproate group. There were no suicides during the course of study.

"Interestingly, look at suicidal ideation ... it’s in the direction we like to see this go." From baseline to assessment at 8 weeks, there was a significant decrease in suicidal ideation in all groups, Dr. Wagner said. "Remember, this is a very impaired group of children."

The most common side effects included drowsiness in the risperidone group, which increased from 18% at baseline to 51% at 8 weeks; frequent urination, dry mouth, and excessive thirst in the lithium group; and difficulty arousing in the morning in the valproate group. "It was not a surprise that side effects differed. What was possibly more surprising was we did not see a significant change in extrapyramidal effects," Dr. Wagner said.

The was a "pretty significant" increase in body weight in the risperidone group, a mean 3.3 kg, compared with 1.4 kg in the lithium group and 1.7 kg in the valproate group. "Remember this was an 8-week study, Dr. Wagner said.

Anyone who dropped out of the study prior to week 8 was considered a nonresponder. The discontinuation rates were 16% for the risperidone group, 32% for the lithium group, and 26% for the valproate group, for an overall rate of 25%. "This is probably what we see clinically. About 25% of children are no longer on the medication you want them to take by 8 weeks," Dr. Wagner said.

A change of mind led the reasons for discontinuation, cited by 54%. "I’d like to be more definitive about that," Dr. Wagner said. An additional 22% cited side effects, and 10% withdrew because of symptom worsening.

The drug assignment was open and known by everyone except the blinded rater at 8 weeks, a potential limitation of the study, Dr. Riddle said. The large number of participants and allowing 8 weeks for response to monotherapy were strengths of the study.

Dr. Wagner said the TEAM results are comparable with reports from other major studies in the literature. For example, the valproate response rate of 24% in TEAM was exactly the same that Dr. Wagner and her colleagues reported in a divalproex extended-release trial (J. Am. Acad. Child Adolesc. Psychiatry 2009;48:519-32). In addition, the 69% response rate with risperidone was similar to the 58% mean response rate reported among five second-generation atypical medication trials in pediatric populations (Bipolar Disord. 2010;12:116-41).

The next step for TEAM researchers is to delve more deeply into primary and secondary outcomes, Dr. Wagner said. Data analysis from additional measures such as the Children’s Depression Rating Scale–Revised (CDRS-R), the CGI-BP, and the Caregiver Strain Questionnaire (CSQ) are forthcoming.

In addition, "We need to see in the long term if these response rates will continue," Dr. Wagner said.

A second phase of TEAM involves re-randomizing partial responders to a second study medication (the add-on paradigm) or switching nonresponders to one of the other two agents as monotherapy.

Dr. Wagner said she receives honoraria from CMP Medica, Contemporary Forums, Physicians Postgraduate Press, and Quantia Communications. Dr. Riddle said he had no financial disclosures.

BOCA RATON, FLA. – Significantly more children and adolescents with bipolar disorder mania or mixed episodes responded to 8 weeks of treatment with risperidone vs. lithium or valproate in a multicenter, initial monotherapy comparison trial.

At study end, 69% treated with risperidone achieved an "improved" or "much improved" rating on the primary outcome measure, Clinical Global Impressions- –Improvement scale for Mania (CGI-IM). In contrast, 36% of participants taking lithium saw such improvement, as did 24% of the patients taking valproate.

Dr. Karen D. Wagner

"About two-thirds responded to risperidone, one-third to lithium, and about one-quarter to valproate, with no significant difference between lithium and valproate," Dr. Karen D. Wagner said at a meeting of the New Clinical Drug Evaluation Unit (NCDEU) sponsored by the National Institute of Mental Health.

The 290 children enrolled in the Treatment of Early Age Mania (TEAM) study included 93 randomized to risperidone, 93 to lithium, and 104 to valproate. A total 210 completed the 8-week acute treatment trial.

All participants had a bipolar disorder I manic or mixed state episode of 4 weeks or longer. Participants were aged 6-15 years old, making this a younger cohort than the 10-year cutoff used in other, industry-sponsored studies, Dr. Wagner said. The NIMH funds the ongoing TEAM study.

"This was a very impaired group," Dr. Mark A. Riddle said in a separate presentation at the NCDEU meeting. The mean initial onset for mania was at 5.3 years and the mean duration was 4.9 years at study entry, so "these were kids who had really early disorder and really early problems."

In addition, the mean Children’s Global Assessment Scale (CGAS) score at baseline was 39.2; the mean Clinical Global Impressions Scale for Bipolar Disorder (CGI-BP) severity-mania score was 6.0; and the mean K-SADS Mania Rating Scale (KMRS) score was 43.6.

"Childhood bipolar disorder is a chronic illness and can be very impairing at home, school, and [with] peer functioning," said Dr. Riddle, director of the division of child and adolescent psychiatry at Johns Hopkins University, Baltimore. He added that little is known about effective pharmacologic treatment. "TEAM was deemed essential so we can get some sense of children’s response to treatment, which can be different from adults."

What is the best agent to use for a child who has not been on any medications for bipolar disorder? Answering that question was the primary aim of the acute phase of the TEAM study. Led by principal investigator Dr. Barbara Geller, investigators compared the three most-common agents prescribed for mania at the time of enrollment.

"There was nothing special about selection of risperidone, other than there was the most information about use of risperidone in young children," including safety data from autism spectrum disorder populations, said Dr. Wagner, director of the child and adolescent psychiatry division at University of Texas Medical Branch at Galveston.

Most of the children had comorbidities such as attention-deficit/hyperactivity disorder, 92%, and oppositional defiant disorder, 90%. A total 70% also had an anxiety disorder, and 32% had a sleep disorder.

The agents were titrated up over 6 weeks and maintained at the maximum dose for the final 2 weeks. The mean dose/level at study end was 2.6 mg/day risperidone, 1.1 mEq/L lithium, and 114 mcg/mL valproate. "These were reasonable, upward doses," Dr. Wagner said. This strategy used was aimed at avoiding criticism that any unresponsiveness was attributable to insufficient dosing, she added.

Secondary outcome measures also supported a greater efficacy with risperidone. For example, 48% of the risperidone group achieved a CGAS score more than 60, compared with 27% of the lithium group and 17% of the valproate group. Similarly, the final KRMS score indicated that 16% of the risperidone group had mild to minimal residual symptoms, compared with 26% of the lithium group and 28% of the valproate group.

The investigators looked beyond clinical improvements. "We have to weigh side effects with efficacy," Dr. Wagner said.

"Suicidality is always a concern." Seven participants had suicidal behaviors, including two in the risperidone group, three in the lithium group, and two in the valproate group. There were no suicides during the course of study.

"Interestingly, look at suicidal ideation ... it’s in the direction we like to see this go." From baseline to assessment at 8 weeks, there was a significant decrease in suicidal ideation in all groups, Dr. Wagner said. "Remember, this is a very impaired group of children."

The most common side effects included drowsiness in the risperidone group, which increased from 18% at baseline to 51% at 8 weeks; frequent urination, dry mouth, and excessive thirst in the lithium group; and difficulty arousing in the morning in the valproate group. "It was not a surprise that side effects differed. What was possibly more surprising was we did not see a significant change in extrapyramidal effects," Dr. Wagner said.

The was a "pretty significant" increase in body weight in the risperidone group, a mean 3.3 kg, compared with 1.4 kg in the lithium group and 1.7 kg in the valproate group. "Remember this was an 8-week study, Dr. Wagner said.

Anyone who dropped out of the study prior to week 8 was considered a nonresponder. The discontinuation rates were 16% for the risperidone group, 32% for the lithium group, and 26% for the valproate group, for an overall rate of 25%. "This is probably what we see clinically. About 25% of children are no longer on the medication you want them to take by 8 weeks," Dr. Wagner said.

A change of mind led the reasons for discontinuation, cited by 54%. "I’d like to be more definitive about that," Dr. Wagner said. An additional 22% cited side effects, and 10% withdrew because of symptom worsening.

The drug assignment was open and known by everyone except the blinded rater at 8 weeks, a potential limitation of the study, Dr. Riddle said. The large number of participants and allowing 8 weeks for response to monotherapy were strengths of the study.

Dr. Wagner said the TEAM results are comparable with reports from other major studies in the literature. For example, the valproate response rate of 24% in TEAM was exactly the same that Dr. Wagner and her colleagues reported in a divalproex extended-release trial (J. Am. Acad. Child Adolesc. Psychiatry 2009;48:519-32). In addition, the 69% response rate with risperidone was similar to the 58% mean response rate reported among five second-generation atypical medication trials in pediatric populations (Bipolar Disord. 2010;12:116-41).

The next step for TEAM researchers is to delve more deeply into primary and secondary outcomes, Dr. Wagner said. Data analysis from additional measures such as the Children’s Depression Rating Scale–Revised (CDRS-R), the CGI-BP, and the Caregiver Strain Questionnaire (CSQ) are forthcoming.

In addition, "We need to see in the long term if these response rates will continue," Dr. Wagner said.

A second phase of TEAM involves re-randomizing partial responders to a second study medication (the add-on paradigm) or switching nonresponders to one of the other two agents as monotherapy.

Dr. Wagner said she receives honoraria from CMP Medica, Contemporary Forums, Physicians Postgraduate Press, and Quantia Communications. Dr. Riddle said he had no financial disclosures.

BOCA RATON, FLA. – Significantly more children and adolescents with bipolar disorder mania or mixed episodes responded to 8 weeks of treatment with risperidone vs. lithium or valproate in a multicenter, initial monotherapy comparison trial.

At study end, 69% treated with risperidone achieved an "improved" or "much improved" rating on the primary outcome measure, Clinical Global Impressions- –Improvement scale for Mania (CGI-IM). In contrast, 36% of participants taking lithium saw such improvement, as did 24% of the patients taking valproate.

Dr. Karen D. Wagner

"About two-thirds responded to risperidone, one-third to lithium, and about one-quarter to valproate, with no significant difference between lithium and valproate," Dr. Karen D. Wagner said at a meeting of the New Clinical Drug Evaluation Unit (NCDEU) sponsored by the National Institute of Mental Health.

The 290 children enrolled in the Treatment of Early Age Mania (TEAM) study included 93 randomized to risperidone, 93 to lithium, and 104 to valproate. A total 210 completed the 8-week acute treatment trial.

All participants had a bipolar disorder I manic or mixed state episode of 4 weeks or longer. Participants were aged 6-15 years old, making this a younger cohort than the 10-year cutoff used in other, industry-sponsored studies, Dr. Wagner said. The NIMH funds the ongoing TEAM study.

"This was a very impaired group," Dr. Mark A. Riddle said in a separate presentation at the NCDEU meeting. The mean initial onset for mania was at 5.3 years and the mean duration was 4.9 years at study entry, so "these were kids who had really early disorder and really early problems."

In addition, the mean Children’s Global Assessment Scale (CGAS) score at baseline was 39.2; the mean Clinical Global Impressions Scale for Bipolar Disorder (CGI-BP) severity-mania score was 6.0; and the mean K-SADS Mania Rating Scale (KMRS) score was 43.6.

"Childhood bipolar disorder is a chronic illness and can be very impairing at home, school, and [with] peer functioning," said Dr. Riddle, director of the division of child and adolescent psychiatry at Johns Hopkins University, Baltimore. He added that little is known about effective pharmacologic treatment. "TEAM was deemed essential so we can get some sense of children’s response to treatment, which can be different from adults."

What is the best agent to use for a child who has not been on any medications for bipolar disorder? Answering that question was the primary aim of the acute phase of the TEAM study. Led by principal investigator Dr. Barbara Geller, investigators compared the three most-common agents prescribed for mania at the time of enrollment.

"There was nothing special about selection of risperidone, other than there was the most information about use of risperidone in young children," including safety data from autism spectrum disorder populations, said Dr. Wagner, director of the child and adolescent psychiatry division at University of Texas Medical Branch at Galveston.

Most of the children had comorbidities such as attention-deficit/hyperactivity disorder, 92%, and oppositional defiant disorder, 90%. A total 70% also had an anxiety disorder, and 32% had a sleep disorder.

The agents were titrated up over 6 weeks and maintained at the maximum dose for the final 2 weeks. The mean dose/level at study end was 2.6 mg/day risperidone, 1.1 mEq/L lithium, and 114 mcg/mL valproate. "These were reasonable, upward doses," Dr. Wagner said. This strategy used was aimed at avoiding criticism that any unresponsiveness was attributable to insufficient dosing, she added.

Secondary outcome measures also supported a greater efficacy with risperidone. For example, 48% of the risperidone group achieved a CGAS score more than 60, compared with 27% of the lithium group and 17% of the valproate group. Similarly, the final KRMS score indicated that 16% of the risperidone group had mild to minimal residual symptoms, compared with 26% of the lithium group and 28% of the valproate group.

The investigators looked beyond clinical improvements. "We have to weigh side effects with efficacy," Dr. Wagner said.

"Suicidality is always a concern." Seven participants had suicidal behaviors, including two in the risperidone group, three in the lithium group, and two in the valproate group. There were no suicides during the course of study.

"Interestingly, look at suicidal ideation ... it’s in the direction we like to see this go." From baseline to assessment at 8 weeks, there was a significant decrease in suicidal ideation in all groups, Dr. Wagner said. "Remember, this is a very impaired group of children."

The most common side effects included drowsiness in the risperidone group, which increased from 18% at baseline to 51% at 8 weeks; frequent urination, dry mouth, and excessive thirst in the lithium group; and difficulty arousing in the morning in the valproate group. "It was not a surprise that side effects differed. What was possibly more surprising was we did not see a significant change in extrapyramidal effects," Dr. Wagner said.

The was a "pretty significant" increase in body weight in the risperidone group, a mean 3.3 kg, compared with 1.4 kg in the lithium group and 1.7 kg in the valproate group. "Remember this was an 8-week study, Dr. Wagner said.

Anyone who dropped out of the study prior to week 8 was considered a nonresponder. The discontinuation rates were 16% for the risperidone group, 32% for the lithium group, and 26% for the valproate group, for an overall rate of 25%. "This is probably what we see clinically. About 25% of children are no longer on the medication you want them to take by 8 weeks," Dr. Wagner said.

A change of mind led the reasons for discontinuation, cited by 54%. "I’d like to be more definitive about that," Dr. Wagner said. An additional 22% cited side effects, and 10% withdrew because of symptom worsening.

The drug assignment was open and known by everyone except the blinded rater at 8 weeks, a potential limitation of the study, Dr. Riddle said. The large number of participants and allowing 8 weeks for response to monotherapy were strengths of the study.

Dr. Wagner said the TEAM results are comparable with reports from other major studies in the literature. For example, the valproate response rate of 24% in TEAM was exactly the same that Dr. Wagner and her colleagues reported in a divalproex extended-release trial (J. Am. Acad. Child Adolesc. Psychiatry 2009;48:519-32). In addition, the 69% response rate with risperidone was similar to the 58% mean response rate reported among five second-generation atypical medication trials in pediatric populations (Bipolar Disord. 2010;12:116-41).

The next step for TEAM researchers is to delve more deeply into primary and secondary outcomes, Dr. Wagner said. Data analysis from additional measures such as the Children’s Depression Rating Scale–Revised (CDRS-R), the CGI-BP, and the Caregiver Strain Questionnaire (CSQ) are forthcoming.

In addition, "We need to see in the long term if these response rates will continue," Dr. Wagner said.

A second phase of TEAM involves re-randomizing partial responders to a second study medication (the add-on paradigm) or switching nonresponders to one of the other two agents as monotherapy.

Dr. Wagner said she receives honoraria from CMP Medica, Contemporary Forums, Physicians Postgraduate Press, and Quantia Communications. Dr. Riddle said he had no financial disclosures.

DENVER – Although some studies show a delay in growth among boys taking stimulants for attention-deficit/hyperactivity disorder, a new study appears to clear the medications of postponing pubertal onset.

"Given that growth has been associated with pubertal onset, one might hypothesize that stimulant medication might affect the onset of puberty," Jennifer M. Steffes said at the annual meeting of the Pediatric Academic Societies. "Few data exist, however, as to the potential association."

Ms. Steffes and her colleagues studied a multiethnic cohort of 3,868 boys who were seen at 141 clinical practices in the SSCIB (Secondary Sexual Characteristics in Boys) study. In all, 277 (7%) were taking stimulant medication. Clinicians received standardized training and evaluated genital development, pubic hair growth, and testicular volume for these boys (aged 6-16 years).

There were no significant differences between medicated and nonmedicated participants. Mean onset of genital growth (Tanner stage II) in the stimulant group was 9.84 years vs. 9.85 years in the nonstimulant group. Mean onset of pubic hair (Tanner stage II) in the stimulant group was 11.49 years vs. 11.14 years, and testicular volume of 3 mL or greater was observed in the stimulant group at a median 10.11 years, compared with 9.80 years among those who were not taking stimulant medication.

"Our results suggest that there is no difference in age of pubertal onset between boys taking stimulant medication and their nonmedicated counterparts," Ms. Steffes said.

"For clinicians, our research should be used as reassurance to parents – should stimulant medication be recommended – that the use of these stimulants will not delay pubertal maturation," said Ms. Steffes, an investigator for the PROS (Pediatric Research in Office Settings) research network at the American Academy of Pediatrics.

In addition, there were no significant differences in age of pubertal onset by race or ethnicity. The study included 1,979 white, 963 black, and 926 Hispanic children. Consecutive children and adolescents who were seen for well-child visits in 2005-2010 in 41 states were recruited through practices that participated in PROS, the Academic Pediatric Association’s CORNET (Continuity Research Network), and the NMA PedsNet (National Medical Association’s Pediatric Research Network).

Participants in the stimulant cohort took the medications regularly for 3 consecutive months within the past year. Testicular volume measurements were standardized via a modified Prader orchidometer.

Rigorous clinician training, use of the orchidometer, and inclusion of a broadly-representative geographic sample of children are among the strengths of the study, Ms. Steffes said. Limitations include its cross-sectional design; she noted that a randomized sample and/or longitudinal study design might have been more rigorous. Also, stimulant use was reported from multiple sources (chart review and self- or parent-report).

A meeting attendee asked about the science behind the evidence pointing to delayed growth with stimulant medications. Ms. Steffes deferred to a study coauthor in the audience.

"There [are some] data for a number of psychoactive medications possibly altering growth hormone release," Dr. Steven A. Dowshen said. "The problem with the studies is ... there really is inconsistency in terms of effects [of stimulants] on linear growth, although those [children] who show it tend to show a slowing of linear growth. The commonly accepted end point, though, is that eventually those kids catch up.

"That brings up the possibility, certainly to an endocrinologist, that the effects on growth might be mediated by delayed puberty. So in essence, the drug might be creating a constitutional growth delay," added Dr. Dowshen, a private practice pediatric endocrinologist in Wilmington, Del. "One of the reasons we were interested in looking at the data from PROS was to [to test] that hypothesis. And that wasn’t the case."

Ms. Steffes disclosed that she received a research grant from Pfizer to fund this project.

DENVER – Although some studies show a delay in growth among boys taking stimulants for attention-deficit/hyperactivity disorder, a new study appears to clear the medications of postponing pubertal onset.

"Given that growth has been associated with pubertal onset, one might hypothesize that stimulant medication might affect the onset of puberty," Jennifer M. Steffes said at the annual meeting of the Pediatric Academic Societies. "Few data exist, however, as to the potential association."

Ms. Steffes and her colleagues studied a multiethnic cohort of 3,868 boys who were seen at 141 clinical practices in the SSCIB (Secondary Sexual Characteristics in Boys) study. In all, 277 (7%) were taking stimulant medication. Clinicians received standardized training and evaluated genital development, pubic hair growth, and testicular volume for these boys (aged 6-16 years).

There were no significant differences between medicated and nonmedicated participants. Mean onset of genital growth (Tanner stage II) in the stimulant group was 9.84 years vs. 9.85 years in the nonstimulant group. Mean onset of pubic hair (Tanner stage II) in the stimulant group was 11.49 years vs. 11.14 years, and testicular volume of 3 mL or greater was observed in the stimulant group at a median 10.11 years, compared with 9.80 years among those who were not taking stimulant medication.

"Our results suggest that there is no difference in age of pubertal onset between boys taking stimulant medication and their nonmedicated counterparts," Ms. Steffes said.

"For clinicians, our research should be used as reassurance to parents – should stimulant medication be recommended – that the use of these stimulants will not delay pubertal maturation," said Ms. Steffes, an investigator for the PROS (Pediatric Research in Office Settings) research network at the American Academy of Pediatrics.

In addition, there were no significant differences in age of pubertal onset by race or ethnicity. The study included 1,979 white, 963 black, and 926 Hispanic children. Consecutive children and adolescents who were seen for well-child visits in 2005-2010 in 41 states were recruited through practices that participated in PROS, the Academic Pediatric Association’s CORNET (Continuity Research Network), and the NMA PedsNet (National Medical Association’s Pediatric Research Network).

Participants in the stimulant cohort took the medications regularly for 3 consecutive months within the past year. Testicular volume measurements were standardized via a modified Prader orchidometer.

Rigorous clinician training, use of the orchidometer, and inclusion of a broadly-representative geographic sample of children are among the strengths of the study, Ms. Steffes said. Limitations include its cross-sectional design; she noted that a randomized sample and/or longitudinal study design might have been more rigorous. Also, stimulant use was reported from multiple sources (chart review and self- or parent-report).

A meeting attendee asked about the science behind the evidence pointing to delayed growth with stimulant medications. Ms. Steffes deferred to a study coauthor in the audience.

"There [are some] data for a number of psychoactive medications possibly altering growth hormone release," Dr. Steven A. Dowshen said. "The problem with the studies is ... there really is inconsistency in terms of effects [of stimulants] on linear growth, although those [children] who show it tend to show a slowing of linear growth. The commonly accepted end point, though, is that eventually those kids catch up.

"That brings up the possibility, certainly to an endocrinologist, that the effects on growth might be mediated by delayed puberty. So in essence, the drug might be creating a constitutional growth delay," added Dr. Dowshen, a private practice pediatric endocrinologist in Wilmington, Del. "One of the reasons we were interested in looking at the data from PROS was to [to test] that hypothesis. And that wasn’t the case."

Ms. Steffes disclosed that she received a research grant from Pfizer to fund this project.

DENVER – Although some studies show a delay in growth among boys taking stimulants for attention-deficit/hyperactivity disorder, a new study appears to clear the medications of postponing pubertal onset.

"Given that growth has been associated with pubertal onset, one might hypothesize that stimulant medication might affect the onset of puberty," Jennifer M. Steffes said at the annual meeting of the Pediatric Academic Societies. "Few data exist, however, as to the potential association."

Ms. Steffes and her colleagues studied a multiethnic cohort of 3,868 boys who were seen at 141 clinical practices in the SSCIB (Secondary Sexual Characteristics in Boys) study. In all, 277 (7%) were taking stimulant medication. Clinicians received standardized training and evaluated genital development, pubic hair growth, and testicular volume for these boys (aged 6-16 years).

There were no significant differences between medicated and nonmedicated participants. Mean onset of genital growth (Tanner stage II) in the stimulant group was 9.84 years vs. 9.85 years in the nonstimulant group. Mean onset of pubic hair (Tanner stage II) in the stimulant group was 11.49 years vs. 11.14 years, and testicular volume of 3 mL or greater was observed in the stimulant group at a median 10.11 years, compared with 9.80 years among those who were not taking stimulant medication.

"Our results suggest that there is no difference in age of pubertal onset between boys taking stimulant medication and their nonmedicated counterparts," Ms. Steffes said.

"For clinicians, our research should be used as reassurance to parents – should stimulant medication be recommended – that the use of these stimulants will not delay pubertal maturation," said Ms. Steffes, an investigator for the PROS (Pediatric Research in Office Settings) research network at the American Academy of Pediatrics.

In addition, there were no significant differences in age of pubertal onset by race or ethnicity. The study included 1,979 white, 963 black, and 926 Hispanic children. Consecutive children and adolescents who were seen for well-child visits in 2005-2010 in 41 states were recruited through practices that participated in PROS, the Academic Pediatric Association’s CORNET (Continuity Research Network), and the NMA PedsNet (National Medical Association’s Pediatric Research Network).

Participants in the stimulant cohort took the medications regularly for 3 consecutive months within the past year. Testicular volume measurements were standardized via a modified Prader orchidometer.

Rigorous clinician training, use of the orchidometer, and inclusion of a broadly-representative geographic sample of children are among the strengths of the study, Ms. Steffes said. Limitations include its cross-sectional design; she noted that a randomized sample and/or longitudinal study design might have been more rigorous. Also, stimulant use was reported from multiple sources (chart review and self- or parent-report).

A meeting attendee asked about the science behind the evidence pointing to delayed growth with stimulant medications. Ms. Steffes deferred to a study coauthor in the audience.

"There [are some] data for a number of psychoactive medications possibly altering growth hormone release," Dr. Steven A. Dowshen said. "The problem with the studies is ... there really is inconsistency in terms of effects [of stimulants] on linear growth, although those [children] who show it tend to show a slowing of linear growth. The commonly accepted end point, though, is that eventually those kids catch up.

"That brings up the possibility, certainly to an endocrinologist, that the effects on growth might be mediated by delayed puberty. So in essence, the drug might be creating a constitutional growth delay," added Dr. Dowshen, a private practice pediatric endocrinologist in Wilmington, Del. "One of the reasons we were interested in looking at the data from PROS was to [to test] that hypothesis. And that wasn’t the case."

Ms. Steffes disclosed that she received a research grant from Pfizer to fund this project.