Nancy Walsh

NEW YORK — Insomnia is a real and pressing concern for children with attention-deficit hyperactivity disorder and their families, Judith A. Owens, M.D., said at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.

“At least 60% of the kids in our ADHD clinic have significant problems with sleep that really impact their quality of life,” said Dr. Owens of the department of pediatrics at Brown University, and director of the pediatric sleep disorders clinic, Hasbro Children's Hospital, Providence, R.I.

The problem is multifaceted and bidirectional. Insufficient or fragmented sleep can lead to excessive daytime sleepiness, which in turn can result in ADHD-like symptoms. The medications, such as psychostimulants used to control ADHD themselves, can affect sleep onset and continuity. Methylphenidate, for example, has been shown to delay sleep onset by 30 minutes, Dr. Owens said.

Other psychotropic medications can affect sleep architecture, altering percentages of rapid eye movement (REM) and slow wave sleep, and can interfere with the neurochemicals responsible for regulation of sleep and wakefulness.

Comorbid conditions may further complicate the situation, with bedtime resistance seen in oppositional defiant disorder, insomnia and early awakening in depression, and night waking in anxiety disorders.

A subset of children with ADHD may have a primary sleep dysfunction involving homeostatic dysregulation, she said.

“But no sleep medications are approved for use in the pediatric population, which some of us have been trying to change,” she said. This has proved difficult, at least in part because of the perception that insomnia in ADHD children is largely a parent-driven complaint. “It has been very difficult to convince the Food and Drug Administration that there is a need for these,” Dr. Owens said.

The lack of approved drugs leaves clinicians relying on drugs that are less than effective and those that may have problematic side effects and questionable long-term safety.

Preliminary data from a recent survey of 1,271 practicing members of the American Academy of Child and Adolescent Psychiatry suggest that 51% use insomnia medications in more than half of their ADHD patients, she said.

On the list of drugs used, clonidine (Catapres) topped the list, with 86%, followed by antihistamines, at 67%.

The central α₂-agonist clonidine has various effects on sleep architecture, including slowing sleep-onset latency, increasing slow-wave sleep, and decreasing REM sleep, she said. Its side effects include hypotension, bradycardia, anticholinergic effects, and dysphoria. It can interact with CNS depressants and stimulants, and tolerance often develops.

“I don't have a lot of arguments to suggest that other things are much better, but I do think there are some problems with this drug,” Dr. Owens said. Interestingly, recent reports have identified a 10-fold increase in overdoses seen in emergency rooms, she said.

Antihistamines generally are viewed as benign by parents and physicians, and they are used quite often in cases when sleep-onset latency problems are less severe. “But they're not terribly effective,” she said.

Trazodone (Desyrel) is also used, though it tends to cause morning hangover. Benzodiazepines are little used in children, nor are zolpidem (Ambien) and zaleplon (Sonata), although the latter appear to be safe and well tolerated in adults and have little effect on sleep architecture.

“We worry about sleep architecture in children because if slow-wave sleep is suppressed, it can alter their production of growth hormone,” she said.

Melatonin is being evaluated as a possible sleep aid for children, but much more information is needed before this dietary supplement can be recommended.

NEW YORK — Insomnia is a real and pressing concern for children with attention-deficit hyperactivity disorder and their families, Judith A. Owens, M.D., said at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.

“At least 60% of the kids in our ADHD clinic have significant problems with sleep that really impact their quality of life,” said Dr. Owens of the department of pediatrics at Brown University, and director of the pediatric sleep disorders clinic, Hasbro Children's Hospital, Providence, R.I.

The problem is multifaceted and bidirectional. Insufficient or fragmented sleep can lead to excessive daytime sleepiness, which in turn can result in ADHD-like symptoms. The medications, such as psychostimulants used to control ADHD themselves, can affect sleep onset and continuity. Methylphenidate, for example, has been shown to delay sleep onset by 30 minutes, Dr. Owens said.

Other psychotropic medications can affect sleep architecture, altering percentages of rapid eye movement (REM) and slow wave sleep, and can interfere with the neurochemicals responsible for regulation of sleep and wakefulness.

Comorbid conditions may further complicate the situation, with bedtime resistance seen in oppositional defiant disorder, insomnia and early awakening in depression, and night waking in anxiety disorders.

A subset of children with ADHD may have a primary sleep dysfunction involving homeostatic dysregulation, she said.

“But no sleep medications are approved for use in the pediatric population, which some of us have been trying to change,” she said. This has proved difficult, at least in part because of the perception that insomnia in ADHD children is largely a parent-driven complaint. “It has been very difficult to convince the Food and Drug Administration that there is a need for these,” Dr. Owens said.

The lack of approved drugs leaves clinicians relying on drugs that are less than effective and those that may have problematic side effects and questionable long-term safety.

Preliminary data from a recent survey of 1,271 practicing members of the American Academy of Child and Adolescent Psychiatry suggest that 51% use insomnia medications in more than half of their ADHD patients, she said.

On the list of drugs used, clonidine (Catapres) topped the list, with 86%, followed by antihistamines, at 67%.

The central α₂-agonist clonidine has various effects on sleep architecture, including slowing sleep-onset latency, increasing slow-wave sleep, and decreasing REM sleep, she said. Its side effects include hypotension, bradycardia, anticholinergic effects, and dysphoria. It can interact with CNS depressants and stimulants, and tolerance often develops.

“I don't have a lot of arguments to suggest that other things are much better, but I do think there are some problems with this drug,” Dr. Owens said. Interestingly, recent reports have identified a 10-fold increase in overdoses seen in emergency rooms, she said.

Antihistamines generally are viewed as benign by parents and physicians, and they are used quite often in cases when sleep-onset latency problems are less severe. “But they're not terribly effective,” she said.

Trazodone (Desyrel) is also used, though it tends to cause morning hangover. Benzodiazepines are little used in children, nor are zolpidem (Ambien) and zaleplon (Sonata), although the latter appear to be safe and well tolerated in adults and have little effect on sleep architecture.

“We worry about sleep architecture in children because if slow-wave sleep is suppressed, it can alter their production of growth hormone,” she said.

Melatonin is being evaluated as a possible sleep aid for children, but much more information is needed before this dietary supplement can be recommended.

NEW YORK — Insomnia is a real and pressing concern for children with attention-deficit hyperactivity disorder and their families, Judith A. Owens, M.D., said at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.

“At least 60% of the kids in our ADHD clinic have significant problems with sleep that really impact their quality of life,” said Dr. Owens of the department of pediatrics at Brown University, and director of the pediatric sleep disorders clinic, Hasbro Children's Hospital, Providence, R.I.

The problem is multifaceted and bidirectional. Insufficient or fragmented sleep can lead to excessive daytime sleepiness, which in turn can result in ADHD-like symptoms. The medications, such as psychostimulants used to control ADHD themselves, can affect sleep onset and continuity. Methylphenidate, for example, has been shown to delay sleep onset by 30 minutes, Dr. Owens said.

Other psychotropic medications can affect sleep architecture, altering percentages of rapid eye movement (REM) and slow wave sleep, and can interfere with the neurochemicals responsible for regulation of sleep and wakefulness.

Comorbid conditions may further complicate the situation, with bedtime resistance seen in oppositional defiant disorder, insomnia and early awakening in depression, and night waking in anxiety disorders.

A subset of children with ADHD may have a primary sleep dysfunction involving homeostatic dysregulation, she said.

“But no sleep medications are approved for use in the pediatric population, which some of us have been trying to change,” she said. This has proved difficult, at least in part because of the perception that insomnia in ADHD children is largely a parent-driven complaint. “It has been very difficult to convince the Food and Drug Administration that there is a need for these,” Dr. Owens said.

The lack of approved drugs leaves clinicians relying on drugs that are less than effective and those that may have problematic side effects and questionable long-term safety.

Preliminary data from a recent survey of 1,271 practicing members of the American Academy of Child and Adolescent Psychiatry suggest that 51% use insomnia medications in more than half of their ADHD patients, she said.

On the list of drugs used, clonidine (Catapres) topped the list, with 86%, followed by antihistamines, at 67%.

The central α₂-agonist clonidine has various effects on sleep architecture, including slowing sleep-onset latency, increasing slow-wave sleep, and decreasing REM sleep, she said. Its side effects include hypotension, bradycardia, anticholinergic effects, and dysphoria. It can interact with CNS depressants and stimulants, and tolerance often develops.

“I don't have a lot of arguments to suggest that other things are much better, but I do think there are some problems with this drug,” Dr. Owens said. Interestingly, recent reports have identified a 10-fold increase in overdoses seen in emergency rooms, she said.

Antihistamines generally are viewed as benign by parents and physicians, and they are used quite often in cases when sleep-onset latency problems are less severe. “But they're not terribly effective,” she said.

Trazodone (Desyrel) is also used, though it tends to cause morning hangover. Benzodiazepines are little used in children, nor are zolpidem (Ambien) and zaleplon (Sonata), although the latter appear to be safe and well tolerated in adults and have little effect on sleep architecture.

“We worry about sleep architecture in children because if slow-wave sleep is suppressed, it can alter their production of growth hormone,” she said.

Melatonin is being evaluated as a possible sleep aid for children, but much more information is needed before this dietary supplement can be recommended.

NEW YORK — Now that all antidepressants carry a black box warning regarding pediatric suicidality, physicians who treat children with depression need to institute closer monitoring and pay careful attention to informed consent, Bruce Waslick, M.D., said at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.

In response to analyses identifying an increased risk of suicide during the early weeks of antidepressant treatment, the Food and Drug Administration recommends that children and adolescents be actively monitored for worsening of depression, response to treatment, and emergence of suicidality.

“I am not trying to dissuade you from using antidepressants,” said Dr. Waslick of the division of child psychiatry at Columbia University, New York.

The importance of pharmacotherapy was highlighted by findings from the Treatment for Adolescents With Depression Study (TADS), which showed that cognitive-behavioral therapy plus fluoxetine was superior to either modality alone. (See box.)

“You will need to make a risk-benefit calculation and try to give patients and parents some understanding about the safety concerns. Try to give them a rational view of the available evidence and take their preferences into account,” he said.

“Based on my experience with TADS and from an objective reading of the literature, I do think antidepressants have a role in the treatment of kids with depression,” Dr. Waslick said.

The FDA's black box decision followed a year of controversy and media attention that left fluoxetine the sole antidepressant with a pediatric indication for major depressive disorders. That decision, in turn, has left clinicians without clear guidance on several issues, such as what to do if an adequate trial of fluoxetine is unsuccessful.

There also are no clear guidelines on medicolegal issues and physician liability, but closer monitoring during the initial phase of treatment is key. According to the FDA, patients should be seen weekly for the first 4 weeks, biweekly for the next 4 weeks, and then monthly or as clinical need dictates.

Informed consent is very important. “I don't know if it will protect you regarding liability issues, but I think it's the right thing to do,” he said.

Besides the black box warning, the FDA plans to send letters to parents. “I've seen a draft of the letter, and it emphasizes the risks and doesn't talk too much about the benefits,” Dr. Waslick said. “This is black box plus.”

After the initial reports of potential suicidality associated with paroxetine (Paxil), the FDA requested that all manufacturers of selective serotonin reuptake inhibitors and atypical antidepressants go through their data to find suicide-related events in both active treatment and placebo patients. Companies were asked to prepare vignettes about these events, detailing the circumstances and outcome, so that FDA officials might determine whether they were indeed drug related and see if there was some way of assessing risk.

The initial analysis of these data, done by chief FDA scientist Andrew Mosholder, M.D., found 109 “possibly suicide-related” events in 4,100 subjects. Twice as many events were reported in patients taking the active drug than in those taking placebo.

In February 2004, a public hearing was held on antidepressant safety but Dr. Mosholder was not permitted to present his data. When word of the FDA's action was leaked to the media, a firestorm resulted, with charges that dangers were being suppressed, leading to congressional investigations.

The FDA's position was that the initial analysis was unreliable and that investigations were ongoing. In an attempt to have the data analyzed in a blinded fashion, FDA officials contracted with a group of independent suicide experts from Columbia University to undertake a more definitive analysis.

The Columbia panel analyzed the suicide events in two ways: when reported as an adverse event/serious adverse event, and according to scores on suicide items on depression questionnaires.

Presenting its findings in September 2004, the panel concluded that there was what Dr. Waslick called a “low-magnitude, low-frequency suicide [ideation or behavior] signal” in the adverse events/serious adverse events data set. However, evaluation of the systematically collected rating scale scores found no evidence of a suicide signal, he said.

Despite that discrepancy, the FDA concluded that no antidepressant is completely risk free and determined that all the drugs—even the older tricyclics and MAO inhibitors—would carry the black box warning.

“I have been using these drugs for 15 years and always assumed any suicidality was a result of the underlying disease,” Dr. Waslick said. “But the FDA has concluded that this adverse event signal is evidence that a relationship exists between antidepressant treatment and emergent suicidality,” he said.

Nonetheless, adolescent suicide rates have been falling in the past decade. “Widespread use of antidepressants doesn't seem to be leading to an epidemic of completed suicides. Whether the falling suicide rate is actually related to the benefits of antidepressant medication—and there's some supportive evidence suggesting that might be the case—we don't know yet. Keep following this story,” he said.

Fluoxetine and CBT Are Teamed Up

The Treatment for Adolescents With Depression Study (TADS) was a multicenter, randomized trial comparing treatment with fluoxetine alone, cognitive-behavioral therapy (CBT) alone, the two combined, and placebo. In the initial 12-week phase of the trial, the response rate for patients in the combination group was 71%, and for the fluoxetine alone group it was 61% (JAMA 2004;292:807-20).

The 43% response rate in the CBT alone group did not differ significantly from the placebo response rate of 35%, said Dr. Waslick, who was an investigator for the trial.

Longer-term data from TADS have yet to be analyzed, but the emerging message is that the combination of medication and CBT is best. This finding was particularly important for the most severely ill patients in the study, who clearly needed medication to get better, he said.

The trial was funded by the National Institute of Mental Health and has a degree of credibility not necessarily shared by all industry-funded trials, which typically have been done under the condition of pediatric exclusivity.

This incentive provides drug companies with a 6-month extension on their patent if they undertake studies of the agent in pediatric populations, but they are under no obligation to publish their findings. Examination of industry-generated data on antidepressants—some of which came out only under the Freedom of Information Act—has found that, aside from fluoxetine, the evidence of their efficacy in children is “underwhelming,” Dr. Waslick said.

NEW YORK — Now that all antidepressants carry a black box warning regarding pediatric suicidality, physicians who treat children with depression need to institute closer monitoring and pay careful attention to informed consent, Bruce Waslick, M.D., said at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.

In response to analyses identifying an increased risk of suicide during the early weeks of antidepressant treatment, the Food and Drug Administration recommends that children and adolescents be actively monitored for worsening of depression, response to treatment, and emergence of suicidality.

“I am not trying to dissuade you from using antidepressants,” said Dr. Waslick of the division of child psychiatry at Columbia University, New York.

The importance of pharmacotherapy was highlighted by findings from the Treatment for Adolescents With Depression Study (TADS), which showed that cognitive-behavioral therapy plus fluoxetine was superior to either modality alone. (See box.)

“You will need to make a risk-benefit calculation and try to give patients and parents some understanding about the safety concerns. Try to give them a rational view of the available evidence and take their preferences into account,” he said.

“Based on my experience with TADS and from an objective reading of the literature, I do think antidepressants have a role in the treatment of kids with depression,” Dr. Waslick said.

The FDA's black box decision followed a year of controversy and media attention that left fluoxetine the sole antidepressant with a pediatric indication for major depressive disorders. That decision, in turn, has left clinicians without clear guidance on several issues, such as what to do if an adequate trial of fluoxetine is unsuccessful.

There also are no clear guidelines on medicolegal issues and physician liability, but closer monitoring during the initial phase of treatment is key. According to the FDA, patients should be seen weekly for the first 4 weeks, biweekly for the next 4 weeks, and then monthly or as clinical need dictates.

Informed consent is very important. “I don't know if it will protect you regarding liability issues, but I think it's the right thing to do,” he said.

Besides the black box warning, the FDA plans to send letters to parents. “I've seen a draft of the letter, and it emphasizes the risks and doesn't talk too much about the benefits,” Dr. Waslick said. “This is black box plus.”

After the initial reports of potential suicidality associated with paroxetine (Paxil), the FDA requested that all manufacturers of selective serotonin reuptake inhibitors and atypical antidepressants go through their data to find suicide-related events in both active treatment and placebo patients. Companies were asked to prepare vignettes about these events, detailing the circumstances and outcome, so that FDA officials might determine whether they were indeed drug related and see if there was some way of assessing risk.

The initial analysis of these data, done by chief FDA scientist Andrew Mosholder, M.D., found 109 “possibly suicide-related” events in 4,100 subjects. Twice as many events were reported in patients taking the active drug than in those taking placebo.

In February 2004, a public hearing was held on antidepressant safety but Dr. Mosholder was not permitted to present his data. When word of the FDA's action was leaked to the media, a firestorm resulted, with charges that dangers were being suppressed, leading to congressional investigations.

The FDA's position was that the initial analysis was unreliable and that investigations were ongoing. In an attempt to have the data analyzed in a blinded fashion, FDA officials contracted with a group of independent suicide experts from Columbia University to undertake a more definitive analysis.

The Columbia panel analyzed the suicide events in two ways: when reported as an adverse event/serious adverse event, and according to scores on suicide items on depression questionnaires.

Presenting its findings in September 2004, the panel concluded that there was what Dr. Waslick called a “low-magnitude, low-frequency suicide [ideation or behavior] signal” in the adverse events/serious adverse events data set. However, evaluation of the systematically collected rating scale scores found no evidence of a suicide signal, he said.

Despite that discrepancy, the FDA concluded that no antidepressant is completely risk free and determined that all the drugs—even the older tricyclics and MAO inhibitors—would carry the black box warning.

“I have been using these drugs for 15 years and always assumed any suicidality was a result of the underlying disease,” Dr. Waslick said. “But the FDA has concluded that this adverse event signal is evidence that a relationship exists between antidepressant treatment and emergent suicidality,” he said.

Nonetheless, adolescent suicide rates have been falling in the past decade. “Widespread use of antidepressants doesn't seem to be leading to an epidemic of completed suicides. Whether the falling suicide rate is actually related to the benefits of antidepressant medication—and there's some supportive evidence suggesting that might be the case—we don't know yet. Keep following this story,” he said.

Fluoxetine and CBT Are Teamed Up

The Treatment for Adolescents With Depression Study (TADS) was a multicenter, randomized trial comparing treatment with fluoxetine alone, cognitive-behavioral therapy (CBT) alone, the two combined, and placebo. In the initial 12-week phase of the trial, the response rate for patients in the combination group was 71%, and for the fluoxetine alone group it was 61% (JAMA 2004;292:807-20).

The 43% response rate in the CBT alone group did not differ significantly from the placebo response rate of 35%, said Dr. Waslick, who was an investigator for the trial.

Longer-term data from TADS have yet to be analyzed, but the emerging message is that the combination of medication and CBT is best. This finding was particularly important for the most severely ill patients in the study, who clearly needed medication to get better, he said.

The trial was funded by the National Institute of Mental Health and has a degree of credibility not necessarily shared by all industry-funded trials, which typically have been done under the condition of pediatric exclusivity.

This incentive provides drug companies with a 6-month extension on their patent if they undertake studies of the agent in pediatric populations, but they are under no obligation to publish their findings. Examination of industry-generated data on antidepressants—some of which came out only under the Freedom of Information Act—has found that, aside from fluoxetine, the evidence of their efficacy in children is “underwhelming,” Dr. Waslick said.

NEW YORK — Now that all antidepressants carry a black box warning regarding pediatric suicidality, physicians who treat children with depression need to institute closer monitoring and pay careful attention to informed consent, Bruce Waslick, M.D., said at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.

In response to analyses identifying an increased risk of suicide during the early weeks of antidepressant treatment, the Food and Drug Administration recommends that children and adolescents be actively monitored for worsening of depression, response to treatment, and emergence of suicidality.

“I am not trying to dissuade you from using antidepressants,” said Dr. Waslick of the division of child psychiatry at Columbia University, New York.

The importance of pharmacotherapy was highlighted by findings from the Treatment for Adolescents With Depression Study (TADS), which showed that cognitive-behavioral therapy plus fluoxetine was superior to either modality alone. (See box.)

“You will need to make a risk-benefit calculation and try to give patients and parents some understanding about the safety concerns. Try to give them a rational view of the available evidence and take their preferences into account,” he said.

“Based on my experience with TADS and from an objective reading of the literature, I do think antidepressants have a role in the treatment of kids with depression,” Dr. Waslick said.

The FDA's black box decision followed a year of controversy and media attention that left fluoxetine the sole antidepressant with a pediatric indication for major depressive disorders. That decision, in turn, has left clinicians without clear guidance on several issues, such as what to do if an adequate trial of fluoxetine is unsuccessful.

There also are no clear guidelines on medicolegal issues and physician liability, but closer monitoring during the initial phase of treatment is key. According to the FDA, patients should be seen weekly for the first 4 weeks, biweekly for the next 4 weeks, and then monthly or as clinical need dictates.

Informed consent is very important. “I don't know if it will protect you regarding liability issues, but I think it's the right thing to do,” he said.

Besides the black box warning, the FDA plans to send letters to parents. “I've seen a draft of the letter, and it emphasizes the risks and doesn't talk too much about the benefits,” Dr. Waslick said. “This is black box plus.”

After the initial reports of potential suicidality associated with paroxetine (Paxil), the FDA requested that all manufacturers of selective serotonin reuptake inhibitors and atypical antidepressants go through their data to find suicide-related events in both active treatment and placebo patients. Companies were asked to prepare vignettes about these events, detailing the circumstances and outcome, so that FDA officials might determine whether they were indeed drug related and see if there was some way of assessing risk.

The initial analysis of these data, done by chief FDA scientist Andrew Mosholder, M.D., found 109 “possibly suicide-related” events in 4,100 subjects. Twice as many events were reported in patients taking the active drug than in those taking placebo.

In February 2004, a public hearing was held on antidepressant safety but Dr. Mosholder was not permitted to present his data. When word of the FDA's action was leaked to the media, a firestorm resulted, with charges that dangers were being suppressed, leading to congressional investigations.

The FDA's position was that the initial analysis was unreliable and that investigations were ongoing. In an attempt to have the data analyzed in a blinded fashion, FDA officials contracted with a group of independent suicide experts from Columbia University to undertake a more definitive analysis.

The Columbia panel analyzed the suicide events in two ways: when reported as an adverse event/serious adverse event, and according to scores on suicide items on depression questionnaires.

Presenting its findings in September 2004, the panel concluded that there was what Dr. Waslick called a “low-magnitude, low-frequency suicide [ideation or behavior] signal” in the adverse events/serious adverse events data set. However, evaluation of the systematically collected rating scale scores found no evidence of a suicide signal, he said.

Despite that discrepancy, the FDA concluded that no antidepressant is completely risk free and determined that all the drugs—even the older tricyclics and MAO inhibitors—would carry the black box warning.

“I have been using these drugs for 15 years and always assumed any suicidality was a result of the underlying disease,” Dr. Waslick said. “But the FDA has concluded that this adverse event signal is evidence that a relationship exists between antidepressant treatment and emergent suicidality,” he said.

Nonetheless, adolescent suicide rates have been falling in the past decade. “Widespread use of antidepressants doesn't seem to be leading to an epidemic of completed suicides. Whether the falling suicide rate is actually related to the benefits of antidepressant medication—and there's some supportive evidence suggesting that might be the case—we don't know yet. Keep following this story,” he said.

Fluoxetine and CBT Are Teamed Up

The Treatment for Adolescents With Depression Study (TADS) was a multicenter, randomized trial comparing treatment with fluoxetine alone, cognitive-behavioral therapy (CBT) alone, the two combined, and placebo. In the initial 12-week phase of the trial, the response rate for patients in the combination group was 71%, and for the fluoxetine alone group it was 61% (JAMA 2004;292:807-20).

The 43% response rate in the CBT alone group did not differ significantly from the placebo response rate of 35%, said Dr. Waslick, who was an investigator for the trial.

Longer-term data from TADS have yet to be analyzed, but the emerging message is that the combination of medication and CBT is best. This finding was particularly important for the most severely ill patients in the study, who clearly needed medication to get better, he said.

The trial was funded by the National Institute of Mental Health and has a degree of credibility not necessarily shared by all industry-funded trials, which typically have been done under the condition of pediatric exclusivity.

This incentive provides drug companies with a 6-month extension on their patent if they undertake studies of the agent in pediatric populations, but they are under no obligation to publish their findings. Examination of industry-generated data on antidepressants—some of which came out only under the Freedom of Information Act—has found that, aside from fluoxetine, the evidence of their efficacy in children is “underwhelming,” Dr. Waslick said.

NEW YORK — The glucose-lowering effects of the investigational agent exenatide were maintained for 80 weeks in an open-label extension study, Daniel J. Drucker, M.D., reported at a conference sponsored by the American Diabetes Association.

The reduction in hemoglobin A_1c (HbA_1c) remained at about 1%, which was initially seen in a 30-week randomized, blinded study. This reduction was accompanied by a mean weight loss of 10 pounds, said Dr. Drucker, director of the Banting and Best Diabetes Centre, University of Toronto.

Exenatide, the synthetic form of exendin-4, is the first of a new class of antidiabetic drugs known as incretin mimetics. Incretins are gut peptides that are secreted in response to nutrient ingestion, stimulating the secretion of insulin, inhibiting the secretion of glucagon, slowing gastric emptying, and reducing food intake. Mimicking their actions is aimed at restoring β-cell function, Dr. Drucker explained.

Exenatide is a potent agonist for glucagon-like peptide-1 (GLP-1). It is derived from the saliva of Heloderma suspectum, the Gila monster.

A total of 963 patients with type 2 diabetes that could not be controlled with metformin and/or a sulfonylurea drug participated in the open-label study, Dr. Drucker said.

The 1% decrease in HbA_1c seen with twice daily injections of exenatide is “fairly reasonable,” but “by no means can you say it normalizes blood glucose. It's another useful drug but type 2 diabetes is still a difficult disease to treat,” he said.

“So why would anybody want to inject themselves twice a day with a substance derived from the saliva of a lizard? Because of the 10-pound weight loss,” Dr. Drucker explained.

And despite the fact that 44% of patients in the placebo-controlled phase of the study complained of nausea, the dropout rate was quite low, he said.

Another observation that has emerged from the long-term study is that antibodies to the peptide do develop, but their presence does not appear to correlate with the magnitude of HbA_1c reduction.

The drug also has pronounced effects on postprandial glucose. “Those of you who are following the debate about postprandial glucose and cardiovascular risk know that most of our drugs don't do a very good job at controlling this,” he said. Recent reports have suggested that postprandial “hyperglycemic spikes” seen in diabetic patients may contribute to the onset of cardiovascular complications (Diabetes 2005;54:1-7).

Dr. Drucker disclosed that he is a board member of and consultant for Amylin Pharmaceuticals Inc., which has partnered with Eli Lilly & Co. to develop exenatide.

NEW YORK — The glucose-lowering effects of the investigational agent exenatide were maintained for 80 weeks in an open-label extension study, Daniel J. Drucker, M.D., reported at a conference sponsored by the American Diabetes Association.

The reduction in hemoglobin A_1c (HbA_1c) remained at about 1%, which was initially seen in a 30-week randomized, blinded study. This reduction was accompanied by a mean weight loss of 10 pounds, said Dr. Drucker, director of the Banting and Best Diabetes Centre, University of Toronto.

Exenatide, the synthetic form of exendin-4, is the first of a new class of antidiabetic drugs known as incretin mimetics. Incretins are gut peptides that are secreted in response to nutrient ingestion, stimulating the secretion of insulin, inhibiting the secretion of glucagon, slowing gastric emptying, and reducing food intake. Mimicking their actions is aimed at restoring β-cell function, Dr. Drucker explained.

Exenatide is a potent agonist for glucagon-like peptide-1 (GLP-1). It is derived from the saliva of Heloderma suspectum, the Gila monster.

A total of 963 patients with type 2 diabetes that could not be controlled with metformin and/or a sulfonylurea drug participated in the open-label study, Dr. Drucker said.

The 1% decrease in HbA_1c seen with twice daily injections of exenatide is “fairly reasonable,” but “by no means can you say it normalizes blood glucose. It's another useful drug but type 2 diabetes is still a difficult disease to treat,” he said.

“So why would anybody want to inject themselves twice a day with a substance derived from the saliva of a lizard? Because of the 10-pound weight loss,” Dr. Drucker explained.

And despite the fact that 44% of patients in the placebo-controlled phase of the study complained of nausea, the dropout rate was quite low, he said.

Another observation that has emerged from the long-term study is that antibodies to the peptide do develop, but their presence does not appear to correlate with the magnitude of HbA_1c reduction.

The drug also has pronounced effects on postprandial glucose. “Those of you who are following the debate about postprandial glucose and cardiovascular risk know that most of our drugs don't do a very good job at controlling this,” he said. Recent reports have suggested that postprandial “hyperglycemic spikes” seen in diabetic patients may contribute to the onset of cardiovascular complications (Diabetes 2005;54:1-7).

Dr. Drucker disclosed that he is a board member of and consultant for Amylin Pharmaceuticals Inc., which has partnered with Eli Lilly & Co. to develop exenatide.

NEW YORK — The glucose-lowering effects of the investigational agent exenatide were maintained for 80 weeks in an open-label extension study, Daniel J. Drucker, M.D., reported at a conference sponsored by the American Diabetes Association.

The reduction in hemoglobin A_1c (HbA_1c) remained at about 1%, which was initially seen in a 30-week randomized, blinded study. This reduction was accompanied by a mean weight loss of 10 pounds, said Dr. Drucker, director of the Banting and Best Diabetes Centre, University of Toronto.

Exenatide, the synthetic form of exendin-4, is the first of a new class of antidiabetic drugs known as incretin mimetics. Incretins are gut peptides that are secreted in response to nutrient ingestion, stimulating the secretion of insulin, inhibiting the secretion of glucagon, slowing gastric emptying, and reducing food intake. Mimicking their actions is aimed at restoring β-cell function, Dr. Drucker explained.

Exenatide is a potent agonist for glucagon-like peptide-1 (GLP-1). It is derived from the saliva of Heloderma suspectum, the Gila monster.

A total of 963 patients with type 2 diabetes that could not be controlled with metformin and/or a sulfonylurea drug participated in the open-label study, Dr. Drucker said.

The 1% decrease in HbA_1c seen with twice daily injections of exenatide is “fairly reasonable,” but “by no means can you say it normalizes blood glucose. It's another useful drug but type 2 diabetes is still a difficult disease to treat,” he said.

“So why would anybody want to inject themselves twice a day with a substance derived from the saliva of a lizard? Because of the 10-pound weight loss,” Dr. Drucker explained.

And despite the fact that 44% of patients in the placebo-controlled phase of the study complained of nausea, the dropout rate was quite low, he said.

Another observation that has emerged from the long-term study is that antibodies to the peptide do develop, but their presence does not appear to correlate with the magnitude of HbA_1c reduction.

The drug also has pronounced effects on postprandial glucose. “Those of you who are following the debate about postprandial glucose and cardiovascular risk know that most of our drugs don't do a very good job at controlling this,” he said. Recent reports have suggested that postprandial “hyperglycemic spikes” seen in diabetic patients may contribute to the onset of cardiovascular complications (Diabetes 2005;54:1-7).

Dr. Drucker disclosed that he is a board member of and consultant for Amylin Pharmaceuticals Inc., which has partnered with Eli Lilly & Co. to develop exenatide.

NEW YORK — The pronounced weight loss experienced by obese patients following gastric bypass surgery is almost always accompanied by a rapid resolution of diabetes, David E. Cummings, M.D., said.

Restoration of normoglycemia in these patients cannot be explained by weight loss alone. Of the 84% whose diabetes remits, more than half have stopped their diabetes medications by the time they leave the hospital after their 2- to 3-day stay for the bypass. Most of the rest will remit over the next few days or weeks, Dr. Cummings said at a conference sponsored by the American Diabetes Association.

“That seems too fast to be explained by weight loss alone,” said Dr. Cummings of the division of metabolism, endocrinology, and nutrition at the University of Washington, Seattle.

No doubt the gastric restriction plays a significant role; patients experience early satiety and consume smaller meals. But they do not compensate by eating more frequent meals or more nutrient-dense foods, as would be expected if energy homeostasis were the only driving factor, he said.

In 2002, Dr. Cummings and his colleagues proposed that impairment of the secretion of ghrelin, an enteric peptide hormone that stimulates appetite, might be responsible for the profound appetite loss and changes in eating behavior exhibited by patients after bypass surgery (N. Engl. J. Med. 2002;346:1623-30).

Because bypass surgery permanently isolates the ghrelin-secreting areas of the stomach and intestine from exposure to food, it stands to reason that levels of the peptide will remain depressed following the procedure, Dr. Cummings said. The result is that appetite remains suppressed.

Ghrelin not only influences food intake, but also exerts diabetogenic effects, including the suppression of insulin levels and actions. Impaired glucose tolerance is almost completely eliminated in patients who undergo gastric bypass, he said.

Moreover, the weight loss over time is associated with increases in adiponectin levels. This hormone increases insulin sensitivity, increases expression of the muscle insulin receptor, and decreases intramuscular lipids and the fatty acyl-coenzyme A molecules that can cause insulin resistance, he explained.

NEW YORK — The pronounced weight loss experienced by obese patients following gastric bypass surgery is almost always accompanied by a rapid resolution of diabetes, David E. Cummings, M.D., said.

Restoration of normoglycemia in these patients cannot be explained by weight loss alone. Of the 84% whose diabetes remits, more than half have stopped their diabetes medications by the time they leave the hospital after their 2- to 3-day stay for the bypass. Most of the rest will remit over the next few days or weeks, Dr. Cummings said at a conference sponsored by the American Diabetes Association.

“That seems too fast to be explained by weight loss alone,” said Dr. Cummings of the division of metabolism, endocrinology, and nutrition at the University of Washington, Seattle.

No doubt the gastric restriction plays a significant role; patients experience early satiety and consume smaller meals. But they do not compensate by eating more frequent meals or more nutrient-dense foods, as would be expected if energy homeostasis were the only driving factor, he said.

In 2002, Dr. Cummings and his colleagues proposed that impairment of the secretion of ghrelin, an enteric peptide hormone that stimulates appetite, might be responsible for the profound appetite loss and changes in eating behavior exhibited by patients after bypass surgery (N. Engl. J. Med. 2002;346:1623-30).

Because bypass surgery permanently isolates the ghrelin-secreting areas of the stomach and intestine from exposure to food, it stands to reason that levels of the peptide will remain depressed following the procedure, Dr. Cummings said. The result is that appetite remains suppressed.

Ghrelin not only influences food intake, but also exerts diabetogenic effects, including the suppression of insulin levels and actions. Impaired glucose tolerance is almost completely eliminated in patients who undergo gastric bypass, he said.

Moreover, the weight loss over time is associated with increases in adiponectin levels. This hormone increases insulin sensitivity, increases expression of the muscle insulin receptor, and decreases intramuscular lipids and the fatty acyl-coenzyme A molecules that can cause insulin resistance, he explained.

NEW YORK — The pronounced weight loss experienced by obese patients following gastric bypass surgery is almost always accompanied by a rapid resolution of diabetes, David E. Cummings, M.D., said.

Restoration of normoglycemia in these patients cannot be explained by weight loss alone. Of the 84% whose diabetes remits, more than half have stopped their diabetes medications by the time they leave the hospital after their 2- to 3-day stay for the bypass. Most of the rest will remit over the next few days or weeks, Dr. Cummings said at a conference sponsored by the American Diabetes Association.

“That seems too fast to be explained by weight loss alone,” said Dr. Cummings of the division of metabolism, endocrinology, and nutrition at the University of Washington, Seattle.

No doubt the gastric restriction plays a significant role; patients experience early satiety and consume smaller meals. But they do not compensate by eating more frequent meals or more nutrient-dense foods, as would be expected if energy homeostasis were the only driving factor, he said.

In 2002, Dr. Cummings and his colleagues proposed that impairment of the secretion of ghrelin, an enteric peptide hormone that stimulates appetite, might be responsible for the profound appetite loss and changes in eating behavior exhibited by patients after bypass surgery (N. Engl. J. Med. 2002;346:1623-30).

Because bypass surgery permanently isolates the ghrelin-secreting areas of the stomach and intestine from exposure to food, it stands to reason that levels of the peptide will remain depressed following the procedure, Dr. Cummings said. The result is that appetite remains suppressed.

Ghrelin not only influences food intake, but also exerts diabetogenic effects, including the suppression of insulin levels and actions. Impaired glucose tolerance is almost completely eliminated in patients who undergo gastric bypass, he said.

Moreover, the weight loss over time is associated with increases in adiponectin levels. This hormone increases insulin sensitivity, increases expression of the muscle insulin receptor, and decreases intramuscular lipids and the fatty acyl-coenzyme A molecules that can cause insulin resistance, he explained.

LONDON — Women with lupus face an elevated risk of having cervical dysplasia, but the underlying cause of such pathology is still unclear, Michelle T. McHenry, M.B., said at the sixth European Lupus Meeting.

Unlike the situation for healthy women, there appeared to be no association between cervical dysplasia and other traditional risk factors, such as a history of sexually transmitted disease, in a cohort of 221 women who had systemic lupus erythematosus (SLE). The women were identified through hospital records and the Northern Ireland pathology database.

Among this entire cohort, 74 (33%) had a lifetime history of having had at least one abnormal cervical smear, Dr. McHenry reported.

Of those, 45% had had more than one abnormal smear and 26% had had a high-grade abnormality, she said.

From the entire cohort, 141 patients agreed to participate in a study that involved answering a risk factor questionnaire and providing a current cervical smear.

Adequate smears were obtained from 133 patients.

Low-grade abnormalities were found on 22 (17%) of these smears, which is twice the expected incidence, according to the Northern Ireland department of health statistics. High-grade abnormalities were identified on six (5%), which is three times the expected incidence, said Dr. McHenry, a rheumatologist at Queen's University Musculoskeletal Education and Research Unit, Belfast.

The abnormality was detected after the time of diagnosis of lupus in 63% of patients.

“Patients with SLE are at increased risk of cervical cancer but the reasons why are unclear, whether it is related to having the disease itself, to having active disease, [or] to the treatments we administer, or if traditional cervical cancer risk factors have a part to play,” Dr. McHenry said.

“When we assessed these patients for traditional cervical cancer risk factors, we found they were more likely to have had more sexual partners and more children,” she said at the meeting, which was sponsored by the British Society for Rheumatology.

There also was an increased risk of having a cervical smear abnormality among patients who had more active disease as reflected by the Systemic Lupus Activity Measure (SLAM) score, she said.

Other risk factors, including age at first sexual contact and history of ever having used oral contraceptives, were not associated with increased risk of cervical dysplasia.

“And surprisingly, there was no association between abnormal cervical smear history and tobacco smoking,” she said. (See chart.)

Although a correlation was seen between high disease activity scores and history of cervical smear abnormality, there was no correlation with lupus damage scores or duration of disease.

Exposure to corticosteroids and immunosuppressive agents also did not differ between patients with normal cervical smear histories and those with abnormalities, she said.

Further analyses will consider cumulative immunosuppressive doses and will compare human papillomavirus DNA findings between lupus patients and controls, she said.

LONDON — Women with lupus face an elevated risk of having cervical dysplasia, but the underlying cause of such pathology is still unclear, Michelle T. McHenry, M.B., said at the sixth European Lupus Meeting.

Unlike the situation for healthy women, there appeared to be no association between cervical dysplasia and other traditional risk factors, such as a history of sexually transmitted disease, in a cohort of 221 women who had systemic lupus erythematosus (SLE). The women were identified through hospital records and the Northern Ireland pathology database.

Among this entire cohort, 74 (33%) had a lifetime history of having had at least one abnormal cervical smear, Dr. McHenry reported.

Of those, 45% had had more than one abnormal smear and 26% had had a high-grade abnormality, she said.

From the entire cohort, 141 patients agreed to participate in a study that involved answering a risk factor questionnaire and providing a current cervical smear.

Adequate smears were obtained from 133 patients.

Low-grade abnormalities were found on 22 (17%) of these smears, which is twice the expected incidence, according to the Northern Ireland department of health statistics. High-grade abnormalities were identified on six (5%), which is three times the expected incidence, said Dr. McHenry, a rheumatologist at Queen's University Musculoskeletal Education and Research Unit, Belfast.

The abnormality was detected after the time of diagnosis of lupus in 63% of patients.

“Patients with SLE are at increased risk of cervical cancer but the reasons why are unclear, whether it is related to having the disease itself, to having active disease, [or] to the treatments we administer, or if traditional cervical cancer risk factors have a part to play,” Dr. McHenry said.

“When we assessed these patients for traditional cervical cancer risk factors, we found they were more likely to have had more sexual partners and more children,” she said at the meeting, which was sponsored by the British Society for Rheumatology.

There also was an increased risk of having a cervical smear abnormality among patients who had more active disease as reflected by the Systemic Lupus Activity Measure (SLAM) score, she said.

Other risk factors, including age at first sexual contact and history of ever having used oral contraceptives, were not associated with increased risk of cervical dysplasia.

“And surprisingly, there was no association between abnormal cervical smear history and tobacco smoking,” she said. (See chart.)

Although a correlation was seen between high disease activity scores and history of cervical smear abnormality, there was no correlation with lupus damage scores or duration of disease.

Exposure to corticosteroids and immunosuppressive agents also did not differ between patients with normal cervical smear histories and those with abnormalities, she said.

Further analyses will consider cumulative immunosuppressive doses and will compare human papillomavirus DNA findings between lupus patients and controls, she said.

LONDON — Women with lupus face an elevated risk of having cervical dysplasia, but the underlying cause of such pathology is still unclear, Michelle T. McHenry, M.B., said at the sixth European Lupus Meeting.

Unlike the situation for healthy women, there appeared to be no association between cervical dysplasia and other traditional risk factors, such as a history of sexually transmitted disease, in a cohort of 221 women who had systemic lupus erythematosus (SLE). The women were identified through hospital records and the Northern Ireland pathology database.

Among this entire cohort, 74 (33%) had a lifetime history of having had at least one abnormal cervical smear, Dr. McHenry reported.

Of those, 45% had had more than one abnormal smear and 26% had had a high-grade abnormality, she said.

From the entire cohort, 141 patients agreed to participate in a study that involved answering a risk factor questionnaire and providing a current cervical smear.

Adequate smears were obtained from 133 patients.

Low-grade abnormalities were found on 22 (17%) of these smears, which is twice the expected incidence, according to the Northern Ireland department of health statistics. High-grade abnormalities were identified on six (5%), which is three times the expected incidence, said Dr. McHenry, a rheumatologist at Queen's University Musculoskeletal Education and Research Unit, Belfast.

The abnormality was detected after the time of diagnosis of lupus in 63% of patients.

“Patients with SLE are at increased risk of cervical cancer but the reasons why are unclear, whether it is related to having the disease itself, to having active disease, [or] to the treatments we administer, or if traditional cervical cancer risk factors have a part to play,” Dr. McHenry said.

“When we assessed these patients for traditional cervical cancer risk factors, we found they were more likely to have had more sexual partners and more children,” she said at the meeting, which was sponsored by the British Society for Rheumatology.

There also was an increased risk of having a cervical smear abnormality among patients who had more active disease as reflected by the Systemic Lupus Activity Measure (SLAM) score, she said.

Other risk factors, including age at first sexual contact and history of ever having used oral contraceptives, were not associated with increased risk of cervical dysplasia.

“And surprisingly, there was no association between abnormal cervical smear history and tobacco smoking,” she said. (See chart.)

Although a correlation was seen between high disease activity scores and history of cervical smear abnormality, there was no correlation with lupus damage scores or duration of disease.

Exposure to corticosteroids and immunosuppressive agents also did not differ between patients with normal cervical smear histories and those with abnormalities, she said.

Further analyses will consider cumulative immunosuppressive doses and will compare human papillomavirus DNA findings between lupus patients and controls, she said.

EXETER, ENGLAND — A standardized ear acupuncture protocol effectively reduced hot flashes in women receiving tamoxifen as adjuvant treatment for breast cancer, according to an interim analysis presented at a symposium on alternative and complementary therapies sponsored by the universities of Exeter and Plymouth.

The National Acupuncture and Detoxification Association (NADA) protocol has been used for 30 years to treat withdrawal symptoms in substance abusers, most famously at the Lincoln Medical and Mental Health Center in New York City's South Bronx, Beverley de Valois said.

Ms. de Valois, a Ph.D. candidate at Thames Valley University, London, and a research acupuncturist at the Lynda Jackson Macmillan Centre at Mount Vernon Hospital, Northwood, had previously done a study of traditional acupuncture for women experiencing adverse effects during tamoxifen treatment. “The results were encouraging, but the methodology is complex and time consuming, and our goal at the center is to make treatment for tamoxifen-related side effects widely and easily available.”

There also were some difficulties in administering traditional acupuncture. Needling the limb on the affected side is discouraged because of fears that this might lead to lymphedema, she said. This restriction was particularly problematic for women who had had bilateral mastectomies.

She had previously worked with the NADA protocol, and because some of the side effects of tamoxifen—night sweats, anxiety, and sleep difficulties—resemble those of withdrawal, she thought this might be useful for these patients as well.

A total of 50 women were recruited for the study. They had to be taking tamoxifen for at least 6 months and having four or more vasomotor incidents per day. The treatment involved eight acupuncture sessions, five patients at a time, during a 29-week period. Participants recorded the frequency and severity of hot flashes in diaries and were asked how they subjectively rated the treatment.

There was no control group, and any placebo effect was not addressed.

An interim analysis of the first 35 patients showed a reduction in frequency from a mean of 10.32 flashes per day at baseline to 7.24 at the end of treatment, a statistically significant mean reduction of 24.4%, Ms. de Valois said. Sleep also improved as nocturnal hot flashes decreased.

Participants gave high marks to receiving the treatment in groups, where they met others with similar problems and were able to share experiences.

EXETER, ENGLAND — A standardized ear acupuncture protocol effectively reduced hot flashes in women receiving tamoxifen as adjuvant treatment for breast cancer, according to an interim analysis presented at a symposium on alternative and complementary therapies sponsored by the universities of Exeter and Plymouth.

The National Acupuncture and Detoxification Association (NADA) protocol has been used for 30 years to treat withdrawal symptoms in substance abusers, most famously at the Lincoln Medical and Mental Health Center in New York City's South Bronx, Beverley de Valois said.

Ms. de Valois, a Ph.D. candidate at Thames Valley University, London, and a research acupuncturist at the Lynda Jackson Macmillan Centre at Mount Vernon Hospital, Northwood, had previously done a study of traditional acupuncture for women experiencing adverse effects during tamoxifen treatment. “The results were encouraging, but the methodology is complex and time consuming, and our goal at the center is to make treatment for tamoxifen-related side effects widely and easily available.”

There also were some difficulties in administering traditional acupuncture. Needling the limb on the affected side is discouraged because of fears that this might lead to lymphedema, she said. This restriction was particularly problematic for women who had had bilateral mastectomies.

She had previously worked with the NADA protocol, and because some of the side effects of tamoxifen—night sweats, anxiety, and sleep difficulties—resemble those of withdrawal, she thought this might be useful for these patients as well.

A total of 50 women were recruited for the study. They had to be taking tamoxifen for at least 6 months and having four or more vasomotor incidents per day. The treatment involved eight acupuncture sessions, five patients at a time, during a 29-week period. Participants recorded the frequency and severity of hot flashes in diaries and were asked how they subjectively rated the treatment.

There was no control group, and any placebo effect was not addressed.

An interim analysis of the first 35 patients showed a reduction in frequency from a mean of 10.32 flashes per day at baseline to 7.24 at the end of treatment, a statistically significant mean reduction of 24.4%, Ms. de Valois said. Sleep also improved as nocturnal hot flashes decreased.

Participants gave high marks to receiving the treatment in groups, where they met others with similar problems and were able to share experiences.

EXETER, ENGLAND — A standardized ear acupuncture protocol effectively reduced hot flashes in women receiving tamoxifen as adjuvant treatment for breast cancer, according to an interim analysis presented at a symposium on alternative and complementary therapies sponsored by the universities of Exeter and Plymouth.

The National Acupuncture and Detoxification Association (NADA) protocol has been used for 30 years to treat withdrawal symptoms in substance abusers, most famously at the Lincoln Medical and Mental Health Center in New York City's South Bronx, Beverley de Valois said.

Ms. de Valois, a Ph.D. candidate at Thames Valley University, London, and a research acupuncturist at the Lynda Jackson Macmillan Centre at Mount Vernon Hospital, Northwood, had previously done a study of traditional acupuncture for women experiencing adverse effects during tamoxifen treatment. “The results were encouraging, but the methodology is complex and time consuming, and our goal at the center is to make treatment for tamoxifen-related side effects widely and easily available.”

There also were some difficulties in administering traditional acupuncture. Needling the limb on the affected side is discouraged because of fears that this might lead to lymphedema, she said. This restriction was particularly problematic for women who had had bilateral mastectomies.

She had previously worked with the NADA protocol, and because some of the side effects of tamoxifen—night sweats, anxiety, and sleep difficulties—resemble those of withdrawal, she thought this might be useful for these patients as well.

A total of 50 women were recruited for the study. They had to be taking tamoxifen for at least 6 months and having four or more vasomotor incidents per day. The treatment involved eight acupuncture sessions, five patients at a time, during a 29-week period. Participants recorded the frequency and severity of hot flashes in diaries and were asked how they subjectively rated the treatment.

There was no control group, and any placebo effect was not addressed.

An interim analysis of the first 35 patients showed a reduction in frequency from a mean of 10.32 flashes per day at baseline to 7.24 at the end of treatment, a statistically significant mean reduction of 24.4%, Ms. de Valois said. Sleep also improved as nocturnal hot flashes decreased.

Participants gave high marks to receiving the treatment in groups, where they met others with similar problems and were able to share experiences.