Nancy Walsh

NEW YORK – Now that all antidepressants carry a black box warning regarding pediatric suicidality, physicians who treat children and adolescents 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,” Dr. Waslick 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.”

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 proved to be 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 in an effort 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 whether 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 University 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. 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, Dr. Waslick 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.

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

Nonetheless, adolescent suicide rates have been falling over the last decade. “Widespread use of antidepressants does not seem to be leading to an epidemic of completed suicides,” he said. “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.”

Lessons From TADS

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.”

NEW YORK – Now that all antidepressants carry a black box warning regarding pediatric suicidality, physicians who treat children and adolescents 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,” Dr. Waslick 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.”

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 proved to be 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 in an effort 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 whether 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 University 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. 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, Dr. Waslick 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.

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

Nonetheless, adolescent suicide rates have been falling over the last decade. “Widespread use of antidepressants does not seem to be leading to an epidemic of completed suicides,” he said. “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.”

Lessons From TADS

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.”

NEW YORK – Now that all antidepressants carry a black box warning regarding pediatric suicidality, physicians who treat children and adolescents 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,” Dr. Waslick 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.”

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 proved to be 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 in an effort 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 whether 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 University 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. 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, Dr. Waslick 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.

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

Nonetheless, adolescent suicide rates have been falling over the last decade. “Widespread use of antidepressants does not seem to be leading to an epidemic of completed suicides,” he said. “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.”

Lessons From TADS

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.”

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 themselves, such as psychostimulants used to control ADHD, 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. Among the concerns with melatonin are reports that it may suppress the hypothalamic-gonadal axis. There have been case reports of its withdrawal triggering precocious puberty, Dr. Owens said.

“The most important thing is that whenever you are evaluating any child, be sure to screen for sleep problems. I never cease to be astonished that, if you don't ask the question, the parents just think it's something they have to live with and won't volunteer the information,” she said. “Do this in some simple systematic way, and you will be addressing a huge issue for families.”

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 themselves, such as psychostimulants used to control ADHD, 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. Among the concerns with melatonin are reports that it may suppress the hypothalamic-gonadal axis. There have been case reports of its withdrawal triggering precocious puberty, Dr. Owens said.

“The most important thing is that whenever you are evaluating any child, be sure to screen for sleep problems. I never cease to be astonished that, if you don't ask the question, the parents just think it's something they have to live with and won't volunteer the information,” she said. “Do this in some simple systematic way, and you will be addressing a huge issue for families.”

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 themselves, such as psychostimulants used to control ADHD, 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. Among the concerns with melatonin are reports that it may suppress the hypothalamic-gonadal axis. There have been case reports of its withdrawal triggering precocious puberty, Dr. Owens said.

“The most important thing is that whenever you are evaluating any child, be sure to screen for sleep problems. I never cease to be astonished that, if you don't ask the question, the parents just think it's something they have to live with and won't volunteer the information,” she said. “Do this in some simple systematic way, and you will be addressing a huge issue for families.”

ST. LOUIS — Beware of the patient who considers liposuction just another type of "extreme makeover," Richard L. Schloemer, M.D., said at the World Congress on Liposuction Surgery.

"You cannot stress enough that liposuction is a major operation, and that if not done right it can lead to deformity, major complications, and death," he said.

Liposuction is not for weight loss, though it can contribute to an overall weight loss plan. It's absolutely essential that patients lower their body mass index one level before surgery, and that they maintain a diet afterward, said Dr. Schloemer, a surgeon in private practice in Troy, Ala. "I recommend the 'no white diet.' If it's white, don't eat it—potatoes, bread, rice, dairy products," he said at the congress, sponsored by the American Academy of Cosmetic Surgery.

Informed consent is vital. "You can't give a person too much information, and even when you do, you'd be surprised at how little they retain," he said. For example, one of his patients ignored instructions and took a soapy whirlpool bath 4 hours post procedure, and then spent 3 days in the hospital with a soap burn.

Preventing hypothermia is another important consideration. A cold operating room, cold solutions, and sedation can contribute to severe shaking.

But never use electric heating pads, he said. That practice resulted in a third-degree burn requiring a skin graft in one of his patients. "A heating pad that may fluctuate to greater than 100° F, and a wet solution in a numb patient can be a terrible combination. You have to warm the room and the solutions even if it is uncomfortable for you," Dr. Schloemer said.

Given the availability of tumescent anesthesia and intravenous sedation, general anesthesia is simply not necessary for liposuction. It's generally advisable to keep the lidocaine dose at 50 mg/kg or below to prevent toxicity, however.

"At the end of the procedure, have the patient stand up so you can assess the effects of gravity and ensure symmetry," he said. "Finally, don't promise too much, and remember that liposuction isn't for everyone. Declining to operate often shows good judgment and gains patient respect," he said.

ST. LOUIS — Beware of the patient who considers liposuction just another type of "extreme makeover," Richard L. Schloemer, M.D., said at the World Congress on Liposuction Surgery.

"You cannot stress enough that liposuction is a major operation, and that if not done right it can lead to deformity, major complications, and death," he said.

Liposuction is not for weight loss, though it can contribute to an overall weight loss plan. It's absolutely essential that patients lower their body mass index one level before surgery, and that they maintain a diet afterward, said Dr. Schloemer, a surgeon in private practice in Troy, Ala. "I recommend the 'no white diet.' If it's white, don't eat it—potatoes, bread, rice, dairy products," he said at the congress, sponsored by the American Academy of Cosmetic Surgery.

Informed consent is vital. "You can't give a person too much information, and even when you do, you'd be surprised at how little they retain," he said. For example, one of his patients ignored instructions and took a soapy whirlpool bath 4 hours post procedure, and then spent 3 days in the hospital with a soap burn.

Preventing hypothermia is another important consideration. A cold operating room, cold solutions, and sedation can contribute to severe shaking.

But never use electric heating pads, he said. That practice resulted in a third-degree burn requiring a skin graft in one of his patients. "A heating pad that may fluctuate to greater than 100° F, and a wet solution in a numb patient can be a terrible combination. You have to warm the room and the solutions even if it is uncomfortable for you," Dr. Schloemer said.

Given the availability of tumescent anesthesia and intravenous sedation, general anesthesia is simply not necessary for liposuction. It's generally advisable to keep the lidocaine dose at 50 mg/kg or below to prevent toxicity, however.

"At the end of the procedure, have the patient stand up so you can assess the effects of gravity and ensure symmetry," he said. "Finally, don't promise too much, and remember that liposuction isn't for everyone. Declining to operate often shows good judgment and gains patient respect," he said.

ST. LOUIS — Beware of the patient who considers liposuction just another type of "extreme makeover," Richard L. Schloemer, M.D., said at the World Congress on Liposuction Surgery.

"You cannot stress enough that liposuction is a major operation, and that if not done right it can lead to deformity, major complications, and death," he said.

Liposuction is not for weight loss, though it can contribute to an overall weight loss plan. It's absolutely essential that patients lower their body mass index one level before surgery, and that they maintain a diet afterward, said Dr. Schloemer, a surgeon in private practice in Troy, Ala. "I recommend the 'no white diet.' If it's white, don't eat it—potatoes, bread, rice, dairy products," he said at the congress, sponsored by the American Academy of Cosmetic Surgery.

Informed consent is vital. "You can't give a person too much information, and even when you do, you'd be surprised at how little they retain," he said. For example, one of his patients ignored instructions and took a soapy whirlpool bath 4 hours post procedure, and then spent 3 days in the hospital with a soap burn.

Preventing hypothermia is another important consideration. A cold operating room, cold solutions, and sedation can contribute to severe shaking.

But never use electric heating pads, he said. That practice resulted in a third-degree burn requiring a skin graft in one of his patients. "A heating pad that may fluctuate to greater than 100° F, and a wet solution in a numb patient can be a terrible combination. You have to warm the room and the solutions even if it is uncomfortable for you," Dr. Schloemer said.

Given the availability of tumescent anesthesia and intravenous sedation, general anesthesia is simply not necessary for liposuction. It's generally advisable to keep the lidocaine dose at 50 mg/kg or below to prevent toxicity, however.

"At the end of the procedure, have the patient stand up so you can assess the effects of gravity and ensure symmetry," he said. "Finally, don't promise too much, and remember that liposuction isn't for everyone. Declining to operate often shows good judgment and gains patient respect," he 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,” she said.

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 the experience of receiving the treatment in groups, where they met others with similar problems and were able to share experiences and information, 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,” she said.

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 the experience of receiving the treatment in groups, where they met others with similar problems and were able to share experiences and information, 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,” she said.

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 the experience of receiving the treatment in groups, where they met others with similar problems and were able to share experiences and information, she said.

▸ Gut-directed hypnotherapy results in significant, long-term improvements in symptoms of irritable bowel syndrome.

▸ A group of clinicians in North Carolina has developed a standardized hypnotherapy protocol that physicians can obtain at no cost.

Rationale for Use

Irritable bowel syndrome (IBS) is estimated to afflict about 10%-20% of the U.S. population. In its most severe form, IBS has an impact on quality of life that rivals that of congestive heart failure or recent stroke. Treatment consists largely of advice, reassurance, and symptomatic management with antidiarrheals, antispasmodics, and laxatives–and is notoriously ineffective.

Although the precise cause of IBS remains uncertain, research has shown that a fundamental physiologic component is dysregulation of the bidirectional communication between the enteric nervous system and the brain. This brain-gut axis involves the activity of numerous neurotransmitters and related receptors, including serotonin and the 5-HT3 and 5-HT4 receptors (Med. Sci. Monit. 2004;10:RA125–31).

Moreover, many patients with the disorder also experience anxiety and other psychological symptoms along with their diarrhea, constipation, and pain, and their digestive symptoms sometimes correlate with mental and emotional states. Because of this link with psychological symptoms, researchers for the past 20 years have been investigating ways of harnessing the brain-gut axis to alleviate the condition. One of the most successful approaches has been hypnosis.

The U.K. Experience

For more than 20 years, patients with IBS referred to University Hospitals of South Manchester, England, have been treated with hypnotherapy in a program devised by gastroenterologist Peter J. Whorwell, M.D. His protocol, known as gut-directed hypnotherapy, involves hypnotic deep progressive relaxation and suggestion directed toward control of gut function. Patients are encouraged to use imagery to gain control over their gut activity. For example, a patient with diarrhea might visualize the digestive tract as a rushing river that can be slowed to a calm stream. Pain can be alleviated by applying warmth generated when the patient places a hand on his or her belly.

The Manchester protocol includes 12 sessions over a 3-month period. Patients also are given audiotapes to use at home on a daily basis.

The first small study evaluating the technique randomized 30 patients with severe, refractory IBS to hypnotherapy or psychotherapy. Both groups showed improvements in abdominal pain and distension and well-being. However, the psychotherapy group had no improvement in bowel habits, while the hypnotherapy group experienced “dramatic improvements” in all outcome measures, and no relapses were seen during 3 months of follow-up (Lancet 1984;2:1232–4). In a subsequent report, clinical improvement was maintained in all of the hypnotherapy patients for 2 years (Gut 1987;28:423–5).

The Manchester center later became the first hypnotherapy unit in the British National Health Service dedicated to IBS treatment. Investigators there have continued to follow their patients, and now have reported on long-term outcomes. Among the first 204 patients who completed a course of gut-directed hypnotherapy and responded to a subjective assessment questionnaire, 106 (52%) reported that their symptoms were “very much better” in the immediate posttreatment period, while 39 (19%) were “moderately better” and 32 (16%) were “slightly better” (Gut 2003;52:1623–9).

And the benefits persisted. Among responders who replied to the questionnaire, 81.3% reported that the initial symptomatic improvements were maintained–or even increased further–for periods up to 5 years. Extracolonic symptoms such as anxiety and depression also continued to improve.

The hypnotherapy must be gut specific, according to Dr. Whorwell. “Over the years we have found that the therapy has to be focused on the gut rather than just directed in a more general way,” he said in an interview.

The U.S. Experience

A group of therapists at the University of North Carolina at Chapel Hill has instituted a similar program with equivalent success. They also have investigated the mechanisms by which hypnosis might affect IBS symptoms. In a series of tests, they found that hypnotherapy did not alter rectal pain thresholds or smooth muscle tone, autonomic nervous system activity, or frontalis muscle EMG activity (Dig. Dis. Sci. 2002;47:2605–14). Rather, they suggested that the effects of hypnosis are mediated through reduction in somatization, “primarily by altering the patient's focus of attention and/or by changing his or her beliefs about the meaning of sensations arising from the gastrointestinal tract.”

The North Carolina clinicians also have spearheaded efforts to make hypnotherapy more widely available to patients in the United States, noting that psychological treatments are currently offered to fewer than 10% of patients with functional GI disorders seen in primary care or gastroenterology clinics. They have established a Web site with links listing hypnotherapists and other resources for patients. Clinicians can request by e-mail their protocol package, free of charge, containing verbatim scripts and other materials, at

www.ibshypnosis.com

Unanswered Questions

Aside from uncertainty about the mechanisms of effect of gut-directed hypnotherapy, questions also remain concerning whether hypnotherapy is superior to other forms of psychological therapy. Benefits have been reported with cognitive-behavioral, interpersonal, and psychodynamic therapies, but no side-by-side comparisons have been done, according to Olafur S. Palsson, Psy.D., of the North Carolina group (Gastroenterology 2002;123:2132–5). Furthermore, data are lacking on using hypnotherapy as adjunctive therapy with medications such as antidepressants and the 5-HT modulators.

▸ Gut-directed hypnotherapy results in significant, long-term improvements in symptoms of irritable bowel syndrome.

▸ A group of clinicians in North Carolina has developed a standardized hypnotherapy protocol that physicians can obtain at no cost.

Rationale for Use

Irritable bowel syndrome (IBS) is estimated to afflict about 10%-20% of the U.S. population. In its most severe form, IBS has an impact on quality of life that rivals that of congestive heart failure or recent stroke. Treatment consists largely of advice, reassurance, and symptomatic management with antidiarrheals, antispasmodics, and laxatives–and is notoriously ineffective.

Although the precise cause of IBS remains uncertain, research has shown that a fundamental physiologic component is dysregulation of the bidirectional communication between the enteric nervous system and the brain. This brain-gut axis involves the activity of numerous neurotransmitters and related receptors, including serotonin and the 5-HT3 and 5-HT4 receptors (Med. Sci. Monit. 2004;10:RA125–31).

Moreover, many patients with the disorder also experience anxiety and other psychological symptoms along with their diarrhea, constipation, and pain, and their digestive symptoms sometimes correlate with mental and emotional states. Because of this link with psychological symptoms, researchers for the past 20 years have been investigating ways of harnessing the brain-gut axis to alleviate the condition. One of the most successful approaches has been hypnosis.

The U.K. Experience

For more than 20 years, patients with IBS referred to University Hospitals of South Manchester, England, have been treated with hypnotherapy in a program devised by gastroenterologist Peter J. Whorwell, M.D. His protocol, known as gut-directed hypnotherapy, involves hypnotic deep progressive relaxation and suggestion directed toward control of gut function. Patients are encouraged to use imagery to gain control over their gut activity. For example, a patient with diarrhea might visualize the digestive tract as a rushing river that can be slowed to a calm stream. Pain can be alleviated by applying warmth generated when the patient places a hand on his or her belly.

The Manchester protocol includes 12 sessions over a 3-month period. Patients also are given audiotapes to use at home on a daily basis.

The first small study evaluating the technique randomized 30 patients with severe, refractory IBS to hypnotherapy or psychotherapy. Both groups showed improvements in abdominal pain and distension and well-being. However, the psychotherapy group had no improvement in bowel habits, while the hypnotherapy group experienced “dramatic improvements” in all outcome measures, and no relapses were seen during 3 months of follow-up (Lancet 1984;2:1232–4). In a subsequent report, clinical improvement was maintained in all of the hypnotherapy patients for 2 years (Gut 1987;28:423–5).

The Manchester center later became the first hypnotherapy unit in the British National Health Service dedicated to IBS treatment. Investigators there have continued to follow their patients, and now have reported on long-term outcomes. Among the first 204 patients who completed a course of gut-directed hypnotherapy and responded to a subjective assessment questionnaire, 106 (52%) reported that their symptoms were “very much better” in the immediate posttreatment period, while 39 (19%) were “moderately better” and 32 (16%) were “slightly better” (Gut 2003;52:1623–9).

And the benefits persisted. Among responders who replied to the questionnaire, 81.3% reported that the initial symptomatic improvements were maintained–or even increased further–for periods up to 5 years. Extracolonic symptoms such as anxiety and depression also continued to improve.

The hypnotherapy must be gut specific, according to Dr. Whorwell. “Over the years we have found that the therapy has to be focused on the gut rather than just directed in a more general way,” he said in an interview.

The U.S. Experience

A group of therapists at the University of North Carolina at Chapel Hill has instituted a similar program with equivalent success. They also have investigated the mechanisms by which hypnosis might affect IBS symptoms. In a series of tests, they found that hypnotherapy did not alter rectal pain thresholds or smooth muscle tone, autonomic nervous system activity, or frontalis muscle EMG activity (Dig. Dis. Sci. 2002;47:2605–14). Rather, they suggested that the effects of hypnosis are mediated through reduction in somatization, “primarily by altering the patient's focus of attention and/or by changing his or her beliefs about the meaning of sensations arising from the gastrointestinal tract.”

The North Carolina clinicians also have spearheaded efforts to make hypnotherapy more widely available to patients in the United States, noting that psychological treatments are currently offered to fewer than 10% of patients with functional GI disorders seen in primary care or gastroenterology clinics. They have established a Web site with links listing hypnotherapists and other resources for patients. Clinicians can request by e-mail their protocol package, free of charge, containing verbatim scripts and other materials, at

www.ibshypnosis.com

Unanswered Questions

Aside from uncertainty about the mechanisms of effect of gut-directed hypnotherapy, questions also remain concerning whether hypnotherapy is superior to other forms of psychological therapy. Benefits have been reported with cognitive-behavioral, interpersonal, and psychodynamic therapies, but no side-by-side comparisons have been done, according to Olafur S. Palsson, Psy.D., of the North Carolina group (Gastroenterology 2002;123:2132–5). Furthermore, data are lacking on using hypnotherapy as adjunctive therapy with medications such as antidepressants and the 5-HT modulators.

▸ Gut-directed hypnotherapy results in significant, long-term improvements in symptoms of irritable bowel syndrome.

▸ A group of clinicians in North Carolina has developed a standardized hypnotherapy protocol that physicians can obtain at no cost.

Rationale for Use

Irritable bowel syndrome (IBS) is estimated to afflict about 10%-20% of the U.S. population. In its most severe form, IBS has an impact on quality of life that rivals that of congestive heart failure or recent stroke. Treatment consists largely of advice, reassurance, and symptomatic management with antidiarrheals, antispasmodics, and laxatives–and is notoriously ineffective.

Although the precise cause of IBS remains uncertain, research has shown that a fundamental physiologic component is dysregulation of the bidirectional communication between the enteric nervous system and the brain. This brain-gut axis involves the activity of numerous neurotransmitters and related receptors, including serotonin and the 5-HT3 and 5-HT4 receptors (Med. Sci. Monit. 2004;10:RA125–31).

Moreover, many patients with the disorder also experience anxiety and other psychological symptoms along with their diarrhea, constipation, and pain, and their digestive symptoms sometimes correlate with mental and emotional states. Because of this link with psychological symptoms, researchers for the past 20 years have been investigating ways of harnessing the brain-gut axis to alleviate the condition. One of the most successful approaches has been hypnosis.

The U.K. Experience

For more than 20 years, patients with IBS referred to University Hospitals of South Manchester, England, have been treated with hypnotherapy in a program devised by gastroenterologist Peter J. Whorwell, M.D. His protocol, known as gut-directed hypnotherapy, involves hypnotic deep progressive relaxation and suggestion directed toward control of gut function. Patients are encouraged to use imagery to gain control over their gut activity. For example, a patient with diarrhea might visualize the digestive tract as a rushing river that can be slowed to a calm stream. Pain can be alleviated by applying warmth generated when the patient places a hand on his or her belly.

The Manchester protocol includes 12 sessions over a 3-month period. Patients also are given audiotapes to use at home on a daily basis.

The first small study evaluating the technique randomized 30 patients with severe, refractory IBS to hypnotherapy or psychotherapy. Both groups showed improvements in abdominal pain and distension and well-being. However, the psychotherapy group had no improvement in bowel habits, while the hypnotherapy group experienced “dramatic improvements” in all outcome measures, and no relapses were seen during 3 months of follow-up (Lancet 1984;2:1232–4). In a subsequent report, clinical improvement was maintained in all of the hypnotherapy patients for 2 years (Gut 1987;28:423–5).

The Manchester center later became the first hypnotherapy unit in the British National Health Service dedicated to IBS treatment. Investigators there have continued to follow their patients, and now have reported on long-term outcomes. Among the first 204 patients who completed a course of gut-directed hypnotherapy and responded to a subjective assessment questionnaire, 106 (52%) reported that their symptoms were “very much better” in the immediate posttreatment period, while 39 (19%) were “moderately better” and 32 (16%) were “slightly better” (Gut 2003;52:1623–9).

And the benefits persisted. Among responders who replied to the questionnaire, 81.3% reported that the initial symptomatic improvements were maintained–or even increased further–for periods up to 5 years. Extracolonic symptoms such as anxiety and depression also continued to improve.

The hypnotherapy must be gut specific, according to Dr. Whorwell. “Over the years we have found that the therapy has to be focused on the gut rather than just directed in a more general way,” he said in an interview.

The U.S. Experience

A group of therapists at the University of North Carolina at Chapel Hill has instituted a similar program with equivalent success. They also have investigated the mechanisms by which hypnosis might affect IBS symptoms. In a series of tests, they found that hypnotherapy did not alter rectal pain thresholds or smooth muscle tone, autonomic nervous system activity, or frontalis muscle EMG activity (Dig. Dis. Sci. 2002;47:2605–14). Rather, they suggested that the effects of hypnosis are mediated through reduction in somatization, “primarily by altering the patient's focus of attention and/or by changing his or her beliefs about the meaning of sensations arising from the gastrointestinal tract.”

The North Carolina clinicians also have spearheaded efforts to make hypnotherapy more widely available to patients in the United States, noting that psychological treatments are currently offered to fewer than 10% of patients with functional GI disorders seen in primary care or gastroenterology clinics. They have established a Web site with links listing hypnotherapists and other resources for patients. Clinicians can request by e-mail their protocol package, free of charge, containing verbatim scripts and other materials, at

www.ibshypnosis.com

Unanswered Questions

Aside from uncertainty about the mechanisms of effect of gut-directed hypnotherapy, questions also remain concerning whether hypnotherapy is superior to other forms of psychological therapy. Benefits have been reported with cognitive-behavioral, interpersonal, and psychodynamic therapies, but no side-by-side comparisons have been done, according to Olafur S. Palsson, Psy.D., of the North Carolina group (Gastroenterology 2002;123:2132–5). Furthermore, data are lacking on using hypnotherapy as adjunctive therapy with medications such as antidepressants and the 5-HT modulators.

SAN ANTONIO — The dopamine-3 receptor agonist pramipexole significantly improved pain, function, and fatigue in patients with severe, longstanding fibromyalgia, Andrew J. Holman, M.D., said in a late-breaking abstract session at the annual meeting of the American College of Rheumatology.

In a double blind, randomized, placebo controlled clinical trial that included 60 patients, pain as measured on a 10-point visual analog scale (VAS) improved by 36%, from a mean score of 7.0 at baseline to 4.5 after 14 weeks of treatment with pramipexole.

By contrast, patients receiving placebo experienced only a 9% decrease in pain, from 7.54 to 6.82. At baseline, all patients had fibromyalgia of at least 6 months' duration and a VAS pain score of at least 5.

“I wanted to make this as close to a real-world study as possible, so patients could continue other medications if they were clinically stable and maintained the same dose for 14 weeks,” said Dr. Holman, a rheumatologist in private practice in Renton, Wash.

Other drugs taken by the patients included anticonvulsants, antidepressants, anxiolytics, and muscle relaxants. Mean disease duration was 8.6 years, and patients had taken an average of 10 different medications during that time.

On study entrance, 24% of the placebo group and 31% of the pramipexole group were clinically disabled. Moreover, 67% of the placebo group and 44% of the pramipexole group were taking daily narcotics for pain relief. The pramipexole dose was titrated up to a target of 4.5 mg/day orally at bedtime. “In terms of measuring efficacy for pain, we generally look at the number of patients who achieve a greater than 50% reduction in pain,” he said. This outcome was achieved by 42% of patients in the pramipexole arm compared with 14% of those in the placebo arm.

Moderate or greater improvement on the Patients' Global Impression of Change questionnaire was reported by 63% of pramipexole-treated patients, compared with 38% of the placebo patients. Statistically significant improvements were seen on the Fibromyalgia Impact Questionnaire and the fatigue and function scores of the multidimensional Health Assessment Questionnaire.

Secondary end points that showed trends toward improvement with the active treatment include tender point scores, the Hamilton Rating Scale for Depression, and the Beck Anxiety Inventory.

“It was interesting to note that no outcomes favored placebo,” he said.

Pramipexole, used for Parkinson's disease and restless legs syndrome, is thought to inhibit excessive autonomic stimulation and arousal in the mesolimbic area of the hippocampus. It is not a sedating medication. Rather, its effects on arousal may allow normal stage IV sleep. The result is that “we're not making them sleep; we're allowing them to sleep,” Dr. Holman said.

The most pronounced side effect was weight loss, with 40% of the pramipexole group losing between 5 and 35 pounds.

Adverse events associated with pramipexole included increased anxiety, morning somnolence, diarrhea, and vomiting. The hallucinations commonly reported by Parkinson's patients did not occur in this study.

One patient experienced unexpected amnesia that lasted for about 4 hours, but there was no diagnosis and she returned to the study without incident.

SAN ANTONIO — The dopamine-3 receptor agonist pramipexole significantly improved pain, function, and fatigue in patients with severe, longstanding fibromyalgia, Andrew J. Holman, M.D., said in a late-breaking abstract session at the annual meeting of the American College of Rheumatology.

In a double blind, randomized, placebo controlled clinical trial that included 60 patients, pain as measured on a 10-point visual analog scale (VAS) improved by 36%, from a mean score of 7.0 at baseline to 4.5 after 14 weeks of treatment with pramipexole.

By contrast, patients receiving placebo experienced only a 9% decrease in pain, from 7.54 to 6.82. At baseline, all patients had fibromyalgia of at least 6 months' duration and a VAS pain score of at least 5.

“I wanted to make this as close to a real-world study as possible, so patients could continue other medications if they were clinically stable and maintained the same dose for 14 weeks,” said Dr. Holman, a rheumatologist in private practice in Renton, Wash.

Other drugs taken by the patients included anticonvulsants, antidepressants, anxiolytics, and muscle relaxants. Mean disease duration was 8.6 years, and patients had taken an average of 10 different medications during that time.

On study entrance, 24% of the placebo group and 31% of the pramipexole group were clinically disabled. Moreover, 67% of the placebo group and 44% of the pramipexole group were taking daily narcotics for pain relief. The pramipexole dose was titrated up to a target of 4.5 mg/day orally at bedtime. “In terms of measuring efficacy for pain, we generally look at the number of patients who achieve a greater than 50% reduction in pain,” he said. This outcome was achieved by 42% of patients in the pramipexole arm compared with 14% of those in the placebo arm.

Moderate or greater improvement on the Patients' Global Impression of Change questionnaire was reported by 63% of pramipexole-treated patients, compared with 38% of the placebo patients. Statistically significant improvements were seen on the Fibromyalgia Impact Questionnaire and the fatigue and function scores of the multidimensional Health Assessment Questionnaire.

Secondary end points that showed trends toward improvement with the active treatment include tender point scores, the Hamilton Rating Scale for Depression, and the Beck Anxiety Inventory.

“It was interesting to note that no outcomes favored placebo,” he said.

Pramipexole, used for Parkinson's disease and restless legs syndrome, is thought to inhibit excessive autonomic stimulation and arousal in the mesolimbic area of the hippocampus. It is not a sedating medication. Rather, its effects on arousal may allow normal stage IV sleep. The result is that “we're not making them sleep; we're allowing them to sleep,” Dr. Holman said.

The most pronounced side effect was weight loss, with 40% of the pramipexole group losing between 5 and 35 pounds.

Adverse events associated with pramipexole included increased anxiety, morning somnolence, diarrhea, and vomiting. The hallucinations commonly reported by Parkinson's patients did not occur in this study.

One patient experienced unexpected amnesia that lasted for about 4 hours, but there was no diagnosis and she returned to the study without incident.

SAN ANTONIO — The dopamine-3 receptor agonist pramipexole significantly improved pain, function, and fatigue in patients with severe, longstanding fibromyalgia, Andrew J. Holman, M.D., said in a late-breaking abstract session at the annual meeting of the American College of Rheumatology.

In a double blind, randomized, placebo controlled clinical trial that included 60 patients, pain as measured on a 10-point visual analog scale (VAS) improved by 36%, from a mean score of 7.0 at baseline to 4.5 after 14 weeks of treatment with pramipexole.

By contrast, patients receiving placebo experienced only a 9% decrease in pain, from 7.54 to 6.82. At baseline, all patients had fibromyalgia of at least 6 months' duration and a VAS pain score of at least 5.

“I wanted to make this as close to a real-world study as possible, so patients could continue other medications if they were clinically stable and maintained the same dose for 14 weeks,” said Dr. Holman, a rheumatologist in private practice in Renton, Wash.

Other drugs taken by the patients included anticonvulsants, antidepressants, anxiolytics, and muscle relaxants. Mean disease duration was 8.6 years, and patients had taken an average of 10 different medications during that time.

On study entrance, 24% of the placebo group and 31% of the pramipexole group were clinically disabled. Moreover, 67% of the placebo group and 44% of the pramipexole group were taking daily narcotics for pain relief. The pramipexole dose was titrated up to a target of 4.5 mg/day orally at bedtime. “In terms of measuring efficacy for pain, we generally look at the number of patients who achieve a greater than 50% reduction in pain,” he said. This outcome was achieved by 42% of patients in the pramipexole arm compared with 14% of those in the placebo arm.

Moderate or greater improvement on the Patients' Global Impression of Change questionnaire was reported by 63% of pramipexole-treated patients, compared with 38% of the placebo patients. Statistically significant improvements were seen on the Fibromyalgia Impact Questionnaire and the fatigue and function scores of the multidimensional Health Assessment Questionnaire.

Secondary end points that showed trends toward improvement with the active treatment include tender point scores, the Hamilton Rating Scale for Depression, and the Beck Anxiety Inventory.

“It was interesting to note that no outcomes favored placebo,” he said.

Pramipexole, used for Parkinson's disease and restless legs syndrome, is thought to inhibit excessive autonomic stimulation and arousal in the mesolimbic area of the hippocampus. It is not a sedating medication. Rather, its effects on arousal may allow normal stage IV sleep. The result is that “we're not making them sleep; we're allowing them to sleep,” Dr. Holman said.

The most pronounced side effect was weight loss, with 40% of the pramipexole group losing between 5 and 35 pounds.

Adverse events associated with pramipexole included increased anxiety, morning somnolence, diarrhea, and vomiting. The hallucinations commonly reported by Parkinson's patients did not occur in this study.

One patient experienced unexpected amnesia that lasted for about 4 hours, but there was no diagnosis and she returned to the study without incident.