Elizabeth Mechcatie

The Food and Drug Administration has issued a warning advising against the use of injectable terbutaline for preventing and for prolonged treatment of preterm labor and against any use of oral terbutaline in this setting, prompted by postmarketing reports of deaths and other serious cardiovascular events associated with the use of the drug in this setting.

"Death and serious adverse reactions, including increased heart rate, transient hyperglycemia, hypokalemia, cardiac arrhythmias, pulmonary edema, and myocardial ischemia have been reported after prolonged administration of oral or injectable terbutaline to pregnant women," according to an FDA statement issued on Feb. 17.

Based on these reports and a review of the medical literature, the agency "has concluded that the risk of serious adverse events outweighs any potential benefit to pregnant women receiving prolonged treatment with terbutaline injection (beyond 48-72 hours), or acute or prolonged treatment with oral terbutaline," the FDA said in the statement.

This is not the first FDA warning issued about the obstetrical-related risks of terbutaline, an FDA-approved treatment for bronchospasm that has been used off label to treat and prevent preterm labor and to treat uterine hyperstimulation. In 1997, the agency notified health care professionals in a letter about concerns over the safety of long-term administration of subcutaneous terbutaline and revised the drug’s labeling about the risk of serious cardiovascular adverse events associated with this use. But despite studies reporting a lack of safety and efficacy of terbutaline for the treatment of recurrent preterm labor and professional association recommendations, "prolonged use of terbutaline continues, with serious and sometimes fatal consequences," the FDA statement said.

Between 1976, when terbutaline was first marketed, and 2009, 16 maternal deaths associated with the obstetric use of terbutaline were reported to the FDA’s Adverse Event Reporting System (AERS), which included 3 in outpatients administered terbutaline via a subcutaneous pump. In 9 of the 16 cases, oral terbutaline was used alone or in combination with subcutaneous or intravenous terbutaline – including 2 cases that reported the outpatient use of oral terbutaline and 7 cases reporting inpatient use of oral terbutaline. The routes of administration for the remaining four cases were subcutaneous, intravenous, or unknown.

Between January 1998, soon after the FDA issued the warning letter, and July 2009, 12 maternal cases of serious cardiovascular events were reported to AERS, including cardiac arrhythmias, MI, pulmonary edema, hypertension, and tachycardia, associated with the use of terbutaline. Of these 12 cases, 3 were administered by a subcutaneous pump, and 5 involved oral terbutaline alone or in combination with subcutaneous terbutaline.

While there are "certain obstetrical conditions" in which health care professionals "may decide that the benefit of terbutaline injection for an individual patient in a hospital setting clearly outweighs the risk," the FDA statement said that terbutaline administered by injection or continuous infusion pump should not be used for more than 48 to 72 hours, and injectable terbutaline should not be used in outpatient settings.

These warnings are being added to a new boxed warning in terbutaline labels. The FDA says these label changes are consistent with statements from the American College of Obstetricians and Gynecologists.

Serious adverse events associated with terbutaline should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch.

The Food and Drug Administration has issued a warning advising against the use of injectable terbutaline for preventing and for prolonged treatment of preterm labor and against any use of oral terbutaline in this setting, prompted by postmarketing reports of deaths and other serious cardiovascular events associated with the use of the drug in this setting.

"Death and serious adverse reactions, including increased heart rate, transient hyperglycemia, hypokalemia, cardiac arrhythmias, pulmonary edema, and myocardial ischemia have been reported after prolonged administration of oral or injectable terbutaline to pregnant women," according to an FDA statement issued on Feb. 17.

Based on these reports and a review of the medical literature, the agency "has concluded that the risk of serious adverse events outweighs any potential benefit to pregnant women receiving prolonged treatment with terbutaline injection (beyond 48-72 hours), or acute or prolonged treatment with oral terbutaline," the FDA said in the statement.

This is not the first FDA warning issued about the obstetrical-related risks of terbutaline, an FDA-approved treatment for bronchospasm that has been used off label to treat and prevent preterm labor and to treat uterine hyperstimulation. In 1997, the agency notified health care professionals in a letter about concerns over the safety of long-term administration of subcutaneous terbutaline and revised the drug’s labeling about the risk of serious cardiovascular adverse events associated with this use. But despite studies reporting a lack of safety and efficacy of terbutaline for the treatment of recurrent preterm labor and professional association recommendations, "prolonged use of terbutaline continues, with serious and sometimes fatal consequences," the FDA statement said.

Between 1976, when terbutaline was first marketed, and 2009, 16 maternal deaths associated with the obstetric use of terbutaline were reported to the FDA’s Adverse Event Reporting System (AERS), which included 3 in outpatients administered terbutaline via a subcutaneous pump. In 9 of the 16 cases, oral terbutaline was used alone or in combination with subcutaneous or intravenous terbutaline – including 2 cases that reported the outpatient use of oral terbutaline and 7 cases reporting inpatient use of oral terbutaline. The routes of administration for the remaining four cases were subcutaneous, intravenous, or unknown.

Between January 1998, soon after the FDA issued the warning letter, and July 2009, 12 maternal cases of serious cardiovascular events were reported to AERS, including cardiac arrhythmias, MI, pulmonary edema, hypertension, and tachycardia, associated with the use of terbutaline. Of these 12 cases, 3 were administered by a subcutaneous pump, and 5 involved oral terbutaline alone or in combination with subcutaneous terbutaline.

While there are "certain obstetrical conditions" in which health care professionals "may decide that the benefit of terbutaline injection for an individual patient in a hospital setting clearly outweighs the risk," the FDA statement said that terbutaline administered by injection or continuous infusion pump should not be used for more than 48 to 72 hours, and injectable terbutaline should not be used in outpatient settings.

These warnings are being added to a new boxed warning in terbutaline labels. The FDA says these label changes are consistent with statements from the American College of Obstetricians and Gynecologists.

Serious adverse events associated with terbutaline should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch.

The Food and Drug Administration has issued a warning advising against the use of injectable terbutaline for preventing and for prolonged treatment of preterm labor and against any use of oral terbutaline in this setting, prompted by postmarketing reports of deaths and other serious cardiovascular events associated with the use of the drug in this setting.

"Death and serious adverse reactions, including increased heart rate, transient hyperglycemia, hypokalemia, cardiac arrhythmias, pulmonary edema, and myocardial ischemia have been reported after prolonged administration of oral or injectable terbutaline to pregnant women," according to an FDA statement issued on Feb. 17.

Based on these reports and a review of the medical literature, the agency "has concluded that the risk of serious adverse events outweighs any potential benefit to pregnant women receiving prolonged treatment with terbutaline injection (beyond 48-72 hours), or acute or prolonged treatment with oral terbutaline," the FDA said in the statement.

This is not the first FDA warning issued about the obstetrical-related risks of terbutaline, an FDA-approved treatment for bronchospasm that has been used off label to treat and prevent preterm labor and to treat uterine hyperstimulation. In 1997, the agency notified health care professionals in a letter about concerns over the safety of long-term administration of subcutaneous terbutaline and revised the drug’s labeling about the risk of serious cardiovascular adverse events associated with this use. But despite studies reporting a lack of safety and efficacy of terbutaline for the treatment of recurrent preterm labor and professional association recommendations, "prolonged use of terbutaline continues, with serious and sometimes fatal consequences," the FDA statement said.

Between 1976, when terbutaline was first marketed, and 2009, 16 maternal deaths associated with the obstetric use of terbutaline were reported to the FDA’s Adverse Event Reporting System (AERS), which included 3 in outpatients administered terbutaline via a subcutaneous pump. In 9 of the 16 cases, oral terbutaline was used alone or in combination with subcutaneous or intravenous terbutaline – including 2 cases that reported the outpatient use of oral terbutaline and 7 cases reporting inpatient use of oral terbutaline. The routes of administration for the remaining four cases were subcutaneous, intravenous, or unknown.

Between January 1998, soon after the FDA issued the warning letter, and July 2009, 12 maternal cases of serious cardiovascular events were reported to AERS, including cardiac arrhythmias, MI, pulmonary edema, hypertension, and tachycardia, associated with the use of terbutaline. Of these 12 cases, 3 were administered by a subcutaneous pump, and 5 involved oral terbutaline alone or in combination with subcutaneous terbutaline.

While there are "certain obstetrical conditions" in which health care professionals "may decide that the benefit of terbutaline injection for an individual patient in a hospital setting clearly outweighs the risk," the FDA statement said that terbutaline administered by injection or continuous infusion pump should not be used for more than 48 to 72 hours, and injectable terbutaline should not be used in outpatient settings.

These warnings are being added to a new boxed warning in terbutaline labels. The FDA says these label changes are consistent with statements from the American College of Obstetricians and Gynecologists.

Serious adverse events associated with terbutaline should be reported to the FDA’s MedWatch program at 800-332-1088 or www.fda.gov/medwatch.

The atypical antipsychotic aripiprazole has been approved by the Food and Drug Administration for the maintenance treatment of people with bipolar I disorder as an adjunct to lithium or valproate, the manufacturers announced Feb. 17.

Aripiprazole, marketed as Abilify by the Bristol-Myers Squibb Co. and Otsuka Pharmaceutical Co., was approved in May 2008 as an adjunct to lithium or valproate for the acute treatment of manic and mixed episodes associated with bipolar I disorder.

The approval of the expanded adjunctive indication was based on a 52-week randomized, double-blind, placebo-controlled maintenance study of adults who met the DSM-IV criteria for bipolar I disorder and who had had a recent manic or mixed episode. The subjects also had a history of one or more manic or mixed episodes that had been severe enough to require hospitalization and/or treatment with a mood stabilizer or antipsychotic. All patients started treatment with lithium or valproate; after 2 weeks, those who had an inadequate response to one of the mood stabilizers alone began treatment with aripiprazole (15 mg/day, with the option to increase the dose to 30 mg/day or reduce the dose to 10 mg/day as early as the fourth day of treatment). After being stabilized for 12 consecutive weeks, 337 patients were randomized to continue treatment with the same aripiprazole dose with lithium or valproate or were switched to placebo with lithium or valproate.

During a period of up to 52 weeks, those who remained on aripiprazole experienced fewer manic episodes compared with those on placebo (7 observed episodes vs. 19). The number of depressive episodes was similar in the two groups (14 among those on aripiprazole vs. 18 among those on placebo), according to the statement and revised label. In the study, the most common adverse event associated with adjunctive aripiprazole was tremor, affecting 6%, compared with 2.4% of those on placebo, according to the company statement.

"An examination of population subgroups did not reveal any clear evidence of differential responsiveness on the basis of age and gender," but there were not enough patients in each of the ethnic groups "to adequately assess inter-group differences," according to a statement in the revised label.

Aripiprazole, an oral dopamine partial agonist, also is approved:

• For the acute treatment of manic or mixed episodes associated with bipolar I disorder as monotherapy in adults and pediatric patients aged 10-17 years.

• As monotherapy for the maintenance treatment of bipolar I disorder in adults and adolescents aged 13-17 years.

• For the treatment of schizophrenia in adults and adolescents aged 13-17 years.

• As an adjunctive treatment for adults with major depressive disorder who have an inadequate response to antidepressant therapy.

For the treatment of irritability associated with autistic disorder in pediatric patients aged 6 to 17 years.

It initially was approved by the FDA in 2002 for the treatment of schizophrenia.

The atypical antipsychotic aripiprazole has been approved by the Food and Drug Administration for the maintenance treatment of people with bipolar I disorder as an adjunct to lithium or valproate, the manufacturers announced Feb. 17.

Aripiprazole, marketed as Abilify by the Bristol-Myers Squibb Co. and Otsuka Pharmaceutical Co., was approved in May 2008 as an adjunct to lithium or valproate for the acute treatment of manic and mixed episodes associated with bipolar I disorder.

The approval of the expanded adjunctive indication was based on a 52-week randomized, double-blind, placebo-controlled maintenance study of adults who met the DSM-IV criteria for bipolar I disorder and who had had a recent manic or mixed episode. The subjects also had a history of one or more manic or mixed episodes that had been severe enough to require hospitalization and/or treatment with a mood stabilizer or antipsychotic. All patients started treatment with lithium or valproate; after 2 weeks, those who had an inadequate response to one of the mood stabilizers alone began treatment with aripiprazole (15 mg/day, with the option to increase the dose to 30 mg/day or reduce the dose to 10 mg/day as early as the fourth day of treatment). After being stabilized for 12 consecutive weeks, 337 patients were randomized to continue treatment with the same aripiprazole dose with lithium or valproate or were switched to placebo with lithium or valproate.

During a period of up to 52 weeks, those who remained on aripiprazole experienced fewer manic episodes compared with those on placebo (7 observed episodes vs. 19). The number of depressive episodes was similar in the two groups (14 among those on aripiprazole vs. 18 among those on placebo), according to the statement and revised label. In the study, the most common adverse event associated with adjunctive aripiprazole was tremor, affecting 6%, compared with 2.4% of those on placebo, according to the company statement.

"An examination of population subgroups did not reveal any clear evidence of differential responsiveness on the basis of age and gender," but there were not enough patients in each of the ethnic groups "to adequately assess inter-group differences," according to a statement in the revised label.

Aripiprazole, an oral dopamine partial agonist, also is approved:

• For the acute treatment of manic or mixed episodes associated with bipolar I disorder as monotherapy in adults and pediatric patients aged 10-17 years.

• As monotherapy for the maintenance treatment of bipolar I disorder in adults and adolescents aged 13-17 years.

• For the treatment of schizophrenia in adults and adolescents aged 13-17 years.

• As an adjunctive treatment for adults with major depressive disorder who have an inadequate response to antidepressant therapy.

For the treatment of irritability associated with autistic disorder in pediatric patients aged 6 to 17 years.

It initially was approved by the FDA in 2002 for the treatment of schizophrenia.

The atypical antipsychotic aripiprazole has been approved by the Food and Drug Administration for the maintenance treatment of people with bipolar I disorder as an adjunct to lithium or valproate, the manufacturers announced Feb. 17.

Aripiprazole, marketed as Abilify by the Bristol-Myers Squibb Co. and Otsuka Pharmaceutical Co., was approved in May 2008 as an adjunct to lithium or valproate for the acute treatment of manic and mixed episodes associated with bipolar I disorder.

The approval of the expanded adjunctive indication was based on a 52-week randomized, double-blind, placebo-controlled maintenance study of adults who met the DSM-IV criteria for bipolar I disorder and who had had a recent manic or mixed episode. The subjects also had a history of one or more manic or mixed episodes that had been severe enough to require hospitalization and/or treatment with a mood stabilizer or antipsychotic. All patients started treatment with lithium or valproate; after 2 weeks, those who had an inadequate response to one of the mood stabilizers alone began treatment with aripiprazole (15 mg/day, with the option to increase the dose to 30 mg/day or reduce the dose to 10 mg/day as early as the fourth day of treatment). After being stabilized for 12 consecutive weeks, 337 patients were randomized to continue treatment with the same aripiprazole dose with lithium or valproate or were switched to placebo with lithium or valproate.

During a period of up to 52 weeks, those who remained on aripiprazole experienced fewer manic episodes compared with those on placebo (7 observed episodes vs. 19). The number of depressive episodes was similar in the two groups (14 among those on aripiprazole vs. 18 among those on placebo), according to the statement and revised label. In the study, the most common adverse event associated with adjunctive aripiprazole was tremor, affecting 6%, compared with 2.4% of those on placebo, according to the company statement.

"An examination of population subgroups did not reveal any clear evidence of differential responsiveness on the basis of age and gender," but there were not enough patients in each of the ethnic groups "to adequately assess inter-group differences," according to a statement in the revised label.

Aripiprazole, an oral dopamine partial agonist, also is approved:

• For the acute treatment of manic or mixed episodes associated with bipolar I disorder as monotherapy in adults and pediatric patients aged 10-17 years.

• As monotherapy for the maintenance treatment of bipolar I disorder in adults and adolescents aged 13-17 years.

• For the treatment of schizophrenia in adults and adolescents aged 13-17 years.

• As an adjunctive treatment for adults with major depressive disorder who have an inadequate response to antidepressant therapy.

For the treatment of irritability associated with autistic disorder in pediatric patients aged 6 to 17 years.

It initially was approved by the FDA in 2002 for the treatment of schizophrenia.

The atypical antipsychotic aripiprazole has been approved by the Food and Drug Administration for the maintenance treatment of people with bipolar I disorder as an adjunct to lithium or valproate, the manufacturers announced Feb. 17.

Aripiprazole, marketed as Abilify by the Bristol-Myers Squibb Co. and Otsuka Pharmaceutical Co., was approved in May 2008 as an adjunct to lithium or valproate for the acute treatment of manic and mixed episodes associated with bipolar I disorder.

The approval of the expanded adjunctive indication was based on a 52-week randomized, double-blind, placebo-controlled maintenance study of adults who met the DSM-IV criteria for bipolar I disorder and who had had a recent manic or mixed episode. The subjects also had a history of one or more manic or mixed episodes that had been severe enough to require hospitalization and/or treatment with a mood stabilizer or antipsychotic. All patients started treatment with lithium or valproate; after 2 weeks, those who had an inadequate response to one of the mood stabilizers alone began treatment with aripiprazole (15 mg/day, with the option to increase the dose to 30 mg/day or reduce the dose to 10 mg/day as early as the fourth day of treatment). After being stabilized for 12 consecutive weeks, 337 patients were randomized to continue treatment with the same aripiprazole dose with lithium or valproate or were switched to placebo with lithium or valproate.

During a period of up to 52 weeks, those who remained on aripiprazole experienced fewer manic episodes compared with those on placebo (7 observed episodes vs. 19). The number of depressive episodes was similar in the two groups (14 among those on aripiprazole vs. 18 among those on placebo), according to the statement and revised label. In the study, the most common adverse event associated with adjunctive aripiprazole was tremor, affecting 6%, compared with 2.4% of those on placebo, according to the company statement.

"An examination of population subgroups did not reveal any clear evidence of differential responsiveness on the basis of age and gender," but there were not enough patients in each of the ethnic groups "to adequately assess inter-group differences," according to a statement in the revised label.

Aripiprazole, an oral dopamine partial agonist, also is approved:

• For the acute treatment of manic or mixed episodes associated with bipolar I disorder as monotherapy in adults and pediatric patients aged 10-17 years.

• As monotherapy for the maintenance treatment of bipolar I disorder in adults and adolescents aged 13-17 years.

• For the treatment of schizophrenia in adults and adolescents aged 13-17 years.

• As an adjunctive treatment for adults with major depressive disorder who have an inadequate response to antidepressant therapy.

For the treatment of irritability associated with autistic disorder in pediatric patients aged 6 to 17 years.

It initially was approved by the FDA in 2002 for the treatment of schizophrenia.

The atypical antipsychotic aripiprazole has been approved by the Food and Drug Administration for the maintenance treatment of people with bipolar I disorder as an adjunct to lithium or valproate, the manufacturers announced Feb. 17.

Aripiprazole, marketed as Abilify by the Bristol-Myers Squibb Co. and Otsuka Pharmaceutical Co., was approved in May 2008 as an adjunct to lithium or valproate for the acute treatment of manic and mixed episodes associated with bipolar I disorder.

The approval of the expanded adjunctive indication was based on a 52-week randomized, double-blind, placebo-controlled maintenance study of adults who met the DSM-IV criteria for bipolar I disorder and who had had a recent manic or mixed episode. The subjects also had a history of one or more manic or mixed episodes that had been severe enough to require hospitalization and/or treatment with a mood stabilizer or antipsychotic. All patients started treatment with lithium or valproate; after 2 weeks, those who had an inadequate response to one of the mood stabilizers alone began treatment with aripiprazole (15 mg/day, with the option to increase the dose to 30 mg/day or reduce the dose to 10 mg/day as early as the fourth day of treatment). After being stabilized for 12 consecutive weeks, 337 patients were randomized to continue treatment with the same aripiprazole dose with lithium or valproate or were switched to placebo with lithium or valproate.

During a period of up to 52 weeks, those who remained on aripiprazole experienced fewer manic episodes compared with those on placebo (7 observed episodes vs. 19). The number of depressive episodes was similar in the two groups (14 among those on aripiprazole vs. 18 among those on placebo), according to the statement and revised label. In the study, the most common adverse event associated with adjunctive aripiprazole was tremor, affecting 6%, compared with 2.4% of those on placebo, according to the company statement.

"An examination of population subgroups did not reveal any clear evidence of differential responsiveness on the basis of age and gender," but there were not enough patients in each of the ethnic groups "to adequately assess inter-group differences," according to a statement in the revised label.

Aripiprazole, an oral dopamine partial agonist, also is approved:

• For the acute treatment of manic or mixed episodes associated with bipolar I disorder as monotherapy in adults and pediatric patients aged 10-17 years.

• As monotherapy for the maintenance treatment of bipolar I disorder in adults and adolescents aged 13-17 years.

• For the treatment of schizophrenia in adults and adolescents aged 13-17 years.

• As an adjunctive treatment for adults with major depressive disorder who have an inadequate response to antidepressant therapy.

For the treatment of irritability associated with autistic disorder in pediatric patients aged 6 to 17 years.

It initially was approved by the FDA in 2002 for the treatment of schizophrenia.

The atypical antipsychotic aripiprazole has been approved by the Food and Drug Administration for the maintenance treatment of people with bipolar I disorder as an adjunct to lithium or valproate, the manufacturers announced Feb. 17.

Aripiprazole, marketed as Abilify by the Bristol-Myers Squibb Co. and Otsuka Pharmaceutical Co., was approved in May 2008 as an adjunct to lithium or valproate for the acute treatment of manic and mixed episodes associated with bipolar I disorder.

The approval of the expanded adjunctive indication was based on a 52-week randomized, double-blind, placebo-controlled maintenance study of adults who met the DSM-IV criteria for bipolar I disorder and who had had a recent manic or mixed episode. The subjects also had a history of one or more manic or mixed episodes that had been severe enough to require hospitalization and/or treatment with a mood stabilizer or antipsychotic. All patients started treatment with lithium or valproate; after 2 weeks, those who had an inadequate response to one of the mood stabilizers alone began treatment with aripiprazole (15 mg/day, with the option to increase the dose to 30 mg/day or reduce the dose to 10 mg/day as early as the fourth day of treatment). After being stabilized for 12 consecutive weeks, 337 patients were randomized to continue treatment with the same aripiprazole dose with lithium or valproate or were switched to placebo with lithium or valproate.

During a period of up to 52 weeks, those who remained on aripiprazole experienced fewer manic episodes compared with those on placebo (7 observed episodes vs. 19). The number of depressive episodes was similar in the two groups (14 among those on aripiprazole vs. 18 among those on placebo), according to the statement and revised label. In the study, the most common adverse event associated with adjunctive aripiprazole was tremor, affecting 6%, compared with 2.4% of those on placebo, according to the company statement.

"An examination of population subgroups did not reveal any clear evidence of differential responsiveness on the basis of age and gender," but there were not enough patients in each of the ethnic groups "to adequately assess inter-group differences," according to a statement in the revised label.

Aripiprazole, an oral dopamine partial agonist, also is approved:

• For the acute treatment of manic or mixed episodes associated with bipolar I disorder as monotherapy in adults and pediatric patients aged 10-17 years.

• As monotherapy for the maintenance treatment of bipolar I disorder in adults and adolescents aged 13-17 years.

• For the treatment of schizophrenia in adults and adolescents aged 13-17 years.

• As an adjunctive treatment for adults with major depressive disorder who have an inadequate response to antidepressant therapy.

For the treatment of irritability associated with autistic disorder in pediatric patients aged 6 to 17 years.

It initially was approved by the FDA in 2002 for the treatment of schizophrenia.

The approval of the quadrivalent meningococcal conjugate vaccine manufactured by Novartis has been expanded to include children aged 2-10 years, but does not yet include infants, the company announced on Jan. 31.

The Food and Drug Administration approved the use of the vaccine for preventing invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 in children aged 2-10 years of age, according to a statement issued by Novartis. The company markets the vaccine (Meningococcal [Groups A, C, Y and W-135] Oligosaccharide Diphtheria CRM 197 Conjugate Vaccine) as Menveo. It was approved in 2010 for use in adolescents and adults aged 11-55 years.

Novartis application for approval included children down to age 2 months. But the statement said that the FDA had not included this age group in the approval because of concerns raised that the company believes are of a "procedural nature," and that the company plans to resubmit the application for approval with more clinical data on children 2 months to 2 years within a few months.

Approval for the children aged 2-10 years was based on data in a phase III study of 5,297 children in that age group comparing the safety and immunogenicity against the four serogroups contained in the vaccine with those in the other meningococcal vaccine licensed in the United States, according to Novartis. The statement said that the company has agreed to conduct postmarketing studies.

The other meningococcal conjugate vaccine approved in the United States is Menactra, manufactured by Sanofi Pasteur, which is also approved for immunizing people aged 2-55 years against invasive meningococcal disease caused by the four serogroups contained in the vaccine, the same included in Menveo.

In the European Union, where Menveo is known as Meningococcal Group A, C, W135 and Y Conjugate Vaccine, Novartis plans to submit data to support the use of the vaccine in children aged 0-10 years in the first half of 2011, according to the statement. In Canada, the application for use in children 2-10 years has been submitted.

The approval of the quadrivalent meningococcal conjugate vaccine manufactured by Novartis has been expanded to include children aged 2-10 years, but does not yet include infants, the company announced on Jan. 31.

The Food and Drug Administration approved the use of the vaccine for preventing invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 in children aged 2-10 years of age, according to a statement issued by Novartis. The company markets the vaccine (Meningococcal [Groups A, C, Y and W-135] Oligosaccharide Diphtheria CRM 197 Conjugate Vaccine) as Menveo. It was approved in 2010 for use in adolescents and adults aged 11-55 years.

Novartis application for approval included children down to age 2 months. But the statement said that the FDA had not included this age group in the approval because of concerns raised that the company believes are of a "procedural nature," and that the company plans to resubmit the application for approval with more clinical data on children 2 months to 2 years within a few months.

Approval for the children aged 2-10 years was based on data in a phase III study of 5,297 children in that age group comparing the safety and immunogenicity against the four serogroups contained in the vaccine with those in the other meningococcal vaccine licensed in the United States, according to Novartis. The statement said that the company has agreed to conduct postmarketing studies.

The other meningococcal conjugate vaccine approved in the United States is Menactra, manufactured by Sanofi Pasteur, which is also approved for immunizing people aged 2-55 years against invasive meningococcal disease caused by the four serogroups contained in the vaccine, the same included in Menveo.

In the European Union, where Menveo is known as Meningococcal Group A, C, W135 and Y Conjugate Vaccine, Novartis plans to submit data to support the use of the vaccine in children aged 0-10 years in the first half of 2011, according to the statement. In Canada, the application for use in children 2-10 years has been submitted.

The approval of the quadrivalent meningococcal conjugate vaccine manufactured by Novartis has been expanded to include children aged 2-10 years, but does not yet include infants, the company announced on Jan. 31.

The Food and Drug Administration approved the use of the vaccine for preventing invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135 in children aged 2-10 years of age, according to a statement issued by Novartis. The company markets the vaccine (Meningococcal [Groups A, C, Y and W-135] Oligosaccharide Diphtheria CRM 197 Conjugate Vaccine) as Menveo. It was approved in 2010 for use in adolescents and adults aged 11-55 years.

Novartis application for approval included children down to age 2 months. But the statement said that the FDA had not included this age group in the approval because of concerns raised that the company believes are of a "procedural nature," and that the company plans to resubmit the application for approval with more clinical data on children 2 months to 2 years within a few months.

Approval for the children aged 2-10 years was based on data in a phase III study of 5,297 children in that age group comparing the safety and immunogenicity against the four serogroups contained in the vaccine with those in the other meningococcal vaccine licensed in the United States, according to Novartis. The statement said that the company has agreed to conduct postmarketing studies.

The other meningococcal conjugate vaccine approved in the United States is Menactra, manufactured by Sanofi Pasteur, which is also approved for immunizing people aged 2-55 years against invasive meningococcal disease caused by the four serogroups contained in the vaccine, the same included in Menveo.

In the European Union, where Menveo is known as Meningococcal Group A, C, W135 and Y Conjugate Vaccine, Novartis plans to submit data to support the use of the vaccine in children aged 0-10 years in the first half of 2011, according to the statement. In Canada, the application for use in children 2-10 years has been submitted.

Rescue therapy with beclomethasone combined with albuterol reduced the risk of exacerbations requiring oral corticosteroid treatment, even without daily steroid use, according to a placebo-controlled study of children and adolescents with mild persistent asthma.

“Assessed from a risk-benefit point of view, our data suggest that, in children with mild persistent asthma, use of rescue inhaled corticosteroid could be an effective step-down alternative to discontinuation of such treatment after asthma control is achieved,” Dr. Fernando D. Martinez of the Arizona Respiratory Center and the University of Tucson (Ariz.), and his associates said.

This approach “could also be an alternative, step 2 therapeutic approach for mild persistent asthma in individuals who have not previously received a course of daily corticosteroid treatment,” they added, although they noted that the 44-month randomized, double-blind study was not designed to address this issue.

The TREXA study, funded by the National Heart, Lung, and Blood Institute, appeared online Feb. 15 in the Lancet (doi:10.1016/S0140-6736(10)62145-9).

The study was conducted to determine whether discontinuing treatment with daily inhaled corticosteroids (ICS) in children with well-controlled mild persistent asthma increased the risk of exacerbations, and whether combining beclomethasone and albuterol as rescue therapy, with or without daily beclomethasone, was more protective against asthma exacerbations than was an albuterol-only rescue strategy.

In the study, 288 children and adolescents aged 5-18 years from five U.S. clinical centers, with mild persistent asthma during the previous 2 years, were randomized to one of four treatment groups:

P Beclomethasone twice daily, with beclomethasone plus albuterol as rescue (combined group).

P Beclomethasone twice daily, with placebo plus albuterol as rescue (daily beclomethasone group).

P Placebo twice daily, with beclomethasone plus albuterol as rescue (rescue beclomethasone group).

P Placebo twice daily, with placebo plus albuterol as rescue (placebo group).

Twice-daily beclomethasone treatment was one puff (40 mcg per puff) in the morning and evening; rescue beclomethasone treatment was two puffs of beclomethasone (80 mcg) for every two puffs of albuterol (180 mcg) needed for relief of symptoms. The primary outcome was the time to first exacerbation requiring treatment with oral corticosteroids.

Among those in the placebo group, who received only albuterol as rescue, the exacerbation rate was 49%, compared with 31% in the combined group, 28% in the daily group, and 35% in the rescue group. “Compared with the placebo group, the hazard ratios for asthma exacerbations were significantly lower in the daily beclomethasone group and the combined group, but the difference was not significant in the rescue beclomethasone group,” they found.

The children in the two groups using daily beclomethasone also showed signs of less linear growth, a secondary end point: Children in these two groups grew a mean of 1.1 cm less than did those in the placebo group, a statistically significant difference. But the children in the rescue beclomethasone group (who received less than a quarter of the total daily ICS dose that the children in the combined and daily beclomethasone groups received) grew a mean of 0.3 cm less than did those in the placebo group, which was not a significant difference.

There were two adverse events considered severe in the study: a case of viral meningitis in the daily beclomethasone group and a case of bronchitis in the combined group.

Noting that children with mild persistent asthma should not be treated with rescue albuterol alone and that daily ICS is the most effective treatment to prevent exacerbations in this age group, the authors said that “our data suggest that inhaled corticosteroids used as rescue together with albuterol show benefits over rescue albuterol alone and avoids the growth effects associated with use of daily inhaled corticosteroids.”

They added that to their knowledge, the study was the first to look at the use of ICS with albuterol as rescue therapy in school-aged children.

These results “have potentially important implications for the management of asthma,” Dr. William Checkley wrote in an accompanying editorial (Lancet 2011 Feb. 15 [doi:10.1016/S0140-6736(10)62313-6]).

He noted that the British Thoracic Society and NHLBI National Asthma Education and Prevention Program guidelines recommend daily ICS use as initial and step-up treatment for persistent asthma, and “step-down is possible if asthma symptoms are well controlled for at least 3 months.” The results of this study, however, “suggest that step-down from daily inhaled corticosteroids to such treatment as rescue in combination with rescue short-acting beta agonists could be a reasonable step-down strategy for patients with mild persistent asthma,” wrote Dr. Checkley of the pulmonary and critical care division at Johns Hopkins University, Baltimore. This strategy would reduce the cumulative exposure to ICS “and obviate concerns about compliance with long-term controller treatment,” he added, noting that more studies are needed.

Beclomethasone and the placebo inhalers were provided by Teva Pharmaceutical Industries, the manufacturer of a generic formulation of beclomethasone. Of the 20 coauthors, 12, including lead author Dr. Martinez, reported having been a board member and/or received consulting fees, honoraria, and/or pending grant support from various pharmaceutical companies, including AstraZeneca, GlaxoSmithKline, MedImmune, and Merck. The remaining authors had no disclosures.

Rescue therapy with beclomethasone combined with albuterol reduced the risk of exacerbations requiring oral corticosteroid treatment, even without daily steroid use, according to a placebo-controlled study of children and adolescents with mild persistent asthma.

“Assessed from a risk-benefit point of view, our data suggest that, in children with mild persistent asthma, use of rescue inhaled corticosteroid could be an effective step-down alternative to discontinuation of such treatment after asthma control is achieved,” Dr. Fernando D. Martinez of the Arizona Respiratory Center and the University of Tucson (Ariz.), and his associates said.

This approach “could also be an alternative, step 2 therapeutic approach for mild persistent asthma in individuals who have not previously received a course of daily corticosteroid treatment,” they added, although they noted that the 44-month randomized, double-blind study was not designed to address this issue.

The TREXA study, funded by the National Heart, Lung, and Blood Institute, appeared online Feb. 15 in the Lancet (doi:10.1016/S0140-6736(10)62145-9).

The study was conducted to determine whether discontinuing treatment with daily inhaled corticosteroids (ICS) in children with well-controlled mild persistent asthma increased the risk of exacerbations, and whether combining beclomethasone and albuterol as rescue therapy, with or without daily beclomethasone, was more protective against asthma exacerbations than was an albuterol-only rescue strategy.

In the study, 288 children and adolescents aged 5-18 years from five U.S. clinical centers, with mild persistent asthma during the previous 2 years, were randomized to one of four treatment groups:

P Beclomethasone twice daily, with beclomethasone plus albuterol as rescue (combined group).

P Beclomethasone twice daily, with placebo plus albuterol as rescue (daily beclomethasone group).

P Placebo twice daily, with beclomethasone plus albuterol as rescue (rescue beclomethasone group).

P Placebo twice daily, with placebo plus albuterol as rescue (placebo group).

Twice-daily beclomethasone treatment was one puff (40 mcg per puff) in the morning and evening; rescue beclomethasone treatment was two puffs of beclomethasone (80 mcg) for every two puffs of albuterol (180 mcg) needed for relief of symptoms. The primary outcome was the time to first exacerbation requiring treatment with oral corticosteroids.

Among those in the placebo group, who received only albuterol as rescue, the exacerbation rate was 49%, compared with 31% in the combined group, 28% in the daily group, and 35% in the rescue group. “Compared with the placebo group, the hazard ratios for asthma exacerbations were significantly lower in the daily beclomethasone group and the combined group, but the difference was not significant in the rescue beclomethasone group,” they found.

The children in the two groups using daily beclomethasone also showed signs of less linear growth, a secondary end point: Children in these two groups grew a mean of 1.1 cm less than did those in the placebo group, a statistically significant difference. But the children in the rescue beclomethasone group (who received less than a quarter of the total daily ICS dose that the children in the combined and daily beclomethasone groups received) grew a mean of 0.3 cm less than did those in the placebo group, which was not a significant difference.

There were two adverse events considered severe in the study: a case of viral meningitis in the daily beclomethasone group and a case of bronchitis in the combined group.

Noting that children with mild persistent asthma should not be treated with rescue albuterol alone and that daily ICS is the most effective treatment to prevent exacerbations in this age group, the authors said that “our data suggest that inhaled corticosteroids used as rescue together with albuterol show benefits over rescue albuterol alone and avoids the growth effects associated with use of daily inhaled corticosteroids.”

They added that to their knowledge, the study was the first to look at the use of ICS with albuterol as rescue therapy in school-aged children.

These results “have potentially important implications for the management of asthma,” Dr. William Checkley wrote in an accompanying editorial (Lancet 2011 Feb. 15 [doi:10.1016/S0140-6736(10)62313-6]).

He noted that the British Thoracic Society and NHLBI National Asthma Education and Prevention Program guidelines recommend daily ICS use as initial and step-up treatment for persistent asthma, and “step-down is possible if asthma symptoms are well controlled for at least 3 months.” The results of this study, however, “suggest that step-down from daily inhaled corticosteroids to such treatment as rescue in combination with rescue short-acting beta agonists could be a reasonable step-down strategy for patients with mild persistent asthma,” wrote Dr. Checkley of the pulmonary and critical care division at Johns Hopkins University, Baltimore. This strategy would reduce the cumulative exposure to ICS “and obviate concerns about compliance with long-term controller treatment,” he added, noting that more studies are needed.

Beclomethasone and the placebo inhalers were provided by Teva Pharmaceutical Industries, the manufacturer of a generic formulation of beclomethasone. Of the 20 coauthors, 12, including lead author Dr. Martinez, reported having been a board member and/or received consulting fees, honoraria, and/or pending grant support from various pharmaceutical companies, including AstraZeneca, GlaxoSmithKline, MedImmune, and Merck. The remaining authors had no disclosures.

Rescue therapy with beclomethasone combined with albuterol reduced the risk of exacerbations requiring oral corticosteroid treatment, even without daily steroid use, according to a placebo-controlled study of children and adolescents with mild persistent asthma.

“Assessed from a risk-benefit point of view, our data suggest that, in children with mild persistent asthma, use of rescue inhaled corticosteroid could be an effective step-down alternative to discontinuation of such treatment after asthma control is achieved,” Dr. Fernando D. Martinez of the Arizona Respiratory Center and the University of Tucson (Ariz.), and his associates said.

This approach “could also be an alternative, step 2 therapeutic approach for mild persistent asthma in individuals who have not previously received a course of daily corticosteroid treatment,” they added, although they noted that the 44-month randomized, double-blind study was not designed to address this issue.

The TREXA study, funded by the National Heart, Lung, and Blood Institute, appeared online Feb. 15 in the Lancet (doi:10.1016/S0140-6736(10)62145-9).

The study was conducted to determine whether discontinuing treatment with daily inhaled corticosteroids (ICS) in children with well-controlled mild persistent asthma increased the risk of exacerbations, and whether combining beclomethasone and albuterol as rescue therapy, with or without daily beclomethasone, was more protective against asthma exacerbations than was an albuterol-only rescue strategy.

In the study, 288 children and adolescents aged 5-18 years from five U.S. clinical centers, with mild persistent asthma during the previous 2 years, were randomized to one of four treatment groups:

P Beclomethasone twice daily, with beclomethasone plus albuterol as rescue (combined group).

P Beclomethasone twice daily, with placebo plus albuterol as rescue (daily beclomethasone group).

P Placebo twice daily, with beclomethasone plus albuterol as rescue (rescue beclomethasone group).

P Placebo twice daily, with placebo plus albuterol as rescue (placebo group).

Twice-daily beclomethasone treatment was one puff (40 mcg per puff) in the morning and evening; rescue beclomethasone treatment was two puffs of beclomethasone (80 mcg) for every two puffs of albuterol (180 mcg) needed for relief of symptoms. The primary outcome was the time to first exacerbation requiring treatment with oral corticosteroids.

Among those in the placebo group, who received only albuterol as rescue, the exacerbation rate was 49%, compared with 31% in the combined group, 28% in the daily group, and 35% in the rescue group. “Compared with the placebo group, the hazard ratios for asthma exacerbations were significantly lower in the daily beclomethasone group and the combined group, but the difference was not significant in the rescue beclomethasone group,” they found.

The children in the two groups using daily beclomethasone also showed signs of less linear growth, a secondary end point: Children in these two groups grew a mean of 1.1 cm less than did those in the placebo group, a statistically significant difference. But the children in the rescue beclomethasone group (who received less than a quarter of the total daily ICS dose that the children in the combined and daily beclomethasone groups received) grew a mean of 0.3 cm less than did those in the placebo group, which was not a significant difference.

There were two adverse events considered severe in the study: a case of viral meningitis in the daily beclomethasone group and a case of bronchitis in the combined group.

Noting that children with mild persistent asthma should not be treated with rescue albuterol alone and that daily ICS is the most effective treatment to prevent exacerbations in this age group, the authors said that “our data suggest that inhaled corticosteroids used as rescue together with albuterol show benefits over rescue albuterol alone and avoids the growth effects associated with use of daily inhaled corticosteroids.”

They added that to their knowledge, the study was the first to look at the use of ICS with albuterol as rescue therapy in school-aged children.

These results “have potentially important implications for the management of asthma,” Dr. William Checkley wrote in an accompanying editorial (Lancet 2011 Feb. 15 [doi:10.1016/S0140-6736(10)62313-6]).

He noted that the British Thoracic Society and NHLBI National Asthma Education and Prevention Program guidelines recommend daily ICS use as initial and step-up treatment for persistent asthma, and “step-down is possible if asthma symptoms are well controlled for at least 3 months.” The results of this study, however, “suggest that step-down from daily inhaled corticosteroids to such treatment as rescue in combination with rescue short-acting beta agonists could be a reasonable step-down strategy for patients with mild persistent asthma,” wrote Dr. Checkley of the pulmonary and critical care division at Johns Hopkins University, Baltimore. This strategy would reduce the cumulative exposure to ICS “and obviate concerns about compliance with long-term controller treatment,” he added, noting that more studies are needed.

Beclomethasone and the placebo inhalers were provided by Teva Pharmaceutical Industries, the manufacturer of a generic formulation of beclomethasone. Of the 20 coauthors, 12, including lead author Dr. Martinez, reported having been a board member and/or received consulting fees, honoraria, and/or pending grant support from various pharmaceutical companies, including AstraZeneca, GlaxoSmithKline, MedImmune, and Merck. The remaining authors had no disclosures.

GAITHERSBURG, MD. – A Food and Drug Administration advisory panel split on whether to recommend that electroconvulsive therapy devices be switched to a less stringent regulatory category when used to treat severe major depressive disorder. But the majority of the panel said that for other indications, ECT machines should be maintained at the level now used to regulate devices deemed as highest risk.

At the end of the 2-day meeting last month, about half of the FDA’s Neurological Devices Advisory Panel recommended that electroconvulsive therapy (ECT) devices be switched from a class III category to class II when used to treat severe depression. Class III devices, which have the most stringent regulatory controls, are used for medical devices such as replacement heart valves and silicone gel–filled breast implants. Class II devices, which are classified as "intermediate risk," include x-ray systems, gas analyzers, and surgical drapes. Currently, ECT devices are cleared for use by the FDA for treating severe depression (unipolar and bipolar), schizophrenia, bipolar manic (and mixed) states, schizoaffective disorder, schizophreniform disorder, and catatonia.

Under the Medical Devices Amendments of 1976, class III devices require manufacturers to submit a premarket approval application (PMA), which includes clinical trial data, to provide adequate evidence that the device is safe and effective for its intended use. But because ECT devices were on the market before 1976, they have been exempted from the approval process. Instead, ECT manufacturers have been required to show that the devices are substantially equivalent to a legally marketed device before they are cleared for marketing.

The FDA is in the process of developing regulations that will either reclassify ECT and other devices marketed before the amendments went into effect or keep them in the class III category. Keeping them in the class III category would require that the manufacturers submit PMAs for them to remain on the market. Reclassification into the intermediate risk (class II) category for devices would avoid requiring manufacturers to apply for approval but could require "special controls" to mitigate the associated risks of the device to "provide reasonable assurance" of their safety and effectiveness. Such controls could include postmarket surveillance, patient registries, and/or development and dissemination of guidelines, according to the FDA, which held the meeting to get feedback on how ECT devices should be classified for severe depression and the other indications cleared by the agency for treatment with ECT.

The panel supported labeling that would require physicians to monitor a patient’s cognitive status as part of the efforts to mitigate risk prior to undergoing ECT and throughout the course of treatment.

Class III or Class II?

Among the reasons cited by panelists supporting the class III category for severe depression were associated memory loss and the lack of long-term data. These panelists included the consumer and patient representatives on the panel, who were concerned about the lack of knowledge about long-term adverse effects associated with ECT. Dr. David Good, professor and chair of neurology, Pennsylvania State College, Hershey, said that despite responses in the public docket describing ECT as lifesaving, he leaned toward supporting class III status because of the absence of long-term data and evidence showing that ECT is associated with memory loss.

Those supporting a switch to the class II category agreed there was adequate evidence that ECT was effective and advocated the use of special controls to help mitigate the associated risks of ECT.

"It would be a mistake to even take the risk of leaving it at as a class III and the possibility that it may be removed from the market," said Dr. Wayne K. Goodman, professor and chairman of the department of psychiatry, Mount Sinai School of Medicine, New York. He pointed out that there is no alternative to ECT for acutely suicidal patients with treatment-resistant depression, for whom ECT is "literally, life saving. ... so to eliminate this option literally would be eliminating a lifeline to many patients." Dr. Goodman referred to what he believes is a disconnect between the strength of the published data on ECT and the clinical impressions of the effectiveness of ECT among psychiatrists like himself, and noted that about 20-25 years ago, "there was such a strong wealth of clinical impression that ECT is so efficacious, that we’ve skipped the step somewhere along the way of clinical trials that normally would convince a panel like this that we have adequate evidence for efficacy and safety."

Panel members also were asked to provide feedback on how the devices should be classified when used for treating schizophrenia, bipolar manic and mixed states, schizoaffective disorder, schizophreniform disorder, and catatonia. Most of the panel agreed that ECT devices remain in class III for schizophrenia, bipolar manic (and mixed) states, and schizoaffective disorder.

Several of the psychiatrists on the panel who supported a switch to class II for ECT when used to treat the bipolar indication cited the need for alternative treatments and the few treatment options available for severely ill treatment resistant patients with bipolar disorder – and the difficulty in conducting clinical trials in such patients.

The panel unanimously recommended that ECT devices remain in class III for schizophreniform disorder. Some panelists also thought that the devices should remain in class III when used to treat catatonia. Others pointed out, however, that this is a relatively rare condition and that ECT could be inappropriately restricted and might not be available for these patients if categorized as class III.

Availability Issues

In an interview after the meeting, Dr. Richard D. Weiner, professor of psychiatry and behavioral sciences at Duke University, Durham, N.C., said he did not expect that a change in classification would result in the unavailability of ECT. In addition, the result of the hearing will not have an effect on the practice of ECT for at least several years, predicted Dr. Weiner, who also spoke during the open comment session of the meeting. An FDA spokesperson said once the agency makes a decision on the classification, it will have to go through the public notice and comment process, which can take at least 1 year.

The FDA received about 3,000 responses about this classification issue in a public docket, between September 2009 and January 2010, from medical and mental health providers, current and former ECT providers, recipients of ECT and their relatives and friends, as well as other groups. Most – 79% – of the responses opposed reclassification to class II; 14% supported reclassification. The most common adverse events reported were related to memory, followed by cognitive decline and brain damage, according to the FDA. Some people also reported that did not think they had been adequately informed about the risks of ECT before they were treated, FDA officials said at the meeting.

Currently, there are two manufacturers of ECT devices in the United States: Mecta Corp. and Somatics.

The FDA usually follows the recommendations of its advisory panels, which are not binding. Members of FDA panels are cleared of potential conflicts related to the topic under review.

After a decline that began in the 1960s, the use of ECT increased in the 1990s, and each year more than 100,000 patients in the United States are treated with ECT, according to the FDA.

GAITHERSBURG, MD. – A Food and Drug Administration advisory panel split on whether to recommend that electroconvulsive therapy devices be switched to a less stringent regulatory category when used to treat severe major depressive disorder. But the majority of the panel said that for other indications, ECT machines should be maintained at the level now used to regulate devices deemed as highest risk.

At the end of the 2-day meeting last month, about half of the FDA’s Neurological Devices Advisory Panel recommended that electroconvulsive therapy (ECT) devices be switched from a class III category to class II when used to treat severe depression. Class III devices, which have the most stringent regulatory controls, are used for medical devices such as replacement heart valves and silicone gel–filled breast implants. Class II devices, which are classified as "intermediate risk," include x-ray systems, gas analyzers, and surgical drapes. Currently, ECT devices are cleared for use by the FDA for treating severe depression (unipolar and bipolar), schizophrenia, bipolar manic (and mixed) states, schizoaffective disorder, schizophreniform disorder, and catatonia.

Under the Medical Devices Amendments of 1976, class III devices require manufacturers to submit a premarket approval application (PMA), which includes clinical trial data, to provide adequate evidence that the device is safe and effective for its intended use. But because ECT devices were on the market before 1976, they have been exempted from the approval process. Instead, ECT manufacturers have been required to show that the devices are substantially equivalent to a legally marketed device before they are cleared for marketing.

The FDA is in the process of developing regulations that will either reclassify ECT and other devices marketed before the amendments went into effect or keep them in the class III category. Keeping them in the class III category would require that the manufacturers submit PMAs for them to remain on the market. Reclassification into the intermediate risk (class II) category for devices would avoid requiring manufacturers to apply for approval but could require "special controls" to mitigate the associated risks of the device to "provide reasonable assurance" of their safety and effectiveness. Such controls could include postmarket surveillance, patient registries, and/or development and dissemination of guidelines, according to the FDA, which held the meeting to get feedback on how ECT devices should be classified for severe depression and the other indications cleared by the agency for treatment with ECT.

The panel supported labeling that would require physicians to monitor a patient’s cognitive status as part of the efforts to mitigate risk prior to undergoing ECT and throughout the course of treatment.

Class III or Class II?

Among the reasons cited by panelists supporting the class III category for severe depression were associated memory loss and the lack of long-term data. These panelists included the consumer and patient representatives on the panel, who were concerned about the lack of knowledge about long-term adverse effects associated with ECT. Dr. David Good, professor and chair of neurology, Pennsylvania State College, Hershey, said that despite responses in the public docket describing ECT as lifesaving, he leaned toward supporting class III status because of the absence of long-term data and evidence showing that ECT is associated with memory loss.

Those supporting a switch to the class II category agreed there was adequate evidence that ECT was effective and advocated the use of special controls to help mitigate the associated risks of ECT.

"It would be a mistake to even take the risk of leaving it at as a class III and the possibility that it may be removed from the market," said Dr. Wayne K. Goodman, professor and chairman of the department of psychiatry, Mount Sinai School of Medicine, New York. He pointed out that there is no alternative to ECT for acutely suicidal patients with treatment-resistant depression, for whom ECT is "literally, life saving. ... so to eliminate this option literally would be eliminating a lifeline to many patients." Dr. Goodman referred to what he believes is a disconnect between the strength of the published data on ECT and the clinical impressions of the effectiveness of ECT among psychiatrists like himself, and noted that about 20-25 years ago, "there was such a strong wealth of clinical impression that ECT is so efficacious, that we’ve skipped the step somewhere along the way of clinical trials that normally would convince a panel like this that we have adequate evidence for efficacy and safety."

Panel members also were asked to provide feedback on how the devices should be classified when used for treating schizophrenia, bipolar manic and mixed states, schizoaffective disorder, schizophreniform disorder, and catatonia. Most of the panel agreed that ECT devices remain in class III for schizophrenia, bipolar manic (and mixed) states, and schizoaffective disorder.

Several of the psychiatrists on the panel who supported a switch to class II for ECT when used to treat the bipolar indication cited the need for alternative treatments and the few treatment options available for severely ill treatment resistant patients with bipolar disorder – and the difficulty in conducting clinical trials in such patients.

The panel unanimously recommended that ECT devices remain in class III for schizophreniform disorder. Some panelists also thought that the devices should remain in class III when used to treat catatonia. Others pointed out, however, that this is a relatively rare condition and that ECT could be inappropriately restricted and might not be available for these patients if categorized as class III.

Availability Issues

In an interview after the meeting, Dr. Richard D. Weiner, professor of psychiatry and behavioral sciences at Duke University, Durham, N.C., said he did not expect that a change in classification would result in the unavailability of ECT. In addition, the result of the hearing will not have an effect on the practice of ECT for at least several years, predicted Dr. Weiner, who also spoke during the open comment session of the meeting. An FDA spokesperson said once the agency makes a decision on the classification, it will have to go through the public notice and comment process, which can take at least 1 year.

The FDA received about 3,000 responses about this classification issue in a public docket, between September 2009 and January 2010, from medical and mental health providers, current and former ECT providers, recipients of ECT and their relatives and friends, as well as other groups. Most – 79% – of the responses opposed reclassification to class II; 14% supported reclassification. The most common adverse events reported were related to memory, followed by cognitive decline and brain damage, according to the FDA. Some people also reported that did not think they had been adequately informed about the risks of ECT before they were treated, FDA officials said at the meeting.

Currently, there are two manufacturers of ECT devices in the United States: Mecta Corp. and Somatics.

The FDA usually follows the recommendations of its advisory panels, which are not binding. Members of FDA panels are cleared of potential conflicts related to the topic under review.

After a decline that began in the 1960s, the use of ECT increased in the 1990s, and each year more than 100,000 patients in the United States are treated with ECT, according to the FDA.

GAITHERSBURG, MD. – A Food and Drug Administration advisory panel split on whether to recommend that electroconvulsive therapy devices be switched to a less stringent regulatory category when used to treat severe major depressive disorder. But the majority of the panel said that for other indications, ECT machines should be maintained at the level now used to regulate devices deemed as highest risk.

At the end of the 2-day meeting last month, about half of the FDA’s Neurological Devices Advisory Panel recommended that electroconvulsive therapy (ECT) devices be switched from a class III category to class II when used to treat severe depression. Class III devices, which have the most stringent regulatory controls, are used for medical devices such as replacement heart valves and silicone gel–filled breast implants. Class II devices, which are classified as "intermediate risk," include x-ray systems, gas analyzers, and surgical drapes. Currently, ECT devices are cleared for use by the FDA for treating severe depression (unipolar and bipolar), schizophrenia, bipolar manic (and mixed) states, schizoaffective disorder, schizophreniform disorder, and catatonia.

Under the Medical Devices Amendments of 1976, class III devices require manufacturers to submit a premarket approval application (PMA), which includes clinical trial data, to provide adequate evidence that the device is safe and effective for its intended use. But because ECT devices were on the market before 1976, they have been exempted from the approval process. Instead, ECT manufacturers have been required to show that the devices are substantially equivalent to a legally marketed device before they are cleared for marketing.

The FDA is in the process of developing regulations that will either reclassify ECT and other devices marketed before the amendments went into effect or keep them in the class III category. Keeping them in the class III category would require that the manufacturers submit PMAs for them to remain on the market. Reclassification into the intermediate risk (class II) category for devices would avoid requiring manufacturers to apply for approval but could require "special controls" to mitigate the associated risks of the device to "provide reasonable assurance" of their safety and effectiveness. Such controls could include postmarket surveillance, patient registries, and/or development and dissemination of guidelines, according to the FDA, which held the meeting to get feedback on how ECT devices should be classified for severe depression and the other indications cleared by the agency for treatment with ECT.

The panel supported labeling that would require physicians to monitor a patient’s cognitive status as part of the efforts to mitigate risk prior to undergoing ECT and throughout the course of treatment.

Class III or Class II?

Among the reasons cited by panelists supporting the class III category for severe depression were associated memory loss and the lack of long-term data. These panelists included the consumer and patient representatives on the panel, who were concerned about the lack of knowledge about long-term adverse effects associated with ECT. Dr. David Good, professor and chair of neurology, Pennsylvania State College, Hershey, said that despite responses in the public docket describing ECT as lifesaving, he leaned toward supporting class III status because of the absence of long-term data and evidence showing that ECT is associated with memory loss.

Those supporting a switch to the class II category agreed there was adequate evidence that ECT was effective and advocated the use of special controls to help mitigate the associated risks of ECT.

"It would be a mistake to even take the risk of leaving it at as a class III and the possibility that it may be removed from the market," said Dr. Wayne K. Goodman, professor and chairman of the department of psychiatry, Mount Sinai School of Medicine, New York. He pointed out that there is no alternative to ECT for acutely suicidal patients with treatment-resistant depression, for whom ECT is "literally, life saving. ... so to eliminate this option literally would be eliminating a lifeline to many patients." Dr. Goodman referred to what he believes is a disconnect between the strength of the published data on ECT and the clinical impressions of the effectiveness of ECT among psychiatrists like himself, and noted that about 20-25 years ago, "there was such a strong wealth of clinical impression that ECT is so efficacious, that we’ve skipped the step somewhere along the way of clinical trials that normally would convince a panel like this that we have adequate evidence for efficacy and safety."

Panel members also were asked to provide feedback on how the devices should be classified when used for treating schizophrenia, bipolar manic and mixed states, schizoaffective disorder, schizophreniform disorder, and catatonia. Most of the panel agreed that ECT devices remain in class III for schizophrenia, bipolar manic (and mixed) states, and schizoaffective disorder.

Several of the psychiatrists on the panel who supported a switch to class II for ECT when used to treat the bipolar indication cited the need for alternative treatments and the few treatment options available for severely ill treatment resistant patients with bipolar disorder – and the difficulty in conducting clinical trials in such patients.

The panel unanimously recommended that ECT devices remain in class III for schizophreniform disorder. Some panelists also thought that the devices should remain in class III when used to treat catatonia. Others pointed out, however, that this is a relatively rare condition and that ECT could be inappropriately restricted and might not be available for these patients if categorized as class III.

Availability Issues

In an interview after the meeting, Dr. Richard D. Weiner, professor of psychiatry and behavioral sciences at Duke University, Durham, N.C., said he did not expect that a change in classification would result in the unavailability of ECT. In addition, the result of the hearing will not have an effect on the practice of ECT for at least several years, predicted Dr. Weiner, who also spoke during the open comment session of the meeting. An FDA spokesperson said once the agency makes a decision on the classification, it will have to go through the public notice and comment process, which can take at least 1 year.

The FDA received about 3,000 responses about this classification issue in a public docket, between September 2009 and January 2010, from medical and mental health providers, current and former ECT providers, recipients of ECT and their relatives and friends, as well as other groups. Most – 79% – of the responses opposed reclassification to class II; 14% supported reclassification. The most common adverse events reported were related to memory, followed by cognitive decline and brain damage, according to the FDA. Some people also reported that did not think they had been adequately informed about the risks of ECT before they were treated, FDA officials said at the meeting.

Currently, there are two manufacturers of ECT devices in the United States: Mecta Corp. and Somatics.

The FDA usually follows the recommendations of its advisory panels, which are not binding. Members of FDA panels are cleared of potential conflicts related to the topic under review.

After a decline that began in the 1960s, the use of ECT increased in the 1990s, and each year more than 100,000 patients in the United States are treated with ECT, according to the FDA.

GAITHERSBURG, MD. – A Food and Drug Administration advisory panel split on whether to recommend that electroconvulsive therapy devices be switched to a less stringent regulatory category when used to treat severe major depressive disorder. But the majority of the panel said that for other indications, ECT machines should be maintained at the level now used to regulate devices deemed as highest risk.

At the end of the 2-day meeting on Jan. 27-28, about half of the FDA’s Neurological Devices Advisory Panel recommended that electroconvulsive therapy (ECT) devices be switched from a class III category to class II when used to treat severe depression. Class III devices, which have the most stringent regulatory controls, are used for medical devices such as replacement heart valves and silicone gel–filled breast implants. Class II devices, which are classified as "intermediate risk," include x-ray systems, gas analyzers, and surgical drapes. Currently, ECT devices are cleared for use by the FDA for treating severe depression (unipolar and bipolar), schizophrenia, bipolar manic (and mixed) states, schizoaffective disorder, schizophreniform disorder, and catatonia.

Under the Medical Devices Amendments of 1976, class III devices require manufacturers to submit a premarket approval application (PMA), which includes clinical trial data, to provide adequate evidence that the device is safe and effective for its intended use. But because ECT devices were on the market before 1976, they have been exempted from the approval process. Instead, ECT manufacturers have been required to show that the devices are substantially equivalent to a legally marketed device before they are cleared for marketing.

The FDA is in the process of developing regulations that will either reclassify ECT and other devices marketed before the amendments went into effect or keep them in the class III category. Keeping them in the class III category would require that the manufacturers submit PMAs for them to remain on the market. Reclassification into the intermediate risk (class II) category for devices would avoid requiring manufacturers to apply for approval but could require "special controls" to mitigate the associated risks of the device to "provide reasonable assurance" of their safety and effectiveness. Such controls could include postmarket surveillance, patient registries, and/or development and dissemination of guidelines, according to the FDA, which held the meeting to get feedback on how ECT devices should be classified for severe depression and the other indications cleared by the agency for treatment with ECT.

The panel supported labeling that would require physicians to monitor a patient’s cognitive status as part of the efforts to mitigate risk prior to undergoing ECT and throughout the course of treatment.

Class III or Class II?

Among the reasons cited by panelists supporting the class III category for severe depression were associated memory loss and the lack of long-term data. These panelists included the consumer and patient representatives on the panel, who were concerned about the lack of knowledge about long-term adverse effects associated with ECT. Dr. David Good, professor and chair of neurology, Pennsylvania State College, Hershey, said that despite responses in the public docket describing ECT as lifesaving, he leaned toward supporting class III status because of the absence of long-term data and evidence showing that ECT is associated with memory loss.

Those supporting a switch to the class II category agreed there was adequate evidence that ECT was effective and advocated the use of special controls to help mitigate the associated risks of ECT.

"It would be a mistake to even take the risk of leaving it at as a class III and the possibility that it may be removed from the market," said Dr. Wayne K. Goodman, professor and chairman of the department of psychiatry, Mount Sinai School of Medicine, New York. He pointed out that there is no alternative to ECT for acutely suicidal patients with treatment-resistant depression, for whom ECT is "literally, life saving. ... So to eliminate this option literally would be eliminating a lifeline to many patients." Dr. Goodman referred to what he believes is a disconnect between the strength of the published data on ECT and the clinical impressions of the effectiveness of ECT among psychiatrists like himself, and noted that about 20-25 years ago, "there was such a strong wealth of clinical impression that ECT is so efficacious, that we’ve skipped the step somewhere along the way of clinical trials that normally would convince a panel like this that we have adequate evidence for efficacy and safety."

Panel members also were asked to provide feedback on how the devices should be classified when used for treating schizophrenia, bipolar manic and mixed states, schizoaffective disorder, schizophreniform disorder, and catatonia. Most of the panel agreed that ECT devices remain in class III for schizophrenia, bipolar manic (and mixed) states, and schizoaffective disorder.

Several of the psychiatrists on the panel who supported a switch to class II for ECT when used to treat the bipolar indication cited the need for alternative treatments and the few treatment options available for severely ill treatment resistant patients with bipolar disorder – and the difficulty in conducting clinical trials in such patients.

The panel unanimously recommended that ECT devices remain in class III for schizophreniform disorder. Some panelists also thought that the devices should remain in class III when used to treat catatonia. Others pointed out, however, that this is a relatively rare condition and that ECT could be inappropriately restricted and might not be available for these patients if categorized as class III.

Availability Issues

In an interview after the meeting, Dr. Richard D. Weiner, professor of psychiatry and behavioral sciences at Duke University, Durham, N.C., said he did not expect that a change in classification would result in the unavailability of ECT. In addition, the result of the hearing will not have an effect on the practice of ECT for at least several years, predicted Dr. Weiner, who also spoke during the open comment session of the meeting. An FDA spokesperson said once the agency makes a decision on the classification, it will have to go through the public notice and comment process, which can take at least 1 year.

The FDA received about 3,000 responses about this classification issue in a public docket, between September 2009 and January 2010, from medical and mental health providers, current and former ECT providers, recipients of ECT and their relatives and friends, as well as other groups. Most – 79% – of the responses opposed reclassification to class II; 14% supported reclassification. The most common adverse events reported were related to memory, followed by cognitive decline and brain damage, according to the FDA. Some people also reported that did not think they had been adequately informed about the risks of ECT before they were treated, FDA officials said at the meeting.

Currently, there are two manufacturers of ECT devices in the United States: Mecta Corp. and Somatics.

The FDA usually follows the recommendations of its advisory panels, which are not binding. Members of FDA panels are cleared of potential conflicts related to the topic under review.

After a decline that began in the 1960s, the use of ECT increased in the 1990s, and each year more than 100,000 patients in the United States are treated with ECT, according to the FDA.

GAITHERSBURG, MD. – A Food and Drug Administration advisory panel split on whether to recommend that electroconvulsive therapy devices be switched to a less stringent regulatory category when used to treat severe major depressive disorder. But the majority of the panel said that for other indications, ECT machines should be maintained at the level now used to regulate devices deemed as highest risk.

At the end of the 2-day meeting on Jan. 27-28, about half of the FDA’s Neurological Devices Advisory Panel recommended that electroconvulsive therapy (ECT) devices be switched from a class III category to class II when used to treat severe depression. Class III devices, which have the most stringent regulatory controls, are used for medical devices such as replacement heart valves and silicone gel–filled breast implants. Class II devices, which are classified as "intermediate risk," include x-ray systems, gas analyzers, and surgical drapes. Currently, ECT devices are cleared for use by the FDA for treating severe depression (unipolar and bipolar), schizophrenia, bipolar manic (and mixed) states, schizoaffective disorder, schizophreniform disorder, and catatonia.

Under the Medical Devices Amendments of 1976, class III devices require manufacturers to submit a premarket approval application (PMA), which includes clinical trial data, to provide adequate evidence that the device is safe and effective for its intended use. But because ECT devices were on the market before 1976, they have been exempted from the approval process. Instead, ECT manufacturers have been required to show that the devices are substantially equivalent to a legally marketed device before they are cleared for marketing.

The FDA is in the process of developing regulations that will either reclassify ECT and other devices marketed before the amendments went into effect or keep them in the class III category. Keeping them in the class III category would require that the manufacturers submit PMAs for them to remain on the market. Reclassification into the intermediate risk (class II) category for devices would avoid requiring manufacturers to apply for approval but could require "special controls" to mitigate the associated risks of the device to "provide reasonable assurance" of their safety and effectiveness. Such controls could include postmarket surveillance, patient registries, and/or development and dissemination of guidelines, according to the FDA, which held the meeting to get feedback on how ECT devices should be classified for severe depression and the other indications cleared by the agency for treatment with ECT.

The panel supported labeling that would require physicians to monitor a patient’s cognitive status as part of the efforts to mitigate risk prior to undergoing ECT and throughout the course of treatment.

Class III or Class II?

Among the reasons cited by panelists supporting the class III category for severe depression were associated memory loss and the lack of long-term data. These panelists included the consumer and patient representatives on the panel, who were concerned about the lack of knowledge about long-term adverse effects associated with ECT. Dr. David Good, professor and chair of neurology, Pennsylvania State College, Hershey, said that despite responses in the public docket describing ECT as lifesaving, he leaned toward supporting class III status because of the absence of long-term data and evidence showing that ECT is associated with memory loss.

Those supporting a switch to the class II category agreed there was adequate evidence that ECT was effective and advocated the use of special controls to help mitigate the associated risks of ECT.

"It would be a mistake to even take the risk of leaving it at as a class III and the possibility that it may be removed from the market," said Dr. Wayne K. Goodman, professor and chairman of the department of psychiatry, Mount Sinai School of Medicine, New York. He pointed out that there is no alternative to ECT for acutely suicidal patients with treatment-resistant depression, for whom ECT is "literally, life saving. ... So to eliminate this option literally would be eliminating a lifeline to many patients." Dr. Goodman referred to what he believes is a disconnect between the strength of the published data on ECT and the clinical impressions of the effectiveness of ECT among psychiatrists like himself, and noted that about 20-25 years ago, "there was such a strong wealth of clinical impression that ECT is so efficacious, that we’ve skipped the step somewhere along the way of clinical trials that normally would convince a panel like this that we have adequate evidence for efficacy and safety."

Panel members also were asked to provide feedback on how the devices should be classified when used for treating schizophrenia, bipolar manic and mixed states, schizoaffective disorder, schizophreniform disorder, and catatonia. Most of the panel agreed that ECT devices remain in class III for schizophrenia, bipolar manic (and mixed) states, and schizoaffective disorder.

Several of the psychiatrists on the panel who supported a switch to class II for ECT when used to treat the bipolar indication cited the need for alternative treatments and the few treatment options available for severely ill treatment resistant patients with bipolar disorder – and the difficulty in conducting clinical trials in such patients.

The panel unanimously recommended that ECT devices remain in class III for schizophreniform disorder. Some panelists also thought that the devices should remain in class III when used to treat catatonia. Others pointed out, however, that this is a relatively rare condition and that ECT could be inappropriately restricted and might not be available for these patients if categorized as class III.

Availability Issues

In an interview after the meeting, Dr. Richard D. Weiner, professor of psychiatry and behavioral sciences at Duke University, Durham, N.C., said he did not expect that a change in classification would result in the unavailability of ECT. In addition, the result of the hearing will not have an effect on the practice of ECT for at least several years, predicted Dr. Weiner, who also spoke during the open comment session of the meeting. An FDA spokesperson said once the agency makes a decision on the classification, it will have to go through the public notice and comment process, which can take at least 1 year.

The FDA received about 3,000 responses about this classification issue in a public docket, between September 2009 and January 2010, from medical and mental health providers, current and former ECT providers, recipients of ECT and their relatives and friends, as well as other groups. Most – 79% – of the responses opposed reclassification to class II; 14% supported reclassification. The most common adverse events reported were related to memory, followed by cognitive decline and brain damage, according to the FDA. Some people also reported that did not think they had been adequately informed about the risks of ECT before they were treated, FDA officials said at the meeting.

Currently, there are two manufacturers of ECT devices in the United States: Mecta Corp. and Somatics.

The FDA usually follows the recommendations of its advisory panels, which are not binding. Members of FDA panels are cleared of potential conflicts related to the topic under review.

After a decline that began in the 1960s, the use of ECT increased in the 1990s, and each year more than 100,000 patients in the United States are treated with ECT, according to the FDA.

GAITHERSBURG, MD. – A Food and Drug Administration advisory panel split on whether to recommend that electroconvulsive therapy devices be switched to a less stringent regulatory category when used to treat severe major depressive disorder. But the majority of the panel said that for other indications, ECT machines should be maintained at the level now used to regulate devices deemed as highest risk.

At the end of the 2-day meeting on Jan. 27-28, about half of the FDA’s Neurological Devices Advisory Panel recommended that electroconvulsive therapy (ECT) devices be switched from a class III category to class II when used to treat severe depression. Class III devices, which have the most stringent regulatory controls, are used for medical devices such as replacement heart valves and silicone gel–filled breast implants. Class II devices, which are classified as "intermediate risk," include x-ray systems, gas analyzers, and surgical drapes. Currently, ECT devices are cleared for use by the FDA for treating severe depression (unipolar and bipolar), schizophrenia, bipolar manic (and mixed) states, schizoaffective disorder, schizophreniform disorder, and catatonia.

Under the Medical Devices Amendments of 1976, class III devices require manufacturers to submit a premarket approval application (PMA), which includes clinical trial data, to provide adequate evidence that the device is safe and effective for its intended use. But because ECT devices were on the market before 1976, they have been exempted from the approval process. Instead, ECT manufacturers have been required to show that the devices are substantially equivalent to a legally marketed device before they are cleared for marketing.

The FDA is in the process of developing regulations that will either reclassify ECT and other devices marketed before the amendments went into effect or keep them in the class III category. Keeping them in the class III category would require that the manufacturers submit PMAs for them to remain on the market. Reclassification into the intermediate risk (class II) category for devices would avoid requiring manufacturers to apply for approval but could require "special controls" to mitigate the associated risks of the device to "provide reasonable assurance" of their safety and effectiveness. Such controls could include postmarket surveillance, patient registries, and/or development and dissemination of guidelines, according to the FDA, which held the meeting to get feedback on how ECT devices should be classified for severe depression and the other indications cleared by the agency for treatment with ECT.

The panel supported labeling that would require physicians to monitor a patient’s cognitive status as part of the efforts to mitigate risk prior to undergoing ECT and throughout the course of treatment.

Class III or Class II?

Among the reasons cited by panelists supporting the class III category for severe depression were associated memory loss and the lack of long-term data. These panelists included the consumer and patient representatives on the panel, who were concerned about the lack of knowledge about long-term adverse effects associated with ECT. Dr. David Good, professor and chair of neurology, Pennsylvania State College, Hershey, said that despite responses in the public docket describing ECT as lifesaving, he leaned toward supporting class III status because of the absence of long-term data and evidence showing that ECT is associated with memory loss.

Those supporting a switch to the class II category agreed there was adequate evidence that ECT was effective and advocated the use of special controls to help mitigate the associated risks of ECT.

"It would be a mistake to even take the risk of leaving it at as a class III and the possibility that it may be removed from the market," said Dr. Wayne K. Goodman, professor and chairman of the department of psychiatry, Mount Sinai School of Medicine, New York. He pointed out that there is no alternative to ECT for acutely suicidal patients with treatment-resistant depression, for whom ECT is "literally, life saving. ... So to eliminate this option literally would be eliminating a lifeline to many patients." Dr. Goodman referred to what he believes is a disconnect between the strength of the published data on ECT and the clinical impressions of the effectiveness of ECT among psychiatrists like himself, and noted that about 20-25 years ago, "there was such a strong wealth of clinical impression that ECT is so efficacious, that we’ve skipped the step somewhere along the way of clinical trials that normally would convince a panel like this that we have adequate evidence for efficacy and safety."

Panel members also were asked to provide feedback on how the devices should be classified when used for treating schizophrenia, bipolar manic and mixed states, schizoaffective disorder, schizophreniform disorder, and catatonia. Most of the panel agreed that ECT devices remain in class III for schizophrenia, bipolar manic (and mixed) states, and schizoaffective disorder.

Several of the psychiatrists on the panel who supported a switch to class II for ECT when used to treat the bipolar indication cited the need for alternative treatments and the few treatment options available for severely ill treatment resistant patients with bipolar disorder – and the difficulty in conducting clinical trials in such patients.

The panel unanimously recommended that ECT devices remain in class III for schizophreniform disorder. Some panelists also thought that the devices should remain in class III when used to treat catatonia. Others pointed out, however, that this is a relatively rare condition and that ECT could be inappropriately restricted and might not be available for these patients if categorized as class III.

Availability Issues

In an interview after the meeting, Dr. Richard D. Weiner, professor of psychiatry and behavioral sciences at Duke University, Durham, N.C., said he did not expect that a change in classification would result in the unavailability of ECT. In addition, the result of the hearing will not have an effect on the practice of ECT for at least several years, predicted Dr. Weiner, who also spoke during the open comment session of the meeting. An FDA spokesperson said once the agency makes a decision on the classification, it will have to go through the public notice and comment process, which can take at least 1 year.

The FDA received about 3,000 responses about this classification issue in a public docket, between September 2009 and January 2010, from medical and mental health providers, current and former ECT providers, recipients of ECT and their relatives and friends, as well as other groups. Most – 79% – of the responses opposed reclassification to class II; 14% supported reclassification. The most common adverse events reported were related to memory, followed by cognitive decline and brain damage, according to the FDA. Some people also reported that did not think they had been adequately informed about the risks of ECT before they were treated, FDA officials said at the meeting.

Currently, there are two manufacturers of ECT devices in the United States: Mecta Corp. and Somatics.

The FDA usually follows the recommendations of its advisory panels, which are not binding. Members of FDA panels are cleared of potential conflicts related to the topic under review.

After a decline that began in the 1960s, the use of ECT increased in the 1990s, and each year more than 100,000 patients in the United States are treated with ECT, according to the FDA.

Dr. Joshua Sharfstein, the Food and Drug Administration's principal deputy commissioner, has left the agency to become Maryland's health secretary.

Dr. Sharfstein was appointed to the FDA position in May 2009 by President Obama after having served as the acting commissioner for food and drugs for several months. Previously, he had served as the Baltimore city health commissioner, during which time he questioned the safety of over-the-counter cough and cold products in young children. His efforts received national attention and resulted in FDA hearings on the topic and, ultimately, product restrictions.

During his nearly 2 years at the FDA, Dr. Sharfstein gained a reputation as a tough, intelligent regulator who, alongside Commissioner Margaret Hamburg, sought to restore the FDA's role as an agency whose foremost mission is to protect and promote public health. Their initiatives included expediting responses to product safety issues and manufacturer violations.

Also during his tenure, the agency re-examined its controversial decision to clear a knee repair device, leading to a current re-evaluation of the how the FDA reviews medical devices.

John Taylor, counselor to the commissioner, has been asked to serve as the acting principal deputy commissioner for the next 60 days, the FDA said in a written statement.

Jessica Bylander of “The Gray Sheet,” also published by Elsevier, contributed to this report.

Dr. Joshua Sharfstein, the Food and Drug Administration's principal deputy commissioner, has left the agency to become Maryland's health secretary.

Dr. Sharfstein was appointed to the FDA position in May 2009 by President Obama after having served as the acting commissioner for food and drugs for several months. Previously, he had served as the Baltimore city health commissioner, during which time he questioned the safety of over-the-counter cough and cold products in young children. His efforts received national attention and resulted in FDA hearings on the topic and, ultimately, product restrictions.

During his nearly 2 years at the FDA, Dr. Sharfstein gained a reputation as a tough, intelligent regulator who, alongside Commissioner Margaret Hamburg, sought to restore the FDA's role as an agency whose foremost mission is to protect and promote public health. Their initiatives included expediting responses to product safety issues and manufacturer violations.

Also during his tenure, the agency re-examined its controversial decision to clear a knee repair device, leading to a current re-evaluation of the how the FDA reviews medical devices.

John Taylor, counselor to the commissioner, has been asked to serve as the acting principal deputy commissioner for the next 60 days, the FDA said in a written statement.

Jessica Bylander of “The Gray Sheet,” also published by Elsevier, contributed to this report.

Dr. Joshua Sharfstein, the Food and Drug Administration's principal deputy commissioner, has left the agency to become Maryland's health secretary.

Dr. Sharfstein was appointed to the FDA position in May 2009 by President Obama after having served as the acting commissioner for food and drugs for several months. Previously, he had served as the Baltimore city health commissioner, during which time he questioned the safety of over-the-counter cough and cold products in young children. His efforts received national attention and resulted in FDA hearings on the topic and, ultimately, product restrictions.

During his nearly 2 years at the FDA, Dr. Sharfstein gained a reputation as a tough, intelligent regulator who, alongside Commissioner Margaret Hamburg, sought to restore the FDA's role as an agency whose foremost mission is to protect and promote public health. Their initiatives included expediting responses to product safety issues and manufacturer violations.

Also during his tenure, the agency re-examined its controversial decision to clear a knee repair device, leading to a current re-evaluation of the how the FDA reviews medical devices.

John Taylor, counselor to the commissioner, has been asked to serve as the acting principal deputy commissioner for the next 60 days, the FDA said in a written statement.

Jessica Bylander of “The Gray Sheet,” also published by Elsevier, contributed to this report.

The Infectious Diseases Society of America rolled out its first-ever guidelines for treating methicillin-resistant Staphylococcus aureus – including recommendations to battle the growing threat posed by MRSA-related skin and soft-tissue infections.

The comprehensive guidelines also outline evidence-based approaches on topics ranging from personal hygiene and wound care to antibiotic therapies for invasive MRSA, as well as options after vancomycin treatment failure.

The guidelines' primary objective is “to provide recommendations on the management of some of the most common clinical syndromes encountered by adult and pediatric clinicians who care for patients with MRSA infections,” according to the executive summary (Clin. Infect. Dis. 2011;52:e18-55).

The guidelines provide adult and pediatric clinicians with guidance on how to treat relatively uncomplicated MRSA infections, as well as more serious infections, according to Dr. Catherine Liu, the guidelines' lead author and assistant clinical professor in the division of infectious diseases, University of California, San Francisco.

The new recommendations cover community- and hospital-associated MRSA infections, Dr. Liu added.

MRSA infections account for about 60% of skin infections seen in U.S. emergency departments, and invasive MRSA infections cause about 18,000 deaths a year, according to the Infectious Diseases Society of America (IDSA).

The evidence-based guidelines have been endorsed by the Pediatric Infectious Diseases Society, the American College of Emergency Physicians, and the American Academy of Pediatrics.

The guidelines are voluntary and “are not intended to take the place of a doctor's judgment, but rather support the decision-making process, which must be individualized according to each patient's circumstances,” according to a statement issued by IDSA, which funded the guidelines.

A 13-member expert panel reviewed hundreds of scientific studies, papers, and presentations to create the recommendations.

The guidelines' sections start with a clinical question, followed by a numbered list of recommendations and a summary of the most relevant evidence to support the recommendations.

In most cases, the sections include information on pediatric considerations.

The guidelines also highlight areas that are controversial because of limited or conflicting data.

The first topic addressed is the management of skin and soft tissue infections due to MRSA, which have become a significant problem over the last decade, Dr. Liu said in an interview.

For example, MRSA is now the predominant organism causing purulent skin infections in patients who present to emergency departments, she noted.

The guidelines address several types of skin infections, including abscesses, cellulitis, and more complicated skin infections.

The guidelines also offer recommendations on the role of antibiotics, including situations in which they may not be indicated, and circumstances where they are recommended.

They also offer guidance “on specific antibiotic choices for the different types of skin infections,” Dr. Liu noted.

Other topics covered include the management of MRSA pneumonia, bacteremia, and infective endocarditis; central nervous system infections; and bone and joint infections.

Additional sections review the role of adjunctive therapies in the treatment of MRSA infections, MRSA infections in neonates, and specific recommendations on vancomycin dosing and monitoring.

IDSA will update the guidelines as more information and newer antibiotics become available.

However, timely updating can be difficult because of the review and publication process, Dr. Liu commented.

For example, the Food and Drug Administration approved the intravenous cephalosporin antibiotic ceftaroline in October 2010 for acute bacterial skin and soft tissue infections, including cases caused by MRSA.

But approval came after the IDSA guidelines were finalized, and that information was not included.

Nonetheless, the guidelines note that ceftaroline “may become available in the near future for the treatment” of complicated skin and skin structure infections, Dr. Liu said.

The guidelines do not address active surveillance testing or other strategies aimed at preventing MRSA in health care settings, topics that have been addressed in previously released guidelines.

IDSA funded the development of the guidelines. Of the expert panel's 13 members, 9 reported having potential conflicts of interest that included honoraria or research support from, or having served as a consultant or adviser to, pharmaceutical companies, including Astellas, Cubist Pharmaceutical, Forest, Merck, Ortho-McNeil, Pfizer, Sanofi-Aventis, Schering-Plough, and Theravance. The remaining authors of the guidelines, including the lead author, Dr. Catherine Liu, reported no conflicts.

The Infectious Diseases Society of America rolled out its first-ever guidelines for treating methicillin-resistant Staphylococcus aureus – including recommendations to battle the growing threat posed by MRSA-related skin and soft-tissue infections.

The comprehensive guidelines also outline evidence-based approaches on topics ranging from personal hygiene and wound care to antibiotic therapies for invasive MRSA, as well as options after vancomycin treatment failure.

The guidelines' primary objective is “to provide recommendations on the management of some of the most common clinical syndromes encountered by adult and pediatric clinicians who care for patients with MRSA infections,” according to the executive summary (Clin. Infect. Dis. 2011;52:e18-55).

The guidelines provide adult and pediatric clinicians with guidance on how to treat relatively uncomplicated MRSA infections, as well as more serious infections, according to Dr. Catherine Liu, the guidelines' lead author and assistant clinical professor in the division of infectious diseases, University of California, San Francisco.

The new recommendations cover community- and hospital-associated MRSA infections, Dr. Liu added.

MRSA infections account for about 60% of skin infections seen in U.S. emergency departments, and invasive MRSA infections cause about 18,000 deaths a year, according to the Infectious Diseases Society of America (IDSA).

The evidence-based guidelines have been endorsed by the Pediatric Infectious Diseases Society, the American College of Emergency Physicians, and the American Academy of Pediatrics.

The guidelines are voluntary and “are not intended to take the place of a doctor's judgment, but rather support the decision-making process, which must be individualized according to each patient's circumstances,” according to a statement issued by IDSA, which funded the guidelines.

A 13-member expert panel reviewed hundreds of scientific studies, papers, and presentations to create the recommendations.

The guidelines' sections start with a clinical question, followed by a numbered list of recommendations and a summary of the most relevant evidence to support the recommendations.

In most cases, the sections include information on pediatric considerations.

The guidelines also highlight areas that are controversial because of limited or conflicting data.

The first topic addressed is the management of skin and soft tissue infections due to MRSA, which have become a significant problem over the last decade, Dr. Liu said in an interview.

For example, MRSA is now the predominant organism causing purulent skin infections in patients who present to emergency departments, she noted.

The guidelines address several types of skin infections, including abscesses, cellulitis, and more complicated skin infections.

The guidelines also offer recommendations on the role of antibiotics, including situations in which they may not be indicated, and circumstances where they are recommended.

They also offer guidance “on specific antibiotic choices for the different types of skin infections,” Dr. Liu noted.

Other topics covered include the management of MRSA pneumonia, bacteremia, and infective endocarditis; central nervous system infections; and bone and joint infections.

Additional sections review the role of adjunctive therapies in the treatment of MRSA infections, MRSA infections in neonates, and specific recommendations on vancomycin dosing and monitoring.

IDSA will update the guidelines as more information and newer antibiotics become available.

However, timely updating can be difficult because of the review and publication process, Dr. Liu commented.

For example, the Food and Drug Administration approved the intravenous cephalosporin antibiotic ceftaroline in October 2010 for acute bacterial skin and soft tissue infections, including cases caused by MRSA.

But approval came after the IDSA guidelines were finalized, and that information was not included.

Nonetheless, the guidelines note that ceftaroline “may become available in the near future for the treatment” of complicated skin and skin structure infections, Dr. Liu said.

The guidelines do not address active surveillance testing or other strategies aimed at preventing MRSA in health care settings, topics that have been addressed in previously released guidelines.

IDSA funded the development of the guidelines. Of the expert panel's 13 members, 9 reported having potential conflicts of interest that included honoraria or research support from, or having served as a consultant or adviser to, pharmaceutical companies, including Astellas, Cubist Pharmaceutical, Forest, Merck, Ortho-McNeil, Pfizer, Sanofi-Aventis, Schering-Plough, and Theravance. The remaining authors of the guidelines, including the lead author, Dr. Catherine Liu, reported no conflicts.

The Infectious Diseases Society of America rolled out its first-ever guidelines for treating methicillin-resistant Staphylococcus aureus – including recommendations to battle the growing threat posed by MRSA-related skin and soft-tissue infections.

The comprehensive guidelines also outline evidence-based approaches on topics ranging from personal hygiene and wound care to antibiotic therapies for invasive MRSA, as well as options after vancomycin treatment failure.

The guidelines' primary objective is “to provide recommendations on the management of some of the most common clinical syndromes encountered by adult and pediatric clinicians who care for patients with MRSA infections,” according to the executive summary (Clin. Infect. Dis. 2011;52:e18-55).

The guidelines provide adult and pediatric clinicians with guidance on how to treat relatively uncomplicated MRSA infections, as well as more serious infections, according to Dr. Catherine Liu, the guidelines' lead author and assistant clinical professor in the division of infectious diseases, University of California, San Francisco.

The new recommendations cover community- and hospital-associated MRSA infections, Dr. Liu added.

MRSA infections account for about 60% of skin infections seen in U.S. emergency departments, and invasive MRSA infections cause about 18,000 deaths a year, according to the Infectious Diseases Society of America (IDSA).

The evidence-based guidelines have been endorsed by the Pediatric Infectious Diseases Society, the American College of Emergency Physicians, and the American Academy of Pediatrics.

The guidelines are voluntary and “are not intended to take the place of a doctor's judgment, but rather support the decision-making process, which must be individualized according to each patient's circumstances,” according to a statement issued by IDSA, which funded the guidelines.

A 13-member expert panel reviewed hundreds of scientific studies, papers, and presentations to create the recommendations.

The guidelines' sections start with a clinical question, followed by a numbered list of recommendations and a summary of the most relevant evidence to support the recommendations.

In most cases, the sections include information on pediatric considerations.

The guidelines also highlight areas that are controversial because of limited or conflicting data.

The first topic addressed is the management of skin and soft tissue infections due to MRSA, which have become a significant problem over the last decade, Dr. Liu said in an interview.

For example, MRSA is now the predominant organism causing purulent skin infections in patients who present to emergency departments, she noted.

The guidelines address several types of skin infections, including abscesses, cellulitis, and more complicated skin infections.

The guidelines also offer recommendations on the role of antibiotics, including situations in which they may not be indicated, and circumstances where they are recommended.

They also offer guidance “on specific antibiotic choices for the different types of skin infections,” Dr. Liu noted.

Other topics covered include the management of MRSA pneumonia, bacteremia, and infective endocarditis; central nervous system infections; and bone and joint infections.

Additional sections review the role of adjunctive therapies in the treatment of MRSA infections, MRSA infections in neonates, and specific recommendations on vancomycin dosing and monitoring.

IDSA will update the guidelines as more information and newer antibiotics become available.

However, timely updating can be difficult because of the review and publication process, Dr. Liu commented.

For example, the Food and Drug Administration approved the intravenous cephalosporin antibiotic ceftaroline in October 2010 for acute bacterial skin and soft tissue infections, including cases caused by MRSA.

But approval came after the IDSA guidelines were finalized, and that information was not included.

Nonetheless, the guidelines note that ceftaroline “may become available in the near future for the treatment” of complicated skin and skin structure infections, Dr. Liu said.

The guidelines do not address active surveillance testing or other strategies aimed at preventing MRSA in health care settings, topics that have been addressed in previously released guidelines.

IDSA funded the development of the guidelines. Of the expert panel's 13 members, 9 reported having potential conflicts of interest that included honoraria or research support from, or having served as a consultant or adviser to, pharmaceutical companies, including Astellas, Cubist Pharmaceutical, Forest, Merck, Ortho-McNeil, Pfizer, Sanofi-Aventis, Schering-Plough, and Theravance. The remaining authors of the guidelines, including the lead author, Dr. Catherine Liu, reported no conflicts.

The Food and Drug Administration has asked manufacturers of prescription pain products containing acetaminophen to include no more than 325 mg of the drug in each capsule, tablet, or other dosage unit.

According to a safety announcement issued Jan. 13 by the agency, the action was taken to address the ongoing problem of acetaminophen overdose, a leading cause of severe liver injury in the United States.

In addition, the FDA requests that manufacturers of these combination products –including Vicodin and Percocet – add a boxed warning to product labels about the potential risk of severe liver injury if acetaminophen is taken in excessive doses or with alcohol.

Manufacturers have until January 2014 to comply with the recommendations, so a shortage of these medications is not anticipated, according to the agency.

The FDA is also asking clinicians to educate their patients about the dangers of acetaminophen overdose and to advise patients to take no more than the maximum daily dose of acetaminophen (4,000 mg).

"For physicians and other health care providers, we want to emphasize that it’s important to talk to patients and make sure that they are aware of the risks of using prescription pain medicines with acetaminophen," Dr. Sandra Kweder said during a press briefing.

"Health care professionals should also make sure their patients know how much acetaminophen is contained in any prescription product," added Dr. Kweder, deputy director of the Office of New Drugs, in the FDA’s Center for Drug Evaluation and Research. By limiting the amount of acetaminophen contained in each dose, "we don’t believe we are making these products less effective," she said, noting that the doses of the drug in these products have gradually "crept up" over the past few decades.

Currently, prescription acetaminophen products contain up to 750 mg of acetaminophen per dosage unit, but there are no data indicating that more than 325 mg of acetaminophen per unit provides greater pain relief, according to the FDA.

The agency’s request does not apply to over-the-counter products, which can contain as much as 500 mg per tablet or capsule in the products marketed as extra strength. Information about the risk of liver injury already is required on the label for OTC products containing acetaminophen. The FDA announcement noted that the agency continues to evaluate ways of reducing the risk of acetaminophen-related liver injury from OTC products.

Almost half of acetaminophen-related cases of liver failure in the United States are caused by overdoses from prescription opioid-acetaminophen products, which are among the most commonly prescribed products in the United States, accounting for almost 200 million prescriptions dispensed per year.

More information is available at www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm165107.htm. Serious adverse events associated with acetaminophen or products that contain acetaminophen should be reported to the FDA’s MedWatch program online or at 800-332-1088.

The Food and Drug Administration has asked manufacturers of prescription pain products containing acetaminophen to include no more than 325 mg of the drug in each capsule, tablet, or other dosage unit.

According to a safety announcement issued Jan. 13 by the agency, the action was taken to address the ongoing problem of acetaminophen overdose, a leading cause of severe liver injury in the United States.

In addition, the FDA requests that manufacturers of these combination products –including Vicodin and Percocet – add a boxed warning to product labels about the potential risk of severe liver injury if acetaminophen is taken in excessive doses or with alcohol.

Manufacturers have until January 2014 to comply with the recommendations, so a shortage of these medications is not anticipated, according to the agency.

The FDA is also asking clinicians to educate their patients about the dangers of acetaminophen overdose and to advise patients to take no more than the maximum daily dose of acetaminophen (4,000 mg).

"For physicians and other health care providers, we want to emphasize that it’s important to talk to patients and make sure that they are aware of the risks of using prescription pain medicines with acetaminophen," Dr. Sandra Kweder said during a press briefing.

"Health care professionals should also make sure their patients know how much acetaminophen is contained in any prescription product," added Dr. Kweder, deputy director of the Office of New Drugs, in the FDA’s Center for Drug Evaluation and Research. By limiting the amount of acetaminophen contained in each dose, "we don’t believe we are making these products less effective," she said, noting that the doses of the drug in these products have gradually "crept up" over the past few decades.

Currently, prescription acetaminophen products contain up to 750 mg of acetaminophen per dosage unit, but there are no data indicating that more than 325 mg of acetaminophen per unit provides greater pain relief, according to the FDA.

The agency’s request does not apply to over-the-counter products, which can contain as much as 500 mg per tablet or capsule in the products marketed as extra strength. Information about the risk of liver injury already is required on the label for OTC products containing acetaminophen. The FDA announcement noted that the agency continues to evaluate ways of reducing the risk of acetaminophen-related liver injury from OTC products.

Almost half of acetaminophen-related cases of liver failure in the United States are caused by overdoses from prescription opioid-acetaminophen products, which are among the most commonly prescribed products in the United States, accounting for almost 200 million prescriptions dispensed per year.

More information is available at www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm165107.htm. Serious adverse events associated with acetaminophen or products that contain acetaminophen should be reported to the FDA’s MedWatch program online or at 800-332-1088.

The Food and Drug Administration has asked manufacturers of prescription pain products containing acetaminophen to include no more than 325 mg of the drug in each capsule, tablet, or other dosage unit.

According to a safety announcement issued Jan. 13 by the agency, the action was taken to address the ongoing problem of acetaminophen overdose, a leading cause of severe liver injury in the United States.

In addition, the FDA requests that manufacturers of these combination products –including Vicodin and Percocet – add a boxed warning to product labels about the potential risk of severe liver injury if acetaminophen is taken in excessive doses or with alcohol.

Manufacturers have until January 2014 to comply with the recommendations, so a shortage of these medications is not anticipated, according to the agency.

The FDA is also asking clinicians to educate their patients about the dangers of acetaminophen overdose and to advise patients to take no more than the maximum daily dose of acetaminophen (4,000 mg).

"For physicians and other health care providers, we want to emphasize that it’s important to talk to patients and make sure that they are aware of the risks of using prescription pain medicines with acetaminophen," Dr. Sandra Kweder said during a press briefing.

"Health care professionals should also make sure their patients know how much acetaminophen is contained in any prescription product," added Dr. Kweder, deputy director of the Office of New Drugs, in the FDA’s Center for Drug Evaluation and Research. By limiting the amount of acetaminophen contained in each dose, "we don’t believe we are making these products less effective," she said, noting that the doses of the drug in these products have gradually "crept up" over the past few decades.

Currently, prescription acetaminophen products contain up to 750 mg of acetaminophen per dosage unit, but there are no data indicating that more than 325 mg of acetaminophen per unit provides greater pain relief, according to the FDA.

The agency’s request does not apply to over-the-counter products, which can contain as much as 500 mg per tablet or capsule in the products marketed as extra strength. Information about the risk of liver injury already is required on the label for OTC products containing acetaminophen. The FDA announcement noted that the agency continues to evaluate ways of reducing the risk of acetaminophen-related liver injury from OTC products.

Almost half of acetaminophen-related cases of liver failure in the United States are caused by overdoses from prescription opioid-acetaminophen products, which are among the most commonly prescribed products in the United States, accounting for almost 200 million prescriptions dispensed per year.

More information is available at www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm165107.htm. Serious adverse events associated with acetaminophen or products that contain acetaminophen should be reported to the FDA’s MedWatch program online or at 800-332-1088.