Elizabeth Mechcatie

While misdiagnosis of restless legs syndrome remains common, the Food and Drug Administration has increased the agents available to treat this movement disorder by approving the dopamine agonist pramipexole for moderate to severe cases.

Pramipexole is the second drug and the second dopamine agonist to be approved for this condition. The first was ropinirole (Requip), another dopamine agonist approved last year for restless legs syndrome (RLS), which affects as many as 3% of the population.

Dopamine agonists have been considered first-line treatments for RLS by expert consensus panels before they were approved, according to Dr. John Winkelman, who is medical director of the sleep health center at Brigham and Women's Hospital, and Harvard Medical School in Boston.

Although it will take more time for recognition of RLS to improve, “the good news is that the treatments are so effective and generally so well tolerated, it is very gratifying to treat,” and treatment typically produces a rapid response, Dr. Winkelman said.

In his experience, it is “the unusual patient who does not have some response to one of the dopamine agonists, and you need to go back and reassess the diagnosis” in patients who have no response.

Both pramipexole, marketed as Mirapex by Boehringer Ingelheim, and ropinirole, marketed as Requip, have been available for almost 10 years, since they were approved for Parkinson's disease. (Dr. Winkelman is a consultant to Boehringer Ingelheim and to ropinirole manufacturer GlaxoSmithKline, as well as other companies that manufacture products for insomnia and other sleep disorders.)

Pramipexole was significantly more effective than placebo in four randomized, double-blind, 3− to 12-week studies of about 1,000 patients with moderate to severe RLS, which evaluated the effect of treatment on a scale based on patient-reported symptoms and a Clinical Global Impressions scale.

Dr. Winkelman was the lead author of one study of 344 patients, published in September, which found that at 12 weeks, the patients on three fixed doses of pramipexole had significantly greater improvements from baseline than those on placebo in a scale that represented patient rating of symptom severity, which covers different aspects of RLS, such as effects on sleep and next-day functioning.

In addition, 70%–75% of patients on the three doses of pramipexole studied were rated as “very much improved” or “much improved” on a clinician rating scale, compared with 51% of those on placebo, a significant difference (Neurology 2006;67:1034–9). A strong placebo effect was seen on both of these primary end points, which Dr. Winkelman noted was true for disorders in which people are asked how they are doing.

Side effects were generally mild, with no serious adverse events considered drug-related, Dr. Winkelman said. Nausea was the main side effect that was more common in patients on the drug (19% vs. almost 5%) but was mild and transient.

Because this was a forced titration study, in which patients were titrated up to the preassigned dose even if they responded to a lower dose, side effects may have been more common than if the doses were individualized, he said.

Interestingly, a benefit of the low dose of 0.125 mg over placebo was seen at 1 week, he pointed out.

Restless legs syndrome becomes more prevalent as people age, with the typical age of onset in the 40s and 50s. The symptoms and effects of the disorder are not well recognized, he said, noting that RLS substantially interferes with a person's ability to fall asleep and stay asleep, and with their daytime functioning. People with moderate to severe RLS have symptoms “more often than not”–at least three times a week.

The indications section of the revised label for pramipexole lists diagnostic criteria for restless legs syndrome, including an urge to move the legs that is “usually accompanied or caused by uncomfortable and unpleasant leg sensations,” symptoms that begin or worsen during periods of inactivity, such as lying or sitting; and symptoms that are partially or totally relieved by movement such as walking or stretching, for at least as long as the activity continues.

“Why a dopamine agonist works in restless legs syndrome is not entirely clear,” he said. Dopamine is involved in the regulation of movement, and potentially in sensorimotor integration, and RLS is considered a sensorimotor disorder.

The dopamine agonist doses used for RLS are much lower than doses used to treat Parkinson's. The FDA-recommended starting dose is 0.125 mg taken once daily 2–3 hours before bedtime. If necessary, the dose can be increased every 4–7 days to 0.25 mg daily, and if necessary, to 0.5 mg daily after another 4–7 days.

The revised label says that there is no evidence that a daily dose of 0.75 mg provides any more benefit than the 0.5-mg dose.

While misdiagnosis of restless legs syndrome remains common, the Food and Drug Administration has increased the agents available to treat this movement disorder by approving the dopamine agonist pramipexole for moderate to severe cases.

Pramipexole is the second drug and the second dopamine agonist to be approved for this condition. The first was ropinirole (Requip), another dopamine agonist approved last year for restless legs syndrome (RLS), which affects as many as 3% of the population.

Dopamine agonists have been considered first-line treatments for RLS by expert consensus panels before they were approved, according to Dr. John Winkelman, who is medical director of the sleep health center at Brigham and Women's Hospital, and Harvard Medical School in Boston.

Although it will take more time for recognition of RLS to improve, “the good news is that the treatments are so effective and generally so well tolerated, it is very gratifying to treat,” and treatment typically produces a rapid response, Dr. Winkelman said.

In his experience, it is “the unusual patient who does not have some response to one of the dopamine agonists, and you need to go back and reassess the diagnosis” in patients who have no response.

Both pramipexole, marketed as Mirapex by Boehringer Ingelheim, and ropinirole, marketed as Requip, have been available for almost 10 years, since they were approved for Parkinson's disease. (Dr. Winkelman is a consultant to Boehringer Ingelheim and to ropinirole manufacturer GlaxoSmithKline, as well as other companies that manufacture products for insomnia and other sleep disorders.)

Pramipexole was significantly more effective than placebo in four randomized, double-blind, 3− to 12-week studies of about 1,000 patients with moderate to severe RLS, which evaluated the effect of treatment on a scale based on patient-reported symptoms and a Clinical Global Impressions scale.

Dr. Winkelman was the lead author of one study of 344 patients, published in September, which found that at 12 weeks, the patients on three fixed doses of pramipexole had significantly greater improvements from baseline than those on placebo in a scale that represented patient rating of symptom severity, which covers different aspects of RLS, such as effects on sleep and next-day functioning.

In addition, 70%–75% of patients on the three doses of pramipexole studied were rated as “very much improved” or “much improved” on a clinician rating scale, compared with 51% of those on placebo, a significant difference (Neurology 2006;67:1034–9). A strong placebo effect was seen on both of these primary end points, which Dr. Winkelman noted was true for disorders in which people are asked how they are doing.

Side effects were generally mild, with no serious adverse events considered drug-related, Dr. Winkelman said. Nausea was the main side effect that was more common in patients on the drug (19% vs. almost 5%) but was mild and transient.

Because this was a forced titration study, in which patients were titrated up to the preassigned dose even if they responded to a lower dose, side effects may have been more common than if the doses were individualized, he said.

Interestingly, a benefit of the low dose of 0.125 mg over placebo was seen at 1 week, he pointed out.

Restless legs syndrome becomes more prevalent as people age, with the typical age of onset in the 40s and 50s. The symptoms and effects of the disorder are not well recognized, he said, noting that RLS substantially interferes with a person's ability to fall asleep and stay asleep, and with their daytime functioning. People with moderate to severe RLS have symptoms “more often than not”–at least three times a week.

The indications section of the revised label for pramipexole lists diagnostic criteria for restless legs syndrome, including an urge to move the legs that is “usually accompanied or caused by uncomfortable and unpleasant leg sensations,” symptoms that begin or worsen during periods of inactivity, such as lying or sitting; and symptoms that are partially or totally relieved by movement such as walking or stretching, for at least as long as the activity continues.

“Why a dopamine agonist works in restless legs syndrome is not entirely clear,” he said. Dopamine is involved in the regulation of movement, and potentially in sensorimotor integration, and RLS is considered a sensorimotor disorder.

The dopamine agonist doses used for RLS are much lower than doses used to treat Parkinson's. The FDA-recommended starting dose is 0.125 mg taken once daily 2–3 hours before bedtime. If necessary, the dose can be increased every 4–7 days to 0.25 mg daily, and if necessary, to 0.5 mg daily after another 4–7 days.

The revised label says that there is no evidence that a daily dose of 0.75 mg provides any more benefit than the 0.5-mg dose.

While misdiagnosis of restless legs syndrome remains common, the Food and Drug Administration has increased the agents available to treat this movement disorder by approving the dopamine agonist pramipexole for moderate to severe cases.

Pramipexole is the second drug and the second dopamine agonist to be approved for this condition. The first was ropinirole (Requip), another dopamine agonist approved last year for restless legs syndrome (RLS), which affects as many as 3% of the population.

Dopamine agonists have been considered first-line treatments for RLS by expert consensus panels before they were approved, according to Dr. John Winkelman, who is medical director of the sleep health center at Brigham and Women's Hospital, and Harvard Medical School in Boston.

Although it will take more time for recognition of RLS to improve, “the good news is that the treatments are so effective and generally so well tolerated, it is very gratifying to treat,” and treatment typically produces a rapid response, Dr. Winkelman said.

In his experience, it is “the unusual patient who does not have some response to one of the dopamine agonists, and you need to go back and reassess the diagnosis” in patients who have no response.

Both pramipexole, marketed as Mirapex by Boehringer Ingelheim, and ropinirole, marketed as Requip, have been available for almost 10 years, since they were approved for Parkinson's disease. (Dr. Winkelman is a consultant to Boehringer Ingelheim and to ropinirole manufacturer GlaxoSmithKline, as well as other companies that manufacture products for insomnia and other sleep disorders.)

Pramipexole was significantly more effective than placebo in four randomized, double-blind, 3− to 12-week studies of about 1,000 patients with moderate to severe RLS, which evaluated the effect of treatment on a scale based on patient-reported symptoms and a Clinical Global Impressions scale.

Dr. Winkelman was the lead author of one study of 344 patients, published in September, which found that at 12 weeks, the patients on three fixed doses of pramipexole had significantly greater improvements from baseline than those on placebo in a scale that represented patient rating of symptom severity, which covers different aspects of RLS, such as effects on sleep and next-day functioning.

In addition, 70%–75% of patients on the three doses of pramipexole studied were rated as “very much improved” or “much improved” on a clinician rating scale, compared with 51% of those on placebo, a significant difference (Neurology 2006;67:1034–9). A strong placebo effect was seen on both of these primary end points, which Dr. Winkelman noted was true for disorders in which people are asked how they are doing.

Side effects were generally mild, with no serious adverse events considered drug-related, Dr. Winkelman said. Nausea was the main side effect that was more common in patients on the drug (19% vs. almost 5%) but was mild and transient.

Because this was a forced titration study, in which patients were titrated up to the preassigned dose even if they responded to a lower dose, side effects may have been more common than if the doses were individualized, he said.

Interestingly, a benefit of the low dose of 0.125 mg over placebo was seen at 1 week, he pointed out.

Restless legs syndrome becomes more prevalent as people age, with the typical age of onset in the 40s and 50s. The symptoms and effects of the disorder are not well recognized, he said, noting that RLS substantially interferes with a person's ability to fall asleep and stay asleep, and with their daytime functioning. People with moderate to severe RLS have symptoms “more often than not”–at least three times a week.

The indications section of the revised label for pramipexole lists diagnostic criteria for restless legs syndrome, including an urge to move the legs that is “usually accompanied or caused by uncomfortable and unpleasant leg sensations,” symptoms that begin or worsen during periods of inactivity, such as lying or sitting; and symptoms that are partially or totally relieved by movement such as walking or stretching, for at least as long as the activity continues.

“Why a dopamine agonist works in restless legs syndrome is not entirely clear,” he said. Dopamine is involved in the regulation of movement, and potentially in sensorimotor integration, and RLS is considered a sensorimotor disorder.

The dopamine agonist doses used for RLS are much lower than doses used to treat Parkinson's. The FDA-recommended starting dose is 0.125 mg taken once daily 2–3 hours before bedtime. If necessary, the dose can be increased every 4–7 days to 0.25 mg daily, and if necessary, to 0.5 mg daily after another 4–7 days.

The revised label says that there is no evidence that a daily dose of 0.75 mg provides any more benefit than the 0.5-mg dose.

GAITHERSBURG, MD. — When used off label, coronary drug-eluting stents are associated with a greater risk of stent thrombosis, death, and myocardial infarction, and this critical information needs to be communicated to physicians and patients, a Food and Drug Administration advisory panel agreed last week.

The safety of drug-eluting stents (DES) was the topic of a 2-day meeting of the FDA's Circulatory System Devices Panel, where expert panelists heard testimony and presentations on DES from FDA officials, manufacturers of the two drug-eluting stents marketed in the United States, and representatives from medical associations and researchers in the United States and Europe. The meeting was convened by the FDA to review the issue of stent thrombosis and the duration of clopidogrel treatment after DES implantation, after concerns about the safety of DES were raised by studies presented at cardiology meetings this year reporting small but significant increases in mortality and MI, possibly due to stent thrombosis in DES recipients, 18 months to 3 years after implantation.

But at least 60% of DES use is off label for conditions that include in-stent restenosis, lesions, coronary artery bypass grafts, overlapping and multiple stents per vessel; in patients with diabetes and those with multivessel disease; and in more complex patients and lesions than were included in the preapproval studies.

The two drug-eluting stents that have been on the U.S. market since 2003 and 2004 are the Cypher sirolimus-eluting coronary stent manufactured by Cordis Corporation, and the Taxus Express paclitaxel-eluting coronary stent system, respectively. The Cypher stent is approved for patients with symptomatic ischemic disease caused by “discrete de novo lesions” that are 30 mm or less in length in native coronary arteries with a reference vessel diameter of at least 2.5 mm to no more than 3.5 mm. The Taxus stent is approved for improving luminal diameter of de novo lesions no more than 28 mm in length, in native coronary arteries of at least 2.5 mm to no more than 3.75 mm in diameter.

The panel unanimously agreed that when used for the approved indications, the safety concerns of drug-eluting stents did not outweigh their benefits, when compared with bare metal stents (BMS). The data indicate that when the stents are used on label, there appears to be a numerical excess of late stent thrombosis in DES recipients, but “the magnitude of that risk is uncertain, based on the available data,” said the panel's chair, Dr. William Maisel of Beth Israel Deaconess Medical Center, Boston. There was no association with an increase in deaths or MIs.

But the panel agreed that when used off label for more complex lesions and other uses, drug-eluting stents appeared to be associated with a greater risk of adverse events—stent thrombosis, death, and MI—and that antiplatelet treatment should be extended for at least 12 months after a DES is implanted. This is also true for bare metal stents.

The need for more studies was clear throughout the meeting. “I think we all agree that we need more data, better data, more patients, and larger studies,” Dr. Maisel remarked. The panel also agreed there were not enough data to comment on how DES compared with BMS, coronary artery bypass surgery, and medical therapy.

The panel also supported the need for a label change describing the greater risks of off-label use of the stents, and the need to provide patients and physicians with the latest information on safety. “We want physicians and patients to understand” if these stents are used off label, the risk of MI, stent thrombosis, and death is higher than if they are used for approved indications, Dr. Maisel said.

While the panel agreed that more studies were necessary to determine the appropriate duration of antiplatelet therapy after implantation of a DES, they agreed that at least 12 months was appropriate, until more data are available.

At the end of the meeting, Dr. Daniel Schultz, director of the FDA's Center for Devices and Radiological Health, said that it was clear that the FDA needs to communicate the latest information to physicians and patients as soon as possible, after considering the panel's comments. Methods of communicating to physicians may include a dear health care professional letter and a public health advisory.

GAITHERSBURG, MD. — When used off label, coronary drug-eluting stents are associated with a greater risk of stent thrombosis, death, and myocardial infarction, and this critical information needs to be communicated to physicians and patients, a Food and Drug Administration advisory panel agreed last week.

The safety of drug-eluting stents (DES) was the topic of a 2-day meeting of the FDA's Circulatory System Devices Panel, where expert panelists heard testimony and presentations on DES from FDA officials, manufacturers of the two drug-eluting stents marketed in the United States, and representatives from medical associations and researchers in the United States and Europe. The meeting was convened by the FDA to review the issue of stent thrombosis and the duration of clopidogrel treatment after DES implantation, after concerns about the safety of DES were raised by studies presented at cardiology meetings this year reporting small but significant increases in mortality and MI, possibly due to stent thrombosis in DES recipients, 18 months to 3 years after implantation.

But at least 60% of DES use is off label for conditions that include in-stent restenosis, lesions, coronary artery bypass grafts, overlapping and multiple stents per vessel; in patients with diabetes and those with multivessel disease; and in more complex patients and lesions than were included in the preapproval studies.

The two drug-eluting stents that have been on the U.S. market since 2003 and 2004 are the Cypher sirolimus-eluting coronary stent manufactured by Cordis Corporation, and the Taxus Express paclitaxel-eluting coronary stent system, respectively. The Cypher stent is approved for patients with symptomatic ischemic disease caused by “discrete de novo lesions” that are 30 mm or less in length in native coronary arteries with a reference vessel diameter of at least 2.5 mm to no more than 3.5 mm. The Taxus stent is approved for improving luminal diameter of de novo lesions no more than 28 mm in length, in native coronary arteries of at least 2.5 mm to no more than 3.75 mm in diameter.

The panel unanimously agreed that when used for the approved indications, the safety concerns of drug-eluting stents did not outweigh their benefits, when compared with bare metal stents (BMS). The data indicate that when the stents are used on label, there appears to be a numerical excess of late stent thrombosis in DES recipients, but “the magnitude of that risk is uncertain, based on the available data,” said the panel's chair, Dr. William Maisel of Beth Israel Deaconess Medical Center, Boston. There was no association with an increase in deaths or MIs.

But the panel agreed that when used off label for more complex lesions and other uses, drug-eluting stents appeared to be associated with a greater risk of adverse events—stent thrombosis, death, and MI—and that antiplatelet treatment should be extended for at least 12 months after a DES is implanted. This is also true for bare metal stents.

The need for more studies was clear throughout the meeting. “I think we all agree that we need more data, better data, more patients, and larger studies,” Dr. Maisel remarked. The panel also agreed there were not enough data to comment on how DES compared with BMS, coronary artery bypass surgery, and medical therapy.

The panel also supported the need for a label change describing the greater risks of off-label use of the stents, and the need to provide patients and physicians with the latest information on safety. “We want physicians and patients to understand” if these stents are used off label, the risk of MI, stent thrombosis, and death is higher than if they are used for approved indications, Dr. Maisel said.

While the panel agreed that more studies were necessary to determine the appropriate duration of antiplatelet therapy after implantation of a DES, they agreed that at least 12 months was appropriate, until more data are available.

At the end of the meeting, Dr. Daniel Schultz, director of the FDA's Center for Devices and Radiological Health, said that it was clear that the FDA needs to communicate the latest information to physicians and patients as soon as possible, after considering the panel's comments. Methods of communicating to physicians may include a dear health care professional letter and a public health advisory.

GAITHERSBURG, MD. — When used off label, coronary drug-eluting stents are associated with a greater risk of stent thrombosis, death, and myocardial infarction, and this critical information needs to be communicated to physicians and patients, a Food and Drug Administration advisory panel agreed last week.

The safety of drug-eluting stents (DES) was the topic of a 2-day meeting of the FDA's Circulatory System Devices Panel, where expert panelists heard testimony and presentations on DES from FDA officials, manufacturers of the two drug-eluting stents marketed in the United States, and representatives from medical associations and researchers in the United States and Europe. The meeting was convened by the FDA to review the issue of stent thrombosis and the duration of clopidogrel treatment after DES implantation, after concerns about the safety of DES were raised by studies presented at cardiology meetings this year reporting small but significant increases in mortality and MI, possibly due to stent thrombosis in DES recipients, 18 months to 3 years after implantation.

But at least 60% of DES use is off label for conditions that include in-stent restenosis, lesions, coronary artery bypass grafts, overlapping and multiple stents per vessel; in patients with diabetes and those with multivessel disease; and in more complex patients and lesions than were included in the preapproval studies.

The two drug-eluting stents that have been on the U.S. market since 2003 and 2004 are the Cypher sirolimus-eluting coronary stent manufactured by Cordis Corporation, and the Taxus Express paclitaxel-eluting coronary stent system, respectively. The Cypher stent is approved for patients with symptomatic ischemic disease caused by “discrete de novo lesions” that are 30 mm or less in length in native coronary arteries with a reference vessel diameter of at least 2.5 mm to no more than 3.5 mm. The Taxus stent is approved for improving luminal diameter of de novo lesions no more than 28 mm in length, in native coronary arteries of at least 2.5 mm to no more than 3.75 mm in diameter.

The panel unanimously agreed that when used for the approved indications, the safety concerns of drug-eluting stents did not outweigh their benefits, when compared with bare metal stents (BMS). The data indicate that when the stents are used on label, there appears to be a numerical excess of late stent thrombosis in DES recipients, but “the magnitude of that risk is uncertain, based on the available data,” said the panel's chair, Dr. William Maisel of Beth Israel Deaconess Medical Center, Boston. There was no association with an increase in deaths or MIs.

But the panel agreed that when used off label for more complex lesions and other uses, drug-eluting stents appeared to be associated with a greater risk of adverse events—stent thrombosis, death, and MI—and that antiplatelet treatment should be extended for at least 12 months after a DES is implanted. This is also true for bare metal stents.

The need for more studies was clear throughout the meeting. “I think we all agree that we need more data, better data, more patients, and larger studies,” Dr. Maisel remarked. The panel also agreed there were not enough data to comment on how DES compared with BMS, coronary artery bypass surgery, and medical therapy.

The panel also supported the need for a label change describing the greater risks of off-label use of the stents, and the need to provide patients and physicians with the latest information on safety. “We want physicians and patients to understand” if these stents are used off label, the risk of MI, stent thrombosis, and death is higher than if they are used for approved indications, Dr. Maisel said.

While the panel agreed that more studies were necessary to determine the appropriate duration of antiplatelet therapy after implantation of a DES, they agreed that at least 12 months was appropriate, until more data are available.

At the end of the meeting, Dr. Daniel Schultz, director of the FDA's Center for Devices and Radiological Health, said that it was clear that the FDA needs to communicate the latest information to physicians and patients as soon as possible, after considering the panel's comments. Methods of communicating to physicians may include a dear health care professional letter and a public health advisory.

ROCKVILLE, MD. — The Food and Drug Administration is reviewing a decade-old regulation that allows clinical studies of emergency treatments to be conducted without obtaining informed consent in people with certain life-threatening conditions.

The FDA's reappraisal and proposed revision of the rule were prompted by concerns that current safeguards do not provide enough protection of human subjects, and by comments that the safeguards are too onerous and impede important research.

At present, a narrow exception to the informed consent requirement exists in the case of patients who cannot provide consent because of their conditions and who have no family members available to give consent.

To be exempt from informed consent, an investigation must meet certain criteria, including the following:

▸ The patient is in a life-threatening situation.

▸ The available treatments are unproven or not satisfactory.

▸ Evidence supports the prospect of direct benefit to the individual.

Since the regulation went into effect in October 1996, the FDA has received 56 requests to conduct emergency research under this rule. A total of 21 studies have been conducted, are being conducted, or are about to start enrollment, according to the FDA.

The FDA has issued draft guidance geared toward institutional review boards, clinical investigators, and sponsors developing and conducting emergency research. The agency also sponsored a public hearing in October on emergency research.

At that hearing, presenters offered examples of emergency research that could not otherwise have been done without the exception.

Although the current rules could be simplified, the exception to informed consent is critical, said Dr. Paul Pepe, professor of surgery, medicine, and public health, and Riggs Family Chair in emergency medicine at the University of Texas Southwestern Medical Center at Dallas.

"Studies of the automated external defibrillator are an example of the tremendous lifesaving potential of emergency treatments," he said. Such studies can also show that treatments that have been widely accepted and appear to be logical may in fact be harmful in some populations, he added. For example, intravenous fluid resuscitation was found to be harmful in certain trauma populations. If these studies had not been done, Dr. Pepe explained, many people would have died.

"Any revisions to current regulations should serve to expand the ability to perform the highest quality emergency research and to enhance patient protections through fairness, openness, and the use of all media that provide explicit detail regarding the research," Dr. Edward P. Sloan and Dr. Charles Cairns said in a statement on behalf of the American College of Emergency Physicians.

The FDA will review written comments on the guidance, as well as comments made at the hearing, to determine whether the rule should be modified.

ROCKVILLE, MD. — The Food and Drug Administration is reviewing a decade-old regulation that allows clinical studies of emergency treatments to be conducted without obtaining informed consent in people with certain life-threatening conditions.

The FDA's reappraisal and proposed revision of the rule were prompted by concerns that current safeguards do not provide enough protection of human subjects, and by comments that the safeguards are too onerous and impede important research.

At present, a narrow exception to the informed consent requirement exists in the case of patients who cannot provide consent because of their conditions and who have no family members available to give consent.

To be exempt from informed consent, an investigation must meet certain criteria, including the following:

▸ The patient is in a life-threatening situation.

▸ The available treatments are unproven or not satisfactory.

▸ Evidence supports the prospect of direct benefit to the individual.

Since the regulation went into effect in October 1996, the FDA has received 56 requests to conduct emergency research under this rule. A total of 21 studies have been conducted, are being conducted, or are about to start enrollment, according to the FDA.

The FDA has issued draft guidance geared toward institutional review boards, clinical investigators, and sponsors developing and conducting emergency research. The agency also sponsored a public hearing in October on emergency research.

At that hearing, presenters offered examples of emergency research that could not otherwise have been done without the exception.

Although the current rules could be simplified, the exception to informed consent is critical, said Dr. Paul Pepe, professor of surgery, medicine, and public health, and Riggs Family Chair in emergency medicine at the University of Texas Southwestern Medical Center at Dallas.

"Studies of the automated external defibrillator are an example of the tremendous lifesaving potential of emergency treatments," he said. Such studies can also show that treatments that have been widely accepted and appear to be logical may in fact be harmful in some populations, he added. For example, intravenous fluid resuscitation was found to be harmful in certain trauma populations. If these studies had not been done, Dr. Pepe explained, many people would have died.

"Any revisions to current regulations should serve to expand the ability to perform the highest quality emergency research and to enhance patient protections through fairness, openness, and the use of all media that provide explicit detail regarding the research," Dr. Edward P. Sloan and Dr. Charles Cairns said in a statement on behalf of the American College of Emergency Physicians.

The FDA will review written comments on the guidance, as well as comments made at the hearing, to determine whether the rule should be modified.

ROCKVILLE, MD. — The Food and Drug Administration is reviewing a decade-old regulation that allows clinical studies of emergency treatments to be conducted without obtaining informed consent in people with certain life-threatening conditions.

The FDA's reappraisal and proposed revision of the rule were prompted by concerns that current safeguards do not provide enough protection of human subjects, and by comments that the safeguards are too onerous and impede important research.

At present, a narrow exception to the informed consent requirement exists in the case of patients who cannot provide consent because of their conditions and who have no family members available to give consent.

To be exempt from informed consent, an investigation must meet certain criteria, including the following:

▸ The patient is in a life-threatening situation.

▸ The available treatments are unproven or not satisfactory.

▸ Evidence supports the prospect of direct benefit to the individual.

Since the regulation went into effect in October 1996, the FDA has received 56 requests to conduct emergency research under this rule. A total of 21 studies have been conducted, are being conducted, or are about to start enrollment, according to the FDA.

The FDA has issued draft guidance geared toward institutional review boards, clinical investigators, and sponsors developing and conducting emergency research. The agency also sponsored a public hearing in October on emergency research.

At that hearing, presenters offered examples of emergency research that could not otherwise have been done without the exception.

Although the current rules could be simplified, the exception to informed consent is critical, said Dr. Paul Pepe, professor of surgery, medicine, and public health, and Riggs Family Chair in emergency medicine at the University of Texas Southwestern Medical Center at Dallas.

"Studies of the automated external defibrillator are an example of the tremendous lifesaving potential of emergency treatments," he said. Such studies can also show that treatments that have been widely accepted and appear to be logical may in fact be harmful in some populations, he added. For example, intravenous fluid resuscitation was found to be harmful in certain trauma populations. If these studies had not been done, Dr. Pepe explained, many people would have died.

"Any revisions to current regulations should serve to expand the ability to perform the highest quality emergency research and to enhance patient protections through fairness, openness, and the use of all media that provide explicit detail regarding the research," Dr. Edward P. Sloan and Dr. Charles Cairns said in a statement on behalf of the American College of Emergency Physicians.

The FDA will review written comments on the guidance, as well as comments made at the hearing, to determine whether the rule should be modified.

ROCKVILLE, MD. — The Food and Drug Administration is reviewing a decade-old regulation that allows clinical studies of emergency treatments to be conducted without obtaining informed consent in people with certain life-threatening conditions.

The FDA's reappraisal and proposed revision of the rule were prompted by concerns that current safeguards do not provide enough protection of human subjects, and by comments that the safeguards are too onerous and impede important research.

At present, a narrow exception to the informed consent requirement exists in the case of patients who cannot provide consent because of their conditions and who have no family members available to give consent.

To be exempt from informed consent, an investigation must meet certain criteria, including the following:

▸ The patient is in a life-threatening situation.

▸ The available treatments are unproven or not satisfactory.

▸ Evidence supports the prospect of direct benefit to the individual.

Since the regulation went into effect in October 1996, the FDA has received 56 requests to conduct emergency research under this rule. A total of 21 studies have been conducted, are being conducted, or are about to start enrollment, according to the FDA.

The FDA has issued draft guidance geared toward institutional review boards, clinical investigators, and sponsors developing and conducting emergency research. The agency also sponsored a public hearing in October on emergency research.

At that hearing, presenters offered examples of emergency research that could not otherwise have been done without the exception.

Although the current rules could be simplified, the exception to informed consent is critical, said Dr. Paul Pepe, professor of surgery, medicine, and public health, and Riggs Family Chair in emergency medicine at the University of Texas Southwestern Medical Center at Dallas.

“Studies of the automated external defibrillator are an example of the tremendous lifesaving potential of emergency treatments,” he said. Such studies can also show that treatments that have been widely accepted and appear to be logical may in fact be harmful in some populations, he added. For example, intravenous fluid resuscitation was found to be harmful in certain trauma populations. If these studies had not been done, Dr. Pepe explained, many people would have died.

The FDA will review written comments on the guidance, as well as comments made at the hearing, to determine whether the rule should be modified.

ROCKVILLE, MD. — The Food and Drug Administration is reviewing a decade-old regulation that allows clinical studies of emergency treatments to be conducted without obtaining informed consent in people with certain life-threatening conditions.

The FDA's reappraisal and proposed revision of the rule were prompted by concerns that current safeguards do not provide enough protection of human subjects, and by comments that the safeguards are too onerous and impede important research.

At present, a narrow exception to the informed consent requirement exists in the case of patients who cannot provide consent because of their conditions and who have no family members available to give consent.

To be exempt from informed consent, an investigation must meet certain criteria, including the following:

▸ The patient is in a life-threatening situation.

▸ The available treatments are unproven or not satisfactory.

▸ Evidence supports the prospect of direct benefit to the individual.

Since the regulation went into effect in October 1996, the FDA has received 56 requests to conduct emergency research under this rule. A total of 21 studies have been conducted, are being conducted, or are about to start enrollment, according to the FDA.

The FDA has issued draft guidance geared toward institutional review boards, clinical investigators, and sponsors developing and conducting emergency research. The agency also sponsored a public hearing in October on emergency research.

At that hearing, presenters offered examples of emergency research that could not otherwise have been done without the exception.

Although the current rules could be simplified, the exception to informed consent is critical, said Dr. Paul Pepe, professor of surgery, medicine, and public health, and Riggs Family Chair in emergency medicine at the University of Texas Southwestern Medical Center at Dallas.

“Studies of the automated external defibrillator are an example of the tremendous lifesaving potential of emergency treatments,” he said. Such studies can also show that treatments that have been widely accepted and appear to be logical may in fact be harmful in some populations, he added. For example, intravenous fluid resuscitation was found to be harmful in certain trauma populations. If these studies had not been done, Dr. Pepe explained, many people would have died.

The FDA will review written comments on the guidance, as well as comments made at the hearing, to determine whether the rule should be modified.

ROCKVILLE, MD. — The Food and Drug Administration is reviewing a decade-old regulation that allows clinical studies of emergency treatments to be conducted without obtaining informed consent in people with certain life-threatening conditions.

The FDA's reappraisal and proposed revision of the rule were prompted by concerns that current safeguards do not provide enough protection of human subjects, and by comments that the safeguards are too onerous and impede important research.

At present, a narrow exception to the informed consent requirement exists in the case of patients who cannot provide consent because of their conditions and who have no family members available to give consent.

To be exempt from informed consent, an investigation must meet certain criteria, including the following:

▸ The patient is in a life-threatening situation.

▸ The available treatments are unproven or not satisfactory.

▸ Evidence supports the prospect of direct benefit to the individual.

Since the regulation went into effect in October 1996, the FDA has received 56 requests to conduct emergency research under this rule. A total of 21 studies have been conducted, are being conducted, or are about to start enrollment, according to the FDA.

The FDA has issued draft guidance geared toward institutional review boards, clinical investigators, and sponsors developing and conducting emergency research. The agency also sponsored a public hearing in October on emergency research.

At that hearing, presenters offered examples of emergency research that could not otherwise have been done without the exception.

Although the current rules could be simplified, the exception to informed consent is critical, said Dr. Paul Pepe, professor of surgery, medicine, and public health, and Riggs Family Chair in emergency medicine at the University of Texas Southwestern Medical Center at Dallas.

“Studies of the automated external defibrillator are an example of the tremendous lifesaving potential of emergency treatments,” he said. Such studies can also show that treatments that have been widely accepted and appear to be logical may in fact be harmful in some populations, he added. For example, intravenous fluid resuscitation was found to be harmful in certain trauma populations. If these studies had not been done, Dr. Pepe explained, many people would have died.

The FDA will review written comments on the guidance, as well as comments made at the hearing, to determine whether the rule should be modified.

GAITHERSBURG, MD. - The Food and Drug Administration's Arthritis Advisory Committee's nearly unanimous support for approving celecoxib for juvenile rheumatoid arthritis in a vote last month may alleviate some of the need for child-friendly drug formulations and add another JRA treatment option.

“We need the advantages an additional formulation will give,” and the advantages of having a different medication which is different from naproxen (Naprosyn) and is a selective cyclooxygenase-2 (COX-2) inhibitor “for at least the potential benefits on bleeding, bruising, and hoped for decrease in GI toxicity,” said Dr. Thomas Lehman, chief of pediatric rheumatology at the Hospital for Special Surgery, New York. He pointed out that noncompliance with medication is one of the most difficult issues in pediatric rheumatology.

He added that many children will respond to one NSAID after not responding to another, and that in his own practice, he said it was “very common” to try two or three different NSAIDs, “looking for a good effect and tolerance” before a more potentially toxic drug is considered, unless the child has obvious aggressive disease.

At the Nov. 29 meeting, the federal advisory panel agreed in a 15–1 vote that the risk-benefit ratio of celecoxib was “adequate” to support its approval for treating JRA.

All panelists agreed that the available data showed the COX-2 selective NSAID was effective for this indication, based on a 3-month randomized, double-blind study comparing naproxen (15 mg/kg daily) with celecoxib (6 mg/kg or 12 mg/kg daily). The study included 242 children and adolescents aged 2–16 years with JRA.

The FDA usually follows the recommendations of its advisory panels.

Celecoxib, marketed as Celebrex by Pfizer, was approved for treating osteoarthritis and RA in adults in 1998. Celecoxib remained available after rofecoxib (Vioxx), which was approved for JRA, was taken off the market in 2004 because of an increased cardiovascular risk seen in a large study. An elevated cardiovascular risk was seen in one of three long-term trials comparing celecoxib with placebo, but it remained on the market with the addition of a boxed warning about the possible increase in serious cardiovascular events.

At the committee meeting for pediatric approval, the panelists' vote on safety was split. All panelists were concerned about the absence of long-term safety data of celecoxib in this population. They strongly recommended that the FDA tie approval to a commitment on the part of Pfizer to use a registry study to follow long-term safety issues, including GI, renal, and cardiovascular safety. They agreed that Pfizer's plan to vigorously investigate spontaneous adverse event reports of celecoxib in children and adolescents was inadequate.

Panelist member Dr. Margaret O'Neil, a pediatric rheumatologist at the University of Oklahoma, Oklahoma City, said that “switching from drug A to drug B may be the magic bullet,” so having more options makes it possible to try another drug before proceeding to drugs that are potentially more toxic.

If approved, the oral suspension used in the trial would not be the formulation marketed because of problems producing it on a large scale, so Pfizer has plans to develop a capsule containing a sprinkle formulation that can be added on top of foods such as apple sauce.

The pediatric study of patients with polyarticular and pauciarticular RA was designed to show that celecoxib was not inferior to naproxen. At 12 weeks, both doses of celecoxib studied were considered as effective as naproxen in terms of the ACR Pediatric 30 responses, which ranged from about 70% to 80% in all three treatment groups. Patients on celecoxib had more abdominal pain and headaches, but overall, common adverse events were similar in patients on either drug, and the safety profile was similar to those known for NSAIDs, according to Pfizer.

The efficacy response to celecoxib was sustained throughout the 12-week open-label study of almost 200 of the study participants, including 70 naproxen-treated patients who switched to celecoxib, and no new safety issues were identified.

Speaking for the American College of Rheumatology during the open public hearing, Dr. Balu Athreya, past executive chair of the ACR's pediatric arthritis committee, said that 22 NSAIDs are approved for RA, 5 of which are approved for JRA. Most require dosing 2–4 times a day, he said, noting that pediatric rheumatologists need additional options, with medications that have dosing and safety profiles that are practical for children.

Surveys of pediatric rheumatologists presented at the meeting showed that the available adult formulation of celecoxib is being used off label for JRA.

GAITHERSBURG, MD. - The Food and Drug Administration's Arthritis Advisory Committee's nearly unanimous support for approving celecoxib for juvenile rheumatoid arthritis in a vote last month may alleviate some of the need for child-friendly drug formulations and add another JRA treatment option.

“We need the advantages an additional formulation will give,” and the advantages of having a different medication which is different from naproxen (Naprosyn) and is a selective cyclooxygenase-2 (COX-2) inhibitor “for at least the potential benefits on bleeding, bruising, and hoped for decrease in GI toxicity,” said Dr. Thomas Lehman, chief of pediatric rheumatology at the Hospital for Special Surgery, New York. He pointed out that noncompliance with medication is one of the most difficult issues in pediatric rheumatology.

He added that many children will respond to one NSAID after not responding to another, and that in his own practice, he said it was “very common” to try two or three different NSAIDs, “looking for a good effect and tolerance” before a more potentially toxic drug is considered, unless the child has obvious aggressive disease.

At the Nov. 29 meeting, the federal advisory panel agreed in a 15–1 vote that the risk-benefit ratio of celecoxib was “adequate” to support its approval for treating JRA.

All panelists agreed that the available data showed the COX-2 selective NSAID was effective for this indication, based on a 3-month randomized, double-blind study comparing naproxen (15 mg/kg daily) with celecoxib (6 mg/kg or 12 mg/kg daily). The study included 242 children and adolescents aged 2–16 years with JRA.

The FDA usually follows the recommendations of its advisory panels.

Celecoxib, marketed as Celebrex by Pfizer, was approved for treating osteoarthritis and RA in adults in 1998. Celecoxib remained available after rofecoxib (Vioxx), which was approved for JRA, was taken off the market in 2004 because of an increased cardiovascular risk seen in a large study. An elevated cardiovascular risk was seen in one of three long-term trials comparing celecoxib with placebo, but it remained on the market with the addition of a boxed warning about the possible increase in serious cardiovascular events.

At the committee meeting for pediatric approval, the panelists' vote on safety was split. All panelists were concerned about the absence of long-term safety data of celecoxib in this population. They strongly recommended that the FDA tie approval to a commitment on the part of Pfizer to use a registry study to follow long-term safety issues, including GI, renal, and cardiovascular safety. They agreed that Pfizer's plan to vigorously investigate spontaneous adverse event reports of celecoxib in children and adolescents was inadequate.

Panelist member Dr. Margaret O'Neil, a pediatric rheumatologist at the University of Oklahoma, Oklahoma City, said that “switching from drug A to drug B may be the magic bullet,” so having more options makes it possible to try another drug before proceeding to drugs that are potentially more toxic.

If approved, the oral suspension used in the trial would not be the formulation marketed because of problems producing it on a large scale, so Pfizer has plans to develop a capsule containing a sprinkle formulation that can be added on top of foods such as apple sauce.

The pediatric study of patients with polyarticular and pauciarticular RA was designed to show that celecoxib was not inferior to naproxen. At 12 weeks, both doses of celecoxib studied were considered as effective as naproxen in terms of the ACR Pediatric 30 responses, which ranged from about 70% to 80% in all three treatment groups. Patients on celecoxib had more abdominal pain and headaches, but overall, common adverse events were similar in patients on either drug, and the safety profile was similar to those known for NSAIDs, according to Pfizer.

The efficacy response to celecoxib was sustained throughout the 12-week open-label study of almost 200 of the study participants, including 70 naproxen-treated patients who switched to celecoxib, and no new safety issues were identified.

Speaking for the American College of Rheumatology during the open public hearing, Dr. Balu Athreya, past executive chair of the ACR's pediatric arthritis committee, said that 22 NSAIDs are approved for RA, 5 of which are approved for JRA. Most require dosing 2–4 times a day, he said, noting that pediatric rheumatologists need additional options, with medications that have dosing and safety profiles that are practical for children.

Surveys of pediatric rheumatologists presented at the meeting showed that the available adult formulation of celecoxib is being used off label for JRA.

GAITHERSBURG, MD. - The Food and Drug Administration's Arthritis Advisory Committee's nearly unanimous support for approving celecoxib for juvenile rheumatoid arthritis in a vote last month may alleviate some of the need for child-friendly drug formulations and add another JRA treatment option.

“We need the advantages an additional formulation will give,” and the advantages of having a different medication which is different from naproxen (Naprosyn) and is a selective cyclooxygenase-2 (COX-2) inhibitor “for at least the potential benefits on bleeding, bruising, and hoped for decrease in GI toxicity,” said Dr. Thomas Lehman, chief of pediatric rheumatology at the Hospital for Special Surgery, New York. He pointed out that noncompliance with medication is one of the most difficult issues in pediatric rheumatology.

He added that many children will respond to one NSAID after not responding to another, and that in his own practice, he said it was “very common” to try two or three different NSAIDs, “looking for a good effect and tolerance” before a more potentially toxic drug is considered, unless the child has obvious aggressive disease.

At the Nov. 29 meeting, the federal advisory panel agreed in a 15–1 vote that the risk-benefit ratio of celecoxib was “adequate” to support its approval for treating JRA.

All panelists agreed that the available data showed the COX-2 selective NSAID was effective for this indication, based on a 3-month randomized, double-blind study comparing naproxen (15 mg/kg daily) with celecoxib (6 mg/kg or 12 mg/kg daily). The study included 242 children and adolescents aged 2–16 years with JRA.

The FDA usually follows the recommendations of its advisory panels.

Celecoxib, marketed as Celebrex by Pfizer, was approved for treating osteoarthritis and RA in adults in 1998. Celecoxib remained available after rofecoxib (Vioxx), which was approved for JRA, was taken off the market in 2004 because of an increased cardiovascular risk seen in a large study. An elevated cardiovascular risk was seen in one of three long-term trials comparing celecoxib with placebo, but it remained on the market with the addition of a boxed warning about the possible increase in serious cardiovascular events.

At the committee meeting for pediatric approval, the panelists' vote on safety was split. All panelists were concerned about the absence of long-term safety data of celecoxib in this population. They strongly recommended that the FDA tie approval to a commitment on the part of Pfizer to use a registry study to follow long-term safety issues, including GI, renal, and cardiovascular safety. They agreed that Pfizer's plan to vigorously investigate spontaneous adverse event reports of celecoxib in children and adolescents was inadequate.

Panelist member Dr. Margaret O'Neil, a pediatric rheumatologist at the University of Oklahoma, Oklahoma City, said that “switching from drug A to drug B may be the magic bullet,” so having more options makes it possible to try another drug before proceeding to drugs that are potentially more toxic.

If approved, the oral suspension used in the trial would not be the formulation marketed because of problems producing it on a large scale, so Pfizer has plans to develop a capsule containing a sprinkle formulation that can be added on top of foods such as apple sauce.

The pediatric study of patients with polyarticular and pauciarticular RA was designed to show that celecoxib was not inferior to naproxen. At 12 weeks, both doses of celecoxib studied were considered as effective as naproxen in terms of the ACR Pediatric 30 responses, which ranged from about 70% to 80% in all three treatment groups. Patients on celecoxib had more abdominal pain and headaches, but overall, common adverse events were similar in patients on either drug, and the safety profile was similar to those known for NSAIDs, according to Pfizer.

The efficacy response to celecoxib was sustained throughout the 12-week open-label study of almost 200 of the study participants, including 70 naproxen-treated patients who switched to celecoxib, and no new safety issues were identified.

Speaking for the American College of Rheumatology during the open public hearing, Dr. Balu Athreya, past executive chair of the ACR's pediatric arthritis committee, said that 22 NSAIDs are approved for RA, 5 of which are approved for JRA. Most require dosing 2–4 times a day, he said, noting that pediatric rheumatologists need additional options, with medications that have dosing and safety profiles that are practical for children.

Surveys of pediatric rheumatologists presented at the meeting showed that the available adult formulation of celecoxib is being used off label for JRA.

The tumor necrosis factor (TNF) blocker adalimumab has been approved by the Food and Drug Administration for inhibiting structural joint damage and improving physical function in patients with psoriatic arthritis, based on study results.

The psoriatic arthritis indication in the product label now says that it is indicated for reducing the signs and symptoms of active arthritis, inhibiting the progression of structural damage, and improving physical function in patients with psoriatic arthritis. Adalimumab, marketed as Humira by Abbott Laboratories, was approved for treating psoriatic arthritis in October 2005.

The latest approval is based on an extension of a trial of patients with moderate to severe psoriatic arthritis, who had inadequate responses to NSAID treatment, comparing 40 mg of adalimumab every other week with placebo in 313 patients, according to a statement issued by Abbott. After 24 weeks, 285 patients continued in an open-label extension of the trial.

At 24 weeks, those on adalimumab had significantly less joint damage than did those on placebo, as determined by the modified total Sharp score, based on x-rays at baseline, 24 weeks, and 48 weeks. Inhibition of radiographic progression on x-rays was significantly greater among those on adalimumab at 24 weeks, and was maintained at 48 weeks.

The physical function indication is based on the significant improvements in physical function documented in the Health Assessment Questionnaire Disability Index (HAQ-DI), and physical component of the Short Form-36 Health Status Survey (SF-36). Those on adalimumab had significantly greater improvements in the HAQ-DI score, with mean decreases of 47% at 12 weeks and 49% at 24 weeks, compared with mean decreases of 1% and 3%, respectively, among those on placebo. Improvements in physical function, as seen on the HAQ-DI, were maintained for up to 84 weeks, according to the revised label. Those on adalimumab also had significantly greater improvements in the physical component of the SF-36 score, compared with those on placebo at weeks 12 and 24.

The tumor necrosis factor (TNF) blocker adalimumab has been approved by the Food and Drug Administration for inhibiting structural joint damage and improving physical function in patients with psoriatic arthritis, based on study results.

The psoriatic arthritis indication in the product label now says that it is indicated for reducing the signs and symptoms of active arthritis, inhibiting the progression of structural damage, and improving physical function in patients with psoriatic arthritis. Adalimumab, marketed as Humira by Abbott Laboratories, was approved for treating psoriatic arthritis in October 2005.

The latest approval is based on an extension of a trial of patients with moderate to severe psoriatic arthritis, who had inadequate responses to NSAID treatment, comparing 40 mg of adalimumab every other week with placebo in 313 patients, according to a statement issued by Abbott. After 24 weeks, 285 patients continued in an open-label extension of the trial.

At 24 weeks, those on adalimumab had significantly less joint damage than did those on placebo, as determined by the modified total Sharp score, based on x-rays at baseline, 24 weeks, and 48 weeks. Inhibition of radiographic progression on x-rays was significantly greater among those on adalimumab at 24 weeks, and was maintained at 48 weeks.

The physical function indication is based on the significant improvements in physical function documented in the Health Assessment Questionnaire Disability Index (HAQ-DI), and physical component of the Short Form-36 Health Status Survey (SF-36). Those on adalimumab had significantly greater improvements in the HAQ-DI score, with mean decreases of 47% at 12 weeks and 49% at 24 weeks, compared with mean decreases of 1% and 3%, respectively, among those on placebo. Improvements in physical function, as seen on the HAQ-DI, were maintained for up to 84 weeks, according to the revised label. Those on adalimumab also had significantly greater improvements in the physical component of the SF-36 score, compared with those on placebo at weeks 12 and 24.

The tumor necrosis factor (TNF) blocker adalimumab has been approved by the Food and Drug Administration for inhibiting structural joint damage and improving physical function in patients with psoriatic arthritis, based on study results.

The psoriatic arthritis indication in the product label now says that it is indicated for reducing the signs and symptoms of active arthritis, inhibiting the progression of structural damage, and improving physical function in patients with psoriatic arthritis. Adalimumab, marketed as Humira by Abbott Laboratories, was approved for treating psoriatic arthritis in October 2005.

The latest approval is based on an extension of a trial of patients with moderate to severe psoriatic arthritis, who had inadequate responses to NSAID treatment, comparing 40 mg of adalimumab every other week with placebo in 313 patients, according to a statement issued by Abbott. After 24 weeks, 285 patients continued in an open-label extension of the trial.

At 24 weeks, those on adalimumab had significantly less joint damage than did those on placebo, as determined by the modified total Sharp score, based on x-rays at baseline, 24 weeks, and 48 weeks. Inhibition of radiographic progression on x-rays was significantly greater among those on adalimumab at 24 weeks, and was maintained at 48 weeks.

The physical function indication is based on the significant improvements in physical function documented in the Health Assessment Questionnaire Disability Index (HAQ-DI), and physical component of the Short Form-36 Health Status Survey (SF-36). Those on adalimumab had significantly greater improvements in the HAQ-DI score, with mean decreases of 47% at 12 weeks and 49% at 24 weeks, compared with mean decreases of 1% and 3%, respectively, among those on placebo. Improvements in physical function, as seen on the HAQ-DI, were maintained for up to 84 weeks, according to the revised label. Those on adalimumab also had significantly greater improvements in the physical component of the SF-36 score, compared with those on placebo at weeks 12 and 24.

Adding acupuncture to routine care in patients with chronic pain from osteoarthritis of the hip or knee was safe and resulted in “a clinically relevant and persistent benefit” in a large study of such patients, Dr. Claudia Witt and her associates have reported.

The investigators evaluated the impact of physician-administered acupuncture on Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores in their study of patients who had osteoarthritis for a mean of 5 years, a baseline WOMAC score of 47, and a mean age of 62 years.

Of the total patients, 322 were randomized to acupuncture and 310 to the control group; 2,921 who refused randomization were treated with acupuncture.

About 57% of the patients had osteoarthritis (OA) of the knee, nearly 15% had OA of the hip, and approximately 30% had both, reported Dr. Witt of Charité University Medical Center, Berlin, and her colleagues.

The patients receiving acupuncture had up to 15 sessions of the therapy over 3 months and no acupuncture during the fourth, fifth, and sixth months; patients in all three groups also received conventional treatment.

At 3 months, scores on the WOMAC had improved by a mean of 17.6 points from baseline among those in the randomized acupuncture group, compared with a mean of 0.9 in the control group, a significant difference.

Almost 35% of those in the acupuncture group were responders (defined as at least a 50% reduction in WOMAC scores), compared with 6.5% of those in the control group.

Improvements in the physical component of the quality-of-life score were also significantly greater at 3 months among those receiving acupuncture.

Responses to treatment among the nonrandomized acupuncture recipients were similar to the responses among those randomized to acupuncture versus osteoarthritis patients in the control group.

In addition, the benefits of acupuncture appeared to persist through 6 months, although patients received no acupuncture after 3 months (Arthritis Rheum. 2006;54:3485–93).

Adding acupuncture to routine care in patients with chronic pain from osteoarthritis of the hip or knee was safe and resulted in “a clinically relevant and persistent benefit” in a large study of such patients, Dr. Claudia Witt and her associates have reported.

The investigators evaluated the impact of physician-administered acupuncture on Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores in their study of patients who had osteoarthritis for a mean of 5 years, a baseline WOMAC score of 47, and a mean age of 62 years.

Of the total patients, 322 were randomized to acupuncture and 310 to the control group; 2,921 who refused randomization were treated with acupuncture.

About 57% of the patients had osteoarthritis (OA) of the knee, nearly 15% had OA of the hip, and approximately 30% had both, reported Dr. Witt of Charité University Medical Center, Berlin, and her colleagues.

The patients receiving acupuncture had up to 15 sessions of the therapy over 3 months and no acupuncture during the fourth, fifth, and sixth months; patients in all three groups also received conventional treatment.

At 3 months, scores on the WOMAC had improved by a mean of 17.6 points from baseline among those in the randomized acupuncture group, compared with a mean of 0.9 in the control group, a significant difference.

Almost 35% of those in the acupuncture group were responders (defined as at least a 50% reduction in WOMAC scores), compared with 6.5% of those in the control group.

Improvements in the physical component of the quality-of-life score were also significantly greater at 3 months among those receiving acupuncture.

Responses to treatment among the nonrandomized acupuncture recipients were similar to the responses among those randomized to acupuncture versus osteoarthritis patients in the control group.

In addition, the benefits of acupuncture appeared to persist through 6 months, although patients received no acupuncture after 3 months (Arthritis Rheum. 2006;54:3485–93).

Adding acupuncture to routine care in patients with chronic pain from osteoarthritis of the hip or knee was safe and resulted in “a clinically relevant and persistent benefit” in a large study of such patients, Dr. Claudia Witt and her associates have reported.

The investigators evaluated the impact of physician-administered acupuncture on Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores in their study of patients who had osteoarthritis for a mean of 5 years, a baseline WOMAC score of 47, and a mean age of 62 years.

Of the total patients, 322 were randomized to acupuncture and 310 to the control group; 2,921 who refused randomization were treated with acupuncture.

About 57% of the patients had osteoarthritis (OA) of the knee, nearly 15% had OA of the hip, and approximately 30% had both, reported Dr. Witt of Charité University Medical Center, Berlin, and her colleagues.

The patients receiving acupuncture had up to 15 sessions of the therapy over 3 months and no acupuncture during the fourth, fifth, and sixth months; patients in all three groups also received conventional treatment.

At 3 months, scores on the WOMAC had improved by a mean of 17.6 points from baseline among those in the randomized acupuncture group, compared with a mean of 0.9 in the control group, a significant difference.

Almost 35% of those in the acupuncture group were responders (defined as at least a 50% reduction in WOMAC scores), compared with 6.5% of those in the control group.

Improvements in the physical component of the quality-of-life score were also significantly greater at 3 months among those receiving acupuncture.

Responses to treatment among the nonrandomized acupuncture recipients were similar to the responses among those randomized to acupuncture versus osteoarthritis patients in the control group.

In addition, the benefits of acupuncture appeared to persist through 6 months, although patients received no acupuncture after 3 months (Arthritis Rheum. 2006;54:3485–93).

ROCKVILLE, MD. — The Food and Drug Administration is reviewing a decade-old regulation that allows clinical studies of emergency treatments, including automated defibrillator implantation, to be conducted without obtaining informed consent in people with certain life-threatening conditions.

The FDA's reappraisal and proposed revision of the rule were prompted by concerns that current safeguards do not provide enough protection of human subjects, and by comments that the safeguards are too onerous and impede important research.

At present, a narrow exception to the informed consent requirement exists in the case of patients who cannot provide consent because of their conditions and who have no family members available to give consent.

To be exempt from informed consent, an investigation must meet certain criteria, including the following:

▸ The patient is in a life-threatening situation.

▸ The available treatments are unproven or not satisfactory.

▸ Evidence supports the prospect of direct benefit to the individual.

Since the regulation went into effect in October 1996, the FDA has received 56 requests to conduct emergency research under this rule. A total of 21 studies have been conducted, are being conducted, or are about to start enrollment, according to the FDA.

The FDA has issued draft guidance geared toward institutional review boards, clinical investigators, and sponsors developing and conducting emergency research. It also sponsored a public hearing in October on emergency research.

At that hearing, presenters offered examples of emergency research that could not otherwise have been done without the exception.

Although the current rules could be simplified, the exception to informed consent is critical, said Dr. Paul Pepe, professor of surgery, medicine, and public health, and Riggs Family Chair in emergency medicine at the University of Texas Southwestern Medical Center at Dallas.

“Studies of the automated external defibrillator are an example of the tremendous lifesaving potential of emergency treatments,” he said. Such studies can also show that treatments that have been widely accepted and appear to be logical may in fact be harmful in some populations, he added. For example, intravenous fluid resuscitation was found to be harmful in certain trauma populations. If these studies had not been done, Dr. Pepe explained, many people would have died.

“Any revisions to current regulations should serve to expand the ability to perform the highest quality emergency research and to enhance patient protections through fairness, openness, and the use of all media that provide explicit detail regarding the research,” Dr. Edward P. Sloan and Dr. Charles Cairns said in a statement on behalf of the American College of Emergency Physicians.

The FDA will review written comments on the guidance, as well as comments made at the hearing, to determine whether the rule should be modified.

ROCKVILLE, MD. — The Food and Drug Administration is reviewing a decade-old regulation that allows clinical studies of emergency treatments, including automated defibrillator implantation, to be conducted without obtaining informed consent in people with certain life-threatening conditions.

The FDA's reappraisal and proposed revision of the rule were prompted by concerns that current safeguards do not provide enough protection of human subjects, and by comments that the safeguards are too onerous and impede important research.

At present, a narrow exception to the informed consent requirement exists in the case of patients who cannot provide consent because of their conditions and who have no family members available to give consent.

To be exempt from informed consent, an investigation must meet certain criteria, including the following:

▸ The patient is in a life-threatening situation.

▸ The available treatments are unproven or not satisfactory.

▸ Evidence supports the prospect of direct benefit to the individual.

Since the regulation went into effect in October 1996, the FDA has received 56 requests to conduct emergency research under this rule. A total of 21 studies have been conducted, are being conducted, or are about to start enrollment, according to the FDA.

The FDA has issued draft guidance geared toward institutional review boards, clinical investigators, and sponsors developing and conducting emergency research. It also sponsored a public hearing in October on emergency research.

At that hearing, presenters offered examples of emergency research that could not otherwise have been done without the exception.

Although the current rules could be simplified, the exception to informed consent is critical, said Dr. Paul Pepe, professor of surgery, medicine, and public health, and Riggs Family Chair in emergency medicine at the University of Texas Southwestern Medical Center at Dallas.

“Studies of the automated external defibrillator are an example of the tremendous lifesaving potential of emergency treatments,” he said. Such studies can also show that treatments that have been widely accepted and appear to be logical may in fact be harmful in some populations, he added. For example, intravenous fluid resuscitation was found to be harmful in certain trauma populations. If these studies had not been done, Dr. Pepe explained, many people would have died.

“Any revisions to current regulations should serve to expand the ability to perform the highest quality emergency research and to enhance patient protections through fairness, openness, and the use of all media that provide explicit detail regarding the research,” Dr. Edward P. Sloan and Dr. Charles Cairns said in a statement on behalf of the American College of Emergency Physicians.

The FDA will review written comments on the guidance, as well as comments made at the hearing, to determine whether the rule should be modified.

ROCKVILLE, MD. — The Food and Drug Administration is reviewing a decade-old regulation that allows clinical studies of emergency treatments, including automated defibrillator implantation, to be conducted without obtaining informed consent in people with certain life-threatening conditions.

The FDA's reappraisal and proposed revision of the rule were prompted by concerns that current safeguards do not provide enough protection of human subjects, and by comments that the safeguards are too onerous and impede important research.

At present, a narrow exception to the informed consent requirement exists in the case of patients who cannot provide consent because of their conditions and who have no family members available to give consent.

To be exempt from informed consent, an investigation must meet certain criteria, including the following:

▸ The patient is in a life-threatening situation.

▸ The available treatments are unproven or not satisfactory.

▸ Evidence supports the prospect of direct benefit to the individual.

Since the regulation went into effect in October 1996, the FDA has received 56 requests to conduct emergency research under this rule. A total of 21 studies have been conducted, are being conducted, or are about to start enrollment, according to the FDA.

The FDA has issued draft guidance geared toward institutional review boards, clinical investigators, and sponsors developing and conducting emergency research. It also sponsored a public hearing in October on emergency research.

At that hearing, presenters offered examples of emergency research that could not otherwise have been done without the exception.

Although the current rules could be simplified, the exception to informed consent is critical, said Dr. Paul Pepe, professor of surgery, medicine, and public health, and Riggs Family Chair in emergency medicine at the University of Texas Southwestern Medical Center at Dallas.

“Studies of the automated external defibrillator are an example of the tremendous lifesaving potential of emergency treatments,” he said. Such studies can also show that treatments that have been widely accepted and appear to be logical may in fact be harmful in some populations, he added. For example, intravenous fluid resuscitation was found to be harmful in certain trauma populations. If these studies had not been done, Dr. Pepe explained, many people would have died.

“Any revisions to current regulations should serve to expand the ability to perform the highest quality emergency research and to enhance patient protections through fairness, openness, and the use of all media that provide explicit detail regarding the research,” Dr. Edward P. Sloan and Dr. Charles Cairns said in a statement on behalf of the American College of Emergency Physicians.

The FDA will review written comments on the guidance, as well as comments made at the hearing, to determine whether the rule should be modified.

The Food and Drug Administration last month gave physicians a new tool in the battle against lung cancer, approving the antiangiogenesis agent bevacizumab in combination with chemotherapy as an initial treatment of unresectable non-small cell lung cancer.

“While this is not a silver bullet or panacea, this is an incremental benefit and represents a significant advance in treatment,” said Dr. W. Michael Alberts, chief medical officer at the H. Lee Moffitt Cancer Center, Tampa, and past president of the American College of Chest Physicians.

The FDA okayed the combination of bevacizumab, a recombinant monoclonal antibody that inhibits angiogenesis, and carboplatin and paclitaxel as initial systemic treatment of unresectable, locally advanced, recurrent or metastatic nonsquamous non-small cell lung cancer. About 75% of the 174,000 new cases of lung cancers expected to be diagnosed this year are non-small cell lung cancer (NSCLC), according to the FDA.

The FDA approval was based on a study of more than 800 patients and demonstrated that adding bevacizumab to the standard chemotherapy regimen increased mean survival by about 2 months, according to the FDA. Bevacizumab, marketed as Avastin by Genentech, is a therapeutic antibody that binds to and inhibits human vascular endothelial growth factor (VEGF), thought to play a role in angiogenesis and maintenance of blood vessels in tumors, according to Genentech.

The randomized, controlled, multicenter trial enrolled 878 patients with unresectable, locally advanced, recurrent or metastatic nonsquamous NSCLC who had not been treated with chemotherapy previously. Median patient age was 63 years. All of the patients were treated with carboplatin and paclitaxel; about of them half also received bevacizumab, administered in an intravenous infusion every 3 weeks.

The median overall survival for patients receiving bevacizumab was 12.3 months, compared with 10.3 months in those who did not receive bevacizumab. One-year survival was 51% in those on bevacizumab and chemotherapy, compared with 44% in those on chemotherapy alone, said Genentech.

This was a median increase, so survival in some patients was more than 2 months, said Dr. Alberts. Some patients in the trial were from his institution, but Dr. Alberts said he has no financial ties to Genentech. The trial was conducted by a network of investigators led by the Eastern Cooperative Oncology Groups and sponsored by the National Cancer Institute, said the company.

Neutropenia, fatigue, hypertension, infection, and hemorrhage were the most common severe adverse events in bevacizumab-treated patients. Of those in the bevacizumab arm, 2.3% had pulmonary hemorrhage requiring medical intervention, compared with 0.5% in those on chemotherapy alone. Pulmonary hemorrhage was fatal in seven patients in the bevacizumab arm and one in the chemotherapy-only arm.

Genentech warned that patients with the squamous cell carcinoma type of NSCLC have a greater risk of experiencing life-threatening or fatal pulmonary hemorrhage. Thus, patients with NSCLC of mixed histology were excluded from the pivotal trial if the predominant cell type was squamous. Genentech plans to launch a program in January to cap the cost of bevacizumab therapy at $55,000 a year for eligible patients for any FDA-approved use of bevacizumab. The drug is also approved as a first-line treatment, in combination with intravenous 5-FU-based chemotherapy, for metastatic colorectal cancer.

Another targeted treatment, erlotinib (Tarceva), is also approved for lung cancer. The agent is indicated for treating patients with locally advanced NSCLC who have failed at least one previous chemotherapy regimen. Erlotinib targets the human epidermal growth factor receptor (HER1) pathway, a factor “critical to cell growth” in NSCLCs as well as pancreatic cancers, according to its manufacturer, Genentech.

The Food and Drug Administration last month gave physicians a new tool in the battle against lung cancer, approving the antiangiogenesis agent bevacizumab in combination with chemotherapy as an initial treatment of unresectable non-small cell lung cancer.

“While this is not a silver bullet or panacea, this is an incremental benefit and represents a significant advance in treatment,” said Dr. W. Michael Alberts, chief medical officer at the H. Lee Moffitt Cancer Center, Tampa, and past president of the American College of Chest Physicians.

The FDA okayed the combination of bevacizumab, a recombinant monoclonal antibody that inhibits angiogenesis, and carboplatin and paclitaxel as initial systemic treatment of unresectable, locally advanced, recurrent or metastatic nonsquamous non-small cell lung cancer. About 75% of the 174,000 new cases of lung cancers expected to be diagnosed this year are non-small cell lung cancer (NSCLC), according to the FDA.

The FDA approval was based on a study of more than 800 patients and demonstrated that adding bevacizumab to the standard chemotherapy regimen increased mean survival by about 2 months, according to the FDA. Bevacizumab, marketed as Avastin by Genentech, is a therapeutic antibody that binds to and inhibits human vascular endothelial growth factor (VEGF), thought to play a role in angiogenesis and maintenance of blood vessels in tumors, according to Genentech.

The randomized, controlled, multicenter trial enrolled 878 patients with unresectable, locally advanced, recurrent or metastatic nonsquamous NSCLC who had not been treated with chemotherapy previously. Median patient age was 63 years. All of the patients were treated with carboplatin and paclitaxel; about of them half also received bevacizumab, administered in an intravenous infusion every 3 weeks.

The median overall survival for patients receiving bevacizumab was 12.3 months, compared with 10.3 months in those who did not receive bevacizumab. One-year survival was 51% in those on bevacizumab and chemotherapy, compared with 44% in those on chemotherapy alone, said Genentech.

This was a median increase, so survival in some patients was more than 2 months, said Dr. Alberts. Some patients in the trial were from his institution, but Dr. Alberts said he has no financial ties to Genentech. The trial was conducted by a network of investigators led by the Eastern Cooperative Oncology Groups and sponsored by the National Cancer Institute, said the company.

Neutropenia, fatigue, hypertension, infection, and hemorrhage were the most common severe adverse events in bevacizumab-treated patients. Of those in the bevacizumab arm, 2.3% had pulmonary hemorrhage requiring medical intervention, compared with 0.5% in those on chemotherapy alone. Pulmonary hemorrhage was fatal in seven patients in the bevacizumab arm and one in the chemotherapy-only arm.

Genentech warned that patients with the squamous cell carcinoma type of NSCLC have a greater risk of experiencing life-threatening or fatal pulmonary hemorrhage. Thus, patients with NSCLC of mixed histology were excluded from the pivotal trial if the predominant cell type was squamous. Genentech plans to launch a program in January to cap the cost of bevacizumab therapy at $55,000 a year for eligible patients for any FDA-approved use of bevacizumab. The drug is also approved as a first-line treatment, in combination with intravenous 5-FU-based chemotherapy, for metastatic colorectal cancer.

Another targeted treatment, erlotinib (Tarceva), is also approved for lung cancer. The agent is indicated for treating patients with locally advanced NSCLC who have failed at least one previous chemotherapy regimen. Erlotinib targets the human epidermal growth factor receptor (HER1) pathway, a factor “critical to cell growth” in NSCLCs as well as pancreatic cancers, according to its manufacturer, Genentech.

The Food and Drug Administration last month gave physicians a new tool in the battle against lung cancer, approving the antiangiogenesis agent bevacizumab in combination with chemotherapy as an initial treatment of unresectable non-small cell lung cancer.

“While this is not a silver bullet or panacea, this is an incremental benefit and represents a significant advance in treatment,” said Dr. W. Michael Alberts, chief medical officer at the H. Lee Moffitt Cancer Center, Tampa, and past president of the American College of Chest Physicians.

The FDA okayed the combination of bevacizumab, a recombinant monoclonal antibody that inhibits angiogenesis, and carboplatin and paclitaxel as initial systemic treatment of unresectable, locally advanced, recurrent or metastatic nonsquamous non-small cell lung cancer. About 75% of the 174,000 new cases of lung cancers expected to be diagnosed this year are non-small cell lung cancer (NSCLC), according to the FDA.

The FDA approval was based on a study of more than 800 patients and demonstrated that adding bevacizumab to the standard chemotherapy regimen increased mean survival by about 2 months, according to the FDA. Bevacizumab, marketed as Avastin by Genentech, is a therapeutic antibody that binds to and inhibits human vascular endothelial growth factor (VEGF), thought to play a role in angiogenesis and maintenance of blood vessels in tumors, according to Genentech.

The randomized, controlled, multicenter trial enrolled 878 patients with unresectable, locally advanced, recurrent or metastatic nonsquamous NSCLC who had not been treated with chemotherapy previously. Median patient age was 63 years. All of the patients were treated with carboplatin and paclitaxel; about of them half also received bevacizumab, administered in an intravenous infusion every 3 weeks.

The median overall survival for patients receiving bevacizumab was 12.3 months, compared with 10.3 months in those who did not receive bevacizumab. One-year survival was 51% in those on bevacizumab and chemotherapy, compared with 44% in those on chemotherapy alone, said Genentech.

This was a median increase, so survival in some patients was more than 2 months, said Dr. Alberts. Some patients in the trial were from his institution, but Dr. Alberts said he has no financial ties to Genentech. The trial was conducted by a network of investigators led by the Eastern Cooperative Oncology Groups and sponsored by the National Cancer Institute, said the company.

Neutropenia, fatigue, hypertension, infection, and hemorrhage were the most common severe adverse events in bevacizumab-treated patients. Of those in the bevacizumab arm, 2.3% had pulmonary hemorrhage requiring medical intervention, compared with 0.5% in those on chemotherapy alone. Pulmonary hemorrhage was fatal in seven patients in the bevacizumab arm and one in the chemotherapy-only arm.

Genentech warned that patients with the squamous cell carcinoma type of NSCLC have a greater risk of experiencing life-threatening or fatal pulmonary hemorrhage. Thus, patients with NSCLC of mixed histology were excluded from the pivotal trial if the predominant cell type was squamous. Genentech plans to launch a program in January to cap the cost of bevacizumab therapy at $55,000 a year for eligible patients for any FDA-approved use of bevacizumab. The drug is also approved as a first-line treatment, in combination with intravenous 5-FU-based chemotherapy, for metastatic colorectal cancer.

Another targeted treatment, erlotinib (Tarceva), is also approved for lung cancer. The agent is indicated for treating patients with locally advanced NSCLC who have failed at least one previous chemotherapy regimen. Erlotinib targets the human epidermal growth factor receptor (HER1) pathway, a factor “critical to cell growth” in NSCLCs as well as pancreatic cancers, according to its manufacturer, Genentech.

Quetiapine has been approved for the treatment of major depressive episodes associated with bipolar disorder.

The approval for this indication was made by the Food and Drug Administration based on two 8-week double-blind, placebo-controlled studies of more than 1,000 outpatients.

Quetiapine (Seroquel), an atypical antipsychotic marketed by AstraZeneca, was first approved for treating schizophrenia in 1997 and is now also approved for treating acute manic episodes associated with bipolar I disorder (as either monotherapy or adjunct therapy to lithium or divalproex).

The most recent approval cited the two BOLDER (BipOLar DEpRession) studies of 1,045 outpatients with bipolar I or II disorder, including those with or without a rapid cycling course. Investigators found that patients on 300 mg or 600 mg quetiapine once a day showed improvements in depressive symptoms starting the first week of treatment through 8 weeks that were “superior” to improvements seen among placebo-treated patients, in terms of the reduction in scores on the Montgomery-Asberg Depression Rating Scale, according to the revised package label.

Patients on the 600 mg dosage showed no additional benefit, so the recommended dosage is 300 mg once a day.

In addition, those on 300 mg showed significantly greater improvements in overall quality of life and satisfaction, related to various areas of functioning.

Dry mouth, sedation, somnolence, dizziness, and constipation were the most common adverse events in the bipolar depression studies, according to AstraZeneca.

Quetiapine has been approved for the treatment of major depressive episodes associated with bipolar disorder.

The approval for this indication was made by the Food and Drug Administration based on two 8-week double-blind, placebo-controlled studies of more than 1,000 outpatients.

Quetiapine (Seroquel), an atypical antipsychotic marketed by AstraZeneca, was first approved for treating schizophrenia in 1997 and is now also approved for treating acute manic episodes associated with bipolar I disorder (as either monotherapy or adjunct therapy to lithium or divalproex).

The most recent approval cited the two BOLDER (BipOLar DEpRession) studies of 1,045 outpatients with bipolar I or II disorder, including those with or without a rapid cycling course. Investigators found that patients on 300 mg or 600 mg quetiapine once a day showed improvements in depressive symptoms starting the first week of treatment through 8 weeks that were “superior” to improvements seen among placebo-treated patients, in terms of the reduction in scores on the Montgomery-Asberg Depression Rating Scale, according to the revised package label.

Patients on the 600 mg dosage showed no additional benefit, so the recommended dosage is 300 mg once a day.

In addition, those on 300 mg showed significantly greater improvements in overall quality of life and satisfaction, related to various areas of functioning.

Dry mouth, sedation, somnolence, dizziness, and constipation were the most common adverse events in the bipolar depression studies, according to AstraZeneca.

Quetiapine has been approved for the treatment of major depressive episodes associated with bipolar disorder.

The approval for this indication was made by the Food and Drug Administration based on two 8-week double-blind, placebo-controlled studies of more than 1,000 outpatients.

Quetiapine (Seroquel), an atypical antipsychotic marketed by AstraZeneca, was first approved for treating schizophrenia in 1997 and is now also approved for treating acute manic episodes associated with bipolar I disorder (as either monotherapy or adjunct therapy to lithium or divalproex).

The most recent approval cited the two BOLDER (BipOLar DEpRession) studies of 1,045 outpatients with bipolar I or II disorder, including those with or without a rapid cycling course. Investigators found that patients on 300 mg or 600 mg quetiapine once a day showed improvements in depressive symptoms starting the first week of treatment through 8 weeks that were “superior” to improvements seen among placebo-treated patients, in terms of the reduction in scores on the Montgomery-Asberg Depression Rating Scale, according to the revised package label.

Patients on the 600 mg dosage showed no additional benefit, so the recommended dosage is 300 mg once a day.

In addition, those on 300 mg showed significantly greater improvements in overall quality of life and satisfaction, related to various areas of functioning.

Dry mouth, sedation, somnolence, dizziness, and constipation were the most common adverse events in the bipolar depression studies, according to AstraZeneca.