Kerri Wachter

ARLINGTON, VA. — Drug-eluting stents may have an advantage over bare-metal stents in major cardiac and cerebrovascular events, but the picture is less clear when it comes to diabetic patients and late thrombosis, according to data presented at a meeting sponsored by the Cardiovascular Research Institute at Washington Hospital Center.

Researchers in Argentina compared outcomes at 1, 2, 3, and 5 years' follow-up in patients with multivessel coronary artery disease (CAD) who were prospectively treated with drug-eluting stents—either the Cypher sirolimus or the Taxus paclitaxel stent in the Argentine Randomized Study: Coronary Angioplasty With Stenting Versus Coronary Bypass Surgery in Patients With Multiple Vessel Disease (ERACI) III—with similar cohorts of patients from the earlier ERACI II trial, which treated CAD patients with either bare metal stents or coronary artery bypass grafting (CABG).

“This multicenter, prospective, controlled study of patients with multivessel CAD treated either with sirolimus- or paclitaxel-eluting stents demonstrated a significant reduction of major adverse cardiac and cerebrovascular events [MACCE] and the need for repeat revascularization procedures when compared with our previous bare-metal data from ERACI II,” said principal investigator Alfredo Rodriguez, Ph.D., of Otamendi Hospital in Buenos Aires.

A total of 225 patients treated with drug-eluting stents (DES) in five centers in Buenos Aires were prospectively enrolled in the ERACI III trial during 2002–2004. Just over a fifth of patients were diabetic (22%) and 37% had type-C lesions. They were compared with 500 patients from the earlier ERACI II, of whom 225 underwent CABG and 225 were treated with bare-metal stents (BMS). Of the combined group, 17% were diabetic and 15% had type-C lesions. Of the DES patients, 48% were treated with paclitaxel-eluting stents and 52% with sirolimus-eluting stents.

“DES versus bare metal and DES versus CABG are associated with lower MACCE at follow-up,” said Dr. Rodriguez. The incidences of MACCE at 1 year were 22%, 20%, and 12% for patients with BMS, CABG, and DES, respectively, on the basis of a univariate analysis. There was no significant difference in the MACCE rate between the two drug-eluting stents.

Drug-eluting stents showed less benefit for diabetic patients in terms of MACCE at 1 year follow-up. In DES patients in ERACI III, there was a nonsignificant trend toward higher mortality in the 47 diabetic patients than in the 178 nondiabetic patients (23% and 9%, respectively). Diabetic patients had a higher incidence of acute myocardial infarction (9%) and repeat percutaneous coronary intervention or CABG (17%), compared with nondiabetic patients (1% and 7%, respectively). Researchers also looked at the incidence of in-stent thrombosis over time. Three BMS patients had in-stent thrombosis, compared with eight DES patients. The times at which thromboses were detected were even more telling: Three patients with BMS and none with DES were identified with in-stent thrombosis while in the hospital.

After hospital discharge and out to 3 years, no BMS patients had in-stent thrombosis. Three DES patients had stent thrombosis after discharge, but still in the first 30 days. Another three in this group developed stent thrombosis in the first year, and one other patient developed stent thrombosis by the 3-year follow-up. Three of the DES patients with stent thrombosis had MIs and three died. Dr. Rodriguez reported no conflicts of interest.

ARLINGTON, VA. — Drug-eluting stents may have an advantage over bare-metal stents in major cardiac and cerebrovascular events, but the picture is less clear when it comes to diabetic patients and late thrombosis, according to data presented at a meeting sponsored by the Cardiovascular Research Institute at Washington Hospital Center.

Researchers in Argentina compared outcomes at 1, 2, 3, and 5 years' follow-up in patients with multivessel coronary artery disease (CAD) who were prospectively treated with drug-eluting stents—either the Cypher sirolimus or the Taxus paclitaxel stent in the Argentine Randomized Study: Coronary Angioplasty With Stenting Versus Coronary Bypass Surgery in Patients With Multiple Vessel Disease (ERACI) III—with similar cohorts of patients from the earlier ERACI II trial, which treated CAD patients with either bare metal stents or coronary artery bypass grafting (CABG).

“This multicenter, prospective, controlled study of patients with multivessel CAD treated either with sirolimus- or paclitaxel-eluting stents demonstrated a significant reduction of major adverse cardiac and cerebrovascular events [MACCE] and the need for repeat revascularization procedures when compared with our previous bare-metal data from ERACI II,” said principal investigator Alfredo Rodriguez, Ph.D., of Otamendi Hospital in Buenos Aires.

A total of 225 patients treated with drug-eluting stents (DES) in five centers in Buenos Aires were prospectively enrolled in the ERACI III trial during 2002–2004. Just over a fifth of patients were diabetic (22%) and 37% had type-C lesions. They were compared with 500 patients from the earlier ERACI II, of whom 225 underwent CABG and 225 were treated with bare-metal stents (BMS). Of the combined group, 17% were diabetic and 15% had type-C lesions. Of the DES patients, 48% were treated with paclitaxel-eluting stents and 52% with sirolimus-eluting stents.

“DES versus bare metal and DES versus CABG are associated with lower MACCE at follow-up,” said Dr. Rodriguez. The incidences of MACCE at 1 year were 22%, 20%, and 12% for patients with BMS, CABG, and DES, respectively, on the basis of a univariate analysis. There was no significant difference in the MACCE rate between the two drug-eluting stents.

Drug-eluting stents showed less benefit for diabetic patients in terms of MACCE at 1 year follow-up. In DES patients in ERACI III, there was a nonsignificant trend toward higher mortality in the 47 diabetic patients than in the 178 nondiabetic patients (23% and 9%, respectively). Diabetic patients had a higher incidence of acute myocardial infarction (9%) and repeat percutaneous coronary intervention or CABG (17%), compared with nondiabetic patients (1% and 7%, respectively). Researchers also looked at the incidence of in-stent thrombosis over time. Three BMS patients had in-stent thrombosis, compared with eight DES patients. The times at which thromboses were detected were even more telling: Three patients with BMS and none with DES were identified with in-stent thrombosis while in the hospital.

After hospital discharge and out to 3 years, no BMS patients had in-stent thrombosis. Three DES patients had stent thrombosis after discharge, but still in the first 30 days. Another three in this group developed stent thrombosis in the first year, and one other patient developed stent thrombosis by the 3-year follow-up. Three of the DES patients with stent thrombosis had MIs and three died. Dr. Rodriguez reported no conflicts of interest.

ARLINGTON, VA. — Drug-eluting stents may have an advantage over bare-metal stents in major cardiac and cerebrovascular events, but the picture is less clear when it comes to diabetic patients and late thrombosis, according to data presented at a meeting sponsored by the Cardiovascular Research Institute at Washington Hospital Center.

Researchers in Argentina compared outcomes at 1, 2, 3, and 5 years' follow-up in patients with multivessel coronary artery disease (CAD) who were prospectively treated with drug-eluting stents—either the Cypher sirolimus or the Taxus paclitaxel stent in the Argentine Randomized Study: Coronary Angioplasty With Stenting Versus Coronary Bypass Surgery in Patients With Multiple Vessel Disease (ERACI) III—with similar cohorts of patients from the earlier ERACI II trial, which treated CAD patients with either bare metal stents or coronary artery bypass grafting (CABG).

“This multicenter, prospective, controlled study of patients with multivessel CAD treated either with sirolimus- or paclitaxel-eluting stents demonstrated a significant reduction of major adverse cardiac and cerebrovascular events [MACCE] and the need for repeat revascularization procedures when compared with our previous bare-metal data from ERACI II,” said principal investigator Alfredo Rodriguez, Ph.D., of Otamendi Hospital in Buenos Aires.

A total of 225 patients treated with drug-eluting stents (DES) in five centers in Buenos Aires were prospectively enrolled in the ERACI III trial during 2002–2004. Just over a fifth of patients were diabetic (22%) and 37% had type-C lesions. They were compared with 500 patients from the earlier ERACI II, of whom 225 underwent CABG and 225 were treated with bare-metal stents (BMS). Of the combined group, 17% were diabetic and 15% had type-C lesions. Of the DES patients, 48% were treated with paclitaxel-eluting stents and 52% with sirolimus-eluting stents.

“DES versus bare metal and DES versus CABG are associated with lower MACCE at follow-up,” said Dr. Rodriguez. The incidences of MACCE at 1 year were 22%, 20%, and 12% for patients with BMS, CABG, and DES, respectively, on the basis of a univariate analysis. There was no significant difference in the MACCE rate between the two drug-eluting stents.

Drug-eluting stents showed less benefit for diabetic patients in terms of MACCE at 1 year follow-up. In DES patients in ERACI III, there was a nonsignificant trend toward higher mortality in the 47 diabetic patients than in the 178 nondiabetic patients (23% and 9%, respectively). Diabetic patients had a higher incidence of acute myocardial infarction (9%) and repeat percutaneous coronary intervention or CABG (17%), compared with nondiabetic patients (1% and 7%, respectively). Researchers also looked at the incidence of in-stent thrombosis over time. Three BMS patients had in-stent thrombosis, compared with eight DES patients. The times at which thromboses were detected were even more telling: Three patients with BMS and none with DES were identified with in-stent thrombosis while in the hospital.

After hospital discharge and out to 3 years, no BMS patients had in-stent thrombosis. Three DES patients had stent thrombosis after discharge, but still in the first 30 days. Another three in this group developed stent thrombosis in the first year, and one other patient developed stent thrombosis by the 3-year follow-up. Three of the DES patients with stent thrombosis had MIs and three died. Dr. Rodriguez reported no conflicts of interest.

SAN JUAN, P.R. – Sleep disorders become more common with increasing age, but effective behavioral and pharmacologic therapies are available, sleep experts said at the annual meeting of the American Association for Geriatric Psychiatry.

“Most older adults are not being treated for their insomnia, and most older adults won't get a diagnosis of insomnia,” despite the high prevalence of the disorder among this age group, said Dr. Phyllis C. Zee, medical director of the Sleep Disorders Center at Northwestern Memorial Hospital in Chicago.

There are several age-related changes in sleep architecture. The number of awakenings during sleep time increases, especially in the early morning. The amount of light sleep is increased, and the amount of deep sleep is decreased. There also is a decrease in REM sleep, said Dr. Zee, who also serves as a professor of neurology, neurobiology, and physiology at Northwestern University, Chicago.

Two major mechanisms regulate sleep in humans: the homeostatic drive and the circadian drive. Control of the circadian system resides in the suprachiasmatic nucleus, which provides timing information for physiologic, hormonal, and behavioral rhythms.

Several changes in circadian sleep rhythms come with age. The amplitude of circadian rhythms decreases, while the variability of circadian rhythms increases. “There's also a very noticeable advance in [the] phase of circadian rhythms,” Dr. Zee said. Severe disruptions of the sleep/wake cycle often occur among older adults with dementia and in those in nursing homes.

The homeostatic drive for sleep depends on accumulating enough hours of wakefulness to trigger sleep, and this drive is reset during sleep. It's thought that the homeostatic drive is regulated by the ventrolateral preoptic area of the hypothalamus.

It's important to understand these sleep mechanisms when treating sleep disorders. “There is not a thing you can do to make yourself go to sleep. … What you can do is arrange the circumstances and timing of your wakefulness in a way that makes the involuntary process of sleep more likely,” said Dr. Daniel J. Buysse, medical director of the sleep evaluation center at the Western Psychiatric Institute and Clinic of the University of Pittsburgh

“Sleep hygiene education is without a doubt the most widely employed and … the least efficacious” of the behavioral treatments for insomnia, Dr. Buysse said. Most patients are already aware of many of the suggestions for good sleep hygiene, such as avoiding caffeine before bed.

To understand the patient's sleep habits, behavioral therapists start by asking about average time in bed, average rise time, total time in bed, time to fall asleep, amount of wakefulness during the night, and total wake time.

Using this information, they calculate the average amount of total sleep (total time in bed minus total wake time). For most individuals with insomnia, there is a discrepancy between the total amount of sleep that they get and the total amount of time they spend in bed, said Dr. Buysse, also a professor of psychiatry at the University of Pittsburgh.

Several common elements are involved in behavioral treatments for insomnia: monitoring sleep-wake patterns, reinforcing associations between bed and sleep, limiting awake time in bed, establishing a regular sleep-wake schedule, and using voluntary behavior to influence the involuntary physiologic process of sleep.

To help patients minimize insomnia, he advised doing the following:

▸ Restrict time in bed.

▸ Establish a regular wake time.

▸ Go to bed only when sleepy.

▸ Stay in bed only when asleep.

By putting these suggestions into practice, a patient's total time in bed should be equal to the total sleep time, plus about 30 minutes, Dr. Buysse said. He and his colleagues have tested the effect of these changes in sleep behavior on sleep quality in a small study of 13 patients who made these changes, compared with 12 subjects who received basic sleep information. Those in the active treatment group showed a significant improvement in sleep quality, while those in the control group showed no change.

In addition, those in the active treatment group also showed improvement in sleep latency–how long it takes to fall asleep–and waking after sleep onset, while controls did not.

Pharmacologic management of acute and chronic insomnia includes benzodiazepine receptor agonists, melatonin, melatonin receptor agonists, and antidepressants.

In 2005, a National Institutes of Health state-of-the-science panel noted that hypnotics are efficacious in the short-term treatment of insomnia. However, with the exception of eszopiclone, the benefits of these agents have not been studied for long-term use.

Zaleplon (Sonata), zolpidem (Ambien), and eszopiclone (Lunesta)–benzodiazepine receptor agonists–are all indicated for the treatment of insomnia.

“These drugs differ [from benzodiazepines] mainly in terms of their pharmacokinetics,” said Dr. Buysse. Otherwise, these drugs are quite similar to benzodiazepines. One note of caution, however: Benzodiazepines and related drugs have been shown to be a risk factor for falls.

Ramelteon, a melatonin receptor agonist, “takes advantage of the circadian system that secretes melatonin at night,” Dr. Buysse said. Ramelteon is short acting and has an active metabolite. Caution should be used with this drug when prescribed for patients also taking fluvoxamine, which inhibits some of the enzymes that degrade ramelteon.

Ramelteon has been shown to reduce sleep latency and increase total sleep time in both younger and older adults. The drug appears to be less effective on wakefulness after sleep onset.

Ramelteon “has fewer side effects of the sort that characterize benzodiazepine receptor agonists,” Dr. Buysse said. In addition, the drug is unscheduled.

Trazodone, an antidepressant, seems to improve sleep continuity. “When it's been assessed in insomnia, there have been variable results. Typically, it decreases wakefulness during the night but doesn't have as much effect on the time to fall asleep,” Dr. Buysse said.

He recommends starting pharmacotherapy with a short-acting benzodiazepine receptor agonist or ramelteon. If that doesn't work, he recommends using a low-dose (20–50 mg) antidepressant such as trazodone, amitriptyline, or doxepin. As a last resort, he suggests combining a benzodiazepine receptor agonist with an antidepressant.

SAN JUAN, P.R. – Sleep disorders become more common with increasing age, but effective behavioral and pharmacologic therapies are available, sleep experts said at the annual meeting of the American Association for Geriatric Psychiatry.

“Most older adults are not being treated for their insomnia, and most older adults won't get a diagnosis of insomnia,” despite the high prevalence of the disorder among this age group, said Dr. Phyllis C. Zee, medical director of the Sleep Disorders Center at Northwestern Memorial Hospital in Chicago.

There are several age-related changes in sleep architecture. The number of awakenings during sleep time increases, especially in the early morning. The amount of light sleep is increased, and the amount of deep sleep is decreased. There also is a decrease in REM sleep, said Dr. Zee, who also serves as a professor of neurology, neurobiology, and physiology at Northwestern University, Chicago.

Two major mechanisms regulate sleep in humans: the homeostatic drive and the circadian drive. Control of the circadian system resides in the suprachiasmatic nucleus, which provides timing information for physiologic, hormonal, and behavioral rhythms.

Several changes in circadian sleep rhythms come with age. The amplitude of circadian rhythms decreases, while the variability of circadian rhythms increases. “There's also a very noticeable advance in [the] phase of circadian rhythms,” Dr. Zee said. Severe disruptions of the sleep/wake cycle often occur among older adults with dementia and in those in nursing homes.

The homeostatic drive for sleep depends on accumulating enough hours of wakefulness to trigger sleep, and this drive is reset during sleep. It's thought that the homeostatic drive is regulated by the ventrolateral preoptic area of the hypothalamus.

It's important to understand these sleep mechanisms when treating sleep disorders. “There is not a thing you can do to make yourself go to sleep. … What you can do is arrange the circumstances and timing of your wakefulness in a way that makes the involuntary process of sleep more likely,” said Dr. Daniel J. Buysse, medical director of the sleep evaluation center at the Western Psychiatric Institute and Clinic of the University of Pittsburgh

“Sleep hygiene education is without a doubt the most widely employed and … the least efficacious” of the behavioral treatments for insomnia, Dr. Buysse said. Most patients are already aware of many of the suggestions for good sleep hygiene, such as avoiding caffeine before bed.

To understand the patient's sleep habits, behavioral therapists start by asking about average time in bed, average rise time, total time in bed, time to fall asleep, amount of wakefulness during the night, and total wake time.

Using this information, they calculate the average amount of total sleep (total time in bed minus total wake time). For most individuals with insomnia, there is a discrepancy between the total amount of sleep that they get and the total amount of time they spend in bed, said Dr. Buysse, also a professor of psychiatry at the University of Pittsburgh.

Several common elements are involved in behavioral treatments for insomnia: monitoring sleep-wake patterns, reinforcing associations between bed and sleep, limiting awake time in bed, establishing a regular sleep-wake schedule, and using voluntary behavior to influence the involuntary physiologic process of sleep.

To help patients minimize insomnia, he advised doing the following:

▸ Restrict time in bed.

▸ Establish a regular wake time.

▸ Go to bed only when sleepy.

▸ Stay in bed only when asleep.

By putting these suggestions into practice, a patient's total time in bed should be equal to the total sleep time, plus about 30 minutes, Dr. Buysse said. He and his colleagues have tested the effect of these changes in sleep behavior on sleep quality in a small study of 13 patients who made these changes, compared with 12 subjects who received basic sleep information. Those in the active treatment group showed a significant improvement in sleep quality, while those in the control group showed no change.

In addition, those in the active treatment group also showed improvement in sleep latency–how long it takes to fall asleep–and waking after sleep onset, while controls did not.

Pharmacologic management of acute and chronic insomnia includes benzodiazepine receptor agonists, melatonin, melatonin receptor agonists, and antidepressants.

In 2005, a National Institutes of Health state-of-the-science panel noted that hypnotics are efficacious in the short-term treatment of insomnia. However, with the exception of eszopiclone, the benefits of these agents have not been studied for long-term use.

Zaleplon (Sonata), zolpidem (Ambien), and eszopiclone (Lunesta)–benzodiazepine receptor agonists–are all indicated for the treatment of insomnia.

“These drugs differ [from benzodiazepines] mainly in terms of their pharmacokinetics,” said Dr. Buysse. Otherwise, these drugs are quite similar to benzodiazepines. One note of caution, however: Benzodiazepines and related drugs have been shown to be a risk factor for falls.

Ramelteon, a melatonin receptor agonist, “takes advantage of the circadian system that secretes melatonin at night,” Dr. Buysse said. Ramelteon is short acting and has an active metabolite. Caution should be used with this drug when prescribed for patients also taking fluvoxamine, which inhibits some of the enzymes that degrade ramelteon.

Ramelteon has been shown to reduce sleep latency and increase total sleep time in both younger and older adults. The drug appears to be less effective on wakefulness after sleep onset.

Ramelteon “has fewer side effects of the sort that characterize benzodiazepine receptor agonists,” Dr. Buysse said. In addition, the drug is unscheduled.

Trazodone, an antidepressant, seems to improve sleep continuity. “When it's been assessed in insomnia, there have been variable results. Typically, it decreases wakefulness during the night but doesn't have as much effect on the time to fall asleep,” Dr. Buysse said.

He recommends starting pharmacotherapy with a short-acting benzodiazepine receptor agonist or ramelteon. If that doesn't work, he recommends using a low-dose (20–50 mg) antidepressant such as trazodone, amitriptyline, or doxepin. As a last resort, he suggests combining a benzodiazepine receptor agonist with an antidepressant.

SAN JUAN, P.R. – Sleep disorders become more common with increasing age, but effective behavioral and pharmacologic therapies are available, sleep experts said at the annual meeting of the American Association for Geriatric Psychiatry.

“Most older adults are not being treated for their insomnia, and most older adults won't get a diagnosis of insomnia,” despite the high prevalence of the disorder among this age group, said Dr. Phyllis C. Zee, medical director of the Sleep Disorders Center at Northwestern Memorial Hospital in Chicago.

There are several age-related changes in sleep architecture. The number of awakenings during sleep time increases, especially in the early morning. The amount of light sleep is increased, and the amount of deep sleep is decreased. There also is a decrease in REM sleep, said Dr. Zee, who also serves as a professor of neurology, neurobiology, and physiology at Northwestern University, Chicago.

Two major mechanisms regulate sleep in humans: the homeostatic drive and the circadian drive. Control of the circadian system resides in the suprachiasmatic nucleus, which provides timing information for physiologic, hormonal, and behavioral rhythms.

Several changes in circadian sleep rhythms come with age. The amplitude of circadian rhythms decreases, while the variability of circadian rhythms increases. “There's also a very noticeable advance in [the] phase of circadian rhythms,” Dr. Zee said. Severe disruptions of the sleep/wake cycle often occur among older adults with dementia and in those in nursing homes.

The homeostatic drive for sleep depends on accumulating enough hours of wakefulness to trigger sleep, and this drive is reset during sleep. It's thought that the homeostatic drive is regulated by the ventrolateral preoptic area of the hypothalamus.

It's important to understand these sleep mechanisms when treating sleep disorders. “There is not a thing you can do to make yourself go to sleep. … What you can do is arrange the circumstances and timing of your wakefulness in a way that makes the involuntary process of sleep more likely,” said Dr. Daniel J. Buysse, medical director of the sleep evaluation center at the Western Psychiatric Institute and Clinic of the University of Pittsburgh

“Sleep hygiene education is without a doubt the most widely employed and … the least efficacious” of the behavioral treatments for insomnia, Dr. Buysse said. Most patients are already aware of many of the suggestions for good sleep hygiene, such as avoiding caffeine before bed.

To understand the patient's sleep habits, behavioral therapists start by asking about average time in bed, average rise time, total time in bed, time to fall asleep, amount of wakefulness during the night, and total wake time.

Using this information, they calculate the average amount of total sleep (total time in bed minus total wake time). For most individuals with insomnia, there is a discrepancy between the total amount of sleep that they get and the total amount of time they spend in bed, said Dr. Buysse, also a professor of psychiatry at the University of Pittsburgh.

Several common elements are involved in behavioral treatments for insomnia: monitoring sleep-wake patterns, reinforcing associations between bed and sleep, limiting awake time in bed, establishing a regular sleep-wake schedule, and using voluntary behavior to influence the involuntary physiologic process of sleep.

To help patients minimize insomnia, he advised doing the following:

▸ Restrict time in bed.

▸ Establish a regular wake time.

▸ Go to bed only when sleepy.

▸ Stay in bed only when asleep.

By putting these suggestions into practice, a patient's total time in bed should be equal to the total sleep time, plus about 30 minutes, Dr. Buysse said. He and his colleagues have tested the effect of these changes in sleep behavior on sleep quality in a small study of 13 patients who made these changes, compared with 12 subjects who received basic sleep information. Those in the active treatment group showed a significant improvement in sleep quality, while those in the control group showed no change.

In addition, those in the active treatment group also showed improvement in sleep latency–how long it takes to fall asleep–and waking after sleep onset, while controls did not.

Pharmacologic management of acute and chronic insomnia includes benzodiazepine receptor agonists, melatonin, melatonin receptor agonists, and antidepressants.

In 2005, a National Institutes of Health state-of-the-science panel noted that hypnotics are efficacious in the short-term treatment of insomnia. However, with the exception of eszopiclone, the benefits of these agents have not been studied for long-term use.

Zaleplon (Sonata), zolpidem (Ambien), and eszopiclone (Lunesta)–benzodiazepine receptor agonists–are all indicated for the treatment of insomnia.

“These drugs differ [from benzodiazepines] mainly in terms of their pharmacokinetics,” said Dr. Buysse. Otherwise, these drugs are quite similar to benzodiazepines. One note of caution, however: Benzodiazepines and related drugs have been shown to be a risk factor for falls.

Ramelteon, a melatonin receptor agonist, “takes advantage of the circadian system that secretes melatonin at night,” Dr. Buysse said. Ramelteon is short acting and has an active metabolite. Caution should be used with this drug when prescribed for patients also taking fluvoxamine, which inhibits some of the enzymes that degrade ramelteon.

Ramelteon has been shown to reduce sleep latency and increase total sleep time in both younger and older adults. The drug appears to be less effective on wakefulness after sleep onset.

Ramelteon “has fewer side effects of the sort that characterize benzodiazepine receptor agonists,” Dr. Buysse said. In addition, the drug is unscheduled.

Trazodone, an antidepressant, seems to improve sleep continuity. “When it's been assessed in insomnia, there have been variable results. Typically, it decreases wakefulness during the night but doesn't have as much effect on the time to fall asleep,” Dr. Buysse said.

He recommends starting pharmacotherapy with a short-acting benzodiazepine receptor agonist or ramelteon. If that doesn't work, he recommends using a low-dose (20–50 mg) antidepressant such as trazodone, amitriptyline, or doxepin. As a last resort, he suggests combining a benzodiazepine receptor agonist with an antidepressant.

Eleven of 648 patients died while taking donepezil (Aricept) in a trial of the drug for the treatment of vascular dementia, according to preliminary study results announced by Eisai Co. Ltd., the drug's maker. None of the 326 patients taking placebo during the 24-week trial died.

The multicenter, randomized, double-blind study was conducted in nine countries and enrolled only people with vascular dementia (VaD), who had no prior diagnosis of Alzheimer's disease. Donepezil is currently approved only for the treatment of mild to moderate Alzheimer's disease in the United States.

Those patients taking donepezil showed improvement on measures of cognition, compared with those on placebo. However, there was no benefit observed on global function, the trial's other primary measure.

An analysis of adverse events data revealed that the mortality rate of 1.7% for the donepezil treatment group in this trial was consistent with that observed in a combined analysis of two previous VaD studies (1.7%) and was lower than that reported in the general population of patients with vascular dementia. However, the mortality rate observed in the placebo group of this study (0%) was lower than that seen in the placebo groups in the combined analysis for the two prior VaD studies (2%), and was lower than the rate for the general VaD population.

In an analysis of all three vascular dementia trials, observed mortality rates were not statistically significant between the donepezil-treated group and the placebo group (1.7% vs. 1.1%).

Additional analyses of vascular events such as stroke and myocardial infarction for the three VaD trials, alone and combined, showed a statistically significant higher risk of a vascular event in the donepezil group, compared with placebo.

In the most recent study, overall adverse events were not significantly different between the treatment and placebo groups. Adverse events in the treatment group occurred at a rate greater than 5%, and twice the rate of placebo, for abdominal pain (5.1% vs. 2.5%), anorexia (5.7% vs. 2.8%), and nausea (9.9% vs. 4.3%).

Eisai has notified regulatory authorities about the mortality findings, and has reported that the results of the most recent vascular dementia study have not changed the overall safety profile of the drug, and that the drug's benefit-risk profile continues to be favorable for its approved indications.

Eleven of 648 patients died while taking donepezil (Aricept) in a trial of the drug for the treatment of vascular dementia, according to preliminary study results announced by Eisai Co. Ltd., the drug's maker. None of the 326 patients taking placebo during the 24-week trial died.

The multicenter, randomized, double-blind study was conducted in nine countries and enrolled only people with vascular dementia (VaD), who had no prior diagnosis of Alzheimer's disease. Donepezil is currently approved only for the treatment of mild to moderate Alzheimer's disease in the United States.

Those patients taking donepezil showed improvement on measures of cognition, compared with those on placebo. However, there was no benefit observed on global function, the trial's other primary measure.

An analysis of adverse events data revealed that the mortality rate of 1.7% for the donepezil treatment group in this trial was consistent with that observed in a combined analysis of two previous VaD studies (1.7%) and was lower than that reported in the general population of patients with vascular dementia. However, the mortality rate observed in the placebo group of this study (0%) was lower than that seen in the placebo groups in the combined analysis for the two prior VaD studies (2%), and was lower than the rate for the general VaD population.

In an analysis of all three vascular dementia trials, observed mortality rates were not statistically significant between the donepezil-treated group and the placebo group (1.7% vs. 1.1%).

Additional analyses of vascular events such as stroke and myocardial infarction for the three VaD trials, alone and combined, showed a statistically significant higher risk of a vascular event in the donepezil group, compared with placebo.

In the most recent study, overall adverse events were not significantly different between the treatment and placebo groups. Adverse events in the treatment group occurred at a rate greater than 5%, and twice the rate of placebo, for abdominal pain (5.1% vs. 2.5%), anorexia (5.7% vs. 2.8%), and nausea (9.9% vs. 4.3%).

Eisai has notified regulatory authorities about the mortality findings, and has reported that the results of the most recent vascular dementia study have not changed the overall safety profile of the drug, and that the drug's benefit-risk profile continues to be favorable for its approved indications.

Eleven of 648 patients died while taking donepezil (Aricept) in a trial of the drug for the treatment of vascular dementia, according to preliminary study results announced by Eisai Co. Ltd., the drug's maker. None of the 326 patients taking placebo during the 24-week trial died.

The multicenter, randomized, double-blind study was conducted in nine countries and enrolled only people with vascular dementia (VaD), who had no prior diagnosis of Alzheimer's disease. Donepezil is currently approved only for the treatment of mild to moderate Alzheimer's disease in the United States.

Those patients taking donepezil showed improvement on measures of cognition, compared with those on placebo. However, there was no benefit observed on global function, the trial's other primary measure.

An analysis of adverse events data revealed that the mortality rate of 1.7% for the donepezil treatment group in this trial was consistent with that observed in a combined analysis of two previous VaD studies (1.7%) and was lower than that reported in the general population of patients with vascular dementia. However, the mortality rate observed in the placebo group of this study (0%) was lower than that seen in the placebo groups in the combined analysis for the two prior VaD studies (2%), and was lower than the rate for the general VaD population.

In an analysis of all three vascular dementia trials, observed mortality rates were not statistically significant between the donepezil-treated group and the placebo group (1.7% vs. 1.1%).

Additional analyses of vascular events such as stroke and myocardial infarction for the three VaD trials, alone and combined, showed a statistically significant higher risk of a vascular event in the donepezil group, compared with placebo.

In the most recent study, overall adverse events were not significantly different between the treatment and placebo groups. Adverse events in the treatment group occurred at a rate greater than 5%, and twice the rate of placebo, for abdominal pain (5.1% vs. 2.5%), anorexia (5.7% vs. 2.8%), and nausea (9.9% vs. 4.3%).

Eisai has notified regulatory authorities about the mortality findings, and has reported that the results of the most recent vascular dementia study have not changed the overall safety profile of the drug, and that the drug's benefit-risk profile continues to be favorable for its approved indications.

WASHINGTON – An orally disintegrating formulation of selegiline appears to be a safe and effective adjunct for patients with Parkinson's disease who are experiencing a deterioration of levodopa response, according to data presented in a poster at the World Parkinson Congress.

Selegiline taken in the orally disintegrating form significantly decreased the amount of levodopa nonresponse time, compared with placebo in two phase III, randomized, double-blind trials, reported Dr. William G. Ondo of the department of neurology at Baylor University, Houston. Dr. Ondo performed a pooled analysis of data from the two trials.

The selective MAO type-B inhibitor selegiline is limited by low bioavailability, extensive first-pass hepatic metabolism, and the production of amphetamine metabolites.

However, orally disintegrating tablets dissolve on the first contact with saliva and undergo pregastric absorption, which minimizes first-pass metabolism while providing high plasma concentrations of the drug, Dr. Ondo wrote.

Until the development of an orally disintegrating form of the drug, selegiline–which was approved for use as an adjunct in the management of patients with Parkinson's disease who experience a deterioration in their response to treatment with levodopa/carbidopa–had been administered as a capsule or tablet to be swallowed.

He analyzed data from two trials of orally disintegrating selegiline versus placebo in patients experiencing an erosion of efficacy with optimized levodopa therapy. Patients were included in the trials if they were older than 30 years, had a confirmed diagnosis of Parkinson's disease, had a documented response to levodopa with a dopa-decarboxylase inhibitor, and experienced at least 3 hours daily when the beneficial effects of levodopa wore off.

Initially, patients in both trials were randomized to receive either 1.25 mg of orally disintegrating selegiline or placebo per day. At week 6, the dosage of orally disintegrating selegiline was increased to 2.5 mg per day. The average baseline number of “off” hours was determined using patient recordings for a 24-hour period for 2 days preceding the initial clinic visit. The average number of “off” hours throughout the trial were also determined using the diaries for the 2 days prior to clinic visits. Six visits were conducted throughout the 12-week trial.

In the first trial, 98 patients were randomized to selegiline and 50 to placebo; in the second, 94 patients were randomized to selegiline and 48 to placebo.

Combined results from both trials showed that orally disintegrating selegiline significantly decreased total levodopa “off” time at weeks 4–6. The treatment group had 5 hours per day during which efficacy wore off, compared with 6 hours per day for the placebo group (10% vs. 6% reductions from baseline, respectively).

Orally disintegrating selegiline also significantly decreased the percentage of levodopa “off” time at weeks 10–12. The treatment group had 4.5 hours per day during which efficacy wore off, compared with 6 hours per day for the placebo group (approximately 13% vs. 7% reductions from baseline, respectively).

Assessment of results from patients with the Clinical Global Impression of Severity and Improvement scales and the Patient Global Improvement scale significantly favored orally disintegrating selegiline as well at weeks 10–12.

Orally disintegrating selegiline was generally well tolerated in both trials. In the first trial, 8% of patients taking selegiline experienced serious adverse events, compared with 2% of patients given placebo. In the second trial, 3% of patients on selegiline experienced serious adverse events, compared with 4% of those on placebo. The most commonly reported adverse events were nausea, dry mouth, and dizziness.

WASHINGTON – An orally disintegrating formulation of selegiline appears to be a safe and effective adjunct for patients with Parkinson's disease who are experiencing a deterioration of levodopa response, according to data presented in a poster at the World Parkinson Congress.

Selegiline taken in the orally disintegrating form significantly decreased the amount of levodopa nonresponse time, compared with placebo in two phase III, randomized, double-blind trials, reported Dr. William G. Ondo of the department of neurology at Baylor University, Houston. Dr. Ondo performed a pooled analysis of data from the two trials.

The selective MAO type-B inhibitor selegiline is limited by low bioavailability, extensive first-pass hepatic metabolism, and the production of amphetamine metabolites.

However, orally disintegrating tablets dissolve on the first contact with saliva and undergo pregastric absorption, which minimizes first-pass metabolism while providing high plasma concentrations of the drug, Dr. Ondo wrote.

Until the development of an orally disintegrating form of the drug, selegiline–which was approved for use as an adjunct in the management of patients with Parkinson's disease who experience a deterioration in their response to treatment with levodopa/carbidopa–had been administered as a capsule or tablet to be swallowed.

He analyzed data from two trials of orally disintegrating selegiline versus placebo in patients experiencing an erosion of efficacy with optimized levodopa therapy. Patients were included in the trials if they were older than 30 years, had a confirmed diagnosis of Parkinson's disease, had a documented response to levodopa with a dopa-decarboxylase inhibitor, and experienced at least 3 hours daily when the beneficial effects of levodopa wore off.

Initially, patients in both trials were randomized to receive either 1.25 mg of orally disintegrating selegiline or placebo per day. At week 6, the dosage of orally disintegrating selegiline was increased to 2.5 mg per day. The average baseline number of “off” hours was determined using patient recordings for a 24-hour period for 2 days preceding the initial clinic visit. The average number of “off” hours throughout the trial were also determined using the diaries for the 2 days prior to clinic visits. Six visits were conducted throughout the 12-week trial.

In the first trial, 98 patients were randomized to selegiline and 50 to placebo; in the second, 94 patients were randomized to selegiline and 48 to placebo.

Combined results from both trials showed that orally disintegrating selegiline significantly decreased total levodopa “off” time at weeks 4–6. The treatment group had 5 hours per day during which efficacy wore off, compared with 6 hours per day for the placebo group (10% vs. 6% reductions from baseline, respectively).

Orally disintegrating selegiline also significantly decreased the percentage of levodopa “off” time at weeks 10–12. The treatment group had 4.5 hours per day during which efficacy wore off, compared with 6 hours per day for the placebo group (approximately 13% vs. 7% reductions from baseline, respectively).

Assessment of results from patients with the Clinical Global Impression of Severity and Improvement scales and the Patient Global Improvement scale significantly favored orally disintegrating selegiline as well at weeks 10–12.

Orally disintegrating selegiline was generally well tolerated in both trials. In the first trial, 8% of patients taking selegiline experienced serious adverse events, compared with 2% of patients given placebo. In the second trial, 3% of patients on selegiline experienced serious adverse events, compared with 4% of those on placebo. The most commonly reported adverse events were nausea, dry mouth, and dizziness.

WASHINGTON – An orally disintegrating formulation of selegiline appears to be a safe and effective adjunct for patients with Parkinson's disease who are experiencing a deterioration of levodopa response, according to data presented in a poster at the World Parkinson Congress.

Selegiline taken in the orally disintegrating form significantly decreased the amount of levodopa nonresponse time, compared with placebo in two phase III, randomized, double-blind trials, reported Dr. William G. Ondo of the department of neurology at Baylor University, Houston. Dr. Ondo performed a pooled analysis of data from the two trials.

The selective MAO type-B inhibitor selegiline is limited by low bioavailability, extensive first-pass hepatic metabolism, and the production of amphetamine metabolites.

However, orally disintegrating tablets dissolve on the first contact with saliva and undergo pregastric absorption, which minimizes first-pass metabolism while providing high plasma concentrations of the drug, Dr. Ondo wrote.

Until the development of an orally disintegrating form of the drug, selegiline–which was approved for use as an adjunct in the management of patients with Parkinson's disease who experience a deterioration in their response to treatment with levodopa/carbidopa–had been administered as a capsule or tablet to be swallowed.

He analyzed data from two trials of orally disintegrating selegiline versus placebo in patients experiencing an erosion of efficacy with optimized levodopa therapy. Patients were included in the trials if they were older than 30 years, had a confirmed diagnosis of Parkinson's disease, had a documented response to levodopa with a dopa-decarboxylase inhibitor, and experienced at least 3 hours daily when the beneficial effects of levodopa wore off.

Initially, patients in both trials were randomized to receive either 1.25 mg of orally disintegrating selegiline or placebo per day. At week 6, the dosage of orally disintegrating selegiline was increased to 2.5 mg per day. The average baseline number of “off” hours was determined using patient recordings for a 24-hour period for 2 days preceding the initial clinic visit. The average number of “off” hours throughout the trial were also determined using the diaries for the 2 days prior to clinic visits. Six visits were conducted throughout the 12-week trial.

In the first trial, 98 patients were randomized to selegiline and 50 to placebo; in the second, 94 patients were randomized to selegiline and 48 to placebo.

Combined results from both trials showed that orally disintegrating selegiline significantly decreased total levodopa “off” time at weeks 4–6. The treatment group had 5 hours per day during which efficacy wore off, compared with 6 hours per day for the placebo group (10% vs. 6% reductions from baseline, respectively).

Orally disintegrating selegiline also significantly decreased the percentage of levodopa “off” time at weeks 10–12. The treatment group had 4.5 hours per day during which efficacy wore off, compared with 6 hours per day for the placebo group (approximately 13% vs. 7% reductions from baseline, respectively).

Assessment of results from patients with the Clinical Global Impression of Severity and Improvement scales and the Patient Global Improvement scale significantly favored orally disintegrating selegiline as well at weeks 10–12.

Orally disintegrating selegiline was generally well tolerated in both trials. In the first trial, 8% of patients taking selegiline experienced serious adverse events, compared with 2% of patients given placebo. In the second trial, 3% of patients on selegiline experienced serious adverse events, compared with 4% of those on placebo. The most commonly reported adverse events were nausea, dry mouth, and dizziness.

SAN JUAN, P.R. – Atypical antipsychotics appear to have a modest effect on behavioral symptoms in elderly patients with dementia, but the effectiveness of nonpharmacologic treatments is less clear, according to a metaanalysis presented at the annual meeting of the American Association for Geriatric Psychiatry.

Dr. Mark B. Snowden of the department of psychiatry and behavioral sciences at the University of Washington in Seattle and his colleagues used metaanalysis techniques to compare the efficacy of nonpharmacologic treatments with that of pharmacologic therapies.

Articles from peer-reviewed, English language publications, including textbooks, from 1970 on were considered for the analysis. Nursing home residents had to make up at least half of the populations being studied. In addition to literature searches in several medical and nursing databases, the researchers submitted articles that they were aware of but that had not previously been identified. Articles were included only if they documented randomized, controlled trials.

The researchers identified five randomized, controlled trials of antipsychotic drugs and three randomized, controlled trials for nonpharmacologic interventions. The drug trials included four atypical drugs and one traditional antipsychotic drug.

The nonpharmacologic trials included 8 hours of nurses' aide training to communicate more effectively with patients with dementia, 8 hours of education/training with weekly follow-ups and hands-on activities of daily living care, 3 hours per day of psychosocial activities, and combined nonpharmacologic approaches.

The calculated effect size for nonpharmacologic interventions was -.088, which was not statistically significant. In comparison, the calculated effect size for pharmacologic interventions was -.23, which “would be considered small to modest at best,” Dr. Snowden said. “In this instance, the finding was consistent enough across studies that it is statistically significant.”

Only the pharmacologic studies provided data on the number of patients whose condition did or did not improve. Those studies yielded a statistically significant mean odds ratio of 1.87; thus, patients had an 87% chance of improving with drug treatment.

The researchers also calculated the benefit-to-harm ratio for antipsychotic treatment. “For every 14 people who got a drug and improved, you would expect one excess death,” Dr. Snowden said.

While Dr. Snowden pointed out that one excess death is not a trivial number, “when presented with this data, I have yet to have a nursing home family say that they don't want an antipsychotic drug given to their relative.”

In 2003, the American Geriatrics Society and the American Association for Geriatric Psychiatry released a consensus statement on the management of behavioral symptoms associated with dementia.

In the statement, the two groups recommended the use of nonpharmacologic interventions as the initial treatment, as long as patients did not display psychotic symptoms and there was no immediate danger to the resident or to others. The statement iterated that antipsychotic drugs should only be considered for first-line treatment in cases with severe behavioral symptoms with psychotic features.

Since that time, the Food and Drug Administration has issued a public health advisory about increased mortality associated with off-label use of atypical antipsychotics among elderly patients.

“Given the modesty of the effect size, I think we probably need to remove the requirement for psychosis or danger. … Danger is a very high standard,” Dr. Snowden said. “If you say you can only use antipsychotics in someone who is dangerous, there are going to be a lot of people who are distressed that you're not going to treat.”

SAN JUAN, P.R. – Atypical antipsychotics appear to have a modest effect on behavioral symptoms in elderly patients with dementia, but the effectiveness of nonpharmacologic treatments is less clear, according to a metaanalysis presented at the annual meeting of the American Association for Geriatric Psychiatry.

Dr. Mark B. Snowden of the department of psychiatry and behavioral sciences at the University of Washington in Seattle and his colleagues used metaanalysis techniques to compare the efficacy of nonpharmacologic treatments with that of pharmacologic therapies.

Articles from peer-reviewed, English language publications, including textbooks, from 1970 on were considered for the analysis. Nursing home residents had to make up at least half of the populations being studied. In addition to literature searches in several medical and nursing databases, the researchers submitted articles that they were aware of but that had not previously been identified. Articles were included only if they documented randomized, controlled trials.

The researchers identified five randomized, controlled trials of antipsychotic drugs and three randomized, controlled trials for nonpharmacologic interventions. The drug trials included four atypical drugs and one traditional antipsychotic drug.

The nonpharmacologic trials included 8 hours of nurses' aide training to communicate more effectively with patients with dementia, 8 hours of education/training with weekly follow-ups and hands-on activities of daily living care, 3 hours per day of psychosocial activities, and combined nonpharmacologic approaches.

The calculated effect size for nonpharmacologic interventions was -.088, which was not statistically significant. In comparison, the calculated effect size for pharmacologic interventions was -.23, which “would be considered small to modest at best,” Dr. Snowden said. “In this instance, the finding was consistent enough across studies that it is statistically significant.”

Only the pharmacologic studies provided data on the number of patients whose condition did or did not improve. Those studies yielded a statistically significant mean odds ratio of 1.87; thus, patients had an 87% chance of improving with drug treatment.

The researchers also calculated the benefit-to-harm ratio for antipsychotic treatment. “For every 14 people who got a drug and improved, you would expect one excess death,” Dr. Snowden said.

While Dr. Snowden pointed out that one excess death is not a trivial number, “when presented with this data, I have yet to have a nursing home family say that they don't want an antipsychotic drug given to their relative.”

In 2003, the American Geriatrics Society and the American Association for Geriatric Psychiatry released a consensus statement on the management of behavioral symptoms associated with dementia.

In the statement, the two groups recommended the use of nonpharmacologic interventions as the initial treatment, as long as patients did not display psychotic symptoms and there was no immediate danger to the resident or to others. The statement iterated that antipsychotic drugs should only be considered for first-line treatment in cases with severe behavioral symptoms with psychotic features.

Since that time, the Food and Drug Administration has issued a public health advisory about increased mortality associated with off-label use of atypical antipsychotics among elderly patients.

“Given the modesty of the effect size, I think we probably need to remove the requirement for psychosis or danger. … Danger is a very high standard,” Dr. Snowden said. “If you say you can only use antipsychotics in someone who is dangerous, there are going to be a lot of people who are distressed that you're not going to treat.”

SAN JUAN, P.R. – Atypical antipsychotics appear to have a modest effect on behavioral symptoms in elderly patients with dementia, but the effectiveness of nonpharmacologic treatments is less clear, according to a metaanalysis presented at the annual meeting of the American Association for Geriatric Psychiatry.

Dr. Mark B. Snowden of the department of psychiatry and behavioral sciences at the University of Washington in Seattle and his colleagues used metaanalysis techniques to compare the efficacy of nonpharmacologic treatments with that of pharmacologic therapies.

Articles from peer-reviewed, English language publications, including textbooks, from 1970 on were considered for the analysis. Nursing home residents had to make up at least half of the populations being studied. In addition to literature searches in several medical and nursing databases, the researchers submitted articles that they were aware of but that had not previously been identified. Articles were included only if they documented randomized, controlled trials.

The researchers identified five randomized, controlled trials of antipsychotic drugs and three randomized, controlled trials for nonpharmacologic interventions. The drug trials included four atypical drugs and one traditional antipsychotic drug.

The nonpharmacologic trials included 8 hours of nurses' aide training to communicate more effectively with patients with dementia, 8 hours of education/training with weekly follow-ups and hands-on activities of daily living care, 3 hours per day of psychosocial activities, and combined nonpharmacologic approaches.

The calculated effect size for nonpharmacologic interventions was -.088, which was not statistically significant. In comparison, the calculated effect size for pharmacologic interventions was -.23, which “would be considered small to modest at best,” Dr. Snowden said. “In this instance, the finding was consistent enough across studies that it is statistically significant.”

Only the pharmacologic studies provided data on the number of patients whose condition did or did not improve. Those studies yielded a statistically significant mean odds ratio of 1.87; thus, patients had an 87% chance of improving with drug treatment.

The researchers also calculated the benefit-to-harm ratio for antipsychotic treatment. “For every 14 people who got a drug and improved, you would expect one excess death,” Dr. Snowden said.

While Dr. Snowden pointed out that one excess death is not a trivial number, “when presented with this data, I have yet to have a nursing home family say that they don't want an antipsychotic drug given to their relative.”

In 2003, the American Geriatrics Society and the American Association for Geriatric Psychiatry released a consensus statement on the management of behavioral symptoms associated with dementia.

In the statement, the two groups recommended the use of nonpharmacologic interventions as the initial treatment, as long as patients did not display psychotic symptoms and there was no immediate danger to the resident or to others. The statement iterated that antipsychotic drugs should only be considered for first-line treatment in cases with severe behavioral symptoms with psychotic features.

Since that time, the Food and Drug Administration has issued a public health advisory about increased mortality associated with off-label use of atypical antipsychotics among elderly patients.

“Given the modesty of the effect size, I think we probably need to remove the requirement for psychosis or danger. … Danger is a very high standard,” Dr. Snowden said. “If you say you can only use antipsychotics in someone who is dangerous, there are going to be a lot of people who are distressed that you're not going to treat.”

SAN JUAN, P.R. – Not all older patients with dementia are dangerous drivers, making individual assessments of fitness to drive crucial for road safety, Dr. John C. Morris said at the annual meeting of the American Association for Geriatric Psychiatry.

It's no surprise that increasing dementia severity is a risk factor for unsafe driving. About 30% of demented people continue to drive. “We know that all demented drivers–at some point in the course of their dementia–will become unsafe,” said Dr. Morris, professor of neurology at Washington University, St. Louis.

Demented drivers also have a twofold increased risk of crashing, compared with age-matched nondemented individuals. “In particular, they're at increased risk of fatal crashes,” said Dr. Morris.

Despite the potential danger, few older adults with dementia want to stop driving. “It's no surprise that older adults do not want to relinquish driving,” Dr. Morris said. Driving is a crucial means of transportation for many older adults–losing the ability to drive means losing autonomy. Without the ability to drive, older adults are at greater risk for social isolation and depression.

For many older adults, the issue of fairness also comes into play. They don't believe it is fair to have to give up their ability to drive when they have never had an accident.

“It's very important for older adults–if they are safe to drive–to be able to continue to do so,” Dr. Morris said. As a starting point, ask not only the patient but also family and caregivers about problematic driving behaviors whenever you evaluate an older adult. In particular, ask about the following unsafe behaviors that are typically exhibited by older adults with dementia:

▸ Failing to stay in their lane or to maintain proper distance.

▸ Driving at improper speeds (too fast or too slow).

▸ Ignoring or failing to comprehend road signs.

▸ Failing to signal, check traffic, or react to other drivers.

▸ Becoming lost.

▸ Having accidents (even “fender benders”).

▸ Receiving citations.

Driving simulators provide a safe testing environment and can help determine whether a person with dementia is safe on the roads. Road tests, however, may be the standard by which other evaluation methods are measured, Dr. Morris said. These tests provide a reliable, direct measure of a person's driving ability but require special equipment and can be costly.

Finally, there is physician judgment based on information from the patient and family, cognitive measures, and physical examinations. Physicians actually do a fairly good job of evaluating a patient's ability to drive safely, Dr. Morris said. According to one study, physicians are accurate roughly three-quarters of the time in determining whether a person has the ability to drive safely (J. Am. Geriatr. Soc. 2005;53:94–8).

Age alone appears to be a risk factor for unsafe driving as well. Studies indicate that periodically monitoring older patients for driving ability is important. At-risk drivers should be reevaluated about every 6 months.

Here's the approach that Dr. Morris and his colleagues at Washington University's Alzheimer's disease research center use when dealing with the issue of dementia and driving:

▸ Routinely ask the patient and family if the patient is driving and, if so, about any problems or risks.

▸ Assess any comorbid factors, such as medications and visual impairment.

▸ If the patient with dementia wishes to drive and reportedly can do so safely, require confirmation with a road test.

▸ If the patient performs safely on the road test, allow continued driving until a follow-up road test is performed in 6–12 months.

▸ If the patient is determined to be an unsafe driver following a road test, initiate driving cessation.

“The most difficult part is, how do we get an older person to stop driving?” Dr. Morris asked. Appealing to the older driver's judgment usually does not work, but it is very important to maintain the patient's dignity during this process, he said. Going over with the patient and family the reasons why he or she should stop driving is sometimes helpful. “It has more weight coming from a physician,” said Dr. Morris, who also gives his patients a written reminder–a prescription–that they may not drive.

The family has to be involved in enforcing the decision. It's also important that the family work to provide an alternative means of transportation for the patient. In extreme situations, when the patient is determined to continue driving, the family may have to consider simply selling the car.

▸ www.ama-assn.org/go/olderdrivers

▸ www.alz.org

▸ www.nhtsa.dot.gov

Dr. Morris recommended the following Web sites for more information about older drivers or drivers with dementia:

KATHRYN DALES, ILLUSTRATION

SAN JUAN, P.R. – Not all older patients with dementia are dangerous drivers, making individual assessments of fitness to drive crucial for road safety, Dr. John C. Morris said at the annual meeting of the American Association for Geriatric Psychiatry.

It's no surprise that increasing dementia severity is a risk factor for unsafe driving. About 30% of demented people continue to drive. “We know that all demented drivers–at some point in the course of their dementia–will become unsafe,” said Dr. Morris, professor of neurology at Washington University, St. Louis.

Demented drivers also have a twofold increased risk of crashing, compared with age-matched nondemented individuals. “In particular, they're at increased risk of fatal crashes,” said Dr. Morris.

Despite the potential danger, few older adults with dementia want to stop driving. “It's no surprise that older adults do not want to relinquish driving,” Dr. Morris said. Driving is a crucial means of transportation for many older adults–losing the ability to drive means losing autonomy. Without the ability to drive, older adults are at greater risk for social isolation and depression.

For many older adults, the issue of fairness also comes into play. They don't believe it is fair to have to give up their ability to drive when they have never had an accident.

“It's very important for older adults–if they are safe to drive–to be able to continue to do so,” Dr. Morris said. As a starting point, ask not only the patient but also family and caregivers about problematic driving behaviors whenever you evaluate an older adult. In particular, ask about the following unsafe behaviors that are typically exhibited by older adults with dementia:

▸ Failing to stay in their lane or to maintain proper distance.

▸ Driving at improper speeds (too fast or too slow).

▸ Ignoring or failing to comprehend road signs.

▸ Failing to signal, check traffic, or react to other drivers.

▸ Becoming lost.

▸ Having accidents (even “fender benders”).

▸ Receiving citations.

Driving simulators provide a safe testing environment and can help determine whether a person with dementia is safe on the roads. Road tests, however, may be the standard by which other evaluation methods are measured, Dr. Morris said. These tests provide a reliable, direct measure of a person's driving ability but require special equipment and can be costly.

Finally, there is physician judgment based on information from the patient and family, cognitive measures, and physical examinations. Physicians actually do a fairly good job of evaluating a patient's ability to drive safely, Dr. Morris said. According to one study, physicians are accurate roughly three-quarters of the time in determining whether a person has the ability to drive safely (J. Am. Geriatr. Soc. 2005;53:94–8).

Age alone appears to be a risk factor for unsafe driving as well. Studies indicate that periodically monitoring older patients for driving ability is important. At-risk drivers should be reevaluated about every 6 months.

Here's the approach that Dr. Morris and his colleagues at Washington University's Alzheimer's disease research center use when dealing with the issue of dementia and driving:

▸ Routinely ask the patient and family if the patient is driving and, if so, about any problems or risks.

▸ Assess any comorbid factors, such as medications and visual impairment.

▸ If the patient with dementia wishes to drive and reportedly can do so safely, require confirmation with a road test.

▸ If the patient performs safely on the road test, allow continued driving until a follow-up road test is performed in 6–12 months.

▸ If the patient is determined to be an unsafe driver following a road test, initiate driving cessation.

“The most difficult part is, how do we get an older person to stop driving?” Dr. Morris asked. Appealing to the older driver's judgment usually does not work, but it is very important to maintain the patient's dignity during this process, he said. Going over with the patient and family the reasons why he or she should stop driving is sometimes helpful. “It has more weight coming from a physician,” said Dr. Morris, who also gives his patients a written reminder–a prescription–that they may not drive.

The family has to be involved in enforcing the decision. It's also important that the family work to provide an alternative means of transportation for the patient. In extreme situations, when the patient is determined to continue driving, the family may have to consider simply selling the car.

▸ www.ama-assn.org/go/olderdrivers

▸ www.alz.org

▸ www.nhtsa.dot.gov

Dr. Morris recommended the following Web sites for more information about older drivers or drivers with dementia:

KATHRYN DALES, ILLUSTRATION

SAN JUAN, P.R. – Not all older patients with dementia are dangerous drivers, making individual assessments of fitness to drive crucial for road safety, Dr. John C. Morris said at the annual meeting of the American Association for Geriatric Psychiatry.

It's no surprise that increasing dementia severity is a risk factor for unsafe driving. About 30% of demented people continue to drive. “We know that all demented drivers–at some point in the course of their dementia–will become unsafe,” said Dr. Morris, professor of neurology at Washington University, St. Louis.

Demented drivers also have a twofold increased risk of crashing, compared with age-matched nondemented individuals. “In particular, they're at increased risk of fatal crashes,” said Dr. Morris.

Despite the potential danger, few older adults with dementia want to stop driving. “It's no surprise that older adults do not want to relinquish driving,” Dr. Morris said. Driving is a crucial means of transportation for many older adults–losing the ability to drive means losing autonomy. Without the ability to drive, older adults are at greater risk for social isolation and depression.

For many older adults, the issue of fairness also comes into play. They don't believe it is fair to have to give up their ability to drive when they have never had an accident.

“It's very important for older adults–if they are safe to drive–to be able to continue to do so,” Dr. Morris said. As a starting point, ask not only the patient but also family and caregivers about problematic driving behaviors whenever you evaluate an older adult. In particular, ask about the following unsafe behaviors that are typically exhibited by older adults with dementia:

▸ Failing to stay in their lane or to maintain proper distance.

▸ Driving at improper speeds (too fast or too slow).

▸ Ignoring or failing to comprehend road signs.

▸ Failing to signal, check traffic, or react to other drivers.

▸ Becoming lost.

▸ Having accidents (even “fender benders”).

▸ Receiving citations.

Driving simulators provide a safe testing environment and can help determine whether a person with dementia is safe on the roads. Road tests, however, may be the standard by which other evaluation methods are measured, Dr. Morris said. These tests provide a reliable, direct measure of a person's driving ability but require special equipment and can be costly.

Finally, there is physician judgment based on information from the patient and family, cognitive measures, and physical examinations. Physicians actually do a fairly good job of evaluating a patient's ability to drive safely, Dr. Morris said. According to one study, physicians are accurate roughly three-quarters of the time in determining whether a person has the ability to drive safely (J. Am. Geriatr. Soc. 2005;53:94–8).

Age alone appears to be a risk factor for unsafe driving as well. Studies indicate that periodically monitoring older patients for driving ability is important. At-risk drivers should be reevaluated about every 6 months.

Here's the approach that Dr. Morris and his colleagues at Washington University's Alzheimer's disease research center use when dealing with the issue of dementia and driving:

▸ Routinely ask the patient and family if the patient is driving and, if so, about any problems or risks.

▸ Assess any comorbid factors, such as medications and visual impairment.

▸ If the patient with dementia wishes to drive and reportedly can do so safely, require confirmation with a road test.

▸ If the patient performs safely on the road test, allow continued driving until a follow-up road test is performed in 6–12 months.

▸ If the patient is determined to be an unsafe driver following a road test, initiate driving cessation.

“The most difficult part is, how do we get an older person to stop driving?” Dr. Morris asked. Appealing to the older driver's judgment usually does not work, but it is very important to maintain the patient's dignity during this process, he said. Going over with the patient and family the reasons why he or she should stop driving is sometimes helpful. “It has more weight coming from a physician,” said Dr. Morris, who also gives his patients a written reminder–a prescription–that they may not drive.

The family has to be involved in enforcing the decision. It's also important that the family work to provide an alternative means of transportation for the patient. In extreme situations, when the patient is determined to continue driving, the family may have to consider simply selling the car.

▸ www.ama-assn.org/go/olderdrivers

▸ www.alz.org

▸ www.nhtsa.dot.gov

Dr. Morris recommended the following Web sites for more information about older drivers or drivers with dementia:

KATHRYN DALES, ILLUSTRATION

SAN JUAN, P.R. – R-flurbiprofen, one of a new class of selective amyloid-β42-lowering drugs, shows some promise at higher doses in delaying cognitive and functional declines associated with Alzheimer's disease, according to phase II trial data presented at the annual meeting of the American Association for Geriatric Psychiatry.

“Subjects with mild AD on the high dose (800 mg) showed a reduced rate of decline on all of the primary outcome measures,” said Dr. Daniel D. Christensen, a psychiatrist and neurologist at the University of Utah, Salt Lake City. This selective amyloid-β 42-lowering agent (SALA) is thought to be an allosteric modulator of γ-secretase.

The proof-of-concept study involved 207 patients with mild to moderate Alzheimer's disease (AD), and was conducted in Canada and the United Kingdom. The trial was sponsored by the drug's developer, Myriad Pharmaceuticals Inc. Dr. Christensen also is a consultant/speaker for the company.

Patients were randomized to receive twice-daily doses of 400 mg R-flurbiprofen, 800 mg R-flurbiprofen, or placebo. The placebo-controlled portion of the trial lasted for 12 months. All trial participants who were stable on anticholinesterase drugs for at least 3 months prior to the study were allowed to continue with them. Patients were assessed using the Alzheimer's Disease Assessment Scale, cognitive section (ADAS-cog), the Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL), and the Clinical Dementia Rating (CDR) sum of box score.

“There was essentially no response in the moderate patients,” said Dr. Christensen. For this reason, the researchers limited their analysis to patients with mild AD (those with a Mini-Mental State Examination score of at least 20). Of the patients who had mild Alzheimer's, 46 received placebo, 36 received 400 mg R-flurbiprofen, and 48 received 800 mg R-flurbiprofen.

In terms of ADAS-cog scores, those who received 400 mg R-flurbiprofen had essentially the same response as those on placebo. Those taking the higher dose of R-flurbiprofen showed a 34% effect size at 12 months, though this was not statistically significant. “This basically means that we prevented 34%–about a third–of the respective decline” seen in the other two groups, Dr. Christensen said.

Those in the 800-mg group showed an effect size of 45% at 12 months, as measured by the ADCS-ADL, though this did not reach statistical significance. The 400-mg dose appeared to have an intermediate effect on daily function. There was little difference at 12 months between the placebo group and those in the 400-mg group in global function, as measured by the CDR. The effect size for the 800-mg group was 36%, though this did not reach statistical significance.

In an exploratory analysis, the researchers found a significant relationship between plasma concentration and response. A total of 29 patients (60% of those in the 800-mg group) had drug plasma concentrations greater than 75 μg/mL.

Both dosing regimens were generally well tolerated, Dr. Christensen said. The numbers of discontinuations attributable to adverse events were comparable among the placebo group and the two active treatment groups. Transient eosinophilia, mild anemia, blood pressure elevation, lower respiratory tract infections, and mild rashes occurred more frequently in the active treatment groups.

Patients in Canada were allowed to participate in a follow-on study after 12 months. Of the 106 patients eligible, 86 enrolled for an additional 12 months; 62 had mild AD. Of the mild-AD patients, 20 had previously been in the placebo group and were randomized to receive either 400 mg or 800 mg R-flurbiprofen twice daily.

A phase III trial is now underway in the United States.

SAN JUAN, P.R. – R-flurbiprofen, one of a new class of selective amyloid-β42-lowering drugs, shows some promise at higher doses in delaying cognitive and functional declines associated with Alzheimer's disease, according to phase II trial data presented at the annual meeting of the American Association for Geriatric Psychiatry.

“Subjects with mild AD on the high dose (800 mg) showed a reduced rate of decline on all of the primary outcome measures,” said Dr. Daniel D. Christensen, a psychiatrist and neurologist at the University of Utah, Salt Lake City. This selective amyloid-β 42-lowering agent (SALA) is thought to be an allosteric modulator of γ-secretase.

The proof-of-concept study involved 207 patients with mild to moderate Alzheimer's disease (AD), and was conducted in Canada and the United Kingdom. The trial was sponsored by the drug's developer, Myriad Pharmaceuticals Inc. Dr. Christensen also is a consultant/speaker for the company.

Patients were randomized to receive twice-daily doses of 400 mg R-flurbiprofen, 800 mg R-flurbiprofen, or placebo. The placebo-controlled portion of the trial lasted for 12 months. All trial participants who were stable on anticholinesterase drugs for at least 3 months prior to the study were allowed to continue with them. Patients were assessed using the Alzheimer's Disease Assessment Scale, cognitive section (ADAS-cog), the Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL), and the Clinical Dementia Rating (CDR) sum of box score.

“There was essentially no response in the moderate patients,” said Dr. Christensen. For this reason, the researchers limited their analysis to patients with mild AD (those with a Mini-Mental State Examination score of at least 20). Of the patients who had mild Alzheimer's, 46 received placebo, 36 received 400 mg R-flurbiprofen, and 48 received 800 mg R-flurbiprofen.

In terms of ADAS-cog scores, those who received 400 mg R-flurbiprofen had essentially the same response as those on placebo. Those taking the higher dose of R-flurbiprofen showed a 34% effect size at 12 months, though this was not statistically significant. “This basically means that we prevented 34%–about a third–of the respective decline” seen in the other two groups, Dr. Christensen said.

Those in the 800-mg group showed an effect size of 45% at 12 months, as measured by the ADCS-ADL, though this did not reach statistical significance. The 400-mg dose appeared to have an intermediate effect on daily function. There was little difference at 12 months between the placebo group and those in the 400-mg group in global function, as measured by the CDR. The effect size for the 800-mg group was 36%, though this did not reach statistical significance.

In an exploratory analysis, the researchers found a significant relationship between plasma concentration and response. A total of 29 patients (60% of those in the 800-mg group) had drug plasma concentrations greater than 75 μg/mL.

Both dosing regimens were generally well tolerated, Dr. Christensen said. The numbers of discontinuations attributable to adverse events were comparable among the placebo group and the two active treatment groups. Transient eosinophilia, mild anemia, blood pressure elevation, lower respiratory tract infections, and mild rashes occurred more frequently in the active treatment groups.

Patients in Canada were allowed to participate in a follow-on study after 12 months. Of the 106 patients eligible, 86 enrolled for an additional 12 months; 62 had mild AD. Of the mild-AD patients, 20 had previously been in the placebo group and were randomized to receive either 400 mg or 800 mg R-flurbiprofen twice daily.

A phase III trial is now underway in the United States.

SAN JUAN, P.R. – R-flurbiprofen, one of a new class of selective amyloid-β42-lowering drugs, shows some promise at higher doses in delaying cognitive and functional declines associated with Alzheimer's disease, according to phase II trial data presented at the annual meeting of the American Association for Geriatric Psychiatry.

“Subjects with mild AD on the high dose (800 mg) showed a reduced rate of decline on all of the primary outcome measures,” said Dr. Daniel D. Christensen, a psychiatrist and neurologist at the University of Utah, Salt Lake City. This selective amyloid-β 42-lowering agent (SALA) is thought to be an allosteric modulator of γ-secretase.

The proof-of-concept study involved 207 patients with mild to moderate Alzheimer's disease (AD), and was conducted in Canada and the United Kingdom. The trial was sponsored by the drug's developer, Myriad Pharmaceuticals Inc. Dr. Christensen also is a consultant/speaker for the company.

Patients were randomized to receive twice-daily doses of 400 mg R-flurbiprofen, 800 mg R-flurbiprofen, or placebo. The placebo-controlled portion of the trial lasted for 12 months. All trial participants who were stable on anticholinesterase drugs for at least 3 months prior to the study were allowed to continue with them. Patients were assessed using the Alzheimer's Disease Assessment Scale, cognitive section (ADAS-cog), the Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL), and the Clinical Dementia Rating (CDR) sum of box score.

“There was essentially no response in the moderate patients,” said Dr. Christensen. For this reason, the researchers limited their analysis to patients with mild AD (those with a Mini-Mental State Examination score of at least 20). Of the patients who had mild Alzheimer's, 46 received placebo, 36 received 400 mg R-flurbiprofen, and 48 received 800 mg R-flurbiprofen.

In terms of ADAS-cog scores, those who received 400 mg R-flurbiprofen had essentially the same response as those on placebo. Those taking the higher dose of R-flurbiprofen showed a 34% effect size at 12 months, though this was not statistically significant. “This basically means that we prevented 34%–about a third–of the respective decline” seen in the other two groups, Dr. Christensen said.

Those in the 800-mg group showed an effect size of 45% at 12 months, as measured by the ADCS-ADL, though this did not reach statistical significance. The 400-mg dose appeared to have an intermediate effect on daily function. There was little difference at 12 months between the placebo group and those in the 400-mg group in global function, as measured by the CDR. The effect size for the 800-mg group was 36%, though this did not reach statistical significance.

In an exploratory analysis, the researchers found a significant relationship between plasma concentration and response. A total of 29 patients (60% of those in the 800-mg group) had drug plasma concentrations greater than 75 μg/mL.

Both dosing regimens were generally well tolerated, Dr. Christensen said. The numbers of discontinuations attributable to adverse events were comparable among the placebo group and the two active treatment groups. Transient eosinophilia, mild anemia, blood pressure elevation, lower respiratory tract infections, and mild rashes occurred more frequently in the active treatment groups.

Patients in Canada were allowed to participate in a follow-on study after 12 months. Of the 106 patients eligible, 86 enrolled for an additional 12 months; 62 had mild AD. Of the mild-AD patients, 20 had previously been in the placebo group and were randomized to receive either 400 mg or 800 mg R-flurbiprofen twice daily.

A phase III trial is now underway in the United States.

The Food and Drug Administration is warning consumers about manufacturers and distributors that still sell illegal steroid products as dietary supplements without the agency's approval.

Consumers who have purchased Anabolic Xtreme Supredrol (manufactured for Anabolic Resources LLC in Gilbert, Ariz., and distributed by Supplements to Go in Cincinnati) and Methyl 1-P (manufactured for Legal Gear in Brighton, Mich., and distributed by Affordable Supplements in Wichita, Kan.) should discontinue use and return the unused portion to the place of purchase.

The supplements are promoted for building muscle and increasing strength, but actually may cause serious long-term adverse health consequences. The products are described as anabolic, and problems associated with anabolic steroids include: liver toxicity, testicular atrophy and male infertility, masculinization of women, breast enlargement in males, short stature in children, adverse effects on blood lipid levels, and a potential to increase the risk of heart attack and stroke.

For more information, contact the FDA by calling 888-463-6332.

The Food and Drug Administration is warning consumers about manufacturers and distributors that still sell illegal steroid products as dietary supplements without the agency's approval.

Consumers who have purchased Anabolic Xtreme Supredrol (manufactured for Anabolic Resources LLC in Gilbert, Ariz., and distributed by Supplements to Go in Cincinnati) and Methyl 1-P (manufactured for Legal Gear in Brighton, Mich., and distributed by Affordable Supplements in Wichita, Kan.) should discontinue use and return the unused portion to the place of purchase.

The supplements are promoted for building muscle and increasing strength, but actually may cause serious long-term adverse health consequences. The products are described as anabolic, and problems associated with anabolic steroids include: liver toxicity, testicular atrophy and male infertility, masculinization of women, breast enlargement in males, short stature in children, adverse effects on blood lipid levels, and a potential to increase the risk of heart attack and stroke.

For more information, contact the FDA by calling 888-463-6332.

The Food and Drug Administration is warning consumers about manufacturers and distributors that still sell illegal steroid products as dietary supplements without the agency's approval.

Consumers who have purchased Anabolic Xtreme Supredrol (manufactured for Anabolic Resources LLC in Gilbert, Ariz., and distributed by Supplements to Go in Cincinnati) and Methyl 1-P (manufactured for Legal Gear in Brighton, Mich., and distributed by Affordable Supplements in Wichita, Kan.) should discontinue use and return the unused portion to the place of purchase.

The supplements are promoted for building muscle and increasing strength, but actually may cause serious long-term adverse health consequences. The products are described as anabolic, and problems associated with anabolic steroids include: liver toxicity, testicular atrophy and male infertility, masculinization of women, breast enlargement in males, short stature in children, adverse effects on blood lipid levels, and a potential to increase the risk of heart attack and stroke.

For more information, contact the FDA by calling 888-463-6332.

WASHINGTON — An orally disintegrating formulation of selegiline appears to be a safe and effective adjunct for patients with Parkinson's disease who are experiencing a deterioration of levodopa response, according to data presented in a poster at the World Parkinson Congress.

Selegiline taken in the orally disintegrating form significantly decreased the amount of levodopa nonresponse time, compared with placebo in two phase III, randomized, double-blind trials, reported Dr. William G. Ondo, of the department of neurology at Baylor College of Medicine, Houston.

A selective MAO type-B inhibitor, selegiline is limited by low bioavailability, extensive first-pass hepatic metabolism, and production of amphetamine metabolites. Orally disintegrating tablets dissolve on first contact with saliva and undergo pregastric absorption, minimizing first-pass metabolism and yielding high plasma levels.

Prior to development of an orally disintegrating form of the drug, selegiline—approved for use as an adjunct in treating patients with Parkinson's disease who experience a deterioration in response to levodopa/carbidopa—had been given as a capsule or tablet to be swallowed.

He analyzed data from two trials of orally disintegrating selegiline versus placebo in patients with erosion of efficacy with optimized levodopa therapy. Patients were older than 30 years, had a confirmed diagnosis of Parkinson's disease, had a documented response to levodopa with a dopa-decarboxylase inhibitor, and had at least 3 hours daily when the beneficial effects of levodopa wore off.

Initially, patients in both trials were randomized to placebo or 1.25 mg of orally disintegrating selegiline per day. At week 6, the selegiline dosage was increased to 2.5 mg per day. The mean baseline number of “off” hours was determined using patient recordings for a 24-hour period for 2 days preceding the initial clinic visit. The mean number of “off” hours throughout the trial were also determined using the diaries for the 2 days prior to clinic visits. Six visits were conducted during the 12-week trial.

In the first trial, 98 patients were randomized to selegiline and 50 to placebo; in the second, 94 patients were randomized to selegiline and 48 to placebo.

Combined results from both trials showed that orally disintegrating selegiline significantly decreased total levodopa “off” time at weeks 4–6. The treatment group had 5 hours per day during which efficacy wore off, compared with 6 hours per day for the placebo group (10% vs. 6% reductions from baseline, respectively).

Orally disintegrating selegiline also significantly decreased the percentage of levodopa “off” time at weeks 10–12. The treatment group had 4.5 hours per day during which efficacy wore off, vs. 6 hours per day for the placebo group (about 13% vs. 7% reductions from baseline, respectively).

Orally disintegrating selegiline was generally well tolerated in both trials.

WASHINGTON — An orally disintegrating formulation of selegiline appears to be a safe and effective adjunct for patients with Parkinson's disease who are experiencing a deterioration of levodopa response, according to data presented in a poster at the World Parkinson Congress.

Selegiline taken in the orally disintegrating form significantly decreased the amount of levodopa nonresponse time, compared with placebo in two phase III, randomized, double-blind trials, reported Dr. William G. Ondo, of the department of neurology at Baylor College of Medicine, Houston.

A selective MAO type-B inhibitor, selegiline is limited by low bioavailability, extensive first-pass hepatic metabolism, and production of amphetamine metabolites. Orally disintegrating tablets dissolve on first contact with saliva and undergo pregastric absorption, minimizing first-pass metabolism and yielding high plasma levels.

Prior to development of an orally disintegrating form of the drug, selegiline—approved for use as an adjunct in treating patients with Parkinson's disease who experience a deterioration in response to levodopa/carbidopa—had been given as a capsule or tablet to be swallowed.

He analyzed data from two trials of orally disintegrating selegiline versus placebo in patients with erosion of efficacy with optimized levodopa therapy. Patients were older than 30 years, had a confirmed diagnosis of Parkinson's disease, had a documented response to levodopa with a dopa-decarboxylase inhibitor, and had at least 3 hours daily when the beneficial effects of levodopa wore off.

Initially, patients in both trials were randomized to placebo or 1.25 mg of orally disintegrating selegiline per day. At week 6, the selegiline dosage was increased to 2.5 mg per day. The mean baseline number of “off” hours was determined using patient recordings for a 24-hour period for 2 days preceding the initial clinic visit. The mean number of “off” hours throughout the trial were also determined using the diaries for the 2 days prior to clinic visits. Six visits were conducted during the 12-week trial.

In the first trial, 98 patients were randomized to selegiline and 50 to placebo; in the second, 94 patients were randomized to selegiline and 48 to placebo.

Combined results from both trials showed that orally disintegrating selegiline significantly decreased total levodopa “off” time at weeks 4–6. The treatment group had 5 hours per day during which efficacy wore off, compared with 6 hours per day for the placebo group (10% vs. 6% reductions from baseline, respectively).

Orally disintegrating selegiline also significantly decreased the percentage of levodopa “off” time at weeks 10–12. The treatment group had 4.5 hours per day during which efficacy wore off, vs. 6 hours per day for the placebo group (about 13% vs. 7% reductions from baseline, respectively).

Orally disintegrating selegiline was generally well tolerated in both trials.

WASHINGTON — An orally disintegrating formulation of selegiline appears to be a safe and effective adjunct for patients with Parkinson's disease who are experiencing a deterioration of levodopa response, according to data presented in a poster at the World Parkinson Congress.

Selegiline taken in the orally disintegrating form significantly decreased the amount of levodopa nonresponse time, compared with placebo in two phase III, randomized, double-blind trials, reported Dr. William G. Ondo, of the department of neurology at Baylor College of Medicine, Houston.

A selective MAO type-B inhibitor, selegiline is limited by low bioavailability, extensive first-pass hepatic metabolism, and production of amphetamine metabolites. Orally disintegrating tablets dissolve on first contact with saliva and undergo pregastric absorption, minimizing first-pass metabolism and yielding high plasma levels.

Prior to development of an orally disintegrating form of the drug, selegiline—approved for use as an adjunct in treating patients with Parkinson's disease who experience a deterioration in response to levodopa/carbidopa—had been given as a capsule or tablet to be swallowed.

He analyzed data from two trials of orally disintegrating selegiline versus placebo in patients with erosion of efficacy with optimized levodopa therapy. Patients were older than 30 years, had a confirmed diagnosis of Parkinson's disease, had a documented response to levodopa with a dopa-decarboxylase inhibitor, and had at least 3 hours daily when the beneficial effects of levodopa wore off.

Initially, patients in both trials were randomized to placebo or 1.25 mg of orally disintegrating selegiline per day. At week 6, the selegiline dosage was increased to 2.5 mg per day. The mean baseline number of “off” hours was determined using patient recordings for a 24-hour period for 2 days preceding the initial clinic visit. The mean number of “off” hours throughout the trial were also determined using the diaries for the 2 days prior to clinic visits. Six visits were conducted during the 12-week trial.

In the first trial, 98 patients were randomized to selegiline and 50 to placebo; in the second, 94 patients were randomized to selegiline and 48 to placebo.

Combined results from both trials showed that orally disintegrating selegiline significantly decreased total levodopa “off” time at weeks 4–6. The treatment group had 5 hours per day during which efficacy wore off, compared with 6 hours per day for the placebo group (10% vs. 6% reductions from baseline, respectively).

Orally disintegrating selegiline also significantly decreased the percentage of levodopa “off” time at weeks 10–12. The treatment group had 4.5 hours per day during which efficacy wore off, vs. 6 hours per day for the placebo group (about 13% vs. 7% reductions from baseline, respectively).

Orally disintegrating selegiline was generally well tolerated in both trials.

WASHINGTON — The diagnosis of drug-induced parkinsonism often gets missed, even by neurologists, according to an informal study of patients at one movement disorder clinic presented at the World Parkinson Congress.

Of all new patients with parkinsonian symptoms seen in the movement-disorders program at Emory University, Atlanta, between January 2004 and January 2006, 8% (23 of 304 patients) were diagnosed with drug-induced parkinsonism (DIP), said Dr. Stewart A. Factor, director of the program. The age range at diagnosis was 49–97 years; the age at onset ranged between 48 and 96 years. Most patients were female (73%). Records were available for 22 patients with DIP.

“Seventeen of the 22 patients had been seen previously by neurologists, and yet only 2 of them were diagnosed with drug-induced parkinsonism,” Dr. Factor said. Of these, 10 were misdiagnosed with Parkinson's disease (PD) and were treated with antiparkinsonian drugs. Seven patients had no clear diagnosis.

The older, conventional antipsychotic drugs have been most commonly associated with DIP. It has been assumed that the risk of DIP was reduced with the introduction of atypical antipsychotic drugs. However, Dr. Factor's experience has been just the opposite.

Only three patients in his clinic developed DIP in response to typical antipsychotics (haloperidol, trifluoperazine, and amoxapine). In contrast, 12 cases were caused by atypical antipsychotics (3 from risperidone, 6 from olanzapine, 1 from ziprasidone, and 2 from aripiprazole). Five cases were caused by metoclopramide and two were caused by drug combinations (metoclopramide/reserpine, metoclopramide/ziprasidone).

In terms of clinical features, 11 patients had tardive dyskinesia (including 5 with respiratory dyskinesia), 2 had akathisia, 19 had tremor (17 with resting tremor and 6 with asymmetric tremor, alone or in combination), and 3 had akinetic rigidity. Clinically, 11 patients had psychiatric diagnoses—primarily mood disorders (9 patients)—and 6 patients had neurologic diagnoses (dementia, Huntington's chorea, hydrocephalus). Of the 13 patients who stopped the drug and returned for follow-up, 12 had an improvement in symptoms within about 6 months.

DIP has a subacute onset and all of the cardinal features of Parkinson's disease—tremor, rigidity, bradykinesia, and abnormalities of posture, gait, and balance—can be seen. Akinetic rigidity (without tremor) is seen in most patients with DIP.

Drug-use history and tardive dyskinesia appear to be key to the differential diagnosis. Other factors that can help differentiate DIP from PD include subacute onset, bilateral features, more postural tremor than resting tremor, and the presence of other extrapyramidal signs.

Among psychiatric patients, 90% of DIP cases start in the first 3 months of drug use or within 3 months of a dosage increase. The condition may reverse spontaneously, but this is rare. The condition also may be chronic and progressive. Withdrawal of the drug does not lead to immediate improvement of symptoms, which typically take up to 6 months to resolve.

Metoclopramide, an antiemetic drug used mainly for gastrointestinal disorders, has been implicated in DIP. The drug is intended for short-term use (2–8 weeks), but many patients are treated long term with this drug. “With chronic use, they develop drug-induced parkinsonism or tardive dyskinesia,” he said.

Up to 25% of psychiatric patients on metoclopramide may have DIP. Women tend to be affected more often than men, particularly older women. Among patients with metoclopramide-induced parkinsonism, up to 70% have tremor, 70% have postural instability, and 40% have tardive dyskinesia. Once the drug is stopped, improvement typically takes 4 months.

The list of other drugs that have been reported as being associated with DIP includes SSRIs, dopamine depleters, bupropion, phenelzine, lithium, valproate, some cardiac drugs (amiodarone, captopril, verapamil, diltiazem, amlodipine, manidipine, methyldopa), and estrogens.

As to risk factors for DIP, women appear to be twice as likely as men to develop the disorder. Age older than 65 is associated with a five times greater risk. Greater drug potency or dose also plays a role. Less frequently described risk factors include prior brain injury, dementia, HIV infection, certain psychiatric disorders (mood disorders in particular), the presence of tardive dyskinesia, and a family history of PD.

“Recognition is the key to proper management because if you recognize that the drug causes it, you stop the drug if you can and the symptoms will reverse in most patients,” Dr. Factor said.

Amantadine and anticholinergics are often used to treat symptoms. Other potential treatments include levodopa, electroconvulsive therapy, propranolol, and clozapine.

WASHINGTON — The diagnosis of drug-induced parkinsonism often gets missed, even by neurologists, according to an informal study of patients at one movement disorder clinic presented at the World Parkinson Congress.

Of all new patients with parkinsonian symptoms seen in the movement-disorders program at Emory University, Atlanta, between January 2004 and January 2006, 8% (23 of 304 patients) were diagnosed with drug-induced parkinsonism (DIP), said Dr. Stewart A. Factor, director of the program. The age range at diagnosis was 49–97 years; the age at onset ranged between 48 and 96 years. Most patients were female (73%). Records were available for 22 patients with DIP.

“Seventeen of the 22 patients had been seen previously by neurologists, and yet only 2 of them were diagnosed with drug-induced parkinsonism,” Dr. Factor said. Of these, 10 were misdiagnosed with Parkinson's disease (PD) and were treated with antiparkinsonian drugs. Seven patients had no clear diagnosis.

The older, conventional antipsychotic drugs have been most commonly associated with DIP. It has been assumed that the risk of DIP was reduced with the introduction of atypical antipsychotic drugs. However, Dr. Factor's experience has been just the opposite.

Only three patients in his clinic developed DIP in response to typical antipsychotics (haloperidol, trifluoperazine, and amoxapine). In contrast, 12 cases were caused by atypical antipsychotics (3 from risperidone, 6 from olanzapine, 1 from ziprasidone, and 2 from aripiprazole). Five cases were caused by metoclopramide and two were caused by drug combinations (metoclopramide/reserpine, metoclopramide/ziprasidone).

In terms of clinical features, 11 patients had tardive dyskinesia (including 5 with respiratory dyskinesia), 2 had akathisia, 19 had tremor (17 with resting tremor and 6 with asymmetric tremor, alone or in combination), and 3 had akinetic rigidity. Clinically, 11 patients had psychiatric diagnoses—primarily mood disorders (9 patients)—and 6 patients had neurologic diagnoses (dementia, Huntington's chorea, hydrocephalus). Of the 13 patients who stopped the drug and returned for follow-up, 12 had an improvement in symptoms within about 6 months.

DIP has a subacute onset and all of the cardinal features of Parkinson's disease—tremor, rigidity, bradykinesia, and abnormalities of posture, gait, and balance—can be seen. Akinetic rigidity (without tremor) is seen in most patients with DIP.

Drug-use history and tardive dyskinesia appear to be key to the differential diagnosis. Other factors that can help differentiate DIP from PD include subacute onset, bilateral features, more postural tremor than resting tremor, and the presence of other extrapyramidal signs.

Among psychiatric patients, 90% of DIP cases start in the first 3 months of drug use or within 3 months of a dosage increase. The condition may reverse spontaneously, but this is rare. The condition also may be chronic and progressive. Withdrawal of the drug does not lead to immediate improvement of symptoms, which typically take up to 6 months to resolve.

Metoclopramide, an antiemetic drug used mainly for gastrointestinal disorders, has been implicated in DIP. The drug is intended for short-term use (2–8 weeks), but many patients are treated long term with this drug. “With chronic use, they develop drug-induced parkinsonism or tardive dyskinesia,” he said.

Up to 25% of psychiatric patients on metoclopramide may have DIP. Women tend to be affected more often than men, particularly older women. Among patients with metoclopramide-induced parkinsonism, up to 70% have tremor, 70% have postural instability, and 40% have tardive dyskinesia. Once the drug is stopped, improvement typically takes 4 months.

The list of other drugs that have been reported as being associated with DIP includes SSRIs, dopamine depleters, bupropion, phenelzine, lithium, valproate, some cardiac drugs (amiodarone, captopril, verapamil, diltiazem, amlodipine, manidipine, methyldopa), and estrogens.

As to risk factors for DIP, women appear to be twice as likely as men to develop the disorder. Age older than 65 is associated with a five times greater risk. Greater drug potency or dose also plays a role. Less frequently described risk factors include prior brain injury, dementia, HIV infection, certain psychiatric disorders (mood disorders in particular), the presence of tardive dyskinesia, and a family history of PD.

“Recognition is the key to proper management because if you recognize that the drug causes it, you stop the drug if you can and the symptoms will reverse in most patients,” Dr. Factor said.

Amantadine and anticholinergics are often used to treat symptoms. Other potential treatments include levodopa, electroconvulsive therapy, propranolol, and clozapine.

WASHINGTON — The diagnosis of drug-induced parkinsonism often gets missed, even by neurologists, according to an informal study of patients at one movement disorder clinic presented at the World Parkinson Congress.

Of all new patients with parkinsonian symptoms seen in the movement-disorders program at Emory University, Atlanta, between January 2004 and January 2006, 8% (23 of 304 patients) were diagnosed with drug-induced parkinsonism (DIP), said Dr. Stewart A. Factor, director of the program. The age range at diagnosis was 49–97 years; the age at onset ranged between 48 and 96 years. Most patients were female (73%). Records were available for 22 patients with DIP.

“Seventeen of the 22 patients had been seen previously by neurologists, and yet only 2 of them were diagnosed with drug-induced parkinsonism,” Dr. Factor said. Of these, 10 were misdiagnosed with Parkinson's disease (PD) and were treated with antiparkinsonian drugs. Seven patients had no clear diagnosis.

The older, conventional antipsychotic drugs have been most commonly associated with DIP. It has been assumed that the risk of DIP was reduced with the introduction of atypical antipsychotic drugs. However, Dr. Factor's experience has been just the opposite.

Only three patients in his clinic developed DIP in response to typical antipsychotics (haloperidol, trifluoperazine, and amoxapine). In contrast, 12 cases were caused by atypical antipsychotics (3 from risperidone, 6 from olanzapine, 1 from ziprasidone, and 2 from aripiprazole). Five cases were caused by metoclopramide and two were caused by drug combinations (metoclopramide/reserpine, metoclopramide/ziprasidone).

In terms of clinical features, 11 patients had tardive dyskinesia (including 5 with respiratory dyskinesia), 2 had akathisia, 19 had tremor (17 with resting tremor and 6 with asymmetric tremor, alone or in combination), and 3 had akinetic rigidity. Clinically, 11 patients had psychiatric diagnoses—primarily mood disorders (9 patients)—and 6 patients had neurologic diagnoses (dementia, Huntington's chorea, hydrocephalus). Of the 13 patients who stopped the drug and returned for follow-up, 12 had an improvement in symptoms within about 6 months.

DIP has a subacute onset and all of the cardinal features of Parkinson's disease—tremor, rigidity, bradykinesia, and abnormalities of posture, gait, and balance—can be seen. Akinetic rigidity (without tremor) is seen in most patients with DIP.

Drug-use history and tardive dyskinesia appear to be key to the differential diagnosis. Other factors that can help differentiate DIP from PD include subacute onset, bilateral features, more postural tremor than resting tremor, and the presence of other extrapyramidal signs.

Among psychiatric patients, 90% of DIP cases start in the first 3 months of drug use or within 3 months of a dosage increase. The condition may reverse spontaneously, but this is rare. The condition also may be chronic and progressive. Withdrawal of the drug does not lead to immediate improvement of symptoms, which typically take up to 6 months to resolve.

Metoclopramide, an antiemetic drug used mainly for gastrointestinal disorders, has been implicated in DIP. The drug is intended for short-term use (2–8 weeks), but many patients are treated long term with this drug. “With chronic use, they develop drug-induced parkinsonism or tardive dyskinesia,” he said.

Up to 25% of psychiatric patients on metoclopramide may have DIP. Women tend to be affected more often than men, particularly older women. Among patients with metoclopramide-induced parkinsonism, up to 70% have tremor, 70% have postural instability, and 40% have tardive dyskinesia. Once the drug is stopped, improvement typically takes 4 months.

The list of other drugs that have been reported as being associated with DIP includes SSRIs, dopamine depleters, bupropion, phenelzine, lithium, valproate, some cardiac drugs (amiodarone, captopril, verapamil, diltiazem, amlodipine, manidipine, methyldopa), and estrogens.

As to risk factors for DIP, women appear to be twice as likely as men to develop the disorder. Age older than 65 is associated with a five times greater risk. Greater drug potency or dose also plays a role. Less frequently described risk factors include prior brain injury, dementia, HIV infection, certain psychiatric disorders (mood disorders in particular), the presence of tardive dyskinesia, and a family history of PD.

“Recognition is the key to proper management because if you recognize that the drug causes it, you stop the drug if you can and the symptoms will reverse in most patients,” Dr. Factor said.

Amantadine and anticholinergics are often used to treat symptoms. Other potential treatments include levodopa, electroconvulsive therapy, propranolol, and clozapine.