Patrice Wendling

CHICAGO – Methylphenidate may be effective in the treatment of apathy associated with dementia of the Alzheimer type, Dr. Prasad Padala and associates reported in a poster at the annual meeting of the American Geriatrics Society.

Results from an open-label study in 13 patients suggest that methylphenidate (Ritalin) has a substantial effect on apathy, with smaller but significant positive effects on mood, cognition, and independent activities of daily living. The findings warrant further testing with a double-blind, placebo-controlled trial, he noted.

Apathy is the most common behavior problem reported in persons with Alzheimer's disease, affecting about 70%–90% of patients. All patients in the study had dementia of the Alzheimer type, Mini-Mental State Examination (MMSE) scores greater than 18, and Apathy Evaluation Scale (AES) scores greater than 30. Their mean age was 69 years.

All patients were started on methylphenidate 5 mg twice daily; the dose was titrated to 10 mg twice daily over a 2-week period. Follow-up visits were scheduled at 4, 8, and 12 weeks.

Significant improvement in apathy (AES 52.6 vs. 31.6) was reported from baseline over 12 weeks, reported Dr. Padala, of the department of psychiatry at the University of Nebraska, Omaha, and a psychiatrist at the Omaha division of the VA (Veterans Affairs) Nebraska Western Iowa Health Care System.

Less robust but significant improvement was noted at 12 weeks in Geriatric Depression Scale scores (93 vs. 63), MMSE scores (24.2 vs. 25.5), and Independent Activities of Daily Living criteria (13.7 vs. 16).

Subjective improvement was noted by caregivers. One caregiver reported that the patient was monitoring his medications better and started taking care of his finances again after a long hiatus.

None of the patients discontinued medication because of adverse events. In one patient, the dose of methylphenidate was reduced because of appetite loss, possibly related to treatment, Dr. Padala reported.

The study was funded by the Nancy and Ronald Reagan Alzheimer's Scholarship Fund, established at the University of Nebraska.

CHICAGO – Methylphenidate may be effective in the treatment of apathy associated with dementia of the Alzheimer type, Dr. Prasad Padala and associates reported in a poster at the annual meeting of the American Geriatrics Society.

Results from an open-label study in 13 patients suggest that methylphenidate (Ritalin) has a substantial effect on apathy, with smaller but significant positive effects on mood, cognition, and independent activities of daily living. The findings warrant further testing with a double-blind, placebo-controlled trial, he noted.

Apathy is the most common behavior problem reported in persons with Alzheimer's disease, affecting about 70%–90% of patients. All patients in the study had dementia of the Alzheimer type, Mini-Mental State Examination (MMSE) scores greater than 18, and Apathy Evaluation Scale (AES) scores greater than 30. Their mean age was 69 years.

All patients were started on methylphenidate 5 mg twice daily; the dose was titrated to 10 mg twice daily over a 2-week period. Follow-up visits were scheduled at 4, 8, and 12 weeks.

Significant improvement in apathy (AES 52.6 vs. 31.6) was reported from baseline over 12 weeks, reported Dr. Padala, of the department of psychiatry at the University of Nebraska, Omaha, and a psychiatrist at the Omaha division of the VA (Veterans Affairs) Nebraska Western Iowa Health Care System.

Less robust but significant improvement was noted at 12 weeks in Geriatric Depression Scale scores (93 vs. 63), MMSE scores (24.2 vs. 25.5), and Independent Activities of Daily Living criteria (13.7 vs. 16).

Subjective improvement was noted by caregivers. One caregiver reported that the patient was monitoring his medications better and started taking care of his finances again after a long hiatus.

None of the patients discontinued medication because of adverse events. In one patient, the dose of methylphenidate was reduced because of appetite loss, possibly related to treatment, Dr. Padala reported.

The study was funded by the Nancy and Ronald Reagan Alzheimer's Scholarship Fund, established at the University of Nebraska.

CHICAGO – Methylphenidate may be effective in the treatment of apathy associated with dementia of the Alzheimer type, Dr. Prasad Padala and associates reported in a poster at the annual meeting of the American Geriatrics Society.

Results from an open-label study in 13 patients suggest that methylphenidate (Ritalin) has a substantial effect on apathy, with smaller but significant positive effects on mood, cognition, and independent activities of daily living. The findings warrant further testing with a double-blind, placebo-controlled trial, he noted.

Apathy is the most common behavior problem reported in persons with Alzheimer's disease, affecting about 70%–90% of patients. All patients in the study had dementia of the Alzheimer type, Mini-Mental State Examination (MMSE) scores greater than 18, and Apathy Evaluation Scale (AES) scores greater than 30. Their mean age was 69 years.

All patients were started on methylphenidate 5 mg twice daily; the dose was titrated to 10 mg twice daily over a 2-week period. Follow-up visits were scheduled at 4, 8, and 12 weeks.

Significant improvement in apathy (AES 52.6 vs. 31.6) was reported from baseline over 12 weeks, reported Dr. Padala, of the department of psychiatry at the University of Nebraska, Omaha, and a psychiatrist at the Omaha division of the VA (Veterans Affairs) Nebraska Western Iowa Health Care System.

Less robust but significant improvement was noted at 12 weeks in Geriatric Depression Scale scores (93 vs. 63), MMSE scores (24.2 vs. 25.5), and Independent Activities of Daily Living criteria (13.7 vs. 16).

Subjective improvement was noted by caregivers. One caregiver reported that the patient was monitoring his medications better and started taking care of his finances again after a long hiatus.

None of the patients discontinued medication because of adverse events. In one patient, the dose of methylphenidate was reduced because of appetite loss, possibly related to treatment, Dr. Padala reported.

The study was funded by the Nancy and Ronald Reagan Alzheimer's Scholarship Fund, established at the University of Nebraska.

PITTSBURGH — Treatment with the investigational drug capromorelin brings growth hormone levels in the elderly back into the normal range for young adults, and improves some measures of function, results from a phase II trial showed.

These results suggest the possibility that long-term treatment with the oral growth hormone secretagogue could prolong the capacity for independent living in older men and women, Dr. George Merriam and his associates reported at the International Congress of Neuroendocrinology.

“One subject said his golf swing improved … but generally it was a sense of more energy, more vim and vigor,” he said in an interview.

Growth hormone secretion declines with age, and studies have looked at the benefits of administering human growth hormone. Alternative approaches under investigation include stimulating endogenous growth hormone secretion with growth-hormone-releasing hormone (GHRH) and growth hormone secretagogues (GHSs).

Both GHRH and GHS have several potential advantages over growth hormone, he said. They stimulate pulsatile rather than continuous growth hormone release, and preserve endogenous feedback, including inhibition of growth hormone release as levels of insulinlike growth factor-I (IGF-I) rise, potentially buffering against overtreatment. Some secretagogues, including capromorelin, a mimetic of the intestinal hormone ghrelin, also have the practical advantage of being orally active, said Dr. Merriam, who has no financial interest in Pfizer Inc., which is developing the drug and sponsored the study.

He presented data from a double-blind, multicenter study in which 395 generally healthy men and women with some functional limitations were randomized to 12 months of treatment with placebo or one of four active doses of capromorelin: 10 mg three times weekly, 3 mg twice daily, 10 mg daily at bedtime, or 10 mg twice daily.

The subjects' ages ranged from 65 to 84 years, and all had a body mass index of less than 30 kg/m

Each dose of capromorelin stimulated an acute rise in growth hormone levels, reported Dr. Merriam, of the University of Washington in Seattle. Capromorelin stimulated a dose-related increase in circulating IGF-I levels, with the greatest increases at the highest dose. These increases were sustained for the duration of treatment, but returned to baseline after the drug was discontinued.

Patients on active treatment gained a mean of 1.6 kg more than those on placebo after 6 months, and 1.3 kg after 12 months. This reflected an increase of 1.4 kg in lean body mass after 6 months and 1.6 kg after 12 months.

Tandem walk times improved significantly at 6 months and even more so at 12 months, compared with placebo. Stair climbing power improved significantly at 12 months.

Nonsignificant trends toward improvement were seen in the 6-minute walk, chair rises, and tandem stand tests.

The drug was generally well tolerated. Insomnia and statistically significant increases in fasting glucose levels were reported in the active treatment groups. But glucose levels remained within the normal range, Dr. Merriam said.

The physical function results are similar to those recently reported for Merck's investigational growth hormone secretagogue, MK677, which has a similar structure to capromorelin, he said. But both drugs face an uphill regulatory battle because the Food and Drug administration does not consider aging to be a disease.

“These are very encouraging data, but they're not the sort of thing that can be sent in to the FDA and get an approval from,” Dr. Merriam said. “It's too small, too limited a study, but it's very intriguing.”

PITTSBURGH — Treatment with the investigational drug capromorelin brings growth hormone levels in the elderly back into the normal range for young adults, and improves some measures of function, results from a phase II trial showed.

These results suggest the possibility that long-term treatment with the oral growth hormone secretagogue could prolong the capacity for independent living in older men and women, Dr. George Merriam and his associates reported at the International Congress of Neuroendocrinology.

“One subject said his golf swing improved … but generally it was a sense of more energy, more vim and vigor,” he said in an interview.

Growth hormone secretion declines with age, and studies have looked at the benefits of administering human growth hormone. Alternative approaches under investigation include stimulating endogenous growth hormone secretion with growth-hormone-releasing hormone (GHRH) and growth hormone secretagogues (GHSs).

Both GHRH and GHS have several potential advantages over growth hormone, he said. They stimulate pulsatile rather than continuous growth hormone release, and preserve endogenous feedback, including inhibition of growth hormone release as levels of insulinlike growth factor-I (IGF-I) rise, potentially buffering against overtreatment. Some secretagogues, including capromorelin, a mimetic of the intestinal hormone ghrelin, also have the practical advantage of being orally active, said Dr. Merriam, who has no financial interest in Pfizer Inc., which is developing the drug and sponsored the study.

He presented data from a double-blind, multicenter study in which 395 generally healthy men and women with some functional limitations were randomized to 12 months of treatment with placebo or one of four active doses of capromorelin: 10 mg three times weekly, 3 mg twice daily, 10 mg daily at bedtime, or 10 mg twice daily.

The subjects' ages ranged from 65 to 84 years, and all had a body mass index of less than 30 kg/m

Each dose of capromorelin stimulated an acute rise in growth hormone levels, reported Dr. Merriam, of the University of Washington in Seattle. Capromorelin stimulated a dose-related increase in circulating IGF-I levels, with the greatest increases at the highest dose. These increases were sustained for the duration of treatment, but returned to baseline after the drug was discontinued.

Patients on active treatment gained a mean of 1.6 kg more than those on placebo after 6 months, and 1.3 kg after 12 months. This reflected an increase of 1.4 kg in lean body mass after 6 months and 1.6 kg after 12 months.

Tandem walk times improved significantly at 6 months and even more so at 12 months, compared with placebo. Stair climbing power improved significantly at 12 months.

Nonsignificant trends toward improvement were seen in the 6-minute walk, chair rises, and tandem stand tests.

The drug was generally well tolerated. Insomnia and statistically significant increases in fasting glucose levels were reported in the active treatment groups. But glucose levels remained within the normal range, Dr. Merriam said.

The physical function results are similar to those recently reported for Merck's investigational growth hormone secretagogue, MK677, which has a similar structure to capromorelin, he said. But both drugs face an uphill regulatory battle because the Food and Drug administration does not consider aging to be a disease.

“These are very encouraging data, but they're not the sort of thing that can be sent in to the FDA and get an approval from,” Dr. Merriam said. “It's too small, too limited a study, but it's very intriguing.”

PITTSBURGH — Treatment with the investigational drug capromorelin brings growth hormone levels in the elderly back into the normal range for young adults, and improves some measures of function, results from a phase II trial showed.

These results suggest the possibility that long-term treatment with the oral growth hormone secretagogue could prolong the capacity for independent living in older men and women, Dr. George Merriam and his associates reported at the International Congress of Neuroendocrinology.

“One subject said his golf swing improved … but generally it was a sense of more energy, more vim and vigor,” he said in an interview.

Growth hormone secretion declines with age, and studies have looked at the benefits of administering human growth hormone. Alternative approaches under investigation include stimulating endogenous growth hormone secretion with growth-hormone-releasing hormone (GHRH) and growth hormone secretagogues (GHSs).

Both GHRH and GHS have several potential advantages over growth hormone, he said. They stimulate pulsatile rather than continuous growth hormone release, and preserve endogenous feedback, including inhibition of growth hormone release as levels of insulinlike growth factor-I (IGF-I) rise, potentially buffering against overtreatment. Some secretagogues, including capromorelin, a mimetic of the intestinal hormone ghrelin, also have the practical advantage of being orally active, said Dr. Merriam, who has no financial interest in Pfizer Inc., which is developing the drug and sponsored the study.

He presented data from a double-blind, multicenter study in which 395 generally healthy men and women with some functional limitations were randomized to 12 months of treatment with placebo or one of four active doses of capromorelin: 10 mg three times weekly, 3 mg twice daily, 10 mg daily at bedtime, or 10 mg twice daily.

The subjects' ages ranged from 65 to 84 years, and all had a body mass index of less than 30 kg/m

Each dose of capromorelin stimulated an acute rise in growth hormone levels, reported Dr. Merriam, of the University of Washington in Seattle. Capromorelin stimulated a dose-related increase in circulating IGF-I levels, with the greatest increases at the highest dose. These increases were sustained for the duration of treatment, but returned to baseline after the drug was discontinued.

Patients on active treatment gained a mean of 1.6 kg more than those on placebo after 6 months, and 1.3 kg after 12 months. This reflected an increase of 1.4 kg in lean body mass after 6 months and 1.6 kg after 12 months.

Tandem walk times improved significantly at 6 months and even more so at 12 months, compared with placebo. Stair climbing power improved significantly at 12 months.

Nonsignificant trends toward improvement were seen in the 6-minute walk, chair rises, and tandem stand tests.

The drug was generally well tolerated. Insomnia and statistically significant increases in fasting glucose levels were reported in the active treatment groups. But glucose levels remained within the normal range, Dr. Merriam said.

The physical function results are similar to those recently reported for Merck's investigational growth hormone secretagogue, MK677, which has a similar structure to capromorelin, he said. But both drugs face an uphill regulatory battle because the Food and Drug administration does not consider aging to be a disease.

“These are very encouraging data, but they're not the sort of thing that can be sent in to the FDA and get an approval from,” Dr. Merriam said. “It's too small, too limited a study, but it's very intriguing.”

CHICAGO — Despite recommendations to the contrary, prostate-specific antigen screening is being performed in many elderly men who are not in good health and have limited life expectancies.

That conclusion was drawn from an analysis of data collected during a cohort study of 597,824 veterans aged 70 years and older who were seen at 104 Veterans Affairs medicalcenters in 2002 and 2003. The subjects did not have a history of prostate cancer, elevated prostate-specific antigen (PSA) levels, or prostate symptoms.

Most guidelines recommend that PSA screening not be performed in elderly men with a life expectancy of fewer than 10 years—most of those over age 80 years, and men aged 70 years or older in poor health—because the known harms outweigh the potential benefits, Dr. Louise Walter and her associates said at the annual meeting of the American Geriatrics Society.

PSA levels are often inaccurate, leading to unnecessary biopsies due to false-positive results. This can cause psychological distress and treatment of irrelevant cancers, which may lead to incontinence or impotence, said Dr. Walter, of the geriatrics division at the University of California, San Francisco, and staff physician at the San Francisco VA Medical Center.

The mean age of the men in the VA-supported study was 77 years, and 333,041 (56%) had a PSA test performed in 2003. Health status was measured with the Charlson-Deyo index using 2002 VA and Medicare claims. The men were stratified into three groups, from best health (score of 0) to worst health (score of 4 or more).

PSA screening rates decreased significantly with advancing age, ranging from 64% in men aged 70–74 years to 27% in men aged 90 or older. But screening rates did not decline with worsening health, she said. Among men aged 85–89 years, 36% in the best-health group had a PSA test, compared with 37% in the worst-health group.

Although men aged 80 years or older in the worst health have less than a 10% chance of living 10 years, 11,391 (41%) of these men had a PSA test.

CHICAGO — Despite recommendations to the contrary, prostate-specific antigen screening is being performed in many elderly men who are not in good health and have limited life expectancies.

That conclusion was drawn from an analysis of data collected during a cohort study of 597,824 veterans aged 70 years and older who were seen at 104 Veterans Affairs medicalcenters in 2002 and 2003. The subjects did not have a history of prostate cancer, elevated prostate-specific antigen (PSA) levels, or prostate symptoms.

Most guidelines recommend that PSA screening not be performed in elderly men with a life expectancy of fewer than 10 years—most of those over age 80 years, and men aged 70 years or older in poor health—because the known harms outweigh the potential benefits, Dr. Louise Walter and her associates said at the annual meeting of the American Geriatrics Society.

PSA levels are often inaccurate, leading to unnecessary biopsies due to false-positive results. This can cause psychological distress and treatment of irrelevant cancers, which may lead to incontinence or impotence, said Dr. Walter, of the geriatrics division at the University of California, San Francisco, and staff physician at the San Francisco VA Medical Center.

The mean age of the men in the VA-supported study was 77 years, and 333,041 (56%) had a PSA test performed in 2003. Health status was measured with the Charlson-Deyo index using 2002 VA and Medicare claims. The men were stratified into three groups, from best health (score of 0) to worst health (score of 4 or more).

PSA screening rates decreased significantly with advancing age, ranging from 64% in men aged 70–74 years to 27% in men aged 90 or older. But screening rates did not decline with worsening health, she said. Among men aged 85–89 years, 36% in the best-health group had a PSA test, compared with 37% in the worst-health group.

Although men aged 80 years or older in the worst health have less than a 10% chance of living 10 years, 11,391 (41%) of these men had a PSA test.

CHICAGO — Despite recommendations to the contrary, prostate-specific antigen screening is being performed in many elderly men who are not in good health and have limited life expectancies.

That conclusion was drawn from an analysis of data collected during a cohort study of 597,824 veterans aged 70 years and older who were seen at 104 Veterans Affairs medicalcenters in 2002 and 2003. The subjects did not have a history of prostate cancer, elevated prostate-specific antigen (PSA) levels, or prostate symptoms.

Most guidelines recommend that PSA screening not be performed in elderly men with a life expectancy of fewer than 10 years—most of those over age 80 years, and men aged 70 years or older in poor health—because the known harms outweigh the potential benefits, Dr. Louise Walter and her associates said at the annual meeting of the American Geriatrics Society.

PSA levels are often inaccurate, leading to unnecessary biopsies due to false-positive results. This can cause psychological distress and treatment of irrelevant cancers, which may lead to incontinence or impotence, said Dr. Walter, of the geriatrics division at the University of California, San Francisco, and staff physician at the San Francisco VA Medical Center.

The mean age of the men in the VA-supported study was 77 years, and 333,041 (56%) had a PSA test performed in 2003. Health status was measured with the Charlson-Deyo index using 2002 VA and Medicare claims. The men were stratified into three groups, from best health (score of 0) to worst health (score of 4 or more).

PSA screening rates decreased significantly with advancing age, ranging from 64% in men aged 70–74 years to 27% in men aged 90 or older. But screening rates did not decline with worsening health, she said. Among men aged 85–89 years, 36% in the best-health group had a PSA test, compared with 37% in the worst-health group.

Although men aged 80 years or older in the worst health have less than a 10% chance of living 10 years, 11,391 (41%) of these men had a PSA test.

CHICAGO — A nasal spray formulation of the osteoporosis drug teriparatide has cleared its first scientific hurdle.

Intranasal parathyroid hormone (PTH1–34) demonstrated a similar absorption profile as the approved injectable product, Forteo, in a phase I, pharmacokinetics study, Dr. Gordon Brandt and colleagues reported in a poster at the annual meeting of the American Association of Clinical Endocrinologists.

Twelve healthy men and women, ages 20–40 years, received a 20-mcg injection of teriparatide on day 1, followed by single doses of the nasal spray on 4 subsequent days. Two nasal formulations of teriparatide were evaluated: Formulation No. 1 was given at 200 mcg and 400 mcg, and No. 2 at 500 mcg and 1,000 mcg. Blood samples were taken up to 4 hours post treatment.

The times of maximal drug concentration for teriparatide nasal spray and Forteo were not statistically different, reported Dr. Brandt, executive vice president, clinical research and medical affairs, Nastech Pharmaceutical Co., Bothell, Wash., which sponsored the study.

While Forteo achieves a 50-pg/mL peak blood level after subcutaneous administration, the tested doses of nasal spray delivered up to a 400-pg/mL peak blood level, Dr. Brandt said in an interview. “In this first-in-man study, we administered higher doses than are required, so in subsequent studies we will adjust the doses,” he said.

Still, while the bioavailability of Forteo was 95%, that of nasal formulation No. 1 was only 5%–8%, and 12%–15% for No. 2.

Intersubject variability for the nasal sprays was similar to or lower than Forteo, suggesting that intranasal dosing may provide consistent dosing.

There was no nasal irritation with the nasal sprays. Interestingly, two patients developed hypercalcemia after the Forteo injection, whereas there were no reports of hypercalcemia with the nasal spray.

Procter & Gamble has signed an agreement with Nastech to further develop the nasal spray formulation, Dr. Brandt said. The U.S. Food and Drug Administration has put the nasal formulation on a 505(b)(2) regulatory path, which requires only a single noninferiority study of the nasal sprays versus Forteo. The timing of this study has not been announced.

In a separate poster at the meeting, cost and side effects were identified as barriers for patients considering teriparatide.

In a retrospective study of 84 patients who had received a recommendation for teriparatide for severe osteoporosis since 2004, 28 patients (33%) refused the drug primarily because of cost, concerns about subcutaneous injections, or anxiety surrounding the incidence of osteosarcomas in rat studies, Dr. Pauline Camacho and Laurie Bachrach, of Loyola University Health System, Chicago, reported. A 28-day supply of teriparatide averaged $96.50.

Of the 56 patients who tried teriparatide, only 34 took the drug for 1 year. At 1 year, the mean change in bone mineral density of the lumbar spine was 6.9%.

Of the 52 patients who responded to a survey about side effects, 26 reported one or more, mostly lower extremity cramps or fatigue, dizziness, and transient elevation of ionized calcium levels.

Seven patients were nonresponders: One showed no change, and six showed decreases in bone mineral density of the lumbar spine. Three of the patients were later found to have underlying disease processes that explained the poor response. The remaining four claimed good compliance with the drug, Ms. Bachrach, a medical student at the university, said in an interview.

CHICAGO — A nasal spray formulation of the osteoporosis drug teriparatide has cleared its first scientific hurdle.

Intranasal parathyroid hormone (PTH1–34) demonstrated a similar absorption profile as the approved injectable product, Forteo, in a phase I, pharmacokinetics study, Dr. Gordon Brandt and colleagues reported in a poster at the annual meeting of the American Association of Clinical Endocrinologists.

Twelve healthy men and women, ages 20–40 years, received a 20-mcg injection of teriparatide on day 1, followed by single doses of the nasal spray on 4 subsequent days. Two nasal formulations of teriparatide were evaluated: Formulation No. 1 was given at 200 mcg and 400 mcg, and No. 2 at 500 mcg and 1,000 mcg. Blood samples were taken up to 4 hours post treatment.

The times of maximal drug concentration for teriparatide nasal spray and Forteo were not statistically different, reported Dr. Brandt, executive vice president, clinical research and medical affairs, Nastech Pharmaceutical Co., Bothell, Wash., which sponsored the study.

While Forteo achieves a 50-pg/mL peak blood level after subcutaneous administration, the tested doses of nasal spray delivered up to a 400-pg/mL peak blood level, Dr. Brandt said in an interview. “In this first-in-man study, we administered higher doses than are required, so in subsequent studies we will adjust the doses,” he said.

Still, while the bioavailability of Forteo was 95%, that of nasal formulation No. 1 was only 5%–8%, and 12%–15% for No. 2.

Intersubject variability for the nasal sprays was similar to or lower than Forteo, suggesting that intranasal dosing may provide consistent dosing.

There was no nasal irritation with the nasal sprays. Interestingly, two patients developed hypercalcemia after the Forteo injection, whereas there were no reports of hypercalcemia with the nasal spray.

Procter & Gamble has signed an agreement with Nastech to further develop the nasal spray formulation, Dr. Brandt said. The U.S. Food and Drug Administration has put the nasal formulation on a 505(b)(2) regulatory path, which requires only a single noninferiority study of the nasal sprays versus Forteo. The timing of this study has not been announced.

In a separate poster at the meeting, cost and side effects were identified as barriers for patients considering teriparatide.

In a retrospective study of 84 patients who had received a recommendation for teriparatide for severe osteoporosis since 2004, 28 patients (33%) refused the drug primarily because of cost, concerns about subcutaneous injections, or anxiety surrounding the incidence of osteosarcomas in rat studies, Dr. Pauline Camacho and Laurie Bachrach, of Loyola University Health System, Chicago, reported. A 28-day supply of teriparatide averaged $96.50.

Of the 56 patients who tried teriparatide, only 34 took the drug for 1 year. At 1 year, the mean change in bone mineral density of the lumbar spine was 6.9%.

Of the 52 patients who responded to a survey about side effects, 26 reported one or more, mostly lower extremity cramps or fatigue, dizziness, and transient elevation of ionized calcium levels.

Seven patients were nonresponders: One showed no change, and six showed decreases in bone mineral density of the lumbar spine. Three of the patients were later found to have underlying disease processes that explained the poor response. The remaining four claimed good compliance with the drug, Ms. Bachrach, a medical student at the university, said in an interview.

CHICAGO — A nasal spray formulation of the osteoporosis drug teriparatide has cleared its first scientific hurdle.

Intranasal parathyroid hormone (PTH1–34) demonstrated a similar absorption profile as the approved injectable product, Forteo, in a phase I, pharmacokinetics study, Dr. Gordon Brandt and colleagues reported in a poster at the annual meeting of the American Association of Clinical Endocrinologists.

Twelve healthy men and women, ages 20–40 years, received a 20-mcg injection of teriparatide on day 1, followed by single doses of the nasal spray on 4 subsequent days. Two nasal formulations of teriparatide were evaluated: Formulation No. 1 was given at 200 mcg and 400 mcg, and No. 2 at 500 mcg and 1,000 mcg. Blood samples were taken up to 4 hours post treatment.

The times of maximal drug concentration for teriparatide nasal spray and Forteo were not statistically different, reported Dr. Brandt, executive vice president, clinical research and medical affairs, Nastech Pharmaceutical Co., Bothell, Wash., which sponsored the study.

While Forteo achieves a 50-pg/mL peak blood level after subcutaneous administration, the tested doses of nasal spray delivered up to a 400-pg/mL peak blood level, Dr. Brandt said in an interview. “In this first-in-man study, we administered higher doses than are required, so in subsequent studies we will adjust the doses,” he said.

Still, while the bioavailability of Forteo was 95%, that of nasal formulation No. 1 was only 5%–8%, and 12%–15% for No. 2.

Intersubject variability for the nasal sprays was similar to or lower than Forteo, suggesting that intranasal dosing may provide consistent dosing.

There was no nasal irritation with the nasal sprays. Interestingly, two patients developed hypercalcemia after the Forteo injection, whereas there were no reports of hypercalcemia with the nasal spray.

Procter & Gamble has signed an agreement with Nastech to further develop the nasal spray formulation, Dr. Brandt said. The U.S. Food and Drug Administration has put the nasal formulation on a 505(b)(2) regulatory path, which requires only a single noninferiority study of the nasal sprays versus Forteo. The timing of this study has not been announced.

In a separate poster at the meeting, cost and side effects were identified as barriers for patients considering teriparatide.

In a retrospective study of 84 patients who had received a recommendation for teriparatide for severe osteoporosis since 2004, 28 patients (33%) refused the drug primarily because of cost, concerns about subcutaneous injections, or anxiety surrounding the incidence of osteosarcomas in rat studies, Dr. Pauline Camacho and Laurie Bachrach, of Loyola University Health System, Chicago, reported. A 28-day supply of teriparatide averaged $96.50.

Of the 56 patients who tried teriparatide, only 34 took the drug for 1 year. At 1 year, the mean change in bone mineral density of the lumbar spine was 6.9%.

Of the 52 patients who responded to a survey about side effects, 26 reported one or more, mostly lower extremity cramps or fatigue, dizziness, and transient elevation of ionized calcium levels.

Seven patients were nonresponders: One showed no change, and six showed decreases in bone mineral density of the lumbar spine. Three of the patients were later found to have underlying disease processes that explained the poor response. The remaining four claimed good compliance with the drug, Ms. Bachrach, a medical student at the university, said in an interview.

CHICAGO — Transnasal esophagoscopy easily identified esophageal abnormalities without sedation in an office-based setting during a small, prospective study.

The procedure, which allows endoscopic visualization of the aerodigestive tract from the nasal vestibule to the gastric cardia, is currently limited to a small number of U.S. centers. But the findings suggest that office-based transnasal esophagoscopy could make screening more accessible in patients with esophageal reflux, globus, and dysphagia, Dr. Thomas Takoudes said at the Combined Otolaryngology Spring Meetings.

Esophageal reflux affects up to 40% of adult Americans, many of whom will develop Barrett's esophagus, a known risk factor for esophageal cancer. “Given the incidence of severe reflux, this [procedure] should be as accessible as digital rectal exams and [prostate-specific antigen] tests for prostate cancer and Pap tests for cervical cancer,” he said.

The study included 21 consecutive transnasal esophagoscopy procedures performed in 19 patients over a 6-month period by Dr. Takoudes. He used the Vision-Sciences Inc. esophagoscope, which has a single-use, disposable sheath. The nose was sprayed with oxymetazoline and lidocaine to reduce discomfort in all patients.

No complications were observed. “With this procedure, the tube goes through the nose without sedation, and a half hour later they go home or go to work. It's so much easier for the patient,” he said.

Indications for the procedure were laryngopharyngeal reflux with failed proton pump inhibitor therapy in 11 patients (58%); dysphagia without a history of reflux in 7 (37%); head/neck cancer in 2 (11%); and abnormal esophagus on CT scan in 1 patient (5%). Some patients had multiple indications. One procedure could not be completed due to patient discomfort.

Significant findings were identified in 10 of 20 procedures (50%). They included two cases of diverticulum, two candida esophagitis, two hiatal hernia, two patulous esophagus, two abnormal motility, two Barrett's esophagus, and one achalasia, reported Dr. Takoudes, of the Ear, Nose, & Throat Medical and Surgical Group in New Haven, Conn. Multiple findings were found in some patients.

The utility of transnasal esophagoscopy as a screening tool was validated in a recent large study in which significant findings were identified in half of 592 procedures performed for reflux, globus, or dysphagia; the study was performed in a large tertiary care center (Laryngoscope 2005;115:321–3).

Procedure failure rates were similar in both studies; 3% at the tertiary care center and 5% in the office-based setting, Dr. Takoudes said.

Dr. Thomas Takoudes shows that the patient sits unsedated during esophagoscopy. Courtesy Dr. Thomas Takoudes

CHICAGO — Transnasal esophagoscopy easily identified esophageal abnormalities without sedation in an office-based setting during a small, prospective study.

The procedure, which allows endoscopic visualization of the aerodigestive tract from the nasal vestibule to the gastric cardia, is currently limited to a small number of U.S. centers. But the findings suggest that office-based transnasal esophagoscopy could make screening more accessible in patients with esophageal reflux, globus, and dysphagia, Dr. Thomas Takoudes said at the Combined Otolaryngology Spring Meetings.

Esophageal reflux affects up to 40% of adult Americans, many of whom will develop Barrett's esophagus, a known risk factor for esophageal cancer. “Given the incidence of severe reflux, this [procedure] should be as accessible as digital rectal exams and [prostate-specific antigen] tests for prostate cancer and Pap tests for cervical cancer,” he said.

The study included 21 consecutive transnasal esophagoscopy procedures performed in 19 patients over a 6-month period by Dr. Takoudes. He used the Vision-Sciences Inc. esophagoscope, which has a single-use, disposable sheath. The nose was sprayed with oxymetazoline and lidocaine to reduce discomfort in all patients.

No complications were observed. “With this procedure, the tube goes through the nose without sedation, and a half hour later they go home or go to work. It's so much easier for the patient,” he said.

Indications for the procedure were laryngopharyngeal reflux with failed proton pump inhibitor therapy in 11 patients (58%); dysphagia without a history of reflux in 7 (37%); head/neck cancer in 2 (11%); and abnormal esophagus on CT scan in 1 patient (5%). Some patients had multiple indications. One procedure could not be completed due to patient discomfort.

Significant findings were identified in 10 of 20 procedures (50%). They included two cases of diverticulum, two candida esophagitis, two hiatal hernia, two patulous esophagus, two abnormal motility, two Barrett's esophagus, and one achalasia, reported Dr. Takoudes, of the Ear, Nose, & Throat Medical and Surgical Group in New Haven, Conn. Multiple findings were found in some patients.

The utility of transnasal esophagoscopy as a screening tool was validated in a recent large study in which significant findings were identified in half of 592 procedures performed for reflux, globus, or dysphagia; the study was performed in a large tertiary care center (Laryngoscope 2005;115:321–3).

Procedure failure rates were similar in both studies; 3% at the tertiary care center and 5% in the office-based setting, Dr. Takoudes said.

Dr. Thomas Takoudes shows that the patient sits unsedated during esophagoscopy. Courtesy Dr. Thomas Takoudes

CHICAGO — Transnasal esophagoscopy easily identified esophageal abnormalities without sedation in an office-based setting during a small, prospective study.

The procedure, which allows endoscopic visualization of the aerodigestive tract from the nasal vestibule to the gastric cardia, is currently limited to a small number of U.S. centers. But the findings suggest that office-based transnasal esophagoscopy could make screening more accessible in patients with esophageal reflux, globus, and dysphagia, Dr. Thomas Takoudes said at the Combined Otolaryngology Spring Meetings.

Esophageal reflux affects up to 40% of adult Americans, many of whom will develop Barrett's esophagus, a known risk factor for esophageal cancer. “Given the incidence of severe reflux, this [procedure] should be as accessible as digital rectal exams and [prostate-specific antigen] tests for prostate cancer and Pap tests for cervical cancer,” he said.

The study included 21 consecutive transnasal esophagoscopy procedures performed in 19 patients over a 6-month period by Dr. Takoudes. He used the Vision-Sciences Inc. esophagoscope, which has a single-use, disposable sheath. The nose was sprayed with oxymetazoline and lidocaine to reduce discomfort in all patients.

No complications were observed. “With this procedure, the tube goes through the nose without sedation, and a half hour later they go home or go to work. It's so much easier for the patient,” he said.

Indications for the procedure were laryngopharyngeal reflux with failed proton pump inhibitor therapy in 11 patients (58%); dysphagia without a history of reflux in 7 (37%); head/neck cancer in 2 (11%); and abnormal esophagus on CT scan in 1 patient (5%). Some patients had multiple indications. One procedure could not be completed due to patient discomfort.

Significant findings were identified in 10 of 20 procedures (50%). They included two cases of diverticulum, two candida esophagitis, two hiatal hernia, two patulous esophagus, two abnormal motility, two Barrett's esophagus, and one achalasia, reported Dr. Takoudes, of the Ear, Nose, & Throat Medical and Surgical Group in New Haven, Conn. Multiple findings were found in some patients.

The utility of transnasal esophagoscopy as a screening tool was validated in a recent large study in which significant findings were identified in half of 592 procedures performed for reflux, globus, or dysphagia; the study was performed in a large tertiary care center (Laryngoscope 2005;115:321–3).

Procedure failure rates were similar in both studies; 3% at the tertiary care center and 5% in the office-based setting, Dr. Takoudes said.

Dr. Thomas Takoudes shows that the patient sits unsedated during esophagoscopy. Courtesy Dr. Thomas Takoudes

CHICAGO — Telephone outreach is relatively inexpensive and successful at raising pneumococcal vaccination rates, Dr. Adrienne Mims reported at the annual meeting of the American Geriatrics Society.

Dr. Mims presented data from an outpatient study conducted in five managed care clinics that compared a telephone intervention with a control condition. A total of 2,395 healthy patients over the age of 65 years and 3,711 patients aged 18 years and older with diabetes, coronary artery disease, or congestive heart failure were randomized to either the telephone-intervention group or the control group.

These populations are targeted for universal immunization, according to practice guidelines. There were 3,053 patients in each of arm of the study, which was funded by the Centers for Disease Control and Prevention.

Patients in the intervention arm were sent a letter explaining the study and received up to four calls during daytime and evening hours from outreach nurses who explained that the shot was free, was available at a nurse visit, and could be scheduled if desired.

The nurses also asked why the patient had not been immunized and then gave scripted information tailored to the reason mentioned by the participant. Most commonly, the patients said “they didn't know or the doctor didn't tell me,” said Dr. Mims of Kaiser Permanente, Atlanta.

At the 6-month follow-up, 489 patients (16%) in the intervention group were vaccinated, compared with 211 (7%) in the control group. Overall, patients who received the telephone intervention were 2.3 times more likely to be vaccinated than were patients in the control group, reported Dr. Mims and associates.

The elderly were more likely to be vaccinated than were younger, chronically ill patients (17% vs. 16%). But the intervention improved immunization rates significantly in both of these populations. Most patients received their pneumococcal vaccine within 3 months of the intervention.

The cost of the nurses' phone calls was $41,520, or $147.00 per additional patient vaccinated. Dr. Mims said pneumococcal immunization is vastly underutilized, and she called the intervention a bargain compared with the cost of an office visit or of hospitalization for treating pneumococcal disease, which costs about $5,000 on average.

Prior to the study, Kaiser Permanente in Atlanta had tried several initiatives to improve pneumococcal immunization rates, such as patient outreach letters, yearly newsletter articles, clinic posters, evidence-based guidelines published in staff pocket notebooks and on the company Web site, chart flags, and financial bonuses for staff and departments.

Those efforts significantly improved immunization rates, to 60% among seniors and about 40%–45% among younger, chronically ill patients. However, the target set by the Healthy People 2010 initiative of the Department of Health and Human Services is 90%, Dr. Mims said.

CHICAGO — Telephone outreach is relatively inexpensive and successful at raising pneumococcal vaccination rates, Dr. Adrienne Mims reported at the annual meeting of the American Geriatrics Society.

Dr. Mims presented data from an outpatient study conducted in five managed care clinics that compared a telephone intervention with a control condition. A total of 2,395 healthy patients over the age of 65 years and 3,711 patients aged 18 years and older with diabetes, coronary artery disease, or congestive heart failure were randomized to either the telephone-intervention group or the control group.

These populations are targeted for universal immunization, according to practice guidelines. There were 3,053 patients in each of arm of the study, which was funded by the Centers for Disease Control and Prevention.

Patients in the intervention arm were sent a letter explaining the study and received up to four calls during daytime and evening hours from outreach nurses who explained that the shot was free, was available at a nurse visit, and could be scheduled if desired.

The nurses also asked why the patient had not been immunized and then gave scripted information tailored to the reason mentioned by the participant. Most commonly, the patients said “they didn't know or the doctor didn't tell me,” said Dr. Mims of Kaiser Permanente, Atlanta.

At the 6-month follow-up, 489 patients (16%) in the intervention group were vaccinated, compared with 211 (7%) in the control group. Overall, patients who received the telephone intervention were 2.3 times more likely to be vaccinated than were patients in the control group, reported Dr. Mims and associates.

The elderly were more likely to be vaccinated than were younger, chronically ill patients (17% vs. 16%). But the intervention improved immunization rates significantly in both of these populations. Most patients received their pneumococcal vaccine within 3 months of the intervention.

The cost of the nurses' phone calls was $41,520, or $147.00 per additional patient vaccinated. Dr. Mims said pneumococcal immunization is vastly underutilized, and she called the intervention a bargain compared with the cost of an office visit or of hospitalization for treating pneumococcal disease, which costs about $5,000 on average.

Prior to the study, Kaiser Permanente in Atlanta had tried several initiatives to improve pneumococcal immunization rates, such as patient outreach letters, yearly newsletter articles, clinic posters, evidence-based guidelines published in staff pocket notebooks and on the company Web site, chart flags, and financial bonuses for staff and departments.

Those efforts significantly improved immunization rates, to 60% among seniors and about 40%–45% among younger, chronically ill patients. However, the target set by the Healthy People 2010 initiative of the Department of Health and Human Services is 90%, Dr. Mims said.

CHICAGO — Telephone outreach is relatively inexpensive and successful at raising pneumococcal vaccination rates, Dr. Adrienne Mims reported at the annual meeting of the American Geriatrics Society.

Dr. Mims presented data from an outpatient study conducted in five managed care clinics that compared a telephone intervention with a control condition. A total of 2,395 healthy patients over the age of 65 years and 3,711 patients aged 18 years and older with diabetes, coronary artery disease, or congestive heart failure were randomized to either the telephone-intervention group or the control group.

These populations are targeted for universal immunization, according to practice guidelines. There were 3,053 patients in each of arm of the study, which was funded by the Centers for Disease Control and Prevention.

Patients in the intervention arm were sent a letter explaining the study and received up to four calls during daytime and evening hours from outreach nurses who explained that the shot was free, was available at a nurse visit, and could be scheduled if desired.

The nurses also asked why the patient had not been immunized and then gave scripted information tailored to the reason mentioned by the participant. Most commonly, the patients said “they didn't know or the doctor didn't tell me,” said Dr. Mims of Kaiser Permanente, Atlanta.

At the 6-month follow-up, 489 patients (16%) in the intervention group were vaccinated, compared with 211 (7%) in the control group. Overall, patients who received the telephone intervention were 2.3 times more likely to be vaccinated than were patients in the control group, reported Dr. Mims and associates.

The elderly were more likely to be vaccinated than were younger, chronically ill patients (17% vs. 16%). But the intervention improved immunization rates significantly in both of these populations. Most patients received their pneumococcal vaccine within 3 months of the intervention.

The cost of the nurses' phone calls was $41,520, or $147.00 per additional patient vaccinated. Dr. Mims said pneumococcal immunization is vastly underutilized, and she called the intervention a bargain compared with the cost of an office visit or of hospitalization for treating pneumococcal disease, which costs about $5,000 on average.

Prior to the study, Kaiser Permanente in Atlanta had tried several initiatives to improve pneumococcal immunization rates, such as patient outreach letters, yearly newsletter articles, clinic posters, evidence-based guidelines published in staff pocket notebooks and on the company Web site, chart flags, and financial bonuses for staff and departments.

Those efforts significantly improved immunization rates, to 60% among seniors and about 40%–45% among younger, chronically ill patients. However, the target set by the Healthy People 2010 initiative of the Department of Health and Human Services is 90%, Dr. Mims said.

CHICAGO — A 2-year analysis has shown that once-monthly ibandronate provides bone mineral density increases in women with postmenopausal osteoporosis superior to those seen with the proven daily dose.

Previously reported 1-year results from the Monthly Oral Ibandronate in Ladies (MOBILE) study showed that once-monthly ibandronate (Boniva) was superior to daily dosing at the spine and total hip, and comparable in other areas. “At 2 years there was actually superiority in all areas of the hip, plus the spine, and the adverse event profile was very comparable at 1 and 2 years,” Dr. Michael A. Bolognese, who headed the prospective, phase III study for Hoffman-La Roche Inc., said in an interview.

Overall, 1,609 women, aged 55–80 years, with postmenopausal osteoporosis were randomized to oral ibandronate 2.5 mg daily or to one of three different monthly ibandronate doses: 150-mg, 100-mg, or two 50-mg doses on 2 consecutive days. The per-protocol population included 395 women in the 2.5-mg daily group and 396 in the 150-mg monthly ibandronate group.

In a per-protocol analysis, mean lumbar spine bone mineral density scores increased 4% from baseline in the daily group and 5% in the monthly group after 1 year, and 5% and 7%, respectively, after 2 years. Similar increases were seen in the intent-to-treat population, Dr. Bolognese and his associates reported in a poster at the annual meeting of the American Association of Clinical Endocrinologists.

After 2 years, superior mean bone mineral density gains were seen at the hip with 150-mg monthly ibandronate, compared with daily dosing (total hip, 4% vs. 3%; femoral neck, 3% vs. 2%; trochanter, 6% vs. 4%).

There was no difference in the incidence of clinical fractures between the daily- and monthly-dose groups (26 vs. 29). The number of withdrawals due to adverse events was low and comparable for daily and monthly treatment (10% vs. 9%), reported Dr. Bolognese, who is in private practice in Bethesda, Md., and is a Roche speaker and grant recipient.

Patients have to sit upright for 60 minutes after taking monthly ibandronate, compared with 30 minutes for the daily dose. But because it's only once a month, it's still easier to tolerate, particularly for patients on multiple medications or in nursing facilities, he said.

In another poster, 1- and 2-year data from the Dosing Intravenous Administration (DIVA) study suggest that intermittent intravenous ibandronate injections are generally well tolerated and provide a safe alternative for patients unable to take oral bisphosphonates.

The phase III study randomized 1,395 postmenopausal women, aged 55–80 years, with osteoporosis to four treatment groups: 2-mg IV ibandronate injection every 2 months plus daily oral placebo; 2.5-mg daily oral ibandronate plus placebo IV injection every 2 months; 3-mg IV ibandronate every 3 months plus daily oral placebo; and 2.5-mg daily oral ibandronate plus placebo IV injection every 3 months.

Adverse events were balanced across treatment arms, noted Dr. Mone Zaidi, professor of medicine at Mount Sinai School of Medicine, New York, and his associates. The most frequently reported adverse events were nasopharyngitis, back pain, hypertension, and arthralgia.

The number of patients who experienced a fracture at 2 years was low (85/1,382 or 6%), and was similar for all treatment groups, according to the study, which also was supported by Roche.

ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO — A 2-year analysis has shown that once-monthly ibandronate provides bone mineral density increases in women with postmenopausal osteoporosis superior to those seen with the proven daily dose.

Previously reported 1-year results from the Monthly Oral Ibandronate in Ladies (MOBILE) study showed that once-monthly ibandronate (Boniva) was superior to daily dosing at the spine and total hip, and comparable in other areas. “At 2 years there was actually superiority in all areas of the hip, plus the spine, and the adverse event profile was very comparable at 1 and 2 years,” Dr. Michael A. Bolognese, who headed the prospective, phase III study for Hoffman-La Roche Inc., said in an interview.

Overall, 1,609 women, aged 55–80 years, with postmenopausal osteoporosis were randomized to oral ibandronate 2.5 mg daily or to one of three different monthly ibandronate doses: 150-mg, 100-mg, or two 50-mg doses on 2 consecutive days. The per-protocol population included 395 women in the 2.5-mg daily group and 396 in the 150-mg monthly ibandronate group.

In a per-protocol analysis, mean lumbar spine bone mineral density scores increased 4% from baseline in the daily group and 5% in the monthly group after 1 year, and 5% and 7%, respectively, after 2 years. Similar increases were seen in the intent-to-treat population, Dr. Bolognese and his associates reported in a poster at the annual meeting of the American Association of Clinical Endocrinologists.

After 2 years, superior mean bone mineral density gains were seen at the hip with 150-mg monthly ibandronate, compared with daily dosing (total hip, 4% vs. 3%; femoral neck, 3% vs. 2%; trochanter, 6% vs. 4%).

There was no difference in the incidence of clinical fractures between the daily- and monthly-dose groups (26 vs. 29). The number of withdrawals due to adverse events was low and comparable for daily and monthly treatment (10% vs. 9%), reported Dr. Bolognese, who is in private practice in Bethesda, Md., and is a Roche speaker and grant recipient.

Patients have to sit upright for 60 minutes after taking monthly ibandronate, compared with 30 minutes for the daily dose. But because it's only once a month, it's still easier to tolerate, particularly for patients on multiple medications or in nursing facilities, he said.

In another poster, 1- and 2-year data from the Dosing Intravenous Administration (DIVA) study suggest that intermittent intravenous ibandronate injections are generally well tolerated and provide a safe alternative for patients unable to take oral bisphosphonates.

The phase III study randomized 1,395 postmenopausal women, aged 55–80 years, with osteoporosis to four treatment groups: 2-mg IV ibandronate injection every 2 months plus daily oral placebo; 2.5-mg daily oral ibandronate plus placebo IV injection every 2 months; 3-mg IV ibandronate every 3 months plus daily oral placebo; and 2.5-mg daily oral ibandronate plus placebo IV injection every 3 months.

Adverse events were balanced across treatment arms, noted Dr. Mone Zaidi, professor of medicine at Mount Sinai School of Medicine, New York, and his associates. The most frequently reported adverse events were nasopharyngitis, back pain, hypertension, and arthralgia.

The number of patients who experienced a fracture at 2 years was low (85/1,382 or 6%), and was similar for all treatment groups, according to the study, which also was supported by Roche.

ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO — A 2-year analysis has shown that once-monthly ibandronate provides bone mineral density increases in women with postmenopausal osteoporosis superior to those seen with the proven daily dose.

Previously reported 1-year results from the Monthly Oral Ibandronate in Ladies (MOBILE) study showed that once-monthly ibandronate (Boniva) was superior to daily dosing at the spine and total hip, and comparable in other areas. “At 2 years there was actually superiority in all areas of the hip, plus the spine, and the adverse event profile was very comparable at 1 and 2 years,” Dr. Michael A. Bolognese, who headed the prospective, phase III study for Hoffman-La Roche Inc., said in an interview.

Overall, 1,609 women, aged 55–80 years, with postmenopausal osteoporosis were randomized to oral ibandronate 2.5 mg daily or to one of three different monthly ibandronate doses: 150-mg, 100-mg, or two 50-mg doses on 2 consecutive days. The per-protocol population included 395 women in the 2.5-mg daily group and 396 in the 150-mg monthly ibandronate group.

In a per-protocol analysis, mean lumbar spine bone mineral density scores increased 4% from baseline in the daily group and 5% in the monthly group after 1 year, and 5% and 7%, respectively, after 2 years. Similar increases were seen in the intent-to-treat population, Dr. Bolognese and his associates reported in a poster at the annual meeting of the American Association of Clinical Endocrinologists.

After 2 years, superior mean bone mineral density gains were seen at the hip with 150-mg monthly ibandronate, compared with daily dosing (total hip, 4% vs. 3%; femoral neck, 3% vs. 2%; trochanter, 6% vs. 4%).

There was no difference in the incidence of clinical fractures between the daily- and monthly-dose groups (26 vs. 29). The number of withdrawals due to adverse events was low and comparable for daily and monthly treatment (10% vs. 9%), reported Dr. Bolognese, who is in private practice in Bethesda, Md., and is a Roche speaker and grant recipient.

Patients have to sit upright for 60 minutes after taking monthly ibandronate, compared with 30 minutes for the daily dose. But because it's only once a month, it's still easier to tolerate, particularly for patients on multiple medications or in nursing facilities, he said.

In another poster, 1- and 2-year data from the Dosing Intravenous Administration (DIVA) study suggest that intermittent intravenous ibandronate injections are generally well tolerated and provide a safe alternative for patients unable to take oral bisphosphonates.

The phase III study randomized 1,395 postmenopausal women, aged 55–80 years, with osteoporosis to four treatment groups: 2-mg IV ibandronate injection every 2 months plus daily oral placebo; 2.5-mg daily oral ibandronate plus placebo IV injection every 2 months; 3-mg IV ibandronate every 3 months plus daily oral placebo; and 2.5-mg daily oral ibandronate plus placebo IV injection every 3 months.

Adverse events were balanced across treatment arms, noted Dr. Mone Zaidi, professor of medicine at Mount Sinai School of Medicine, New York, and his associates. The most frequently reported adverse events were nasopharyngitis, back pain, hypertension, and arthralgia.

The number of patients who experienced a fracture at 2 years was low (85/1,382 or 6%), and was similar for all treatment groups, according to the study, which also was supported by Roche.

ELSEVIER GLOBAL MEDICAL NEWS

TUCSON, ARIZ. – Complementary herbal and nutritional therapies can play an important role in an integrated psychiatric practice, Dr. Iris R. Bell said at a psychopharmacology conference sponsored by the University of Arizona.

Disputes remain about the lack of randomized trials supporting the use of complementary and alternative medicine (CAM). But evidence continues to mount about the benefits of CAM therapy that is individualized to a patient's specific needs and preferences.

The use of broad-based nutritional supplements has been reported to ameliorate psychiatric symptoms such as mood swings, depression, and aggression in a variety of patients, including young criminal offenders. The mechanisms by which these changes occur are not established. But the supplements may provide the nutritional support needed to improve brain chemistry and promote better use of traditional medications, said Dr. Bell, a professor at the university and director of research for its integrative medicine program.

Activated forms of pyridoxine, niacin, iron, and tetrahydrobiopterin are cofactors for the enzymes tyrosine hydroxylase and tryptophan 5-hydroxylase, which participate in brain biosynthesis of catecholamines and serotonin. It has been shown that patients with the melancholic form of depression have low levels of folate and respond poorly to fluoxetine, in part because they don't have adequate neurotransmitters to use it, she said.

Studies of high-dose antioxidant supplements by themselves, such as vitamin E alone in Parkinson's disease, may have failed because the vitamin needs other components of its biochemical network, such as vitamin C and other nutrients, to regenerate antioxidant forms from prooxidant forms of the vitamin, Dr. Bell said. Folate, B₁₂, and B₆ vitamin supplements are now being used together as a low-risk strategy to lower homocysteine levels in Alzheimer's patients. Studies suggest that elevated homocysteine is an independent risk factor for Alzheimer's disease and a variety of vascular diseases. “We may have a more preventive role to play than we thought,” she said.

Ginkgo biloba has produced mixed results in patients with dementia and should be used with caution in those patients on concomitant warfarin or other anticoagulant agents, Dr. Bell said.

Small controlled studies have shown that kava kava can reduce anxiety over a 4-week period, but Dr. Bell said she is uncomfortable recommending its because of the potential for serious liver damage from the forms available in Western countries.

The folk remedy passion flower has been helpful in generalized anxiety and when used in combination with clonidine to reduce mental symptoms in opiate addicts. “It might provide an added benefit to get them through acute withdrawal, but it's not a long-term solution,” Dr. Bell said.

TUCSON, ARIZ. – Complementary herbal and nutritional therapies can play an important role in an integrated psychiatric practice, Dr. Iris R. Bell said at a psychopharmacology conference sponsored by the University of Arizona.

Disputes remain about the lack of randomized trials supporting the use of complementary and alternative medicine (CAM). But evidence continues to mount about the benefits of CAM therapy that is individualized to a patient's specific needs and preferences.

The use of broad-based nutritional supplements has been reported to ameliorate psychiatric symptoms such as mood swings, depression, and aggression in a variety of patients, including young criminal offenders. The mechanisms by which these changes occur are not established. But the supplements may provide the nutritional support needed to improve brain chemistry and promote better use of traditional medications, said Dr. Bell, a professor at the university and director of research for its integrative medicine program.

Activated forms of pyridoxine, niacin, iron, and tetrahydrobiopterin are cofactors for the enzymes tyrosine hydroxylase and tryptophan 5-hydroxylase, which participate in brain biosynthesis of catecholamines and serotonin. It has been shown that patients with the melancholic form of depression have low levels of folate and respond poorly to fluoxetine, in part because they don't have adequate neurotransmitters to use it, she said.

Studies of high-dose antioxidant supplements by themselves, such as vitamin E alone in Parkinson's disease, may have failed because the vitamin needs other components of its biochemical network, such as vitamin C and other nutrients, to regenerate antioxidant forms from prooxidant forms of the vitamin, Dr. Bell said. Folate, B₁₂, and B₆ vitamin supplements are now being used together as a low-risk strategy to lower homocysteine levels in Alzheimer's patients. Studies suggest that elevated homocysteine is an independent risk factor for Alzheimer's disease and a variety of vascular diseases. “We may have a more preventive role to play than we thought,” she said.

Ginkgo biloba has produced mixed results in patients with dementia and should be used with caution in those patients on concomitant warfarin or other anticoagulant agents, Dr. Bell said.

Small controlled studies have shown that kava kava can reduce anxiety over a 4-week period, but Dr. Bell said she is uncomfortable recommending its because of the potential for serious liver damage from the forms available in Western countries.

The folk remedy passion flower has been helpful in generalized anxiety and when used in combination with clonidine to reduce mental symptoms in opiate addicts. “It might provide an added benefit to get them through acute withdrawal, but it's not a long-term solution,” Dr. Bell said.

TUCSON, ARIZ. – Complementary herbal and nutritional therapies can play an important role in an integrated psychiatric practice, Dr. Iris R. Bell said at a psychopharmacology conference sponsored by the University of Arizona.

Disputes remain about the lack of randomized trials supporting the use of complementary and alternative medicine (CAM). But evidence continues to mount about the benefits of CAM therapy that is individualized to a patient's specific needs and preferences.

The use of broad-based nutritional supplements has been reported to ameliorate psychiatric symptoms such as mood swings, depression, and aggression in a variety of patients, including young criminal offenders. The mechanisms by which these changes occur are not established. But the supplements may provide the nutritional support needed to improve brain chemistry and promote better use of traditional medications, said Dr. Bell, a professor at the university and director of research for its integrative medicine program.

Activated forms of pyridoxine, niacin, iron, and tetrahydrobiopterin are cofactors for the enzymes tyrosine hydroxylase and tryptophan 5-hydroxylase, which participate in brain biosynthesis of catecholamines and serotonin. It has been shown that patients with the melancholic form of depression have low levels of folate and respond poorly to fluoxetine, in part because they don't have adequate neurotransmitters to use it, she said.

Studies of high-dose antioxidant supplements by themselves, such as vitamin E alone in Parkinson's disease, may have failed because the vitamin needs other components of its biochemical network, such as vitamin C and other nutrients, to regenerate antioxidant forms from prooxidant forms of the vitamin, Dr. Bell said. Folate, B₁₂, and B₆ vitamin supplements are now being used together as a low-risk strategy to lower homocysteine levels in Alzheimer's patients. Studies suggest that elevated homocysteine is an independent risk factor for Alzheimer's disease and a variety of vascular diseases. “We may have a more preventive role to play than we thought,” she said.

Ginkgo biloba has produced mixed results in patients with dementia and should be used with caution in those patients on concomitant warfarin or other anticoagulant agents, Dr. Bell said.

Small controlled studies have shown that kava kava can reduce anxiety over a 4-week period, but Dr. Bell said she is uncomfortable recommending its because of the potential for serious liver damage from the forms available in Western countries.

The folk remedy passion flower has been helpful in generalized anxiety and when used in combination with clonidine to reduce mental symptoms in opiate addicts. “It might provide an added benefit to get them through acute withdrawal, but it's not a long-term solution,” Dr. Bell said.

CHICAGO – Exogenous testosterone, taken either alone or with finasteride for 36 months, did not significantly improve cognition in a randomized, placebo-controlled trial involving healthy older men.

The findings do little to settle the debate over the effect of hormone therapy on cognition in elderly men. About half of randomized, controlled trials of testosterone therapy in older men have shown positive effects on cognitive function, particularly spatial cognition, Dr. Camille Vaughan said at the annual meeting of the American Geriatrics Society.

She presented data from a study in which 70 healthy men, aged 65–83 years, with low levels of testosterone (less than 350 ng/dL) and normal performance on the Mini-Mental State Examination (MMSE) were randomly assigned to receive one of three regimens: 200 mg of IM testosterone enanthate every 2 weeks with placebo pills; 200 mg of IM testosterone enanthate every 2 weeks with 5 mg of finasteride daily, or placebo injections and placebo pills.

At baseline, there were no significant differences in hormone levels between groups. Their mean age was 72 years. All patients had a MMSE score of 28 or higher, out of 30. Patients in the placebo group did have higher scores on the Spielberger State-Trait Anxiety Inventory, reported Dr. Vaughan, an internal medicine resident at Emory University in Atlanta, and colleagues.

Cognitive testing performed at baseline, 4 months, and 36 months included a comprehensive battery assessing attention, executive function, visuospatial skills, and visual and verbal memory skills. Serum hormone levels also were measured at the indicated intervals.

Sixty-nine men completed baseline testing, 65 completed at least 4 months, and 46 completed all 36 months.

Serum total testosterone, bioavailable testosterone, and estradiol levels increased significantly in the treatment groups throughout the study period. Hormone levels did not change for the placebo group at any time.

The three groups didn't demonstrate significant differences in cognitive performance on any of the tests at the 4-month or 36-month evaluations, Dr. Vaughan said.

There was a trend in the active treatment groups toward improved performance in the Benton Visual Retention Test and in visuospatial skills on the Visual Patterns Test. But scores were not significantly different from the placebo group at any time. All groups improved slightly over time on parts A and B of the Trail Making Test, but this was most likely due to the effects of practice, she said.

Further studies are warranted to determine if hormone therapy in men with preexisting cognitive impairment is beneficial, Dr. Vaughan concluded.

CHICAGO – Exogenous testosterone, taken either alone or with finasteride for 36 months, did not significantly improve cognition in a randomized, placebo-controlled trial involving healthy older men.

The findings do little to settle the debate over the effect of hormone therapy on cognition in elderly men. About half of randomized, controlled trials of testosterone therapy in older men have shown positive effects on cognitive function, particularly spatial cognition, Dr. Camille Vaughan said at the annual meeting of the American Geriatrics Society.

She presented data from a study in which 70 healthy men, aged 65–83 years, with low levels of testosterone (less than 350 ng/dL) and normal performance on the Mini-Mental State Examination (MMSE) were randomly assigned to receive one of three regimens: 200 mg of IM testosterone enanthate every 2 weeks with placebo pills; 200 mg of IM testosterone enanthate every 2 weeks with 5 mg of finasteride daily, or placebo injections and placebo pills.

At baseline, there were no significant differences in hormone levels between groups. Their mean age was 72 years. All patients had a MMSE score of 28 or higher, out of 30. Patients in the placebo group did have higher scores on the Spielberger State-Trait Anxiety Inventory, reported Dr. Vaughan, an internal medicine resident at Emory University in Atlanta, and colleagues.

Cognitive testing performed at baseline, 4 months, and 36 months included a comprehensive battery assessing attention, executive function, visuospatial skills, and visual and verbal memory skills. Serum hormone levels also were measured at the indicated intervals.

Sixty-nine men completed baseline testing, 65 completed at least 4 months, and 46 completed all 36 months.

Serum total testosterone, bioavailable testosterone, and estradiol levels increased significantly in the treatment groups throughout the study period. Hormone levels did not change for the placebo group at any time.

The three groups didn't demonstrate significant differences in cognitive performance on any of the tests at the 4-month or 36-month evaluations, Dr. Vaughan said.

There was a trend in the active treatment groups toward improved performance in the Benton Visual Retention Test and in visuospatial skills on the Visual Patterns Test. But scores were not significantly different from the placebo group at any time. All groups improved slightly over time on parts A and B of the Trail Making Test, but this was most likely due to the effects of practice, she said.

Further studies are warranted to determine if hormone therapy in men with preexisting cognitive impairment is beneficial, Dr. Vaughan concluded.

CHICAGO – Exogenous testosterone, taken either alone or with finasteride for 36 months, did not significantly improve cognition in a randomized, placebo-controlled trial involving healthy older men.

The findings do little to settle the debate over the effect of hormone therapy on cognition in elderly men. About half of randomized, controlled trials of testosterone therapy in older men have shown positive effects on cognitive function, particularly spatial cognition, Dr. Camille Vaughan said at the annual meeting of the American Geriatrics Society.

She presented data from a study in which 70 healthy men, aged 65–83 years, with low levels of testosterone (less than 350 ng/dL) and normal performance on the Mini-Mental State Examination (MMSE) were randomly assigned to receive one of three regimens: 200 mg of IM testosterone enanthate every 2 weeks with placebo pills; 200 mg of IM testosterone enanthate every 2 weeks with 5 mg of finasteride daily, or placebo injections and placebo pills.

At baseline, there were no significant differences in hormone levels between groups. Their mean age was 72 years. All patients had a MMSE score of 28 or higher, out of 30. Patients in the placebo group did have higher scores on the Spielberger State-Trait Anxiety Inventory, reported Dr. Vaughan, an internal medicine resident at Emory University in Atlanta, and colleagues.

Cognitive testing performed at baseline, 4 months, and 36 months included a comprehensive battery assessing attention, executive function, visuospatial skills, and visual and verbal memory skills. Serum hormone levels also were measured at the indicated intervals.

Sixty-nine men completed baseline testing, 65 completed at least 4 months, and 46 completed all 36 months.

Serum total testosterone, bioavailable testosterone, and estradiol levels increased significantly in the treatment groups throughout the study period. Hormone levels did not change for the placebo group at any time.

The three groups didn't demonstrate significant differences in cognitive performance on any of the tests at the 4-month or 36-month evaluations, Dr. Vaughan said.

There was a trend in the active treatment groups toward improved performance in the Benton Visual Retention Test and in visuospatial skills on the Visual Patterns Test. But scores were not significantly different from the placebo group at any time. All groups improved slightly over time on parts A and B of the Trail Making Test, but this was most likely due to the effects of practice, she said.

Further studies are warranted to determine if hormone therapy in men with preexisting cognitive impairment is beneficial, Dr. Vaughan concluded.

CHICAGO – Patients with severe Alzheimer's disease showed improved cognition and function when treated with donepezil in a 24-week, placebo-controlled trial, Dr. Sandra Black and her associates reported in a poster at the annual meeting of the American Geriatrics Society.

The results are consistent with a Swedish nursing home study in a similar, institutionalized population (Lancet 2006;367:1262–70), suggesting that even patients with severe disease can benefit from treatment with donepezil.

“The two studies taken together suggest that this stage of disease can show measurable benefits of treatment with donepezil,” Dr. Black, professor of medicine and head of neurology at Sunnybrook Health Sciences Centre, University of Toronto, said in an interview. “They give a new evidence-based option for treatment, which gives hope for a better quality of life in the final phase of this devastating disease.”

Currently, donepezil (Aricept) is approved for mild to moderate Alzheimer's disease. In February 2006, the U.S. Food and Drug Administration accepted a supplemental new drug application for donepezil in severe Alzheimer's disease.

Doses of 5 mg and 10 mg of donepezil are typically administered once daily, although the higher 10-mg dose did not provide significantly greater clinical benefit in previous clinical trials.

In their study, Dr. Black and her colleagues randomized 343 patients with severe Alzheimer's disease to an initial dose of donepezil of 5 mg/day for 6 weeks and then 10 mg/day of donepezil (176 patients) or placebo (167 patients) for 24 weeks. Patients resided in the community or in assisted-living facilities. Baseline characteristics were similar in both groups. Their mean age was 78 years, mean Mini-Mental State Exam score was 7.5, and the majority (86.3%) had Functional Assessment Staging scores of 6.a–6.e.

Overall, 117 of the 176 donepezil-treated patients and 127 of the 167 placebo patients completed the study, which was supported by Eisai Inc. and Pfizer Inc.

Dr. Black holds no financial interest in either firm, but has been a study investigator for both. She is an ad hoc consultant and speaker, and has received honoraria from Pfizer.

The primary end points were change from baseline in Severe Impairment Battery (SIB) total score and Clinician's Interview-Based Impression of Change-Plus (CIBIC-plus) at 24 weeks.

The primary analysis was based on the intent-to-treat population using a last observation carried forward analysis at 24 weeks. The intent-to-treat population consisted of all patients who were randomized, received at least one dose of either donepezil or placebo, and had a baseline and at least one postbaseline efficacy value.

Categories in the CIBIC-plus analysis were collapsed (1–3 equals improved; 4 equals no change; and 5–7 equals worsened) because the distribution of values was sparse in categories 1, 2, and 7.

Donepezil was significantly superior to placebo on the SIB score at week 24 in the intent-to-treat population (mean difference 5.3), and at weeks 8, 16, and 24 in patients who completed the study, Dr. Black reported.

The collapsed category CIBIC-plus analysis significantly favored donepezil at week 24 in the intent-to-treat population and in patients who completed the study. Among donepezil-treated patients, 28% improved, 38% had no change, and 34% worsened, compared with 23%, 29%, and 48% of placebo patients, respectively.

Most reported adverse events were mild to moderate (74%), the most common of which were diarrhea, nausea, and insomnia. Placebo patients reported more serious and severe adverse events than donepezil-treated patients. However, more patients discontinued treatment because of adverse events in the donepezil group than in the placebo group (18.3% vs. 10.8%, respectively), Dr. Black reported.

CHICAGO – Patients with severe Alzheimer's disease showed improved cognition and function when treated with donepezil in a 24-week, placebo-controlled trial, Dr. Sandra Black and her associates reported in a poster at the annual meeting of the American Geriatrics Society.

The results are consistent with a Swedish nursing home study in a similar, institutionalized population (Lancet 2006;367:1262–70), suggesting that even patients with severe disease can benefit from treatment with donepezil.

“The two studies taken together suggest that this stage of disease can show measurable benefits of treatment with donepezil,” Dr. Black, professor of medicine and head of neurology at Sunnybrook Health Sciences Centre, University of Toronto, said in an interview. “They give a new evidence-based option for treatment, which gives hope for a better quality of life in the final phase of this devastating disease.”

Currently, donepezil (Aricept) is approved for mild to moderate Alzheimer's disease. In February 2006, the U.S. Food and Drug Administration accepted a supplemental new drug application for donepezil in severe Alzheimer's disease.

Doses of 5 mg and 10 mg of donepezil are typically administered once daily, although the higher 10-mg dose did not provide significantly greater clinical benefit in previous clinical trials.

In their study, Dr. Black and her colleagues randomized 343 patients with severe Alzheimer's disease to an initial dose of donepezil of 5 mg/day for 6 weeks and then 10 mg/day of donepezil (176 patients) or placebo (167 patients) for 24 weeks. Patients resided in the community or in assisted-living facilities. Baseline characteristics were similar in both groups. Their mean age was 78 years, mean Mini-Mental State Exam score was 7.5, and the majority (86.3%) had Functional Assessment Staging scores of 6.a–6.e.

Overall, 117 of the 176 donepezil-treated patients and 127 of the 167 placebo patients completed the study, which was supported by Eisai Inc. and Pfizer Inc.

Dr. Black holds no financial interest in either firm, but has been a study investigator for both. She is an ad hoc consultant and speaker, and has received honoraria from Pfizer.

The primary end points were change from baseline in Severe Impairment Battery (SIB) total score and Clinician's Interview-Based Impression of Change-Plus (CIBIC-plus) at 24 weeks.

The primary analysis was based on the intent-to-treat population using a last observation carried forward analysis at 24 weeks. The intent-to-treat population consisted of all patients who were randomized, received at least one dose of either donepezil or placebo, and had a baseline and at least one postbaseline efficacy value.

Categories in the CIBIC-plus analysis were collapsed (1–3 equals improved; 4 equals no change; and 5–7 equals worsened) because the distribution of values was sparse in categories 1, 2, and 7.

Donepezil was significantly superior to placebo on the SIB score at week 24 in the intent-to-treat population (mean difference 5.3), and at weeks 8, 16, and 24 in patients who completed the study, Dr. Black reported.

The collapsed category CIBIC-plus analysis significantly favored donepezil at week 24 in the intent-to-treat population and in patients who completed the study. Among donepezil-treated patients, 28% improved, 38% had no change, and 34% worsened, compared with 23%, 29%, and 48% of placebo patients, respectively.

Most reported adverse events were mild to moderate (74%), the most common of which were diarrhea, nausea, and insomnia. Placebo patients reported more serious and severe adverse events than donepezil-treated patients. However, more patients discontinued treatment because of adverse events in the donepezil group than in the placebo group (18.3% vs. 10.8%, respectively), Dr. Black reported.

CHICAGO – Patients with severe Alzheimer's disease showed improved cognition and function when treated with donepezil in a 24-week, placebo-controlled trial, Dr. Sandra Black and her associates reported in a poster at the annual meeting of the American Geriatrics Society.

The results are consistent with a Swedish nursing home study in a similar, institutionalized population (Lancet 2006;367:1262–70), suggesting that even patients with severe disease can benefit from treatment with donepezil.

“The two studies taken together suggest that this stage of disease can show measurable benefits of treatment with donepezil,” Dr. Black, professor of medicine and head of neurology at Sunnybrook Health Sciences Centre, University of Toronto, said in an interview. “They give a new evidence-based option for treatment, which gives hope for a better quality of life in the final phase of this devastating disease.”

Currently, donepezil (Aricept) is approved for mild to moderate Alzheimer's disease. In February 2006, the U.S. Food and Drug Administration accepted a supplemental new drug application for donepezil in severe Alzheimer's disease.

Doses of 5 mg and 10 mg of donepezil are typically administered once daily, although the higher 10-mg dose did not provide significantly greater clinical benefit in previous clinical trials.

In their study, Dr. Black and her colleagues randomized 343 patients with severe Alzheimer's disease to an initial dose of donepezil of 5 mg/day for 6 weeks and then 10 mg/day of donepezil (176 patients) or placebo (167 patients) for 24 weeks. Patients resided in the community or in assisted-living facilities. Baseline characteristics were similar in both groups. Their mean age was 78 years, mean Mini-Mental State Exam score was 7.5, and the majority (86.3%) had Functional Assessment Staging scores of 6.a–6.e.

Overall, 117 of the 176 donepezil-treated patients and 127 of the 167 placebo patients completed the study, which was supported by Eisai Inc. and Pfizer Inc.

Dr. Black holds no financial interest in either firm, but has been a study investigator for both. She is an ad hoc consultant and speaker, and has received honoraria from Pfizer.

The primary end points were change from baseline in Severe Impairment Battery (SIB) total score and Clinician's Interview-Based Impression of Change-Plus (CIBIC-plus) at 24 weeks.

The primary analysis was based on the intent-to-treat population using a last observation carried forward analysis at 24 weeks. The intent-to-treat population consisted of all patients who were randomized, received at least one dose of either donepezil or placebo, and had a baseline and at least one postbaseline efficacy value.

Categories in the CIBIC-plus analysis were collapsed (1–3 equals improved; 4 equals no change; and 5–7 equals worsened) because the distribution of values was sparse in categories 1, 2, and 7.

Donepezil was significantly superior to placebo on the SIB score at week 24 in the intent-to-treat population (mean difference 5.3), and at weeks 8, 16, and 24 in patients who completed the study, Dr. Black reported.

The collapsed category CIBIC-plus analysis significantly favored donepezil at week 24 in the intent-to-treat population and in patients who completed the study. Among donepezil-treated patients, 28% improved, 38% had no change, and 34% worsened, compared with 23%, 29%, and 48% of placebo patients, respectively.

Most reported adverse events were mild to moderate (74%), the most common of which were diarrhea, nausea, and insomnia. Placebo patients reported more serious and severe adverse events than donepezil-treated patients. However, more patients discontinued treatment because of adverse events in the donepezil group than in the placebo group (18.3% vs. 10.8%, respectively), Dr. Black reported.