AAGP Annual Meeting

NEW ORLEANS – Psychotic, not physical, symptoms, might be the most distressing aspect of Parkinson’s disease for patients, families, and caregivers.

Psychosis is common and persistent, especially as the disease progresses, and it can be devastating, Dr. Laura Marsh said at the annual meeting of the American Association for Geriatric Psychiatry.

“What’s most disabling to families is not the on-off fluctuations, the falling, the other motor symptoms,” said Dr. Marsh, executive director of mental health at Michael E. DeBakey Veterans Affairs Medical Center, Houston. “It’s the cognitive and psychiatric problems that occur with increasing frequency over the disease course. This is what makes it really tough to handle this disease ... These can be very challenging patients with multiple comorbidities,” treated with medications that can exacerbate psychiatric symptoms. The trick is balancing the drugs needed to manage their physical problems with the sometimes-related exacerbations of psychiatric symptoms.”

Despite the difficulties PD psychosis can cause, research doesn’t really have a firm grasp on its extent, Dr. Marsh said. Most studies find an incidence of 8%-40%, but the rate varies depending on the presence of comorbid dementia – as low as 5%-17% in those without it, and as high as 81% in those with it.

Among those with psychoses, visual and auditory hallucinations are most common. But other systems also can be affected, with olfactory, tactile, and visceral hallucinations. Visceral hallucinations frequently manifest as a sense of an unseen presence or passage near the patient, which can be highly disturbing.

Delusions might be somewhat less common but no less problematic, occurring in about 60% of those with psychosis. Feelings that a spouse has been unfaithful might be the most painful for couples, especially when the spouse is the primary caregiver, Dr. Marsh said.

“We may classify some of these – like presence – as ‘minor’ or benign, but in truth none of them are really minor,” Dr. Marsh said.

Patients’ often-complicated medical regimens, including drugs for motor function, mood, and cognition, complicate the picture. “They are often taking low doses of just about everything, so nothing is really effective,” she said. “Their motor function isn’t better, their mood isn’t better, and now they end up psychotic, too.”

As is often the case, prevention is the most effective therapy. Seemingly small things, like constipation or a urinary tract infection, can easily throw a Parkinson’s patient off kilter, especially an older patient. Sleep problems can predispose to psychotic symptoms; sleep management can help moderate them.

A medication review is crucial. Psychosis is a well-known side effect of anticholinergic medications, and it’s not unusual for patients to be taking several of these. Slowly peeling off one at a time, until psychiatric symptoms improve but before motor symptoms decline, is a must.

“I recommend starting with the monoamine oxidase inhibitors and going down the list until you get to the L-dopa,” Dr. Marsh said. “You want to keep that person moving and engaged.”

Controlled-release anticholinergics are the most unpredictable of these culprit medications. “I like to get rid of that and use the regular 25-100 mg every 3 hours and have them track their symptoms.”

Choosing an antipsychotic medication, should it be necessary, is a delicate process. The D2-receptor agonists can actually cause Parkinsonism. Of the more appropriate atypical antipsychotics, clozapine possesses the most data and the best clinical track record. Quetiapine, though not backed by as much evidence, is fairly well tolerated and can be useful. Risperidone and olanzapine are poorly tolerated, and impose unnecessary risks, including falls, seizures, worsened Parkinsonism, and even death.

Unfortunately, Dr. Marsh said, a recent study suggests that clinicians aren’t incorporating these facts into clinical practice. She referred to a 2013 claims database study of Parkinson’s patients in long-term care. Quetiapine was being prescribed to 40%, risperidone to 39%, olanzapine to 17%, and typical antipsychotics to the remainder.

“This is simply inappropriate use of these medications,” she said.

Some promise may lie ahead, however. Pimavanserin, a serotonin 5-HT2A inverse agonist, performed well in a 2013 placebo-controlled trial carried out in 200 patients (Drugs Aging 2013;30:19-22). Pimavanserin was associated with an almost 6-point decrease in Scale to Assess Psychosis in PD (SAPS-PD), compared with a 3-point decrease associated with placebo. Ten patients in the pimavanserin group discontinued because of an adverse event (four because of psychotic disorder or hallucination within 10 days of start of the study drug), compared with two in the placebo group. Overall, though, pimavanserin was well tolerated, and there were no significant safety concerns or worsening of motor function.

The drug also is being investigated for Alzheimer’s disease psychosis.

Dr. Marsh disclosed that she had received honoraria from Roche Pharmaceuticals in 2013, and has received royalties from Taylor & Francis/Informa.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

NEW ORLEANS – Psychotic, not physical, symptoms, might be the most distressing aspect of Parkinson’s disease for patients, families, and caregivers.

Psychosis is common and persistent, especially as the disease progresses, and it can be devastating, Dr. Laura Marsh said at the annual meeting of the American Association for Geriatric Psychiatry.

“What’s most disabling to families is not the on-off fluctuations, the falling, the other motor symptoms,” said Dr. Marsh, executive director of mental health at Michael E. DeBakey Veterans Affairs Medical Center, Houston. “It’s the cognitive and psychiatric problems that occur with increasing frequency over the disease course. This is what makes it really tough to handle this disease ... These can be very challenging patients with multiple comorbidities,” treated with medications that can exacerbate psychiatric symptoms. The trick is balancing the drugs needed to manage their physical problems with the sometimes-related exacerbations of psychiatric symptoms.”

Despite the difficulties PD psychosis can cause, research doesn’t really have a firm grasp on its extent, Dr. Marsh said. Most studies find an incidence of 8%-40%, but the rate varies depending on the presence of comorbid dementia – as low as 5%-17% in those without it, and as high as 81% in those with it.

Among those with psychoses, visual and auditory hallucinations are most common. But other systems also can be affected, with olfactory, tactile, and visceral hallucinations. Visceral hallucinations frequently manifest as a sense of an unseen presence or passage near the patient, which can be highly disturbing.

Delusions might be somewhat less common but no less problematic, occurring in about 60% of those with psychosis. Feelings that a spouse has been unfaithful might be the most painful for couples, especially when the spouse is the primary caregiver, Dr. Marsh said.

“We may classify some of these – like presence – as ‘minor’ or benign, but in truth none of them are really minor,” Dr. Marsh said.

Patients’ often-complicated medical regimens, including drugs for motor function, mood, and cognition, complicate the picture. “They are often taking low doses of just about everything, so nothing is really effective,” she said. “Their motor function isn’t better, their mood isn’t better, and now they end up psychotic, too.”

As is often the case, prevention is the most effective therapy. Seemingly small things, like constipation or a urinary tract infection, can easily throw a Parkinson’s patient off kilter, especially an older patient. Sleep problems can predispose to psychotic symptoms; sleep management can help moderate them.

A medication review is crucial. Psychosis is a well-known side effect of anticholinergic medications, and it’s not unusual for patients to be taking several of these. Slowly peeling off one at a time, until psychiatric symptoms improve but before motor symptoms decline, is a must.

“I recommend starting with the monoamine oxidase inhibitors and going down the list until you get to the L-dopa,” Dr. Marsh said. “You want to keep that person moving and engaged.”

Controlled-release anticholinergics are the most unpredictable of these culprit medications. “I like to get rid of that and use the regular 25-100 mg every 3 hours and have them track their symptoms.”

Choosing an antipsychotic medication, should it be necessary, is a delicate process. The D2-receptor agonists can actually cause Parkinsonism. Of the more appropriate atypical antipsychotics, clozapine possesses the most data and the best clinical track record. Quetiapine, though not backed by as much evidence, is fairly well tolerated and can be useful. Risperidone and olanzapine are poorly tolerated, and impose unnecessary risks, including falls, seizures, worsened Parkinsonism, and even death.

Unfortunately, Dr. Marsh said, a recent study suggests that clinicians aren’t incorporating these facts into clinical practice. She referred to a 2013 claims database study of Parkinson’s patients in long-term care. Quetiapine was being prescribed to 40%, risperidone to 39%, olanzapine to 17%, and typical antipsychotics to the remainder.

“This is simply inappropriate use of these medications,” she said.

Some promise may lie ahead, however. Pimavanserin, a serotonin 5-HT2A inverse agonist, performed well in a 2013 placebo-controlled trial carried out in 200 patients (Drugs Aging 2013;30:19-22). Pimavanserin was associated with an almost 6-point decrease in Scale to Assess Psychosis in PD (SAPS-PD), compared with a 3-point decrease associated with placebo. Ten patients in the pimavanserin group discontinued because of an adverse event (four because of psychotic disorder or hallucination within 10 days of start of the study drug), compared with two in the placebo group. Overall, though, pimavanserin was well tolerated, and there were no significant safety concerns or worsening of motor function.

The drug also is being investigated for Alzheimer’s disease psychosis.

Dr. Marsh disclosed that she had received honoraria from Roche Pharmaceuticals in 2013, and has received royalties from Taylor & Francis/Informa.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

NEW ORLEANS – Psychotic, not physical, symptoms, might be the most distressing aspect of Parkinson’s disease for patients, families, and caregivers.

Psychosis is common and persistent, especially as the disease progresses, and it can be devastating, Dr. Laura Marsh said at the annual meeting of the American Association for Geriatric Psychiatry.

“What’s most disabling to families is not the on-off fluctuations, the falling, the other motor symptoms,” said Dr. Marsh, executive director of mental health at Michael E. DeBakey Veterans Affairs Medical Center, Houston. “It’s the cognitive and psychiatric problems that occur with increasing frequency over the disease course. This is what makes it really tough to handle this disease ... These can be very challenging patients with multiple comorbidities,” treated with medications that can exacerbate psychiatric symptoms. The trick is balancing the drugs needed to manage their physical problems with the sometimes-related exacerbations of psychiatric symptoms.”

Despite the difficulties PD psychosis can cause, research doesn’t really have a firm grasp on its extent, Dr. Marsh said. Most studies find an incidence of 8%-40%, but the rate varies depending on the presence of comorbid dementia – as low as 5%-17% in those without it, and as high as 81% in those with it.

Among those with psychoses, visual and auditory hallucinations are most common. But other systems also can be affected, with olfactory, tactile, and visceral hallucinations. Visceral hallucinations frequently manifest as a sense of an unseen presence or passage near the patient, which can be highly disturbing.

Delusions might be somewhat less common but no less problematic, occurring in about 60% of those with psychosis. Feelings that a spouse has been unfaithful might be the most painful for couples, especially when the spouse is the primary caregiver, Dr. Marsh said.

“We may classify some of these – like presence – as ‘minor’ or benign, but in truth none of them are really minor,” Dr. Marsh said.

Patients’ often-complicated medical regimens, including drugs for motor function, mood, and cognition, complicate the picture. “They are often taking low doses of just about everything, so nothing is really effective,” she said. “Their motor function isn’t better, their mood isn’t better, and now they end up psychotic, too.”

As is often the case, prevention is the most effective therapy. Seemingly small things, like constipation or a urinary tract infection, can easily throw a Parkinson’s patient off kilter, especially an older patient. Sleep problems can predispose to psychotic symptoms; sleep management can help moderate them.

A medication review is crucial. Psychosis is a well-known side effect of anticholinergic medications, and it’s not unusual for patients to be taking several of these. Slowly peeling off one at a time, until psychiatric symptoms improve but before motor symptoms decline, is a must.

“I recommend starting with the monoamine oxidase inhibitors and going down the list until you get to the L-dopa,” Dr. Marsh said. “You want to keep that person moving and engaged.”

Controlled-release anticholinergics are the most unpredictable of these culprit medications. “I like to get rid of that and use the regular 25-100 mg every 3 hours and have them track their symptoms.”

Choosing an antipsychotic medication, should it be necessary, is a delicate process. The D2-receptor agonists can actually cause Parkinsonism. Of the more appropriate atypical antipsychotics, clozapine possesses the most data and the best clinical track record. Quetiapine, though not backed by as much evidence, is fairly well tolerated and can be useful. Risperidone and olanzapine are poorly tolerated, and impose unnecessary risks, including falls, seizures, worsened Parkinsonism, and even death.

Unfortunately, Dr. Marsh said, a recent study suggests that clinicians aren’t incorporating these facts into clinical practice. She referred to a 2013 claims database study of Parkinson’s patients in long-term care. Quetiapine was being prescribed to 40%, risperidone to 39%, olanzapine to 17%, and typical antipsychotics to the remainder.

“This is simply inappropriate use of these medications,” she said.

Some promise may lie ahead, however. Pimavanserin, a serotonin 5-HT2A inverse agonist, performed well in a 2013 placebo-controlled trial carried out in 200 patients (Drugs Aging 2013;30:19-22). Pimavanserin was associated with an almost 6-point decrease in Scale to Assess Psychosis in PD (SAPS-PD), compared with a 3-point decrease associated with placebo. Ten patients in the pimavanserin group discontinued because of an adverse event (four because of psychotic disorder or hallucination within 10 days of start of the study drug), compared with two in the placebo group. Overall, though, pimavanserin was well tolerated, and there were no significant safety concerns or worsening of motor function.

The drug also is being investigated for Alzheimer’s disease psychosis.

Dr. Marsh disclosed that she had received honoraria from Roche Pharmaceuticals in 2013, and has received royalties from Taylor & Francis/Informa.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

NEW ORLEANS – Suicidal thoughts and actions are not rare among the elderly, and seem to have diverse drivers, including physical disability, pain, and loneliness.

Overall, about 6% of those aged 65 years and older expressed some sort of death wish or suicidal behavior, a large population-based study has found. But that number almost tripled among subjects who had high levels of functional disability, Dr. Margda Waern reported at the annual meeting of the American Association for Geriatric Psychiatry.

Dr. Waern, a psychiatrist at the University of Gothenburg, Sweden, discussed a pooled analysis of the classic EURODEP study, which examined the relationship between depressive symptoms and physical functioning in 14 cross-sectional European cohorts. EURODEP comprised almost 23,000 respondents aged 65 years and older and has been mined many times since its original publication in 2005.

Dr. Waern examined pooled data from 11 of the EURODEP studies, comprising 15,580 subjects. Most of the centers – but not all – used the Katz Index of Independence in Activities of Daily Living scale to assess physical function. In order to harmonize the data on functional disability, Dr. Waern instead trichotomized them into no disability, intermediate disability, and high disability. She also examined a broad measure of suicidality – “death wishes” – which she said encompassed the continuum of suicidal thoughts to active ideation.

“We saw what I would call a very nice dose-response relationship between high levels of functional disability and death wishes,” she said.

About 4% of those without a functional disability expressed ever having had a death wish, compared to 8% of those with moderate disability, and 17% of those with high functional disability. Those findings were similar among both men and women.

She tried to tease out more detailed data with a multivariate regression model of 11,000 subjects. In this model, functional disability remained a strong independent risk factor. Intermediate disability conferred a 60% increased risk of death wish, and a high level more than doubled the risk (odds ratio, 2.4). Perceived loneliness also was a strong independent risk factor, associated with a near tripling, compared with those who did not feel lonely (OR, 2.7).

Subjects with chronic illnesses also were at significantly higher risk of having death wishes, Dr. Waern said.

She also discussed a population-based study of suicidal feelings in people aged 97 years and older. All residents of Gothenburg who had reached that age were invited to participate in the survey. Dr. Waern had a 60% response rate – about 600 residents. Of these, 269 without a diagnosis of dementia participated in the survey, which asked about suicidal thoughts and actions in the previous month.

There were no recent suicide attempts, she said. But 12% of the cohort reported some kind of suicidal feeling or thought during that time frame. These included the idea that “life is not worth living” (8%); death wishes (10%); and thoughts about committing suicide (4%).

She looked for associations between these thoughts and several physical characteristics. Most (77%) of those who reported such feelings fulfilled criteria for neither major nor minor depression. There were no associations with vision or hearing loss, overall motor function, or with a perception of poor physical health. Suicidal feelings were significantly more common among those who had experienced a stroke (23% vs. 16%) and among those who reported living with physical pain (41% vs. 24%).

“In a multivariate model, however, pain fell out as an independent predictor,” Dr. Waern said. “What did show up was problematic sleep and also the feeling of having deficient social contacts.”

Sleep difficulties were associated with a tripling of the risk (OR, 3.5). Three forms of social isolation conferred a significant increase in the risk of suicidal thoughts: Too little time spent with neighbors (adjusted OR, 5.0); too little time spent with friends (OR, 6.6); and perceived loneliness (OR, 3.3).

Dr. Waern had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

NEW ORLEANS – Suicidal thoughts and actions are not rare among the elderly, and seem to have diverse drivers, including physical disability, pain, and loneliness.

Overall, about 6% of those aged 65 years and older expressed some sort of death wish or suicidal behavior, a large population-based study has found. But that number almost tripled among subjects who had high levels of functional disability, Dr. Margda Waern reported at the annual meeting of the American Association for Geriatric Psychiatry.

Dr. Waern, a psychiatrist at the University of Gothenburg, Sweden, discussed a pooled analysis of the classic EURODEP study, which examined the relationship between depressive symptoms and physical functioning in 14 cross-sectional European cohorts. EURODEP comprised almost 23,000 respondents aged 65 years and older and has been mined many times since its original publication in 2005.

Dr. Waern examined pooled data from 11 of the EURODEP studies, comprising 15,580 subjects. Most of the centers – but not all – used the Katz Index of Independence in Activities of Daily Living scale to assess physical function. In order to harmonize the data on functional disability, Dr. Waern instead trichotomized them into no disability, intermediate disability, and high disability. She also examined a broad measure of suicidality – “death wishes” – which she said encompassed the continuum of suicidal thoughts to active ideation.

“We saw what I would call a very nice dose-response relationship between high levels of functional disability and death wishes,” she said.

About 4% of those without a functional disability expressed ever having had a death wish, compared to 8% of those with moderate disability, and 17% of those with high functional disability. Those findings were similar among both men and women.

She tried to tease out more detailed data with a multivariate regression model of 11,000 subjects. In this model, functional disability remained a strong independent risk factor. Intermediate disability conferred a 60% increased risk of death wish, and a high level more than doubled the risk (odds ratio, 2.4). Perceived loneliness also was a strong independent risk factor, associated with a near tripling, compared with those who did not feel lonely (OR, 2.7).

Subjects with chronic illnesses also were at significantly higher risk of having death wishes, Dr. Waern said.

She also discussed a population-based study of suicidal feelings in people aged 97 years and older. All residents of Gothenburg who had reached that age were invited to participate in the survey. Dr. Waern had a 60% response rate – about 600 residents. Of these, 269 without a diagnosis of dementia participated in the survey, which asked about suicidal thoughts and actions in the previous month.

There were no recent suicide attempts, she said. But 12% of the cohort reported some kind of suicidal feeling or thought during that time frame. These included the idea that “life is not worth living” (8%); death wishes (10%); and thoughts about committing suicide (4%).

She looked for associations between these thoughts and several physical characteristics. Most (77%) of those who reported such feelings fulfilled criteria for neither major nor minor depression. There were no associations with vision or hearing loss, overall motor function, or with a perception of poor physical health. Suicidal feelings were significantly more common among those who had experienced a stroke (23% vs. 16%) and among those who reported living with physical pain (41% vs. 24%).

“In a multivariate model, however, pain fell out as an independent predictor,” Dr. Waern said. “What did show up was problematic sleep and also the feeling of having deficient social contacts.”

Sleep difficulties were associated with a tripling of the risk (OR, 3.5). Three forms of social isolation conferred a significant increase in the risk of suicidal thoughts: Too little time spent with neighbors (adjusted OR, 5.0); too little time spent with friends (OR, 6.6); and perceived loneliness (OR, 3.3).

Dr. Waern had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

NEW ORLEANS – Suicidal thoughts and actions are not rare among the elderly, and seem to have diverse drivers, including physical disability, pain, and loneliness.

Overall, about 6% of those aged 65 years and older expressed some sort of death wish or suicidal behavior, a large population-based study has found. But that number almost tripled among subjects who had high levels of functional disability, Dr. Margda Waern reported at the annual meeting of the American Association for Geriatric Psychiatry.

Dr. Waern, a psychiatrist at the University of Gothenburg, Sweden, discussed a pooled analysis of the classic EURODEP study, which examined the relationship between depressive symptoms and physical functioning in 14 cross-sectional European cohorts. EURODEP comprised almost 23,000 respondents aged 65 years and older and has been mined many times since its original publication in 2005.

Dr. Waern examined pooled data from 11 of the EURODEP studies, comprising 15,580 subjects. Most of the centers – but not all – used the Katz Index of Independence in Activities of Daily Living scale to assess physical function. In order to harmonize the data on functional disability, Dr. Waern instead trichotomized them into no disability, intermediate disability, and high disability. She also examined a broad measure of suicidality – “death wishes” – which she said encompassed the continuum of suicidal thoughts to active ideation.

“We saw what I would call a very nice dose-response relationship between high levels of functional disability and death wishes,” she said.

About 4% of those without a functional disability expressed ever having had a death wish, compared to 8% of those with moderate disability, and 17% of those with high functional disability. Those findings were similar among both men and women.

She tried to tease out more detailed data with a multivariate regression model of 11,000 subjects. In this model, functional disability remained a strong independent risk factor. Intermediate disability conferred a 60% increased risk of death wish, and a high level more than doubled the risk (odds ratio, 2.4). Perceived loneliness also was a strong independent risk factor, associated with a near tripling, compared with those who did not feel lonely (OR, 2.7).

Subjects with chronic illnesses also were at significantly higher risk of having death wishes, Dr. Waern said.

She also discussed a population-based study of suicidal feelings in people aged 97 years and older. All residents of Gothenburg who had reached that age were invited to participate in the survey. Dr. Waern had a 60% response rate – about 600 residents. Of these, 269 without a diagnosis of dementia participated in the survey, which asked about suicidal thoughts and actions in the previous month.

There were no recent suicide attempts, she said. But 12% of the cohort reported some kind of suicidal feeling or thought during that time frame. These included the idea that “life is not worth living” (8%); death wishes (10%); and thoughts about committing suicide (4%).

She looked for associations between these thoughts and several physical characteristics. Most (77%) of those who reported such feelings fulfilled criteria for neither major nor minor depression. There were no associations with vision or hearing loss, overall motor function, or with a perception of poor physical health. Suicidal feelings were significantly more common among those who had experienced a stroke (23% vs. 16%) and among those who reported living with physical pain (41% vs. 24%).

“In a multivariate model, however, pain fell out as an independent predictor,” Dr. Waern said. “What did show up was problematic sleep and also the feeling of having deficient social contacts.”

Sleep difficulties were associated with a tripling of the risk (OR, 3.5). Three forms of social isolation conferred a significant increase in the risk of suicidal thoughts: Too little time spent with neighbors (adjusted OR, 5.0); too little time spent with friends (OR, 6.6); and perceived loneliness (OR, 3.3).

Dr. Waern had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

NEW ORLEANS – The combination of memantine and a cholinesterase inhibitor improved behavioral symptoms in patients with moderate-severe Alzheimer’s dementia, according to two pooled, post hoc analyses.

The combination not only significantly improved total scores on the Neuropsychiatric Inventory (NPI), but individual scores on agitation/aggression, elation/euphoria, emotional lability, and appetite, Suzanne Hendrix, Ph.D., reported in two posters presented at the annual meeting of the American Association for Geriatric Psychiatry.

The studies, sponsored by the Forest Research Institute, examined pooled data from five randomized, placebo-controlled trials; three of these were included in both analyses.

The first study comprised a total of about 1,250 patients with moderate-severe Alzheimer’s included in three placebo-controlled trials. The first randomized patients to 10 mg memantine or placebo plus donepezil. The second randomized to 20 mg memantine or placebo plus any existing cholinesterase inhibitor (ChEI). The third randomized to extended-release 28 mg memantine or placebo plus any existing ChEI. All were 24 weeks’ duration.

The primary outcome was change on the total NPI; the secondary outcomes were changes in individual subscores.

Patients were a mean age of 75 years. Total NPI scores ranged from 14 to 17; only 7%-14% had an NPI of 0.

By week 24, all memantine doses combined with ChEI had significantly outperformed ChEI alone on both the total NPI score and on the subscores for delusions, agitation/aggression, irritability/lability, and nighttime behaviors. The mean total score improvement was about 2.25 points.

When considering only those patients who were symptomatic at baseline, combination therapy also significantly outperformed ChEI alone in total NPI and on the subscores for agitation/aggression, irritability/lability, and appetite – all by about 0.5 points. Aberrant motor behavior improved by a nearly statistically significant amount with a P value of .051.

The second analysis comprised about 1,800 patients with moderate-severe disease. Its primary endpoint was change agitation among the subset of patients who did not display this symptom or who displayed clinically insignificant symptoms (474 with NPI 1, 2, or 3; 596 with NPI 1, 2, 3, or 4). It included the previous three trials, plus two more, both of which randomized to 10 mg memantine twice a day or placebo. Patient characteristics were similar in all the studies. Comparisons were made between combination therapy, placebo plus ChEI, and placebo only.

By week 12, mean agitation/aggression scores were unchanged in those on combination therapy and nonsignificantly worse for those taking either memantine alone or ChEI alone. Agitation/aggression scores had worsened by almost 0.6 points among those taking placebo – a significant difference from combination therapy.

By the end of the studies, the mean score among those with NPI scores of 1-3 who took combination therapy actually had improved significantly from baseline (about 0.5 points). Patients taking either monotherapy remained unchanged, while those taking only placebo worsened by almost a full point.

Findings were similar among those with NPI scores of 1-4. By the end of the studies, those taking combination therapy experienced a mean improvement of almost 1 point, while those taking placebo worsened by a mean of 0.6 points. Scores in the monotherapy groups remained unchanged.

Given the expected worsening of agitation and aggression as AD progresses, the results suggest a clinical benefit of memantine when added to existing cholinesterase inhibition, Dr. Hendricks said.

“This argues for the potential benefit of earlier addition of memantine. This may in turn prevent the expected worsening of agitation/aggression, delay considerably additional diagnoses, and also delay the introduction of other medications.”

The Forest Research Institute supported the analysis. Dr. Hendricks is president of the Pentara Corp., which consults with pharmaceutical companies and nonprofit or academic groups in Alzheimer’s disease clinical study design and analysis.

msullivan@frontlinemedcom.com


On Twitter @alz_gal

NEW ORLEANS – The combination of memantine and a cholinesterase inhibitor improved behavioral symptoms in patients with moderate-severe Alzheimer’s dementia, according to two pooled, post hoc analyses.

The combination not only significantly improved total scores on the Neuropsychiatric Inventory (NPI), but individual scores on agitation/aggression, elation/euphoria, emotional lability, and appetite, Suzanne Hendrix, Ph.D., reported in two posters presented at the annual meeting of the American Association for Geriatric Psychiatry.

The studies, sponsored by the Forest Research Institute, examined pooled data from five randomized, placebo-controlled trials; three of these were included in both analyses.

The first study comprised a total of about 1,250 patients with moderate-severe Alzheimer’s included in three placebo-controlled trials. The first randomized patients to 10 mg memantine or placebo plus donepezil. The second randomized to 20 mg memantine or placebo plus any existing cholinesterase inhibitor (ChEI). The third randomized to extended-release 28 mg memantine or placebo plus any existing ChEI. All were 24 weeks’ duration.

The primary outcome was change on the total NPI; the secondary outcomes were changes in individual subscores.

Patients were a mean age of 75 years. Total NPI scores ranged from 14 to 17; only 7%-14% had an NPI of 0.

By week 24, all memantine doses combined with ChEI had significantly outperformed ChEI alone on both the total NPI score and on the subscores for delusions, agitation/aggression, irritability/lability, and nighttime behaviors. The mean total score improvement was about 2.25 points.

When considering only those patients who were symptomatic at baseline, combination therapy also significantly outperformed ChEI alone in total NPI and on the subscores for agitation/aggression, irritability/lability, and appetite – all by about 0.5 points. Aberrant motor behavior improved by a nearly statistically significant amount with a P value of .051.

The second analysis comprised about 1,800 patients with moderate-severe disease. Its primary endpoint was change agitation among the subset of patients who did not display this symptom or who displayed clinically insignificant symptoms (474 with NPI 1, 2, or 3; 596 with NPI 1, 2, 3, or 4). It included the previous three trials, plus two more, both of which randomized to 10 mg memantine twice a day or placebo. Patient characteristics were similar in all the studies. Comparisons were made between combination therapy, placebo plus ChEI, and placebo only.

By week 12, mean agitation/aggression scores were unchanged in those on combination therapy and nonsignificantly worse for those taking either memantine alone or ChEI alone. Agitation/aggression scores had worsened by almost 0.6 points among those taking placebo – a significant difference from combination therapy.

By the end of the studies, the mean score among those with NPI scores of 1-3 who took combination therapy actually had improved significantly from baseline (about 0.5 points). Patients taking either monotherapy remained unchanged, while those taking only placebo worsened by almost a full point.

Findings were similar among those with NPI scores of 1-4. By the end of the studies, those taking combination therapy experienced a mean improvement of almost 1 point, while those taking placebo worsened by a mean of 0.6 points. Scores in the monotherapy groups remained unchanged.

Given the expected worsening of agitation and aggression as AD progresses, the results suggest a clinical benefit of memantine when added to existing cholinesterase inhibition, Dr. Hendricks said.

“This argues for the potential benefit of earlier addition of memantine. This may in turn prevent the expected worsening of agitation/aggression, delay considerably additional diagnoses, and also delay the introduction of other medications.”

The Forest Research Institute supported the analysis. Dr. Hendricks is president of the Pentara Corp., which consults with pharmaceutical companies and nonprofit or academic groups in Alzheimer’s disease clinical study design and analysis.

msullivan@frontlinemedcom.com


On Twitter @alz_gal

NEW ORLEANS – The combination of memantine and a cholinesterase inhibitor improved behavioral symptoms in patients with moderate-severe Alzheimer’s dementia, according to two pooled, post hoc analyses.

The combination not only significantly improved total scores on the Neuropsychiatric Inventory (NPI), but individual scores on agitation/aggression, elation/euphoria, emotional lability, and appetite, Suzanne Hendrix, Ph.D., reported in two posters presented at the annual meeting of the American Association for Geriatric Psychiatry.

The studies, sponsored by the Forest Research Institute, examined pooled data from five randomized, placebo-controlled trials; three of these were included in both analyses.

The first study comprised a total of about 1,250 patients with moderate-severe Alzheimer’s included in three placebo-controlled trials. The first randomized patients to 10 mg memantine or placebo plus donepezil. The second randomized to 20 mg memantine or placebo plus any existing cholinesterase inhibitor (ChEI). The third randomized to extended-release 28 mg memantine or placebo plus any existing ChEI. All were 24 weeks’ duration.

The primary outcome was change on the total NPI; the secondary outcomes were changes in individual subscores.

Patients were a mean age of 75 years. Total NPI scores ranged from 14 to 17; only 7%-14% had an NPI of 0.

By week 24, all memantine doses combined with ChEI had significantly outperformed ChEI alone on both the total NPI score and on the subscores for delusions, agitation/aggression, irritability/lability, and nighttime behaviors. The mean total score improvement was about 2.25 points.

When considering only those patients who were symptomatic at baseline, combination therapy also significantly outperformed ChEI alone in total NPI and on the subscores for agitation/aggression, irritability/lability, and appetite – all by about 0.5 points. Aberrant motor behavior improved by a nearly statistically significant amount with a P value of .051.

The second analysis comprised about 1,800 patients with moderate-severe disease. Its primary endpoint was change agitation among the subset of patients who did not display this symptom or who displayed clinically insignificant symptoms (474 with NPI 1, 2, or 3; 596 with NPI 1, 2, 3, or 4). It included the previous three trials, plus two more, both of which randomized to 10 mg memantine twice a day or placebo. Patient characteristics were similar in all the studies. Comparisons were made between combination therapy, placebo plus ChEI, and placebo only.

By week 12, mean agitation/aggression scores were unchanged in those on combination therapy and nonsignificantly worse for those taking either memantine alone or ChEI alone. Agitation/aggression scores had worsened by almost 0.6 points among those taking placebo – a significant difference from combination therapy.

By the end of the studies, the mean score among those with NPI scores of 1-3 who took combination therapy actually had improved significantly from baseline (about 0.5 points). Patients taking either monotherapy remained unchanged, while those taking only placebo worsened by almost a full point.

Findings were similar among those with NPI scores of 1-4. By the end of the studies, those taking combination therapy experienced a mean improvement of almost 1 point, while those taking placebo worsened by a mean of 0.6 points. Scores in the monotherapy groups remained unchanged.

Given the expected worsening of agitation and aggression as AD progresses, the results suggest a clinical benefit of memantine when added to existing cholinesterase inhibition, Dr. Hendricks said.

“This argues for the potential benefit of earlier addition of memantine. This may in turn prevent the expected worsening of agitation/aggression, delay considerably additional diagnoses, and also delay the introduction of other medications.”

The Forest Research Institute supported the analysis. Dr. Hendricks is president of the Pentara Corp., which consults with pharmaceutical companies and nonprofit or academic groups in Alzheimer’s disease clinical study design and analysis.

msullivan@frontlinemedcom.com


On Twitter @alz_gal

NEW ORLEANS – Elderly dementia patients who take antipsychotics are significantly less likely to have guideline-concordant metabolic checkups than are patients without dementia who take the drugs.

There seems to be no universal reason why this should be so, but the findings of a large retrospective study do suggest that providers should be aware of the problem and make an effort to improve follow-up monitoring, Dr. Dinesh Mittal said at the annual meeting of the American Association for Geriatric Psychiatry.

“Metabolic side effects possibly contribute to mortality in elderly patients,” said Dr. Mittal of the Central Arkansas Veterans Healthcare System, North Little Rock. “Because of this, it’s important to monitor outpatients with dementia receiving antipsychotics, especially because the drugs do not have demonstrated efficacy in managing behavioral symptoms of dementia.”

He presented a retrospective cohort analysis of 1,576 matched pairs of elderly Veterans Affairs patients with an index prescription for an antipsychotic. Half of the group had dementia but not psychosis, and the other half had a psychosis but not dementia.

The primary outcomes were metabolic monitoring at both baseline and the 3-month follow-up visit. Metabolic measures considered were weight, glucose or hemoglobin A_1c, and low-density lipoprotein (LDL) cholesterol.

Because the patients with dementia were significantly older and differed on most demographic and clinical variables than those without dementia, the authors used propensity matching to even the groups. Their mean age in the matched sample was 73 years. A quarter had diabetes at baseline. Half had dyslipidemia and half hypertension, 30% were obese, and 15% had some form of heart disease.

About 10% were taking a medication with a high risk of metabolic derangement (clozapine, olanzapine). Most (70%) were taking a drug with a moderate risk (risperidone, chlorpromazine, paliperidone, thiothixene, or trifluoperazine). A low-risk drug was prescribed to the rest of the patients (aripiprazole, ziprasidone, haloperidol, fluphenazine, molindone, pimozide, or mesoridazine).

Even at baseline, the frequency of metabolic measurements was suboptimal, Dr. Mittal said. Weight most often was recorded (68% of dementia patents vs. 64% for the psychosis patients). Less than half of each group had a glucose measurement obtained (41% in the dementia group vs. 44% in the psychosis group). LDL cholesterol was obtained in just a quarter (24% vs. 27%, respectively).

Compared with baseline, significantly fewer patients in each group had 3-month measurements; there also were significant between-group differences, with dementia patients getting less attention. Weight was obtained in 46% of the group with dementia and 51% of the psychosis group, glucose in 26% of the dementia group and 31% of the psychosis group, and LDL in 13% of the dementia group and 18% of the psychosis group.

“We were quite surprised at the findings, as we had expected the rates to be much higher given the [Food and Drug Administration] warnings about the risk of metabolic derangement and mortality with antipsychotic medications,” Dr. Mittal noted.

Reasons for the poor monitoring, especially in dementia patients, are unclear, he said.

“One possible reason may be that monitoring recommendations were developed to apply to any patient treated with a second-generation antipsychotic but did not specifically mention monitoring for patients with dementia. The perception among providers may be that these guidelines apply to patients with psychosis only,” he suggested.

It’s unlikely that transportation problems for patients cared for at home, or lack of understanding about the need for tests, are the cause. An exploratory analysis concluded that 95% of the dementia patients had at least one baseline visit and 75% had at least one follow-up visit during the 3 months after medication initiation.

Some clinicians could view medication-related weight gain as helpful for dementia patients, who tend to lose weight as the disease progresses, but “our sample included only patients with dementia who were being managed in the outpatient setting and were thus likely to have less advanced dementia than those in nursing homes who are more likely to have lost significant weight to warrant such a drastic intervention,” Dr. Mittal said.

The findings are in sharp contrast to the existing guidelines, he pointed out.

In 2004, the American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, and North American Association for the Study of Obesity published a consensus statement on the issue. It recommended assessing metabolic parameters at baseline and at 4, 8, and 12 weeks after treatment initiation. Monitoring also should be conducted quarterly, annually, and every 5 years, the statement noted.

A 2012 literature review upheld this recommendation, suggesting that patients with a history of cardiac disease receive extra attention.

Dr. Mittal had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

NEW ORLEANS – Elderly dementia patients who take antipsychotics are significantly less likely to have guideline-concordant metabolic checkups than are patients without dementia who take the drugs.

There seems to be no universal reason why this should be so, but the findings of a large retrospective study do suggest that providers should be aware of the problem and make an effort to improve follow-up monitoring, Dr. Dinesh Mittal said at the annual meeting of the American Association for Geriatric Psychiatry.

“Metabolic side effects possibly contribute to mortality in elderly patients,” said Dr. Mittal of the Central Arkansas Veterans Healthcare System, North Little Rock. “Because of this, it’s important to monitor outpatients with dementia receiving antipsychotics, especially because the drugs do not have demonstrated efficacy in managing behavioral symptoms of dementia.”

He presented a retrospective cohort analysis of 1,576 matched pairs of elderly Veterans Affairs patients with an index prescription for an antipsychotic. Half of the group had dementia but not psychosis, and the other half had a psychosis but not dementia.

The primary outcomes were metabolic monitoring at both baseline and the 3-month follow-up visit. Metabolic measures considered were weight, glucose or hemoglobin A_1c, and low-density lipoprotein (LDL) cholesterol.

Because the patients with dementia were significantly older and differed on most demographic and clinical variables than those without dementia, the authors used propensity matching to even the groups. Their mean age in the matched sample was 73 years. A quarter had diabetes at baseline. Half had dyslipidemia and half hypertension, 30% were obese, and 15% had some form of heart disease.

About 10% were taking a medication with a high risk of metabolic derangement (clozapine, olanzapine). Most (70%) were taking a drug with a moderate risk (risperidone, chlorpromazine, paliperidone, thiothixene, or trifluoperazine). A low-risk drug was prescribed to the rest of the patients (aripiprazole, ziprasidone, haloperidol, fluphenazine, molindone, pimozide, or mesoridazine).

Even at baseline, the frequency of metabolic measurements was suboptimal, Dr. Mittal said. Weight most often was recorded (68% of dementia patents vs. 64% for the psychosis patients). Less than half of each group had a glucose measurement obtained (41% in the dementia group vs. 44% in the psychosis group). LDL cholesterol was obtained in just a quarter (24% vs. 27%, respectively).

Compared with baseline, significantly fewer patients in each group had 3-month measurements; there also were significant between-group differences, with dementia patients getting less attention. Weight was obtained in 46% of the group with dementia and 51% of the psychosis group, glucose in 26% of the dementia group and 31% of the psychosis group, and LDL in 13% of the dementia group and 18% of the psychosis group.

“We were quite surprised at the findings, as we had expected the rates to be much higher given the [Food and Drug Administration] warnings about the risk of metabolic derangement and mortality with antipsychotic medications,” Dr. Mittal noted.

Reasons for the poor monitoring, especially in dementia patients, are unclear, he said.

“One possible reason may be that monitoring recommendations were developed to apply to any patient treated with a second-generation antipsychotic but did not specifically mention monitoring for patients with dementia. The perception among providers may be that these guidelines apply to patients with psychosis only,” he suggested.

It’s unlikely that transportation problems for patients cared for at home, or lack of understanding about the need for tests, are the cause. An exploratory analysis concluded that 95% of the dementia patients had at least one baseline visit and 75% had at least one follow-up visit during the 3 months after medication initiation.

Some clinicians could view medication-related weight gain as helpful for dementia patients, who tend to lose weight as the disease progresses, but “our sample included only patients with dementia who were being managed in the outpatient setting and were thus likely to have less advanced dementia than those in nursing homes who are more likely to have lost significant weight to warrant such a drastic intervention,” Dr. Mittal said.

The findings are in sharp contrast to the existing guidelines, he pointed out.

In 2004, the American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, and North American Association for the Study of Obesity published a consensus statement on the issue. It recommended assessing metabolic parameters at baseline and at 4, 8, and 12 weeks after treatment initiation. Monitoring also should be conducted quarterly, annually, and every 5 years, the statement noted.

A 2012 literature review upheld this recommendation, suggesting that patients with a history of cardiac disease receive extra attention.

Dr. Mittal had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

NEW ORLEANS – Elderly dementia patients who take antipsychotics are significantly less likely to have guideline-concordant metabolic checkups than are patients without dementia who take the drugs.

There seems to be no universal reason why this should be so, but the findings of a large retrospective study do suggest that providers should be aware of the problem and make an effort to improve follow-up monitoring, Dr. Dinesh Mittal said at the annual meeting of the American Association for Geriatric Psychiatry.

“Metabolic side effects possibly contribute to mortality in elderly patients,” said Dr. Mittal of the Central Arkansas Veterans Healthcare System, North Little Rock. “Because of this, it’s important to monitor outpatients with dementia receiving antipsychotics, especially because the drugs do not have demonstrated efficacy in managing behavioral symptoms of dementia.”

He presented a retrospective cohort analysis of 1,576 matched pairs of elderly Veterans Affairs patients with an index prescription for an antipsychotic. Half of the group had dementia but not psychosis, and the other half had a psychosis but not dementia.

The primary outcomes were metabolic monitoring at both baseline and the 3-month follow-up visit. Metabolic measures considered were weight, glucose or hemoglobin A_1c, and low-density lipoprotein (LDL) cholesterol.

Because the patients with dementia were significantly older and differed on most demographic and clinical variables than those without dementia, the authors used propensity matching to even the groups. Their mean age in the matched sample was 73 years. A quarter had diabetes at baseline. Half had dyslipidemia and half hypertension, 30% were obese, and 15% had some form of heart disease.

About 10% were taking a medication with a high risk of metabolic derangement (clozapine, olanzapine). Most (70%) were taking a drug with a moderate risk (risperidone, chlorpromazine, paliperidone, thiothixene, or trifluoperazine). A low-risk drug was prescribed to the rest of the patients (aripiprazole, ziprasidone, haloperidol, fluphenazine, molindone, pimozide, or mesoridazine).

Even at baseline, the frequency of metabolic measurements was suboptimal, Dr. Mittal said. Weight most often was recorded (68% of dementia patents vs. 64% for the psychosis patients). Less than half of each group had a glucose measurement obtained (41% in the dementia group vs. 44% in the psychosis group). LDL cholesterol was obtained in just a quarter (24% vs. 27%, respectively).

Compared with baseline, significantly fewer patients in each group had 3-month measurements; there also were significant between-group differences, with dementia patients getting less attention. Weight was obtained in 46% of the group with dementia and 51% of the psychosis group, glucose in 26% of the dementia group and 31% of the psychosis group, and LDL in 13% of the dementia group and 18% of the psychosis group.

“We were quite surprised at the findings, as we had expected the rates to be much higher given the [Food and Drug Administration] warnings about the risk of metabolic derangement and mortality with antipsychotic medications,” Dr. Mittal noted.

Reasons for the poor monitoring, especially in dementia patients, are unclear, he said.

“One possible reason may be that monitoring recommendations were developed to apply to any patient treated with a second-generation antipsychotic but did not specifically mention monitoring for patients with dementia. The perception among providers may be that these guidelines apply to patients with psychosis only,” he suggested.

It’s unlikely that transportation problems for patients cared for at home, or lack of understanding about the need for tests, are the cause. An exploratory analysis concluded that 95% of the dementia patients had at least one baseline visit and 75% had at least one follow-up visit during the 3 months after medication initiation.

Some clinicians could view medication-related weight gain as helpful for dementia patients, who tend to lose weight as the disease progresses, but “our sample included only patients with dementia who were being managed in the outpatient setting and were thus likely to have less advanced dementia than those in nursing homes who are more likely to have lost significant weight to warrant such a drastic intervention,” Dr. Mittal said.

The findings are in sharp contrast to the existing guidelines, he pointed out.

In 2004, the American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, and North American Association for the Study of Obesity published a consensus statement on the issue. It recommended assessing metabolic parameters at baseline and at 4, 8, and 12 weeks after treatment initiation. Monitoring also should be conducted quarterly, annually, and every 5 years, the statement noted.

A 2012 literature review upheld this recommendation, suggesting that patients with a history of cardiac disease receive extra attention.

Dr. Mittal had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

NEW ORLEANS–An individualized, step-by-step plan is the best way to treat psychiatric and behavioral problems that might arise in patients with dementia.

But, according to Dr. Rajesh R. Tampi, “There’s no one silver bullet” for these symptoms, which can make things very hard not only on the patient but [also on] the family and caregiving staff.

No medications are approved for treating these symptoms in dementia patients, Dr. Tampi said at the annual meeting of the American Association for Geriatric Psychiatry. Furthermore, some of the most commonly used medications simply aren’t effective, and those that are often come at the price of side effects that prompt discontinuation.

Benzodiazepines, which are still quite often employed, are usually much more harmful than useful, he said. “The data for using benzodiazepines for behavioral problems in dementia simply do not exist. And given the new data we have on worsening of cognition, and a fivefold increase in the risk of falls, I do not think they are useful. I use them only for alcohol- or benzodiazepine-withdrawal or as an intramuscular injection to sedate but never for continuing management.”

Prevention is always the best medicine, said Dr. Tampi, chief of geriatric psychiatry at MetroHealth, Cleveland. Behavioral and psychiatric symptoms often arise as dementia worsens, so delaying disease progression may delay symptom onset as well. Cholinesterase inhibitors and memantine are the only medications approved for this purpose, and studies have found that donepezil, galantamine, and memantine also seem to exert some modest benefit on existing behavioral symptoms. These drugs generally are well tolerated, too, he added.

Prevention also can come in the form of a general physical and psychiatric health assessment. “Just because a person has dementia doesn’t mean there can’t be other psychiatric or physical conditions going on as well. For example, about 20% of dementia patients have a comorbid depression.” Pain, too, is common in these patients and can cause or exacerbate behavioral problems. Getting a handle on these underlying issues is the first step in building an effective treatment paradigm.

Most behavioral symptoms that occur in dementia patients are nonemergent. Because an emergency behavioral situation, like dangerous aggression, is rare, time is on everyone’s side. After making sure the proper cognition-enhancing medications are on board and pain or underlying illnesses addressed, psychological and behavioral interventions should be next in line.

But as dementia progresses, these lower-order approaches may become less and less effective. Eventually, medical therapy may be necessary. Dr. Tampi shared a treatment algorithm that he and his Veterans Affairs colleagues developed. The algorithm, published in 2011, divides behavioral symptoms by clinical presentation: depressed/anxious, hypomanic/manic, psychotic, and agitation/aggression.

In line with moving from least to highest treatment intensity, Dr. Tampi suggested always starting with low-dose monotherapy. For mood disorders in dementia patients, data support the use of SSRIs. For mania/hypomania, the algorithm recommends carbamazepine or divalproex, or an atypical antipsychotic. He also uses atypical antipsychotics for patients with psychotic symptoms. For those who exhibit agitation or aggression, the algorithm suggests carbamazepine, SSRIs, divalproex, or trazodone.

“If monotherapy doesn’t work, some drug combinations – like an SSRI with an antipsychotic or a mood stabilizer, do make sense and are effective, but they must be used judiciously,” Dr. Tampi said. Any behavioral or psychological interventions already in place should be continued, and even reinforced, when medical therapy comes on board, he added.

Emergent behaviors, or course, need quick solutions. However, Dr. Tampi still incorporates a judicious approach to handling them. “We always use oral medications at first. We only go with intramuscular if there’s no response or if the patient refuses.”

He recommended starting with risperidone, aripiprazole, quetiapine, or olanzapine, with a second dose 30 minutes to 1 hour later if needed. “You may need one or two repeats before the patient calms down, though,” he said.

If the agitation or aggression is very severe, or if the patient refuses oral medications, Dr. Tampi said injections are in order. His preferences are aripiprazole 1.875-7.7 mg, olanzapine 2.5-5 mg, or haloperidol 0.5-2 mg.

“Again, you can repeat the dose in 30 minutes to 1 hour if needed, and you might need to repeat once or twice before the patient calms down.”

He had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

NEW ORLEANS–An individualized, step-by-step plan is the best way to treat psychiatric and behavioral problems that might arise in patients with dementia.

But, according to Dr. Rajesh R. Tampi, “There’s no one silver bullet” for these symptoms, which can make things very hard not only on the patient but [also on] the family and caregiving staff.

No medications are approved for treating these symptoms in dementia patients, Dr. Tampi said at the annual meeting of the American Association for Geriatric Psychiatry. Furthermore, some of the most commonly used medications simply aren’t effective, and those that are often come at the price of side effects that prompt discontinuation.

Benzodiazepines, which are still quite often employed, are usually much more harmful than useful, he said. “The data for using benzodiazepines for behavioral problems in dementia simply do not exist. And given the new data we have on worsening of cognition, and a fivefold increase in the risk of falls, I do not think they are useful. I use them only for alcohol- or benzodiazepine-withdrawal or as an intramuscular injection to sedate but never for continuing management.”

Prevention is always the best medicine, said Dr. Tampi, chief of geriatric psychiatry at MetroHealth, Cleveland. Behavioral and psychiatric symptoms often arise as dementia worsens, so delaying disease progression may delay symptom onset as well. Cholinesterase inhibitors and memantine are the only medications approved for this purpose, and studies have found that donepezil, galantamine, and memantine also seem to exert some modest benefit on existing behavioral symptoms. These drugs generally are well tolerated, too, he added.

Prevention also can come in the form of a general physical and psychiatric health assessment. “Just because a person has dementia doesn’t mean there can’t be other psychiatric or physical conditions going on as well. For example, about 20% of dementia patients have a comorbid depression.” Pain, too, is common in these patients and can cause or exacerbate behavioral problems. Getting a handle on these underlying issues is the first step in building an effective treatment paradigm.

Most behavioral symptoms that occur in dementia patients are nonemergent. Because an emergency behavioral situation, like dangerous aggression, is rare, time is on everyone’s side. After making sure the proper cognition-enhancing medications are on board and pain or underlying illnesses addressed, psychological and behavioral interventions should be next in line.

But as dementia progresses, these lower-order approaches may become less and less effective. Eventually, medical therapy may be necessary. Dr. Tampi shared a treatment algorithm that he and his Veterans Affairs colleagues developed. The algorithm, published in 2011, divides behavioral symptoms by clinical presentation: depressed/anxious, hypomanic/manic, psychotic, and agitation/aggression.

In line with moving from least to highest treatment intensity, Dr. Tampi suggested always starting with low-dose monotherapy. For mood disorders in dementia patients, data support the use of SSRIs. For mania/hypomania, the algorithm recommends carbamazepine or divalproex, or an atypical antipsychotic. He also uses atypical antipsychotics for patients with psychotic symptoms. For those who exhibit agitation or aggression, the algorithm suggests carbamazepine, SSRIs, divalproex, or trazodone.

“If monotherapy doesn’t work, some drug combinations – like an SSRI with an antipsychotic or a mood stabilizer, do make sense and are effective, but they must be used judiciously,” Dr. Tampi said. Any behavioral or psychological interventions already in place should be continued, and even reinforced, when medical therapy comes on board, he added.

Emergent behaviors, or course, need quick solutions. However, Dr. Tampi still incorporates a judicious approach to handling them. “We always use oral medications at first. We only go with intramuscular if there’s no response or if the patient refuses.”

He recommended starting with risperidone, aripiprazole, quetiapine, or olanzapine, with a second dose 30 minutes to 1 hour later if needed. “You may need one or two repeats before the patient calms down, though,” he said.

If the agitation or aggression is very severe, or if the patient refuses oral medications, Dr. Tampi said injections are in order. His preferences are aripiprazole 1.875-7.7 mg, olanzapine 2.5-5 mg, or haloperidol 0.5-2 mg.

“Again, you can repeat the dose in 30 minutes to 1 hour if needed, and you might need to repeat once or twice before the patient calms down.”

He had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

NEW ORLEANS–An individualized, step-by-step plan is the best way to treat psychiatric and behavioral problems that might arise in patients with dementia.

But, according to Dr. Rajesh R. Tampi, “There’s no one silver bullet” for these symptoms, which can make things very hard not only on the patient but [also on] the family and caregiving staff.

No medications are approved for treating these symptoms in dementia patients, Dr. Tampi said at the annual meeting of the American Association for Geriatric Psychiatry. Furthermore, some of the most commonly used medications simply aren’t effective, and those that are often come at the price of side effects that prompt discontinuation.

Benzodiazepines, which are still quite often employed, are usually much more harmful than useful, he said. “The data for using benzodiazepines for behavioral problems in dementia simply do not exist. And given the new data we have on worsening of cognition, and a fivefold increase in the risk of falls, I do not think they are useful. I use them only for alcohol- or benzodiazepine-withdrawal or as an intramuscular injection to sedate but never for continuing management.”

Prevention is always the best medicine, said Dr. Tampi, chief of geriatric psychiatry at MetroHealth, Cleveland. Behavioral and psychiatric symptoms often arise as dementia worsens, so delaying disease progression may delay symptom onset as well. Cholinesterase inhibitors and memantine are the only medications approved for this purpose, and studies have found that donepezil, galantamine, and memantine also seem to exert some modest benefit on existing behavioral symptoms. These drugs generally are well tolerated, too, he added.

Prevention also can come in the form of a general physical and psychiatric health assessment. “Just because a person has dementia doesn’t mean there can’t be other psychiatric or physical conditions going on as well. For example, about 20% of dementia patients have a comorbid depression.” Pain, too, is common in these patients and can cause or exacerbate behavioral problems. Getting a handle on these underlying issues is the first step in building an effective treatment paradigm.

Most behavioral symptoms that occur in dementia patients are nonemergent. Because an emergency behavioral situation, like dangerous aggression, is rare, time is on everyone’s side. After making sure the proper cognition-enhancing medications are on board and pain or underlying illnesses addressed, psychological and behavioral interventions should be next in line.

But as dementia progresses, these lower-order approaches may become less and less effective. Eventually, medical therapy may be necessary. Dr. Tampi shared a treatment algorithm that he and his Veterans Affairs colleagues developed. The algorithm, published in 2011, divides behavioral symptoms by clinical presentation: depressed/anxious, hypomanic/manic, psychotic, and agitation/aggression.

In line with moving from least to highest treatment intensity, Dr. Tampi suggested always starting with low-dose monotherapy. For mood disorders in dementia patients, data support the use of SSRIs. For mania/hypomania, the algorithm recommends carbamazepine or divalproex, or an atypical antipsychotic. He also uses atypical antipsychotics for patients with psychotic symptoms. For those who exhibit agitation or aggression, the algorithm suggests carbamazepine, SSRIs, divalproex, or trazodone.

“If monotherapy doesn’t work, some drug combinations – like an SSRI with an antipsychotic or a mood stabilizer, do make sense and are effective, but they must be used judiciously,” Dr. Tampi said. Any behavioral or psychological interventions already in place should be continued, and even reinforced, when medical therapy comes on board, he added.

Emergent behaviors, or course, need quick solutions. However, Dr. Tampi still incorporates a judicious approach to handling them. “We always use oral medications at first. We only go with intramuscular if there’s no response or if the patient refuses.”

He recommended starting with risperidone, aripiprazole, quetiapine, or olanzapine, with a second dose 30 minutes to 1 hour later if needed. “You may need one or two repeats before the patient calms down, though,” he said.

If the agitation or aggression is very severe, or if the patient refuses oral medications, Dr. Tampi said injections are in order. His preferences are aripiprazole 1.875-7.7 mg, olanzapine 2.5-5 mg, or haloperidol 0.5-2 mg.

“Again, you can repeat the dose in 30 minutes to 1 hour if needed, and you might need to repeat once or twice before the patient calms down.”

He had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

NEW ORLEANS – Both problem-solving and lifestyle interventions significantly reduced the incidence of major depression among black and white community-living elders who had some mild symptoms of the disorder.

By 2 years, both interventions conferred a 4-point decrease in the Beck Depression Inventory (BDI) score, with whites and blacks experiencing the same benefit, Dr. Charles F. Reynolds III said at the annual meeting of the American Association for Geriatric Psychiatry.

“Perhaps not surprisingly, improving scores in [problem solving] predicted lower depression scores, and falling depression scores predicted better scores in [problem solving],” said Dr. Reynolds, the UPMC Endowed Professor in Geriatric Psychiatry at the University of Pittsburgh. “This suggests a bidirectional effect. Better problem-solving leads to improvement in depression, and improvement in depression leads to better problem solving.”

Dr. Reynolds and his colleagues conducted a 2-year study of a problem-solving intervention and a dietary intervention in a cohort of elderly subjects with subsyndromal depressive symptoms. The primary endpoint was a three-way comparison: problem-solving vs. dietary intervention overall, black vs. white response overall, and overall response vs. response in comparable groups undergoing usual care.

Their study comprised 154 white participants and 90 black participants. “Getting black participants into clinical trials has always been challenging for us,” he said. “Typically, we get about 10%-12% rates. This cohort approached 40%, which I think reflected several things,” the most crucial of which was recruitment technique.

“We identified ‘community champions’ – people who had leadership positions in the black community, especially in the religious communities. They gave us the imprimatur of their approval to participate. We also recruited through churches and community centers, and saw patients there. We didn’t ask them to come into the lab,” said Dr. Reynolds, also professor of neurology, behavioral and community health sciences, and clinical and translational science at the university.

All subjects also received financial compensation for being in the study – a total of $450 each over the full 2-year period.

The subjects were a mean of 65 years old. Scores on the Hamilton Depression Rating Scale (HAM-D) and the BDI indicated mild depression in each group.

The black participants had more traditional risk factors for depression. Fewer were married (25% vs. 88% of whites), and fewer were employed (27% vs. 71%). Median household income was $31,000 vs. $58,000. Blacks had fewer years of education as well (13 vs. 15). They also had poorer overall health and more medical comorbidities. About 60% of each group had a body mass index greater than 30 kg/m2 – the prime factor that motivated choosing diet as the comparator therapy.

Problem-solving therapy was talk based, with the subject and the clinician collaborating to identify problems and focus on solving them with a structured approach. It also included assessments of the subjects’ general approach to problems. Dietary therapy focused on improving healthful eating through better shopping, cooking, and eating. The cumulative “face time” between subjects and clinicians was just 6 hours over the 2 years – a “remarkably short period,” Dr. Reynolds noted, with short booster sessions conducted every 6 months.

At the end of 2 years, both interventions conferred a 13% lower risk of major depression, corresponding to an overall incidence of about 8%. Blacks and whites achieved comparable results. Archival data suggest a 20%-25% rate of major depression when elderly adults with subsyndromal symptoms receive usual care.

Both groups achieved a 4-point decrease in the BDI score, which was evidenced by 6 months and sustained over the duration of the study.

Dr. Reynolds cautioned against overinterpreting the results, however.

“In the absence of a direct comparator of usual care, we need to consider these results promising but still preliminary.”

He said he had no relevant financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

NEW ORLEANS – Both problem-solving and lifestyle interventions significantly reduced the incidence of major depression among black and white community-living elders who had some mild symptoms of the disorder.

By 2 years, both interventions conferred a 4-point decrease in the Beck Depression Inventory (BDI) score, with whites and blacks experiencing the same benefit, Dr. Charles F. Reynolds III said at the annual meeting of the American Association for Geriatric Psychiatry.

“Perhaps not surprisingly, improving scores in [problem solving] predicted lower depression scores, and falling depression scores predicted better scores in [problem solving],” said Dr. Reynolds, the UPMC Endowed Professor in Geriatric Psychiatry at the University of Pittsburgh. “This suggests a bidirectional effect. Better problem-solving leads to improvement in depression, and improvement in depression leads to better problem solving.”

Dr. Reynolds and his colleagues conducted a 2-year study of a problem-solving intervention and a dietary intervention in a cohort of elderly subjects with subsyndromal depressive symptoms. The primary endpoint was a three-way comparison: problem-solving vs. dietary intervention overall, black vs. white response overall, and overall response vs. response in comparable groups undergoing usual care.

Their study comprised 154 white participants and 90 black participants. “Getting black participants into clinical trials has always been challenging for us,” he said. “Typically, we get about 10%-12% rates. This cohort approached 40%, which I think reflected several things,” the most crucial of which was recruitment technique.

“We identified ‘community champions’ – people who had leadership positions in the black community, especially in the religious communities. They gave us the imprimatur of their approval to participate. We also recruited through churches and community centers, and saw patients there. We didn’t ask them to come into the lab,” said Dr. Reynolds, also professor of neurology, behavioral and community health sciences, and clinical and translational science at the university.

All subjects also received financial compensation for being in the study – a total of $450 each over the full 2-year period.

The subjects were a mean of 65 years old. Scores on the Hamilton Depression Rating Scale (HAM-D) and the BDI indicated mild depression in each group.

The black participants had more traditional risk factors for depression. Fewer were married (25% vs. 88% of whites), and fewer were employed (27% vs. 71%). Median household income was $31,000 vs. $58,000. Blacks had fewer years of education as well (13 vs. 15). They also had poorer overall health and more medical comorbidities. About 60% of each group had a body mass index greater than 30 kg/m2 – the prime factor that motivated choosing diet as the comparator therapy.

Problem-solving therapy was talk based, with the subject and the clinician collaborating to identify problems and focus on solving them with a structured approach. It also included assessments of the subjects’ general approach to problems. Dietary therapy focused on improving healthful eating through better shopping, cooking, and eating. The cumulative “face time” between subjects and clinicians was just 6 hours over the 2 years – a “remarkably short period,” Dr. Reynolds noted, with short booster sessions conducted every 6 months.

At the end of 2 years, both interventions conferred a 13% lower risk of major depression, corresponding to an overall incidence of about 8%. Blacks and whites achieved comparable results. Archival data suggest a 20%-25% rate of major depression when elderly adults with subsyndromal symptoms receive usual care.

Both groups achieved a 4-point decrease in the BDI score, which was evidenced by 6 months and sustained over the duration of the study.

Dr. Reynolds cautioned against overinterpreting the results, however.

“In the absence of a direct comparator of usual care, we need to consider these results promising but still preliminary.”

He said he had no relevant financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

NEW ORLEANS – Both problem-solving and lifestyle interventions significantly reduced the incidence of major depression among black and white community-living elders who had some mild symptoms of the disorder.

By 2 years, both interventions conferred a 4-point decrease in the Beck Depression Inventory (BDI) score, with whites and blacks experiencing the same benefit, Dr. Charles F. Reynolds III said at the annual meeting of the American Association for Geriatric Psychiatry.

“Perhaps not surprisingly, improving scores in [problem solving] predicted lower depression scores, and falling depression scores predicted better scores in [problem solving],” said Dr. Reynolds, the UPMC Endowed Professor in Geriatric Psychiatry at the University of Pittsburgh. “This suggests a bidirectional effect. Better problem-solving leads to improvement in depression, and improvement in depression leads to better problem solving.”

Dr. Reynolds and his colleagues conducted a 2-year study of a problem-solving intervention and a dietary intervention in a cohort of elderly subjects with subsyndromal depressive symptoms. The primary endpoint was a three-way comparison: problem-solving vs. dietary intervention overall, black vs. white response overall, and overall response vs. response in comparable groups undergoing usual care.

Their study comprised 154 white participants and 90 black participants. “Getting black participants into clinical trials has always been challenging for us,” he said. “Typically, we get about 10%-12% rates. This cohort approached 40%, which I think reflected several things,” the most crucial of which was recruitment technique.

“We identified ‘community champions’ – people who had leadership positions in the black community, especially in the religious communities. They gave us the imprimatur of their approval to participate. We also recruited through churches and community centers, and saw patients there. We didn’t ask them to come into the lab,” said Dr. Reynolds, also professor of neurology, behavioral and community health sciences, and clinical and translational science at the university.

All subjects also received financial compensation for being in the study – a total of $450 each over the full 2-year period.

The subjects were a mean of 65 years old. Scores on the Hamilton Depression Rating Scale (HAM-D) and the BDI indicated mild depression in each group.

The black participants had more traditional risk factors for depression. Fewer were married (25% vs. 88% of whites), and fewer were employed (27% vs. 71%). Median household income was $31,000 vs. $58,000. Blacks had fewer years of education as well (13 vs. 15). They also had poorer overall health and more medical comorbidities. About 60% of each group had a body mass index greater than 30 kg/m2 – the prime factor that motivated choosing diet as the comparator therapy.

Problem-solving therapy was talk based, with the subject and the clinician collaborating to identify problems and focus on solving them with a structured approach. It also included assessments of the subjects’ general approach to problems. Dietary therapy focused on improving healthful eating through better shopping, cooking, and eating. The cumulative “face time” between subjects and clinicians was just 6 hours over the 2 years – a “remarkably short period,” Dr. Reynolds noted, with short booster sessions conducted every 6 months.

At the end of 2 years, both interventions conferred a 13% lower risk of major depression, corresponding to an overall incidence of about 8%. Blacks and whites achieved comparable results. Archival data suggest a 20%-25% rate of major depression when elderly adults with subsyndromal symptoms receive usual care.

Both groups achieved a 4-point decrease in the BDI score, which was evidenced by 6 months and sustained over the duration of the study.

Dr. Reynolds cautioned against overinterpreting the results, however.

“In the absence of a direct comparator of usual care, we need to consider these results promising but still preliminary.”

He said he had no relevant financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @alz_gal