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 Namenda can improve some symptoms in DLB but not PDD 
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Post Namenda can improve some symptoms in DLB but not PDD
In this clinical trial of the medication Namenda, "patients (>/=50 years of age) with mild to moderate PDD or DLB were recruited from 30 specialist centres in Austria, France, Germany, the UK, Greece, Italy, Spain, and Turkey. They were randomly assigned to placebo or memantine (20 mg per day)... Patients and all physicians who had contact with them were masked to treatment assignment."

Interestingly, the researchers found that Namenda worked in patients with a clinical diagnosis of DLB but not in those with a clinical diagnosis of PDD, when two inventories were looked at:

* "At week 24, patients with DLB who received memantine showed greater improvement according to Alzheimer's disease cooperative study (ADCS)-clinical global impression of change scores than did those who received placebo. No significant differences were noted between the two treatments in patients with PDD or in the total population."

* "Neuropsychiatric-inventory scores showed significantly greater improvement in the memantine group than in the placebo group in patients with DLB, but not in those with PDD or in the total patient population."

"In most of the cognitive test scores, ADCS-activities of daily living, and Zarit caregiver burden scores, there were no significant differences between the two treatment groups in any of the study populations."

The authors conclude: "Memantine seems to improve global clinical status and behavioural symptoms of patients with mild to moderate DLB, and might be an option for treatment of these patients."

Robin



Lancet Neurology. 2010 Aug 20. [Epub ahead of print]

Memantine for patients with Parkinson's disease dementia or dementia with Lewy bodies: a randomised, double-blind, placebo-controlled trial.

Emre M, Tsolaki M, Bonuccelli U, Destée A, Tolosa E, Kutzelnigg A, Ceballos-Baumann A, Zdravkovic S, Bladström A, Jones R; on behalf of the 11018 Study Investigators.
Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey.

Abstract
BACKGROUND: Previous studies have suggested that patients with Lewy-body-related dementias might benefit from treatment with the N-methyl D-aspartate receptor antagonist memantine, but further data are needed. Therefore, the efficacy and safety of memantine were investigated in patients with mild to moderate Parkinson's disease dementia (PDD) or dementia with Lewy bodies (DLB).

METHODS: Patients (>/=50 years of age) with mild to moderate PDD or DLB were recruited from 30 specialist centres in Austria, France, Germany, the UK, Greece, Italy, Spain, and Turkey. They were randomly assigned to placebo or memantine (20 mg per day) according to a computer-generated list. Patients and all physicians who had contact with them were masked to treatment assignment. No primary endpoint was defined. Safety analyses were done for all patients who took at least one dose of memantine or placebo, and efficacy analyses were done for all patients who had at least one valid postbaseline assessment. This trial is registered with ClinicalTrials.gov, number NCT00855686.

FINDINGS: Of the 199 patients randomly assigned to treatment, 34 with DLB and 62 with PDD were given memantine, and 41 with DLB and 58 with PDD were given placebo. 159 (80%) patients completed the study: 80 in the memantine group and 79 in the placebo group.

93 patients treated with memantine and 97 patients treated with placebo were included in the efficacy analysis. At week 24, patients with DLB who received memantine showed greater improvement according to Alzheimer's disease cooperative study (ADCS)-clinical global impression of change scores than did those who received placebo (mean change from baseline 3.3 vs 3.9, respectively, difference -0.6 [95% CI -1.2 to -0.1]; p=0.023). No significant differences were noted between the two treatments in patients with PDD (3.6 with memantine vs 3.8 with placebo, -0.1 [-0.6 to 0.3]; p=0.576) or in the total population (3.5 with memantine vs 3.8 with placebo, -0.3 [-0.7 to 0.1]; p=0.120).

Neuropsychiatric-inventory scores showed significantly greater improvement in the memantine group than in the placebo group (-4.3 vs 1.7, respectively, -5.9 [-11.6 to -0.2]; p=0.041) in patients with DLB, but not in those with PDD (-1.6 vs -0.1, respectively, -1.4 [-5.9 to 3.0]; p=0.522) or in the total patient population (-2.6 vs 0.4, respectively, -2.9 [-6.3 to 0.5]; p=0.092).

In most of the cognitive test scores, ADCS-activities of daily living, and Zarit caregiver burden scores, there were no significant differences between the two treatment groups in any of the study populations.

The incidence of adverse events and number of discontinuations due to adverse events were similar in the two groups. The most common serious adverse events were stroke (n=3 in memantine group), falls (n=2 in memantine group; n=1 in placebo group), and worsening of dementia (n=2 in memantine group).

INTERPRETATION: Memantine seems to improve global clinical status and behavioural symptoms of patients with mild to moderate DLB, and might be an option for treatment of these patients.

FUNDING: Lundbeck.

PMID: 20729148


Tue Aug 24, 2010 4:21 pm
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Post Re: Namenda can improve some symptoms in DLB but not PDD
Dr. Laura Marsh, a psychiatrist at Baylor in Houston and a member of the LBDA Scientific Advisory Board, wrote a comment on this Namenda study; the comment was published in the same issue of "The Lancet Neurology" as the study. Buried in the comment are several interesting points:

* She uses the term "motion-emotion conundrum" to describe the situation in PDD and DLB where medication given to help with motor problems confounds the emotional or psychiatric problems, and vice versa.

* Since those with PDD and DLB are in this "motion-emotion conundrum," it's very challenging to design and implement clinical trials involving medications.

* In this Namenda study, some patients were taking benzodiazepines (such as Ativan and Xanax) and dopamine agonists (such as Mirapex and Requip). In "individual patients with PDD or DLB, eliminating benzodiazepines and dopamine agonists and addressing other causes of delirium often improves functional status." So maybe these patients would've done better in the study if they had been off these medications.

* Dr. Marsh wonders if mood disturbances in PDD and DLB are being under-treated.

* Dr. Marsh also wonders if Namenda "has a beneficial effect on mood symptoms, and this benefit could contribute to improved measures of global function and cognition."


Wed Oct 20, 2010 1:17 am
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Post Re: Namenda can improve some symptoms in DLB but not PDD
Dr. Alexander Troster, a neuropsychologist, mentioned this study during last week's webinar on Cognitive Issues in Parkinson's Disease. So perhaps Namenda shouldn't be prescribed for those with PDD?

Dr. Troster said:

Treating Cognitive Dysfunction in Parkinson's Disease: Cholinesterase Inhibitors and Other Agents
* Recent study of Namenda, a glutamate NMDA antagonist. It was found to be more helpful in those with DLB than in those with PDD.


Sat Mar 26, 2011 5:40 pm
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Post Re: Namenda can improve some symptoms in DLB but not PDD
There really are some serious trade-offs when medicating these disorders. I'm glad to see they are taking a closer look at mood/behavior issues. Sometimes enhanced mobility is not worth resultant aggression unless it can be properly treated. Interesting post, Robin. Thank you.

_________________
Pat [68] married to Derek [84] for 38 years; husband dx PDD/LBD 2005, probably began 2002 or earlier; late stage and in a SNF as of January 2011. Hospitalized 11/2/2013 and discharged to home Hospice. Passed away at home on 11/9/2013.


Sat Mar 26, 2011 5:54 pm
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Post Re: Namenda can improve some symptoms in DLB but not PDD
In fact, to add an example, Derek's new neuro wanted his Stalevo increased back to where it was a few months ago. It was reduced because of combativeness toward the SNF staff. They increased it yesterday and, the first thing I heard this morning when I arrived was, "Your husband is really on the warpath this morning!" :cry:

_________________
Pat [68] married to Derek [84] for 38 years; husband dx PDD/LBD 2005, probably began 2002 or earlier; late stage and in a SNF as of January 2011. Hospitalized 11/2/2013 and discharged to home Hospice. Passed away at home on 11/9/2013.


Sat Mar 26, 2011 5:57 pm
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Post Re: Namenda can improve some symptoms in DLB but not PDD
Odd that he would've wanted to increase it given the presumption that the reduction in Stalevo led to better behavior.


Sat Mar 26, 2011 11:28 pm
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Post Re: Namenda can improve some symptoms in DLB but not PDD
He's a new neuro for Derek and we only had time to cover some of the myriad issues at hand at the first visit. He was concerned about the extreme bradykinesia. It's a trial--we'll have to see how it works out. Maybe he is not convinced it was the cause of the combativeness.

_________________
Pat [68] married to Derek [84] for 38 years; husband dx PDD/LBD 2005, probably began 2002 or earlier; late stage and in a SNF as of January 2011. Hospitalized 11/2/2013 and discharged to home Hospice. Passed away at home on 11/9/2013.


Sat Mar 26, 2011 11:37 pm
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Post Re: Namenda can improve some symptoms in DLB but not PDD
This was the second time I tried to eleminate the night dose of Namenda, 10mg, and after night 4 he wandered around in a "fog like" state and was getting mean. This is also what happened the first time so I'm convinced that the Namenda is helping.
Gerry

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Gerry 67, cared for Frank 71, married 49 yrs; dx 2004, passed away October 26, 2011.


Sun Mar 27, 2011 7:23 am
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