Memantine in Clinical Practice

1
Memantine in Clinical Practice Results of an
Observational Study

• Calabrese P., Essner U. and Förstl H.
• Dementia and Geriatric Cognitive Disorders
  2007 24 111-117

2
Study Design
No. of patients N 1845 Diagnosis moderate to
severe Alzheimers disease (based on ICD-10
criteria) Design Open-label, multicenter,
post-marketing observational study Dose
duration 20 mg memantine/day 6 months Outcome
measures MMSE, NOSGER, EMD (Explorationsmodul
Demenz)
Overall clinical
impression, cognition and activities of daily
living (rated by physician) Safety and
tolerability
Calabrese et al., Dement Geriatr Cogn Disord 2007
3
Baseline Characteristics
Memantine
Gender, female 58.2 Mean age,years (SD)
76.3 ( 8.7) Mean height,cm (SD) 167.1 (
8.1) Mean weight,

kg (SD) 70.3 (
11.5) MMSE score,

mean (SD) 15.4 ( 5.7)
Mean duration of AD,years (SD) 2.4 ( 1.9)
Calabrese et al., Dement Geriatr Cogn Disord 2007
4
Concomitant Diseases and Comedication
Concomitant disease patients
Hypertension 44.5 Heart failure
24.0 Arteriosclerosis 19.7 Other cardiac
diseases 2.6 Diabetes mellitus 17.2 Other 22.4
Comedication patients
Antihypertensive drugs 41.2 Antidiabetic drugs
13.4 Antidepressants 11.3 Neuroleptic drugs 9.3
Calabrese et al., Dement Geriatr Cogn Disord 2007
5
Significant Improvement of Mean MMSE Scores after
3 and 6 Months
OC analysis
Baseline

3 months

6 months
5
10
15
20
25
Mean MMSE score
p lt 0.0001 vs baseline
Calabrese et al., Dement Geriatr Cogn Disord 2007
6
Responder Analysis Stabilization and
Improvement under Memantine
MMSE Score
6 points improvement 3-6 points improvement 1-2
points improvement Stabilization
68.2 of patients showed improvement
5
10
15
20
25
30
35
40
Proportion of patients ()
Calabrese et al., Dement Geriatr Cogn Disord 2007
7
Significant Improvement in All Items of the
NOSGER Score
Mean change from baseline
Memory Instrumental Activities of Daily
Living Activities of Daily Living Mood Social
Behavior Disruptive Behavior
? 3 months ? 6 months
p lt 0.0001 vs baseline for all items at 3 and 6
months
-0.8
-0.2
-0.4
-0.6
-1.0
-1.2
-1.4
-1.6
0
NOSGER score difference
Improvement
Calabrese et al., Dement Geriatr Cogn Disord 2007
8
Significant Improvement in EMD Total Score
(Patient and Caregiver)
Area A cognition Area B everyday behavior and
affectivity Area C disease-related
self-awareness
Area AB Area A Area B Area C
Patient

Area AB Area A Area B Area C
? Baseline ? 6 months
Caregiver
6
9
8
7
5
4
3
1
2
0
10
Mean EMD score
Improvement
p lt 0.0001
Calabrese et al., Dement Geriatr Cogn Disord 2007
9
Overall Clinical Impression Improvement or
Stabilization after 6 Months under Memantine
78.8 of patients improved or stabilized
Improvement Stabilization Deterioration No answer
10
20
30
40
50
Proportion of patients ()
Calabrese et al., Dement Geriatr Cogn Disord 2007
10
Positive Effect of Memantine Treatment on
Cognition and Function after 6 months of treatment
Good/Very Good Moderate Poor
? Cognition ? Daily functioning
40
10
20
30
50
0
Proportion of patients ()
Calabrese et al., Dement Geriatr Cogn Disord 2007
11
Safety and Tolerability
Adverse event patients
Restlessness 0.5 Dizziness 0.4 Pneumonia
0.4 Deterioration of AD 0.4 Confusion 0.3
Cerebrovascular events 0.3 Heart
failure 0.3 Aggression 0.3 Dehydration 0.3 Nausea
0.2 Paranoia 0.2 Agitation 0.2 Urinary tract
infection 0.2
Calabrese et al., Dement Geriatr Cogn Disord 2007
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Summary

• This study demonstrated memantines efficacy and
  safety in a real world patient population over
  six months of treatment
• Significant improvement on the MMSE Score (2.5
  points on average)
• Improvement in memory, activities of daily living
  and behavior as assessed by the NOSGER
• These effects were also visible to the treating
  physician, proven by the global assessments
• This observational study confirms the efficacy of
  memantine already seen in placebo-controlled
  clinical studies
• Memantine showed an excellent safety and
  tolerability profile
• 74.4 patients had concomitant diseases with
  65.4 receiving corresponding comedication
• None of the individual AEs occurred at a higher
  frequency than 0.5
• These findings demonstrate the relevance of
  memantines efficacy in every day practice

Calabrese et al., Dement Geriatr Cogn Disord 2007