Tolerability of switching from donepezil to memantine treatment in patients with moderate to severe Alzheimer

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Tolerability of switching from donepezil to
memantine treatment in patients with moderate to
severe Alzheimers disease (AD)

• Waldemar G., Hyvärinen M., Josiassen M. K.,
  KØrner A., Lehto H. and Wetterberg P.
• International Journal of Geriatric Psychiatry
  2008, 23 979-981

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Study Design
No. of patients N 46 (outpatients) Diagnosis Pr
obable Alzheimers disease Design Double-blind,
randomized, placebo-controlled study Age 50
years Severity MMSE 18 Dose duration 20 mg
memantine/day 8 weeks Outcome CGI-S, MMSE,
CGI-C parameters
Safety and tolerability
Waldemar et al., Int J Geriatr Psychiatry 2008
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Study Design
Memantine with stepwise discontinuation of
Donepezil
5 mg/day Donepezil
Memantinetitration W1 to W3
Memantine 20 mg/day W4 to W8
10 mg/day Donepezil
Memantinetitration W1 to W3
Memantine 20 mg/day W4 to W8
Placebo
Memantine with abrupt discontinuation of Donepezil
W2
W4
W6
W8
W0
W-1
Screeningperiod
Baseline
Donepezil/placebo treatment stops
Waldemar et al., Int J Geriatr Psychiatry 2008
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Disposition of Patients
Patients screened N 52
Screen failuresN 5 (10)
Patients randomized N 47
1 withdrawal of consent
MEM (stepwise) N 22
MEM (abrupt) N 24
WithdrewN 1(4) Lack of efficacy
CompletedN 21(96)
CompletedN 22(92)
WithdrewN 2(8) Adverse events
Waldemar et al., Poster presented at EFNS 2005
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Baseline Characteristics
Abrupt Group Stepwise Group N 24 N 22
Mean age,years (SD) 76.5 (?8.4) 79.9
(?5.4) Gender, femaleN () 19 (79) 18
(82) MMSE score,

mean (SD) 13.4 (?2.7) 13.0
(?3.5) CGI-S score,

mean (SD) 5.2 (?0.7) 5.1 (?0.7)
Waldemar et al., Int J Geriatr Psychiatry 2008
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Adverse Events
50 40 30 20 10 0
45.8
31.8
? Memantine (stepwise) ? Memantine (abrupt)
Percentage ()
16.7
7 patients
11 patients
4 patients
0
Total number of patients with AEs
AEs in Week 1

2 Vertigo, 1 Athrosis, 1 Pruritus none judged
related to treatment
Waldemar et al., Int J Geriatr Psychiatry 2008
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Adverse Events
Most frequently reported adverse events
(incidence 5)
MEM (abrupt) MEM (stepwise)
No. of patients N 24 (100) N 22 (100)
Patients with AEs 11 (45.8) 7 (31.8) Accidental
injury 1 (4.2) 3 (13.6)Anxiety 2
(8.3) -Vertigo 2 (8.3) -
Waldemar et al., Int J Geriatr Psychiatry 2008
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Distribution of Patients by CGI Score at
Week 8
74 Improved or No Change Worse
40 30 20 10 0
? Memantine (stepwise) ? Memantine (abrupt)
of patients
much improved
slightly improved
no change
slightly worse
much worse
Waldemar et al., Poster presented at EFNS 2005
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Summary

• Only 3 patients withdrew from the study (1 due to
  lack of efficacy, 2 due to AEs)
• No clinically important differences in AEs
  between the two groups
• No clinically important differences between the
  two groups in the incidence of potentially
  clinically significant vital signs or weight
• After the switch to memantine 74 of the patients
  improved or were stabilized (CGI-C)
• The safety and tolerability of switching AD
  patients from donepezil to memantine was good
  with either switching schedule
• After being switched to memantine the majority of
  the patients either remained stable or improved

Waldemar et al., Int J Geriatr Psychiatry 2008