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Memantina para la demencia
Rupert McShanea, Maggie J Westbya, Emmert Roberts, Neda Minakaran, Lon Schneider, Lucy E Farrimond, Nicola Maayan, Jennifer Ware, Jean Debarros | 20 marzo 2019

Topics

Temas

Comparison 1 Memantine versus placebo in patients with Alzheimer disease, Outcome 1 Cognition.
Figuras y tablas -
Analysis 1.1

Comparison 1 Memantine versus placebo in patients with Alzheimer disease, Outcome 1 Cognition.

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Comparison 1 Memantine versus placebo in patients with Alzheimer disease, Outcome 2 Activities of daily living.
Figuras y tablas -
Analysis 1.2

Comparison 1 Memantine versus placebo in patients with Alzheimer disease, Outcome 2 Activities of daily living.

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Comparison 1 Memantine versus placebo in patients with Alzheimer disease, Outcome 3 Global.
Figuras y tablas -
Analysis 1.3

Comparison 1 Memantine versus placebo in patients with Alzheimer disease, Outcome 3 Global.

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Comparison 1 Memantine versus placebo in patients with Alzheimer disease, Outcome 4 Mood and behaviour.
Figuras y tablas -
Analysis 1.4

Comparison 1 Memantine versus placebo in patients with Alzheimer disease, Outcome 4 Mood and behaviour.

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Comparison 1 Memantine versus placebo in patients with Alzheimer disease, Outcome 5 Dropouts by the end of treatment.
Figuras y tablas -
Analysis 1.5

Comparison 1 Memantine versus placebo in patients with Alzheimer disease, Outcome 5 Dropouts by the end of treatment.

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Comparison 1 Memantine versus placebo in patients with Alzheimer disease, Outcome 6 At least one adverse effect.
Figuras y tablas -
Analysis 1.6

Comparison 1 Memantine versus placebo in patients with Alzheimer disease, Outcome 6 At least one adverse effect.

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Comparison 1 Memantine versus placebo in patients with Alzheimer disease, Outcome 7 At least one effect of agitation by the end of the treatment.
Figuras y tablas -
Analysis 1.7

Comparison 1 Memantine versus placebo in patients with Alzheimer disease, Outcome 7 At least one effect of agitation by the end of the treatment.

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Comparison 2 Memantine vs placebo in patients with Alzheimer disease and vascular dementia, Outcome 1 Cognition.
Figuras y tablas -
Analysis 2.1

Comparison 2 Memantine vs placebo in patients with Alzheimer disease and vascular dementia, Outcome 1 Cognition.

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Comparison 2 Memantine vs placebo in patients with Alzheimer disease and vascular dementia, Outcome 2 Activities of daily living.
Figuras y tablas -
Analysis 2.2

Comparison 2 Memantine vs placebo in patients with Alzheimer disease and vascular dementia, Outcome 2 Activities of daily living.

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Comparison 2 Memantine vs placebo in patients with Alzheimer disease and vascular dementia, Outcome 3 Mood and behaviour.
Figuras y tablas -
Analysis 2.3

Comparison 2 Memantine vs placebo in patients with Alzheimer disease and vascular dementia, Outcome 3 Mood and behaviour.

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Comparison 2 Memantine vs placebo in patients with Alzheimer disease and vascular dementia, Outcome 4 Global.
Figuras y tablas -
Analysis 2.4

Comparison 2 Memantine vs placebo in patients with Alzheimer disease and vascular dementia, Outcome 4 Global.

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Comparison 2 Memantine vs placebo in patients with Alzheimer disease and vascular dementia, Outcome 5 CGIC (numbers improved).
Figuras y tablas -
Analysis 2.5

Comparison 2 Memantine vs placebo in patients with Alzheimer disease and vascular dementia, Outcome 5 CGIC (numbers improved).

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Comparison 2 Memantine vs placebo in patients with Alzheimer disease and vascular dementia, Outcome 6 Dropouts by the end of the treatment.
Figuras y tablas -
Analysis 2.6

Comparison 2 Memantine vs placebo in patients with Alzheimer disease and vascular dementia, Outcome 6 Dropouts by the end of the treatment.

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Comparison 2 Memantine vs placebo in patients with Alzheimer disease and vascular dementia, Outcome 7 At least one adverse event.
Figuras y tablas -
Analysis 2.7

Comparison 2 Memantine vs placebo in patients with Alzheimer disease and vascular dementia, Outcome 7 At least one adverse event.

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Comparison 2 Memantine vs placebo in patients with Alzheimer disease and vascular dementia, Outcome 8 At least one adverse event of agitation by end of treatment.
Figuras y tablas -
Analysis 2.8

Comparison 2 Memantine vs placebo in patients with Alzheimer disease and vascular dementia, Outcome 8 At least one adverse event of agitation by end of treatment.

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Comparison 2 Memantine vs placebo in patients with Alzheimer disease and vascular dementia, Outcome 9 At least one advese event of restlessness by the end of treatment.
Figuras y tablas -
Analysis 2.9

Comparison 2 Memantine vs placebo in patients with Alzheimer disease and vascular dementia, Outcome 9 At least one advese event of restlessness by the end of treatment.

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Comparison 3 Memantine vs placebo in vascular dementia, Outcome 1 Cognition.
Figuras y tablas -
Analysis 3.1

Comparison 3 Memantine vs placebo in vascular dementia, Outcome 1 Cognition.

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Comparison 3 Memantine vs placebo in vascular dementia, Outcome 2 Clinical impression of change.
Figuras y tablas -
Analysis 3.2

Comparison 3 Memantine vs placebo in vascular dementia, Outcome 2 Clinical impression of change.

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Comparison 3 Memantine vs placebo in vascular dementia, Outcome 3 Activities of daily living.
Figuras y tablas -
Analysis 3.3

Comparison 3 Memantine vs placebo in vascular dementia, Outcome 3 Activities of daily living.

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Comparison 3 Memantine vs placebo in vascular dementia, Outcome 4 Global scales.
Figuras y tablas -
Analysis 3.4

Comparison 3 Memantine vs placebo in vascular dementia, Outcome 4 Global scales.

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Comparison 3 Memantine vs placebo in vascular dementia, Outcome 5 Dropout by the end of the treatment.
Figuras y tablas -
Analysis 3.5

Comparison 3 Memantine vs placebo in vascular dementia, Outcome 5 Dropout by the end of the treatment.

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Comparison 3 Memantine vs placebo in vascular dementia, Outcome 6 At least one adverse event of agitation by the end of the treatment.
Figuras y tablas -
Analysis 3.6

Comparison 3 Memantine vs placebo in vascular dementia, Outcome 6 At least one adverse event of agitation by the end of the treatment.

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Comparison 3 Memantine vs placebo in vascular dementia, Outcome 7 At least one adverse event of confusion by the end of the treatment.
Figuras y tablas -
Analysis 3.7

Comparison 3 Memantine vs placebo in vascular dementia, Outcome 7 At least one adverse event of confusion by the end of the treatment.

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Comparison 3 Memantine vs placebo in vascular dementia, Outcome 8 At least one event of dizziness by the end of the treatment.
Figuras y tablas -
Analysis 3.8

Comparison 3 Memantine vs placebo in vascular dementia, Outcome 8 At least one event of dizziness by the end of the treatment.

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Comparison 3 Memantine vs placebo in vascular dementia, Outcome 9 At least one adverse event.
Figuras y tablas -
Analysis 3.9

Comparison 3 Memantine vs placebo in vascular dementia, Outcome 9 At least one adverse event.

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Table 1. Baseline characteristics of participants in the included studies

Study

Number randomized

Diagnosis

Severity of disease

Mean age (s.e.)

Mean MMSE (s.e.)

Mean SCAG (s.e.)

Mean ADAS‐Cog (s.e.)

% female

Ditzler 1991

66

AD (6%), VD (79%), MD (15%)

mild to moderate

72.2

63.3

65

Gortelmeyer 1992

88

AD (9%), VD (76%), MD (15%)

mild to moderate

71.5

24.1

64.2

68

MMM300

321

VD

mild to moderate

76.4 (6.7)

16.9 (2.5)

21.0 (9.1)

47

Pantev 1993

60

all dementias

mild to moderately severe

72.4 (5.7)

85.3 (3.8)

75

Reisberg 2000

252

AD

moderately severe to severe

76,1 (8,07)

7,9 (3,64)

67

MMM500

579

VD

mild to moderate

77

48

Winblad 1999

167

AD (48%), VD + MD (52%)

severe

71.6 (5.6)

6.3 (2.7)

58
Figuras y tablas -
Table 1. Baseline characteristics of participants in the included studies
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Comparison 1. Memantine versus placebo in patients with Alzheimer disease

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Cognition Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 Dose 20 mg/day, SIB (Change fom baseline at 28 weeks)

1

247

Mean Difference (IV, Fixed, 95% CI)

6.1 [2.99, 9.21]

2 Activities of daily living Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

2.2 Dose 20 mg/day, ADCS‐ADLsev (change from baseline at 28 weeks)

1

247

Mean Difference (IV, Fixed, 95% CI)

2.1 [0.46, 3.74]

3 Global Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

3.1 Dose 20 mg/day, CIBIC‐Plus (Change from baseline at 28 weeks)

1

236

Mean Difference (IV, Fixed, 95% CI)

‐0.30 [‐0.58, ‐0.02]

4 Mood and behaviour Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

4.1 Dose 20 mg/day, NPI (Change from baseline at 28 weeks)

1

239

Mean Difference (IV, Fixed, 95% CI)

‐3.3 [‐7.33, 0.73]

5 Dropouts by the end of treatment Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5.1 Dose 20 mg/day, time 6 weeks

1

252

Odds Ratio (M‐H, Fixed, 95% CI)

0.60 [0.34, 1.04]

6 At least one adverse effect Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

6.1 Dose 20 mg/day, time 28 weeks

1

252

Odds Ratio (M‐H, Fixed, 95% CI)

0.83 [0.41, 1.66]

7 At least one effect of agitation by the end of the treatment Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

7.1 Dose 20 mg/day, time 28 weeks

1

252

Odds Ratio (M‐H, Fixed, 95% CI)

0.48 [0.27, 0.86]
Figuras y tablas -
Comparison 1. Memantine versus placebo in patients with Alzheimer disease
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Comparison 2. Memantine vs placebo in patients with Alzheimer disease and vascular dementia

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Cognition Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 Dose 30mg/day, SKT (change from baseline at 6 weeks)

1

59

Mean Difference (IV, Fixed, 95% CI)

‐3.04 [‐5.68, ‐0.40]

2 Activities of daily living Show forest plot

3

Std. Mean Difference (IV, Fixed, 95% CI)

Subtotals only

2.1 Dose 30mg/day, (change from baseline at 4‐6 weeks)

2

119

Std. Mean Difference (IV, Fixed, 95% CI)

‐1.36 [‐1.77, ‐0.96]

2.2 Dose 10mg/day, BGP subscore care dependence (change from baseline at 12 weeks)

1

166

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.17 [‐0.47, 0.14]

3 Mood and behaviour Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

3.1 Dose 30mg/day, NOSIE (change from baseline at 4‐6 weeks)

1

60

Mean Difference (IV, Fixed, 95% CI)

23.3 [17.83, 28.77]

4 Global Show forest plot

3

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

4.1 Dose 20mg/day, SCAG (change from baseline at 6 weeks)

1

82

Mean Difference (IV, Fixed, 95% CI)

‐12.3 [‐16.90, ‐7.70]

4.2 Dose 30mg/day, SCAG (change from baseline at 4‐6 weeks)

2

119

Mean Difference (IV, Fixed, 95% CI)

‐10.77 [‐13.46, ‐8.09]

5 CGIC (numbers improved) Show forest plot

3

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5.1 Dose 20mg/day, time 6 weeks

1

82

Odds Ratio (M‐H, Fixed, 95% CI)

3.85 [1.52, 9.75]

5.2 Dose 30mg/day, time 6 weeks

1

59

Odds Ratio (M‐H, Fixed, 95% CI)

5.25 [1.72, 15.98]

5.3 Dose 10mg/day, time 12 weeks

1

166

Odds Ratio (M‐H, Fixed, 95% CI)

3.30 [1.72, 6.33]

6 Dropouts by the end of the treatment Show forest plot

3

305

Odds Ratio (M‐H, Fixed, 95% CI)

0.87 [0.40, 1.89]

6.1 Dose 20 mg/day, time 6 weeks

1

88

Odds Ratio (M‐H, Fixed, 95% CI)

2.0 [0.35, 11.53]

6.2 Dose 30 mg/day, time 6 weeks

1

66

Odds Ratio (M‐H, Fixed, 95% CI)

0.39 [0.07, 2.15]

6.3 Dose 10 mg/day, time 12 weeks

1

151

Odds Ratio (M‐H, Fixed, 95% CI)

0.88 [0.30, 2.55]

7 At least one adverse event Show forest plot

2

248

Odds Ratio (M‐H, Fixed, 95% CI)

1.36 [0.77, 2.38]

7.1 Dose 20 mg/day, time 6 weeks

1

82

Odds Ratio (M‐H, Fixed, 95% CI)

2.00 [0.83, 4.81]

7.2 Dose 10 mg/day, time 12 weeks

1

166

Odds Ratio (M‐H, Fixed, 95% CI)

1.03 [0.49, 2.16]

8 At least one adverse event of agitation by end of treatment Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

8.1 Dose 30 mg/day, time 6 weeks

1

59

Odds Ratio (M‐H, Fixed, 95% CI)

2.7 [0.48, 15.19]

9 At least one advese event of restlessness by the end of treatment Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

9.1 Dose 30 mg/day, time 6 weeks

1

59

Odds Ratio (M‐H, Fixed, 95% CI)

13.5 [2.71, 67.18]
Figuras y tablas -
Comparison 2. Memantine vs placebo in patients with Alzheimer disease and vascular dementia
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Comparison 3. Memantine vs placebo in vascular dementia

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Cognition Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 Dose 20 mg/day, ADAS‐Cog (Change from baseline at 28 weeks)

2

752

Mean Difference (IV, Fixed, 95% CI)

‐2.19 [‐3.16, ‐1.21]

2 Clinical impression of change Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

2.2 Dose 20 mg/day, CIBIC‐plus (Change from baseline at 28 weeks)

1

228

Mean Difference (IV, Fixed, 95% CI)

‐0.29 [‐0.66, 0.08]

3 Activities of daily living Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

3.1 Dose 20mg/day, NOSGER subscale ADL (change from baseline at 28 weeks)

1

188

Mean Difference (IV, Fixed, 95% CI)

0.21 [‐4.65, 5.07]

4 Global scales Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

4.1 Dose 20 mg/day, NOSGER (Change at 28 weeks) in TPP.

2

525

Mean Difference (IV, Fixed, 95% CI)

‐0.92 [‐2.90, 1.05]

4.2 Dose 20 mg/day, GBS (Change at 28 weeks) in the TPP

2

595

Mean Difference (IV, Fixed, 95% CI)

‐1.81 [‐4.21, 0.58]

5 Dropout by the end of the treatment Show forest plot

2

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5.1 Dose 20mg/day, time 28 weeks

2

900

Odds Ratio (M‐H, Fixed, 95% CI)

1.10 [0.80, 1.51]

6 At least one adverse event of agitation by the end of the treatment Show forest plot

2

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

6.1 Dose 20 mg/day, time 28 weeks

2

900

Odds Ratio (M‐H, Fixed, 95% CI)

0.54 [0.31, 0.96]

7 At least one adverse event of confusion by the end of the treatment Show forest plot

2

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

7.1 Dose 20 mg/day, time 28 weeks

2

900

Odds Ratio (M‐H, Fixed, 95% CI)

0.95 [0.57, 1.61]

8 At least one event of dizziness by the end of the treatment Show forest plot

2

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

8.1 Dose 20 mg/day, time 28 weeks

2

900

Odds Ratio (M‐H, Fixed, 95% CI)

1.53 [0.93, 2.51]

9 At least one adverse event Show forest plot

2

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

9.1 Dose 20 mg/day, time 28 weeks

2

900

Odds Ratio (M‐H, Fixed, 95% CI)

1.11 [0.82, 1.51]
Figuras y tablas -
Comparison 3. Memantine vs placebo in vascular dementia
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