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. 2000;2002(2):CD000147.
doi: 10.1002/14651858.CD000147.

Nimodipine for primary degenerative, mixed and vascular dementia

J M López-Arrieta  1 , J Birks
Affiliations

Nimodipine for primary degenerative, mixed and vascular dementia

J M López-Arrieta et al. Cochrane Database Syst Rev. 2000.

Update in

Abstract

Background: Dementia is an age-related condition in which Alzheimer's disease (AD) and cerebrovascular disease account for the bulk of cases. The role played by calcium in regulating brain functions is well known - the calcium ion links membrane excitation to subsequent intracellular enzymatic response. Change in calcium homeostasis is one important effect of aging with repercussions on higher cortical functions. Nimodipine is an isopropyl calcium channel blocker which can easily cross the blood brain barrier. Its primary action is to reduce the number of open channels, thus restricting influx of calcium ions into the cell. The usefulness of nimodipine in patients with Alzheimer's disease and vascular dementia and unspecified dementia is still controversial with mixed results. In spite of the uncertainties about its efficacy in dementia, nimodipine is currently a frequently prescribed drug for cognitive impairment and dementia in several European countries. This review will be conducted in two phases; the current review is based on evidence from published data only. The second phase will be based on individual-patient data analysed centrally and added to this review in due course.

Objectives: To determine the clinical efficacy of nimodipine for the symptoms of dementia, either unclassified or according to the major subtypes - Alzheimer's disease, vascular, or mixed Alzheimer's and vascular dementia.

Search strategy: The Cochrane Dementia Group Register of Clinical Trials was searched using the terms 'nimodipine' and 'isopropyl (2-methoxy-ethyl) 1,4-dihydro-2, 6-dimethyl-4-(3-nitrophenyl)-3, 5-pyridinedicarboxylate'.

Selection criteria: All unconfounded, double-blind, randomised trials in which treatment with nimodipine was administered for more than a day and compared to placebo in patients with dementia, either unclassified or according to the major subtypes - Alzheimer's disease, vascular, or mixed Alzheimer's and vascular dementia.

Data collection and analysis: Data were extracted independently by the reviewers and the odds ratio (95%CI) or the average difference (95%CI) were estimated. Both intention-to-treat and on-treatment results were extracted.

Main results: This review produced no clear results. Many of the data published were not capable of being sensibly pooled. The data were compatible with nimodipine producing improvement, no change or even harm for those with Alzheimer's disease, vascular dementia, or mixed Alzheimer's and vascular dementia. It was not possible to use many of the published results in a combined analysis. For measures of overall clinical improvement, the intention-to-treat analysis, based on one study only, failed to detect any difference between nimodipine and placebo (OR 0.53; 95%CI 0.25 - 1.13). An on-treatment analysis, based on one study only, produced a statistically significant difference in favour of nimodipine (SMD 4.4; 95%CI 3.9 - 5.0). For cognitive function, the effect of nimodipine was statistically significantly different from placebo for the Mini Mental State Examination score (0-30; high =good) (SMD 0.9; 95%CI 0.59 - 1.22) and there was a statistically significant effect in favour of treatment for the Wechsler Memory Scale (SMD 0.47; 95%CI 0.17 - 0.77). These analyses were based only on those who completed the study and not intention-to-treat analyses. There were no results presented in a form suitable for pooling for functional autonomy, behaviour, quality of life dependency (eg institutionalization), effect on carer, death, acceptability of treatment (as measured by withdrawal rate, safety (as measured by the incidence of adverse effects, including side effects, leading to withdrawal).

Reviewer's conclusions: This review provides no convincing evidence that nimodipine is a useful treatment for the symptoms of dementia, either unclassified or according to the major subtypes - Alzheimer's disease, vascular, or mixed Alzheimer's and vascular dementia. (ABSTRACT TRUNCATED)

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Conflict of interest statement

None known.

Figures

1.1
1.1. Analysis
Comparison 1 Nimodipine vs placebo (all types of dementia), Outcome 1 SCAG ‐ change from baseline.
1.2
1.2. Analysis
Comparison 1 Nimodipine vs placebo (all types of dementia), Outcome 2 Cognitive function ‐ change from baseline.
1.3
1.3. Analysis
Comparison 1 Nimodipine vs placebo (all types of dementia), Outcome 3 CGI ‐ Numbers improved compared with baseline.
1.4
1.4. Analysis
Comparison 1 Nimodipine vs placebo (all types of dementia), Outcome 4 Clinical Global Impression ‐ global.
1.5
1.5. Analysis
Comparison 1 Nimodipine vs placebo (all types of dementia), Outcome 5 Clinical Global Impression ‐ Severity of disease.
1.6
1.6. Analysis
Comparison 1 Nimodipine vs placebo (all types of dementia), Outcome 6 Activities of Daily Living.
1.7
1.7. Analysis
Comparison 1 Nimodipine vs placebo (all types of dementia), Outcome 7 Withdrawals before end of treatment.
1.8
1.8. Analysis
Comparison 1 Nimodipine vs placebo (all types of dementia), Outcome 8 Withdrawals before end of treatment due to an adverse event.
1.9
1.9. Analysis
Comparison 1 Nimodipine vs placebo (all types of dementia), Outcome 9 number of patients with at least one adverse event by end of treatment.
1.10
1.10. Analysis
Comparison 1 Nimodipine vs placebo (all types of dementia), Outcome 10 number of patients with at least one serious adverse event before end of treatment.
1.11
1.11. Analysis
Comparison 1 Nimodipine vs placebo (all types of dementia), Outcome 11 number of patients with at least one adverse event of a cerebrovascular problem during treatment.
1.12
1.12. Analysis
Comparison 1 Nimodipine vs placebo (all types of dementia), Outcome 12 number of patients with at least one adverse event of a psychiatricproblem during treatment.
1.13
1.13. Analysis
Comparison 1 Nimodipine vs placebo (all types of dementia), Outcome 13 number of patients with at least one adverse event of a CNS problem during treatment.
1.14
1.14. Analysis
Comparison 1 Nimodipine vs placebo (all types of dementia), Outcome 14 number of patients with at least one adverse event of problems due to circulation.
1.15
1.15. Analysis
Comparison 1 Nimodipine vs placebo (all types of dementia), Outcome 15 number of patients with at least one adverse event due to cardiac problems during treatment.
1.16
1.16. Analysis
Comparison 1 Nimodipine vs placebo (all types of dementia), Outcome 16 number of patients with at least one adverse event of a gastrointestinal problem during treatment.
1.17
1.17. Analysis
Comparison 1 Nimodipine vs placebo (all types of dementia), Outcome 17 number of patients with at least one adverse event of urogenital problems during treatment.
1.18
1.18. Analysis
Comparison 1 Nimodipine vs placebo (all types of dementia), Outcome 18 number of patients with at least one adverse event of a pulmonary problem during treatment.
1.19
1.19. Analysis
Comparison 1 Nimodipine vs placebo (all types of dementia), Outcome 19 number of patients with at least one adverse event (skeletal) during treatment.
1.20
1.20. Analysis
Comparison 1 Nimodipine vs placebo (all types of dementia), Outcome 20 number of patients with at least one adverse event of a skin problem during treatment.
1.21
1.21. Analysis
Comparison 1 Nimodipine vs placebo (all types of dementia), Outcome 21 number of patients with at least one adverse event of a blood problem during treatment.
1.22
1.22. Analysis
Comparison 1 Nimodipine vs placebo (all types of dementia), Outcome 22 number of patients with at least one adverse event of an autonomic problem during treatment.
1.23
1.23. Analysis
Comparison 1 Nimodipine vs placebo (all types of dementia), Outcome 23 Number of deaths before end of treatment.
2.1
2.1. Analysis
Comparison 2 Nimodipine vs placebo (primary degenerative dementia), Outcome 1 SCAG ‐ change from baseline.
2.2
2.2. Analysis
Comparison 2 Nimodipine vs placebo (primary degenerative dementia), Outcome 2 Cognitive function ‐ change from baseline.
2.3
2.3. Analysis
Comparison 2 Nimodipine vs placebo (primary degenerative dementia), Outcome 3 CGI ‐ Numbers improved compared with baseline.
2.4
2.4. Analysis
Comparison 2 Nimodipine vs placebo (primary degenerative dementia), Outcome 4 Clinical Global Impression ‐ global.
2.5
2.5. Analysis
Comparison 2 Nimodipine vs placebo (primary degenerative dementia), Outcome 5 Clinical Global Impression ‐ Severity of disease.
2.6
2.6. Analysis
Comparison 2 Nimodipine vs placebo (primary degenerative dementia), Outcome 6 Activities of Daily Living.
2.7
2.7. Analysis
Comparison 2 Nimodipine vs placebo (primary degenerative dementia), Outcome 7 Withdrawals before end of treatment.
2.8
2.8. Analysis
Comparison 2 Nimodipine vs placebo (primary degenerative dementia), Outcome 8 Withdrawals before end of treatment due to an adverse event.
2.9
2.9. Analysis
Comparison 2 Nimodipine vs placebo (primary degenerative dementia), Outcome 9 number of patients with at least one adverse event by end of treatment.
2.10
2.10. Analysis
Comparison 2 Nimodipine vs placebo (primary degenerative dementia), Outcome 10 number of patients with at least one serious adverse event before end of treatment.
3.1
3.1. Analysis
Comparison 3 Nimodipine vs placebo (vascular dementia), Outcome 1 SCAG ‐ change from baseline.
3.2
3.2. Analysis
Comparison 3 Nimodipine vs placebo (vascular dementia), Outcome 2 Cognitive function ‐ change from baseline.
3.3
3.3. Analysis
Comparison 3 Nimodipine vs placebo (vascular dementia), Outcome 3 CGI ‐ Numbers improved compared with baseline.
3.4
3.4. Analysis
Comparison 3 Nimodipine vs placebo (vascular dementia), Outcome 4 Clinical Global Impression ‐ global.
3.5
3.5. Analysis
Comparison 3 Nimodipine vs placebo (vascular dementia), Outcome 5 Clinical Global Impression ‐ Severity of disease.
3.6
3.6. Analysis
Comparison 3 Nimodipine vs placebo (vascular dementia), Outcome 6 Activities of Daily Living.
3.7
3.7. Analysis
Comparison 3 Nimodipine vs placebo (vascular dementia), Outcome 7 Withdrawals before end of treatment.
3.8
3.8. Analysis
Comparison 3 Nimodipine vs placebo (vascular dementia), Outcome 8 number of patients with at least one adverse event by end of treatment.
3.9
3.9. Analysis
Comparison 3 Nimodipine vs placebo (vascular dementia), Outcome 9 number of patients with at least one serious adverse event before end of treatment.
See this image and copyright information in PMC

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