Six RCTs with 2,312 patients were included in the review.
The results for the intention-to-treat analysis are reported below.
Cognition.
There was a statistically significant effect in favour of memantine measured using the ADAS-COG (random-effects model, SMD -0.21, 95% CI: -0.34, -0.08, p=0.001; 6 studies). Significant heterogeneity was found (p=0.04). This effect was also found by the 2 studies which used the MMSE (fixed-effect model, SMD 0.18, 95% CI: 0.03, 0.34, p=0.02). In moderate to severe AD there was a statistically significant effect in favour of memantine (random-effects model, SMD -0.29, 95% CI: -0.54, -0.03, p=0.03). In mild to moderate AD there was a statistically significant effect in favour of memantine (fixed-effect model, SMD -0.15, 95% CI: -0.26, -0.03, p=0.01).
Clinician's global impression.
There was a statistically significant effect in favour of memantine measured using the CIBIC-Plus (SMD -0.19, 95% CI: -0.27, -0.10, p<0.01). In moderate to severe AD there was a statistically significant effect in favour of memantine (SMD 0.27, 95% CI: -0.39, -0.14, p<0.001). In mild to moderate AD there was a statistically significant effect in favour of memantine (SMD -0.12, 95% CI: -0.23, -0.01, p=0.03). Fixed-effect models were used for all of these analyses.
Activities of daily living.
There was a statistically significant effect in favour of memantine measured using the ADCS-ADL (SMD -0.10, 95% CI: -0.18, -0.01, p=0.02). In moderate to severe AD there was a statistically significant effect in favour of memantine (SMD -0.19, 95% CI: -0.32, -0.06, p=0.003). In mild to moderate AD there was no statistically significant difference between the groups (SMD -0.22, 95% CI: -0.13, 0.09, p=0.72). Fixed-effect models were used for all of these analyses.
Behavioural symptoms.
There was no significant difference between the memantine and placebo groups (random-effects model, SMD -0.09, 95% CI: -0.22, 0.04, p=0.05). Significant heterogeneity was found (p=0.05). In moderate to severe AD there was a statistically significant effect in favour of memantine (fixed-effect model, SMD -0.17, 95% CI: -0.30, -0.04, p=0.01). In mild to moderate AD there was no statistically significant difference between the groups (random-effects model, SMD -0.03, 95% CI: -0.21, 0.16, p=0.79).
Subgroup analyses for trials with and without concomitant ChEI treatment were also reported for all outcomes.
There were no significant differences between the memantine and placebo groups on any outcome related to adverse events, including treatment discontinuations, adverse events, serious adverse events and deaths.