Table 1.
Study reports for meta-analysis of randomized, double-blind, placebo-controlled trial.
| Studies | Number of Trials | Patients | Drugs | Outcomes |
|---|---|---|---|---|
| Kishi et al. 2013 [24] | 8 (n = 406) | Schizophrenia 85.5%, Bipolar disorder 14.5% |
Memantine (3 trials, n = 186), Amantadine (5 trials, n = 220) |
Not significant compared to placebo: overall symptoms (p = 0.31), positive symptoms (p = 0.44), negative symptoms (p = 0.16), and Clinical Global Impression Severity scale (p = 0.56). Memantine was favorable compared to placebo in Mini-Mental State Examination score in schizophrenia (p = 0.002). |
| Matsuda et al. (Kishi’s group) 2013 [26] |
9 (n = 446) | Schizophrenia, Bipolar disorder |
Memantine (4 trials, n = 226), Amantadine (5 trials, n = 220) |
Not significant compared to placebo: overall symptoms (p = 0.08), positive symptoms (p = 0.43), and negative symptoms (p = 0.05). Individually, only memantine adjunctive therapy showed a trend towards superior efficacy of overall symptoms (p = 0.06) and negative symptoms (p = 0.06) compared to placebo. |
| Kishi et al. 2017 [27] |
8 (n = 448) | Schizophrenia | Memantine | Significant compared to placebo: negative symptoms (p = 0.006), Positive and Negative Syndrome Scale general subscale (p = 0.002), and Mini-Mental Status Examination score (p < 0.0001). Not significant compared to placebo: overall (p = 0.06), positive (p = 0.07), and depressive symptoms (p = 0.326). Patient age was associated with memantine-associated amelioration of negative symptoms (slope = 0.171, p = 0.0206). The effect on negative symptoms may be greater in younger adult patients. |
| Zheng et al. 2018 [33] |
8 (n = 452) | Schizophrenia | Memantine | Significant compared to placebo: Positive and Negative Syndrome Scale and Brief Psychiatric Rating Scale negative symptoms (p = 0.009) and Mini-Mental State Examination score (p < 0.00001). Not significant compared to placebo: total, positive and general symptoms (p = 0.06–0.60) and Clinical Global Impression Severity Scale (p = 0.78). There was no significant difference in the discontinuation rate (p = 0.31) and adverse drug reactions between the two groups. |
| Zheng et al. 2019 [34] |
15 (n = 988) | Schizophrenia (9 trials, n = 512), Bipolar disorder (3 trials, n = 319), Major depressive disorder (3 trials, n = 157) |
Memantine | In schizophrenia, significant compared to placebo: total psychopathology (p = 0.01), negative symptoms (p = 0.0003), and Mini-Mental State Examination score (p < 0.0001). Not significant compared to placebo: positive symptoms (p = 0.05) and general psychopathology (p = 0.14) in schizophrenia, depressive (p = 0.37) and manic (p = 0.09) symptoms in bipolar disorder, and depressive symptoms (p = 0.75) in major depressive disorder. |