Table 4.
Summary of subgroup meta-analyses.
| Outcome Treatment | Ketamine | Esketamine | Subgroup test (p-value) |
|---|---|---|---|
| Response | RR = 3.0096 [1.9599; 4.6220] | RR = 1.3779 [1.0623; 1.7874] | 0.0023 |
| Remission | RR = 3.6999 [2.2772; 6.0112] | RR = 1.4724 [1.1197; 1.9361] | 0.0012 |
| Score | SMD = −1.1140 [−1.4551; −0.7729] | SMD = −1.1932 [−1.7539; −0.6326] | 0.8129 |
| Suicidality | SMD = −0.4323 [−0.7729; −0.0917] | SMD = 0.0450 [−0.4385; 0.5284] | 0.1137 |
| Completion | RR = 1.0088 [0.9553; 1.0652] | RR = 0.9759 [0.9313; 1.0227] | 0.3662 |
| Dropouts | RR = 0.7557 [0.5245; 1.0889] | RR = 1.3616 [0.9129; 2.0307] | 0.0331 |
| Adverse events | RR = 1.0601 [0.4307; 25601] | RR = 3.0168 [1.3412; 6.7856] | 0.0860 |
| Treatment-resistance | Non-TRD | TRD | Subgroup test (p-value) |
| Response | RR = 3.0967 [1.2143; 7.8973] | RR = 1.9265 [1.4637; 2.5358] | 0.3404 |
| Remission | RR = 2.5747 [0.9236; 7.1776] | RR = 2.0454 [1.4754; 2.8356] | 0.6751 |
| Score | SMD = −0.8008 [−1.1184; −0.4831] | SMD = −1.2343 [−1.6159; −0.8526] | 0.0871 |
| Suicidality | SMD = −0.3173 [−0.8435; 0.2090] | SMD = −0.4347 [−0.8777; 0.0083] | 0.7379 |
| Completion | RR = 1.0048 [0.9555; 1.0566] | RR = 0.9887 [0.9578; 1.0205] | 0.5950 |
| Dropouts | RR = 0.9245 [0.5309; 1.6099] | RR = 0.9754 [0.6922; 1.3744] | 0.8722 |
| Adverse events | RR = 4.4286 [0.5467; 35.8730] | RR = 1.7319 [0.9262; 3.2386] | 0.3994 |
| Depression type | MDD only | BD only | Subgroup test (p-value) |
| Response | RR = 1.8658 [1.4505; 2.4000] | RR = 7.9859 [2.3698; 26.9114] | 0.0564 |
| Remission | RR = 1.8233 [1.3733; 2.4208] | RR = 6.1295 [1.7744; 21.1733] | 0.1176 |
| Score | SMD = −1.1906 [−1.5378; −0.8434] | SMD = −0.7111 [−1.2257; −0.1964] | 0.3116 |
| Suicidality | SMD = −0.2988 [−0.6110; 0.0134] | SMD = −1.0438 [−2.5431; 0.4556] | 0.3404 |
| Completion | RR = 0.9921 [0.9652; 1.0197] | RR = 0.9908 [0.7574; 1.2960] | 0.9988 |
| Dropouts | RR = 0.9507 [0.6843; 1.3207] | RR = 1.2615 [0.7435; 2.1402] | 0.6725 |
| Adverse events | RR = 2.2547 [1.1751; 4.3260] | RR = 0.6667 [0.1440; 3.0855] | 0.1515 |
| Trial type | Crossover trial | Parallel trial | Subgroup test (p-value) |
| Response | RR = 7.2920 [3.8053; 13.9737] | RR = 1.5838 [1.2761; 1.9657] | < 0.0001 |
| Remission | RR = 8.1568 [3.5519; 18.7320] | RR = 1.5500 [1.2431; 1.9327] | 0.0002 |
| Score | SMD = −0.6863 [−0.9428; −0.4339] | SMD = −1.3112 [−1.7015; −0.9208] | 0.0088 |
| Suicidality | SMD = −0.7928 [−1.8251; 0.2395] | SMD = −0.2752 [−0.5706; 0.0203] | 0.3447 |
| Completion | RR = 1.0521 [0.8948; 1.2371] | RR = 0.9906 [0.9637; 1.0183] | 0.4723 |
| Dropouts | RR = 1.0468 [0.8013; 1.3675] | RR = 0.9766 [0.6191; 1.5404] | 0.7966 |
| Adverse events | RR = 0.5848 [0.1472; 2.3238] | RR = 2.4527 [1.2603; 4.7731] | 0.0666 |
| Treatment strategy | Monotherapy | Adjunctive | Subgroup test (p-value) |
| Response | RR = 2.5714 [0.5883; 11.2394] | RR = 2.0586 [1.5727; 2.6946] | 0.7712 |
| Remission | RR = 2.8075 [0.7458; 10.5678] | RR = 1.9845 [1.4670; 2.6845] | 0.6170 |
| Score | SMD = −2.0618 [−4.5233; 0.3997] | SMD = −1.0288 [−1.3281; −0.7294] | 0.4142 |
| Suicidality | SMD = −0.1999 [−0.6863; 0.2864] | SMD = −0.4051 [−0.7604; −0.0499] | 0.5043 |
| Completion | RR = 1.1001 [0.9705; 1.2470] | RR = 0.9891 [0.9643; 1.0145] | 0.1031 |
| Dropouts | RR = 0.3923 [0.1199; 1.2830] | RR = 1.0158 [0.7516; 1.3730] | 0.1272 |
| Adverse events | RR = 2.6842 [0.1339; 53.8059] | RR = 1.8429 [0.9993; 3.3985] | 0.8096 |
| Comparator | Placebo | Active | Subgroup test (p-value) |
| Response | RR = 2.2107 [1.6780; 2.9125] | RR = 1.6145 [0.7625; 3.4184] | 0.4408 |
| Remission | RR = 2.0228 [1.5364; 2.6633] | RR = 1.8103 [0.5393; 6.0762] | 0.8609 |
| Score | SMD = −1.0634 [−1.3862; −0.7406] | SMD = −1.4133 [−2.4375; −0.3892] | 0.5230 |
| Suicidality | SMD = −0.3431 [−0.8222; 0.1360] | SMD = −0.4828 [−0.8570; −0.1087] | 0.6524 |
| Completion | RR = 0.9901 [0.9603; 1.0209] | RR = 0.9998 [0.9510; 1.0510] | 0.7457 |
| Dropouts | RR = 0.9989 [0.6997; 1.4259] | RR = 0.9178 [0.6388; 1.3185] | 0.7439 |
| Adverse events | RR = 1.9688 [1.0552; 3.6735] | RR = 1.0035 [0.1135; 8.8691] | 0.5600 |
RR = rate ratio; SMD = standardized mean difference: TRD = treatment-resistant depression; MDD = major depressive disorder (i.e., unipolar depression); BD = bipolar depression.