Table 1.
Study characteristics
| Study | Design | Population | N | Female (%) | Mean age | Formulation | Dose | Scale | Comparator |
|---|---|---|---|---|---|---|---|---|---|
| Berman 2000 (Berman et al., 2000) | Crossover | Non-TRD MDD | 9 | 55.6 | 37.0 | Racemic, monotherapy | 0.5 mg/kg IV, multiple | HDRS | Placebo |
| Kudoh 2002 (Kudoh et al., 2002) | Parallel | Non-TRD | 70 | N/R | 47.6 | Racemic, adjunctive | 1 mg/kg IV, single | HDRS | Placebo |
| Zarate 2006 (Zarate et al., 2006) | Crossover | TRD MDD | 18 | 66.7 | 46.7 | Racemic, monotherapy | 0.5 mg/kg IV, multiple | HDRS | Placebo |
| Diazgranados 2010 (Diazgranados et al., 2010) | Crossover | TRD BD | 9 | 66.7 | 47.9 | Racemic, adjunctive | 0.5 mg/kg IV, multiple | MADRS | Placebo |
| Zarate 2012 (Zarate et al., 2012) | Crossover | TRD BD | 15 | 53.3 | 46.7 | Racemic, adjunctive | 0.5 mg/kg IV, multiple | MADRS | Placebo |
| Sos 2013 (Sos et al., 2013) | Crossover | Non-TRD | 30 | 50.0 | 43.4 | Racemic, adjunctive | 0.5 mg/kg IV, single | MADRS | Placebo |
| Murrough 2013 (Murrough et al., 2013a) | Parallel | TRD MDD | 72 | 51.4 | 44.8 | Racemic, monotherapy | 0.5 mg/kg IV, single | MADRS | Midazolam |
| Lapidus 2014 (Lapidus et al., 2014) | Crossover | TRD MDD | 20 | 25.0 | 48.0 | Esketamine, adjunctive | 50 mg/day IN | MADRS | Placebo |
| Hu 2016 (Hu et al., 2016) | Parallel | TRD MDD | 27 | 63.0 | 38.9 | Racemic, adjunctive | 0.5 mg/kg IV, multiple | MADRS | Placebo |
| Singh 2016a (Singh et al., 2016b) | Parallel | TRD MDD | 67 | 70.6 | 43.0 | Racemic, adjunctive | 0.5 mg/kg IV, multiple | MADRS | Placebo |
| Singh 2016b (Singh et al., 2016a) | Parallel | TRD MDD | 40 | 57.9 | 43.7 | Esketamine, adjunctive | 0.2–0.4 mg/kg IV, single | MADRS | Placebo |
| Li 2016 (Li et al., 2016) | Parallel | TRD MDD | 64 | 75.0 | 46.6 | Racemic, adjunctive | 0.2–0.5 mg/kg IV | HDRS | Placebo |
| Grunebaum 2017 (Grunebaum et al., 2017) | Parallel | Non-TRD BD | 16 | 62.5 | 41.0 | Racemic, adjunctive | 0.5 mg/kg IV, single | HDRS | Midazolam |
| Su 2017 (Su et al., 2017) | Parallel | TRD MDD | 95 | 71.0 | 47.3 | Racemic, adjunctive | 0.2–0.5 mg/kg IV, single | HDRS | Placebo |
| Canuso 2018 (Canuso et al., 2018) | Parallel | Non-TRD | 66 | 65.2 | 35.9 | Esketamine, adjunctive | 84 mg twice/week IN | MADRS | Placebo |
| Grunebaum 2018 (Grunebaum et al., 2018) | Parallel | TRD MDD | 80 | 60.0 | 39.6 | Racemic, adjunctive | 0.5 mg/kg IV, single | HDRS | Midazolam |
| Daly 2018 (Daly et al., 2018) | Parallel | Non-TRD | 133 | 57.0 | 45.4 | Esketamine, adjunctive | 28–84 mg twice/week IN | MADRS | Placebo |
| Fava 2018 (Fava et al., 2018) | Parallel | TRD MDD | 99 | 57.6 | 46.5 | Racemic, adjunctive | 0.1–1 mg/kg IV, single | HDRS | Midazolam |
| Phillips 2019 (Phillips et al., 2019) | Crossover | TRD MDD | 43 | 55.8 | 41.7 | Racemic, adjunctive | 0.5 mg/kg IV, single | MADRS | Midazolam |
| Ionescu 2019 (Ionescu et al., 2019) | Parallel | TRD MDD | 26 | 38.5 | 45.4 | Racemic, adjunctive | 0.5 mg/kg IV, multiple | HDRS | Placebo |
| Popova 2019 (Popova et al., 2019) | Parallel | TRD MDD | 223 | 61.9 | 45.7 | Esketamine, adjunctive | 56–84 mg twice/week IN | MADRS | Placebo |
| Fedgchin 2019 (Fedgchin et al., 2019) | Parallel | TRD MDD | 455 | 71.1 | 46.6 | Esketamine, adjunctive | 56–84 mg twice/week IN | MADRS | Placebo |
| Correia-Melo 2019 (Correia-Melo et al., 2020) | Parallel | TRD MDD | 63 | 60.3 | 47.1 | Esketamine, adjunctive | 0.25 mg/kg IN, single | MADRS | Racemic ketamine (0.5 mg/kg IV) |
| Ochs-Ross 2020 (Ochs-Ross et al., 2020) | Parallel | TRD MDD | 137 | 62.0 | 70.0 | Esketamine, adjunctive | 28– 84 mg twice/week IN | MADRS | Placebo |
IV = intravenous; IN = intranasal; TRD = Treatment-Resistant Depression; MADRS = Montgomery-Åsberg Depression Rating Scale; HDRS = Hamilton Depression Rating Scale