Table 2.
Completed double-blind, placebo-controlled trials assessing ketamine and other putative rapid-acting antidepressants
Drug | Study design | Drug administration regimen | Placebo | N | Patient condition | Primary outcome | Results | Ref |
---|---|---|---|---|---|---|---|---|
Ketamine | Double-blind, crossover | Single 0.5 mg/kg, 40-min intravenous infusion | Saline | 9 | Major and bipolar depressed patients | HDRS |
|
[20] |
Double-blind, crossover | Single 0.5 mg/kg, 40-min intravenous infusion | Saline | 18 | Treatment-resistant depressed patients | HDRS |
|
[21] | |
Double-blind, crossover (augmentation to mood stabilizer) | Maintained lithium or valproate therapy + Single 0.5 mg/kg, 40-min intravenous ketamine infusion | Saline | 18 | Treatment-resistant bipolar depressed patients | MADRS |
|
[37] | |
Double-blind, crossover (augmentation to mood stabilizer) | Maintained lithium or valproate therapy + Single 0.5 mg/kg, 40-min intravenous ketamine infusion | Saline | 15 | Treatment-resistant bipolar depressed patients | MADRS |
|
[38] | |
Double-blind, parallel arm | Single 0.5 mg/kg, 40-min intravenous infusion | Midazolam | 73 | Treatment-resistant depressed patients | MADRS |
|
[36] | |
Double-blind, crossover | Single 0.54 mg/kg, 30-min intravenous infusion | Saline | 27 | Major depressed patients | MADRS |
|
[358] | |
Double-blind, crossover | Single 50 mg intranasal administration | Saline | 20 | Major depressed patients | MADRS |
|
[24] | |
Double-blind, parallel arm (augmentation to SSRIs) | Newly 4-week escitalopram treatment + Single 0.5 mg/kg, 40-min intravenous ketamine infusion | Saline | 30 | Major depressed patients | MADRS |
|
[359] | |
Double-blind | 0.5 mg/kg, 40-min intravenous infusion 2–3 times a week over a 15-day period | Saline | 67 | Treatment-resistant depressed patients | MADRS |
|
[360] | |
(S)-ketamine | Double-blind, parallel arm | Single 0.2 or 0.4 mg/kg, 40-min intravenous infusion | Saline | 29 | Treatment-resistant depressed patients | MADRS |
|
[35] |
Memantine | Double-blind, parallel arm | Starting dose of 5 mg/day (capsules) up to a maximum of 20 mg/day for a total period of 8 weeks | Saline | 26 | Major depressed patients | MADRS |
|
[110] |
Double-blind | One capsule daily; dosing titration: week 1, 5 mg/day; week 2, 10 mg/day; weeks 3–8, 20 mg/day | Saline | 117 | Major depressed patients | PANSS |
|
[361] | |
Double-blind, (augmentation to traditional antidepressant) | Flexible dose 5–20 mg/day (capsules); target dose of 20 mg/day; total augmentation period: 8 weeks | Saline | 31 | Major depressed patients (partial or non-responsive to their antidepressant) | MADRS |
|
[362] | |
AZD6765 (lanicemine) | Double-blind | Single 100 mg, 60-min intravenous infusion | Saline | 34 | Treatment-resistant depressed patients | MADRS |
|
[114] |
Double-blind | 3-week period of 100–150 mg, 60-min intravenous infusions (3 non-consecutive infusions per week) – patients were allowed to be on their prior antidepressant medications | Saline | 152 | Treatment-resistant depressed patients | MADRS |
|
[114] | |
Double-blind, parallel arm | 15 intravenous infusions of 50 or 100 mg lanicemine over a 12-week period | Saline | 240 | Treatment-resistant depressed patients | MADRS |
|
[115] | |
CP-101,606 (taxoprodil) | Double-blind, parallel arm | 40 mg paroxetine + 0.75 mg/kg CP-101,606 intravenous infusion for 1.5 h followed by 0.15 mg/kg/h for 6.5 h | Saline | 30 | Major depressed patients (paroxetine treatment non-responders) | MADRS |
|
[116] |
MK-0657 (CERC-301) | Double-blind, crossover | Oral capsules of 4 mg/day and increased 2 mg/day until reaching 8 mg/day; total administration period - 12 days | Saline | 5 | Treatment-resistant depressed patients | MADRS |
|
[122] |
GLYX-13 (Rapastinel) | Double-blind, parallel arm | Single 1, 5 or 10 mg/kg, 40-min intravenous infusion | Saline | 116 | Major depressed patients | HDRS |
|
[127] |
Scopolamine | Double-blind, crossover | 15-min intravenous infusion of 4 μg/kg scopolamine for 7 sessions (3–4 days no-drug intervals between sessions) | Saline | 20 | Major and bipolar depressed patients | MADRS |
|
[76] |
Double-blind, crossover | 15-min intravenous infusion of 4 μg/kg scopolamine for 3 sessions (3–5 days no-drug intervals between sessions) | Saline | 22 | Major depressed patients | MADRS |
|
[77] | |
Double-blind, crossover | 15-min intravenous infusion of 4 μg/kg scopolamine for 3 sessions (3–5 days no-drug intervals between sessions) | Saline | 5 | Major depressed patients | MADRS |
|
[78] | |
RG1578 (decoglurant) | Double-blind, parallel arm | 6-week treatment with 5, 15 or 30 mg RG1578 | Saline | 310 | Treatment-resistant depressed patients (on SSRI or SNRI during the study) | MADRS |
|
[199] |
Abbreviations: HDRS, Hamilton Depression Rating Scale; MADRS, Montgomery-Asberg Depression Rating Scale; SNRI, serotonin-norepinephrine reuptake inhibitor; SSRI, serotonin-selective reuptake inhibitor