Cochrane · systematic review · CD011612
Ketamine and other glutamate receptor modulators for depression in adults with unipolar major depressive disorder
Dean, RL, Hurducas, C, Hawton, K, et al. · Cochrane Database of Systematic Reviews · 2021 · Cochrane Library
SoF tableOnly the outcomes this review put in its Summary of Findings table are listed (the Cochrane Handbook caps them at about seven per comparison). Its other analyses are not shown here.
Questions
15
current version
GRADE rated
12
No studies
3
Included studies
NR
No studies 3 · 20%Ungraded 0 · 0%Very low 6 · 40%Low 3 · 20%Moderate 3 · 20%High 0 · 0%
Ungraded means an effect was reported without a GRADE rating; it is not a gap. No studies means the review found nothing to answer the question. The six categories are a display order, not a score.
Questions and results
Current version onlyKetamine compared to placebo for adults with unipolar major depressive disorder
Population: adults (aged 18 years+) with unipolar major depressive disorder
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Efficacy: number of participants who respond to treatment ‐ at 24 hours (Response) Ketamine vs placebo | OR 3.94 [1.54, 10.1] | NR | Very low |
Efficacy: number of participants who achieve remission ‐ at 24 hours (Remission) Ketamine vs placebo | OR 5.6 [1.07, 29.46] | NR | Very low Downgraded: risk of bias, inconsistency |
Depression rating scale score ‐ at 24 hours Ketamine vs placebo | no estimate extracted | NR | Very low |
Acceptability: total dropouts№ of participants: 201(6 RCTs) Ketamine vs placebo | OR 1.25 [0.19, 8.28] | NR | Very low |
Acceptability: dropouts due to adverse effects ‐ not reported Ketamine vs placebo | no estimate extracted | NR | No studies |
Ketamine compared to midazolam for adults with unipolar major depressive disorder
Population: adults (aged 18 years+) with unipolar major depressive disorder
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Efficacy: number of participants who respond to treatment ‐ at 24 hours Ketamine vs midazolam | OR 2.48 [1, 6.18] | NR | Very low Downgraded: risk of bias |
Efficacy: number of participants who achieve remission ‐ at 24 hours Ketamine vs midazolam | OR 2.21 [0.67, 7.32] | NR | Low Downgraded: risk of bias, inconsistency |
Depression rating scale score ‐ at 24 hours Ketamine vs midazolam | no estimate extracted | NR | Very low Downgraded: risk of bias |
Acceptability: total dropouts№ of participants: 72(1 RCT) Ketamine vs midazolam | OR 0.33 [0.05, 2.09] | NR | Low Downgraded: risk of bias, inconsistency |
Acceptability: dropouts due to adverse effects ‐ not reported Ketamine vs midazolam | no estimate extracted | NR | No studies |
Esketamine compared to placebo for adults with unipolar major depressive disorder
Population: adults (aged 18 years+) with unipolar major depressive disorder
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Efficacy: number of participants who respond to treatment ‐ at 24 hours (Response) Esketamine vs placebo | OR 2.11 [1.2, 3.68] | NR | Low Downgraded: risk of bias |
Efficacy: number of participants who achieve remission ‐ at 24 hours (Remission) Esketamine vs placebo | OR 2.74 [1.71, 4.4] | NR | Moderate Downgraded: risk of bias |
Depression rating scale score ‐ at 24 hours Esketamine vs placebo | no estimate extracted | NR | Moderate Downgraded: risk of bias |
Acceptability: total dropouts№ of participants: 773(5 RCTs) Esketamine vs placebo | OR 1.58 [0.92, 2.73] | NR | Moderate Downgraded: risk of bias |
Acceptability: dropouts due to adverse effects ‐ not reported Esketamine vs placebo | no estimate extracted | NR | No studies |
Ketamine compared to placebo for depression in adults
Population: adults with depression
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Response rate ‐ at 24 hours Ketamine vs placebo | OR 10.77 [2, 58] | 3 studies · 56 participants | Low |
Response rate ‐ at 72 hours Ketamine vs placebo | OR 12.59 [2.38, 66.73] | 3 studies · 56 participants | Low |
Response rate ‐ at 1 week Ketamine vs placebo | OR 3.41 [0.95, 12.27] | 3 studies · 99 participants | Low |
Response rate ‐ at 2 weeks Ketamine vs placebo | OR 0.93 [0.31, 2.83] | 1 study · 51 participants | Low |
Remission rate ‐ at 1 week Ketamine vs placebo | OR 7.24 [1.7, 30.81] | 3 studies · 99 participants | Low |
Depression rating scale score ‐ at 1 week Ketamine vs placebo | no estimate extracted | 4 studies · 98 participants | Low |
Acceptability ‐ total dropouts Ketamine vs placebo | OR 3.77 [0.97, 14.68] | 4 studies · 107 participants | Low |
Acceptability ‐ dropouts due to adverse effects Ketamine vs placebo | no estimate extracted | NR | No studies |
Ketamine compared to midazolam for depression in adults
Population: depression in adults
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Response rate ‐ at 24 hours Ketamine vs midazolam | OR 4.54 [1.58, 13.05] | 1 study · 72 participants | Low |
Response rate ‐ at 72 hours Ketamine vs midazolam | OR 5.4 [1.73, 16.85] | 1 study · 72 participants | Low |
Response rate ‐ at 1 week Ketamine vs midazolam | OR 4.24 [1.26, 14.28] | 1 study · 72 participants | Low |
Remission rate ‐ at 1 week Ketamine vs midazolam | OR 1.37 [0.42, 4.46] | 1 study · 72 participants | Low |
Montgomery Asberg Rating Scale score ‐ at 1 week Ketamine vs midazolam | no estimate extracted | 1 study · 67 participants | Low |
Acceptability ‐ total dropouts Ketamine vs midazolam | OR 0.33 [0.05, 2.09] | 1 study · 72 participants | Low |
Acceptability ‐ dropouts due to adverse effects Ketamine vs midazolam | no estimate extracted | NR | No studies |
Ketamine compared to thiopental for depression in adults
Population: depression in adults
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Response rate ‐ at 3 days Ketamine vs thiopental | OR 2.64 [0.1, 69.88] | 1 study · 31 participants | Very low |
Response rate ‐ at 4 weeks Ketamine vs thiopental | OR 0.81 [0.05, 14.28] | 1 study · 31 participants | Very low |
Hamilton Depression Rating Scale score ‐ at 2 weeks Ketamine vs thiopental | no estimate extracted | 1 study · 29 participants | Very low |
Acceptability ‐ total dropouts Ketamine vs thiopental | OR 4.68 [0.21, 105.89] | 1 study · 31 participants | Very low |
Remission Ketamine vs thiopental | no estimate extracted | NR | No studies |
Acceptability ‐ dropouts due to adverse effects Ketamine vs thiopental | no estimate extracted | NR | No studies |
AZD6765 compared to placebo for depression in adults
Population: depression in adults
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Response rate ‐ at 24 hours AZD6765 vs placebo | OR 7.74 [0.35, 170.1] | 1 study · 22 participants | Very low |
Response rate ‐ at 72 hours AZD6765 vs placebo | OR 2.74 [0.1, 74.87] | 1 study · 22 participants | Very low |
Response rate ‐ at 1 week AZD6765 vs placebo | OR 2.74 [0.1, 74.87] | 1 study · 22 participants | Very low |
Remission rate ‐ at 1 week AZD6765 vs placebo | OR 2.74 [0.1, 74.87] | 1 study · 22 participants | Very low |
Montgomery Asberg Rating Scale score ‐ at 1 week AZD6765 vs placebo | no estimate extracted | 1 study · 21 participants | Very low |
Acceptability ‐ total dropouts AZD6765 vs placebo | OR 2.74 [0.1, 74.87] | 1 study · 22 participants | Very low |
Acceptability ‐ dropouts due to adverse effects AZD6765 vs placebo | no estimate extracted | NR | No studies |
Atomoxetine compared to placebo for depression in adults
Population: depression in adults
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Response rate ‐ at 3 months Atomoxetine vs placebo | OR 1.25 [0.63, 2.47] | 1 study · 146 participants | Low |
Remission rate ‐ at 3 months Atomoxetine vs placebo | OR 1.34 [0.67, 2.67] | 1 study · 146 participants | Low |
Acceptability ‐ total dropouts Atomoxetine vs placebo | OR 1.03 [0.44, 2.41] | 1 study · 146 participants | Low |
Acceptability‐ dropouts due to adverse effects Atomoxetine vs placebo | OR 1.88 [0.53, 6.74] | 1 study · 146 participants | Low |
Hamilton Depression Rating Scale score ‐ at 3 months Atomoxetine vs placebo | no estimate extracted | 1 study · 141 participants | Low |
CP‐101,606 compared to placebo for depression in adults
Population: depression in adults
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Response CP‐101,606 vs placebo | no estimate extracted | NR | No studies |
Remission CP‐101,606 vs placebo | no estimate extracted | NR | No studies |
Montgomery Asberg Rating Scale score ‐ at 1 week CP‐101,606 vs placebo | no estimate extracted | 1 study · 26 participants | Very low |
Acceptability ‐ total dropouts CP‐101,606 vs placebo | OR 0.29 [0.06, 1.45] | 1 study · 30 participants | Very low |
Acceptability‐ dropouts due to adverse events CP‐101,606 vs placebo | no estimate extracted | 1 study · 30 participants | Very low |
D‐cycloserine compared to placebo for depression in adults
Population: depression in adults
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Response rate ‐ at 2 weeks D‐cycloserine vs placebo | OR 5.33 [0.51, 56.24] | 1 study · 26 participants | Very low |
Response rate ‐ at 4 weeks D‐cycloserine vs placebo | OR 3.44 [0.53, 22.43] | 1 study · 26 participants | Very low |
Remission rate ‐ at 4 weeks D‐cycloserine vs placebo | OR 9 [0.42, 194.07] | 1 study · 26 participants | Very low |
Hamilton Depression Rating Scale score ‐ at 2 weeks D‐cycloserine vs placebo | no estimate extracted | 1 study · 26 participants | Very low |
Acceptability ‐ total dropouts D‐cycloserine vs placebo | OR 3.6 [0.32, 40.23] | 1 study · 26 participants | Very low |
Acceptability ‐ dropouts to due to adverse effects D‐cycloserine vs placebo | no estimate extracted | NR | No studies |
MK‐0657 compared to placebo for depression in adults
Population: depression in adults
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Montgomery Asberg Rating Scale score ‐ at 1 week MK‐0657 vs placebo | no estimate extracted | 1 study · 5 participants | Very low |
Response MK‐0657 vs placebo | no estimate extracted | NR | No studies |
Remission MK‐0657 vs placebo | no estimate extracted | NR | No studies |
Acceptability ‐ total dropouts MK‐0657 vs placebo | no estimate extracted | NR | No studies |
Acceptability ‐ dropouts due to adverse effects MK‐0657 vs placebo | no estimate extracted | NR | No studies |
Memantine compared to placebo for depression in adults
Population: depression in adults
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Response rate ‐ at 1 week Memantine vs placebo | OR 1.07 [0.06, 18.82] | 2 studies · 63 participants | Low |
Response rate ‐ at 2 weeks Memantine vs placebo | OR 0.31 [0.01, 8.28] | 1 study · 32 participants | Low |
Response rate ‐ at 4 weeks Memantine vs placebo | OR 0.49 [0.11, 2.1] | 3 studies · 123 participants | Moderate |
Response rate ‐ at 3 months Memantine vs placebo | OR 0.47 [0.18, 1.21] | 3 studies · 123 participants | Moderate |
Remission rate ‐ at 1 week Memantine vs placebo | OR 6.11 [0.27, 138.45] | 2 studies · 63 participants | Low |
Montgomery Asberg Rating Scale score ‐ at 1 week Memantine vs placebo | no estimate extracted | 2 studies · 59 participants | Low |
Acceptability ‐ total dropouts Memantine vs placebo | OR 0.74 [0.24, 2.29] | 3 studies · 123 participants | Moderate |
Acceptability‐ dropouts due to adverse events Memantine vs placebo | OR 0.67 [0.1, 4.33] | 2 studies · 63 participants | Low |
N‐acetylcysteine compared to placebo for depression in adults
Population: depression in adults
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Response rate ‐ at 2 weeks N‐acetylcysteine vs placebo | OR 0.77 [0.38, 1.55] | 1 study · 269 participants | Low |
Response rate ‐ at 4 weeks N‐acetylcysteine vs placebo | OR 0.91 [0.52, 1.61] | 1 study · 269 participants | Low |
Response rate ‐ at 3 months N‐acetylcysteine vs placebo | OR 1.38 [0.83, 2.3] | 1 study · 269 participants | Low |
Remission rate ‐ at 2 weeks N‐acetylcysteine vs placebo | OR 0.48 [0.12, 1.98] | 1 study · 269 participants | Low |
Montgomery Asberg Rating Scale score ‐ at 2 weeks N‐acetylcysteine vs placebo | no estimate extracted | 1 study · 252 participants | Low |
Acceptability ‐ total dropouts N‐acetylcysteine vs placebo | OR 0.67 [0.36, 1.24] | 1 study · 269 participants | Low |
Acceptability‐ dropouts due to adverse events N‐acetylcysteine vs placebo | OR 0.49 [0.04, 5.5] | 1 study · 269 participants | Low |
Org 26576 compared to placebo for depression in adults
Population: depression in adults
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Response rate ‐ at 24 hours Org 26576 vs placebo | OR 0.84 [0.1, 6.87] | 2 studies · 54 participants | Low |
Response rate ‐ at 72 hours Org 26576 vs placebo | OR 0.8 [0.17, 3.89] | 2 studies · 54 participants | Low |
Response rate ‐ at 1 week Org 26576 vs placebo | OR 1.43 [0.33, 6.29] | 2 studies · 54 participants | Low |
Response rate ‐ at 2 weeks Org 26576 vs placebo | OR 2.24 [0.61, 8.22] | 2 studies · 54 participants | Low |
Response rate ‐ at 4 weeks Org 26576 vs placebo | OR 0.82 [0.18, 3.74] | 1 study · 30 participants | Low |
Remission rate ‐ at 1 week Org 26576 vs placebo | OR 1.61 [0.23, 11.17] | 2 studies · 54 participants | Low |
Montgomery Asberg Rating Scale ‐ at 1 week Org 26576 vs placebo | no estimate extracted | 2 studies · 54 participants | Low |
Acceptability ‐ total dropouts Org 26576 vs placebo | no estimate extracted | NR | No studies |
Acceptability ‐ dropouts due to adverse effects Org 26576 vs placebo | OR 0.5 [0.05, 5.17] | 2 studies · 54 participants | Ungraded |
Riluzole compared to placebo for depression in adults
Population: depression in adults
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Response rate ‐ at 24 hours Riluzole vs placebo | OR 1.23 [0.35, 4.36] | 1 study · 42 participants | Low |
Response rate ‐ at 72 hours Riluzole vs placebo | OR 2.62 [0.64, 10.61] | 1 study · 42 participants | Low |
Response rate ‐ at 1 week Riluzole vs placebo | OR 2.4 [0.51, 11.26] | 1 study · 42 participants | Low |
Response rate ‐ at 2 weeks Riluzole vs placebo | OR 1.41 [0.27, 7.26] | 1 study · 42 participants | Low |
Response rate ‐ at 4 weeks Riluzole vs placebo | OR 0.3 [0.03, 3.15] | 1 study · 42 participants | Low |
Remission rate ‐ at 1 week Riluzole vs placebo | OR 1 [0.18, 5.63] | 1 study · 42 participants | Low |
Montgomery Asberg Rating Scale score ‐ at 1 week Riluzole vs placebo | no estimate extracted | 1 study · 38 participants | Low |
Acceptability ‐ total dropouts Riluzole vs placebo | OR 0.81 [0.23, 2.88] | 1 study · 42 participants | Ungraded |
Acceptability ‐ dropouts due to adverse effects Riluzole vs placebo | no estimate extracted | NR | No studies |
Sarcosine compared to citalopram for depression in adults
Population: depression in adults
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Response rate ‐ at 2 weeks Sarcosine vs citalopram | OR 8.14 [0.88, 75.48] | 1 study · 40 participants | Low |
Response rate ‐ at 4 weeks Sarcosine vs citalopram | OR 6.93 [1.53, 31.38] | 1 study · 40 participants | Low |
Remission rate ‐ at 2 weeks Sarcosine vs citalopram | OR 14.55 [0.75, 283.37] | 1 study · 40 participants | Low |
Hamilton Depression Rating Scale score ‐ at 2 weeks Sarcosine vs citalopram | no estimate extracted | 1 study · 40 participants | Low |
Acceptability ‐ total dropouts Sarcosine vs citalopram | OR 0.52 [0.14, 1.92] | 1 study · 40 participants | Low |
Acceptability ‐ dropouts due to adverse events Sarcosine vs citalopram | no estimate extracted | 1 study · 40 participants | Low |
Ketamine compared to ECT for depression in adults
Population: depression in adults
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Response rate ‐ at 24 hours Ketamine vs ECT | OR 28 [2.07, 379.25] | 1 study · 18 participants | Very low |
Response rate ‐ at 72 hours Ketamine vs ECT | OR 12.25 [1.33, 113.06] | 1 study · 18 participants | Very low |
Response rate ‐ at 1 week Ketamine vs ECT | OR 3.35 [0.12, 93.83] | 1 study · 18 participants | Very low |
Response rate ‐ at 2 weeks Ketamine vs ECT | OR 3.35 [0.12, 93.83] | 1 study · 18 participants | Very low |
Remission rate ‐ at 1 week Ketamine vs ECT | OR 10.23 [0.45, 233.23] | 1 study · 18 participants | Very low |
Hamilton Depression Rating Scale score ‐ at 1 week Ketamine vs ECT | no estimate extracted | 1 study · 18 participants | Low |
Acceptability ‐ total dropouts Ketamine vs ECT | no estimate extracted | NR | No studies |
Acceptability ‐ dropouts due to adverse effects Ketamine vs ECT | no estimate extracted | NR | No studies |