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Supplementary Table S1: Study, Patient and Treatment Characteristics

Supplementary Table S2: Risk of Bias Assessment: Ketamine and Non-Ketamine Studies

Supplementary Fig. S1: Search Results

Supplementary Fig. S2: Ketamine Studies, All Cause Discontinuation, Random Effects Model

Supplementary Fig. S3: Non-Ketamine NMDAR Antagonist Studies, All Cause Discontinuation, Random Effects Model

Supplementary Fig. S4: Ketamine Studies, BPRS, Random Effects Model

Supplementary Fig. S5: Non-Ketamine NMDAR Antagonist Studies, BPRS, Random Effects Model

Supplementary Fig. S6. Ketamine Studies, YMRS, Random Effects Model

Supplementary Fig. S7: Ketamine Studies, CADSS, Random Effects Model

Supplementary Fig. S8: Ketamine Studies, Other Adverse Events, Random Effects Model

Supplementary Fig. S9: Non-Ketamine NMDAR Antagonist Studies, Other Adverse Events, Random Effects Model

|Supplementary Table S1. Study, patient and treatment characteristics |

|Study; |

|Sponsor |

|1. Berman et. al. 2000 10; |

|NIMH, VA and Foundation |

|4. Zarate et al. 2012; |

|NIMH |

|7. Singh et al. 2014 2X/week; Janssen |

|10. Preskorn et al. 2008; |

|Pfizer |

|13. Sanacora et al. 2013 24 (study 9); AstraZeneca |

Supplementary Table S2. Risk of bias assessment: ketamine and non-ketamine studies

|Random sequence generation |Allocation concealment |Blinding of participants and personnel |Blinding of outcome assessment |Incomplete outcome data addressed |Selective reporting |Other sources of bias | |Berman 2000 |? |? |? |? |+ |- |+ | |Diazgranados 2010 |+ |? |? |? |+ |- |+ | |Lai 2014 |? |? |- |- |- |- |- | |Murrough 2013 |? |? |+ |+ |+ |- |+ | |Singh 2014

2X/week |? |? |? |? |+ |- |- | |Singh 2014

3X/wek |? |? |? |? |+ |- |- | |Sos 2013 |? |? |? |? |+ |? |+ | |Zarate 2006 |+ |? |? |? |+ |- |+ | |Zarate 2012 |+ |? |? |? |+ |- |+ | |Subtotal Ketamine |Low risk=3 (33.3%)

Unclear=6 (66.7%) |Unclear=9 (100%) |Low risk=1

(11.1%)

Unclear=7 (77.8%)

High risk=1

(11.1) |Low risk=1

(11.1%)

Unclear=7 (77.8%)

High risk=1

(11.1%) |Low risk=8 (88.9%)

High risk=1 (11.1%) |Unclear=1 (11.1%)

High risk=8

(88.9%) |Low risk=6 (66.7%)

High risk=3

(33.3%) | |Preskorn 2008 |? |? |- |+ |- |? |- | |Preskorn 2015 |? |? |? |? |- |- |+ | |Sanacora 2014 study 1 |? |? |? |? |- |+ |+ | |Sanacora 2014 study 9 |? |? |? |? |+ |- |+ | |Zarate 2013 |+ |? |+ |? |+ |- |+ | |Subtotal Non-Ketamine |Low risk=1 (20%)

Unclear=4 (80%) |Unclear=5 (100%) |Low risk=1 (20%)

Unclear=3 (60%)

High risk=1

(20%) |Low risk=1 (20%)

Unclear=4 (80%) |Low risk=2 (40%)

High risk=3

(60%) |Low risk=1 (20%)

Unclear=1 (20%)

High risk=3

(60%) |Low risk=4 (80%)

High risk=1

(20%) | |Total |Low risk=4 (28.6%)

Unclear=10 (71.4%) |Unclear=14 (100%) |Low risk=2 (14.3%)

Unclear=10 (71.4%)

High risk=2

(14.3%) |Low risk=2 (14.3%)

Unclear=11 (78.6%)

High risk=1

(7.1%) |Low risk=10

(71.4%)

High risk=4

(28.6%) |Low risk=1 (7.1%)

Unclear=2

(14.3%)

High risk=11

(78.6%) |Low risk=10 (71.4%)

High risk=4

(28.6%) | |

+ : Low risk of bias, - : High risk of bias, ? : Unclear risk of bias, nd : not determined

Supplementary Fig. S1. Search results

Supplementary Fig. S2. Ketamine studies, all cause discontinuation, random effects model

[pic]

Supplementary Fig. S3. Non-ketamine NMDAR antagonist studies, all cause discontinuation, random effects model

[pic]

Supplementary Fig. S4. Ketamine studies, BPRS, random effects model

[pic]

Supplementary Fig. S5. Ketamine studies, YMRS, random effects model

[pic]

Supplementary Fig. S6. Ketamine studies, CADSS, random effects model

[pic]

Supplementary Fig. S7. Non-ketamine NMDAR antagonist studies, BPRS, random effects model

[pic]

Supplementary Fig. S8. Ketamine studies, other adverse events, random effects model

[pic]

Supplementary Fig. S9. Non-ketamine NMDAR antagonist studies, other adverse events, random effects model

[pic]

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Records identified through database searching

(N=1571 )

Studies identified through hand searching and scientific poster session

(N=3 )

Identification

Included

Eligibility

Screening

Full-text articles and posters assessed for eligibility

(N=26)

Records excluded

(N=1506)

Records screened

(N=26)

Records after duplicates removed

(N=1532)

Articles excluded (N=14):

Review articles (N=5)

Data based on same sample (N=5)

No available data before the 2nd injection (N=2)

Non randomized studies (N=1)

Non intravenous infusion studies (N=1)

Studies included in quantitative synthesis (meta-analysis)

(N=12 articles; 14 trials)

Studies included in qualitative synthesis

(N=12 articles; 14 trials)

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