Table 2.

Selected open-label studies examining the rapid antidepressant effects of ketamine

Study	Subjects	Treatment	ADE 4 h-3 days	ADE 7 days	Response rate	Additional findings
Carlson et al.83	N20-MDD	Ketaminea 0.5 mg/kg	YES	—	30% at 4 h	Reduced activity in the right habenula
Chilukuri et al.55	N9-MDD	Ketaminea 0.5 mg/kg	YES	—	59% at 2 h	Improvement sustained at 3 days in all groups; two subjects attempted suicide—both were non-responders to ketamineb.
	N9-MDD	Ketamineb 0.5 mg/kg	YES	—	60% at 2 h
	N9-MDD	Ketamineb 0.25 mg/kg	YES	—	57% at 2 h
Diazgrandos, et al.19	N33-MDD, MF	Ketaminea 0.5 mg/kg	YES	—	—	Decreased suicidal ideations
Ibrahim et al.15	N17-MDD-ER, MF	Ketaminea 0.5 mg/kg	YES	—	—	Lower effect size with ECT-resistant (MDD-ER) group
	N23-MDD, MF	Ketaminea 0.5 mg/kg	YES	—	—
Ibrahim et al.84	N42-MDD, MF	Ketaminea 0.5 mg/kg	YES	YES	62% at 4–6 h	Riluzole following ketamine had no effects; ADE maintained at 28 days
Larkin & Beautrais85	N14-MDD-SI	Ketaminec 0.2 mg/kg	YES	YES	85% at 10 days	Decreased suicidal ideations
Machado et al.74	N23-MDD, MF	Ketaminea0.5 mg/kg	YES	—	48% at 4 h	Serum BDNF did not correlate with ADE.
Mathew et al.86	N26-MDD, MF	Ketaminea 0.5 mg/kg	YES	YES	65% at 1 day; 54% at 3 days	Lamotrigine prior to ketamine and riluzole following ketamine had no effects.
Murrough et al.20	N24-MDD, MF	Ketaminea 0.5 mg/kg 3×/w for 2w	YES	—	71% at 24 h after last infusion	Significant ADE within 2 h; decreased suicidal ideations in ketamine responders as well as non-responders; median time to relapse was 18 days.
Okamoto et al.87	N11-MDD	Ketaminec 0.86 mg/kg + ECT 2×/w for 4w	—	YES	—	ADE in both groups; ketamine group had lower depression scores at 2nd & 4th ECT sessions and longer seizure at 1st & 6th ECT session.
	N20-MDD	Propofol 0.94 mg/kg + ECT 2×/w for 4w	—	YES	—
Phelps et al.88	N26-MDD, MF	Ketaminea 0.5 mg/kg	YES	—	43% at 4 h (67% in FH+; 18% in FH−)	Plasma ketamine/norketamine did not correlate with ADE.
Rasmussen et al.51	N10-MDD	Ketaminea 0.5 mg/kg 2×/w for 2w	YES	—	30% at 1 day; 80% at 4 days	Decreased suicidal ideations
Salvadore et al.68	N11-MDD, N11-HS, MF	Ketaminea 0.5 mg/kg	YES	—	—	Repeated exposure to fearful faces: increased rACC activity in MDD but not HS; rACC activity correlated with ADE; rAG negatively correlated ADE.
Salvadore et al.69	N15-MDD, MF	Ketaminea 0.5 mg/kg	YES	—	—	N-back test (working memory): pgACC activity negatively correlated with ADE.
Salvadore et al.89	N15-MDD, MF	Ketaminea 0.5 mg/kg	YES	—	—	Frontal glx/glutamate negatively correlated with ADE, while glutamate positively correlated with anxiety improvement.

^aintravenous ketamine infusion over 40 minutes.

^bintramuscular ketamine.

^cintravenous ketamine bolus.

—, not reported.

Abbrevations: ADE: antidepressant effect; N, number of subjects; MDD, major depressive disorder; MDD-SI, major depressive disorder with suicidal ideation; MDD-ER, ECT-resistant major depressive disorder; BD, bipolar disorder; MF, medication free; HS, healthy subjects; FH^+/−, family history of alcohol abuse positive/negative; ¹H-MRS, proton magnetic resonance spectroscopy; MEG, magnetoencephalography; rACC, rostral anterior cingulate cortex; pgACC, pregenual anterior cingulate cortex; rAG, rostral amygdala; Glx, a ¹H-MRS measure reflecting glutamate and glutamine; ECT, electroconvulsive therapy.