Table 1.

Clinical Efficacy and Safety.

Author (Year)	Groups Studied and Intervention	Results and Findings	Conclusions
Study 1: [2]	Psychiatric (n  =  29; 15 PTSD, 14 MDD) and healthy control group (n  =  29) groups were recruited. General inclusion criteria: Adults 18–60 years old, no recent regular history of psychiatric medication use. Psychiatric group with MDD and/or PTSD, experiencing current major depressive episode (those with MDD), no other psychiatric conditions (except anxiety disorders), and free of psychotropic medications for at least two months (at time of ketamine injection). Racemic ketamine was administered to half the subjects in each group with an initial bolus of 0.23 mg/kg over 1 min followed by a constant infusion of 0.58 mg/kg per hour over 1 h. The remaining half received constant IV infusion 0.5 mg/kg ketamine over 40 min.	MDD/PTSD individuals showed significant improvement in the severity of depressive symptoms at both 2-h and one-day post-ketamine administration (severity decreased from moderate depression at baseline to mild depression). IV ketamine-induced declines in attention (ATTN), executive function (EF), and verbal memory (VM) 2 h post-administration, all resolved by one-day post-ketamine across groups. Degree of cognitive decline is larger in MDD/PTSD relative to HC solely on attention. No effect on working memory (WM) performance in either group.	Intravenous subanesthetic doses of ketamine have shown reduced psychiatric distress in both MDD and PTSD. However, it has an acute transient deleterious effect on cognitive domains in both MDD/PTSD and HC (most notably attention). The effect of ketamine on cognitive function in these disorders remains poorly understood.
Study 2: [3]	Adults 21–80 years of age with major depressive disorder (MDD) with a poor response to at least three therapeutic trials of an antidepressant. A single IV infusion of ketamine (0.5 mg/kg) or midazolam (0.045 mg/kg) over 40 min is infused. Neurocognitive tests were done.	At day seven post-treatment, improvement in processing speed, verbal learning, and visual learning from the baseline was noticed. ketamine responders had significantly slower processing speed at baseline than ketamine non-responders.	Processing speed, verbal learning, and visual learning improved at the end of the study after receiving ketamine compared with baseline. A rapid antidepressant effect at 24 h following ketamine is obtained with slower processing time at baseline.
Study 3: [4]	Inclusion criteria: Adults ranging from 18–65 years old, at least moderate depression (Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥ 25), evidence of treatment resistance, and secondary analysis baseline MADRS-SI suicide item score ≥ 2. A three-phase trial was conducted to assess the antidepressant effects of ketamine in treatment-resistant depression (TRD). Ketamine hydrochloride (0.5 mg/kg, diluted in 0.9% saline) and midazolam (30 μg/kg diluted in saline) infused over a 40 min. Separation of each infusion was by at least seven days. Followed up, infusion of six open-label ketamine thrice-weekly over two weeks. Participants showing antidepressant response (≥50% decrease in MADRS total score from baseline) of ketamine following	Ketamine MADRS-SI scores were lower than that of midazolam at 2 h and seven days post-infusion. Maximal effect of ketamine on SI measured at seven days post-infusion (mean decrease 1.7 points). At start of Phase 2, MADRS-SI scores were significantly lower than study baseline. Estimated mean MADRS-SI score for participants at post-Phase 2 follow-up visit was 1.0. with estimated mean reduction of 2.3 points on the MADRS-SI at end of Phase 2 from baseline.	Compared with midazolam, a single ketamine infusion elicited larger reduction in SI, with maximal effects measured at seven days post-infusion. 69% of participants had a complete alleviation of SI following repeated infusions. In TRD, single and repeated ketamine infusions resulted in decreases in SI which were maintained with once-weekly maintenance infusions.
Study 4: Ketamine vs. midazolam [5]	Adults (n = 41), ranging from 18–65, with treatment-resistant depression. Inclusion criteria: ≥25 on the Montgomery-Åsberg Depression Rating Scale (MADRS). Participants completed a single-site randomized double-blind crossover comparison of single infusions of ketamine and midazolam. After relapse of depressive symptoms, participants received a course of six open-label ketamine infusions administered thrice weekly over two weeks. Responders (participants with ≥50% decrease in their scores on MADRS) received four additional infusions administered once weekly (maintenance phase).	A single ketamine infusion elicited a significantly greater reduction in depressive symptoms at the primary efficacy endpoint compared with midazolam (24 h post-infusion). 59% of participants met response criteria after repeated infusions (median of three infusions needed before achieving response). Participants had no further change in MADRS scores during weekly maintenance infusions.	Repeated ketamine infusions have cumulative and sustained antidepressant effects that were maintained among responders through once-weekly infusions. Future studies should further expand on optimizing administration of ketamine in clinical settings, especially those associated with patients who suffer from treatment-resistant depression.
Study 5: Ketamine vs. ECT [6]	Fifty patients suffering from depression were treated with either serial ketamine infusions or ECT. Depression severity and cognitive functions were assessed before, during, and after treatment.	ECT and ketamine administration were equally effective. However, the antidepressant effects of ketamine occurred faster. Ketamine improved neurocognitive functioning, especially attention and executive functions, whereas ECT was related to a small overall decrease in cognitive performance.	Related to its pro-cognitive effects and faster antidepressant effect, serial ketamine administration might be a more favorable short-term treatment option than ECT.
Study 6: Ketamine vs. Haloperidol [7]	Pre-anesthetic, pharmacologic prevention of postoperative brain dysfunction with haloperidol, ketamine, and the combination of both vs. placebo in 182 patients.	None of the three pharmacologic interventions (haloperidol, ketamine, or both drugs combined) was significantly superior to placebo for preventing postoperative brain dysfunction and delirium. Measured levels of postoperative cortisol were significantly higher in delirious patients.	The study results offer no opportunity for an unprecedented option for preventing postoperative cognitive decline including delirium.