Table 1.

Most relevant case reports/series reporting the antidepressant efficacy of ketamine on suicidality in patients with TRD.

Author(s), Year	Sample Characteristics	Main Results	Number of Infusions Needed for Achieving Antidepressant Effects	Route of Administration	Limitations	Conclusions
Szymkowicz et al. 2013 [24]	Three patients were administered ketamine at 0.5 mg/kg for 40 minutes and evaluated with the MADRS.	All three patients responded (after 5 infusions) and remitted after ketamine infusions. No significant side-effects have been reported.	6.6 infusions	Intravenous infusions	This was an open-label naturalistic study without blinding, randomization, or placebo control. The small sample size did not allow the generalization of the findings.	Low-dose repeated intravenous ketamine has a rapid and safe antidepressant activity in patients with TRD.
Segmiller et al. 2013 [26]	Six patients with TRD were treated with 40-minute ketamine infusion (0.25 mg) and evaluated with HDRS21 before and 120 minutes after each infusion.	Three patients (50%) showed an improvement in depressive symptoms in both short and longer term period. Specifically, patients responded after one ketamine infusion. Remission has been reached in two patients (33.3%); two patients reported dissociative symptoms.	Single infusion	Intravenous infusions	The small sample size did not allow the generalization of the findings. Dissociative symptoms should represent a limitation when interpreting the present findings. Dissociative symptoms could be observed more frequently in patients treated with S-ketamine.	The most relevant antidepressant effect has been reported after the first ketamine administration. Multiple administrations of S-ketamine appear to be well tolerated in most cases.
Murrough et al. 2011 [25]	A 45-year-old women with TRD who took a three-times-weekly intravenous infusions (0.5 mg/kg) of ketamine every two weeks	After 24 hours following the first dose of ketamine, a significant antidepressant activity (89% change in her MADRS scores) of ketamine has been reported. Remission from depression has been reported for the following three months.	Single infusion	Intravenous infusions	This a case report, the results of which may not be generalized to the whole population.	Ketamine has rapid and sustained antidepressant properties as it may enhance neurogenesis and neuroplasticity mechanisms.
Messer et al. 2010 [27]	Two adult patients with TRD randomized to six 0.5 mg/kg infusions of ketamine (on days 1, 3, 5, 7, 9 and 11), and four saline infusions (on days 3, 5, 9, and 11), respectively	Patients reported robust changes in depressive symptoms in response to ketamine treatment (after 1.5 infusions) as measured by the BDI scores. No memory or concentration impairments have been associated with ketamine infusions.	1.5 infusions	Intravenous infusions	This study is a report of two cases and its results did not allow the generalization to other samples.	Multiple treatments of ketamine may have a prolonged benefit for TRD patients.
Paslakis et al. 2010 [28]	Two cases in which oral administration of (S)-ketamine (1.25 mg/kg) for 14 days was performed as add-on therapy	A significant improvement was obtained with the use of ketamine. Response and remission rates are achieved in 50% of cases, respectively. No significant side effects were reported.	Not specified	Oral administration	This a case report, the results of which may not be generalized to the whole population.	S-ketamine showed relevant antidepressant effects and was better tolerated than (R)-ketamine.
Liebrenz et al. 2009 [29]	A 55-year-old male subject with a TRD and co-occurring alcohol and benzodiazepines dependence. The same patient received two intrave-nous infusions of 0.5 mg/kg ketamine over the course of 6 weeks.	After the second day of infusion, the subject experienced a significant improvement of his symptoms (-56.6% at the HDRS; -65.4% at the BDI. He continued to improve throughout the subsequent 7 days. The second infusion was less efficacious (HDRS and BDI were reduced by 43 and 35%, respectively). He returned to baseline by day 7.	Single infusion	Intravenous infusions	This is a case report, the results of which may not be generalized to the whole population. The patient was depressed but also affected by alcohol dependence. Doses and administrations of ketamine need to be carefully investigated.	Ketamine has potent antidepressant effects and act very swiftly. Repeated administrations of ketamine produced positive results.
Paul et al. 2009 [30]	Two patients with TRD treated with ketamine and S-ketamine; the severity of depression was rated using the HDRS and BDI.	One patient did not respond to both treatments whereas in the other patient both intravenous administration of ketamine and S-ketamine showed an antidepressant effect as assessed by a decrease in HDRS21 and BDI at days 1 and day 3 but not until day 6 (response rate 50%). Both patients experienced psychomimetic side effects during ketamine infusion which were absent during treatment with S-ketamine.	Single infusion	Intravenous infusions	This a case report, the results of which may not be generalized to the whole depressed population.	S-ketamine could show similar antidepressant effects as ketamine in drug-resistant depression and was better tolerated than ketamine.