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Retrospective data analysis to determine the effectiveness of intravenous ketamine therapy on patients suffering from depression with suicidal ideation


 Department of Psychiatry, GMERS Medical College and Hospital, Sola, Ahmedabad, Gujarat, India

Date of Submission06-Nov-2021
Date of Acceptance09-Jun-2022
Date of Web Publication10-Nov-2022

Correspondence Address:
Pradhyuman Chaudhary,
GMERS Medical College, Sola, Ahmedabad, Gujarat
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ipj.ipj_231_21

   Abstract 


Background: Depression is often a debilitating and recurrent psychiatric disorder. Depression with suicidal ideation, being a psychiatric emergency, often needs intensive intervention such as Electro-Convulsive Therapy (ECT). ECT may be refused because of stigma and perceived risk. Intravenous ketamine therapy, being an alternative to ECT for quick response compared to routine pharmaco-therapy, is analyzed to determine its effectiveness. Methods: Among patients suffering from depression with suicidal ideation, intravenous ketamine therapy is routinely offered as an alternative to ECT to the needy in the Department of Psychiatry affiliated with a teaching institute. There is a standard operative procedure laid down for ketamine therapy. Baseline and periodical assessment of depression by Hamilton Depression Rating Scale and suicidality by Columbia Suicide Severity Rating Scale is a part of it. Taking advantage of it, retrospective data analysis was done to determine the effectiveness of the therapy. Result: Significant improvement of depression and suicidality found at all the evaluation points after intravenous ketamine therapy. Conclusion: Intravenous ketamine therapy is an effective alternative to ECT among patients suffering from depression with suicidal ideation.

Keywords: Depression, ketamine, suicidal ideation



How to cite this URL:
Chaudhary P, Shah P, Mehta P. Retrospective data analysis to determine the effectiveness of intravenous ketamine therapy on patients suffering from depression with suicidal ideation. Ind Psychiatry J [Epub ahead of print] [cited 2022 Nov 30]. Available from: https://www.industrialpsychiatry.org/preprintarticle.asp?id=360858



The first clinical trial reporting antidepressant actions of ketamine was published in 2000, where ketamine was administered intravenously (40-min infusion) at the sub-anesthetic dose of 0.5 mg/kg.[1] This contrasts with the typical dose of ketamine used in anaesthesia of up to 2 mg/kg.[2] Ketamine was shown to elicit a rapid (within hours) and sustained (up to 7 days) antidepressant effect of a single dose in sub-anaesthetic repeated doses,[1],[3],[4],[5],[6] which was shown to remain in effect (48 h) beyond its half-life[7],[8],[9],[10] and 18–19 days following repeated infusions.[11],[12] The actions of ketamine to induce rapid antidepressant effects are in sharp contrast with the delayed effect onset of currently approved antidepressant treatments, which is particularly important in cases of patients with suicidal ideation (SI), where a lag in the onset of antidepressant action has been associated with increased risk for suicidal behavior.[13] Ketamine has been also shown to induce a rapid amelioration of SI in major depressed patients[14],[15] and to rapidly reduce anhedonia.[16],[17],[18]

The evidence suggesting specific anti-suicidal effects of ketamine independent of its anti-depressive effect[14] is consistent with the growing body of research implicating the glutamate system in the neurobiology of suicide.[19] In study on initial single- and repeated-dose, the impact of ketamine on SI in treatment-resistant depression (TRD) found that IV ketamine (0.5 mg/kg over 40 min) was associated with rapid reductions in explicit and implicit suicidal cognitions within the first 24 h after infusion, which persisted for patients who received additional infusions.[14] Ketamine is a new and effective option in future with rapid onset of action, but studies are limited with multiple doses of ketamine that have assessed depressive symptoms and SI comprehensively. Hence, index study aimed to assess the efficacy of multiple doses of intravenous (IV) ketamine in patients with severe depression with SI.


   Subjects and Methods Top


Data extraction from records

Records of all indoor patients during the period of June 2019–June 2020 were extracted. There were 10 cases of depression with SI treated with ketamine therapy. These records were anonymised and demographic information, diagnosis, treatment, and outcome data were extracted.

There is a standard operative procedure (SOP) for ketamine therapy in the Department of Psychiatry, which is affiliated with a teaching institute. As per SOP, IV ketamine infusion was given in the dose range of 0.4–0.7 mg/kg over the period of 50 min. Usually, six such sessions, daily during the first week for four sessions and two sessions on alternate days on the second week were given. All patients were assessed by Hamilton Depression Rating Scale (HAM-D)[20] and Columbia Suicidal Severity Rating Scale (C-SSRS)[21] at baseline, at periodic interval, and post ketamine therapy. Assessment schedule is pre-treatment, 2 h after each session, and 7 days and 1 month after last session.

Statistical analysis

Because of the small sample size, outcome data are presented descriptively for subjects receiving infusions of ketamine. Study results used a last observation carried forward approach for those in the intent-to-treat population, defined as any subject who received all six infusions. Continuous parametric data were analyzed using the Student's t test for independent groups and the χ2 test or Fisher exact test, as appropriate, for categorical data. The HAM-D and C-SSRS were compared before and after ketamine injection by Friedman's test and Wilcoxon Signed-Rank Test paired t-test. The Friedman's test can also be used in place of the F test for repeated measures with interval- or ratio-level data that do not meet the assumptions of normality and homogeneity of variance and covariance.[22] All statistical analyses were performed using SPSS 20, with P < 0.05 set for statistical significance and graphs drawn by Excel 2013.


   Result Top


Patient demographics details: (n = 10)

The data were collected on a sample of 10 patients having depression with SI who were treated between June 2019 and July 2020. Out of 10 patients, three patients' records revealed lost follow up at month but received all six doses of IV ketamine and had follow-up at a week after the last infusion. The participants' age ranged from 22 to 49 years, with a mean of 33.1 (SD = 9.01). The majority of the patients were Hindu (80%) and educated up to secondary education (75%). Most of them were unemployed (55%) and married (70%). All patients were living with their joint family (100%) and most of them belonged to urban backgrounds (70%).

Clinical characteristics of the sample population: Patients (n = 10)

The mean age of onset of depression was 27.80 ± 10.72 years. Mean duration of the depression was 6.95 ± 4.31 months. All the patients had a diagnosis of a moderate depressive episode with SI. Two of them have a history of diabetes mellitus. None of them has a family history of medical illness or mental illness. Half of the patients were drug naïve.

Effect of ketamine treatment over time: Changes in the HAM-D scores

This study has shown that IV ketamine injection in sub-anesthetic doses results in a significant reduction of depressive symptoms in patients with major depression at 2 h, which was sustained until the 30 day after the last injection [Table 1].
Table 1: Effect of ketamine treatment over time: Changes in the Hamilton Rating Scale for depression scores (n=10)a

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Mean and standard deviation of HAM-D scores before and 2 h after each IV ketamine, one week after last dose, and one month after last dose show significant improvement in score serially and compared to baseline. There was a statistically significant difference in HAM-D score on Friedman's score after each doses, χ2 = 36.688, P = 0.000 (Serial means: 22.400 ± 1.7127; 9.400 ± 5.5817; 8.700 ± 5.8509; 8.300 ± 5.8699; 8.400 ± 6.1500; 7.500 ± 6.4679; 7.500 ± 6.4679; and 9.100 ± 7.5638). Post hoc analysis with Wilcoxon signed-rank tests was conducted, resulting in a significance level set at P < 0.01. There were statistically significant differences between the baseline score and score after each dose. Z and P values are shown in [Table 2].
Table 2: Effect of ketamine treatment over time: Changes in the Hamilton Rating Scale for depression scores (n=10)a

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One patient had not shown improvement of HAM-D scoring after six infusions and needed administration of ECT. Mean score of HAM-D was increased on the first week and one month follow-up but on sub analysis, it was not found statistically significant (P > 0.05) [[Table 1], sub analysis 1]. In addition, the baseline mean score of HAM-D was significantly reduced after the first dosage of IV ketamine infusion (P = 0.002) [[Table 1], sub analysis 2]. Serial HAM-D score before and after each dose of ketamine showed in [Figure 1].
Figure 1: HAM-D score before and after ketamine dose

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C-SSRS SI and behaviour

IV ketamine significantly reduced C-SSRS score following the first dose and remained improved throughout all assessments [Table 3]. Nine patients reported no SI after the first dose that was sustained for 30 days. Serial C-SSRS score before and after each dose of ketamine showed in [Figure 2].
Figure 2: C-SSRC score before and after ketamine dose – suicidal ideation category shifting

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Table 3: Effect of ketamine treatment over time: Shifting of suicidal ideation category in the C-SSRC (n=10)

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Suicide-related adverse events: No completed suicides, suicide ideation, or suicidal behaviour occurred during study. Other adverse effects such as nausea and vomiting were reported by two subjects but they subsided within an hour of the injection.


   Discussion Top


In this study, parenteral ketamine has resulted in a rapid and significant improvement in the depressive symptoms and SI. In addition, this study presents data indicating that repetitive ketamine infusions may be safe and feasible and, thus, may be an acceptable adjunct to standard antidepressant therapies for rapid relief of SI in inpatients with major depressive disorder (MDD). Two hours after the first injection of ketamine showed a significant reduction in the HAM-D and C-SSRS mean score of 58.04% and 88.46%, respectively. This improvement was sustained 1 month after the last dose (58.48% and 88.46%). Adverse effects noticed were of mild nature and transient lasting less than an hour. In this study, rapid decrease in HAM-D scores suggests overall improvement in depressive symptoms supporting rapid antidepressant effect of IV ketamine as similar results were found in a randomized placebo-controlled trials by Berman,[1] Zarate,[3] Murrough,[23] and Sos.[24]

In this study, rapid reduction in C-SSRC scores suggests overall improvement in SI supporting rapid anti-suicidal effect of IV ketamine as similar results were found in previous studies.[5],[9],[14],[15],[25] This rapid antidepressant and anti-suicidal effects are in contrast to traditional monoamine-based antidepressants that take weeks to months to exert their full antidepressant effect.[26] Studies focusing on of IV ketamine on depression and SI across the world showed in [Table 4].
Table 4: Studies focusing on effect of intravenous ketamine on depression and suicidal ideation

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Previous studies suggested repeated-dose ketamine as a potential antidepressant continuation strategy for patients who show initial response to ketamine infusion. For instance, a group of researchers used repeated-dose open-label ketamine (6 infusions over 12 days) in 10 medication-free TRD patients.[12] In another study, a treatment-refractory MDD patient was treated with six doses of ketamine (0.5 mg/kg, IV, days 1, 3, 5, 8, 11, and 13) and his depressive symptoms were significantly improved within 13 days and persisted for 3 months.[23] These data together with our data suggest that repeated doses of ketamine could also be effective in improving depressive symptoms in depressed patients.

No cognitive or psychotic symptoms were observed post infusion as similar finding was observed in previous studies with sub anaesthetic dose.[12],[33] However, ketamine ranks highly on the list of commonly abused substances.[34],[35],[36],[37],[38] Ketamine abusers also have high rates of depression[39] and experience significant brain dysfunction.[40] Whereas these risks have not been demonstrated in serial infusions for depressed patients.[41] Cognitive performance of poly-drug users and healthy controls were compared with the following three groups: ketamine ex-users, infrequent users, and frequent users. Cognitive impairments were significant among frequent users who self-administered greater than 1 g of ketamine at a minimum frequency of four times per week. Frequent users also showed impairments in recognition and working memory. No significant differences in performance were observed between controls, poly-drug users, and infrequent or ex-users of ketamine. This report also suggested that cognitive impairment associated with chronic and frequent ketamine use are reversible with abstinence.[42]

There are some limitations to this study. First, like other published studies, this study suffers from its retrospective design. It is not randomized, controlled, blinded, or prospective in nature. Second, small sample size from a single site limits the interpretations that can be drawn and the generalizability of the sample to the broader population of patients. Third, treatment was open label and adjunct to any existing antidepressant treatments, with the absence of a control.

Although the sample size was limited, most of the patients with depression who were treated with low-dose IV ketamine experienced rapid (within hours), robust, and persistent improvement of depressive symptoms and SI with limited adverse effects. Ketamine in sub anaesthetic doses has demonstrated efficacy for anxious or non-anxious depression,[43] unipolar depression,[27] bipolar depression,[44] TRD,[30] and SI associated with depression.[30] However, low doses (less than 0.5 mg/kg) of IV ketamine cannot ensure an antidepressant effect. In terms of treatment frequency, two to three repeated ketamine administrations per week may be required to maintain antidepressant efficacy. Furthermore, weekly maintenance doses could be used for maintaining remission or a significant response.[45] Our findings support the need for large adequately powered randomized controlled trials to determine both the efficacy and safety of serial ketamine infusions as an adjunct to usual treatment in patients with depression with SI in real world settings.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry 2000;47:351-4.  Back to cited text no. 1
    
2.
Marland S, Ellerton J, Andolfatto G, Strapazzon G, Thomassen O, Brandner B, et al. Ketamine: Use in anesthesia. CNS Neurosci Ther 2013;19:381-9.  Back to cited text no. 2
    
3.
Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 2006;63:856-64.  Back to cited text no. 3
    
4.
Price RB, Iosifescu DV, Murrough JW, Chang LC, Al Jurdi RK, Iqbal SZ, et al. Effects of ketamine on explicit and implicit suicidal cognition: A randomized controlled trial in treatment-resistant depression. Depress Anxiety 2014;31:335-43.  Back to cited text no. 4
    
5.
DiazGranados N, Ibrahim LA, Brutsche NE, Ameli R, Henter ID, Luckenbaugh DA, et al. Rapid resolution of suicidal ideation after a single infusion of an N-methyl-D-aspartate antagonist in patients with treatment-resistant major depressive disorder. J Clin Psychiatry 2010;71:1605-11.  Back to cited text no. 5
    
6.
Lapidus KA, Levitch CF, Perez AM, Brallier JW, Parides MK, Soleimani L, et al. A randomized controlled trial of intranasal ketamine in major depressive disorder. Biol Psychiatry 2014;76:970-6.  Back to cited text no. 6
    
7.
Murrough JW, Iosifescu DV, Chang LC, Al Jurdi RK, Green CE, Perez AM, et al. Antidepressant efficacy of ketamine in treatment-resistant major depression: A twosite randomized controlled trial. Am J Psychiatr 2013;170:1134-42.  Back to cited text no. 7
    
8.
Coyle CM, Laws KR. The use of ketamine as an antidepressant: A systematic review and meta-analysis. Hum Psychopharmacol Clin Exp 2015;30:152-63.  Back to cited text no. 8
    
9.
Wilkinson ST, Ballard ED, Bloch MH, Mathew SJ, Murrough JW, Feder A, et al. The effect of a single dose of intravenous ketamine on suicidal ideation: A systematic review and individual participant data meta-analysis. Am J Psychiatry 2018;175:150-8.  Back to cited text no. 9
    
10.
McIntyre RS, Carvalho IP, Lui LM, Majeed A, Masand PS, Gill H, et al. The effect of intravenous, intranasal, and oral ketamine in mood disorders: A meta-analysis. J Affect Disord 2020;276:576-84.  Back to cited text no. 10
    
11.
Murrough JW, Perez AM, Pillemer S, Stern J, Parides MK, aan het Rot M, et al. Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment resistant major depression. Biol Psychiatry 2013;74:250-6.  Back to cited text no. 11
    
12.
aan hetRot M, Collins KA, Murrough JW, Perez AM, Reich DL, Charney DS, et al. Safety and efficacy of repeated-dose intravenous ketamine for treatment-resistant depression. Biol Psychiatry 2010;67:139-45.  Back to cited text no. 12
    
13.
Jick H, Kaye JA, Jick SS. Antidepressants and the risk of suicidal behaviors. JAMA 2004;292:338-43.  Back to cited text no. 13
    
14.
Price RB, Nock MK, Charney DS, Mathew SJ. Effects of intravenous ketamine on explicit and implicit measures of suicidality in treatment-resistant depression. Biol Psychiatry 2009;66:522-6.  Back to cited text no. 14
    
15.
Ballard ED, Ionescu DF, Vande Voort JL, Niciu MJ, Richards EM, Luckenbaugh DA, et al. Improvement in suicidal ideation after ketamine infusion: Relationship to reductions in depression and anxiety. J Psychiatr Res 2014;58:161-6.  Back to cited text no. 15
    
16.
Ballard ED, Wills K, Lally N, Richards EM, Luckenbaugh DA, Walls T, et al. Anhedonia as a clinical correlate of suicidal thoughts in clinical ketamine trials. J Affect Disord 2017;218:195-200.  Back to cited text no. 16
    
17.
Lally N, Nugent AC, Luckenbaugh DA, Niciu MJ, Roiser JP, Zarate CA Jr. Neural correlates of change in major depressive disorder anhedonia following open-label ketamine. J Psychopharmacol 2015;29:596-607.  Back to cited text no. 17
    
18.
Lally N, Nugent AC, Luckenbaugh DA, Ameli R, Roiser JP, Zarate CA. Anti-anhedonic effect of ketamine and its neural correlates in treatment-resistant bipolar depression. Transl Psychiatry 2014;4:e469. doi: 10.1038/tp. 2014.105.  Back to cited text no. 18
    
19.
Oquendo MA, Sullivan GM, Sudol K, Baca-Garcia E, Stanley BH, Sublette ME, et al. Toward a biosignature for suicide. Am J Psychiatry 2014;171:1259-77.  Back to cited text no. 19
    
20.
Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23:56-62.  Back to cited text no. 20
    
21.
Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, et al. The Columbia–Suicide Severity Rating Scale: Initial validity and internal consistency findings from three multisite studies with adolescents and adults. Am J Psychiatry 2011;168:1266-77.  Back to cited text no. 21
    
22.
Ferguson GA. Statistical Analysis in Psychology and Education (fourth edition). New York: McGraw- Hill; 1976.  Back to cited text no. 22
    
23.
Murrough JW, Burdick KE, Levitch CF, Perez AM, Brallier JW, Chang LC, et al. Neurocognitive effects of ketamine and association with antidepressant response in individuals with treatment-resistant depression: A randomized controlled trial. Neuropsychopharmacology 2015;40:1084-90.  Back to cited text no. 23
    
24.
Sos P, Klirova M, Novak T, Kohutova B, Horacek J, Palenicek T. Relationship of ketamine's antidepressant and psychotomimetic effects in unipolar depression. Neuro Endocrinol Lett 2013;34:287-93.  Back to cited text no. 24
    
25.
Grunebaum MF, Galfalvy HC, Choo TH, Keilp JG, Moitra VK, Parris MS, et al. Ketamine for rapid reduction of suicidal thoughts in major depression: A midazolam-controlled randomized clinical trial. Am J Psychiatry 2018;175:327-35.  Back to cited text no. 25
    
26.
Katz MM, Tekell JL, Bowden CL, Brannan S, Houston JP, Berman N, et al. Onset and early behavioral effects of pharmacologically different antidepressants and placebo in depression. Neuropsychopharmacology 2004;29:566-79.  Back to cited text no. 26
    
27.
Mandal S, Sinha VK, Goyal N. Efficacy of ketamine therapy in the treatment of depression. Indian J Psychiatry 2019;61:480-5.  Back to cited text no. 27
[PUBMED]  [Full text]  
28.
Chilukuri H, Reddy NP, Pathapati RM, Manu AN, Jollu S, Shaik AB. Acute antidepressant effects of intramuscular versus intravenous ketamine [published correction appears in Indian J Psychol Med 2015;37:379]. Indian J Psychol Med 2014;36:71-6.  Back to cited text no. 28
[PUBMED]  [Full text]  
29.
Thakurta RG, Das R, Bhattacharya AK, Saha D, Sen S, Singh OP, et al. Rapid response with ketamine on suicidal cognition in resistant depression. Indian J Psychol Med 2012;34:170-5.  Back to cited text no. 29
[PUBMED]  [Full text]  
30.
Su TP, Chen MH, Li CT, Lin WC, Hong CJ, Gueorguieva R, et al. Dose-related effects of adjunctive ketamine in Taiwanese patients with treatment-resistant depression [published correction appears in Neuropsychopharmacology 2019;44:655-6]. Neuropsychopharmacology 2017;42:2482-92.  Back to cited text no. 30
    
31.
Zhan Y, Zhang B, Zhou Y, Zheng W, Liu W, Wang C, et al. A preliminary study of anti-suicidal efficacy of repeated ketamine infusions in depression with suicidal ideation [published correction appears in J Affect Disord 2020;274:1220]. J Affect Disord 2019;251:205-12.  Back to cited text no. 31
    
32.
Sinyor M, Williams M, Belo S, Orser B, Vincent M, Mah L, et al. Ketamine augmentation for major depressive disorder and suicidal ideation: Preliminary experience in an inpatient psychiatry setting. J Affect Disord 2018;241:103-9.  Back to cited text no. 32
    
33.
Souza-Marques B, Santos-Lima C, Araújo-de-Freitas L, Vieira F, Jesus-Nunes AP, Quarantini LC, et al. Neurocognitive effects of ketamine and esketamine for treatment-resistant major depressive disorder: A systematic review. Harv Rev Psychiatry 2021;29:340-50.  Back to cited text no. 33
    
34.
Liao Y, Tang J, Ma M, Wu Z, Yang M, Wang X, et al. Frontal white matter abnormalities following chronic ketamine use: A diffusion tensor imaging study. Brain 2010;133:2115-22.  Back to cited text no. 34
    
35.
Sassano-Higgins S, Baron D, Juarez G, Esmaili N, Gold M. A review of ketamine abuse and diversion. Depress Anxiety 2016;33:718-27.  Back to cited text no. 35
    
36.
Fang YX, Wang YB, Shi J, Liu ZM, Lu L. Recent trends in drug abuse in China. Acta Pharmacol Sin 2006;27:140-4.  Back to cited text no. 36
    
37.
Ahmed SN, Petchkovsky L. Abuse of ketamine. Br J Psychiatry 1980;137:303. doi: 10.1192/bjp. 137.3.303b.  Back to cited text no. 37
    
38.
Amann LC, Halene TB, Ehrlichman RS, Luminais SN, Ma N, Abel T, et al. Chronic ketamine impairs fear conditioning and produces long-lasting reductions in auditory evoked potentials. Neurobiol Dis 2009;35:311-7.  Back to cited text no. 38
    
39.
Rodríguez-Muñoz M, Sánchez-Blázquez P, Vicente-Sánchez A, Berrocoso E, Garzón J. The mu-opioid receptor and the NMDA receptor associate in PAG neurons: Implications in pain control. Neuropsychopharmacology 2012;37:338-49.  Back to cited text no. 39
    
40.
Morgan CJ, Dodds CM, Furby H, Pepper F, Fam J, Freeman TP, et al. Long-term heavy ketamine use is associated with spatial memory impairment and altered hippocampal activation. Front Psychiatry 2014;5:149. doi: 10.3389/fpsyt. 2014.00149.  Back to cited text no. 40
    
41.
Shiroma PR, Albott CS, Johns B, Thuras P, Wels J, Lim KO. Neurocognitive performance and serial intravenous subanesthetic ketamine in treatment-resistant depression. Int J Neuropsychopharmacol 2014;17:1805-13.  Back to cited text no. 41
    
42.
Morgan CJ, Muetzelfeldt L, Curran HV. Consequences of chronic ketamine self-administration upon neurocognitive function and psychological wellbeing: A 1-year longitudinal study [published correction appears in Addiction. 2010;105:766]. Addiction 2010;105:121-33.  Back to cited text no. 42
    
43.
Salloum NC, Fava M, Freeman MP, Flynn M, Hoeppner B, Hock RS, et al. Efficacy of intravenous ketamine treatment in anxious versus nonanxious unipolar treatment-resistant depression. Depress Anxiety 2019;36:235-43.  Back to cited text no. 43
    
44.
Zarate CA Jr, Brutsche NE, Ibrahim L, Franco-Chaves J, Diazgranados N, Cravchik A, et al. Replication of ketamine's antidepressant efficacy in bipolar depression: A randomized controlled add-on trial. Biol Psychiatry 2012;71:939-46.  Back to cited text no. 44
    
45.
Shin C, Kim YK. Ketamine in major depressive disorder: Mechanisms and future perspectives. Psychiatry Investig 2020;17:181-92.  Back to cited text no. 45
    


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  [Table 1], [Table 2], [Table 3], [Table 4]



 

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