• Users Online: 44
  • Print this page
  • Email this page

Table of Contents
Year : 2021  |  Volume : 20  |  Issue : 2  |  Page : 27-31

Ketamine for treatment-resistant depression

General Psychiatrist in Department of Psychiatry, Almahmodya General Hospital, Baghdad, Iraq

Date of Submission25-Apr-2021
Date of Decision20-Jun-2021
Date of Acceptance25-Jul-2021
Date of Web Publication15-Dec-2021

Correspondence Address:
Dr. Raad Saady Madhloom
General Psychiatrist in Department of Psychiatry, Almahmodya General Hospital, Baghdad
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/mj.mj_15_21

Rights and Permissions

Major depressive disorder (MDD) is of influence on about 350 million individuals worldwide, which is causing disability consecution and damaging consequences to the affected community and individuals. Treatments as antidepressant are affecting the system of monoamine where symptoms of depressive were relived in about 50% of cases. Such ratio turns into obviously low in depressed persons who failed already to cure following 2 or additional antidepressant drugs at sufficient duration and doses regarding it a treatment-resistant depression (TRD). There is an obvious requisite for quick action and influenced treatments. Ketamine (KMN) is considered an anesthetic old drug that has a promising quick action as an antidepressant in TRD patients with MDD, concentrating on clinical issues, i.e. administration route, dose, and action duration. Other indication proposes that KMN might be influenced in stress disorder as posttraumatic and ideation as acute suicidal.

Keywords: Ketamine, Esketamine, Resistant Depression

How to cite this article:
Madhloom RS. Ketamine for treatment-resistant depression. Mustansiriya Med J 2021;20:27-31

How to cite this URL:
Madhloom RS. Ketamine for treatment-resistant depression. Mustansiriya Med J [serial online] 2021 [cited 2022 May 23];20:27-31. Available from: https://www.mmjonweb.org/text.asp?2021/20/2/27/332559

  Introduction Top

Ketamine (KMN), as an anesthetic agent introduced in the 1960s, has assembled striking interest for the past 20 years as an arising management for major depressive disorder (MDD). With its high efficacy evidence in treatment-resistant depression (TRD) and its potential action as antisuicidal, investigations have been structured on brain clarify influences of KMN. The KMN strength to put out quick antidepressant influences as early as a small number of hours following administration. Such is in striking difference to the delayed influences recognized with customary antidepressants, frequently need several therapy weeks for response clinically. In addition, KMN seems to have an exclusive action mechanism involvement glutamate modification through receptors actions of N-methyl-D-aspartate (NMDA) and amino 3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, as well as besides subsequent activation of brain-derived neurotrophic factor (BDNF) and mechanistic target of rapamycin synaptic plasticity.[1] KMN is an antagonist non-competitive (NMDA) receptor and was untypically utilized as anesthetic being dissociative. It was 1st recorded to have antidepressant characteristics in 2000, when it was determined that subanesthetic KMN dose intravenous (IV) administration in MDD symptoms abatement immediately and lasting to 72 h following treatment.[2] Foregoing as randomized controlled trials (RCTs) imprint such spotting, determining a 60%–70% level of KMN response in population of TRD.[3] KMN following administration is of a quick influence clinically within 2–4 h. Despite antidepressant of KMN characteristics are as well short lived, enduring 1 week average after infusion being single (10–14) and (18–19) days after subsequent infusions.[4],[5] In addition, KMN has also been well known of actions as antianhedonic and antisuicidal.[6] Esketamine has a quickly clinical influence through numerous hours and sustain capability in cases where patients not responding to other different antidepressants, it emerge of having a peculiar action mechanism which is different from traditional drugs as antidepressant. Reports at this time on other KMN administration types are inadequate. Whereas one RCT on intranasal (IN) KMN,[7] imply that administration as IN might be alternative as possible, another report was canceled early because of poor endurance to the formulation as IN.[8] Other studies[9],[10] have described that despite it rests experimental naturally, preservation of IN KMN is clinically helpful in cases where patients are of noncompliance other treatments options. Researches on sublingual and normal oral KMN were the susceptible of a current systematic assessment.[11] One pilot preceding investigation is also recommended that subcutaneous or intramuscular paths might be choices being possible.[12] Esketamine as IN was permitted via FDA in USA in March 2019 for MDD which not responding to 2 or further antidepressants. Such recommendation was according to 2 maintenance-phase and 3 acute-phase studies. Trial of phase III over two hundred cases utilizing esketamine concomitant to an antidepressant sustained serious recovery in depression at 4 weeks in comparison to those utilizing a placebo nasal spray. Retrospective data as actual-world clinically reveal a 44% response rate following 6 IV KMN treatments in a complex patient's society with multiple co morbidities and depression of ultra-resistant.[13],[14]

  Methodology Top

It is review of the available knowledge and papers on the subject of using ketamine in depression, we use search engines:- (Google scholar, Research gate, Google books) and the key words to search were:- ketamine therapy, desketamine, depression, after this search we include relevant article that were puplished during (2000-2020).

  Adverse Influences of Ketamine Top

KMN side influence associated with use of KMN include emergence reactions, increased cardiac output, double vision, vivid dreams, increased intra ocular pressure and injection site pain, mostly of which happen throughout the period of infusion and thereafter shortly. Such doses as subanesthetic can also be related with neuropsychiatric influences as short-lasting. Such transient and acute influences including an upsurge in blood pressure (typically asymptomatic), vomiting and nausea, dizziness, drowsiness, and dissociation, less common side influence include muscle twitching and spasm, increased salivation.[14] Blood pressure must be check up previous and following KMN administration till it proceeds to values being normal.[15]

  Biomarkers Predicting Response to Ketamine Sleep Top

KMN has strong influences on rising sleep as total and of slow-wave sleep, slow-wave activity (SWS, SWA).[16] and its antidepressant influence were related to such influence.[17] SWA and SWS improvement, peculiarly at initial night, is regarded a demanding aspect in mechanism of KMN as quick action of antidepressant in MDD, and same issue were observed with as repetitive transcranial magnetic stimulation.[18] Such SWA increment strongly correspond with rising in pre-clinically plasma BDNF and synaptic plasticity.[19] Also in KMN responsive MDD patients.[16],[17] BDNF is a recognized possible antidepressant response marker.[20] The increased degree was observed to anticipate acute response mood to KMN.[21] Excitingly, such improvement in SWA, SWS might be particular to unipolar depression patients.[22] Total sleep improvement, peculiarly minimization in holy electroencephalogram, early night awakening, can be apparatus where KMN apply its antisuicidal influences.[23] Such must be an attractive future study area as mechanisms of nonantidepressant requisite to be enlightened to fully elucidate the KMN anti-suicidal influences.[24] KMN also shows of having serious consequence on systems of circadian rhythm, and its influences on glutamate possible inhibit portion of such symultaneity of light/dark and The internal clock is moderatly mediated via glutamate in the retinothalamic tract.[25]

  Cognition Top

Treatment of KMN in a definite MDD treatment agreement also display encouraging outcome in cognition and cognitive symptoms. Three patients groups with resistant treatment as bipolar and unipolar depression; TRD anxious and nonanxious depression were received 6 KMN infusions for 12 days along with alike cognitive examining in a period of 2 weeks of follow-up. Of the studies, in cognitive function, no any deterioration was observed. Verbal learning and processing speed were improved, but such was correlated significantly with depressive symptoms' improvement.[26],[27],[28] In TRD patients, 0.5 mg/kg single infusion also was observed as beneficial slightly in response control and attention as well.[29] This was a concern in which chronic KMN utilize might cause deficits as cognitive ones. KMN chronic and heavy utilizers were noticed of having a diversity of deficits of cognitive function through numerous domains. They include memory verbal/visual memory and word reading, executive function and motor speed, besides verbal fluency, verbal learning specific to medial temporal and frontal cognition, and speed of processing. Chronic KMN small group utilizers have also revealed spatial disturbances of memory and altered activity as hippocampal.[30],[31],[32]

  Metabolism and Inflammation Top

Metabolic syndrome, with a variety of manifestation counting: Hypercholesterolemia, hypertension, hyperglycemia and widening WC is prevalent in mood disorders patients. A new research shows a metabolic syndrome of 38% prevalence in TRD patients, and it was predicted that relatively 1/3 of patients that depressed have increased markers of inflammation.[33] A serious earlier complicated accord found between syndrome as metabolic and disorders of mood and such association show to prove inflammation. Metabolic syndrome in TRD patient is 3 times extra prevalent in patients of high (C-reactive protein [CRP]), marker of inflammation.[34] Organized report studying at predeators of feedback in TRD advocate that markers of inflammation of interleukin-6, CRP and antidepressant drug response of anti-inflammatory characteristics, as well as KMN.[35] Communications mechanisms among KMN, depression, inflammation and metabolism still ambiguous, but are possible arbiterate via various factors. Increased (body mass index) has been formed as response to KMN prediction.[36],[37]

  Neuroimaging Top

A widely spreading literature is there on neuro-anatomical of response to KMN biomarkers medication. MDD was approved to influence, among other areas, the pre frontal cortex, anterior cingulate, the hippocampus and there is proof that mode of action of KMN on these areas specifically.[38],[39]

  Route of Administration Top

KMN is administrated via several rout include: IV infusion, IN, sublingual, intramuscular, oral, rectally (suppository). In many studies, depressive symptoms considerably corrected following KMN IV administration in comparison to placebo. Whereas other research correlated the antidepressants influence duration with IN KMN and IV,[40],[41] and achieve no difference was there between IV and IN administration from day 1 over the correlation is according to a single research with IN KMN.[7] Also, it is essential to analyze the KMN treatment interaction with current antidepressant and/or therapy of enhancement (antipsychotics, anxiolytics, and mood stabilizers). Clinical trials are mostly of need a complementary medication washout, whereas just few have examined efficacy of KMN as a continuing antidepressant treatment associate or therapy as electroconvulsive. Both designs of trials have demonstrated that KMN is efficient in depression correction.[3] Hence, in practice as clinical, it is not mandatory for specialist to washout patient's current antidepressant medication.[40] KMN is mostly administered frequently in 0.5 mg/kg dose, but a seldom dose of 0.1 mg/kg being low is adequate, while others might need 0.75 mg/kg. The KMN dose is properly applied through forty min, though efficacy and safety have been confirmed in a period between 2 and 100 min. Administration of Bolus is influenceive and safe if the drug is administered in IM and SC rout, whereas the IV route is the most frequently employed. KMN infusion therapy involves[6] low-dose IV KMN infusions over the course of 2 weeks.[41]

  Single Intravenous Infusion Efficacy Against Intravenous Infusions Being Repeated Top

KMN administration is as single doses of IN and IV have always revealed antidepressant influence for concurently 7 days. Less reports have displayed the influences of recurrent KMN administrations. In an exploratory examining the[6] IV KMN infusions influence over 2 weeks, revealed that 24 participant of 70.8% with depression as unipolar and contemporary medications free responded with an ordinary response continuing duration of 18 days, response following 6 IV KMN infusions was expected strongly for responding at 4 h following the 1st infusion. The responding duration after the[6] infusion continued between (25–168) days; studies achieve that responding to a repeated KMN applications sequence can be expected following the 1st one or 2 infusions. This is significant as in clinical practice longer KMN administrations successions would just be confirmed in patients undergoing early responding to the 1st 2 treatments.[41]

  Influence of Ketamine on Anhedonia and Suicidal Ideation Top

Suicidal ideation in the midst of the highest clinically regarding of depression, and still a dominant cause of death. Studies always reveal a serious decline in SL following administration of KMN. In a report appraise implement of KMN on suicidality in TRD patients, single KMN doses declined both SL and depression, with provide recovery for 2 weeks after infusions being repeated.[42],[43] In a 14 patients study with MDD expressing suicide enter to the Department of Emergency, a KMN single dose (0.20 mg/kg) carry out for 1–2 min diminish Sl obviously when seeing 40 min postinfusion.[43],[44] A suicidal patients study with a different anxiety and mood disorders enter to unit of inpatient psychiatric revealed fast Sl improvement following IV KMN in comparison to midazolam.[4] Last research recommend that defenit anti suicidal KMN influences might be associated to recovery in executive functioning and cognitive emotional, (planning, memory, behavioral inhibition, cognitive flexibility); the networks as neural including the prefrontal support of cortex both recovery in cognition and depression.[45] Also, Lally et al. described that following a single IV KMN dose, patients of 87% display recovery in anhedonia at 4 h post infusion advancement in anhedonia was correspond with improvement in total depression;[46] therefore, it is confused if in anhedonia the improvement is pseudo-specific (because of antidepressant influence). Given that deterioration in the reward brain system is affiliated with suicidality, depression, and anhedonia, where such might be possible where targets of KMN such circuit as neural that consists of the dorsal areas being anterior cingulate orbitofrontal cortex, basal ganglia, cortex, and hippocampus.[45],[46],[47]

  Contraindications Top

KMN is contraindicated in those with elevated blood pressure would face complications risk like uncontrolled hypertension, aortic dissection, aneurysms, or myocardial infarction. It is restricted in those with prior history of hypersensitivity to the drug. It is not needed for utilize throughout pregnancy, obstetrics, or for breastfeeding women as it is unknown if such drug enter into breast milk. Utilize in patient severely alcohol-intoxicated might cause death. Also, its restricted in patients with schizophrenia because of the possible exacerbating of the underlying condition and in patients with elevations of cerebrospinal fluid (CSF). Few studies attribute that the CSF elevation worry with KMN has been overmentioned.[48]

  How to Prepare for Ketamine Treatment Top

In general, fasting before each KMN infusion is recommended. This could mean avoiding food and drink the night before and the morning of treatment, depending on when infusion is scheduled. Also shouldn't have caffeine, including soda and coffee, before treatment. Certain medications may also need to be discontinued temporarily before undergo KMN treatment. It is best not to be overtired or stressed, so that relax during treatment and get a good night sleep.

The treatment takes about 90 min from start to finish, KMN can have a sedating influence, since sit for some time in a relaxed state, shouldn't wear any binding or uncomfortable clothing.

Following the treatment, should not drive for the rest of the day, so a family member needed to accompany the patient for driving to home.[49]

  Conclusion Top

There has been raising concern about KMN in the last decades, largely due to its quick and promising antisuicidal and antidepressant actions in TRD patients. The preclinical and clinical researches have caused eventual consideration of it's utilize in psychiatry, and such will carry on to be an influenceive more investigations area. Individual differences among patients include differences in sex and suitable regimens determination for therapy of maintenance need to be studied. Also, a requisite is there for investigating extra dependable biomarkers to predict KMN response. KMN rests an auspicious choice for such TRD suffering, and it is led to follow the theory which realizing neurochemical mechanism of KMN.

Administration of KMN was correlated with quick clinical recovery (within 24 h) in patients of TRD, depression as bipolar, PTSD, and such with acute SI. The single KMN influence dose emerges to stay up to 7 days in TRD as unipolar and 3–4 days in bipolar depression. Severe depression with anxiety or cognitive dysfunction might be an excellent target for KMN treatment. Repeated KMN doses are stated to be harmless and offer prolong responding clinically. Responding to a frequent KMN administrations series might be expected following the 1st one or 2 infusions. IN KMN has positive influences in comparison with IV KMN and is developed nowadays for patients of self-administrated. The 0.5 mg/kg dose as IV KMN typically was used. We can be use KMN in besides ongoing treatment as antidepressant. Further monitoring must be necessary for patients with previous cardiovascular disease history. Previous psychosis history might be regarded contraindication as relative.

  Limitation and Criticism Top

Review of previous articles on KMN use in depression shows that long-term efficacy of KMN has not been investigated also regarding side effect of longer period of use and multiple infusion. They are only tested injected type of drug, so we cannot know whether nasal application might change the way that side effect appear. Therefore, following of patient more than 3 month is needed to measure craving and dependence or abuse. Interest in KMN use will continue because of work of KMN to relief depression is so swiftly when comparing it with other failed antidepressant drug. However, many questions in regard to extended use is must put in mind.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Matveychuk D, Thomas RK, Swainson J, Khullar A, MacKay MA, Baker GB, et al. KMN as an antidepressant: Overview of its mechanisms of action and potential predictive biomarkers. Ther Adv Psychopharmacol 2020;10:1-21.  Back to cited text no. 1
Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, et al. Antidepressant influences of KMN in depressed patients. Biol Psychiatry 2000;47:351-4.  Back to cited text no. 2
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 two-site randomized controlled trial. Am J Psychiatry 2013;170:1134-42.  Back to cited text no. 3
Murrough JW, Perez AM, Pillemer S, Stern J, Parides MK, Aan Het Rot M, et al. Quick and longer-term antidepressant influences of repeated KMN infusions in treatment resistant major depression. Biol Psychiatry 2013;74:250-6.  Back to cited text no. 4
Rot M, Collins KA, Murrough JW, Perez AM, Reich DL, Charney DS, et al. Safety and efficacy of repeated – Dose intravenous KMN for treatment – Resistant depression. Biol Psychiatry 2010;67:139-45.  Back to cited text no. 5
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. 6
Lapidus KA, Levitch CF, Perez AM, Brallier JW, Parides MK, Soleimani L, et al. A randomized controlled trial of intranasal KMN in MD. Biol Psychiatry 2014;76:970-6.  Back to cited text no. 7
Gálvez V, Li A, Huggins C, Glue P, Martin D, Somogyi AA, et al. Repeated intranasal ketamine for treatment-resistant depression – The way to go? Results from a pilot randomised controlled trial. J Psychopharmacol 2018;32:397-407.  Back to cited text no. 8
Lee V, Archer S, Chrenek C, Swainson J. A response to: Repeated intranasal ketamine for treatment resistant depression: The way to go? Results from a pilot randomised controlled trial. J Psychopharmacol 2019;33:258-9.  Back to cited text no. 9
Andrade C. Intranasal drug delivery in neuropsychiatry: Focus on intranasal KMN for refractory depression. J Clin Psychiatry 2015;76:e628-31.  Back to cited text no. 10
Rosenblat JD, Carvalho AF, Li M, Lee Y, Subramanieapillai M, McIntyre RS. Oral KMN for depression: A systematic review. J Clin Psychiatry 2019;80:18r12475.  Back to cited text no. 11
Loo CK, Galvez V, O'Keefe E, Mitchell PB, Hadzi-Pavlovic D, Leyden J, et al. Placebo- controlled pilot trial testing dose titration andintravenous, intramuscular and subcutaneous routes for KMN in depression. Acta Psychiatr Scand 2016;134:48-56.  Back to cited text no. 12
Popova V, Daly EJ, Trivedi M, Cooper K, Lane R, Lim P, et al. Efficacy and safety of flexibly dosed esketamine nasal spray combined with a newly initiated oral antidepressant in treatment-resistant depression: A randomized double-blind active-controlled study. Am J Psychiatry 2019;176:428-38.  Back to cited text no. 13
Andrade C. KMN for depression, 1: Clinical summary of issues related to efficacy, adverse influences, and mechanism of action. Clin Psychiatry 2017;78:e415-9.  Back to cited text no. 14
Szarmach J, Cubala WJ, Wlodarczyk A, Wiglusz MS. Short-term KMN administration in treatment – Resistant depression: Focus on cardiovascular safety. Psychiatr Danub 2019;31 Suppl 3:585-90.  Back to cited text no. 15
Duncan WC Jr., Zarate CA Jr. KMN, sleep, and depression: Current status and new questions. Curr Psychiatry Rep 2013;15:394.  Back to cited text no. 16
Duncan WC, Sarasso S, Ferrarelli F, Selter J, Riedner BA, Hejazi NS, et al. Concomitant BDNF and sleep slow wave changes indicate KMN – Induced plasticity in MDD. Int J Neuropsychopharmacol 2013;16:301-11.  Back to cited text no. 17
Duncan WC Jr., Ballard ED, Zarate CA. Ketamine-induced glutamatergic mechanisms of sleep and wakefulness: Insights for developing novel treatments for disturbed sleep and mood. Handb Exp Pharmacol 2019;253:337-58.  Back to cited text no. 18
Huber R, Tononi G, Cirelli C. Exploratory behavior, cortical BDNF expression, and sleep homeostasis. Sleep 2007;30:129-39.  Back to cited text no. 19
Björkholm C, Monteggia LM. BDNF – A key transducer of antidepressant effects. Neuropharmacology 2016;102:72-9.  Back to cited text no. 20
Haile CN, Murrough JW, Iosifescu DV, Chang LC, Al Jurdi RK, Foulkes A, et al. Plasma brain derived neurotrophic factor (BDNF) and response to KMN intreatment – Resistant depression. Int J Neuropsychopharmacol 2014;17:331-6.  Back to cited text no. 21
Geoffroy PA, Hoertel N, Etain B, Bellivier F, Delorme R, Limosin F, et al. Insomnia and hypersomnia in major depressive episode: Prevalence, sociodemographic characteristics and psychiatric comorbidity in a population-based study. J Affect Disord 2018;226:132-41.  Back to cited text no. 22
Vande Voort JL, Ballard ED, Luckenbaugh DA, Bernert RA, Richards EM, Niciu MJ, et al. Antisuicidal response following ketamine infusion is associated with decreased nighttime wakefulness in major depressive disorder and bipolar disorder. J Clin Psychiatry 2017;78:1068-74.  Back to cited text no. 23
Ballard ED, Ionescu DF, Vande Voort JL, Philips J, Normis S, Ortiz A, et al. Improvement in SI following KMN infusion: Relationship to reductions in depression and anxiety. Psychiatr Res 2014;58:161-6.  Back to cited text no. 24
Duncan WC Jr., Slonena E, Hejazi NS, Brutsche N, Yu KC, Park L, et al. Motor-activity markers of circadian timekeeping are related to ketamine's rapid antidepressant properties. Biol Psychiatry 2017;82:361-9.  Back to cited text no. 25
Zhou Y, Zheng W, Liu W, Wang C, Zhan Y, Li H, et al. Neurocognitive effects of six ketamine infusions and the association with antidepressant response in patients with unipolar and bipolar depression. J Psychopharmacol 2018;32:1118-26.  Back to cited text no. 26
Zheng W, Zhou YL, Liu WJ, Wang CY, Zhan YN, Li HQ, et al. Neurocognitive performance and repeated-dose intravenous ketamine in major depressive disorder. J Affect Disord 2019;246:241-7.  Back to cited text no. 27
Liu W, Zhou Y, Zheng W, Wang C, Zhan Y, Lan X, et al. Repeated intravenous infusions of KMN: Neurocognition in patients with anxious and nonanxious treatment – Resistant depression. J Affect Disord 2019;259:1-6.  Back to cited text no. 28
Chen MH, Li CT, Lin WC, Hong CJ, Tu PC, Bai YM, et al. Cognitive L. function of patients with treatment – Resistant depression following a single low dose of KMN infusion. J Affect Disord 2018;241:1-7.  Back to cited text no. 29
Ke X, Ding Y, Xu K, He H, Wang D, Deng X, et al. The profile of cognitive impairments in chronic KMN users. Psychiatry Res 2018;266:124-31.  Back to cited text no. 30
Chan KW, Lee TM, Siu AM, Wong DP, Kam CM, Tsang SK, et al. Effects of chronic ketamine use on frontal and medial temporal cognition. Addict Behav 2013;38:2128-32.  Back to cited text no. 31
Morgan CJ, Dodds CM, Furby H, Pepper F, Fam J, Freeman TP, et al. Long term heavy KMN use is associated with spatial memory impairment and altered hippocampal activation. Front Psychiatry 2014;5:149.  Back to cited text no. 32
Haroon E, Miller AH. Inflammation influences on brain glutamate in depression: Mechanistic considerations and treatment implications. Curr Top Behav Neurosci 2017;31:173-98.  Back to cited text no. 33
Godin O, Bennabi D, Yrondi A, Richieri R, D'Amato T, Bellivier F, et al. Prevalence of metabolic syndrome and associated factors in a cohort of individuals with treatment-resistant depression: Results from the FACE-DR study. J Clin Psychiatry 2019;80:19m12755.  Back to cited text no. 34
Yang C, Wardenaar KJ, Bosker FJ, Li J, Schoevers RA. Inflammatory markers and treatment outcome in treatment resistant depression: A systematic review. J Affect Disord 2019;257:640-9.  Back to cited text no. 35
Niciu MJ, Luckenbaugh DA, Ionescu DF, Guevara S, Machado-Vieira R, Richards EM, et al. Clinical predictors of KMN response in treatment – Resistant major depression. Clin Psychiatry 2014;75:e417-23.  Back to cited text no. 36
Abdallah CG, Sanacora G, Duman RS, Krystal JH. The neurobiology of depression, KMN and quick-acting antidepressants: Is it glutamate inhibition or activation? Pharmacol Ther 2018;190:148-58.  Back to cited text no. 37
Ionescu DF, Felicione JM, Gosai A, Cusin C, Shin P, Shapero BG, et al. Ketamine-associated brain changes: A review of the neuroimaging literature. Harv Rev Psychiatry 2018;26:320-39.  Back to cited text no. 38
Zhong M, Wang X, Xiao J, Yi J, Zhu X, Liao J, et al. Amygdala hyperactivation and prefrontal hypoactivation in subjects with cognitive vulnerability to depression. Biol Psychol 2011;88:233-42.  Back to cited text no. 39
McGirr A, Berlim MT, Bond DJ, Fleck MP, Yatham LN, Lam RW. A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials of ketamine in the rapid treatment of major depressive episodes. Psychol Med 2015;45:693-704.  Back to cited text no. 40
Diamond PR, Farmery AD, Atkinson S, Haldar J, Williams N, Cowen PJ, et al. Ketamine infusions for treatment resistant depression: A series of 28 patients treated weekly or twice weekly in an ECT clinic. J Psychopharmacol 2014;28:536-44.  Back to cited text no. 41
Nock MK, Borges G, Bromet EJ, Cha CB, Kessler RC, Lee S. Suicide and suicidal behavior. Epidemiol Rev 2008;30:133-54.  Back to cited text no. 42
Price RB, Mathew SJ. Does KMN have anti – Suicidal characteristics? Current status and future directions. CNS Drugs 2015;29:181-8.  Back to cited text no. 43
Larkin GL, Beautrais AL. A preliminary naturalistic study of low-dose ketamine for depression and suicide ideation in the emergency department. Int J Neuropsychopharmacol 2011;14:1127-31.  Back to cited text no. 44
Lee Y, Syeda K, Maruschak NA, Cha DS, Mansur RB, Wium-Andersen IK, et al. A new perspective on the anti – Suicide influences with KMN treatment: A procognitive influence. J Clin Psychopharmacol 2016;36:50-6.  Back to cited text no. 45
Lally N, Nugent AC, Luckenbaugh DA, Niciu MJ, Roiser JP, Zarate CA Jr. Neural correlates of change in MDD anhedonia following open – Label KMN. J Psychopharmacol 2015;29:596-607.  Back to cited text no. 46
Murrough JW, Collins KA, Fields J, DeWilde KE, Phillips ML, Mathew SJ, et al. Regulation of neural responses to emotion perception by KMN in individuals with treatment – Resistant MDD. Trans Psychiatry 2015;5:e509.  Back to cited text no. 47
Andrade C. KMN for depression, 4: In what dose, at what rate, by what route, for how long, and at what frequency. J Clin Psychiatry 2017;78:e852-7.  Back to cited text no. 48
Lusko AA, DO Gilbert, AZ, Palo Alto Mind Body, Blog who to prepear for your KMN treatment, KMN Integrative Medicine 480;877:0908.  Back to cited text no. 49


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article
Adverse Influenc...
Biomarkers Predi...
Metabolism and I...
Route of Adminis...
Single Intraveno...
Influence of Ket...
How to Prepare f...
Limitation and C...

 Article Access Statistics
    PDF Downloaded138    
    Comments [Add]    

Recommend this journal