Why Might Ketamine Infusion Therapy Work for Me?

Antidepressant therapy has been available for over 50 years, and its emergence was heralded as a major victory for medical science. Despite this success, many patients do not experience relief with antidepressants, with cumulative rates of remission standing at 67% (Rush et al 2006). This means, that on average, 33% of those treated fail to achieve any meaningful improvement in their depression symptoms.


Through a fortuitous discovery, ketamine was found to dramatically and rapidly alleviate depression in adults after receiving only one low-dose IV infusion (Berman et al. 2000). Later studies by Zarate et al. (2006) and Murrough et al. (2013) confirmed these findings in larger randomized controlled trials involving patients with treatment resistant depression.


Ketamine’s acts on the NMDA receptor, antagonizing glutamate signaling. Both depression and prolonged stress are associated with atrophy of neurons and damage of synapse function (Kang et al. 2012). Prolonged stress induces changes in glutamate release and reuptake, leading to toxic levels of glutamate in the synapse. This, in turn, has a damaging effect on synapse, stripping the fine connections between nerves within the brain regions regulating mood. Evidence suggests that ketamine acts to block and reverse the damaging effect associated with toxic levels of glutamate and accelerates new synapse formation (Duman and Aghajanian 2012, Li et al. 2010).


Several trials consistently report rapid antidepressant effects beginning within 4 hours of IV infusion (Abdallah et al. 2015; Berman et al. 2000; Bessa et al. 2009,2013; Caddy et al. 2014; Duman and Aghajaninan 2012; Fond et al. 2014; Kang et al. 2012). In the short term, patient response rates were found to range from 43% up to 90% (Phelps et al. 2009, aan het Rot et al. 2008). Some sustained effects were seen for as long as 28 days after a single infusion (Ibrahim et al. 2012, Zarate et al. 2006).



aan het Rot M, Charney DS, Mathew SJ (2008) Intravenous ketamine for treatment-resistant major depressive disorder. Primary Psychiatry 15(4):39–47

Abdallah CG, Averill LA, Krystal JH (2015a) Ketamine as a promising prototype for a new generation of rapid-acting antidepressants. Ann N Y Acad Sci 1344:66–77

Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH (2000) Antidepressant effects of ketamine in depressed patients. Biol Psychiatry 47(4):351–354

Bessa JM, Ferreira D, Melo I, Marques F, Cerqueira JJ, Palha JA, Almeida OF, Sousa N (2009) The mood-improving actions of antidepressants do not depend on neurogenesis but are associated with neuronal remodeling. Mol Psychiatry 14(8):764–773, 739

Caddy C, Giaroli G, White TP, Shergill SS, Tracy DK (2014) Ketamine as the prototype glutamatergic antidepressant: pharmacodynamic actions, and a systematic review and meta-analysis of efficacy. Ther Adv Psychopharmacol 4(2):75–99

Duman RS, Aghajanian GK (2012) Synaptic dysfunction in depression: potential therapeutic targets. Science 338(6103):68–72

Fond G, Loundou A, Rabu C, Macgregor A, Lancon C, Brittner M, Micoulaud-Franchi JA, Richieri R, Courtet P, Abbar M, Roger M, Leboyer M, Boyer L (2014) Ketamine administration in depressive disorders: a systematic review and meta-analysis. Psychopharmacology (Berl) 231(18):3663–3676

Ibrahim L, Diazgranados N, Franco-Chaves J, Brutsche N, Henter ID, Kronstein P, Moaddel R, Wainer I, Luckenbaugh DA, Manji HK, Zarate CA Jr (2012) Course of improvement in depressive symptoms to a single intravenous infusion of ketamine vs add-on riluzole: results from a 4-week, double-blind, placebo-controlled study. Neuropsychopharmacology 37:1526–1533

Kang HJ, Voleti B, Hajszan T, Rajkowska G, Stockmeier CA, Licznerski P, Lepack A, Majik MS, Jeong LS, Banasr M, Son H, Duman RS (2012) Decreased expression of synapse-related genes
and loss of synapses in major depressive disorder. Nat Med 18(9):1413–1417

Li N, Lee B, Liu RJ, Banasr M, Dwyer JM, Iwata M, Li XY, Aghajanian G, Duman RS (2010) mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science 329(5994):959–964

Murrough JW, Iosifescu DV, Chang LC, Al Jurdi RK, Green CE, Perez AM, Iqbal S, Pillemer S, Foulkes A, Shah A, Charney DS, Mathew SJ (2013a) Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry 170(10):1134–1142

Phelps LE, Brutsche N, Moral JR, Luckenbaugh DA, Manji HK, Zarate CA Jr (2009) Family history of alcohol dependence and initial antidepressant response to an N-methyl-D-aspartate antagonist. Biol Psychiatry 65(2):181–184

Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, Niederehe G, Thase ME, Lavori PW, Lebowitz BD, McGrath PJ, Rosenbaum JF, Sackeim HA, Kupfer DJ Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK (2006) A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 63(8):856–864