Fortschr Neurol Psychiatr 2015; 83(02): 91-97
DOI: 10.1055/s-0034-1398967
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Ketamin – Eine neue Option in der Behandlung der therapieresistenten Depression

Ketamine – A New Treatment Option for Therapy-Resistant Depression
S. Köhler
,
F. Betzler
Further Information

Publication History

23 November 2014

22 January 2015

Publication Date:
27 February 2015 (online)

Zusammenfassung

In den letzten zwei Jahren konnte für das Anästhetikum Ketamin in mehreren doppelblind-kontrollierten Untersuchungen ein antidepressiver Effekt nachgewiesen werden. Für Patienten mit schwerer therapieresistenter Depression konnten Response-Raten von bis zu 70 % nach einmaliger intravenöser Gabe erreicht werden. Im Unterschied zu allen zur Verfügung stehenden antidepressiven Behandlungsmethoden zeigte sich dieser robuste antidepressive Effekt bereits 24 Stunden nach der Infusion. Dem gegenüber steht jedoch eine zeitlich begrenzte Wirksamkeit einer Ketaminbehandlung mit Rezidivraten von bis zu 70 % innerhalb von zwei Wochen nach der Behandlung. Der vorliegende Artikel gibt einen Überblick sowohl über die klinischen Studien zur Wirksamkeit von Ketamin in der Behandlung depressiver Störungen als auch über antidepressive Wirkfaktoren von Ketamin und über aktuelle Studien und praktische Hinweise.

Abstract

The anaesthetic ketamine has been demonstrated to have an antidepressive effect in several randomised controlled studies. Patients with a severe therapy-resistant depression showed response rates of up to 70 % after one single ketamine infusion. In contrast to all other antidepressant treatment options, this effect was already apparent at 24 hours post infusion. However, the antidepressant effect is limited and after two weeks the relapse rate is around 70 %. This review gives a summary of the clinical value of ketamine in the treatment of depression focussing on clinical trials and the therapeutic mechanism of action.

 
  • Literatur

  • 1 Kessler RC, Berglund P, Demler O et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA 2003; 289: 3095-3105
  • 2 Kessler RC, Aguilar-Gaxiola S, Alonso J et al. The global burden of mental disorders: an update from the WHO World Mental Health (WMH) surveys. Epidemiol Psichiatr Soc 2009; 18: 23-33
  • 3 Trivedi MH, Rush AJ, Wisniewski SR et al. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry 2006; 163: 28-40
  • 4 Köhler S, Arndt A, Sterzer P et al. Individualized treatment with antidepressants. Fortschr Neurol Psychiatr 2013; 81: 104-116 quiz 117–108
  • 5 Köhler S, Stöver LA, Bschor T. MAO-inhibitors – a treatment option for treatment resistant depression: application, efficacy and characteristics. Fortschr Neurol Psychiatr 2014; 82: 228-236 quiz 237–228
  • 6 O'Connor RM, Finger BC, Flor PJ et al. Metabotropic glutamate receptor 7: at the interface of cognition and emotion. Eur J Pharmacol 2010; 639: 123-131
  • 7 Marland S, Ellerton J, Andolfatto G et al. Ketamine: use in anesthesia. CNS Neurosci Ther 2013; 19: 381-389
  • 8 Stahl SM. Mechanism of action of ketamine. CNS Spectr 2013; 18: 171-174
  • 9 Berman RM, Cappiello A, Anand A et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry 2000; 47: 351-354
  • 10 Zarate Jr CA, Singh JB, Carlson PJ et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 2006; 63: 856-864
  • 11 Sos P, Klirova M, Novak T et al. Relationship of ketamine’s antidepressant and psychotomimetic effects in unipolar depression. Neuro Endocrinol Lett 2013; 34: 287-293
  • 12 Diazgranados N, Ibrahim L, Brutsche NE et al. A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression. Arch Gen Psychiatry 2010; 67: 793-802
  • 13 Zarate Jr CA , Brutsche NE, Ibrahim L et al. Replication of ketamine’s antidepressant efficacy in bipolar depression: a randomized controlled add-on trial. Biol Psychiatry 2012; 71: 939-946
  • 14 Murrough JW, Iosifescu DV, Chang LC et al. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry 2013; 170: 1134-1142
  • 15 Segmiller F, Ruther T, Linhardt A et al. Repeated S-ketamine infusions in therapy resistant depression: a case series. J Clin Pharmacol 2013; 53: 996-998
  • 16 Murrough JW, Perez AM, Pillemer S et al. Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression. Biol Psychiatry 2013; 74: 250-256
  • 17 Shiroma PR, Johns B, Kuskowski M et al. Augmentation of response and remission to serial intravenous subanesthetic ketamine in treatment resistant depression. J Affect Disord 2014; 155: 123-129
  • 18 Lapidus KA, Levitch CF, Perez AM et al. A Randomized Controlled Trial of Intranasal Ketamine in Major Depressive Disorder. Biol Psychiatry 2014; DOI: 10.1016/j.biopsych.2014.03.026.
  • 19 Abdallah CG, Fasula M, Kelmendi B et al. Rapid antidepressant effect of ketamine in the electroconvulsive therapy setting. J ECT 2012; 28: 157-161
  • 20 Ghasemi M, Kazemi MH, Yoosefi A et al. Rapid antidepressant effects of repeated doses of ketamine compared with electroconvulsive therapy in hospitalized patients with major depressive disorder. Psychiatry Res 2014; 215: 355-361
  • 21 Ibrahim L, Diazgranados N, Luckenbaugh DA et al. Rapid decrease in depressive symptoms with an N-methyl-d-aspartate antagonist in ECT-resistant major depression. Prog Neuropsychopharmacol Biol Psychiatry 2011; 35: 1155-1159
  • 22 Price RB, Iosifescu DV, Murrough JW et al. Effects of ketamine on explicit and implicit suicidal cognition: a randomized controlled trial in treatment-resistant depression. Depress Anxiety 2014; 31: 335-343
  • 23 Ionescu DF, Luckenbaugh DA, Niciu MJ et al. A single infusion of ketamine improves depression scores in patients with anxious bipolar depression. Bipolar Disord 2014; DOI: 10.1111/bdi.12277.
  • 24 Li N, Lee B, Liu RJ et al. mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science 2010; 329: 959-964
  • 25 McEwen BS. Central effects of stress hormones in health and disease: Understanding the protective and damaging effects of stress and stress mediators. Eur J Pharmacol 2008; 583: 174-185
  • 26 Shansky RM, Morrison JH. Stress-induced dendritic remodeling in the medial prefrontal cortex: effects of circuit, hormones and rest. Brain Res 2009; 1293: 108-113
  • 27 Li N, Liu RJ, Dwyer JM et al. Glutamate N-methyl-D-aspartate receptor antagonists rapidly reverse behavioral and synaptic deficits caused by chronic stress exposure. Biol Psychiatry 2011; 69: 754-761
  • 28 Naughton M, Clarke G, O’Leary OF et al. A review of ketamine in affective disorders: current evidence of clinical efficacy, limitations of use and pre-clinical evidence on proposed mechanisms of action. J Affect Disord 2014; 156: 24-35
  • 29 Monteggia LM, Gideons E, Kavalali ET. The role of eukaryotic elongation factor 2 kinase in rapid antidepressant action of ketamine. Biol Psychiatry 2013; 73: 1199-1203
  • 30 Haile CN, Murrough JW, Iosifescu DV et al. Plasma brain derived neurotrophic factor (BDNF) and response to ketamine in treatment-resistant depression. Int J Neuropsychopharmacol 2014; 17: 331-336
  • 31 Klein PS, Melton DA. A molecular mechanism for the effect of lithium on development. Proc Natl Acad Sci U S A 1996; 93: 8455-8459
  • 32 Ma XC, Dang YH, Jia M et al. Long-lasting antidepressant action of ketamine, but not glycogen synthase kinase-3 inhibitor SB216763, in the chronic mild stress model of mice. PLoS One 2013; 8: e56053
  • 33 Andreasen JT, Gynther M, Rygaard A et al. Does increasing the ratio of AMPA-to-NMDA receptor mediated neurotransmission engender antidepressant action? Studies in the mouse forced swim and tail suspension tests. Neurosci Lett 2013; 546: 6-10
  • 34 O'Neill MJ, Bleakman D, Zimmerman DM et al. AMPA receptor potentiators for the treatment of CNS disorders. Curr Drug Targets CNS Neurol Disord 2004; 3: 181-194
  • 35 Garcia LS, Comim CM, Valvassori SS et al. Acute administration of ketamine induces antidepressant-like effects in the forced swimming test and increases BDNF levels in the rat hippocampus. Prog Neuropsychopharmacol Biol Psychiatry 2008; 32: 140-144
  • 36 Akinfiresoye L, Tizabi Y. Antidepressant effects of AMPA and ketamine combination: role of hippocampal BDNF, synapsin, and mTOR. Psychopharmacology (Berl) 2013; 230: 291-298
  • 37 Raichle ME, MacLeod AM, Snyder AZ et al. A default mode of brain function. Proc Natl Acad Sci U S A 2001; 98: 676-682
  • 38 Caddy C, Giaroli G, White TP et al. Ketamine as the prototype glutamatergic antidepressant: pharmacodynamic actions, and a systematic review and meta-analysis of efficacy. Ther Adv Psychopharmacol 2014; 4: 75-99
  • 39 Kettner A, Schröder K et al. Drug Scouts. In: http://drugscouts.de/de/lexikon/ketamin
  • 40 Nutt D, King LA, Saulsbury W et al. Development of a rational scale to assess the harm of drugs of potential misuse. Lancet 2007; 369: 1047-1053
  • 41 Köhler S, Wiethoff K, Ricken R et al. Characteristics and differences in treatment outcome of inpatients with chronic vs. episodic major depressive disorders. J Affect Disord 2014; 173C: 126-133
  • 42 Fava GA, Tomba E. New modalities of assessment and treatment planning in depression: the sequential approach. CNS Drugs 2010; 24: 453-465
  • 43 Köhler S, Fischer T, Brakemeier EL et al. Successful treatment of severe persistent depressive disorder with a sequential approach: ECT followed by CBASP. Psychother Psychosom in press
  • 44 Köhler S, Sterzer P, Brakemeier EL. Das Cognitive Behavioral Analysis System of Psychotherapy (CBASP) als schulenübergreifende Psychotherapie der chronischen Depression. Nervenheilkunde 2014; 4: 241-251
  • 45 Feder A, Parides MK, Murrough JW et al. Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial. JAMA Psychiatry 2014; 71: 681-688