Download PDF
Nervenheilkunde 2022; 41(04): 240-245
DOI: 10.1055/a-1761-3192
Schwerpunkt

Suizidpräventive Effekte von Ketamin und Esketamin

Suicide-preventive effects of ketamine and esketamine
Martin Plöderl∗
1   Bereich für Krisenintervention und Suizidprävention und Institut für klinische Psychologie, Unversitätsklinik für Psychiatrie, Psychotherapie und Psychosomatik, Paracelsus Medizinische Universität Salzburg
,
Michael P. Hengartner∗
2   Fachgruppe Klinische Psychologie und Gesundheitspsychologie, Zürcher Hochschule für Angewandte Wissenschaften, Zürich
,
Constantin Volkmann∗
3   Klinik für Psychiatrie und Psychotherapie, Charité —Universitätsmedizin Berlin, Campus Charité Mitte, Berlin
› Author Affiliations
› Further Information
Also available at
    Permissions and Reprints

ZUSAMMENFASSUNG

Ketamin und Esketamin werden als rasch und stark wirksame Mittel zur Reduktion von Depressivität und Suizidalität beschrieben. Dieser Beitrag gibt einen Überblick zur Wirksamkeit von Ketamin und Esketamin zur Reduktion von suizidalen Gedanken und Handlungen, basierend auf randomisierten kontrollierten Studien, die bis Dezember 2021 publiziert wurden. Für Ketamin gibt es Hinweise für eine beträchtliche Reduktion von Suizidgedanken, aber nur in den ersten 3 Tagen und die tatsächliche Effektstärke ist aufgrund der Schätzunsicherheit ungewiss. Für suizidale Handlungen fehlen zudem Daten. Die wenigen, aber qualitativ hochwertigeren Studien zu Esketamin fanden bestenfalls schwache Effekte bezüglich Suizidgedanken, auch unter Berücksichtigung der Schätzunsicherheit, und für suizidale Handlungen können keine gesicherten Aussagen getroffen werden. Das Nutzen-Schaden-Verhältnis von Ketamin und Esketamin in der Suizidprävention ist deshalb ungewiss.

ABSTRACT

Ketamine and esketamine are considered to be rapidly and strongly effective in reducing depression and suicidality. In this article, we give an overview about the efficacy of ketamine and esketamine for the reduction of suicidal ideation and behavior. We base our assessment on randomized controlled trials published until December 2021. For ketamine, there seems to be a substantial reduction of suicide ideation, but only in the first 3 days. The actual size of the effect remains uncertain due to the imprecision in estimates. Furthermore, evidence for suicidal behavior is lacking. For esketamine, the few but qualitatively superior studies found weak effects at best, even when accounting for imprecision of the estimates. No firm conclusions can be drawn regarding suicidal behavior. The benefit-harm ratio of ketamine and esketamine in suicide prevention thus remains uncertain.

Schlüsselwörter

Ketamin - Esketamin - Suizid

Key words

Ketamine - esketamine - suicide


Publication History

Article published online:
04 April 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • Literatur

  • 1 Munkholm K, Paludan-Müller AS, Boesen K. Considering the methodological limitations in the evidence base of antidepressants for depression: a reanalysis of a network meta-analysis.. BMJ Open 2019; 09: e024886
    CrossrefPubMedSearch in Google Scholar
  • 2 Hengartner MP, Plöderl M. Estimates of the minimal important difference to evaluate the clinical significance of antidepressants in the acute treatment of moderate-to-severe depression.. BMJ Evid Based Med 2021
    CrossrefPubMedSearch in Google Scholar
  • 3 Hengartner MP, Amendola S, Kaminski JA. et al Suicide risk with selective serotonin reuptake inhibitors and other new-generation antidepressants in adults: a systematic review and meta-analysis of observational studies.. J Epidemiol Community Health 2021; 75: 523-530
    CrossrefPubMedSearch in Google Scholar
  • 4 Plöderl M, Hengartner MP, Bschor T. et al Commentary to „antidepressants and suicidality: A re-analysis of the re-analysis“.. J Affect Disord 2020; 273: 252-253
    CrossrefPubMedSearch in Google Scholar
  • 5 Wilkinson ST, Ballard ED, Bloch MH. 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: 150-158
    CrossrefPubMedSearch in Google Scholar
  • 6 Jansen KLR, Darracot-Cankovic R. The Nonmedical Use of Ketamlne, Part Two: A Review of Problent Use and Dependence.. J Psychoactive Drugs 2001; 33: 151-158
    CrossrefPubMedSearch in Google Scholar
  • 7 European Medicines Agency. Produktinformation zu Spravato, Anhang 1, Zusammenfassung der Merkmale des Arzneimittels. 2021
  • 8 Plöderl M, Volkmann C. Esketamin. Ein berechtigter Hype in der Suizidprävention?. Suizidprophylaxe 2021; 48: 10-14
    Search in Google Scholar
  • 9 Siegel AN, Di Vincenzo JD, Brietzke E. et al Antisuicidal and antidepressant effects of ketamine and esketamine in patients with baseline suicidality: A systematic review.. J Psychiatr Res 2021; 137: 426-436
    CrossrefPubMedSearch in Google Scholar
  • 10 Dean RL, Hurducas C, Hawton K. et al Ketamine and other glutamate receptor modulators for depression in adults with unipolar major depressive disorder.. Cochrane Database Syst Rev 2021
    CrossrefPubMedSearch in Google Scholar
  • 11 Walsh Z, Mollaahmetoglu OM, Rootman J. et al Ketamine for the treatment of mental health and substance use disorders: comprehensive systematic review.. BJPsych Open 2022; 08: e19
    CrossrefPubMedSearch in Google Scholar
  • 12 D’Anci KE, Uhl S, Giradi G. et al Treatments for the Prevention and Management of Suicide: A Systematic Review.. Ann Intern Med 2019; 171: 334
    CrossrefPubMedSearch in Google Scholar
  • 13 Bartoli F, Riboldi I, Crocamo C. et al Ketamine as a rapid-acting agent for suicidal ideation: A meta-analysis.. Neurosci Biobehav Rev 2017; 77: 232-236
    CrossrefPubMedSearch in Google Scholar
  • 14 Witt K, Potts J, Hubers A. et al Ketamine for suicidal ideation in adults with psychiatric disorders: A systematic review and meta-analysis of treatment trials.. Aust N Z J Psychiatry 2020; 54: 29-45
    CrossrefPubMedSearch in Google Scholar
  • 15 Reinstatler L, Youssef NA. Ketamine as a Potential Treatment for Suicidal Ideation: A Systematic Review of the Literature.. Drugs R D 2015; 15: 37-43
    CrossrefPubMedSearch in Google Scholar
  • 16 Dadiomov D, Lee K. The effects of ketamine on suicidality across various formulations and study settings.. Mental Health Clinician 2019; 09: 48-60
    CrossrefPubMedSearch in Google Scholar
  • 17 Su T-P, Chen M-H, Li C-T. et al Dose-Related Effects of Adjunctive Ketamine in Taiwanese Patients with Treatment-Resistant Depression.. Neuropsychopharmacol 2017; 42: 2482-2492
    CrossrefPubMedSearch in Google Scholar
  • 18 Ionescu DF, Bentley KH, Eikermann M. et al Repeat-dose ketamine augmentation for treatment-resistant depression with chronic suicidal ideation: A randomized, double blind, placebo controlled trial.. J Affect Disord 2019; 243: 516-524
    CrossrefPubMedSearch in Google Scholar
  • 19 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
    CrossrefPubMedSearch in Google Scholar
  • 20 Zarate 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
    CrossrefPubMedSearch in Google Scholar
  • 21 Grunebaum MF, Ellis SP, Keilp JG. et al Ketamine versus midazolam in bipolar depression with suicidal thoughts: A pilot midazolam-controlled randomized clinical trial.. Bipolar Disord 2017; 19: 176-183
    CrossrefPubMedSearch in Google Scholar
  • 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
    CrossrefPubMedSearch in Google Scholar
  • 23 George D, Gálvez V, Martin D. et al Pilot Randomized Controlled Trial of Titrated Subcutaneous Ketamine in Older Patients with Treatment-Resistant Depression.. Am J Geriatr Psychiatry 2017; 25: 1199-1209
    CrossrefPubMedSearch in Google Scholar
  • 24 Loo CK, Gálvez V, O’Keefe E. et al Placebo-controlled pilot trial testing dose titration and intravenous, intramuscular and subcutaneous routes for ketamine in depression.. Acta Psychiatr Scand 2016; 134: 48-56
    CrossrefPubMedSearch in Google Scholar
  • 25 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
    CrossrefPubMedSearch in Google Scholar
  • 26 Ballard ED, Ionescu DF, Vande Voort JL. et al Improvement in suicidal ideation after ketamine infusion: Relationship to reductions in depression and anxiety.. J Psychiatric Res 2014; 58: 161-166
    CrossrefPubMedSearch in Google Scholar
  • 27 Zarate CA, Singh JB, Quiroz JA. et al A Double-Blind, Placebo-Controlled Study of Memantine in the Treatment of Major Depression.. Am J Psychiatry 2006; 163: 153-155
    CrossrefPubMedSearch in Google Scholar
  • 28 Ionescu DF, Baer L, Petrie SR. et al ACNP 55th Annual Meeting: Poster Session II: December 6, 2016.. Neuropsychopharmacol 2016; 41: S289-S454
    CrossrefSearch in Google Scholar
  • 29 Grunebaum MF, Galfalvy HC, Choo T-H. et al Ketamine for Rapid Reduction of Suicidal Thoughts in Major Depression: A Midazolam-Controlled Randomized Clinical Trial.. Am J Psychiatry 2018; 175: 327-335
    CrossrefPubMedSearch in Google Scholar
  • 30 Murrough JW, Soleimani L, DeWilde KE. et al Ketamine for rapid reduction of suicidal ideation: a randomized controlled trial.. Psychol Med 2015; 45: 3571-3580
    CrossrefPubMedSearch in Google Scholar
  • 31 Daly EJ, Singh JB, Fedgchin M. et al Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression: A Randomized Clinical Trial.. JAMA Psychiatry 2018; 75: 139
    CrossrefPubMedSearch in Google Scholar
  • 32 Singh JB, Fedgchin M, Daly E. et al Intravenous Esketamine in Adult Treatment-Resistant Depression: A Double-Blind, Double-Randomization, Placebo-Controlled Study.. Biol Psychiatry 2016; 80: 424-431
    CrossrefPubMedSearch in Google Scholar
  • 33 Food and Drug Administration. FDA Briefing Document. Psychopharmacologic Drugs Advisory Committee (PDAC) and Drug Safety and Risk Management (DSaRM) Advisory Committee Meeting. 2019;
  • 34 Popova V, Daly EJ, Trivedi M. 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: 428-438
    CrossrefPubMedSearch in Google Scholar
  • 35 Ochs-Ross R, Daly EJ, Zhang Y. et al Efficacy and Safety of Esketamine Nasal Spray Plus an Oral Antidepressant in Elderly Patients With Treatment-Resistant Depression TRANSFORM-3.. Am J Geriatr Psychiatry 2020; 28: 121-141
    CrossrefPubMedSearch in Google Scholar
  • 36 Fedgchin M, Trivedi M, Daly EJ. et al Efficacy and Safety of Fixed-Dose Esketamine Nasal Spray Combined With a New Oral Antidepressant in Treatment-Resistant Depression: Results of a Randomized, Double-Blind, Active-Controlled Study (TRANSFORM-1).. Int J Neuropsychopharmacol 2019; 22: 616-630
    CrossrefPubMedSearch in Google Scholar
  • 37 Takahashi N, Yamada A, Shiraishi A. et al Efficacy and safety of fixed doses of intranasal Esketamine as an add-on therapy to Oral antidepressants in Japanese patients with treatment-resistant depression: a phase 2b randomized clinical study.. BMC Psychiatry 2021; 21: 526
    CrossrefPubMedSearch in Google Scholar
  • 38 Ionescu DF, Fu D-J, Qiu X. et al Esketamine Nasal Spray for Rapid Reduction of Depressive Symptoms in Patients with Major Depressive Disorder Who Have Active Suicide Ideation with Intent: Results of a Phase 3, Double-Blind, Randomized Study (ASPIRE II).. Int J Neuropsychopharmacol 2020
    CrossrefPubMedSearch in Google Scholar
  • 39 Fu D-J, Ionescu DF, Li X. et al Esketamine Nasal Spray for Rapid Reduction of Major Depressive Disorder Symptoms in Patients Who Have Active Suicidal Ideation With Intent: Double-Blind, Randomized Study (ASPIRE I).. Journal Clin Psychiatry 2020; 81: 19m13191
    Search in Google Scholar
  • 40 Vieira F, Correia-Melo FS, Santos-Lima C. et al Ketamine and Esketamine augmentation for suicidal ideation: A randomized, double-blinded clinical trial.. Gen Hosp Psychiatry 2021; 68: 97-99
    CrossrefPubMedSearch in Google Scholar
  • 41 Bahji A, Vazquez GH, Zarate CA. Comparative efficacy of racemic ketamine and esketamine for depression: A systematic review and meta-analysis.. J Affect Disord 2021; 278: 542-555
    CrossrefPubMedSearch in Google Scholar
  • 42 Wortzel HS, Gutierrez PM, Homaifar BY. et al Surrogate endpoints in suicide research.. Suicide Life Threat Behav 2010; 40: 500-505
    CrossrefPubMedSearch in Google Scholar
  • 43 Gastaldon C, Raschi E, Kane JM. et al Post-Marketing Safety Concerns with Esketamine: A Disproportionality Analysis of Spontaneous Reports Submitted to the FDA Adverse Event Reporting System.. Psychother Psychosom 2020: 1-8
    CrossrefPubMedSearch in Google Scholar
  • 44 Taillefer de Laportalière T, Yrondi A, Jullien A. et al How to deprescribe esketamine in resistant depression? A point of view after first clinical uses.. Epidemiol Psychiatr Sci 2022; 31: e4
    CrossrefPubMedSearch in Google Scholar
  • 45 Vanicek T, Unterholzner J, Lanzenberger R. et al Intravenous Esketamine Leads to an Increase in Impulsive and Suicidal Behavior in a Patient with Recurrent Major Depression and Borderline Personality Disorder.. World J Biol Psychiatry 2022: 1-9
    PubMedSearch in Google Scholar