PDF herunterladen
Pharmacopsychiatry
DOI: 10.1055/a-2499-7207
Original Paper

Rapid Antidepressant and Antisuicidal Effects of Low-Dose Ketamine Infusion in Patients With Treatment-Resistant Depression With or Without Low-Grade Inflammation

Mu-Hong Chen
1   Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan
2   Division of Psychiatry, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
4   Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei, Taiwan
,
Tung-Ping Su
1   Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan
2   Division of Psychiatry, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
3   Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan
4   Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei, Taiwan
5   Department of Psychiatry, Cheng Hsin General Hospital, Taipei, Taiwan
,
Wei-Chen Lin
1   Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan
2   Division of Psychiatry, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
4   Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei, Taiwan
,
Cheng-Ta Li
1   Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan
2   Division of Psychiatry, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
4   Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei, Taiwan
,
Hui-Ju Wu
1   Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan
,
Shih-Jen Tsai
1   Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan
2   Division of Psychiatry, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
4   Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei, Taiwan
,
Ya-Mei Bai
1   Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan
2   Division of Psychiatry, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
4   Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei, Taiwan
,
Wei-Chung Mao
5   Department of Psychiatry, Cheng Hsin General Hospital, Taipei, Taiwan
,
Pei-Chi Tu
1   Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan
2   Division of Psychiatry, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
3   Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan
› Institutsangaben Funding The study was supported by grant from Taipei Veterans General Hospital (V111C-010, V111C-040, V111C-029, V112C-033, V113C-010, V113C-011, V113C-039), Yen Tjing Ling Medical Foundation (CI-109-21, CI-109-22, CI-110-30, CI-113-30, CI-113-31, CI-113-32), Ministry of Science and Technology, Taiwan (MOST110-2314-B-075-026, MOST110-2314-B-075-024 -MY3, MOST 109-2314-B-010-050-MY3, MOST111-2314-B-075 -014 -MY2, MOST 111-2314-B-075 -013, NSTC111-2314-B-A49-089-MY2), Taipei, Taichung, Kaohsiung Veterans General Hospital, Tri-Service General Hospital, Academia Sinica Joint Research Program (VTA112-V1-6-1, VTA113-V1-5-1) and Veterans General Hospitals and University System of Taiwan Joint Research Program (VGHUST112-G1-8-1, VGHUST113-G1-8-1). The funding source had no role in any process of our study.
› Weitere Informationen
Auch verfügbar auf
    Lizenzen und Reprints

Abstract

Background

Low-grade inflammation (LGI) contributes to resistance against traditional antidepressants. However, whether the antidepressant and antisuicidal effects of ketamine on patients with treatment-resistant depression (TRD) differ between those with LGI and those without LGI remains unknown.

Methods

This study included 167 patients with TRD, among whom 46 had LGI and 121 did not have LGI. The patients received a single infusion of either low-dose ketamine or a placebo. A C-reactive protein level of≥3 mg/L indicated LGI. Depressive symptoms were measured from baseline to day 3 by using the 17-item Hamilton Depression Rating Scale (HDRS) and the Montgomery-Asberg Depression Rating Scale (MADRS).

Results

Generalized estimating equation models revealed antidepressant effect of ketamine in patients with no LGI (HDRS scores: p<0.001; MADRS scores: p<0.001) but not in patients with LGI (all p>0.05). The antisuicidal effect of ketamine (indicated by the score on item 10 of the MADRS) was observed in both groups of patients with (p=0.046) and without LGI (p<0.001). However, ketamine was effective for TRD regardless of whether inflammation levels were high or low, while the placebo response was notably greater only in patients with LGI.

Discussion

This study suggests that among patients with TRD, only those without LGI respond to low-dose ketamine infusion. Whether the negative findings of the antidepressant effect of ketamine among patients with LGI may be because of the effect of the placebo infusion needs further investigation. Further randomized, placebo-controlled studies are needed to validate these findings.

Keywords

low-grade inflammation - ketamine - antidepressant effect - antisuicidal effect


Publikationsverlauf

Eingereicht: 09. Oktober 2024

Angenommen: 01. Dezember 2024

Artikel online veröffentlicht:
20. Dezember 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Osimo EF, Baxter LJ, Lewis G. et al. Prevalence of low-grade inflammation in depression: A systematic review and meta-analysis of CRP levels. Psychol Med 2019; 49: 1958-1970
    CrossrefPubMedSuche in Google Scholar
  • 2 Pietzner M, Kaul A, Henning AK. et al. Comprehensive metabolic profiling of chronic low-grade inflammation among generally healthy individuals. BMC Med 2017; 15: 210
    CrossrefPubMedSuche in Google Scholar
  • 3 Furman D, Campisi J, Verdin E. et al. Chronic inflammation in the etiology of disease across the life span. Nat Med 2019; 25: 1822-1832
    CrossrefPubMedSuche in Google Scholar
  • 4 Jeng JS, Li CT, Chen MH. et al. Repeated low-grade infections predict antidepressant-resistant depression: A nationwide population-based cohort study. J Clin Psychiatry. 2018 79. 17m11540
    CrossrefPubMedSuche in Google Scholar
  • 5 Gares-Caballer M, Sanchez-Orti JV, Correa-Ghisays P. et al. Immune-inflammatory biomarkers predict cognition and social functioning in patients with type 2 diabetes mellitus, major depressive disorder, bipolar disorder, and schizophrenia: A 1-year follow-up study. Front Neurol 2022; 13: 883927
    CrossrefPubMedSuche in Google Scholar
  • 6 Arteaga-Henriquez G, Simon MS, Burger B. et al. Low-grade inflammation as a predictor of antidepressant and anti-inflammatory therapy response in MDD patients: A systematic review of the literature in combination with an analysis of experimental data collected in the EU-MOODINFLAME consortium. Front Psychiatry 2019; 10: 458
    CrossrefPubMedSuche in Google Scholar
  • 7 Price RB, Kissel N, Baumeister A. et al. International pooled patient-level meta-analysis of ketamine infusion for depression: In search of clinical moderators. Mol Psychiatry 2022; 27: 5096-5112
    CrossrefPubMedSuche in Google Scholar
  • 8 Su TP, Chen MH, Li CT. et al. Dose-related effects of adjunctive ketamine in Taiwanese patients with treatment-resistant depression. Neuropsychopharmacology 2017; 42: 2482-2492
    CrossrefPubMedSuche in Google Scholar
  • 9 Su TP, Li CT, Lin WC. et al. A randomized, double-blind, midazolam-controlled trial of low-dose ketamine infusion in patients with treatment-resistant depression and prominent suicidal ideation. Int J Neuropsychopharmacol 2023; 26: 331-339
    CrossrefPubMedSuche in Google Scholar
  • 10 Tsai SJ, Kao CF, Su TP. et al. Cytokine- and vascular endothelial growth factor-related gene-based genome-wide association study of low-dose ketamine infusion in patients with treatment-resistant depression. CNS Drugs 2023; 37: 243-253
    CrossrefPubMedSuche in Google Scholar
  • 11 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
    CrossrefPubMedSuche in Google Scholar
  • 12 Chen MH, Li CT, Lin WC. et al. Rapid inflammation modulation and antidepressant efficacy of a low-dose ketamine infusion in treatment-resistant depression: A randomized, double-blind control study. Psychiatry Res 2018; 269: 207-211
    CrossrefPubMedSuche in Google Scholar
  • 13 Wang T, Weng H, Zhou H. et al. Esketamine alleviates postoperative depression-like behavior through anti-inflammatory actions in mouse prefrontal cortex. J Affect Disord 2022; 307: 97-107
    CrossrefPubMedSuche in Google Scholar
  • 14 Yang C, Wardenaar KJ, Bosker FJ. et al. Inflammatory markers and treatment outcome in treatment resistant depression: A systematic review. J Affect Disord 2019; 257: 640-649
    CrossrefPubMedSuche in Google Scholar
  • 15 Chen MH, Cheng CM, Gueorguieva R. et al. Maintenance of antidepressant and antisuicidal effects by D-cycloserine among patients with treatment-resistant depression who responded to low-dose ketamine infusion: A double-blind randomized placebo-control study. Neuropsychopharmacology 2019; 44: 2112-2118
    CrossrefPubMedSuche in Google Scholar
  • 16 Teng CT, Demetrio FN. Memantine may acutely improve cognition and have a mood stabilizing effect in treatment-resistant bipolar disorder. Rev Bras Psiquiatr 2006; 28: 252-254
    CrossrefPubMedSuche in Google Scholar
  • 17 van Belkum SM, Geugies H, Lysen TS. et al. Validity of the Maudsley staging method in predicting treatment-resistant depression outcome using the Netherlands Study of Depression and Anxiety. J Clin Psychiatry. 2018 79. 17m11475
    PubMedSuche in Google Scholar
  • 18 Milaneschi Y, Lamers F, Berk M. et al. Depression heterogeneity and its biological underpinnings: Toward immunometabolic depression. Biol Psychiatry 2020; 88: 369-380
    CrossrefPubMedSuche in Google Scholar
  • 19 Park LT, Luckenbaugh DA, Pennybaker SJ. et al. The effects of ketamine on typical and atypical depressive symptoms. Acta Psychiatr Scand 2020; 142: 394-401
    CrossrefPubMedSuche in Google Scholar
  • 20 Hellmann-Regen J, Clemens V, Grozinger M. et al. Effect of minocycline on depressive symptoms in patients with treatment-resistant depression: A randomized clinical trial. JAMA Netw Open 2022; 5: e2230367
    CrossrefPubMedSuche in Google Scholar
  • 21 Kohler O, Benros ME, Nordentoft M. et al. Effect of anti-inflammatory treatment on depression, depressive symptoms, and adverse effects: A systematic review and meta-analysis of randomized clinical trials. JAMA Psychiatry 2014; 71: 1381-1391
    CrossrefPubMedSuche in Google Scholar
  • 22 Husain MI, Chaudhry IB, Khoso AB. et al. Minocycline and celecoxib as adjunctive treatments for bipolar depression: A multicentre, factorial design randomised controlled trial. Lancet Psychiatry 2020; 7: 515-527
    CrossrefPubMedSuche in Google Scholar
  • 23 Nettis MA, Lombardo G, Hastings C. et al. Augmentation therapy with minocycline in treatment-resistant depression patients with low-grade peripheral inflammation: Results from a double-blind randomised clinical trial. Neuropsychopharmacology 2021; 46: 939-948
    CrossrefPubMedSuche in Google Scholar
  • 24 Ballard ED, Yarrington JS, Farmer CA. et al. Characterizing the course of suicidal ideation response to ketamine. J Affect Disord 2018; 241: 86-93
    CrossrefPubMedSuche in Google Scholar
  • 25 Grunebaum MF, Galfalvy HC, Choo TH. 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
    CrossrefPubMedSuche in Google Scholar
  • 26 Erhardt S, Lim CK, Linderholm KR. et al. Connecting inflammation with glutamate agonism in suicidality. Neuropsychopharmacology 2013; 38: 743-752
    CrossrefPubMedSuche in Google Scholar
  • 27 Duman RS, Aghajanian GK. Synaptic dysfunction in depression: Potential therapeutic targets. Science 2012; 338: 68-72
    CrossrefPubMedSuche in Google Scholar
  • 28 Oken BS. Placebo effects: Clinical aspects and neurobiology. Brain 2008; 131: 2812-2823
    CrossrefPubMedSuche in Google Scholar
  • 29 Kokkotou E, Conboy LA, Ziogas DC. et al. Serum correlates of the placebo effect in irritable bowel syndrome. Neurogastroenterol Motil 2010; 22: 285-e81
    CrossrefPubMedSuche in Google Scholar
  • 30 Evans D. Suppression of the acute-phase response as a biological mechanism for the placebo effect. Med Hypotheses 2005; 64: 1-7
    CrossrefPubMedSuche in Google Scholar