Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jan 24;16(2):173.
doi: 10.3390/ph16020173.

Safety and Tolerability of the Acute Ketamine Treatment in Treatment-Resistant Depression: Focus on Comorbidities Interplay with Dissociation and Psychomimetic Symptoms

Adam Włodarczyk  1 , Alicja Dywel  1 , Wiesław Jerzy Cubała  1
Affiliations

Safety and Tolerability of the Acute Ketamine Treatment in Treatment-Resistant Depression: Focus on Comorbidities Interplay with Dissociation and Psychomimetic Symptoms

Adam Włodarczyk et al. Pharmaceuticals (Basel). .

Abstract

There is evidence for ketamine use in treatment-resistant depression (TRD). Several safety concerns arise regarding adverse drug reactions in specific subpopulations. The aim of this study was to investigate the safety of intravenous ketamine treatment in relation to dissociative and psychotic measures in TRD inpatients with Major Depressive Disorder (MDD) and Bipolar depression (BP) with comorbidities. In total, 49 inpatients with MDD or BP were treated with ketamine following the registered naturalistic observational protocol in a tertiary reference unit for mood disorders (NCT04226963). This dataset represents an intermittent analysis of an observational study performed for interim modeling of observational learning. The observations were applied to the inhomogeneous TRD population in a single site with no blinding and were limited to acute administration. The presence of epilepsy was significantly associated with an elevation in the BPRS over time (p = 0.008). Psychotic symptomatology with BPRS scores for comorbid conditions excluding epilepsy turned out to be insignificant (p = 0.198) regardless of the diagnosis. However, for a subgroup of patients with epilepsy (n = 6), a substantial fluctuation was seen across all administrations in the time course of the study. The study results contribute to the literature on the safety and tolerability profile of CNS adverse drug reactions in short-term treatment with intravenous ketamine as an add-on intervention to current standard-of-care psychotropic medication in TRD-MDD and TRD-BP inpatients with comorbidities. The careful consideration of comorbidities and concomitant medication is needed with ketamine administration along with close-clinical supervision at every visit.

Keywords: antidepressants; comorbidity; dissociation; ketamine; major depression; psychosis; safety; treatment-resistant depression.

PubMed Disclaimer

Conflict of interest statement

Alicja Dywel has no conflict of interest. Adam Włodarczyk has received research support from Actavis, Eli Lilly, Minerva Neurosciences, Sunovion Pharmaceuticals, KCR, Janssen, Otsuka, Apodemus, Cortexyme, Acadia. Wiesław Jerzy Cubała has received research support from Acadia, Alkermes, Allergan, Angleini, Auspex Pharmaceuticals, BMS, Celon, Cephalon, Cortexyme, Ferrier, Forest Laboratories, GedeonRichter, GWPharmaceuticals, HMNC Brain Health, IntraCellular Therapies, Janssen, KCR, Lilly, Lundbeck, Minerva, MSD, NIH, Novartis, Orion, Otsuka, Sanofi, Servier, Honoraria: Adamed, Angleini, AstraZeneca, BMS, Celon, GSK, Janssen, KRKA, Lekam, Lundbeck, Minerva, Neurog, Novartis, Orion, Pfizer, Polfa Tarchomin, Douglas Pharm., Sanofi, Servier, Zentiva. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Similar articles

See all similar articles

Cited by

References

    1. McIntyre R.S., Rodrigues N.B., Lee Y., Lipsitz O., Subramaniapillai M., Gill H., Nasri F., Majeed A., Lui L.M.W., Senyk O., et al. The effectiveness of repeated intravenous ketamine on depressive symptoms, suicidal ideation and functional disability in adults with major depressive disorder and bipolar disorder: Results from the Canadian Rapid Treatment Center of Excellence. J. Affect. Disord. 2020;274:903–910. doi: 10.1016/j.jad.2020.05.088. - DOI - PubMed
    1. Włodarczyk A., Cubała W.J., Szarmach J., Małyszko A., Wiglusz M.S. Short-term ketamine administration in treatment-resistant depression patients: Focus on adverse effects on the central nervous system. Psychiatr. Danub. 2019;31((Suppl. S3)):530–533. - PubMed
    1. Correia-Melo F.S., Argolo F.C., Araújo-de-Freitas L., Leal G.C., Kapczinski F., Lacerda A.L., Quarantini L.C. Rapid infusion of esketamine for unipolar and bipolar depression: A retrospective chart review. Neuropsychiatr. Dis. Treat. 2017;13:1627–1632. doi: 10.2147/NDT.S135623. - DOI - PMC - PubMed
    1. McCloud T.L., Caddy C., Jochim J., Rendell J.M., Diamond P.R., Shuttleworth C., Brett D., Amit B.H., McShane R., Hamadi L., et al. Ketamine and other glutamate receptor modulators for depression in bipolar disorder in adults. Cochrane Database Syst. Rev. 2015;9:CD011611:1–CD011611:56. doi: 10.1002/14651858.CD011611.pub2. - DOI - PubMed
    1. Bremner J.D., Krystal J.H., Putnam F.W., Southwick S.M., Marmar C., Charney D.S., Mazure C.M. Measurement of Dissociative States with the Clinician-Administered Dissociative States Scale (CADSS) J. Trauma. Stress. 1998;11:125–136. doi: 10.1023/A:1024465317902. - DOI - PubMed

LinkOut - more resources