Ketamine Resources

Chris Griffiths a. Kate Walker a. Isabel Reid a. Ksenija Maravicda Silva b. Alex O’Neill-Kerr a.
Northamptonshire Healthcare NHS Foundation Trust, Berrywood Hospital, Northampton NN5 6DU, United Kingdom
Coventry University, United Kingdom
Received 26 December 2020, Revised 2 January 2021, Accepted 11 January 2021, Available online 15 January 2021.

Alina Wilkowska,1 Łukasz Szałach,1 and Wiesław J Cubała1

Author information

Department of Psychiatry, Faculty of Medicine, Medical University of Gdańsk, Gdańsk, Poland
Correspondence: Alina Wilkowska Department of Psychiatry, Faculty of Medicine, Medical University of Gdańsk, Dębinki 7 Str, Gdańsk, 80-211, Poland, Phone: Tel + 48 58 349 26 50, Fax: Fax + 48 349 27 48, Email ali.wilkowska@gmail.com

Abstract

Bipolar disorder (BD) is a psychiatric illness associated with high morbidity, mortality and suicide rate. It has neuroprogressive course and a high rate of treatment resistance. Hence, there is an unquestionable need for new BD treatment strategies. Ketamine appears to have rapid antidepressive and antisuicidal effects. Since most of the available studies concern unipolar depression, here we present a novel insight arguing that ketamine might be a promising treatment for bipolar disorder.

Keywords: ketamine, bipolar disorder, staging, neuroprogression, treatment resistance

Tapan Parikh, M.D., M.P.H., John T. Walkup, M.D.
Published Online:1 Apr 2021 https://doi.org/10.1176/ appi.ajp.2020.21020172

In this month’s issue, Dwyer et al. (1) report the results of a randomized crossover trial of single-dose ketamine compared with midazolam for the treatment of refractory depression in adolescents. This controlled trial follows reports of adult studies and of open trials or case series in adolescents suggesting ketamine’s value as a treatment for depression (2, 3).

Linda Li1 and Phillip E. Vlisides2,*

Author information Article notes  Copyright  and License information Disclaimer

1Department of Internal Medicine, St. Joseph Mercy Hospital, Ann Arbor, MI, USA

2Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, MI, USA

Edited by: Mikhail Lebedev, Duke University, USA

Reviewed by: Axel Hutt, German Weather Service, Germany; Fabio Sambataro, Fondazione Istituto Italiano di Technologia, Italy; Yingtang Shi, University of Virginia, USA

*Correspondence: Phillip E. Vlisides ude.hcimu.dem@edisilvp

Received 2016 Sep 6; Accepted 2016 Nov 15.

Copyright © 2016 Li and Vlisides.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution and reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Abstract

Ketamine was introduced into clinical practice in the 1960s and continues to be both clinically useful and scientifically fascinating. With considerably diverse molecular targets and neurophysiological properties, ketamine’s effects on the central nervous system remain incompletely understood. Investigators have leveraged the unique characteristics of ketamine to explore the invariant, fundamental mechanisms of anesthetic action. Emerging evidence indicates that ketamine-mediated anesthesia may occur via disruption of corticocortical information transfer in a frontal-to-parietal (“top down”) distribution. This proposed mechanism of general anesthesia has since been demonstrated with anesthetics in other pharmacological classes as well. Ketamine remains invaluable to the fields of anesthesiology and critical care medicine, in large part due to its ability to maintain cardiorespiratory stability while providing effective sedation and analgesia. Furthermore, there may be an emerging role for ketamine in treatment of refractory depression and Post-Traumatic Stress Disorder. In this article, we review the history of ketamine, its pharmacology, putative mechanisms of action and current clinical applications.

Keywords: ketamine, neuropharmacology, consciousness, anesthesia, functional connectivity, depression, post-traumatic stress disorder

Neuropsychiatr Dis Treat. 2020; 16: 2707–2717.
Published online 2020 Nov 12. doi: 10.2147/NDT.S282208

Alina Wilkowska,1 Łukasz Szałach,1 and Wiesław J Cubała1

Author information
Department of Psychiatry, Faculty of Medicine, Medical University of Gdańsk, Gdańsk, Poland
Correspondence: Alina WilkowskaDepartment of Psychiatry, Faculty of Medicine, Medical University of Gdańsk, Dębinki 7 Str, Gdańsk, 80-211, Poland, Phone: Tel + 48 58 349 26 50, Fax: Fax + 48 349 27 48, Email ali.wilkowska@gmail.com

Abstract

Bipolar disorder (BD) is a psychiatric illness associated with high morbidity, mortality and suicide rate. It has neuroprogressive course and a high rate of treatment resistance. Hence, there is an unquestionable need for new BD treatment strategies. Ketamine appears to have rapid antidepressive and antisuicidal effects. Since most of the available studies concern unipolar depression, here we present a novel insight arguing that ketamine might be a promising treatment for bipolar disorder.

Keywords: ketamine, bipolar disorder, staging, neuroprogression, treatment resistance

Jennifer L Phillips 1 2, Sandhaya Norris 3 4, Jeanne Talbot 3 4, Taylor Hatchard 3, Abigail Ortiz 3, Meagan Birmingham 3, Olabisi Owoeye 3 4, Lisa A Batten 3, Pierre Blier 3 4 5

PMID: 31759333 PMCID: PMC7021716 DOI: 10.1038/s41386-019-0570-x

Abstract
Repeated administration of subanesthetic intravenous ketamine may prolong the rapid decrease in suicidal ideation (SI) elicited by single infusions. The purpose of this secondary analysis was to evaluate reduction in SI with a single ketamine infusion compared with an active control, and prolonged suppression of SI with repeated and maintenance infusions.

Jennifer L Phillips 1, Sandhaya Norris 1, Jeanne Talbot 1, Meagan Birmingham 1, Taylor Hatchard 1, Abigail Ortiz 1, Olabisi Owoeye 1, Lisa A Batten 1, Pierre Blier 1

PMID: 30922101 DOI: 10.1176/appi.ajp.2018.18070834

Abstract
Objective: Subanesthetic ketamine doses have been shown to have rapid yet transient antidepressant effects in  patients with treatment-resistant depression, which may be prolonged by repeated administration. The purpose of this study was to evaluate the antidepressant effects of a single ketamine infusion, a series of repeated ketamine infusions, and prolongation of response with maintenance infusions.

Albott CS, et al. J Clin Psychiatry. 2018 May/Jun.

Abstract
OBJECTIVE: The present study examined the efficacy, safety, and durability of repeated ketamine infusions for the treatment of comorbid posttraumatic stress disorder (PTSD) and treatment-resistant depression (TRD) in a sample of veterans.

Ketamine has brought hope to a psychiatric field desperate to find new treatments for severe OCD, a chronic condition marked by debilitating obsessions and repetitive behaviors.

Ketamine and Treatment-Resistant Depression

Murrough, Perez, et al. “Rapid and Longer-Term Antidepressant Effects of Repeated Ketamine Infusions in Treatment-Resistant Major Depression”Biological Psychiatry  2013 Aug 15;  74(4): 250–256.

http://www. ncbi.nlm.nih.gov/pmc/ articles/PMC3725185/

SUMMARY: In this article, there were 24 patients treated with six IV infusions of ketamine (.5mg/kg) over 12 days. The overall response rate was 71% as defined  as a reduction in the MADRS scale by greater than 50%. The median time to relapse after the last ketamine infusion was 18 days. 25% were symptom free at   90 days, 75% of patients had symptoms free days between 11-27 days. Side effects were reported to be a mild significant increase in dissociative symptoms. One patient had to discontinue therapy due to an increase in blood pressure that did not respond to medications (highest BP 180/115).

  • Shiroma, Johns et al. “Augmentation of response and remission to serial intravenous subanesthetic ketamine in treatment resistant depression” Journal of Affective Disorders. 2014 Feb;155:123-9.

http://www.jad-journal.com/article/S0165-0327%2813%2900778-7/abstract

SUMMARY: In this article, there were 14 patients treated with six IV infusions during a 12 day period. 12 subjects finished all six infusions with 92% response rate and 66% went into remission. 5 out of 11 responders remained in “response status” during the next 28 days. For the 6 out of 11 responders that relapsed, the mean time was 16 days. Response was defined as ≥50% improvement in baseline MADRS score and remission was defined as MADRS score ≤9. No subject experienced severe dissociative symptoms or hemodynamic changes that required stopping the infusions.

  • Sanacora, Frye, McDonald, et al. “A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders” JAMA Psychiatry. April 2017;74(4):399-405.

http://jamanetwork.com /journals/jamapsychiatry /fullarticle/2605202

SUMMARY: This review and consensus statement provides a general overview of the data on the use of ketamine for the treatment of mood disorders and highlights the limitations of the existing knowledge. The suggestions provided are intended to facilitate clinical decision making and encourage an evidence-based approach to using ketamine in the treatment of psychiatric disorders considering the limited information that is currently available. This article provides information on potentially important issues related to the off-label treatment approach that should be considered to help ensure patient safety.

Ketamine and Complex Regional Pain Syndrome

Correll, Maleki et al. “Subanesthetic ketamine infusion therapy: a retrospective analysis of a novel therapeutic approach to complex regional pain syndrome.” Pain Medicine. 2004 Sep;5(3):263-75.

http://painmedicine. oxfordjournals.org/content/ painmedicine/5/3/263.full .pdf

SUMMARY: This article reviewed 33 cases of patients with CRPS that were treated with Ketamine infusion. The patients received a prolonged low dose infusion of ketamine, on average 10-20mg/hr over 2-4 days. 76% of patients experienced complete pain relief after the first course of treatment. Pain relief lasted at least three months for most patients. Adding a second course of treatment allowed over 50% to be pain free for over a year. One patient had to discontinue additional treatments after the first infusion after developing elevated liver enzymes. These did normalize after treatment was stopped.

Ketamine and Chronic Pain Syndromes (headache, CRPS and back pain)

Patil S, Anitescu M. “Efficacy of outpatient ketamine infusions in refractory chronic pain syndromes: a 5-year retrospective analysis. Pain Medicine. 2012 Feb;13(2):263-9.

http://painmedicine.oxfordjournals.org/ content/13/2/263.long SUMMARY: This article reviewed 49 patients receiving outpatient ketamine infusions for various pain syndrome – 18 with CRPS. For patients with CRPS, the average reduction in the pain score on a ten point scale was 7.2. For the other pain conditions, the average reduction in the pain score was 5.1. Average pain relief was at least three weeks.

Ketamine and PTSD

Feder, Parides et al. “Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: a randomized clinical trial.” JAMA Psychiatry. 2014 Jun;71(6):681-8.

http:// archpsyc.jamanetwork. com/article.aspx? articleid=1860851 SUMMARY: In this double blind, placebo-controlled cross over study, a single dose of Ketamine (.5mg/kg over 40 minutes) was compared to midazolam. Authors note a significant immediate reduction in the CAPS score and frequently this reduction was maintained for over 2 weeks. The only side effects noted were transient dissociative symptoms, none of which required stopping the infusion.

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