PubMed Search For “IV Ketamine For Depression”

In this post, I link to and list some of the articles that I reviewed in doing a PubMed search on IV ketamine for depression.

The PubMed search yielded 322 results.

Here are links to the abstracts of some of the articles I reviewed.

Developing an IV Ketamine Clinic for Treatment-Resistant Depression: a Primer. Psychopharmacol Bull. 2021 Jun 1;51(3):109-124. Free Full-Text Article.

Sagar V Parikh 1Daniela Lopez 1Jennifer L Vande Voort 1Jose Rico 1Eric Achtyes 1William Coryell 1Andrew Goddard 1Fernando Goes 1John F Greden 1Balwinder Singh 1Adam Kaplin 1Mark A Frye 1Daniel Maixner 1Brendon Watson 1Karina Drake 1Vijay Tarnal 1Patricio Riva-Posse 1William V Bobo 1Bio-K Study Team 1


  • 1Parikh, MD, Lopez, MS, Maixner, MD, Watson, MD, Drake, MD, Bio-K Study Team, Department of Psychiatry and Depression Center, University of Michigan, Ann Arbor, Michigan. Voort, MD, Rico, MBA, Singh, MD, Frye, MD, Bobo, MD, Bio-K Study Team, Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota. Achtyes, MD, Bio-K Study Team, Pine Rest Christian Mental Health Services, Grand Rapids, Michigan. Coryell, MD, Bio-K Study Team, University of Iowa, Iowa City, Iowa. Goddard, MD, Bio-K Study Team, University of California San Francisco, San Francisco, California. Goes, MD, Bio-K Study Team, Department of Psychiatry and Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Riva-Posse, MD, Bio-K Study Team, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia. Tarnal, MD, Bio-K Study Team, Department of Anesthesiology, University of Michigan, Ann Arbor. Greden, MD, Bio-K Study Team, Department of Psychiatry and Depression Center, University of Michigan, Ann Arbor, Michigan; National Network of Depression Centers, Ann Arbor, Michigan. Kaplin, MD, Bio-K Study Team, Department of Psychiatry and Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland; MyMD Pharmaceuticals Inc, Baltimore, Maryland.

When a decision to start a ketamine clinic is made by an institution, all interested stakeholders should be included in the decision-making process. A ketamine clinic will usually benefit from the participation of different departments (primarily psychiatry and anesthesia) along with key administrative committees (such as a Pharmacy and Therapeutics or Medical Practice Committee), and also members of relevant professions. In addition to the department of psychiatry, other key clinical stakeholders will include the anesthesiology department, whose practitioners possess particular expertise and often explicit medical authority over the administration of ketamine; the nursing department that can ensure best practices in nursing are followed during the administration and monitoring of ketamine; and finally the billing and financial departments together with the administrators who will determine the appropriate costs, reimbursements, and administrative operations responsible for space and equipment allocations to allow IV ketamine to be administered.

For clinical administrative purposes, a series of detailed standard operating procedures (SOPs), aligned with larger institutional clinical practice committees, will need to be developed to clarify hospital-based vs clinic-based service, the roles and training for all staff, the detailed evaluation of the patient, and specific instructions on administration and monitoring of the ketamine infusions. Examples of such policies currently are not published as peer-reviewed articles but are often available on the internet; additionally, a useful document is the consensus statement on ketamine for mood disorders. Such policies have been designed based on the clinical experience of the providers, often inspired by protocols used in research studies, with incorporation of safety monitoring requirements relevant to clinical rather than research settings. Several such policies from the authors’ institutions have been consulted in constructing this article, particularly those from the Mayo Clinic and the University of Michigan. Finally, a robust process must be designed for ensuring proper informed consent, with the development of both a sufficiently detailed consent form as well as patient education materials. Each of these steps in preparing to launch a ketamine clinic, from administrative to clinical, is discussed below.

The Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Recommendations for the Use of Racemic Ketamine in Adults with Major Depressive Disorder: Recommandations Du Groupe De Travail Du Réseau Canadien Pour Les Traitements De L’humeur Et De L’anxiété (Canmat) Concernant L’utilisation De La Kétamine Racémique Chez Les Adultes Souffrant De Trouble Dépressif Majeur. Can J Psychiatry. 2021 Feb;66(2):113-125. Free Full Text Article.

Jennifer Swainson 1Alexander McGirr 2Pierre Blier 3Elisa Brietzke 4Stéphane Richard-Devantoy 5Nisha Ravindran 6Jean Blier 7Serge Beaulieu 5Benicio N Frey 8Sidney H Kennedy 6Roger S McIntyre 6Roumen V Milev 4Sagar V Parikh 9Ayal Schaffer 6Valerie H Taylor 2Valérie Tourjman 10Michael van Ameringen 8Lakshmi N Yatham 11Arun V Ravindran 6Raymond W Lam 11


  • 1Department of Psychiatry, 12357University of Alberta, Edmonton, Alberta, Canada.
  • 2Department of Psychiatry, 70401University of Calgary, Alberta, Canada.
  • 3Department of Psychiatry, 12365University of Ottawa, Ontario, Canada.
  • 4Department of Psychiatry, 104820Queen’s University, Kingston, Ontario, Canada.
  • 5Department of Psychiatry, 12367McGill University, Montreal, Quebec, Canada.
  • 6Department of Psychiatry, 12366University of Toronto, Ontario, Canada.
  • 7Department of Anesthesiology and Pain Medicine, 12365University of Ottawa, Ontario, Canada.
  • 8Department of Psychiatry and Behavioural Neurosciences, 62703McMaster University, Hamilton, Ontario, Canada.
  • 9Department of Psychiatry, 12266University of Michigan, Ann Arbor, Michigan, USA.
  • 10Department of Psychiatry, 12368Université de Montréal, Québec, Canada.
  • 11Department of Psychiatry, 8166University of British Columbia, Vancouver, British Columbia, Canada.

Free PMC article

Erratum in
The Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Recommendations for the Use of Racemic Ketamine in Adults with Major Depressive Disorder.
[No authors listed]
Can J Psychiatry. 2021 Dec;66(12):1102. doi: 10.1177/07067437211035276. Epub 2021 Aug 12.
PMID: 34382885 Free PMC article. No abstract available.

Abstract in English, French
Objective: Patients with major depressive disorder often have limited response to first-line and second-line medications; hence, novel pharmacological treatments are needed for treatment-resistant depression (TRD). Ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, has demonstrated rapid antidepressant effects in patients with TRD. The Canadian Network for Mood and Anxiety Treatments (CANMAT) convened a task force to review the evidence for efficacy and safety of racemic ketamine and to provide recommendations for its use in clinical practice.

Methods: A systematic review was conducted with computerized search of electronic databases up to January 31, 2020 using combinations of search terms, inspection of bibliographies, and review of other ketamine guidelines and consensus statements. The level of evidence and lines of treatment were assigned according to CANMAT criteria. Recommendations were given in question-answer format.

Results: Intravenous (IV) racemic ketamine given as a single infusion has Level 1 evidence for efficacy in adults with TRD. The evidence for multiple infusions, given as an acute series or as ongoing maintenance treatment, is limited to Level 3. Adverse events associated with ketamine infusions include behavioral (e.g., dissociative symptoms) and physiological (e.g., hypertension) events. There is only Level 3 or 4 evidence for non-IV formulations of racemic ketamine. Consensus recommendations are given for clinical administration of IV ketamine including patient selection, facility and personnel issues, monitoring, and maintaining response.

Conclusions: Single-dose IV racemic ketamine is a third-line recommendation for adults with TRD. The need for repeated and maintenance ketamine infusions should be carefully assessed on a case-by-case basis with consideration of potential risks and benefits. Because of limited evidence for efficacy and risk for misuse and diversion, the use of oral and other formulations of racemic ketamine should be limited to specialists with ketamine-prescribing expertise and affiliations with tertiary or specialized centers.

Keywords: antidepressants; depression; esketamine; glutamate; ketamine; major depressive disorder; treatment-resistant depression.

Double-blind, placebo-controlled, dose-ranging trial of intravenous ketamine as adjunctive therapy in treatment-resistant depression (TRD) Mol Psychiatry. 2020 Jul;25(7):1592-1603. Free Full-Text Article.

Maurizio Fava1Marlene P Freeman2Martina Flynn2Heidi Judge2Bettina B Hoeppner2Cristina Cusin2Dawn F Ionescu2Sanjay J Mathew3Lee C Chang3Dan V Iosifescu4James Murrough4Charles Debattista5Alan F Schatzberg5Madhukar H Trivedi6Manish K Jha6Gerard Sanacora7Samuel T Wilkinson7George I Papakostas2


  • 1Massachusetts General Hospital, Boston, MA, USA.
  • 2Massachusetts General Hospital, Boston, MA, USA.
  • 3Baylor College of Medicine/Michael E. Debakey VA Medical Center, Houston, TX, USA.
  • 4Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 5Stanford University School of Medicine, Stanford, CA, USA.
  • 6University of Texas Southwestern, Dallas, TX, USA.
  • 7Yale University, New Haven, CT, USA.

Free PMC article

Erratum in
Correction: Double-blind, placebo-controlled, dose-ranging trial of intravenous ketamine as adjunctive therapy in treatment-resistant depression (TRD).
Fava M, Freeman MP, Flynn M, Judge H, Hoeppner BB, Cusin C, Ionescu DF, Mathew SJ, Chang LC, Iosifescu DV, Murrough J, Debattista C, Schatzberg AF, Trivedi MH, Jha MK, Sanacora G, Wilkinson ST, Papakostas GI.
Mol Psychiatry. 2020 Jul;25(7):1604. doi: 10.1038/s41380-018-0311-2.
PMID: 30617276 Free PMC article.

Numerous placebo-controlled studies have demonstrated the ability of ketamine, an NMDA receptor antagonist, to induce rapid (within hours), transient antidepressant effects when administered intravenously (IV) at subanesthetic doses (0.5 mg/kg over 40 min). However, the optimal antidepressant dose remains unknown. We aimed to compare to active placebo the rapid acting antidepressant properties of a broad range of subanesthetic doses of IV ketamine among outpatients with treatment-resistant depression (TRD). A range of IV ketamine doses were compared to active placebo in the treatment of adult TRD over a 3-day period following a single infusion over 40 min. This was an outpatient study conducted across six US academic sites. Outpatients were 18-70 years old with TRD, defined as failure to achieve a satisfactory response (e.g., less than 50% improvement of depression symptoms) to at least two adequate treatment courses during the current depressive episode. Following a washout period, 99 eligible subjects were randomly assigned to one of the five arms in a 1:1:1:1:1 fashion: a single intravenous dose of ketamine 0.1 mg/kg (n = 18), a single dose of ketamine 0.2 mg/kg (n = 20), a single dose of ketamine 0.5 mg/kg (n = 22), a single dose of ketamine 1.0 mg/kg (n = 20), and a single dose of midazolam 0.045 mg/kg (active placebo) (n = 19). The study assessments (HAM-D-6, MADRS, SDQ, PAS, CGI-S, and CGI-I) were performed at days 0, 1, 3 (endpoint), 5, 7, 14, and 30 to assess the safety and efficacy. The overall group × time interaction effect was significant for the primary outcome measure, the HAM-D-6. In post hoc pairwise comparisons controlling for multiple comparisons, standard dose (0.5 mg/kg) and high dose (1 mg/kg) of intravenous ketamine were superior to active placebo; a low dose (0.1 mg/kg) was significant only prior to adjustment (p = 0.02, p-adj = 0.14, d = -0.82 at day 1). Most of the interaction effect was due to differences at day 1, with no significant adjusted pairwise differences at day 3. This pattern generally held for secondary outcomes. The infusions of ketamine were relatively well tolerated compared to active placebo, except for greater dissociative symptoms and transient blood pressure elevations with the higher doses. Our results suggest that there is evidence for the efficacy of the 0.5 mg/kg and 1.0 mg/kg subanesthetic doses of IV ketamine and no clear or consistent evidence for clinically meaningful efficacy of lower doses of IV ketamine. Trial Registration: NCT01920555.

Subcutaneous Ketamine in Depression: A Systematic Review


  • 1Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil.
  • 2Programa de Transtornos Afetivos, Laboratório Interdisciplinar de Neurociências Clínicas, Department of Psychiatry, Federal University of São Paulo, São Paulo, Brazil.
  • 3University Hospital, University of São Paulo, São Paulo, Brazil.

Free PMC article


Background: Ketamine has been shown to produce a rapid and robust antidepressant effect. Though numerous routes of administration have been studied, subcutaneous (SC) has proven to be a convenient and cost-effective route making its use particularly relevant in developing countries. Here we provide a systematic review covering the use of SC racemic ketamine and esketamine in depression, including its efficacy, safety and tolerability. Methods: A systematic literature search was carried out, from inception through March, 2021, using PubMed/MEDLINE, EMBASE and Web of Science, with no limits of language. After identifying 159 potentially relevant articles, 12 articles were selected after applying our inclusion/exclusion criteria. These comprised two randomized clinical trials, five case-reports and five retrospective studies. Given the small number of studies found and their heterogeneous nature, a meta-analysis was not considered appropriate. Here we provide a synthesis of these data including participant characteristics, dose range, efficacy, safety/ tolerability. Risk of bias was accessed using the Cochrane risk of bias tool. Results: SC Ketamine was administered to unipolar and bipolar patients a single or multiple doses, weekly or twice-weekly, a dose-titration approach was made in major studies, dose ranged from 0.1 to 0.5 mg/Kg of racemic ketamine and 0.5-1 mg/Kg of esketamine. Across all studies, SC ketamine showed a rapid and robust antidepressant effect, with response/ remission rates from 50 to 100% following both single or multiple doses, with transitory side effects. Conclusion: SC racemic ketamine and esketamine in depression is a promising strategy showing beneficial efficacy and tolerability. Future studies exploring the SC route, its cost-effectiveness, and a direct comparison with IV and intranasal (IN) protocols are warranted. Systematic Review Registration: CRD42019137434.

Keywords: antidepressant; depression; glutamate; ketamine; subcutaneous.

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