Anxiety DisordersBipolar DisorderDepressive DisordersMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Headache Disorders (Cluster & Migraine)SuicidalitySafety & Risk ManagementChronic PainKetamine

Administration of ketamine for unipolar and bipolar depression

This review (2017) examined clinical trials that investigated the antidepressant efficacy of ketamine for unipolar (MDD) and bipolar depression (BD). Results indicate that intravenous and intranasal ketamine produces strong reductions of depressive symptoms within a short period and with response rates up to 88%, however, depressive relapse occurs in up to 90% of patients within 2 weeks after treatment.

Authors

  • Siegfried Kasper

Published

International Journal of Psychiatry in Clinical Practice
meta Study

Abstract

Objective

Clinical trials demonstrated that ketamine exhibits rapid antidepressant efficacy when administered in subanaesthetic dosages. We reviewed currently available literature investigating efficacy, response rates and safety profile.

Methods

Twelve studies investigating unipolar, seven on bipolar depression were included after search in medline, scopus and web of science.

Results

Randomized, placebo-controlled or open-label trials reported antidepressant response rates after 24 h on primary outcome measures at 61%. The average reduction of Hamilton Depression Rating Scale (HAM-D) was 10.9 points, Beck Depression Inventory (BDI) 15.7 points and Montgomery-Asberg Depression Rating Scale (MADRS) 20.8 points. Ketamine was always superior to placebo. Most common side effects were dizziness, blurred vision, restlessness, nausea/vomiting and headache, which were all reversible. Relapse rates ranged between 60% and 92%. To provide best practice-based information to patients, a consent-form for application and modification in local language is included.

Conclusions

Ketamine constitutes a novel, rapid and efficacious treatment option for patients suffering from treatment resistant depression and exhibits rapid and significant anti-suicidal effects. New administration routes might serve as alternative to intravenous regimes for potential usage in outpatient settings. However, long-term side effects are not known and short duration of antidepressant response need ways to prolong ketamine’s efficacy.

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Research Summary of 'Administration of ketamine for unipolar and bipolar depression'

Introduction

Treatment-resistant depression (TRD), commonly defined as failure to respond to more than two antidepressant trials, affects an estimated 10–30% of people with major depressive disorder and carries high risks of suicide, relapse and socioeconomic burden. Ketamine, an NMDA-receptor antagonist first introduced as an anaesthetic, attracted interest after animal and serendipitous clinical observations suggested rapid antidepressant effects; subsequent small clinical trials have reported robust, short-lived reductions in depressive symptoms. Despite ketamine's long history in anaesthesia and known pharmacology, uncertainties remain about optimal dosing and administration, duration of benefit, long-term safety, interaction with other medications and how to translate trial protocols into routine clinical practice. Kraus and colleagues set out to review clinical trials of ketamine in unipolar and bipolar depression to summarise efficacy, response and remission rates, and the safety profile, and to offer practical information for clinicians. The review sought studies using standardised depression outcome measures and aimed to focus on clinically relevant end points, primarily 24-h post-treatment effects; a patient consent form for clinical application was developed as supplementary material to aid implementation in practice.

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Study Details

References (12)

Papers cited by this study that are also in Blossom

Antidepressant effects of ketamine in depressed patients

Berman, R. M., Cappiello, A., Anand, A. et al. · Biological Psychiatry (2000)

The use of ketamine as an antidepressant: a systematic review and meta-analysis

Coyle, C. M., Laws, K. R. · Human Psychopharmacology (2015)

Ketamine-induced modulation of the thalamo-cortical network in healthy volunteers as a model for schizophrenia

Höflich, A., Hahn, A., Küblböck, M. et al. · International Journal of Neuropsychopharmacology (2015)

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Luckenbaugh, D. A., Niciu, M. J., Ionescu, D. F. et al. · Journal of Affective Disorders (2014)

Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial

Murrough, J. W., Iosifescu, D. V., Chang, L. C. et al. · American Journal of Psychiatry (2013)

Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression

Newport, D. J., Carpenter, L. L., Mcdonald, W. M. et al. · American Journal of Psychiatry (2015)

Single Ketamine Infusion and Neurocognitive Performance in Bipolar Depression

Permoda-Osip, A., Kisielewski, J., Bartkowska- Sniatkowska, A. et al. · Pharmacopsychiatry (2014)

Oral ketamine for the treatment of pain and treatment-resistant depression

Schoevers, R. A., Chaves, T. V., Balukova, S. M. et al. · brazilian Journal of Psychiatry (2016)

Relationship of ketamine’s antidepressant and psychotomimetic effects in unipolar depression

Sos, P., Klirova, M., Novák, T. et al. · Neuropsychiatric Disease And Treatment (2013)

R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects

Yang, C., Shirayama, Y., Zhang, J-C. et al. · Translational Psychiatry (2020)

Show all 12 references
NMDAR inhibition-independent antidepressant actions of ketamine metabolites

Zanos, P., Moaddel, P. J., Morris, P. J. et al. · Nature (2016)

Replication of Ketamine’s Antidepressant Efficacy in Bipolar Depression: A Randomized Controlled Add-On Trial

Zarate, C. A., Brutsche, N. E., Ibrahim, L. et al. · Biological Psychiatry (2012)

757 cited

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