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Ketamine’s effects on suicidal ideation seems independent of its antidepressant effect.22 A post hoc analysis of 2 trials in TRD found that open-label intravenous ketamine was associated with rapid reductions in explicit and implicit suicidal cognition within the first 24 hours.
There has been some skepticism regarding the practicality of administering intravenous ketamine infusions in clinical practice.28 However, one of the most important features of the Larkin and Beautrais study is that it took place in the ED, which suggests the feasibility of using ketamine in a busy ED setting.
Intramuscular formulation could be considered for acutely suicidal patients when access to intravenous lines are limited.29-31 An intranasal formulation with a controlled delivery system may address concerns of ketamine abuse if prescribed in outpatient settings. Another advantage of ketamine is the potential use of BDNF, a peripheral biomarker, to predict antidepressant response to ketamine.12,33 Thus, within 24 hours of the first ketamine dose, clinicians are able to make informed decisions on whether to continue ketamine or use a different therapeutic modality.
It is important to recognize that RCTs for ketamine as treatment for MDD are still in their early stages, and the evidence is limited. While there is understandable enthusiasm regarding ketamine’s potential, there are insufficient data to support its integration in clinical care at this time. Acknowledgment—This article is the result of work supported with resources from and the use of facilities at the Michael E.
Slideshare uses cookies to improve functionality and performance, and to provide you with relevant advertising. However, ketamine’s safety and utility in specific clinical populations is well characterized based on years of use in anesthesiology and emergency medicine.
The optimal dose of ketamine has not been established, which is the focus of a new NIMH-sponsored trial ( Identifier NCT01920555). Most patients relapse within 2 weeks of a single infusion.22,41 Repeated ketamine infusions have not led to substantial prolongation of the antidepressant effects.
Several treatment modalities have been recommended for patients who have inadequate responses to repeated antidepressant trials, including augmentation with lithium, triiodothyronine, or second-generation anti- psychotics, and neuromodulatory techniques, such as repetitive transcranial magnetic stimulation.
The broader effectiveness of ketamine in varied clinical settings has not been systematically examined. DeBakey Veterans Affairs Medical Center and the Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston. Usually, suturing or nerve grafts are employed depending on the injury distance between the proximal and distal nerve segments. Nerve grafts can come in various forms, including nerves, veins, muscles, and even arteries.4 The current gold standard for treating patients with peripheral nerve injury is using autologous nerve grafts.
Perry and colleagues34 reviewed the safety of ketamine in a psychiatric research setting and concluded that ketamine was safe in healthy volunteers. Although, its use is curtailed by cognitive adverse effects and the public’s opinion about “shock therapy,” ECT remains the most effective therapy for patients with TRD.
More studies are needed on critical issues, such as dose optimization, alternative drug delivery routes, methods to prevent relapse following resolution of depressive symptoms, and understanding neurobiological mechanisms underlying the putative antidepressant actions of ketamine.

Dr Al Jurdi reports no conflicts of interest concerning the subject matter of this article. The Global Burden of Disease: A Comprehensive Assessment of Mortality and Disability From Diseases, Injuries and Risk Factors in 1990 and Projected to 2020. The purpose of suturing two nerve segments is to facilitate proper alignment between the fascicles, mimicking the native nerve before damage in order to preserve function. The emerging evidence of patients with TRD who receive subanesthetic doses of ketamine further cements its safety and tolerability. The augmentation of a single ketamine infusion with the glutamate modulator riluzole showed no difference from placebo in preventing relapse post-ketamine.44,45 Using ketamine in combination with electroconvulsive therapy (ECT) did not improve outcomes whether at anesthetic or subanesthetic dose.
Dr Mathew reports that he has received research support from Janssen Research and Development, AstraZeneca, and the NIMH; he is a consultant to Bristol-Myers Squibb, Genentech, and Naurex.
Figure 1 shows two examples of direct nerve suturing.2 This procedure is only used when the injury distance is small, because of biomechanics. In addition, this can help facilitate proper axon regeneration by using a healthy nerve as a substrate. Non-normal physiological tension created as a result of suturing will negatively affect the nerve trunk. However, acquiring an autologous nerve graft requires an additional surgery to dissect a nerve, which usually is from sural or saphenous nerve.
Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. By losing function at this site, the patient hopes to regenerate some function at the injured site, but there is no guarantee. Properties of the interaction between ketamine and opiate binding sites in vivo and in vitro. Properties of the optical isomers and metabolites of ketamine on the high affinity transport and catabolism of monoamines.
Glutamate modulators as potential therapeutic drugs in schizophrenia and affective disorders. Glutamate N-methyl-D-aspartate receptor antagonists rapidly reverse behavioral and synaptic deficits caused by chronic stress exposure. Plasma brain derived neurotrophic factor (BDNF) and response to ketamine in treatment-resistant depression. Antidepressant effects of ketamine: mechanisms underlying fast-acting novel antidepressants. A neurotrophic hypothesis of depression: role of synaptogenesis in the actions of NMDA receptor antagonists.

Pathophysiology of depression and innovative treatments: remodeling glutamatergic synaptic connections. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Ketamine as the prototype glutamatergic antidepressant: pharmacodynamics actions, and a systematic review and meta-analysis of efficacy. Effects of intravenous ketamine on explicit and implicit measures of suicidality in treatment-resistant depression. Effects of ketamine on explicit and implicit suicidal cognition: a randomized controlled trial in treatment-resistant depression. Rapid resolution of suicidal ideation after a single infusion of an N-methyl-D-aspartate antagonist in patients with treatment-resistant major depressive disorder. A preliminary naturalistic study of low-dose ketamine for depression and suicide ideation in the emergency department.
Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder. Ketamine in adults: what emergency physicians need to know about patient selection and emergence reactions. Ketamine potentiates cerebrocortical damage induced by the common anaesthetic agent nitrous oxide in adult rats. Safety and efficacy of repeated-dose intravenous ketamine for treatment-resistant depression. Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression. Riluzole for relapse prevention following intravenous ketamine in treatment-resistant depression: a pilot randomized, placebo-controlled continua-tion trial. Course of improvement in depressive symptoms to a single intravenous infusion of ketamine vs add-on riluzole: results from a 4-week, double-blind, placebo-controlled study. Neuropsychological and mood effects of ketamine in electroconvulsive therapy: a randomised controlled trial. Rapid antidepressant effect of ketamine anesthesia during electroconvulsive therapy of treatment-resistant depression: comparing ketamine and propofol anesthesia.

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