The effects of ketamine on various formulations and study settings in 2020

Abstract

Introduction

Suicidality and self-injurious behavior afflict patients with a wide variety of psychiatric illnesses. Currently, there are few pharmacologic treatments for suicidality and self-injurious behavior and none that treat these conditions emergently. Recently, ketamine has demonstrated efficacy in treating both depression and acute suicidal ideation. An increasing usage of Ketamine online, of a variety of formulations, has been studied for these indications. This article reviews the evidence for use of ketamine in self-injurious behavior and suicidality.

Methods

A review of the MEDLINE database for articles relating to ketamine, self-injurious behavior, suicidality, and self-harm was conducted. Additional articles were assessed via cross-reference.

Results

A total of 24 articles that included clinical trials, meta-analyses, case series, and case reports were analyzed. The majority of studies of ketamine for suicidal ideation include the intravenous route using a dose of 0.5 mg/kg over 40 minutes. These studies suggest that intravenous ketamine may be effective at reducing suicidal ideation acutely. Data on use of ketamine in the intramuscular, intranasal, and oral forms are limited and of poorer quality. Studies on these formulations contain greater variability of positive and negative results of ketamine for reducing suicidality and self-injurious behavior. The durability of the antisuicidal effects across all formulations is limited.

Discussion

Ketamine may be an effective option for the treatment of suicidal ideation in patients across inpatient, outpatient, or emergent settings. At this time, more research is needed on the efficacy of ketamine across all formulations being used in clinical practice.

Introduction

Self-injurious behavior (SIB), including both nonsuicidal self-harm and suicidal behavior, affects millions of patients annually.1  An estimated 800 000 people die by suicide each year, and nonfatal self-harm occurs 20 times more frequently.  Each episode of self-harm increases the likelihood of a future suicide or SIB.3  Although these behaviors are commonly associated with major depressive disorder (MDD), patients with schizophrenia, personality disorders, autism, bipolar disorder, and substance use disorders may also exhibit these characteristics.

In addition to the detriment to the patient and those close to the patient, SIB contributes to numerous hospitalizations each year, which, in turn, result in significant cost to patients, communities, and health systems. 

Despite the prevalence of SIB across several psychiatric conditions, advances in the treatment options for these behaviors have been limited. Currently, the management options for patients with depression are limited by pharmacologic modality and the inability to treat acute suicidal behaviors in a targeted manner. Additionally, first-line antidepressants may take several weeks for therapeutic effect and about two-thirds of patients will require either augmentation or a trial of an alternate pharmacotherapy for their depressive symptoms.6  The black box warning of antidepressants for suicidality among children and adolescents may also present as barriers for using these agents. Furthermore, most clinical trials of antidepressants exclude suicidal patients, which limits the generalizability of the results of efficacy trials for patients who display behaviors of self-harm.7  Non Antidepressants, such as lithium or clozapine, have demonstrated benefit in reducing suicidal behaviors; however, these outcomes were not demonstrated in the emergent setting. Electroconvulsive therapy may provide the most rapid response for reducing acute suicidality, but access to this treatment modality may be limited and may not be considered a favorable option for patients. Additionally, several sessions of treatment are usually necessary for full remission.

Ketamine is an NMDA (N-methyl-D-aspartate) antagonist that has received attention as a novel pharmacologic option for major depression and, more importantly, for reducing acute suicidality.   Since development, ketamine has predominantly been viewed as an anesthetic as well as an illicit drug of abuse; however, ketamine (as well as the S-enantiomer ketamine) has demonstrated benefit in rapidly reducing symptoms of depression in refractory patients at subanesthetic doses.