Reference Excerpt 12

Intravenous Ketamine for Adults with Treatment-Resistant Depression or Post-Traumatic Stress Disorder: A Review of Clinical Effectiveness, Cost-Effectiveness and Guidelines

(English) By: Li KX; Loshak H, 2019 Oct 24; Publisher: Canadian Agency for Drugs and Technologies in Health; PMID: 31873996;

Treatment-resistant depression (TRD) is a condition that affects patients with depression who have not achieved an adequate response to conventional antidepressant therapies.1 TRD is commonly defined as major depressive disorder (MDD) with at least two prior treatment failures given adequate dose and duration.2 For patients with bipolar disorder, TRD is defined as a minimum of one prior treatment failure.2 Compared to non-treatment resistant MDD, TRD is associated with reduced quality of life, social and occupational impairment, comorbidities, and higher likelihood of prior suicide attempts.1 Patients with TRD are twice as likely to be hospitalized than patients with non-treatment resistant MDD; and increased hospitalization is associated with substantially increased resource utilization.1,2 Risk factors for TRD include old age, divorced or widowed marital status, and concomitant psychiatric disorders such as anxiety and personality disorders.2 Post-traumatic stress disorder (PTSD) occurs as a response to a traumatic event or extreme stressor (such as military combat, sexual assault, torture, being kidnapped, severe car accidents, and natural disasters).3 Patients experience symptoms that may include emotional impairment due to depression, anxiety, flashbacks, insomnia, feelings of guilt of having survived, and difficulty concentrating.3 In 2008, the Canadian lifetime prevalence rate of PTSD was estimated to be 9.2%.4 Antidepressants including selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are commonly prescribed agents for depression, while electroconvulsive therapy (ECT) is the gold standard and a late-line therapy for TRD.5,6 Ketamine is a N-methyl-d-aspartate (NMDA) receptor antagonist that leads to increased synaptic plasticity and may elicit a rapid antidepressant response in individuals with depression.7In Canada, a number of formulations of ketamine are approved for general anesthesia.8 However, antidepressant effects of ketamine have been observed in animal models of depression and in human studies of depression, and ketamine has showed potential as a novel, rapid-acting therapeutic option for patients with TRD and PTSD.9,10 The purpose of this report is to update the previous 2017 CADTH report11 and to examine the clinical effectiveness, cost-effectiveness and evidence-based guidelines on the use of intravenous ketamine for adults with TRD or PTSD.

Copyright © 2019 Canadian Agency for Drugs and Technologies in Health.