Research Update: International Expert Opinion Statement on Ketamine for Treatment Resistant Depression
May 25, 2021
Treatment-resistant depression is a major worldwide issue. Surveys in 21 countries indicate that in any given year, 5% of the population suffers with depression. The lifetime prevalence of depression worldwide is estimated at around 12%.
A panel of worldwide ketamine researchers, including many at prominent US centers such as Yale and the National Institute of Mental Health, recently published a statement on the current knowledge of ketamine for treatment-resistant depression.
The article, entitled “Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression; An International Expert Opinion on the Available Evidence and Implementation”, was published online on March 17 by the American Journal of Psychiatry.
The authors state that the purpose of the article is twofold. First, to provide a synthesis of the current understanding of ketamine’s pharmacology, efficacy, tolerability, and safety. Second, to review the clinical aspects of administration at the point of care. This review will focus on intravenous ketamine.
The article notes that the majority of patients who are treated with standard medications such as SSRIs fail to achieve full recovery with the first treatment. Although there is some debate on the issue, most studies define treatment-resistant depression as an insufficient response to a course of 2 standard antidepressants.
The prevailing view is that ketamine improves depression by strengthening and increasing the number of connections between certain neurons, referred to as synaptogenesis and synaptic potentiation. This effect is mediated by blocking the NMDA receptor which in turn causes a surge in glutamate, the major excitatory neurotransmitter in the brain.
The authors note that repeated studies have unequivocally shown that ketamine provides a rapid and significant improvement in patients with treatment-resistant depression.
The most common psychiatric side effects of ketamine include dissociation, perceptual disturbances, abnormal sensations, and depersonalization. Results are mixed as to whether dissociation correlates with the anti-depressant effects. These effects are transient, usually resolving after 1-2 hours.
Other common side effects include elevation of blood pressure and heart rate. Most patients remain asymptomatic, but some may require medication to lower the blood pressure.
The panel recommends that personnel administering ketamine have expertise in assessing and managing mood disorders. The staff should also have expertise in assessing cardiovascular and respiratory function and have Advanced Cardiac Life Support training.
The authors recommend that patients have a physical exam prior to infusion treatment. Monitoring of ECG tracing and pulse oximetry are essential. Evaluation of depression symptom severity with a standard assessment tool is required. Such tools include the Patient Health Questionnaire-9, Beck Depression Inventory, or the 16 item Quick Inventory of Depression Symptom Self Report.
The article recommends starting the treatment dose at 0.5 mg per kilogram, administered intravenously over 40 minutes. Upon completion of 4-6 treatments, a follow-up assessment should be done. If there is less than 20% improvement in symptoms at that point, then the patient would be deemed nonresponsive and further treatments would not be warranted.