Ketamine and depression: the first days of treatment

March 1, 2024

Reviewed and approved by Clínica Synaptica

Written by

Òscar Parés Franquero

CEO Clinica Synaptica

What is depression, what impact does it have, and how is it treated?

Depression, technically known as major depressive disorder or clinical depression, is a disorder that affects our mood, thoughts, cognitive abilities (such as attention and memory), and physical state. According to the World Health Organization (WHO), it is currently the leading cause of global disability. In Europe alone, it is estimated to cost around 92 million euros annually, primarily due to productivity losses. References to this affliction date back to antiquity, with one of the earliest descriptions found in the works of the famous Greek physician Hippocrates, who termed it “melancholia.”

Conventional treatment and limitations

Currently, the treatment of depression typically involves a combination of medications, such as selective serotonin reuptake inhibitors (SSRIs), and psychotherapy. Unfortunately, no single medication works for everyone, with approximately 33% of patients not responding to commonly used medications. When a patient does not respond to one or more treatments, it is considered treatment-resistant depression. This has driven ongoing research and innovation into new treatments, such as psilocybin or ketamine.

Ketamine: A breakthrough in depression treatment

Ketamine is a dissociative anesthetic known for its sedative and analgesic properties. Over the past two decades, its antidepressant properties have also been explored, showing significant reduction in depressive symptoms within hours of administration. Ketamine is generally considered safe, with occasional and mild side effects (such as nausea and dizziness) and pleasant effects like relaxation. It is important to note that long-term misuse of ketamine, like any medication, can lead to health problems, though this is primarily seen in those who abuse it recreationally at high frequency. However, in its therapeutic use for depression, there is no evidence of long-term cognitive deficits. Typically, very low doses are administered intravenously, intramuscularly, or intranasally.

Scientific evidence on ketamine

In subsequent entries, we will summarize the scientific evidence regarding ketamine’s antidepressant properties. We will begin with a meta-analysis published in 2016 that explored ketamine’s efficacy in reducing depression symptoms within the first seven days of administration. This publication analyzed nine double-blind randomized studies. In all these studies, patients diagnosed with depression were divided into two groups: those receiving ketamine treatment and those receiving a placebo. Neither the clinicians nor the patients knew which treatment they were receiving (a hallmark of double-blind studies to prevent bias in treatment response evaluation). The placebo in seven studies was inert, providing no pharmacological effects, while in two studies, an active treatment (midazolam or electroconvulsive therapy) was used.

Researchers found a rapid improvement in depressive symptoms within the first 24 hours, continuing through the seventh day. This improvement was significantly greater compared to placebo or other treatments. Thirty-three out of 126 patients showed remission by the seventh day, indicating complete absence of depressive symptoms. All studies assessed this using one or more of the following questionnaires: Hamilton Depression Rating Scale (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS), and Clinical Global Impression (CGI) scale. These questionnaires are completed by clinical staff and assess present symptoms, severity, and improvement since the start of treatment.

These results are promising for the future treatment of this disorder, offering a new alternative for those who suffer and have not found relief. It is important to emphasize that, like any other depression treatment, ketamine does not work for everyone, and for those it does help, it often requires psychotherapeutic support and follow-up. Research in this field continues to progress, aiming to refine the best methods for delivering this medication. Long-term effects also require further investigation, a topic we will explore in future posts and something that Clínica Synaptica hopes to contribute valuable new insights to.

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