Depression is not a one-size-fits-all disorder. While many people find relief with traditional antidepressant treatments, approximately 30% of patients diagnosed with major depressive disorder (MDD) fall into the category of treatment-resistant Depression (TRD). For these individuals, achieving remission can feel nearly impossible.
This blog article delves into a groundbreaking multi-site observational study, recently published in Psychiatry Research, that explores the effectiveness and tolerability of two therapies for TRD: intravenous (IV) ketamine and intranasal (IN) esketamine. These therapies offer hope to those for whom standard antidepressants have failed.
Why is Treatment-Resistant Depression So Challenging?
TRD is diagnosed when a patient does not respond to at least two adequate trials of antidepressant medications from different classes. For these patients, the traditional approach—targeting serotonin or norepinephrine—may not address the underlying neurobiology of their Depression. TRD is associated with:
- Higher rates of suicide: Up to 15% of individuals with untreated TRD attempt suicide.
- Increased healthcare utilization: Due to frequent hospitalizations and long-term disability.
- Impaired quality of life: Affecting relationships, employment, and overall functionality.
Traditional antidepressants often take at least 4-6 weeks to produce noticeable effects, leaving patients vulnerable during that critical waiting period. This is where ketamine-based therapies, which act much more quickly, can make a life-saving difference.
Overview of the Study
The study aimed to assess real-world outcomes for TRD patients receiving either IV ketamine or IN esketamine (Spravato). By analyzing data across multiple clinical sites, the researchers sought to answer three key questions:
- How effective are IV ketamine and IN esketamine in reducing depressive symptoms?
- Do these therapies significantly reduce suicidal ideation?
- Are these treatments safe and well-tolerated by patients?
Patient Demographics
The study included 53 patients diagnosed with TRD. These participants were divided into two groups:
- IV Ketamine Group
- Number: 26 patients
- Gender: 69.23% female
- Age: Average of 52.81 years
- IN Esketamine Group
- Number: 27 patients
- Gender: 51.85% female
- Age: Average of 43.93 years
Treatment Protocols
- IV Ketamine: Administered through infusion at specialized clinical centers.
- IN Esketamine: Delivered as a nasal spray, combined with a supervised clinical session to ensure patient safety.
Assessment Tools
The researchers employed several validated tools to measure outcomes:
- Montgomery and Åsberg Depression Rating Scale (MADRS): To track changes in Depression severity.
- MADRS Item 10: Specifically used to evaluate suicidal ideation.
- Clinician-Administered Dissociative Symptom Scale (CADSS-6): To monitor dissociative side effects and tolerability.
Key Findings
- Rapid and Significant Reduction in Depressive Symptoms
Patients in both groups showed substantial improvements in their MADRS scores, indicating that both IV ketamine and IN esketamine effectively reduced depressive symptoms. This reduction was observed relatively quickly, aligning with the rapid-acting nature of ketamine-based treatments.
- Reduction in Suicidal Ideation
One of the most significant findings was the dramatic decrease in suicidal thoughts reported by patients. Suicidal ideation, often resistant to traditional treatments, was significantly alleviated in both groups. This underscores the potential life-saving role of ketamine-based therapies for high-risk individuals.
- Comparable and Favorable Tolerability
- Side Effects: Both treatments were well-tolerated, with mild side effects such as transient dizziness, nausea, and dissociation.
- No Discontinuations: Importantly, no patients discontinued treatment due to adverse effects.
- Dissociation Scores: CADSS-6 assessments revealed no significant differences in dissociative symptoms between the two groups.
These findings suggest that both IV ketamine and IN esketamine are safe options when administered under medical supervision.
How Do These Therapies Work?
Traditional antidepressants target neurotransmitters like serotonin, norepinephrine, or dopamine. In contrast, ketamine-based therapies work through the glutamate system, which plays a key role in synaptic plasticity and mood regulation.
- Ketamine: Acts as an NMDA receptor antagonist, promoting the release of glutamate and stimulating the growth of new neural connections. This “reset” effect helps the brain recover from the patterns associated with chronic Depression.
- Esketamine: A derivative of ketamine, esketamine is more potent and specifically targets Depression-related pathways while reducing the risk of some side effects associated with ketamine.
What Sets Ketamine and Esketamine Apart from Traditional Antidepressants?
- Speed: Effects can be seen within hours or days compared to the weeks required for SSRIs or SNRIs.
- Unique Mechanism: By targeting the glutamate system, ketamine therapies provide relief for patients who do not respond to serotonin-based treatments.
- Impact on Suicidal Thoughts: Traditional antidepressants often take weeks to affect suicidal ideation, whereas ketamine therapies can reduce such thoughts almost immediately.
Implications for Mental Health Treatment
This study reinforces the growing role of ketamine-based therapies in addressing treatment-resistant Depression. These therapies could:
- Reduce hospitalization rates By rapidly stabilizing patients in crisis.
- Improve quality of life: Offering relief to those who have struggled for years with inadequate treatments.
- Expand access to care: IN esketamine, which we offer at Mid City TMS, in particular, provides a more accessible option due to its non-invasive administration and being usually covered by insurance. IV Ketamine can be expensive, with no eligibility for insurance coverage when used for Depression.
A Lifeline for Those in Crisis
The findings of this study are a testament to the potential of ketamine-based therapies to transform the treatment landscape for Depression. By offering rapid relief and targeting previously untouchable symptoms, such as suicidal ideation, these therapies represent a paradigm shift in mental health care.
If you or someone you know is struggling with treatment-resistant Depression, schedule a consultation with us today to discuss whether IV ketamine or IN esketamine could be an appropriate option.
Key Takeaway
Ketamine and esketamine are not just treatments—they are lifelines for individuals battling the darkest forms of Depression. As research continues, they are becoming a cornerstone of modern psychiatric care, offering hope where it was once lost.
Sources:
- Johns Hopkins Medicine. (n.d.). Treatment-resistant depression. Retrieved from https://www.hopkinsmedicine.org/health/conditions-and-diseases/mood-disorders/treatment-resistant-depression
- ScienceDirect. (2024).IN Esketamine and IV Ketamine: Results of a multi-site observational study assessing the effectiveness and tolerability of two novel therapies for treatment-resistant depression Psychiatry Research. Retrieved from https://www.sciencedirect.com/science/article/pii/S0165178124004104