Research Update: Intravenous Ketamine for Adolescent Treatment Resistant Depression

Major depressive disorder affects 4%-8% of adolescents at any given time. Approximately 1 in 5 children will experience depression by the end of adolescence. Although therapy and medications are effective for many, a substantial portion of people will not experience a sustained remission with these traditional treatments. Approximately 40% of patients will remain depressed despite taking an SSRI medication, and 20% remain depressed with SSRI and therapy.

 

Researchers at the Yale school of medicine recently published their work on the effectiveness of intravenous ketamine for the treatment of adolescent depression.

 

The article, entitled “Efficacy of Intravenous Ketamine in Adolescent Treatment-Resistant Depression: A Randomized Midazolam Controlled Trial,” was published in the American Journal of Psychiatry, April 2021 issue.

 

Individuals enrolled in the study had a primary diagnosis of Major Depressive Disorder as per the DSM-5 criteria. The age range was 13-17 years. All participants must have had at least 1 previous trial of standard antidepressant medication for 8 weeks. All participants remained on their current medications during the trial.

 

The patients were divided into 2 groups. Everyone received either intravenous ketamine or midazolam on Day 1 and then the alternate medication on Day 14. All patients received EKG, blood pressure, and pulse oximetry monitoring during the infusions. A physician was present during all infusions to monitor the patients.

 

77% of the patients receiving ketamine obtained a response in the first 3 days, defined as a 50% reduction in depression symptoms measured on the Montgomery-Asberg Depression Rating Scale (MADRS). 35% of the patients receiving midazolam obtained a similar response.

 

At 24 hours, ketamine significantly reduced depression symptoms on the MADRS score compared to midazolam.

 

Among the ketamine responders, the improvements in the MADRS score lasted 14 days, which was the end of the scoring period in the study.

 

One patient improved significantly after the first ketamine infusion and dropped out of the study to receive further ketamine treatment in the community.

 

Side-effects of the ketamine included dissociative symptoms, elevation in heart rate and blood pressure. All of the side effects were transient and none required any treatment. No serious adverse effects were observed.

 

The authors point out that while ketamine has an excellent safety record in pediatric patients, more research is needed to assess the risk of repeated ketamine dosing.

 

The mechanism behind ketamine’s rapid antidepressant effects is not fully understood. Current research suggests that ketamine blocks the NMDA receptor of certain GABA interneurons in the prefrontal cortex of the brain. The prefrontal cortex is believed to play a critical role in depression. GABA is the major inhibitory transmitter in the human brain. By blocking the NMDA receptor, causes an increase in glutamate production in downstream nerve cells. This in turn causes activation of AMPA receptors, an increase in Brain-Derived Neurotrophic Factor, and mTORC1 activation. Ultimately, these steps lead to increased nerve cell growth and connectivity. Depression causes atrophy and decreased connectivity in certain brain regions, and ketamine seems to reverse these effects.

 

If you or your loved one is struggling with depression and traditional therapies have failed, please call us at MD Infusions for a free consultation to see if Ketamine IV Infusion Therapy is right for you.