Depression is among the most disabling conditions in our society. According to the World Health Organization, depression is the leading cause of ill health and disability worldwide. In America, 12.5% of individuals over the age of 12 have filled an antidepressant prescription. Yet, the effectiveness of these medications are still lacking. Many patients don’t respond to antidepressant medications, and it can take months for the medicine to kick in. Unfortunately, many patients will regain their depression after being on medications long term.
Over 50 years ago, the hypothesis that low concentrations of serotonin in the central nervous caused depression was proposed. This appealed to many doctors & scientists, because we finally had a potential biological mechanism to explain depression. Accordingly, many antidepressants were developed to increase serotonin to help relieve depression. Although, it can work for some patients many patients do not respond or have significant side effects.
So what is a person to do if they have treatment-resistant depression?
One cutting-edge option is targeting a completely different neurotransmitter - GLUTAMATE. Glutamate is an excitatory neurotransmitter and the most abundant neurotransmitter in the brain and central nervous system. Ketamine works on the glutamate system by blocking it’s activity at the N-Methyl-D-Aspartate (NMDA) receptor.
Ketamine raises brain derived neurotrophic factor (BDNF) levels, thereby enhancing connections between neurons and increasing neuroplasticity. It’s literally changing the brain. In animal studies, the cascade of effects from ketamine created a rapid proliferation of dendritic spines that was associated with less depression. In a functional MRI brain study of humans, ketamine seemed to restore the functional connectivity in those patients with depression.
Interestingly, ketamine is known to affect other receptors beyond the NMDA receptor, and have anti-inflammatory as well as epigenetic effects. Also, the breakdown products of ketamine, like (S)-norketamine and (2R, 6R)-hydroxynorketamine, may also play a role in helping with depression.
Even though we have some understanding of how ketamine works, we still don’t fully comprehend how ketamine is working exactly in patients with depression.
As we continue to learn more about ketamine and depression, more questions and unknowns will surely develop.
Therefore, it’s critical to expand our understanding of depression beyond the simple serotonin and even glutamate neurotransmitters. The human body, brain, and consciousness is one of the most complex systems we have ever encountered. Although, we may never fully understand the intricacy of it all, we can still take action.
We can be pragmatic and responsibly use ketamine for carefully selected patients. In addition to ketamine infusions, we can encourage psychotherapy, exercise, meditation, prayer, positive community, a good night’s rest, and a healthy diet to help people with depression.
At Reset Ketamine, we utilize the bio-psycho-social-spiritual model that encompasses a whole person approach to health. We believe health is not merely the absence of illness, but a state of physical, social, mental, and spiritual well-being. We believe ketamine can be the catalyst to create paradigm shifts to help patients live a full life.
Krystal, J. H., Abdallah, C. G., Sanacora, G., Charney, D. S., & Duman, R. S. (2019). Ketamine: A Paradigm Shift for Depression Research and Treatment. Neuron, 101(5), 774-778. doi:10.1016/j.neuron.2019.02.005