New research from Washington University School of Medicine (led by pharmacologist Tao Che) found that ketamine directly binds to and activates opioid receptors, not just the NMDA receptors it’s known for. Using cryo-electron microscopy, the team saw ketamine sitting in the same binding pocket that conventional opioids use. In mouse studies, blocking opioid receptors wiped out ketamine’s pain relieving effect, showing that opioid activity plays a real role. Researchers caution ketamine’s effects still involve multiple systems, and it’s unclear if this explains its antidepressant benefits.
If you have tried medication after medication and still don’t feel like yourself, you are not alone, and you are not out of options. For people living with treatment-resistant depression and/or anxiety, physician-supervised ketamine therapy is an alternative that can provide rapid symptom relief when standard treatments fail. At the Charleston Ketamine Center, 80% of patients with depression and 90% suffering from anxiety experience a positive response.
What Is Treatment-Resistant Depression?
Doctors generally define treatment-resistant depression as depression that has not improved after at least two different antidepressants, each taken at a full dose for six to eight weeks. Treatment-resistant anxiety follows a similar pattern: medication and therapy help around the edges but never quite resolve the underlying distress.
If this sounds like your experience, it does not mean you are untreatable. It likely means the next step needs to work through a different pathway in the brain than the one standard antidepressants target.
Depression and Anxiety: Similar Struggles, Different Conditions
Depression and anxiety show up together often, but they are not the same condition, and they don’t always respond to the same treatment. One way to look at depression is that it is depressed brain function. It usually includes altered mood such as sadness or irritability, but not always. Energy levels, motivation, ability to concentrate, decision making, and sleep function can all be affected. In addition, depression can also cause the loss of enjoyment of activities that normally give one pleasure, as well as feelings of guilt and hopelessness.
Anxiety, on the other hand, according to the American Psychological Association is: “An emotion characterized by apprehension and somatic symptoms of tension in which an individual anticipates impending danger, catastrophe, or misfortune. The body often mobilizes itself to meet the perceived threat: Muscles become tense, breathing is faster, and the heart beats more rapidly. Anxiety is considered a future-oriented, long-acting response broadly focused on a diffuse threat, whereas fear is an appropriate, present-oriented, and short-lived response to a clearly identifiable and specific threat.”
Some people with anxiety also experience panic attacks which occur when the body’s fight or flight system gets activated. It is a normal response to life threatening situations but in the case of panic attacks there is no perceived threat.
According to the Anxiety and Depression Association of America, nearly half of people diagnosed with depression also meet the criteria for an anxiety disorder. The two conditions can also feed each other. Ongoing anxiety can wear a person down into depression, and depression can bring on new worry about falling behind at work, in relationships, or at home.
How Ketamine Works Differently: The NMDA Connection
Most antidepressants work on the brain chemical messengers, serotonin and or norepinepherine. Response time which can take four to six weeks to build up an effect. Ketamine works on a different target: primarily the NMDA receptor, a docking site on brain cells that helps regulate glutamate, one the brain’s most common signaling chemical.
By temporarily blocking this receptor, ketamine appears to increase the number of synapses/connections in certain brain regions. Research suggests this is part of the reason why ketamine and esketamine are able to bring relief within hours or days, rather than weeks. However, at least in the near-term, the relief is not permanent. After an initial series of treatments, most patients need to receive booster treatments for five to six months. After this, the need to get boosters varies significantly from patient to patient.
Taking the Next Step
You do not have to keep waiting for an antidepressant to finally work. If standard treatment has not gotten you the relief you need, physician-supervised intravenous ketamine and SPRAVATO are available at Charleston Ketamine Center. Reach out to schedule a free consultation and find out whether this approach is a good fit for you.
