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Ketamine for Treatment Resistant Depression

Here at the Cincinnati Anxiety Center, we strive to provide innovative, evidence based treatments. We are excited to announce that we will soon be offering esketamine intranasal spray (SPRAVATO™) and intravenous (IV) ketamine infusions to help our patients who have Treatment Resistant Depression (TRD) or depression with suicidal ideation. Patients with TRD have not achieved remission despite trying other treatment modalities such as oral medications, psychotherapy, electroconvulsive therapy (ECT), or transcranial magnetic stimulation (TMS).

What is ketamine and how does it work ?

Ketamine was approved by the Food and Drug Administration (FDA) for use as an anesthetic agent in 1970. It began being studied for use in depression in 2000. Research on ketamine as an antidepressant is ongoing and we continue to learn more about why it works, how it works, and how we can safely and efficiently maximize its benefits.

At one point, the primary cause of depression was thought to be a lack of certain neurotransmitters, or chemicals, in the brain. One reason for this belief is that many people experience reduced depression when given medications that increase neurotransmitters in the brain, such as selective serotonin reuptake inhibitors (SSRIs). While an imbalance of neurotransmitters plays a role in depression, we now understand that it is not that simple. More recent research has examined changes in connections between cells in the brain and changes in the structure of the brain in people who are depressed. These changes may explain why some people with depression benefit from medications that increase certain neurotransmitters in the brain while others do not.

Newer treatment modalities, including ketamine, aim to target these changes in connections and structure. Ketamine improves depression in part by blocking N-methyl-d-aspartate (NMDA) glutamate receptors, resulting in increased glutamate levels in the brain. The increase in glutamate is thought to activate AMPA receptors, which leads to a chain reaction that increases brain-derived neurotrophic factor (BDNF) in the brain. BDNF is thought to be decreased in people with depression. BDNF plays a large role in the growth, survival, and connections between neurons. When it is decreased, it can lead to both functional and structural changes in the brain. When BDNF increases, neurons are able to form and develop new connections in areas of the brain including the prefrontal cortex and hippocampus which help regulate mood, behavior, and cognition. The end result is that ketamine increases the brain's plasticity, or ability to change.

How is ketamine administered to treat depression?

Ketamine was initially used in the form of IV infusions for depression. Studies have shown that a single infusion of ketamine can improve depression and reduce suicidal thoughts within hours and these effects can last for up to a week. There is a cumulative effect with repeated ketamine infusions, so it is recommended that someone have 4-6 ketamine infusions over the course of two weeks. Intravenous ketamine is considered an off label treatment for depression

In 2018, a form of ketamine, esketamine intranasal spray (SPRAVATO™), was approved by the FDA for use in conjunction with an oral antidepressant for people with TRD or depression with suicidal thoughts or actions. Esketamine intranasal spray (SPRAVATO™) is self-administered under the supervision of a healthcare provider. Treatment with esketamine involves a twice weekly induction period for 4 weeks followed by a once weekly maintenance phase for 4 weeks. After that, patients can continue to receive esketamine treatment every 1-2 weeks as needed to maintain their improvement in symptoms.

Which type of ketamine treatment is right for me?

Your healthcare provider can help you decide which type of ketamine treatment will be the best for you. However, there are a few things to consider:

Ketamine infusions:

  • Off label use means insurance will not cover treatments

    • Since it is not billed through insurance, you can receive intravenous ketamine infusions even if your insurance determines that you do not qualify for coverage of esketamine intranasal spray (SPRAVATO™).

  • Time for each treatment is approximately 1.5 hours (40 minute infusion followed by observation)

  • No requirement to be on an oral antidepressant during treatment

  • Requires IV access

  • Used as an acute treatment, generally over the course of 2 weeks

  • No eating for 6 hours prior to arrival (may have clear liquids up to 2 hours prior to arrival).

  • No driving for 24 hours after treatment

Esketamine intranasal spray (SPRAVATO™)

  • May be covered by insurance since it is FDA approved

    • Insurance may have specific requirements that must be met as well as exclusion criteria for coverage

  • Time for each treatment is approximately 2.5 hours (administration of intranasal spray followed by 2 hours of observation).

  • Must stay on oral antidepressant during treatment with esketamine intranasal spray (SPRAVATO™)

  • Less invasive

  • Evidence supports use for long term maintenance treatments

  • No eating for 2 hours prior to arrival (may have clear liquids for up to 30 minutes prior to arrival).

  • No driving until you have had a restful night sleep following treatment

What should I expect during ketamine treatment?

When you arrive at the office, you will be led to a private room that was designed specifically for ketamine treatments. The room was made to be relaxing, with limited stimulation to provide a comfortable experience. You will be monitored continuously by a member of our clinical team. Most patients report feeling sleepy during their treatment. You may also feel detached from your thoughts or feelings (dissociation) or experience changes in how you experience things around you. These symptoms do not last for long and will resolve prior to you leaving the office. Some people experience nausea and vomiting during ketamine treatments. For this reason, we ask that patients refrain from eating and drinking prior to their appointment. You will be unable to drive after your treatment and must have a responsible adult to provide transportation.

What are the common side effects of ketamine treatment?

In addition to the above, other side effects that may occur during your treatment include increases in blood pressure, dizziness, vertigo, feeling loopy or drunk, feeling euphoric, or feeling as if you are in a dream-like state.

Who should not receive ketamine treatment?

Prior to treatment, you will be assessed for medical conditions and medications which might put you at risk for adverse effects if you receive ketamine treatment. In general, you should not receive ketamine treatment if you have any of the following: uncontrolled hypertension (high blood pressure), aneurysmal vascular disease, intracerebral hemorrhage (brain bleed); current or a history of psychosis or a psychotic disorder (such as schizophrenia), current or recent history of substance abuse, or if you are pregnant or breastfeeding.

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