balloons overcoming depression concept

Ketamine Infusion vs. Nasal Spray in Treating Depression

Depression is one of humankind’s oldest brain disorders. Major depressive disorder (MDD) is the most common psychiatric disorder in the world, affecting approximately 17% of the population in developed areas at any given time. The World Health Organization ranks depression third among the leading causes of global disease burden.

Ketamine infusion therapy has proven to be rapidly effective in remission of depressive symptoms of MDD, TDD, and BD, sometimes providing temporary relief within hours of the first infusion. It is remarkably effective in aborting suicidal ideations with a single IV infusion. Ketamine is 70% effective in TDD. Although the response to a single infusion is short-lived (a matter of days), repeat administration over a short period of time (typically two weeks) can extend the length of remission, with some patients enjoying improvement for as long as six months. Administering additional “booster” treatments can continually extend the length of remission of symptoms. Ketamine infusions are safe, rapid, and effective. Consequently, ketamine infusion therapy is revolutionizing the treatment of depressive disorders.

Ketamine IV therapy is considered “off-label,” while in 2019, the FDA approved the use of Ketamine for depression via a nasal spray. It is unclear why the FDA approved the nasal spray version. However, research by Bahji and colleagues—from Queen’s University in Canada and the National Institute of Mental Health in the US—suggests racemic Ketamine might be more effective than esketamine (nasal spray). Published in the January 2021 issue of the Journal of Affective Disorders, the article reports the results of the “first systematic review and meta-analysis that has compared the performance of intravenous ketamine to intranasal esketamine for the treatment of unipolar and bipolar depression.”

Sources of Data

The authors sourced electronic databases and found randomized controlled trials using intranasal esketamine or intravenous Ketamine to treat depression. They included studies where the drug was used alone and studies where it was used as an augmenting agent—meaning in addition to another antidepressant medication, such as a selective serotonin reuptake inhibitor (SSRI), like Prozac or Zoloft.

The final list of trials to be included in the meta-analysis and systematic review consisted of 24 randomized controlled trials—1877 participants; 61% females; average age ranging from 36 to 70 years; 98% with major depression and 2% with bipolar depression.

In most of the investigations included in the meta-analysis, the drug had been used as an augmenting agent. In three-quarters of the trials, participants had depressive symptoms that had not responded to previous treatments. In other words, they had treatment-resistant depression. However, depending on the investigation, treatment-resistant depression was defined differently. The most common definition of treatment-resistant depression (used in over 60% of trials) was a lack of response to two or more antidepressants.

Results: IV vs. Nasal Spray 

The results showed that, compared with esketamine, racemic ketamine (IV ketamine) produced a greater response (rate ratio = 3.0 vs. 1.4), remission rate (ratio rate= 3.7 vs. 1.5), and lower dropouts (rate ratio = 0.8 vs. = 1.4).

Thus, compared to “intranasal esketamine, intravenous racemic ketamine demonstrated more significant overall response and remission rates, as well as lower drop-outs due to adverse events” (p. 548).

Their findings also showed a “clear and consistent antidepressive effect of ketamine vs. esketamine treatment, relative to a variety of control conditions, beginning within hours of administration, and lasting up to 7 days after a single dose” (p. 549).

If so, why has the FDA approved only intranasal esketamine (Spravato) for the treatment of depression even though the present review showed a lower drop-out rate due to adverse events in patients treated with IV ketamine compared with Spravato? A likely explanation is that the lack of FDA approval is related to a lack of quality research on the long-term effects (e.g., safety, efficacy) of ketamine infusion.

So How Does It Work?

Ketamine is a dissociative anesthetic with various mechanisms of action and binds to multiple receptors in the brain. Consequently, it is difficult to pin down the precise mode of action, and it appears that there are numerous mechanisms through which Ketamine exerts its action on the brain.

Research suggests that one of Ketamine’s major actions is as an N-methyl-D-aspartate (NMDA) receptor antagonist, which blocks activation of the NMDA receptor. This action leads to increased release of glutamate, which is involved in neuronal plasticity and synaptic growth and repair. These effects through complex pathways lead to the release of Brain-derived neurotrophic factor (BDNF), a substance responsible for maintaining healthy neurons and their connections, known as synapses.

Increased BDNF has been shown to repair, and regrowth damaged synapses and their neuronal connections caused by chronic stress in animal models. Likewise, in humans, Ketamine is thought to lead to the creation of new neuronal circuits and/or repair of the healthy neuronal connections that existed in the brain before the patient suffered from depression, PTSD, OCD, and/or chronic anxiety.

brain view after ketamine treatment method

Ketamine Treatment Methods: In-Clinic Ketamine Infusions vs. At Home Ketamine Tablet

Ketamine is a dissociative anesthetic with various mechanisms of action and binds to multiple receptors in the brain. There are various ketamine treatment methods being used, let’s look at the two most popular.

Regarding depression, posttraumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), and chronic anxiety, these mental health disorders are all thought to be due to the destructive effect of continual stress on the brain, leading to neuronal damage and the creation of maladaptive neural activity and abnormal thought patterns indicative of these disorders.

How Ketamine Works

Research suggests that Ketamine can block activation of the NMDA receptor, leading to neuronal plasticity and synaptic growth and repair. These effects lead to the maintenance of healthy neurons and their connections, known as synapses. Ketamine is thought to lead to new neuronal circuits and repair of the healthy neuronal connections that existed in the brain before the patient suffered from depression, PTSD, OCD, or chronic anxiety.

Two Popular Ketamine Treatment Methods

It is easy to see why Ketamine is being used to treat these conditions with research like this. Currently, there are two popular ketamine treatment methods used to administer the drug. The first is a reasonably new method that involves the patient taking a dose of Ketamine at home after filling out some online forms and agreeing to follow some specific guidelines given by a virtual doctor. The Ketamine dose is in the form of a tablet dissolved under the tongue. In addition, the patient must agree to have a person present (a friend or loved one) to ensure their safety.

The other, more traditional method of treatment is Ketamine Infusion Therapy. Here the treatment is administered via IV in a medical setting with the guidance of doctors or nurses. The treatment takes about 40 minutes on average, followed by 45 minutes of relaxation, giving the medication time to wear off.

Each treatment experience may feel different, depending on your mood and what’s on your mind that day. Experienced meditators may find they can achieve a prolonged sense of inner stillness and peace that they have only briefly glimpsed during previous meditation sessions. Although anxiety reactions can occur, these are usually short-lived and become less frequent with repeated treatments.

Tranquility Ketamine Clinic Treatment Method

At Tranquility Ketamine Clinic, medication is given intravenously, using National Institute of Mental Health dosing protocols. These protocols vary depending upon whether you are being treated for mental health or chronic pain syndromes. However, we understand that the NIH dosing protocol was decided upon arbitrarily. Depending on the individual, both up and down dosage adjustments may be necessary for maximum effect and comfort. If the patient experiences more severe or prolonged anxiety reactions in our setting, they will be treated by administering an anxiolytic medication as needed. Nausea may rarely occur and can be treated with anti-nausea medications. We believe our medically trained staff gives an added layer of care, allowing us to address any discomfort or reactions immediately.

As with any treatment, it is essential to evaluate the options available before deciding which treatment method is suitable for you. If you or someone you know is suffering from depression, posttraumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), or chronic anxiety and would like to learn more about Ketamine Infusion therapy, click here or call 505-639-4973