How Can Ketamine-Based Medications Treat Depression?

Depression is a serious mood disorder that can cause a range of physical and emotional problems. It can make it difficult to function at work or school, and can even lead to thoughts of suicide.

Traditional oral antidepressants can be life-changing, but they don’t work for everyone, and they can take some time to provide relief for depression — sometimes weeks or months. In recent years, many patients and providers are choosing to treat depression with an alternative approach: ketamine-based treatments, which include IV ketamine, and Spravato (esketamine). So how does ketamine treat depression?

Ketamine is a medication that has been used for decades as a safe anesthetic. It is approved for use in children, as well as higher-risk scenarios like battlefield injuries. Although ketamine has been used safely as an FDA-approved anesthetic since the 1960s, the emergence of ketamine as a highly effective and rapid-acting treatment for a wide range of mood disorders and neuropathic pain has been hailed as arguably the most significant development in psychiatry during the past few decades.

What Is Major Depressive Disorder?

Major depression is a common mood disorder that can cause a range of physical and emotional problems. It is more than just feeling “down” or “sad” for a few days — depression is a serious condition that can last for weeks, months, or even years.

Mild, moderate, and severe depression is caused by a combination of genetic, biological, and environmental factors. Depression is not caused by a single event or experience — that said, trauma and environmental factors can contribute to depression’s development or prolong a depressive episode. And while depression does not discriminate and can happen to anyone, certain groups of people are at higher risk. These include people who have a family history of depression, those who have experienced trauma or abuse, women who are pregnant or postpartum, and those who have another co-occuring mental health condition.

Related: Navigating Perinatal Depression

What is treatment-resistant depression (TRD)?

Treatment-resistant depression (TRD) is a form of depression that occurs in individuals who have tried multiple treatments options and have not achieved adequate symptom relief. For these individuals, traditional therapy for depression or antidepressants do not work as well, or some may experience relief followed by a depression relapse.

Here are some symptoms of TRD:

• Inability to tolerate antidepressants’ side effects, regardless of dose.
• Depression symptoms do not improve after taking antidepressants, even after adjusting dosages and trying two or more medications.
• Worsening of depression symptoms.
• Symptoms of severe depression, including suicidal thoughts or ideation, mood swings, and self-isolation behaviors.

What Is Ketamine?

Ketamine is an anesthetic medication that has shown promise in treating depression and anxiety. Esketamine is a ketamine derivative available as an FDA-approved nasal spray for TRD. Other forms of ketamine can be used off-label to treat various mood and anxiety disorders, delivered as IV infusions, injections, or lozenges.

At doses lower than are used for anesthesia, ketamine can rapidly and effectively alleviate depression symptoms. A therapeutic dose of ketamine to treat depression can cause dissociation, which is a feeling of detachment from one’s self and surroundings. Additionally, ketamine is a Schedule III controlled substance in the United States, meaning that it has medical use and a moderate to low potential for physical and psychological dependence or misuse.

How does ketamine work?

Ketamine works by blocking N-methyl-D-aspartate (NMDA) receptors in the brain, which are involved in pain perception, memory, and learning. By blocking these receptors, ketamine can cause dissociation and analgesia — otherwise known as pain relief. In the context of depression treatment, it’s thought to work as an antidepressant by increasing levels of glutamate — a neurotransmitter that is involved in mood, emotion, and the formation of new memories.

Some research suggests that ketamine may also increase levels of brain-derived neurotrophic factor (BDNF), which is a protein that helps to support the health of neurons. Low levels of BDNF have been linked to depression and associated symptoms.

Related: What Postpartum Depression Treatment Is the Safest?

How Does Ketamine Treat Depression?

One of the contributing factors of TRD is thought to be the result of fewer serotonin receptors in the brain. If there are not enough receptors, SSRIs will be largely ineffective. Studies have found that ketamine can stimulate receptor growth and improve the efficacy of SSRIs for treating depression.

For those that have been battling depression all their lives, the use of low-dose ketamine for their depression therapy brings hope that they can start to experience improvements. The new receptor growth also improves neuroplasticity — the brain’s ability to heal itself — which can be effective in helping to improve depression symptoms. Another benefit from low-dose ketamine therapy is its ability to increase the release and absorption of dopamine — another “feel good” chemical that can help counteract depressive symptoms. 

Most people who use ketamine to treat their depression report feeling significant improvements within the first few treatments. Additionally, many even report feeling general relief and an improvement in mood as early as the completion of the first treatment session. 

Can ketamine for depression replace SSRIs?

Ketamine for depression is typically used for treatment-resistant depression — when standard antidepressants like selective serotonin reuptake inhibitors (SSRIs) haven’t been effective. It’s usually given alongside existing antidepressant medications as an adjunct treatment, though it can also be started at the same time as SSRIs or, in some cases, used as a standalone treatment.

Related: SSRI Weight Gain

What Does the Research Say About Ketamine Treatment?

Research into the full pharmacological action of ketamine is revealing just how complex the response to this drug is, with the most research having been conducted on IV ketamine infusions. Here’s a look at what multiple studies have indicated about ketamine and its antidepressant effects:

• Research in animal subjects have observed increased synaptic connections and the growth of neurons. This neuronal growth and increased neuronal interconnectivity improve mood and cognition and allow patients to disengage from their routine thought patterns, heal unhealthy neural pathways, and better achieve mental clarity.¹
• Clinical trials found that ketamine was more effective than a placebo in reducing depression symptoms within 24 hours. The effects of ketamine were also found to last longer than those of the placebo when working with TRD.²
• A 2019 study on ketamine as a treatment for depression found that it was effective in reducing depression symptoms within one hour after treatment. Ketamine was also shown to work significantly faster than traditional antidepressant medications, which typically take 4 to 12 weeks to take effect.³

While ketamine is generally well-tolerated, you may experience some side effects, including dizziness, nausea, vomiting, blurred vision, and increased blood pressure. Ketamine can also cause dissociation, which can be a pleasant experience for some people but may be uncomfortable or even scary for others. This dissociative effect is one reason why ketamine is sometimes abused, but when used as directed by a doctor, the risk of misuse and addiction is considered to be low.

If you are considering ketamine as a treatment for depression, it is important to speak with your doctor about the risks and benefits.

Related: Holistic Treatments for Depression

Types of Ketamine Medications for Treatment-Resistant Depression

Ketamine is a medication that has been used for decades as an anesthetic. Since the early 2000s, ketamine therapy has shown promise as a treatment for TRD, especially in people who have not responded to other medications.

There are two main types of low-dose ketamine therapies that are being studied for the treatment of depression, which include:

• Esketamine or Spravato: Esketamine is a nasal spray that contains the active ingredient S-ketamine. Spravato is approved by the FDA for the treatment of depression in adults who have not responded to other medications.
• IV ketamine: Sometimes called racemic ketamine, IV ketamine given as an infusion into the bloodstream and is a mixture of two mirror-image molecules: “R” and “S” ketamine. Racemic ketamine is FDA-approved as an anesthetic and used off-label to treat mood and chronic pain disorders.

Both IV ketamine and Spravato are thought to work by increasing levels of the neurotransmitter glutamate, which is involved in the formation of new memories and plays an important role in the health of neurons. It’s important to note that there is currently no cure for depression — it’s a chronic illness that can enter remission and never reoccur, or conversely, you may experience a relapse. Although not considered a cure, ketamine is a powerful alternative treatment for depression that can help patients achieve remission.

Related: Depression and Memory Loss

What To Expect During Treatment

The first part of the ketamine infusion process is a consultation, which is a thorough review of your medical history, depression symptoms, and previous treatments to help inform the course of your treatment, such as the dosage and length of treatment. Generally speaking, there are a series of treatments over several weeks — though individualized plans will vary.

Initially, three to four treatments are given in the first week. The second week, two to three treatments are given, and in the third week, one or two treatments are given. Then, the patient moves to one treatment given bimonthly or monthly. Sessions last for about 40 minutes to an hour, and patients are monitored by qualified specialists to ensure safety and comfort. Some effects, like dissociative feelings or wooziness, will dissipate within 20 minutes after the drip has been stopped, but it’s normal to still feel mildly sleepy after receiving treatment. 

Many people who have never used ketamine to treat their depression symptoms may be nervous about what to expect during treatment. Since ketamine is administered intravenously in low doses, there are very few side effects. However, you may experience several side effects, including:

• Wooziness or dizziness.
• Feeling “high” or slightly euphoric.
• Dissociation or feeling like you are leaving your body.
• Sleepiness.
• Visual and other sensory distortions.

Related: Is Spravato Addictive?

How Neuro Wellness Spa Can Treat Those With Depression in California

Ketamine-based medications show promise as a treatment for depression, especially in people who have not responded to other medications. Ketamine is thought to work by increasing levels of the neurotransmitter glutamate, and it’s overall well-tolerated and with side effects that are usually mild.

If you would like to learn more about ketamine based medications, or you need a referral to a trusted provider, schedule an appointment today. Neuro Wellness Spa also offers a range of effective mental health treatments known to treat depression successfully, including talk therapy, psychiatric medication management, and TMS therapy. Schedule a consultation today.

References

1. Wu, H., Savalia, N. K., & Kwan, A. C. (2021). Ketamine for a boost of neural plasticity: How, but also when? Biological Psychiatry, 89(11), 1030–1032. https://doi.org/10.1016/j.biopsych.2021.03.014

2. Yavi, M., Lee, H., Henter, I. D., Park, L. T., & Zarate, C. A. (2022). Ketamine treatment for depression: a review. Discover Mental Health, 2(1). https://doi.org/10.1007/s44192-022-00012-3

3. Mandal, S., Sinha, V., & Goyal, N. (2019). Efficacy of ketamine therapy in the treatment of depression. Indian Journal of Psychiatry, 61(5), 480. https://doi.org/10.4103/psychiatry.indianjpsychiatry_484_18