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. However, they don’t work for everyone and they can take weeks or even months to reach their full efficacy. For over 20 years, many patients and providers are now choosing to treat depression with a different class with ketamine-based treatments including IV ketamine, and Spravato or 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 discovery 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 – although, trauma and environmental factors can contribute to depression’s development and/or prolong the 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 mental health condition.

What is Ketamine?

Ketamine is an FDA-approved anesthetic that is also used to treat mood, anxiety, and pain. Ketamine therapy may be provided as an infusion, a nasal spray, a troche or lozenge or as an injection.

At lower doses 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.

Ketamine is a Schedule III controlled substance in the United States. This means that it has medical use and a moderate to low potential for physical and psychological dependence or abuse.

How Does Ketamine Work?

Ketamine works by blocking NMDA receptors in the brain. NMDA receptors are involved in pain perception, memory, and learning. By blocking these receptors, ketamine can cause dissociation and analgesia (pain relief).

Ketamine is thought to work as an antidepressant by increasing levels of glutamate, a neurotransmitter that is involved in mood and emotion. Glutamate is also involved in the formation of new memories.

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

How Does Ketamine Treat Depression?

Ketamine as a nasal spray, also known as esketamine or Spravato, is approved by the FDA for the treatment of depression. Additionally, IV ketamine as well as ketamine-assisted psychotherapy (KAP) can be used “off-label” for this purpose. This means that a doctor may prescribe ketamine for a purpose other than the ones that are approved by the FDA.

Off-label use of medications is common, and it is up to the doctor to determine if a medication is safe and effective for a particular use. When ketamine treatments are used to address treatment resistant depression, they may be given as an injection or an IV infusion.

A single IV ketamine treatment usually lasts for about 40 minutes and most patients experience symptom improvement within hours of their first treatment. Generally, people need 6-12 treatments, given over a period of 2-4 weeks, to see a prolonged improvement in their symptoms.

What Does the Research Say about Ketamine Treatment?

Ketamine works in several ways at the same time. Research into the full pharmacological action of ketamine is revealing just how complex the response to this drug is. Thus far, the most research has been conducted on IV ketamine infusions.

In patients treated with ketamine therapy, researchers 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 achieve clarity.

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 treatment resistant depression.

Another study looked at the effects of ketamine in people who had not responded to other antidepressant medications. The study found that ketamine was more effective than a placebo in reducing depression symptoms.

A 2018 review of the research on ketamine as a treatment for depression found that it was effective in reducing depression symptoms within 2 hours. The effects of ketamine were also found to last longer than those of other antidepressant medications.

Ketamine is well-tolerated. The side effects of ketamine therapy may include 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.

Ketamine is also sometimes abused. When used as directed by a doctor, however, the risk of abuse and addiction is thought 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.

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 treatment-resistant depression, 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:

Esketamine also known as 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– Given as an infusion into the bloodstream, racemic ketamine 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. Glutamate is involved in the formation of new memories and it is thought to be important for the health of neurons.

It is important to note that currently, there is no cure for depression. Depression is a chronic illness that can enter remission and never reoccur. However, depression can recur. Although it is not a cure, ketamine is a powerful treatment alternative for depression that can help patients achieve remission.

Final Thoughts

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. Overall, ketamine is well-tolerated and side effects are usually mild.

If you are considering ketamine as a treatment for depression, it is important to speak with your doctor about the risks and benefits. Ketamine is not right for everyone, and it is important to make sure that it is safe for you before starting treatment.

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