Can Ketamine Be Used to Treat Depression That is Resistant to Treatment?

Worldwide, millions of people suffer from depression. There are numerous effective treatment options available, but finding relief for some can seem impossible. For those with treatment-resistant depression, they are beginning to turn to ketamine, a medication with a long and somewhat controversial history.

What is ketamine?

In the 1960s, Ketamine was developed as an anesthetic. Since then, it has been used to treat chronic coughs and pain. Research has, however, focused on its potential as a depression treatment over the past few years as part of psychedelic therapy.

How does Ketamine treat depression?

Ketamine works by binding to brain receptors that produce glutamate. Basically, it activates glutamate in the brain.

It is not clear exactly how glutamate affects depression symptoms, but it is known that it plays a critical role in mood regulation. There is a possibility that depression symptoms are caused by low glutamate levels in the brain.

Also, ketotamine can stimulate brain-derived neurotrophic factor production. As you experience new things, this protein plays an important role in neuroplasticity. It is believed that ketamine contributes to the reduction of depression by supporting neuroplasticity.

Additionally, ketamine works very quickly, which is another major advantage. Contrary to traditional antidepressants, you may not notice improvement in your symptoms for weeks. Ketamine, however, may provide relief within 1 hour.

The use of ketamine may also be beneficial for treating:

• Anxiety

• Bipolar disorder

• Obsessive-compulsive disorder (OCD)

• Post-traumatic stress disorder (PTSD)

Is this claim supported by evidence?

In 2019, the FDA approved the nasal spray form of ketamine, esketamine (Spravato), for treating TRDs; however, it must be administered "under the supervision of a health care provider in a certified doctor's office or clinic." In other words, medical professionals should monitor you when you use it, then check your vital signs and how you feel afterward.

Researchers first demonstrated the effectiveness of ketamine in treating TRD for a short period in studies comparing ketamine to placebo, resulting in significant clinically and statistically significant reductions in depression scores. The patients in both groups continued to take their regular antidepressants because they were concerned about not treating TRD. In one study, nasal ketamine was found to help people stay in stable remission 16 weeks after taking it.

The effects of ketamine on TRD are rapid. It takes about 40 minutes for people suffering from depression to feel the benefits of ketamine instead of waiting weeks for an SSRI to provide some relief.

What is the administration method for Ketamine?

In most cases, ketamine treatment is administered in one of three ways. 

In intravenous infusions, ketamine is administered directly into the bloodstream through a needle inserted into the arm vein. During the infusion, you will be monitored for about 40 minutes to an hour.

Another option is to administer ketamine through an intranasal spray. Only FDA-approved nasal spray formulation of intranasal esketamine is available for use in clinical settings. As a nasal medication, esketamine is absorbed into the body through the nose lining. For people who fear needles or have difficult access to veins for IV infusions, this method may be preferred.

Sublingual troches are another way to administer ketamine, such as a soft dissolvable placed on your cheek.

How long does Ketamine last?

Taking long-term antidepressants can alleviate depression for weeks at a time. In contrast, ketamine offers immediate relief, but the effects often fade after a few days or weeks. For patients to relieve symptoms, a series of treatments or an ongoing schedule of intermittent treatments may be required.  

The safety of Ketamine and its side effects.

There are generally few side effects associated with ketamine therapy. A 2021 review found the most common side effects included

• Dissociation, in which you feel disconnected from your body, mind, and emotions

• Dizziness

• Drowsiness

• Dysgeusia, or altered sense of taste

• Headaches

• Nausea

• Psychosis, including hallucinations and delusions

• Vertigo is a sensation of spinning and losing balance when you aren't moving

There are rare cases in which ketamine can cause adverse effects, including:

• Akathisia, the inability to sit still

• Ataxia, a lack of coordination or muscle control

• Autoscopy, also known as out-of-body experiences

• Mania

• Panic attacks

• Thoughts of self-harm

It has also been found that ketamine can worsen depression in some people.

In addition, repeated use of ketamine can lead to bladder dysfunction and memory loss.

Are you a good candidate for ketamine treatment?

Discuss this with your primary care doctor, your mental health provider, and any other health care providers who take care of you. In general, ketamine is only used if other, more established treatments haven't worked for depression. 

This treatment does not cure but rather improves symptoms for a limited period. Using the side effects of ketamine as a guide, it is easier to determine who isn't a good candidate for the treatment.

Trying to find hope in the dark.

There can be a feeling of loneliness and isolation associated with depression. But don't forget that you're not alone. For those struggling with this debilitating illness, there is help available, and new treatment options like ketamine offer renewed hope.

For more information on ketamine treatment for depression, it’s encouraged you to do your own research. Specifically, and most importantly, contact your doctor or mental health professional with any questions or concerns.