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Ketamine & Esketamine: Could This Depression Treatment Be Right for You?

By LifeStance Health on August 11, 2022

The last two years of the COVID epidemic has caused a 25% spike in anxiety and globally. It has been a condition that can affect anyone but young people and women have experienced higher rates of stress and depression. Almost three years into the pandemic and mental health professionals have more experience with COVID-induced symptoms of various mental health conditions and one of their most effective tools for depression is ketamine and esketamine.

What is ketamine and esketamine?  

Ketamine and esketamine are the first truly “new” medications to treat depression in years by increasing the brain’s synaptic plasticity.

Stress often contributes or exacerbates depression. At the cellular level, stress shrinks the dendritic spines, the spokes that allow neurons to communicate with each other, of neurons or brain cells. Esketamine and ketamine work rapidly to reverse this process by increasing a hormone in the brain called brain derived neurotrophic factor (BDNF). BDNF encourages regrowth of the dendritic spines. These healthy neurons are then able to communicate more easily with each other to connect areas of the brain impacting mood. 

This gives the brain’s frontal lobe, which controls logic and executive function, better control over the amygdala, or the emotional memory center part of the brain.  This circuit is referred to as the default mode network and an imbalance in this circuit is associated with depression and certain other mood and anxiety disorders

Ketamine has been used as an anesthetic for more than 50 years and studied at sub-anesthetic doses for depression for about 20 years.  Ketamine and esketamine are both in-office treatments; ketamine is an IV infusion. Research on ketamine led to the development and FDA approval in 2019 of the nasal spray form esketamine.Esketamine is approved for treating two types of major depressive disorders (MDD): treatment resistant MDD and MDD in patients with suicidal ideation. For ketamine, current research is exploring whether it is also an effective treatment for other psychiatric disorders including:

Who can benefit from ketamine and esketamine treatments?  

Those suffering from treatment resistance depression benefit the most. Patients who fail to respond or do not tolerate trials of two traditional antidepressants are considered treatment resistant.  

Prior to esketamine, antidepressant medications developed over the past 50 years, were based on the “monoamine neurotransmitter deficiency” hypothesis of depression.  Using different versions of the same medication to treat depression didn’t work for 30% of sufferers because their depression wasn’t caused by a lack of neurotransmitters in the brain. Treatment resistance might be linked to the underlying cause of depression so it would be beneficial for more clinical psychologists to incorporate ketamine and esketamine treatments in sooner for patients who haven’t been responsive, or haven’t tolerated traditional antidepressant therapies.

How fast does the treatment work?

These are some of the most effective, rapidly acting treatments for depression currently available. Ketamine and esketamine increase BDNF, and many patients experience relief within four hours, while typical antidepressants could take weeks to take effect. The brain’s amazing ability to adapt to stress and relief means that synaptic plasticity is restored very quickly. Ketamine and esketamine treatments have a very high rate of response, close to 70%, so clinicians and patients know within the first week or so whether this is a treatment option.

What does a ketamine treatment look like?  

Patients consult with their mental health practitioner and are screened to assess whether this treatment might be beneficial for them and for contraindications to ensure they have a high likelihood of a positive outcome. Contraindications to ketamine treatment include: uncontrolled hypertension, cardiovascular disease, aneurysmal vascular disease, history of stroke, pregnancy, active substance abuse, mania or psychosis. 

If they are found to be a good candidate for this treatment, the next step is the induction treatment. Each treatment is in office and lasts approximately two hours.  Generally, treatments start off at twice a week for several weeks to get a patient into remission and then taper them down to every other week or even every other month to maintain response. 

What are the potential side effects? 

Side effects to ketamine and esketamine treatments are very transient and dissipate before the patient leaves the clinician’s office. This is in comparison to side effects with some anti-depression medication that include sexual dysfunction and obesity, problems that are experienced every day with that medicine.

With these treatments, temporary side effects include increased blood pressure, nausea and sedation. Another side effect is dissociation, which is an altered level of consciousness. Dissociation is common but not unpleasant and patients may feel like time and space are distorted, or they may have colorful hallucinations or an out of body experience.  For most patients, they are back to their baseline in about an hour after treatment.