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Ketamine for Generalized/Severe Anxiety

A diagram of the comorbidities that ketamine treats

Key Points:

  • Generalized Anxiety Disorder is a common psychiatric diagnosis which includes excessive worry about a number of events for at least 6 months.

  • Ketamine appears to be effective for resistant Generalized Anxiety Disorder.

  • Patients with Generalized Anxiety Disorder may benefit from a full course of ketamine infusions.

What is Generalized Anxiety Disorder (GAD)?

Although it is normal to feel anxiety from time to time, generalized anxiety disorder (GAD) is usually defined by significant uncontrolled worrying about a number of events that occurs on most days and for at least 6 months.

GAD is associated with three (or more) of the following symptoms):

  • Restlessness or feeling on edge

  • Being easily fatigued

  • Difficulty concentrating or mind going blank

  • Irritability

  • Muscle tension

  • Sleep disturbances (difficulty falling or staying asleep, or restless, unsatisfying sleep)

Lifetime prevalence of GAD is 7.7% in women and just under 5% in men.

What is Treatment Resistant GAD?

Treatment resistant GAD is when an individual fails to respond to at least 1 trial of antidepressant therapy that has been given at an adequate dose and duration.

The literature suggests that between 30-50% of people undergoing treatment for GAD are “treatmentresistant”.

What Causes Generalized Anxiety?

Although it is not fully understood why certain people suffer from GAD and others do not, generally, it develops when one is unable to cope well with their internal stress for a prolonged period. It can run in families, be due to medical conditions such as hyperthyroidism, and can sometimes be a side effect of a medication or substance abuse. GAD can be triggered by environmental stress as well as chronic illness.

Examining the brain’s structures, generalized anxiety as well as treatment resistant anxiety can lead to glutamate neurotransmitter imbalances.

Glutamate is important in several functions:

  • Regulation of the brains ability to form and reorganize synaptic connections (neuroplasticity)

  • Maintenance of dendrite density (dendrites are small branches on neurons that receive signalsfrom other neurons)

  • Modulation of brain function such as cognition, learning, memory, and mood

Glutamate receptor damage can occur in the hippocampus and neuron breakdown can occur in the prefrontal cortex. Additionally, the amygdala (responsible for regulating fear and emotions) can be disproportionately enlarged and over-reactive. These changes decrease the patient’s ability to perform executive functions, maintain appropriate cognition, and regulate emotions

How Does Ketamine Treat Generalized Anxiety Disorders?

The exact mechanism of action of ketamine is not fully understood. However, broadly speaking, there are two major ways in which ketamine exerts its effects.

  • First, within the first couple hours of a ketamine infusion, a patient can feel its anti-anxiety effects. This is due to ketamine’s effects on the release of glutamate in the prefrontal cortex, hippocampus, and amygdala. This leads to rapid anti-depressive/anxiety affects that occur within hours of treatment.

  • Second, ketamine aids in the restoration of lost dendritic density (increasing dendritic spine number) through increasing brain-derived neurotrophic factor (BDNF). Significant increases in density begin to occur approximately 2-7 days after an infusion. It is believed that increases in dendrite density leads to the longer-term anti-anxiety effects of ketamine.

Overall, ketamine rapidly facilitates synaptic plasticity and modifies neural function in the prefrontal cortex and hippocampus as well as reduces amygdala hyperreactivity to emotional stimuli. Because of ketamine’s effect on dendrite density (increasing the neuron’s ability to receive neurotransmitters), it works synergistically with other antidepressants (which work to increase the amount of neurotransmitters in specific regions of the brain).

Additionally, the literature has shown that ketamine infusion therapy results in several neurocognitive improvements for most people. These include faster processing speed, improved visual learning, and improved memory.

How Effective is Ketamine for Generalized Anxiety Disorders?

Although there is less research on ketamine for generalized anxiety disorders compared to depression, a 2022 systematic review on ketamine treatment for treatment resistant anxiety found that a single dose of ketamine has rapid acting mood enhancing and anxiolytic effects that persist up to a week after treatment.

It is important to note that receiving a loading dose of ketamine (6 infusions over a period of a few weeks) has been shown to be far more effective than just a single treatment of ketamine.

How Can I Find Out More Information?

For more information, contact us or submit a request for a 15 minute consultation on our contact form.

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