Ketamine for Major Depressive & Bipolar Disorder

Key Points:

Ketamine works through changes in the neurotransmitter Glutamate.
Ketamine has both short-term and long-term impact on the brain.
Ketamine is an effective treatment for Resistant Depression.

What is Major Depressive Disorder?

Major depressive disorder is a clinical diagnosis where the individual has a persistently low or depressed mood. They can have difficulty experiencing pleasure, decreased interest in activities, feelings of extreme guilt or worthlessness, lack of energy, poor concentration, appetite changes, sleep disturbances, or suicidal thoughts.

MDD affects nearly 20 million American adults each year (over 7% of the US population).

What is Bipolar Disorder?

Bipolar disorder is general defined by extreme mood swings that include extremely high emotional states (mania or hypomania) as well as extremely low emotional states (depression).

It is a condition that affects over 1% of the population and has a significant impact on a person’s mood, energy, and ability to function.

What Happens to the Brain with Major Depressive Disorder and Bipolar Disorders?

It is important to understand that long periods of chronic stress, such as that which occurs in major depressive disorder (MDD) and bipolar disorder, can lead to the dysfunction of a neurotransmitter called glutamate.

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 signals from other neurons)
Modulation of brain function such as cognition, learning, memory, and mood

Additionally, chronic stress causes glutamate changes in the prefrontal cortex, amygdala, and hippocampus.

In the prefrontal cortex, this leads to dendritic shrinkage/impairment and impaired attention.
In the hippocampus, this can cause shrinkage of the hippocampus itself, dendriticshrinkage/impairment, and decreased ability for the individual to learn and maintain memory.
In the amygdala, this leads to overactivity of the structure, dendritic hypertrophy, and increased anxiety.

How Does Ketamine Treat MDD and Bipolar Disorder?

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.

Short Term: Within the first couple hours of a ketamine infusion, a patient can feel ketamine’s anti-depressant 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 effects that occur within hours of treatment.
Long Term: 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 lead to the longer term anti-depressive 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).

How Effective is Ketamine for Depression and Bipolar Disorder?

While traditional antidepressant medications can take weeks to months for the body to respond, ketamine works within days of starting treatments. Additionally, the literature suggests that it has a response rate of 60-80% in treatment resistant depression (depression that has not responded to one medication from two different anti-depressant medication categories).

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.