Ketamine for OCD

Key Points:

Obsessive Compulsive Disorder is a psychiatric diagnosis characterized by frequent intrusive thoughts and images and accompanying mental rituals or physical acts to reduce anxiety.
Many patients with OCD fail to respond to serotonin medications alone (SSRIs).
OCD may also be modulated by glutamate receptors.
In preliminary studies, ketamine combined with exposure based psychotherapy produced reduction in OCD symptoms.

What is Obsessive Compulsive Disorder (OCD)?

Obsessive compulsive disorder is one of the five major types of anxiety disorders and is a condition where the individual has frequent intrusive thoughts and sensations that cause them to perform tasks repetitively. These compulsions cause significant interference with social interactions and the performance of daily tasks.

It is estimated that the lifetime prevalence of OCD is between 2-3%.

What Causes OCD?

It is uncertain what exactly causes OCD. We do know that genetics, brain abnormalities, and environment shape the likelihood of OCD occurring. It is also common for other anxiety disorders, depression, eating disorder, or substance abuse to occur with OCD.

It has been shown in the literature that a significant proportion of individuals do not respond to selective serotonin reuptake inhibitors (SSRIs) indicating the serotonergic dysfunction that occurs in OCD does not fully explain the illness. Magnetic resonance spectroscopy, cerebrospinal fluid, genetic studies, and animal models of OCD have found evidence of dysfunction related to 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 signalsfrom other neurons)
Modulation of brain function such as cognition, learning, memory, and mood

Structurally, OCD is associated with dysfunction in two frontal cortical regions:

The orbitofrontal cortex (OFC)
The dorsal anterior cingulate cortex (dACC)

These regions have consistently been shown to be hyperactive at rest in adults with OCD compared to healthy adults, increased in activity with increased OCD symptoms, and no longer hyperactive following successful treatment.

How Does Ketamine Treat OCD?

The exact mechanism of action of ketamine is not fully understood. However, we do know that:

In the first couple hours of a ketamine infusion, the release of glutamate is significantly effected in key areas of the brain.
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 leading to increased functionality of brain structures

Additionally, ketamine has inhibiting/normalizing effects on both the orbitofrontal cortex (OFC) and dorsal anterior cingulate cortex (dACC) – two areas of the brain in which their hyperactivity is believed to lead to OCD symptoms.

How Effective is Ketamine Infusion Therapy for OCD?

Although there is less research on ketamine for OCD compared to depression, a small open-label study of patients with OCD found that a single dose of ketamine added to exposure-based cognitive behavioral therapy led to an initial reduction in OCD symptoms and was sustained for over two weeks. The study suggests that ketamine can have a synergistic effect on other OCD related treatments.

Other studies have shown similarly that a single dose of ketamine rapidly and dramatically decreased OCD thoughts and lasted for at least one week.

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?

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