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Ketamine For The Treatment of Obsessive-Compulsive Disorder

Obsessive-compulsive disorder (OCD) is a common and debilitating condition characterized by unwanted and persistent thoughts, urges, or images (obsessions) that often lead to repetitive behaviors (compulsions). These behaviors or mental acts (such as repeated hand washing, counting, or checking) are intended to reduce distress or prevent an unrealistic disastrous event or situation. OCD interferes with daily life, causes significant distress, and is commonly associated with anxiety.

OCD is frequently misdiagnosed, left untreated, or inadequately treated with pharmacological agents such as selective serotonin reuptake inhibitors (SSRIs) and other treatment strategies, including cognitive behavioral therapy. Long-term outcome studies show that the majority of patients still suffer from clinically significant symptoms of OCD despite the use of first-line treatments. More effective treatment options for OCD are needed, and ketamine may be a novel solution.

New research suggests that glutamatergic neurotransmission contributes to the pathophysiology of this debilitating disorder. Ketamine’s primary mechanism of action involves inhibition of the glutamate-mediated n-methyl-d-aspartate (NMDA) receptor. Today we will briefly review OCD, including epidemiology, symptoms, current treatment, and lastly discuss how ketamine therapy may be an option for treatment.

How common is Obsessive-Compulsive Disorder?

The lifetime prevalence of OCD is 2-3%, making it one of the most common mental disorders globally. Women are two times more likely to suffer from OCD than men. Approximately 85% of people with OCD have serious or moderate impairment, with symptoms generally starting at a young age. Severity may very throughout life, with symptoms generally worsening during times of greater stress or major life-changing events (i.e., new career, divorce, or financial problems). OCD tends to be chronic, with people suffering throughout their lifetime.

Risk factors for Obsessive-Compulsive Disorder

Environment

There is an association of childhood trauma and birth complications with OCD, along with its impact on the level of severity. Environmental and home stressors (i.e., death of a loved one, serious illness, or hostile home life), especially experienced at a young age, may prime an individual for the development of this disorder.

Infection

Studies have also found a link between the development of OCD and Streptococcus bacterial infections (PANDAS). Left untreated these infections have been shown to trigger the onset of OCD in children.  

Genetics

Having a first degree relative with OCD has been found to be a risk factor. Variants in glutamatergic genes suggest a potential role in the development of OCD which has led to interest in the use of ketamine as a target for therapy.

Brain structure

Research suggests that there are structural and functional differences between healthy individuals and those that suffer from OCD. Neuroimaging and studies examining lesions of the brain show that the basal ganglia, prefrontal cortex (orbitofrontal and anterior cingulate cortexes), and thalamus are involved in the pathogenesis of OCD.  

Symptoms of Obsessive-Compulsive Disorder

OCD symptoms can be separated by those that include obsessions and compulsions. Some individuals may have symptoms from both categories, while others suffer from just one. By definition, OCD symptoms are intrusive, unwanted, and cause significant distress or impairment in social, occupational, or important areas of functioning. Symptoms are unrelated to substance use, physical health conditions, or caused by other mental heal conditions. However, it’s important to note that many people who suffer from OCD may have coexisting mental illness that includes depression, anxiety, bipolar disorder, and substance abuse disorder.

Obsessive symptoms

  • Recurrent thoughts or worry (i.e., wondering if the stove is left on or doors are unlocked)
  • Fear of contact with contaminated substances
  • Anxiety about harm, doubt or making mistakes
  • Intrusive mental imagery
  • Need for perfection, neatness, and symmetry

Compulsion symptoms

  • Washing hands or bathing excessively
  • Counting or arranging things a certain way
  • Repeating tasks (i.e., checking locks)
  • Ordered or ritual behavior
  • Hoarding items
  • Saying certain words over and over

Current treatment for Obsessive-Compulsive Disorder

The gold standard for treating OCD typically includes a combination of Cognitive Behavioral Therapy (CBT), particularly a subtype called Exposure and Response Prevention (ERP), and medication.

Exposure and Response Prevention (ERP)

  • Exposure: Gradually exposing patients to thoughts, images, objects, and situations that make them anxious and trigger their obsessions.
  • Response Prevention: Helping patients to avoid performing their usual compulsive behaviors in response to these triggers.

This method helps patients learn that their anxiety will eventually decrease even without performing their compulsions, and it reduces the overall intensity of their obsessive thoughts over time​

Medications

Medications such as SSRIs (e.g., fluoxetine, paroxetine, and sertraline) and tricyclic antidepressants (e.g., clomipramine) in combination with psychotherapy are often the preferred treatment strategy over either treatment alone. Unfortunately, it’s not uncommon for first-line treatments to fail or stop working. Poor tolerance due to side effects such as weight gain, sexual dysfunction, and gastrointestinal upset is often why medical management fails. Additionally, there is a delayed onset of action with the use of conventional antidepressants, with around half of patients incompletely responding to SSRIs.

Ketamine for the treatment of Obsessive-Compulsive Disorder

IV ketamine has been shown to significantly improve OCD symptoms in some individuals, with its effects being both rapid (within hours) and prolonged when combined with psychotherapy. Studies have demonstrated that ketamine infusions may be effective for patients with treatment-resistant OCD, and symptoms have been found not to persist or progress after the acute effects of ketamine have worn off.

Dr. Carolyn Rodriguez, associate dean at Stanford University and professor of psychiatry and behavioral sciences who has extensively studied and contributed to the growing knowledge of ketamine use for the treatment of OCD commented,

“First-line treatments can help approximately half of individuals with OCD, but half of those individuals will not be helped. There is a lot of pioneering research out there and a lot of hope, both for patients who have been recently diagnosed with OCD and those who have struggled with it for a long time”.

Ketamine therapy for the treatment of OCD has been reported to be safe and effective. The dissociative effects of ketamine are well tolerated, while other potential side effects including dizziness and nausea, are rare and easily treated in a clinical, monitored setting. Side effects are relatively brief with most patients returning comfortably to baseline after the first hour of an infusion. At Innerbloom Ketamine Therapy, patients with a predisposition to nausea are pre-medicated with ondansetron (Zofran) to reduce the risk of nausea.

Summary

Exposure and Response Prevention (ERP), a specific form of Cognitive Behavioral Therapy (CBT), and medication remain the first-line therapies for OCD. However, for treatment-resistant cases or those who wish to avoid medications, ketamine offers a potentially safe and rapidly acting alternative. While further research is still needed, studies show promise in the use of ketamine for obsessive-compulsive disorder.

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