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Ketamine For The Treatment of Obsessive-Compulsive Disorder

Obsessive-compulsive disorder (OCD) is a common and debilitating disorder with features that include unwanted and persistent thoughts, urges, or images (obsessions) that may lead to repetitive behaviors (compulsions). These behaviors or mental acts (i.e., repeated hand washing, counting, checking) are aimed to lessen distress or 'prevent' an unrealistic disastrous event or situation if not performed. This interferes with daily life, causes significant distress, and is commonly associated with anxiety.

I would argue that OCD is on a spectrum, and many people, including myself, have ‘OCD tendencies’ that may benefit from ketamine therapy. I vividly recall obsessing about my studies during my medical training - perfection to a fault. OCD is frequently misdiagnosed, left untreated, or inadequately treated with pharmacological agents such as selective serotonin reuptake inhibitors (SSRIs) and other treatment strategies (i.e., cognitive behavioral therapy and exposure and response prevention). These conventional OCD therapies may not be effective for some people, with most adult OCD patients not achieving remission. Long-term outcome studies show that majority of patients still suffer from clinically significant symptoms of OCD despite use of first-line treatment. 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 OCD?

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 OCD

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 OCD

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 OCD

Medicines such as SSRI (i.e., fluoxetine, paroxetine, and sertraline) and tricyclics antidepressants (clomipramine) in combination with psychotherapy is the preferred treatment strategy other than either treatments alone, or other forms of treatment. Cognitive behavior therapy (CBT) which is structured and goal-orientated, is the preferred style of therapy for OCD. There are many examples of CBT techniques, but my personal favorite for anxiety is behavior rehearsal. I often used this technique as a surgeon. Behavioral rehearsal may include mentally going through the motions of an anxiety provoking task or upcoming event (i.e. preparing for a surgery), while thinking of all the potential pitfalls, roadblocks, of complications in order to prepare for a real life situation.

Unfortunately, it’s not uncommon for first-line treatment to fail or stops working. Ever since treating our first patient at Innerbloom, we have heard horror stories from our patients about their previous medications (i.e., SSRIs) causing awful side effects. Complaints of weight gain, sexual dysfunction, and GI-upset come up time and time again. Additionally, there is a delay with the use of antidepressants, with around half of patients incompletely responding to SSRIs. At least eight weeks of sustained treatment (and side effects) typically are needed before any meaningful clinical improvement.

Ketamine as treatment for OCD

IV ketamine has been shown to significantly improve OCD symptoms, with its effects being rapid (within hours) and prolonged with the combination of psychotherapy. Studies have shown that ketamine infusions are effective for patients with treatment-resistant OCD and symptoms do not 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.

Symmetrical pattern with OCD in the middle and ketamine at the outer perimeter

Summary

SSRIs and psychotherapy remain as first-line therapy for OCD, however, this treatment approach is often inadequate or may be associated with significant side effects which limits compliance. New options for OCD treatment are needed. An effective, rapid, and safe alternative is ketamine. While I agree that further research is still needed, studies are showing promise in the use of ketamine for many neurological and mental disorders that extends beyond pain, depression and anxiety.

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