Obsessive Compulsive Disorder (OCD)

OCD is a mental disorder characterized by intrusive thoughts (obsessions) and recurring behaviors (compulsions). Prevalence is approximately 1% of the population with the average age of onset being 19. Symptoms include repeated thoughts, urges, or mental images and may result in repetitive behaviors such as obsessive cleaning and/or handwashing, repeated arranging and checking on things, and compulsive counting. Individuals with OCD typically cannot control their thoughts and behaviors related to their compulsions. These symptoms can greatly interfere with daily activities including work, school, and personal relationships. People with first-degree relatives diagnosed with OCD are at higher risk for developing the disorder themselves. Those also at risk for developing OCD are individuals who have experienced physical or sexual abuse in childhood or other trauma.

Treatment consists of psychotherapy and medications like SSRIs, TCAs, and sometimes antipsychotics. The limitations of conventional therapy are great. OCD individuals experience only a 20-40% reduction in symptoms, treatment response doesn’t begin for two-three months, and unwanted side effects are many (Matthew, 2016). Studies in humans and animals suggest OCD individuals have abnormalities in the cortico-striato thalamo-cortical (CSTC) (Matthew, 2016). Other systems likely involved are serotonin, dopamine, glutamate, and gamma-aminobutyric acid (GABA) neurotransmitter systems.

OCD symptoms are thought to originate from glutamatergic abnormalities in the cortico-striatal circuits. OCD patients not only present with hyperactivity of CSTC circuits but also baseline GABA deficits in the mPFC. Glutamate is the most common excitatory neurotransmitter in the nervous system and works on NMDA, AMPA, kainite (KA) subtypes, and G-protein-coupled receptors. Animal studies indicate that changes in fronto-striatal activity and elevated NMDAR expression are critical operators in OCD-like repetitive behaviors (Matthew, 2016). Therefore, NMDAR antagonism may better target mechanisms driving OCD-like behaviors (Matthew, 2016). Research on the treatment of OCD with ketamine is still in the initial stages of validation, however, several studies have been conducted.

In one case report, an unmedicated OCD patient was treated with 0.5 mg/kg of IV ketamine over a 40-minute period. This resulted in rapid anti-obsessional effects. However, the patient returned to baseline one-week post ketamine infusion. In 2013, Rodriquez et al. conducted a proof-of-concept, randomized-controlled, double-blind, crossover study on single dose ketamine in OCD individuals. One dose of 0.5 mg/kg IV ketamine given over 40 minutes produced rapid anti-obsessional effects in adults with OCD. Complete resolution of symptoms was noted during the infusion with sustained effects in 50% of subjects one-week post-infusion. In this study, only unmedicated individuals with near-constant intrusive obsessions (greater than 8 hours/day) were included (Matthew, 2016). An isolated case report documented two intravenous (IV) ketamine infusions (0.5 mg/kg) one week apart on a 24-year-old female with OCD. No symptom reduction was observed after placebo; on ketamine infusion, almost complete reduction of obsessions was observed up to 7 days post injection. In an open-label trial of IV ketamine 0.5 mg/kg in ten patients with refractory OCD, the initial symptom reduction of OCD symptoms was observed, along with decreases in the Hamilton Depression Rating Scale-17, a clinician-administered Dissociative States Scale, and the Clinical Global Impression (CGI) scale. Though the decrease in symptoms was maintained at 50% in four out of seven depressed patients, none of the OCD patients sustained significant improvements. In a recent randomized, double-blind, placebo crossover study, adults with OCD received two IV ketamine infusion treatments. The comparison groups received saline and low-dose ketamine (0.5 mg/kg). Those in the full-dose experimental group reported substantial improvements in OCD symptom severity, with 50% meeting the criteria for treatment response (35% Y-BOCS reduction) using the OCD visual analog scale and the Y-BOCS. The residual effects of ketamine lasted longer than the expected one-week post-infusion (Grados et al., 2015).

Ketamine is shown to enhance plasticity and extinction learning in rodents. Another study was done to test whether ketamine would enhance extinction learning and facilitate CBT gains in OCD individuals when applied together. Ketamine was administered to unmedicated OCD adults followed by ten one-hour exposure sessions of exposure and response prevention (EX/RP) therapy. These therapies were conducted within 14 days of ketamine administration during which ketamine is thought to facilitate extinction learning. At the end of EX/RP therapy (two weeks), 63% of patients demonstrated treatment response with a minimum 35% Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) reduction. Although promising, limitations of this study include a lack of randomization (Matthew, 2016).