Ketamine for OCD: Can Ketamine Treat Obsessive-Compulsive Disorder?

Ketamine is a psychoactive drug that binds to the excitatory NMDA receptor and increases neural plasticity and learning. It has historically been used as a potent anaesthetic, but recent years have seen an insurgence in the use of ketamine to treat psychiatric conditions. OCD stands for obsessive-compulsive disorder, which is a psychiatric condition in which people experience intrusive and repetitive thoughts that interfere with their daily activities. In this article, we will cover the exciting evidence about whether ketamine can alleviate symptoms of OCD.
Klara Hatinova

Klara Hatinova

Klara is postgraduate researcher in experimental psychology at the
University of Oxford.

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Can Ketamine be used to treat OCD?

Ketamine has been used and investigated for the treatment of OCD for over 10 years, but it still does not have FDA approval as a treatment for OCD. However, several studies show that ketamine could dramatically reduce the urges felt by people with OCD.

Interestingly, ketamine for bipolar disorder, does have FDA approval, if it administered as esketamine.

Let us examine ketamine therapy for OCD in more detail.

What is Ketamine?

Ketamine is the common name for ketamine hydrochloride, which was first synthesised and administered in the 1960s.

Ketamine binds to a side pocket in the excitatory NMDA receptor. The NMDA receptor is a critical receptor for glutamate, the primary excitatory neurotransmitter in the nervous system, essential for synaptic plasticity [1]. Ketamine can also bind to opioid receptors, which may be responsible for some of its anaesthetic properties. However, ketamine is not an opioid.

For anaesthetic purposes, ketamine is administered intravenously and thereby acts within 5-30 minutes of injection. Its effects last 2-4 hours, after which it is eliminated in urine [1, 2].

Ketamine comes in a mixture of two forms: S-ketamine and R-ketamine. Esketamine is a pure S-ketamine marketed independently to Ketamine (the mixture), sometimes known as "Special K" or Ket. Esketamine has been approved by the FDA for treating treatment-resistant depression in 2019 [3], marketed by Boehringer Ingelheim [4]

How does Ketamine work?

Ketamine works as a non-competitive antagonist of the NMDA receptor. This means that it binds to the side pocket of the NMDA receptor, distinct from the primary pocket to which glutamate binds, and reduces the ability of glutamate to initialise an excitatory neural response. Ketamine thereby disrupts communication among critical brain centres and reduces the ability of the mind to perceive pain [3, 5].

Ketamine also binds to several other targets, including opioids, voltage-gated ion channels controlling heart rate and respiration, and GABA inhibitory and serotonin neurotransmission [3].

What is Ketamine used for?

Ketamine was first developed as an anaesthetic in the 1960s. Since then, it has been used as a primary anaesthetic agent during surgery or as an adjunct to weaker forms of anaesthesia, such as nitric oxide [6, 7]. Ketamine can also be used alongside opioids, as the drug effects do not interact in a negative way [7].

More recently, ketamine has been tested as a treatment for a spectrum of exciting conditions, including OCD, depression, post-traumatic stress disorder, anxiety, anorexia and neuropathic pain [6]. Ketamine is also an excellent model to study schizophrenia since, at high doses, it mimics many of the hallucinations and cognitive symptoms [8].

Recently, esketamine, the S-Ketamine only version of ketamine, was approved by the FDA for treating treatment-resistant depression in 2019 [3].

What is OCD?

OCD, short for obsessive-compulsive disorder, is a severe psychiatric condition in which patients experience intrusive thoughts and urges to carry out rituals, repetitive behaviour or specific mental processes [9]. According to the World Health Organisation, OCD is among the top 10 conditions with the highest impact on quality of life and productivity [10]. In the Diagnostic and Statistic Manual 5th edition (DSM-V), which came out in 2013, OCD has been expanded to obsessive-compulsive disorder and related disorders, which include body dysmorphia, skin picking disorder (Excoriation disorder), hair pulling and hoarding disorder.

Individuals with OCD feel compelled to carry out their compulsions to alleviate anxiety and distress and express worry over what would happen if they did not. These thoughts, urges and behaviours are very disruptive to their daily lives and activities.

The neurobiology of OCD is still not well understood but likely involves a disbalance between the excitatory glutamate neurotransmitter and inhibitory GABA neurotransmitter. This chemical disbalance results in miscommunication between the front of the brain and the midbrain, generating a discrepancy between the urge and conscious control and restraint [11].

OCD can co-occur with ADHD, but it is important to know that OCD and ADHD are different conditions.

What is the prevalence of OCD?

The prevalence of OCD in the general population is around 1%, and the average age of onset is just before turning 20 years old [12]. In more specific populations, the prevalence of OCD is much higher. For example, in patients with eating disorders, such as anorexia, the prevalence of OCD is up to 50%. There are also twin studies that support generic associations between anorexia and OCD, which may account for the increased prevalence of OCD in this population [13].

Generally, 90% of patients with OCD have a co-morbid psychiatric diagnosis, which influences their experience and treatment outcomes [14].

What are the conventional treatments for OCD?

The first line of treatment for OCD is Cognitive Behavioural Therapy (CBT), which addresses the urges and behaviours the patients experience. The patient needs to have the support of their surroundings - friends, relatives, colleagues and an adapted environment to tackle the urges. "Booster" CBT sessions may be needed to maintain treatment outcomes of CBT.

For OCD patients who do not respond to CBT alone, selective serotonin reuptake inhibitors (SSRIs), a class of antidepressants including fluoxetine or escitalopram can be a beneficial treatment supplement.

Suppose the combination of SSRIs and CBT is insufficient to help the patient. In that case, clinicians try to either change the antidepressant used, increase the antidepressant dose or add an antipsychotic drug.

How can Ketamine be used for treating OCD?

Ketamine has been used and investigated for the treatment of OCD for over 10 years [15]. Nonetheless, it does not have FDA approval as a treatment for OCD, meaning it has only been used off-label or in experimental settings.

Ketamine, as described above, is an NMDA antagonist, meaning it interferes with the transmission of excitatory glutamate signals. Therefore, ketamine can adjust the balance between excitation and inhibition, which is implicated in OCD [11]. Ketamine also promotes neuroplasticity through brain-derived neurotrophic factor, which could be necessary to re-learn healthy associations [16].

Amazingly, ketamine improved the urges and reduced patients' tendency to act on them in several studies [15, 16, 17, 18]. Recent studies have started to explore how the benefits of ketamine on neuroplasticity could be combined with CBT to enhance the positive effects of both the therapy and the drug. This is an ongoing research effort, but it could dramatically reduce the urges felt by people with OCD.

More studies looking at more participants are needed to gain approval for ketamine as an FDA-backed treatment for OCD. These studies must investigate how quickly it is eliminated, what combination of S and R-ketamine works best, and the dose and administration methods.

However, not everyone should undertake Ketamine therapy, and it is important to find out who is a good candidate for ketamine therapy.

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Klara Hatinova

Klara Hatinova

Klara is a postgraduate researcher in experimental psychology at the University of Oxford. She has worked across a spectrum of hot topics in neuroscience, including her current project measuring reinforcement learning strategies in Parkinson’s disease. Previously, she studied the efficacy of psilocybin as a therapy for critical mental health conditions and examined molecular circadian rhythms of migraine disorders. She completed her undergraduate degree in Neuroscience at the University of Glasgow and participated in a year abroad at the University of California, where she worked on a clinical trial for spinal cord injury.