Rapastinel for OCD: A New Frontier in Treatment?

Some people with OCD struggle to find the “right” treatment. Sometimes, all it takes to “quiet” the noise in one’s mind is cognitive-behavioral therapy (CBT) and exposure-response and prevention (ERP) therapy. Moreover, sometimes, psychotherapy is combined with natural remedies like hypnosis, art therapy, mindfulness meditation, CBD, probiotics, and/or OCD support groups. Still, other times, it may take psychotherapy, SSRI antidepressants, and homeopathic treatments to get an OCD sufferer’s symptoms under control.

But what happens when none of these “treatments” work or work well? Well, the good thing about natural remedies and self-help tools, like Impulse Therapy, is that they can be used with almost any and every OCD treatment with little-to-no side effects. But, unfortunately, OCD usually requires more than these holistic or alternative treatments. So, what happens when standard or traditional OCD remedies simply do not work? Well, when this occurs, it is often time to look for alternatives – even ones that are still being studied.

Rapastinel is one of these possible treatments. Although this medication is still being studied, it has shown promise – more so for depression, but also for OCD. The possibility of finally receiving relief from treatment-resistant OCD has peaked OCD sufferers who are desperate for a treatment that actually works. Rapastinel is touted as a fast-acting, long-lasting alternative to standard OCD medications.

But does it work? Well, results have been mixed when it comes to depression, so the jury is still out. But, if nothing else has worked for you, it may be worth a try. If you are wondering if Rapastinel may work for your type of OCD, look no further because in this article you will learn what Rapastinel is and how it could possibly reduce or even eliminate your non-stop and unwanted obsession and/or compulsions.

What is OCD?

Obsessive-compulsive disorder (OCD) is a mental health condition triggered by stress and anxiety and characterized by non-stop, unwanted, and intrusive or upsetting obsessions and compulsions. The obsessions typically consist of disturbing or emotionally distressing thoughts, worries, visions, fears, thoughts, and urges, while the compulsions typically consist of checking, counting, cleaning, hoarding, repeating mantras, avoidance, and seeking reassurance behaviors.

Some people only have obsessions or compulsions, while most have both obsessions and compulsions. OCD is a common anxiety disorder, affecting millions of people worldwide. Researchers believe that its origins lie in biology, the environment, and/or in one’s gene pool, but the cause of this condition varies from person to person. Making this condition even more complicated is that there are at least 20 or more different types of OCD.

But, although OCD comes in different shapes and sizes, all the different forms are treated mostly the same – with psychotherapy, namely cognitive-behavioral therapy (CBT), exposure-response and prevention (ERP) therapy, and acceptance and commitment therapy (ACT). Other OCD treatments like neurofeedback therapy, electroconvulsive therapy (ECT), and/or dialectical behavioral therapy (DBT) may be added to the treatment plan if traditional OCD therapies are unsuccessful. Many OCD sufferers have also turned to natural remedies, homeotherapy, and self-help tools like Impulse Therapy, an online OCD recovery treatment plan.

When psychotherapy is ineffective or unsafe, medications are typically added to the treatment plan. The most common OCD medications are SSRI antidepressants and antipsychotics. When the combination of psychotherapy and medication is ineffective, then this is termed “treatment-resistant OCD.” Treatment-resistant OCD is hard to treat and must be treated in other ways, such as with experimental medications.

Rapastinel could be placed in this category because it is still being studied in trials and has, so far, been unable to garner FDA approval for mental health conditions like depression, anxiety, and OCD. People struggling with treatment-resistant OCD are waiting with bated breath for Rapastinel research trials to end so it can enter the prescription drug market. Studies on Rapastinel’s effectiveness for OCD are limited, although results have been positive. Rapastinel will most likely be available as an IV solution (intravenously).

What is Rapastinel?

Rapastinel (GLYX-13) is a new antidepressant that is being developed by Allergan (formerly Naurex) as an intravenous adjunctive therapy for major depressive disorder (MDD), treatment-resistant depression, and possibly obsessive-compulsive disorder (OCD). While it is not approved for anxiety, OCD, or depression, it may in the future be used “off-label” to treat these conditions. 

Rapastinel is an amidated tetrapeptide that behaves like a selective modulator of the  N-methyl-D-aspartate receptor (NMDAR) positive allosteric modulator that triggers rapid antidepressant actions in rodents and people with neurological and mood disorders. An NMDA receptor is an amino acid derivative similar to glutamate, an important neurotransmitter in the brain. 

NMDA receptors are involved in a variety of neurological functions, such as the regulation or control of your breathing, learning, memory development, ability to move, and neuroplasticity (the brain’s ability to learn new information and form new connections and habits). 

Researchers suspect that an NMDA receptor malfunction may be to blame or at the very least contribute to the development of several neurodegenerative diseases like Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), Huntington’s disease, Parkinson’s disease, and epilepsy, and central nervous system conditions like fibromyalgia, chronic fatigue syndrome, migraines with aura, headaches, anxiety, depression, schizophrenia, post-traumatic stress disorder (PTSD), and obsessive-compulsive disorder (OCD). 

Rapastinel is a fast-acting, long-lasting antidepressant and a super strong cognitive supplement primarily because of its ability to strengthen NMDA receptor-mediated signal transduction (a process that involves using a virus or viral vector to introduce DNA into a cell) and synaptic plasticity (the ability of neurons or nerves to communicate). Rapastinel is currently in the second phase of the FDA approval process.

Is Rapastinel Effective for OCD?

The jury is still out on the effectiveness of Rapastinel in the treatment of OCD. Preliminary results and study results concerning its effectiveness in the treatment of depression signal that it could be a promising new treatment for anxiety conditions like OCD. However, more research is needed to validate this claim. Rapastinel is still being studied so its relationship to mental health conditions is still vague and somewhat unclear. However, limited results suggest that this medication may be a viable alternative or supplement medication for OCD.

How Does Rapastinel Work for OCD?

Researchers suggest that Rapastinel may restore NMDA receptor function, thereby stabilizing or regulating one’s mood, improving cognitive function, and reducing cognitive loops or obsessions and compulsions.

Which NMDA Inhibitor is More Effective in Treating Mental Health Conditions – Ketamine or Rapastinel?

According to a 2020 study, although, ketamine, a dissociative anesthetic that blocks N-methyl-d-aspartate (NMDA) receptor channel activity, causes fast-acting (in a couple of hours) and long-lasting (up to 10 days) antidepressant effects, Rapastinel appears to be just as effective, if not more effective, than ketamine without the dreaded side effects of cognitive impairment or symptoms of psychosis like delirium, hallucinations, or delusions. 

Researchers also suggest that Rapastinel may be an effective alternative or supplement for treatment-resistant OCD (i.e., fewer obsessions and compulsions). However, more research is needed to definitely determine its effectiveness in the treatment of this form of OCD. 

Conversely, however, another 2020 study suggests that ketamine, an NDMAR inhibitor, is still more effective than Rapastinel (GLYX-13) in triggering an antidepressant response (a reduction in depression symptoms). This finding stems from ketamine’s ability to rapidly metabolize norketamine (NK), dehydronorketamine, hydroxyketone, and hydroxynorketamine (HNK) metabolites – all of which have been shown to regulate moods and produce antidepressant effects in rodents (mice). 

Rapastinel is unable to metabolize these metabolites (small molecules that play a part in metabolism). This is why these researchers concluded that ketamine is more effective than Rapastinel in the reduction of depression symptoms. Researchers also found that using ketamine has shown promise in the treatment of depression, for OCD, it has garnered mixed results. 

Studies on the effectiveness of intranasal esketamine have also been mixed. Some researchers have found that CBT may strengthen the effects of IV ketamine/intranasal esketamine in the treatment of OCD. However, according to studies, intravenous Rapastinel appeared to acutely improve OCD symptoms beginning at 1-week post-infusion in an open-label trial. 

Earlier studies found that ketamine produced longer-lasting effects (fewer depression symptoms) in the body than Rapastinel, signaling the possibility of supplementing Rapastinel with another medication that stimulates the hippocampus and prefrontal cortex. 

Thus, the general consensus is that ketamine is more effective and longer-lasting than Rapastinel in treating depression, however, there is little evidence to support Rapastinel’s effectiveness in treating anxiety conditions like OCD. Still, more research is needed to determine Rapastinel’s full effectiveness. 

References

• Kato, T., & Duman, R. S. (2020). Rapastinel, a novel glutamatergic agent with ketamine-like antidepressant actions: Convergent mechanisms. Pharmacology, Biochemistry, and Behavior, 188, 172827. Retrieved from https://doi.org/10.1016/j.pbb.2019.172827
• Widman, A. J., & McMahon, L. L. (2020). Effects of ketamine and other rapidly acting antidepressants on hippocampal excitatory and inhibitory transmission. Advances in Pharmacology (San Diego, Calif.), 89, 3–41. Retrieved from https://doi.org/10.1016/bs.apha.2020.05.001
• Yang, B., Zhang, J. C., Han, M., Yao, W., Yang, C., Ren, Q., Ma, M., Chen, Q. X., & Hashimoto, K. (2016). Comparison of R-ketamine and Rapastinel antidepressant effects in the social defeat stress model of depression. Psychopharmacology, 233(19-20), 3647–3657. Retrieved from https://doi.org/10.1007/s00213-016-4399-2
• Rodriguez, C. I., Lapidus, K. A. B., Zwerling, J., Levinson, A., Mahnke, A., Steinman, S. A., Kalanthroff, E., & Simpson, H. B. (2017). Challenges in testing intranasal ketamine in obsessive-compulsive disorder. The Journal of Clinical Psychiatry, 78(4), 466–467. Retrieved from https://doi.org/10.4088/JCP.16cr11234
• Bloch, M. H., Wasylink, S., Landeros-Weisenberger, A., Panza, K. E., Billingslea, E., Leckman, J. F., Krystal, J. H., Bhagwagar, Z., Sanacora, G., & Pittenger, C. (2012). Effects of ketamine in treatment-refractory obsessive-compulsive disorder. Biological Psychiatry, 72(11), 964–970. Retrieved from https://doi.org/10.1016/j.biopsych.2012.05.028
• Adams, T. G., Bloch, M. H., & Pittenger, C. (2017). Intranasal ketamine and cognitive-behavioral therapy for treatment-refractory obsessive-compulsive disorder. Journal of Clinical Psychopharmacology, 37(2), 269–271. Retrieved from https://doi.org/10.1097/JCP.0000000000000659
• Rodriguez, C. I., Zwerling, J., Kalanthroff, E., Shen, H., Filippou, M., Jo, B., Simpson, H. B., Burch, R. M., & Moskal, J. R. (2016). Effect of a novel NMDA receptor modulator, Rapastinel (Formerly GLYX-13), in OCD: Proof of concept. The American Journal of Psychiatry, 173(12), 1239–1241. Retrieved from https://doi.org/10.1176/appi.ajp.2016.16080868
• Pittenger, C., Bloch, M. H., & Williams, K. (2011). Glutamate abnormalities in obsessive-compulsive disorder: neurobiology, pathophysiology, and treatment. Pharmacology & Therapeutics, 132(3), 314–332. Retrieved from https://doi.org/10.1016/j.pharmthera.2011.09.006
• Pauls, D. L. (2010). The genetics of obsessive-compulsive disorder: A review. Dialogues in Clinical Neuroscience, 12(2), 149–163. Retrieved from https://doi.org/10.31887/DCNS.2010.12.2/dpauls