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Exclusion Criteria for Patients with Medication Washout:. Hide glossary Glossary Study record managers: refer to the Data Element Definitions if submitting registration or results information. Search for terms x. COVID is an emerging, rapidly evolving situation.
Save this study. Warning You have reached the maximum number of saved studies Listing a study does not mean it has been evaluated by the U. Federal Government. Read our disclaimer for details. Results First Posted : May 10, Last Update Posted : July 18, Study Description. This is not a treatment study. Results from this study will allow doctors and researchers to better understand if you and others with OCD may respond to a class of medications that target the NMDA brain receptor.
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Inclusion Criteria for Patients with No medication Washout: Age Physically healthy and not currently pregnant Primary Diagnosis of OCD currently off all psychotropic medications and other drugs Able to provide informed consent Exclusion Criteria for Patients with No Medication Washout: Psychiatric conditions that make participation unsafe schizophrenia [either self or first degree relative e.An article in The Morning Calla newspaper for Allentown and the Lehigh Valley area of Pennsylvania, announced that a local company, the Lehigh Center for Clinical Research, would be conducting clinical trials for two pharmaceutical companies to gain FDA approval for modified versions of ketamine as a treatment for depression.
The psychiatrist running the trials said the drugs could hit the market in the next few years. There have been waves of excitement and concern over the past few years about the development and use of ketamine and ketamine-like drugs to treat depression. Ketamine has been an FDA approved medication sincewhere it was used as an anesthetic in the Vietnam War. Ketamine is also a recreational drug known as Special K because of its dissociative properties. The excitement over ketamine, as a treatment for depression, centers on its rapid relief of depressive symptoms; sometimes within hours of it being administered.
But the effects fade rapidly and require frequent, repeated treatments.
The Latest OCD Research: An Interview with Dr. Carolyn Rodriguez
Currently ketamine is administered intravenously, similar to its use as an anesthetic. There is an intranasal spray version Esketamine in the works. While Esketamine is a nasal spray, Rapastinel is administered by weekly IV injections.
Both are currently in Phase 3 clinical trials. This involves randomized, double blind testing in several hundred to several thousand patients. Upon successful completion of their Phase 3 trials, a pharmaceutical company can request FDA approval for marketing their drug. Somewhere around 70 to 80 percent of drugs that make it to Phase 3 are eventually approved.
Although Esketamine and Rapastinel are similar to ketamine in several ways, they are still distinct NMEs new molecular entitiespatented by their respective pharmaceutical companies. Ketamine was first developed in the s and has been off patent for decades, meaning there is no profit in Pharma companies pursuing ketamine-based treatment for depression.
But since ketamine is an FDA approved drug, it can be used off label to treat depression. And there are a growing number of ketamine treatment facilities around the U.
He has personally treated hundreds of people with low dose ketamine. They also noted the increasing evidence from small studies that ketamine has rapid antidepressant effects in patients with treatment-resistant depression.
They commented how ketamine is having a major effect on psychiatry. Because of the limited data to guide clinical practice, these limitations extend to almost every recommendation in the consensus statement, including, perhaps most importantly, patient selection.
The bulk of the literature describes the effects of ketamine in patients with treatment-refractory major depression. The definition of treatment-refractory major depression and where treatments such as ketamine fall in the algorithm for managing treatment-refractory depression remain poorly understood.Ketamine, which acts on brain glutamate receptors, has shown remarkable therapeutic effects in OCD; however, patients reported side effects including transient dissociation.
The glutamate receptor modulator rapastinel may reduce symptoms of OCD without the dissociative side effects reported by patients treated with ketamine. Learn more. Carolyn Rodriguez utilizes her training as a psychiatrist, neuroscientist, and clinical researcher to innovate rapid-acting treatments to relieve the suffering of patients with severe mental illnesses, including Obsessive-Compulsive Disorder OCD.
She has led landmark clinical trials that pioneered new targeted treatments and investigated the role of glutamatergic and opioid pathways. As the Director of the Translational Therapeutics Lab and Assistant Professor in the Department of Psychiatry and Behavioral Science at Stanford, she developed methods that combine in vivo drug infusions with magnetic resonance spectroscopy MRSfunctional magnetic resonance imaging fMRI and electroencephalograpy EEG to map human brain circuit dysfunction in real time.
This experimental medicine approach is critical to understanding the brain basis of psychiatric illnesses and will transform mental health care. Jeffrey Borenstein, M.
Glutamate OCD: The Role of Glutamate in OCD
The program, which is broadcast nationwide, focuses on topics in psychiatry in order to educate the public, reduce stigma and offer a message of hope. Eating Disorders.
Mental Illness General. Suicide Prevention.obsessive compulsive disorder (ocd): my story
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Multimedia Library. Connect Ask the Expert Join Us. Sign up for upcoming webinars. View other past webinar recordings.Glutamate is the main neurotransmitter in the nervous system and one of 20 amino acids that are needed to make proteins; it is responsible for mediating the excitatory signals in the nervous system.
Most importantly, glutamate is directly linked to normal brain functions such as memory, learning, and cognition Danbolt, A delicate balance of glutamate must be maintained; although it is needed for healthy brain functions, too much can be toxic.
Ongoing research is being conducted to determine if and how glutamate levels contribute to OCD. Although the study of glutamate and OCD is relatively new, there have been some exciting discoveries that hold promise for future treatment of OCD.
It would appear that science is on the threshold of decoding OCD. The following information is based on the data collected from some of these studies. So far, studies have shown that there is clear difference between glutamate levels in individuals with OCD and those without the disorder.
Researchers believe that this difference in levels may contribute to the obsessive and compulsive behaviors found in OCD. One such study focuses on a glutamate transporter gene called SLC1A1. This particular gene regulates the flow of glutamate in the brain.
This gene is the only one that has been consistently linked to OCD. The most compelling evidence, thus far, supporting the role of glutamate in OCD comes from researchers at the Ruhr University in Germany. Here, they studied the cerebrospinal fluid CSF of individuals with OCD and compared it to that of healthy individuals. Numerous other studies have been conducted that reveal higher levels of glutamate in OCD patients.
Other methods of research include using glutamate-modulating agents which reduce the amount of glutamate that is released in the brain. These medications have been shown to reduce OCD symptoms in clinical trials, thus supporting the hypothesis that high levels of glutamate are related to OCD. While data suggests that glutamate is linked to OCD, it is not yet understood how.
The role of glutamate in OCD needs further research before any real assumptions can be made. To date, it is unclear if abnormal glutamate levels are the cause of OCD or just a byproduct of the disorder.
There is no question that there is some connection between glutamate levels and OCD, but for now researchers can only speculate as to what this connection is. Bloch, M.
New horizons in OCD research and the potential importance of glutamate: Can we develop treatments that work better and faster? Danbolt, N. Glutamate as a neurotransmitter-Overview. Gavin, K. New genetic findings add to understanding of OCD.
A conservative estimate has at least a third of patients with depression not adequately responsive to these monoaminergic medications. A host of medications in various stages of development might each offer unique additions to the current therapeutic paradigm. Compounds closest to market include N -methyl-D-aspartate NMDA blockers such as esketamine or rapastinel; opioid receptor partial agonists and antagonists, such as Alkermes ; and a GABA A receptor modulator, brexanolone.
A further off, more speculative intervention involves the use of psychedelic drugs like psilocybin. NMDA antagonists have gained the highest visibility after some promising results in early studies looking at intravenous ketamine, an anesthetic agent approved by the FDA in for treatment-resistant depression.
This has led to several companies trying to develop a patentable NMDA antagonist for depression. The most likely first candidate is one of the enantiomers of ketamine, esketamine, which, because of higher binding affinity, can be dosed intranasally rather than intravenously. Studies are completed to establish efficacy in TRD 2 [treatment-resistant depression] as well as acute suicidality 3.
Another promising NMDA antagonist, rapastinel, is wending its way through clinical trials — but should it be approved, its use might be limited by the requirement for intravenous delivery. Despite only early evidence for efficacy in depression, the easy availability of ketamine for infusion has created a cadre of independent clinicians as well as some academic clinics offering intravenous ketamine infusions for those with difficult-to-treat depression and adequate finances to pay for off-label treatment some insurance companies as well have supported its use.
It is understandable to try to offer patients suffering with refractory illnesses anything the field has to offer, but the limitations on our knowledge, especially about the efficacy and safety of long-term use of ketamine for depression, need to be taken into account 4.
As more evidence and experience are collected, NMDA antagonists might offer a unique efficacy profile within safe boundaries. Opioid agonists have some antidepressant activity, but tolerance to it quickly develops — requiring users to take increasingly higher doses.
Would a partial opioid agonist coupled with a pure opioid antagonist provide ongoing efficacy at a continuous dose with adequate safety?
The phase 3 studies are not yet published. However, the phase 2 published trial demonstrated efficacy at low doses 2 mg of buprenorphine with 2 mg of samidorphan as an adjunctive medication in treatment-resistant depression 5. Brexanolone, an intravenous formulation of allopregnanolone, a positive allosteric modulator of gamma-aminobutyric acid GABA A receptors, has been studied for the treatment of postpartum depression 6. Early development has focused on an intravenous delivery system and a unique target population of postpartum depression, but the novel concept of targeting GABA A receptors might prove fruitful with a wider population of depressed patients with inadequate responses to existing antidepressants.
An oral formulation, SAGE, is in early clinical trials. While much earlier in the development for FDA approval, psychedelics, particularly psilocybin, have been investigated for use in treatment-resistant depression. A small double-blind trial in terminal cancer patients showed that psilocybin had a remarkable palliative effect on depression and anxiety 7. An open label study of treatment-resistant depressed patients demonstrated lasting benefit over 6 months after two doses of psilocybin 8.
A neuroimaging study supported the idea that changes in resting state functional connectivity in specific brain regions from exposure to psilocybin might account for alleviation in depressive symptoms 9. These findings are preliminary, but they have sparked the commencement of a few phase 2 randomized trials for psychedelic drugs.
It should be noted that all these trial to date — and those planned — require dosing to be done in a very controlled and supervised psychologically supportive environment. Which of these treatments will make it to market? That remains unclear, but it is reassuring that so many different novel paradigms for addressing treatment-resistant depression are in development.
Skip to main content.This article briefly reviews the pharmacology of this drug and its current investigative and clinical uses and adverse effects.
It also reports on our experience to date in the study of the drug in children, with emphasis on adverse effects noted so far in these younger patients. In ALS, a motor neuron disease that results in nerve cell degeneration in the central nervous system CNS and peripheral nervous system, riluzole has been reported to extend the time before the need for respirator use by some months Lacomblez et al. The mechanism of action of riluzole in the nervous system is complex. A considerable number of actions have been demonstrated in vitrobut some of these may have little relevance in vivowhere much lower concentrations of riluzole are achieved.
Pittenger and colleagues have recently reviewed the subject very capably Pittenger et al. Riluzole inhibits the release of glutamate at the presynaptic nerve cell terminus, most likely by blockade of voltage-gated sodium channels, and this effect may be achieved at low riluzole concentrations demonstrated most recently by Urbani and Belluzzi It also likely reduces glutamate neurotransmitter vesicle fusion with the presynaptic cell membrane, either directly by opening voltage-gated calcium channels Wang et al.
Riluzole's effects on potassium channels have also been measured, but possibly not at clinically meaningful riluzole concentrations Ahn et al. Downstream effects of riluzole have been noted as well, but clinical significance remains unclear.
These effects are stimulation of growth factor synthesis, including brain-derived neurotrophic factor Fumagalli et al. Riluzole has not been found to interact with any glutamate receptors at clinically meaningful concentrations Habibi-Asl et al.
Riluzole increases glial glutamate reuptake, possibly at the low levels found only extrasynaptically Frizzo et al. In the same study, the investigators demonstrated that metabolic and mRNA expression effects of stress were also attenuated by riluzole. These results are consistent with the evidence for the riluzole-enhanced reuptake of glutamate by glial cells.
There have been reports of riluzole effects on other neurotransmitters, but there has been little replication of these findings so far. A fatty meal delays or reduces absorption. Peak serum level in healthy volunteers is achieved after about 1—1. Steady-state levels at stable dose are achieved after about 5 days. Plasma elimination half-life ranges from about 9 to 14 hours, independently of dose.
Steady-state trough serum levels are significantly higher with larger doses, but values under the serum concentration—time curve do not change Le Liboux et al.Carolyn Rodriguez is a foremost expert on obsessive-compulsive disorder OCD and conducts cutting-edge research aimed at improving our understanding of the brain and suggesting new treatment possibilities for people around the world.
How did you get involved in researching OCD? Can you tell us a bit of your story? I saw firsthand the impact of mental illness in my extended family, and I became interested in how differences in our brains can shape differences in our behavior. I trained to be a psychiatrist and neuroscientist and seek improved treatments for mental illness.
Early in my career, I met someone with OCD. I was immediately struck not only by his private suffering, but also by all of the physical manifestations that made his life harder.
His distressing intrusive thoughts about contamination caused him to always wear gloves when he went outside. He washed his hands excessively. When he took his hands out of his gloves, they were red and raw. His pain made a big impression on me. I became curious about what might be driving these behaviors. I wondered how an obsession forms, and how it transitions into a disorder.
But where along the way do these types of thoughts and behaviors cross a line, becoming the condition we know as OCD? The diagnostic standard is that intrusive thoughts and repetitive behaviors that occupy more than 1 hour a day, cause distress, and interfere with daily functioning cross that line. As I treated more individuals with OCD, I became very frustrated by our current first-line treatments.
There is also often a lag time of months before substantial symptom relief is achieved.
Effect of a Novel NMDA Receptor Modulator, Rapastinel (Formerly GLYX-13), in OCD: Proof of Concept.
We urgently need more effective and faster-acting treatments for OCD. The mission of our lab is to innovate targeted, rapid-acting treatments and derive insights into the brain basis of OCD and related disorders in order to relieve patients' suffering. We collaborate across disciplines to accelerate the discovery of treatments. But we increasingly think of mental illnesses as the result of brain circuits gone awry. OCD symptoms are associated with hyperactivity in the thought control circuit, which is comprised of the orbitofrontal cortex important for decision-makingthe striatum motor movementand the thalamus a relay station back to the cortex.
The hyperactivity may be due to imbalances of chemical messengers, called neurotransmitters, like serotonin and glutamate. Increasing evidence indicates that glutamate plays a role in OCD symptoms. Ketamine— which at high doses is used primarily as an anesthetic— acts on brain receptors for glutamate, and has shown remarkable therapeutic effects in depression and other disorders. I led the first randomized proof-of-concept clinical trial comparing low-dose intravenous ketamine with placebo in fifteen OCD patients suffering from constant obsessions.
After a single ketamine infusion, half the patients met the response criterion 35 percent or greater reduction in the Yale-Brown Obsessive Compulsive Scale, or Y-BOCS, one week after infusion. The effect was rapid within hoursand patients reported remarkable benefit. The effects persisted long past the half-life of ketamine, suggesting that beneficial effects remained long after ketamine had been cleared from the body.
In some but not all individuals, the therapeutic effects persisted for two to four weeks. Although these results are promising, patients did report side effects, including transient dissociation— a temporary experience of detachment from reality. They reported that even though their obsessive thoughts went away, they still had an inclination to check. Like you, we are curious how obsessions influence compulsions, and we wonder how we can pull apart and understand these differences.
We are conducting a large, randomized NIMH-funded study to examine how ketamine acts on the building blocks of brain function: the receptor, the circuit, and the circuit network. It makes me wonder, though, how can medication and therapy can work together for someone who is trying to get better.