Suicidal Ideation – though related to depression and anxiety – may be a separate Medical Target
Recent studies indicate that the anti-suicidal effect of NMDA antagonists - such as ketamine - is not due solely to the antidepressant or anti-anxiety effects of these drugs.1,2,3
Hence, Suicidal Ideation though it may be present in psychiatric disorders such as Bipolar Depression, PTSD, and Major Depressive Disorder, may be thought of as a distinct target (medical indication).
The N-methyl-D-aspartate (NMDA) receptor is a glutamate receptor found in nerve cells. It is critical to the memory function as it controls signaling from neuron to neuron. NMDA also directly regulates a calcium ion channel that controls the rate of ideation (formation of new ideas) in the brain.
The NMDA channel can be thought of as a gate for calcium ions, regulating the rate at which new thoughts are produced in the brain. At excessive rates of NMDA activity, thoughts and the rate at which new thoughts are generated (ideation) is slowed. People tend to ruminate on those few thoughts, which are often negative and self-destructive in nature. When the NMDA channel is blocked, thoughts are generated rapidly and, often incoherently, leading to hallucinations and psychosis. The challenge is to strike a healthy balance and to maintain thought generation at a pace that is consistent with clear and creative thinking.
NeuroRx’s Co-Founder, and Chair of our Scientific Advisory Board, Prof. Daniel Javitt, M.D., Ph.D., has 30 years of basic science and clinical expertise in understanding the role of the brain’s NMDA receptor in regulating human thought processes and in regulating depression and suicidality. Additionally, recent scientific breakthroughs have indicated that the chemical target for suicidality in bipolar depression may be localized in the brain’s NMDA receptor.
D-cycloserine is an FDA–approved anti-infective, primarily used for the treatment of tuberculosis. Although it’s anti-infective activity is based on its ability to disrupt bacterial cell walls, it also acts as an NMDA antagonist when used at high doses (> 750 mg). By targeting the NMDA receptor and modulating NMDA activity,
D-cycloserine seems to foster a normal pace of thought generation. Multiple human studies have demonstrated that administration of D-cycloserine triggers an antidepressant effect.
It is important to note that the American Psychiatric Association published a task force report in October 2015 identifying D-cycloserine as one of the most promising, clinical stage, orally-active drugs for the NMDA target.4
NeuroRx is pursuing a strategic combination
treatment approach based on scientific rationale that supports pairing a NMDA
antagonist with additional therapeutic targets in the treatment of Acute Suicidal Ideation/Behavior (ASIB) when it is part of psychiatric disorders, including Bipolar Depression and PTSD.