Study: Ketamine more effective than common sedative in reducing suicidal thoughts

In continuation of my update on ketamine

Ketamine was significantly more effective than a commonly used sedative in reducing suicidal thoughts in depressed patients, according to researchers at Columbia University Medical Center (CUMC). They also found that ketamine's anti-suicidal effects occurred within hours after its administration.

The findings were published online last week in the American Journal of Psychiatry.

According to the Centers for Disease Control and Prevention, suicide rates in the U.S. increased by 26.5 percent between 1999 and 2015.

"There is a critical window in which depressed patients who are suicidal need rapid relief to prevent self-harm," said Michael Grunebaum, MD, a research psychiatrist at CUMC, who led the study. "Currently available antidepressants can be effective in reducing suicidal thoughts in patients with depression, but they can take weeks to have an effect. Suicidal, depressed patients need treatments that are rapidly effective in reducing suicidal thoughts when they are at highest risk. Currently, there is no such treatment for rapid relief of suicidal thoughts in depressed patients."

Most antidepressant trials have excluded patients with suicidal thoughts and behavior, limiting data on the effectiveness of antidepressants in this population. However, previous studies have shown that low doses of ketamine, an anesthetic drug, causes a rapid reduction in depression symptoms and may be accompanied by a decrease in suicidal thoughts.

The 80 depressed adults with clinically significant suicidal thoughts who enrolled in this study were randomly assigned to receive an infusion of low-dose ketamine or midazolam, a sedative. Within 24 hours, the ketamine group had a clinically significant reduction in suicidal thoughts that was greater than with the midazolam group. The improvement in suicidal thoughts and depression in the ketamine group appeared to persist for up to six weeks.

Those in the ketamine group also had greater improvement in overall mood, depression, and fatigue compared with the midazolam group. Ketamine's effect on depression accounted for approximately one-third of its effect on suicidal thoughts, suggesting the treatment has a specific anti-suicidal effect.

Side effects, mainly dissociation (feeling spacey) and an increase in blood pressure during the infusion, were mild to moderate and typically resolved within minutes to hours after receiving ketamine.

"This study shows that ketamine offers promise as a rapidly acting treatment for reducing suicidal thoughts in patients with depression," said Dr. Grunebaum. "Additional research to evaluate ketamine's antidepressant and anti-suicidal effects may pave the way for the development of new antidepressant medications that are faster acting and have the potential to help individuals who do not respond to currently available treatments."

Study: Ketamine more effective than common sedative in reducing suicidal thoughts

Understanding potential of illicit drug ketamine in treating depression

In continuation of my update on Ketamine 

Advancing the understanding and treatment of psychiatric disorders is
a principal goal of neuroscientists. As mental disorders are the
leading cause of disabilities worldwide, it is concerning that there are
few effective therapeutics on the market due to the lack of knowledge
regarding pathophysiology. In particular, the main treatment for major
depressive disorders are antidepressants, which target the monoaminergic
system and include selective serotonin reuptake inhibitors (SSRIs).
However, these drugs take six weeks on average before symptom relief and
many individuals are unaffected by them.

Ketamine, a synthetic analogue of PCP, has recently taken the
spotlight as a novel, fast-acting antidepressant. The benefits of
ketamine include a one-time, low-dose IV infusion, where symptoms are
alleviated within hours and which lasts for up to two weeks in patients
with depression. Even more compelling is that this regimen affects
patients with treatment-resistant depression, meaning those who do not
respond to current antidepressants. These effects are especially
important in helping individuals with depression who may be experiencing
suicidal ideation because of ketamine's fast-acting nature and it is
the only treatment effective for treatment resistant patients.

However, there are many downsides to the use of ketamine as an
antidepressant, especially with long-term or repeated use. For example,
ketamine is an illicit drug with high abuse potential, commonly known as
the party drug "Special K." Therefore, close clinical monitoring of the
use of this drug is necessary. In regards to neuroscience research in
the past decade, it has been demonstrated that chronic, low-dose
ketamine has been used to study learning and memory deficits in a rodent
model of schizophrenia. The biochemical data from these animals reveal a
change in a specific type of neuron in the brain that is important for
network activity underlying normal cognitive functioning. This begs the
question: Can ketamine work as an antidepressant without producing
cognitive deficits associated long-term use?

In order to address this question, we need to understand the molecular
mechanisms that ketamine is utilizing to produce these beneficial
antidepressant effects. Although researchers do not know exactly how
ketamine works, we know that it is in a different way than current
antidepressants on the market. There is no clear answer yet, but researchers have produced some promising results. Using ketamine to
deepen our understanding of depression will advance the field of neuroscience and ultimately lead to a more effective treatment for the  disorder.

New antidepressant acts very rapidly and is long lasting

A first-of-its-kind antidepressant drug discovered by a Northwestern University professor and now tested on adults who have failed other antidepressant therapies has been shown to alleviate symptoms within hours, have good safety and produce positive effects that last for about seven days from a single dose.

The compound, called GLYX-13, (see the structure) is the result of more than two decades of work by Joseph Moskal, research professor of biomedical engineering at Northwestern's McCormick School of Engineering and Applied Science and director of the University's Falk Center for Molecular Therapeutics.

"Our study showed that this compound is capable of eliciting a robust and rapid antidepressant effect without the typical side effects seen with other drugs that also modulate the NMDA receptor," said Moskal, who is founder and chief scientific officer of the Evanston-based biotechnology company Naurex Inc., which conducted the clinical study.

GLYX-13 works by modulating the NMDA (N-methyl-D-aspartate) receptor in the brain, as do current NMDA receptor antagonists such as ketamine, but GLYX-13 does not have their serious and limiting side effects, such as hallucinations and schizophrenia-like effects. (An antagonist is a substance that inhibits the physiological action of another.)

The positive effects of GLYX-13 were evident within 24 hours and lasted an average of seven days. The effect size, a measure of the magnitude of the drug's antidepressant efficacy, at both these times after a single dose was nearly double the effect size seen with most other antidepressant drugs after four to six weeks of repeated dosing.

Side effects of GLYX-13 were mild to moderate and were consistent with those observed in subjects receiving a placebo.

GLYX-13 is a four-amino acid peptide that modulates one of a large family of glutamate receptors, the NMDA (N-methyl-D-aspartate) receptor, in the brain. NMDA receptors play a key role in regulating synaptic plasticity -- the quality of the connection between neurons -- and thus are important in regulating learning and memory functions.

GLYX-13 is administered intravenously. Moskal said Naurex also is working on an oral drug with similar properties and potential.

Moskal hopes that these positive GLYX-13 results and the research efforts of his team and colleagues will help shepherd in more research and grant support for studying the role of the glutamate-mediated processes in neuropsychiatric disorders...

Ref : http://www.nature.com/npp/journal/vaop/naam/abs/npp2012246a.html

New antidepressant acts very rapidly and is long lasting