New Drug Combo Involving Ketamine Shows Promise for Bipolar Depression

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Adding two existing medications to the drug ketamine, which has been shown in previous studies to provide a rapid — though short-lived — antidepressant effect, may prolong the effect of the ketamine and effectively reduce symptoms of depression and suicidality in patients with bipolar depression, according to a small study.

Researchers at Columbia University, led by Joshua Kantrowitz, MD, an assistant professor of psychiatry, conducted an open label study in eight patients who were suffering from bipolar depression. The participants were randomly assigned to one of several drugs commonly prescribed for the condition. Four of them were taking the drug lurasidone (Latuda), which is approved for bipolar depression. Two of them were taking a combination of olanzapine (Zyprexa)/fluoxetine (Prozac). And the other two were taking quetiapine (Seroquel).

 After nearly four weeks, the participants, on average, showed no improvement.

The subjects then received ketamine. The following day, the subjects were given the drug D-cycloserine, which is used in the treatment of tuberculosis, and continued on it for eight weeks. Unlike most antidepressants on the market that target the brain’s serotonin pathway, ketamine and D-cycloserine target the brain’s NMDA receptors (NMDAR).

When given the combination of their existing regimen, ketamine and D-cycloserine, the subjects showed a 50% reduction in depression symptoms and a 75% reduction in suicidality, the researchers reported in the Journal of Clinical Psychiatry. In addition, results indicated that the D-cycloserine helped to maintain the benefits of the ketamine over eight weeks as the participants remained on their starting regimen.  

“These findings provide proof-of-concept for further study of combined treatment with NMDAR antagonists and FDA-approved medications for bipolar depression,” the researchers wrote.

A small pharmaceutical company, NeuroRx, Inc., is developing a staged treatment approach involving ketamine administration followed by a combination, known as Cyclurad, of D-cycloserine and lurasidone, to maintain the effect of ketamine. Although the Columbia study is the second human study demonstrating the antidepressant effect of D-cycloserine, it is the first one to use the combination of D-cycloserine and lurasidone following ketamine infusion.

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Adding two existing drugs following an infusion of ketamine helped prolong the antidepressant effects of ketamine in small study.

NeuroRx, Inc., a clinical phase pharmaceutical company, reports first-in-man efficacy data for a newly-purposed class of drugs targeted towards rapidly reducing symptoms of depression and suicidality in patients with bipolar disorder and maintaining that effect over time. The peer-reviewed open label study in eight patients, elements of which were published in the Journal of Clinical Psychiatry, demonstrated a 50% reduction in symptoms of depression and a 75% reduction in suicidality in patients with treatment-resistant bipolar depression.

While the use of ketamine for rapid reversal of depression is known, though not yet approved by FDA, its effect is known to be short-lived. This is the first clinical report showing that the ketamine effect can potentially be sustained for two months with additional agents.

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