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Ketamine — A New Drug Treatment For Depression?

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Credit: Koratmember at FreeDigitalPhotos.net

Remember ketamine, the old veterinary (and sometimes street) drug? Apparently it rapidly and significantly reduces anhedonia in those with treatment-resistant bipolar disorder, according to a new study.

Anhedonia, which is a lack of interest in activities that once gave a person pleasure, is a key feature of treatment-resistant bipolar disorder. According to a recent NIH-funded clinical trial, ketamine restored pleasure-seeking behavior independent of its other antidepressant properties in these patients. What’s more, it did so about 40 minutes after a single infusion, and the effect lasted as long as 14 days.

To me the most interesting part of this study is that ketamine did not act on the midbrain areas typically involved in depressive symptoms. Rather, PET scans on patients in the depressive phase of bipolar disorder showed that after ketamine infusion, there was activity in the dorsal anterior cingulate cortex (dACC). This region lies deep within the brain, resting on the medial surface of the frontal lobes. Its precise role remains somewhat elusive, though it is thought to govern conscious control of goal-directed behavior. The most recent significant study I could find on its function was a 2012 paper in Nature suggesting that the dACC is involved in optimizing behavioral adaptations to continuously evolving demands by predicting the difficulty of a task.

“Our findings help to deconstruct what has traditionally been lumped together as depression,” explained Carlos Zarate, M.D., of NIMH. “We break out a component that responds uniquely to a treatment that works through different brain systems than conventional antidepressants — and link that response to different circuitry than other depression symptoms.”

Imaging studies similar to the one just published are underway in patients with major depression, though results are not yet available. Other studies have suggested that ketamine may be exerting these effects through glutamate and dopamine pathways. Research is underway to explore easier methods of drug delivery, such as nasal spray.

Of late, ketamine has been studied for its rapid antidepressant properties, providing relief within hours rather than the weeks required for traditional medications to work. At present, ketamine is not FDA approved for treatment of depression and it is still used primarily in a veterinary setting.

Ketamine is an NMDA receptor antagonist, though it also inhibits reuptake of dopamine, serotonin, and norepinephrine. It was developed in 1962 and has been used in both humans and animals. It is categorized as a dissociative agent. It has been used for general anesthesia, sedation, and as a pain killer. Side effects include amnesia and agitation, and its street use has led to hallucinations, delirium, and death.

Now that NIH NCATS Is Replacing NCRR, Where Have The NCRR Programs Gone?

It has been over a year since NIH Director Francis Collins announced the creation of the National Center for Advancing Translational Science. From the NIH website:  “The goal of NCATS will be to develop new ways of doing translational research that the public and private research and development communities can adopt. Innovations that come out of NCATS are intended to cut down the time or expense needed to develop a new drug, or allow us to predict which compounds will work best and be safe earlier in development.”

CLICK HERE for more information on the mission of NCATS.

One casualty of the formation of NCATS has been the National Center for Research Resources (NCRR.) Where have the NCRR programs gone? Two have wound up at NIGMS. From a NIGMS blog post by Judith Greenberg:

“In the first major reorganization of NIGMS since 1994, we have just established two new divisions that bring together existing NIGMS programs with programs transferred to NIGMS from the former National Center for Research Resources (NCRR). These changes give us the opportunity to create synergies and strengthen efforts in areas that are central to our mission.

“The Division of Training, Workforce Development, and Diversity (TWD) merges NIGMS research training programs with activities that were previously in the Institute’s Division of Minority Opportunities in Research (MORE). It also houses the Institutional Development Award program from NCRR. Our decision to create this division was informed by input we received from many stakeholders, and it responds to key goals and recommendations of our strategic plans. Its director is Clif Poodry, who formerly directed the MORE Division.

“The Division of Biomedical Technology, Bioinformatics, and Computational Biology (BBCB) combines programs of our Center for Bioinformatics and Computational Biology (CBCB) with biomedical technology programs from NCRR. Karin Remington, who previously directed CBCB, is the director of this new division.

“You might be wondering what the reorganization will mean for your current or future funding. The amount of money allocated to programs in the new divisions will not change as a result of the reorganization or the transfer of NCRR programs to NIGMS. The review of applications will stay the same, too, as will most of the staff who manage the grants and review the applications.”

 

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