An interesting study looked at similarities and differences in the effects of two medications that have anti-depressant effects and yet are extremely different in terms of how they work: ketamine and imipramine (a tricyclic antidepressant). This industry supported study looked at the effects of these two agents on a reward circuit (involving the prefrontal cortex (PFC), nucleus accumbens, hippocampus, and amygdala – …
A Better Ketamine
A better ketamine may be coming. That is the conclusion of NEJM Journal Watch Psychiatry reviewer Barbara Geller. A common pathway to identifying new drugs, is looking at metabolites of a medication to see if there is one metabolite that works better than the active drug (desvenlafaxine – one of the metabolites of venlafaxine – may or may not be …
Rapastinel for Depression
The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to rapastinel, which follows the medication receiving a 2014 Fast Track Designation from the FDA. Rapastinel, an investigational medication for adjunctive treatment of major depressive disorder, is an intravenous drug that is a novel NMDA receptor agonist. It is being developed by Allergan. The Breakthrough Therapy designation is a new …
Ketamine for Depression Update
Probably the most exciting development in psychopharmacology in years is the discovery of the dramatic effects of ketamine on depression. However, a recent report from the American Psychiatric Association (APA) Task Force on Novel Biomarkers and Treatments highlights not only the reason for the excitement about ketamine but also the significant areas of uncertainty that make it not yet ready to …
NMDA Receptor and Depression
A new drug that stimulates the glycine site of NMDA receptors had rapid antidepressant effects in the just released results of a phase II clinical trial. The drug substantially reduced depression symptoms, with no severe side effects. The NMDA receptor has 2 sites that are involved in its activation. One site is stimulated by glutamate or aspartate. Another site is stimulated by glycine. For …
Anhedonia and Ketamine
Anhedonia, meaning the loss of the normal experience of pleasure in life, can be one of the most troubling symptoms of depression. And also one for which we have relatively few treatments. We know that a small group of dopamine neurons in the ventral tegmentum (limbic system) which project to the prefrontal cortex, among other locations in the brain, are …
Beta Catenin and Depression
Beta catenin is a molecule that may play a key role in preventing depression in those exposed to stress, at least if mice and humans share the same biology. Beta catenin is involved in a number of quite different functions in the cell. To give you an idea, it may be involved in the development of cancer (it is a …
Anhedonia Treatment with Ketamine
The treatment of anhedonia and bipolar depression can be very difficult. An article published in Translational Psychiatry in October of 2014 highlights the role of glutametergic transmission in anhedonia and points to the potentially unique efficacy of ketamine in treating this stubborn problem. Anhedonia, the lack (an-) of pleasure (-hedonia), is one of the 2 main symptoms of a major …
Ketamine for Depression – Mechanism of Action
Ketamine for Depression: How does it work? We ran across a useful review of the basic science literature in an interview of David Nichols on the Psych Congress Network. http://www.psychcongress.com/video/ketamine-quick-guide-receptors-19116 Although ketamine blocks the NMDA subtype of glutamate receptors (blocks an excitatory neurotransmitter) the net effect seems to be an increase in excitatory neurotransmission. This image from Nature may help …
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