{"id":128434,"date":"2025-05-24T16:23:08","date_gmt":"2025-05-24T16:23:08","guid":{"rendered":"https:\/\/www.europesays.com\/uk\/128434\/"},"modified":"2025-05-24T16:23:08","modified_gmt":"2025-05-24T16:23:08","slug":"boosting-ketamines-antidepressant-effects-to-last-two-months","status":"publish","type":"post","link":"https:\/\/www.europesays.com\/uk\/128434\/","title":{"rendered":"Boosting Ketamine\u2019s Antidepressant Effects to Last Two Months"},"content":{"rendered":"<p><strong>Summary: <\/strong>Ketamine is a fast-acting antidepressant that can relieve symptoms of major depressive disorder (MDD) within hours, even in treatment-resistant cases. However, its effects typically last only a week, and frequent dosing poses risks like dissociation or addiction.<\/p>\n<p>A new study demonstrates that ketamine\u2019s benefits can be extended up to two months by using a compound that enhances ERK signaling, a pathway essential to ketamine\u2019s long-term action. This breakthrough offers a proof of principle for safer, more sustained depression treatment strategies targeting intracellular mechanisms.<\/p>\n<p><strong>Key Facts:<\/strong><\/p>\n<ul class=\"wp-block-list\">\n<li><strong>Rapid-Acting Relief:<\/strong> Ketamine alleviates depression symptoms within hours, even in resistant patients.<\/li>\n<li><strong>Extended Efficacy:<\/strong> A compound called BCI prolonged ketamine\u2019s antidepressant effect up to two months.<\/li>\n<li><strong>Mechanism-Based Strategy:<\/strong> Enhancing ERK signaling may help sustain antidepressant effects from a single dose.<\/li>\n<\/ul>\n<p><strong>Source: <\/strong>Vanderbilt University<\/p>\n<p><strong>Roughly\u00a010 percent\u00a0of the U.S. population is afflicted with major depressive disorder at any given time, and up to 20 percent will exhibit MDD symptoms over their lifetimes.<\/strong><\/p>\n<p>Yet despite its prevalence, methods to treat MDD often fall short for a not-insignificant portion of the population. Antidepressants\u2014the standard of treatment\u2014don\u2019t work for 30 percent with MDD.<\/p>\n<p>When infused at a low dose ketamine shows remarkable efficacy as a rapidly acting antidepressant, with effects observed within hours even in patients who have been resistant to other antidepressant treatments.<\/p>\n<p>  <img fetchpriority=\"high\" decoding=\"async\" width=\"1200\" height=\"801\" src=\"https:\/\/www.europesays.com\/uk\/wp-content\/uploads\/2025\/05\/ketamine-antidepressant-effect-neuroscience.jpg\" alt=\"This shows a brain.\"  \/> By inhibiting the phosphatase, the authors retained ERK\u2019s activity and augmented the synaptic plasticity that drives ketamine\u2019s prolonged antidepressant effects. Credit: Neuroscience News<\/p>\n<p>However, consistent infusions of ketamine are needed to maintain symptoms at bay, which could result in side effects, such as dissociative behaviors and the possibility of addiction, and stopping treatment can result in relapse.<\/p>\n<p>In a new\u00a0study published in\u00a0Science,\u00a0Lisa Monteggia\u2019s and\u00a0Ege Kavalali\u2019s labs show that it is feasible to substantially extend the efficacy of a single dose of ketamine from its current duration of up to a week to a longer period of up to two months.<\/p>\n<p>\u00a0\u201cThe premise of this study, which was led by\u00a0Zhenzhong Ma, a fantastic research assistant professor, was based on a testable mechanistic model that we developed that accounts for ketamine\u2019s rapid antidepressant action,\u201d Monteggia said.<\/p>\n<p>Monteggia holds the Lee E. Limbird Chair in Pharmacology and is the Barlow Family Director of the Vanderbilt Brain Institute.<\/p>\n<p>Previously, researchers in the field had determined that ketamine\u2019s antidepressant effect requires the activation of a key signaling pathway called ERK, but only ketamine\u2019s long-term effects\u2014not its rapid effects\u2014are abolished when ERK is inhibited.<\/p>\n<p>As a fast-acting antidepressant, ketamine relies on ERK-dependent synaptic plasticity to produce its rapid behavioral effects. Ma and colleagues hypothesized that they could maintain ketamine\u2019s effects for longer periods by enhancing ERK activity.<\/p>\n<p>In the recent paper, Ma discovered that ketamine\u2019s antidepressant effects could be sustained for up to two months by using a drug called BCI, which inhibits a protein phosphatase and results in increased ERK activity.<\/p>\n<p>By inhibiting the phosphatase, the authors retained ERK\u2019s activity and augmented the synaptic plasticity that drives ketamine\u2019s prolonged antidepressant effects.<\/p>\n<p>Although the use of BCI make the application of these results to the clinic difficult, Monteggia said that the results provide a proof of principle that ketamine\u2019s antidepressant action can be sustained by targeting intracellular signaling.<\/p>\n<p>She and Kavalali, the William Stokes Professor of Experimental Therapeutics and the chair of the Department of Pharmacology, have worked on the project since its inception and hope that it fosters other studies looking to identify specific molecules that will enhance and sustain the action of a single dose of ketamine.<\/p>\n<p>Ultimately, this work will be a\u00a0steppingstone\u00a0toward improving MDD patients\u2019 lives by reducing the burden of treatment.<\/p>\n<p>About this psychopharmacology and depression research news<\/p>\n<p class=\"has-background\" style=\"background-color:#ffffe8\"><strong>Author: <\/strong><a href=\"http:\/\/neurosciencenews.com\/cdn-cgi\/l\/email-protection#8be6eaf9e2f8f8eaa5f8e3eafbe2f9e4cbfdeae5efeef9e9e2e7ffa5eeeffe\" target=\"_blank\" rel=\"noreferrer noopener\">Marissa Shapiro<\/a><br \/><strong>Source: <\/strong><a href=\"https:\/\/vanderbilt.edu\" target=\"_blank\" rel=\"noreferrer noopener\">Vanderbilt University<\/a><br \/><strong>Contact: <\/strong>Marissa Shapiro \u2013 Vanderbilt University<br \/><strong>Image: <\/strong>The image is credited to Neuroscience News<\/p>\n<p class=\"has-background\" style=\"background-color:#ffffe8\"><strong>Original Research: <\/strong>Closed access.<br \/>\u201c<a href=\"https:\/\/dx.doi.org\/10.1126\/science.abb6748\" target=\"_blank\" rel=\"noreferrer noopener\">Enhanced ERK activity extends ketamine\u2019s antidepressant effects by augmenting synaptic plasticity<\/a>\u201d by Lisa Monteggia et al. Science<\/p>\n<p><strong>Abstract<\/strong><\/p>\n<p><strong>Enhanced ERK activity extends ketamine\u2019s antidepressant effects by augmenting synaptic plasticity<\/strong><\/p>\n<p>Repeated ketamine treatment to maintain a rapid antidepressant effect can lead to side effects over time, highlighting an unmet clinical need for sustaining this drug\u2019s antidepressant action from a single administration.<\/p>\n<p>Ketamine-induced synaptic potentiation at CA3-CA1 synapses has been proposed to be a key synaptic substrate for antidepressant action.<\/p>\n<p>Here, we found that ketamine-induced CA3-CA1 synaptic potentiation could be augmented by transiently increasing extracellular signal\u2013regulated kinase (ERK) activity through pharmacological inhibition of dual-specificity phosphatases 6 (DUSP6).<\/p>\n<p>The antidepressant-like behavioral effects of acute ketamine treatment were extended by DUSP6 inhibition for up to 2 months.<\/p>\n<p>The selective deletion of tropomyosin receptor kinase B (TrkB) in excitatory neurons abolished these DUSP6 inhibition\u2013mediated synaptic and behavioral effects.<\/p>\n<p>These data suggest that ketamine\u2019s rapid antidepressant effects can be sustained by selectively targeting downstream intracellular signaling.<\/p>\n","protected":false},"excerpt":{"rendered":"Summary: Ketamine is a fast-acting antidepressant that can relieve symptoms of major depressive disorder (MDD) within hours, even&hellip;\n","protected":false},"author":2,"featured_media":128435,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[11],"tags":[39564,215,1301,56638,105,29421,218,219,220,222,13971,757,16,15,51220],"class_list":{"0":"post-128434","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-health","8":"tag-antidepressants","9":"tag-brain-research","10":"tag-depression","11":"tag-erk","12":"tag-health","13":"tag-ketamine","14":"tag-mental-health","15":"tag-neurobiology","16":"tag-neuroscience","17":"tag-psychology","18":"tag-psychopharmacology","19":"tag-synaptic-plasticity","20":"tag-uk","21":"tag-united-kingdom","22":"tag-vanderbilt-university"},"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@uk\/114563737396169358","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts\/128434","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/comments?post=128434"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts\/128434\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/media\/128435"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/media?parent=128434"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/categories?post=128434"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/tags?post=128434"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}