Prolonging the Antidepressant Efficacy of Ketamine for a Duration of Two Months

Prolonging the Antidepressant Efficacy of Ketamine for a Duration of Two Months

Breakthrough Research Extension of Ketamine's Antidepressant Effects

A groundbreaking study published in Science, led by researchers at Vanderbilt University, has discovered a way to significantly prolong the antidepressant effects of ketamine, a rapid-acting antidepressant, from up to a week to up to two months.

The study, conducted by Lisa Monteggia and Ege Kavalali, found that a compound called BCI, which enhances ERK signaling, a key pathway in ketamine's long-term action, could extend ketamine's antidepressant benefits. This potential solution offers a viable approach towards safer, sustained depression treatment strategies that target intracellular mechanisms.

Approximately 10% of the U.S. population and 20% of individuals throughout their lifetime grapple with major depressive disorder (MDD). For a considerable number of these individuals, existing antidepressants are ineffective. Ketamine, however, demonstrates remarkable efficacy in treating MDD within hours, even in patients resistant to other antidepressant treatments.

Despite its rapid effects, the need for frequent ketamine infusions to maintain symptom relief raises concerns about side effects, including dissociative behaviors and the risk of addiction. This new research may pave the way for reduced treatment burden and fewer side effects for MDD patients.

Monteggia, holding the Lee E. Limbird Chair in Pharmacology and the Barlow Family Director of the Vanderbilt Brain Institute, explained the study's premise, which was based on a mechanistic model accounting for ketamine's rapid antidepressant action. Previous research had established that ketamine's antidepressant effect required the activation of the ERK signaling pathway, although only long-term effects—not the rapid effects—were abolished when ERK was inhibited.

To prolong ketamine's effects, researchers hypothesized that they could maintain ERK activity and, consequently, synaptic plasticity, which drives ketamine's antidepressant effects. Using BCI, a drug that inhibits a protein phosphatase and results in increased ERK activity, they achieved exactly that, leading to sustained antidepressant effects for up to two months.

While the use of BCI makes the clinical application of this research challenging, the results provide a proof of principle that ketamine's antidepressant action can be sustained by targeting intracellular signaling. Researchers hope this work fosters further studies exploring specific molecules that will enhance and sustain the action of a single dose of ketamine, ultimately aiming to improve MDD patients' lives by reducing the treatment burden.

About this psychopharmacology and depression research news:

Author: Marissa ShapiroSource: Vanderbilt UniversityContact: Marissa Shapiro - Vanderbilt UniversityImage: Credit to our website

Original Research: Closed access.

"Enhanced ERK activity extends ketamine's antidepressant effects by augmenting synaptic plasticity" by Lisa Monteggia et al., Science.

Key Facts:

• Rapid-Acting Relief: Ketamine alleviates depression symptoms within hours, even in resistant patients.
• Extended Efficacy: A compound called BCI prolonged ketamine's antidepressant effect up to two months.
• Mechanism-Based Strategy: Enhancing ERK signaling may help sustain antidepressant effects from a single dose.

Approximately 10% of the U.S. population and up to 20% over their lifetimes are afflicted by major depressive disorder (MDD). Although methods to treat MDD often fall short for a significant portion of the population, a new study published in Science has provided a promising breakthrough for depression treatment. By using a compound called BCI, which enhances ERK signaling, a key pathway in ketamine's long-term action, researchers extended ketamine's antidepressant effects, potentially paving the way for reduced treatment burden and fewer side effects for MDD patients.

ERK (extracellular signal–regulated kinase) signaling plays a pivotal role in ketamine's antidepressant action: it promotes the synthesis of proteins supporting synaptic strengthening and neural circuit remodeling, critical components driving the antidepressant action of ketamine. In the study, researchers found that by inhibiting a protein phosphatase, DUSP6, they could retain ERK's activity and augment synaptic plasticity, leading to a prolonged antidepressant response lasting up to two months. These findings offer hope for the development of sustained, safer depression treatment strategies based on intracellular mechanisms.

While the use of BCI makes clinical application challenging, the study provides a crucial proof of principle for future research investigating specific molecules that enhance and sustain the action of a single dose of ketamine. Future studies may bring us one step closer to better depression treatment and potentially transform how depression is managed in clinical practice.

1. The study published in Science, led by researchers at Vanderbilt University, discovered a compound called BCI that can extend ketamine's antidepressant effects from up to a week to up to two months.
2. This new research in neuroscience offers a viable approach towards safer, sustained depression treatment strategies, targeting intracellular mechanisms for improved mental health and health-and-wellness.
3. Key to this breakthrough is the role of ERK (extracellular signal–regulated kinase) signaling, which plays a pivotal role in ketamine's antidepressant action, promoting synaptic strengthening and neural circuit remodeling.
4. Further advancements in neuroscience news, such as the identification of specific molecules to enhance and sustain the action of a single dose of ketamine, could pave the way for better depression treatment and transform how depression is managed in mental-health therapies-and-treatments.

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