Trial reportBiological psychiatry2025
Effects of the KCNQ (Kv7) Channel Opener Ezogabine on Resting-State Functional Connectivity of Striatal Brain Reward Regions, Depression, and Anhedonia in Major Depressive Disorder: Results From a Randomized Controlled Trial.
Trial report in Biological psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed.
- Towards precision psychiatry: initial foundations and future directions.Nature reviews. Drug discovery · 2026Review
- Probing biomarkers and clinical utility of reward learning across species using the Probabilistic Reward Task: 20 years of findings.Nature. Mental health · 2026Article
- Synaptic Plasticity-Intrinsic Excitability and Antidepressant Discovery.Biomedicines · 2026Review
- Negative Contextual Valence Unmasks Altered Counterfactual Decision-Making in Major Depressive Disorder.medRxiv : the preprint server for health sciences · 2026Article
- Intermittent Theta-Burst Stimulation (iTBS) Modulates Abnormal Brain Activity During Emotional Arousal in Adolescent Depression: A Pilot Study.Brain topography · 2026Article
- The nature of depression and the biomedical model: ten questions in search of an answer.Translational psychiatry · 2026Review
- VTA network dominance in depression confers distinct psychopathological states through blunted neural tracking of reward prediction errors.Research square · 2025Article
- The Pathogenesis and Medical Treatment of Depression: Opportunity and Challenge.Neurology international · 2025Review
- Neuropeptidergic systems in psychiatric disorders.Frontiers in endocrinology · 2025Review
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
backgroundMajor depressive disorder (MDD) is a leading cause of disability worldwide, with available treatments often showing limited efficacy. Recent research suggests that targeting specific subtypes of depression and understanding the underlying brain mechanisms can improve treatment outcomes. This study investigates the potential of the potassium KCNQ (Kv7) channel opener ezogabine to modulate the resting-state functional connectivity (RSFC) of the brain's reward circuitry and alleviate depressive symptoms, including anhedonia, a core feature of MDD.
methodsA double-blind, randomized, placebo-controlled clinical trial in individuals with MDD ages 18 to 65 years compared daily dosing with ezogabine (n= 19) with placebo (n = 21) for 5 weeks. Functional magnetic resonance imaging assessed RSFC of the brain's key reward regions (ventral caudate, nucleus accumbens) at baseline and posttreatment. Clinical symptoms were measured using the Snaith-Hamilton Pleasure Scale (SHAPS), Montgomery-Åsberg Depression Rating Scale (MADRS), and other clinical symptom scales.
resultsEzogabine significantly reduced RSFC between the reward seeds and the posterior cingulate cortex (PCC)/precuneus compared with placebo, which was associated with a reduction in depression severity. Improvements in anhedonia (SHAPS) and depressive symptoms (MADRS) with ezogabine compared with placebo were also associated with decreased connectivity between the reward seeds and mid/posterior cingulate regions (midcingulate cortex, PCC, precuneus).
conclusionsThe findings suggest that ezogabine's antidepressant effects are mediated through modulation of striatal-mid/posterior cingulate connectivity, indicating a potential therapeutic mechanism for KCNQ-targeted drugs for MDD and anhedonia. Future studies should validate these results in larger trials.
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