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Propofol for depression: mechanisms and therapeutic potential
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DOI：10.3389/fphys.2026.1876988.png)
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Abstract
En 中文
Propofol; one of the most widely used intravenous anesthetics; is undergoing a transformative identity shift from a purely surgical agent to a potential therapeutic tool for neuropsychiatric disorders. This review synthesizes current evidence on the emerging field of propofol therapeutics; with a focus on its rapid antidepressant; anti-anhedonia; and anxiolytic effects. We first examine preliminary clinical evidence from open-label studies suggesting that propofol may produce dose-dependent mood-elevating effects in treatment-resistant depression; however; this evidence remains limited by small sample sizes and lack of large controlled trials. Next; we explore putative mechanisms; including GABAA receptor modulation; dopamine transporter inhibition; BDNF/TrkB signaling; and network-level reorganization of the default mode network and sleep architecture. We then compare propofol with other anesthetic agents possessing antidepressant properties; particularly ketamine; highlighting their distinct receptor targets; efficacy profiles; and safety considerations. Finally; we discuss major challenges including optimal dosing strategies; tolerance with repeated administration; long-term safety concerns; and implementation barriers. Despite these challenges; propofol represents a promising candidate for anesthetic repurposing in psychiatry; offering a mechanistically distinct alternative to ketamine that targets both GABAergic and dopaminergic systems with a well-established clinical safety profile for surgical anesthesia.
Keywords:
depression
drug repurposing
anesthesia
propofol
treatment-resistant depression
GABAergic transmission
rapid antidepressant
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3.4
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1.9W
Citations:
6.2W
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