Propofol for depression: mechanisms and therapeutic potential
Dan Yu, Ye Liao, Jie Li, Aiqiu Zheng, Xin Meng, Shumin Gong, Can Li, K.Y. Wu
Frontiers in Physiology August 10, 2026 DOI: 10.3389/fphys.2026.1876988 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Open-label Peer reviewed |
|---|---|
| Intervention | Propofol |
| Topics | Depression |
| Key findings | The authors argue that propofol is a promising candidate for anesthetic repurposing in psychiatry, offering a mechanistically distinct alternative to ketamine that targets both GABAergic and dopaminergic systems. They report that preliminary open-label evidence suggests dose-dependent mood-elevating effects in treatment-resistant depression, while cautioning that this evidence remains limited by small sample sizes and lack of large controlled trials. |
Abstract
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 GABA A 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.
Comparable studies
Other narrative reviews on depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Synaptic Dysfunction in Depression: Potential Therapeutic Targets | 2012 | Review | |
| Mindfulness-Based Cognitive Therapy for Depression: A New Approach to Preventing Relapse | 2003 | Review | |
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. General population | 2019 | Integrative review | |
| Sudarshan Kriya Yogic Breathing in the Treatment of Stress, Anxiety, and Depression: Part II—Clinical Applications and Guidelines | 2005 | Review |
Citations in the library
Cites 18
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
- Ketamine: a paradigm shift for depression research and treatment Neuron March 1, 2019
and 13 more in the library