Trends in research on novel antidepressant treatments.
Agnieszka Zelek-Molik, Ewa Litwa
Frontiers in Pharmacology 2025 DOI: 10.3389/fphar.2025.1544795 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Depression Ketamine |
| Keywords | Raad Trd Animal models Psylocin Depression therapy Rapid antidepressants Antidepressant research |
| Citations | 19 |
| Key findings | Rapid-acting antidepressants with multi-directional mechanisms offer potential for high efficacy in treatment-resistant depression, with animal models remaining crucial for guiding development. |
Abstract
Mood disorders, such as major depressive disorder and bipolar disorder, are among the most common mental illnesses and a leading cause of disability worldwide. Key symptoms of these conditions include a depressed mood or anhedonia, sleep and psychomotor disturbances, changes in appetite or weight, and fatigue or loss of energy. Prolonged cognitive disturbances further impair the ability to think or concentrate and are often accompanied by persistent feelings of worthlessness or excessive guilt. Collectively, these symptoms underscore depression as a serious, long-term global health issue. In addition, clinical studies indicate a growing number of patients experiencing difficulties in responding to treatment, even in the long term. This phenomenon poses significant challenges for healthcare professionals, families, and patients alike. As a result, there is an urgent need for therapies that are both rapid-acting and safe. This review aims to summarize the prevailing trends in research on novel antidepressants, emphasizing their diversity and multi-directional mechanisms of action. The development of rapid-acting drugs is increasingly focused on achieving high efficacy, particularly for treatment-resistant depression. Such advances offer the potential for rapid therapeutic effects without the prolonged and often tedious administration of older generation antidepressants. Findings from studies using animal models of depression continue to play a crucial role in predicting and designing new therapeutic strategies. These models remain indispensable for understanding the physiological effects of newly developed compounds, thereby guiding the creation of innovative treatments.
Comparable studies
Other narrative reviews on ketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| 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 | |
| Ketamine: a paradigm shift for depression research and treatment | 2019 | Review | |
| Rapid‐acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective | 2019 | Review | |
| Ketamine: A tale of two enantiomers | 2020 | Review | |
| Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor | 2021 | Review |
Citations in the library
Cited by 3
- A review of the therapeutic and neuroprotective properties of ketamine Medical Science of Ukraine June 30, 2026
- Next-Generation Pharmacotherapy for Depressive Disorders: From Novel Compounds to Optimized Use of Available Drugs. Drug Design, Development and Therapy 2026
- Appetite measures during ketamine administration in treatment-resistant mood disorders: a naturalistic study. Frontiers in Nutrition August 21, 2026
Cites 20
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels Neuropsychopharmacology January 26, 2019
- Psychedelics promote plasticity by directly binding to BDNF receptor TrkB Nature Neuroscience June 1, 2023
- Single-dose infusion ketamine and non-ketamine N-methyl-D-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories Psychological Medicine February 12, 2016
- Hallucinogens and Serotonin 5-HT2A Receptor-Mediated Signaling Pathways Current Topics in Behavioral Neurosciences 2017
and 15 more in the library