Investigational drugs in recent clinical trials for treatment-resistant depression
Ricardo Pablo Garay, Carlos A. Zarate, Thomas Charpeaud, Leslie Citrome, Christoph Ulrich Correll, Ahcène Hameg, Pierre-Michel Llorca
Expert Review of Neurotherapeutics January 16, 2017 DOI: 10.1080/14737175.2017.1283217 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Interventions | Ketamine intranasal esketamine AVP-786 AVP-923 AV-101 rapastinel monoclonal antibodies |
| Topics | Depression |
| Citations | 79 |
| Key findings | The authors report that a single intravenous ketamine dose produces a robust, rapid antidepressant effect in treatment-resistant depression that stays significant for one week, and argue that glutamatergic modulators are a promising alternative to monoaminergic antidepressant monotherapy, with a rapid-acting antidepressant possibly arriving soon. |
Abstract
INTRODUCTION: The authors describe the medications for treatment-resistant depression (TRD) in phase II/III of clinical development in the EU and USA and provide an opinion on how current treatment can be improved in the near future. Areas covered: Sixty-two trials were identified in US and EU clinical trial registries that included six investigational compounds in recent phase III development and 12 others in recent phase II clinical trials. Glutamatergic agents have been the focus of many studies. A single intravenous dose of the glutamatergic modulator ketamine produces a robust and rapid antidepressant effect in persons with TRD; this effect continues to remain significant for 1 week. This observation was a turning point that opened the way for other, more selective glutamatergic modulators (intranasal esketamine, AVP-786, AVP-923, AV-101, and rapastinel). Of the remaining compounds, monoclonal antibodies open highly innovative therapeutic options, based on new pathophysiological approaches to depression. Expert commentary: Promising new agents are emerging for TRD treatment. Glutamatergic modulators likely represent a very promising alternative to monoaminergic antidepressant monotherapy. We could see the arrival of the first robust and rapid acting antidepressant drug in the near future, which would strongly facilitate the ultimate goal of recovery in persons with TRD.
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
Cited by 12
- Ketamine and rapid-acting antidepressants: a new era in the battle against depression and suicide F1000Research May 24, 2018
- Ketamine for the treatment of mental health and substance use disorders: comprehensive systematic review BJPsych Open December 23, 2021
- Novel drug developmental strategies for treatment‐resistant depression British Journal of Pharmacology November 25, 2021
- Rapid-acting antidepressants. Advances in pharmacology (San Diego, Calif.) 2019
- Rapid-Acting Antidepressants Current Pharmaceutical Design October 19, 2018
and 7 more in the library
Cites 25
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Ketamine Anesthesia & Analgesia November 1, 1998
and 20 more in the library