Despite significant advances in neuroscience, pharmacologic treatment options for depression and psychosis remain limited by incomplete efficacy, treatment resistance, and substantial side effect burden. This session will review emerging medications and novel mechanisms of action that have the potential to transform treatment approaches for these disabling disorders.
The course will begin with a discussion of rapid-acting antidepressants, focusing on ketamine and S-ketamine, which have demonstrated superior efficacy compared to standard treatments and non-inferiority to electroconvulsive therapy in treatment-resistant depression. The neurobiological mechanisms underlying their effects—including restoration of glutamate synaptic function, synaptogenesis, and anti-inflammatory actions—will be explored, along with concepts of homeostatic and non-homeostatic neuroplasticity. Additional novel antidepressant strategies targeting neuroplasticity will be reviewed, including classical psychedelics such as psilocybin, MDMA-assisted approaches, Kv7 agonists, 5-HT1A agonists, and kappa opioid receptor antagonists with anti-anhedonic properties.
The session will also examine new approaches to the treatment of psychosis that move beyond dopamine receptor antagonism, which has historically been associated with significant neurological, endocrine, and metabolic adverse effects and limited efficacy for many patients. Faculty will review emerging pharmacologic strategies that modulate dopaminergic signaling without direct receptor blockade, including muscarinic receptor agonists and positive allosteric modulators, trace amine-associated receptor 1 (TAAR1) agonists, glutamatergic modulators, PDE10 inhibitors, and agents acting on serotonin and sigma receptors. Particular attention will be given to clinical data on efficacy, tolerability, and safety, including the recently available combination medication xanomeline–trospium.
Through an evidence-based review of these novel therapies, this session will equip clinicians with the knowledge needed to evaluate emerging treatments and consider their role in addressing persistent efficacy gaps in the pharmacologic management of depression and psychosis.
Format
Recorded webinar, non-interactive, self-paced distance learning activity.
This presentation was recorded at the 2025 American Psychiatric Association Annual Meeting.
Learning Objectives
- To introduce several novel classes of antidepressant medications (ketamine/Esketamine, psychedelics, Kv7 agonism, kappa opioid receptor antagonism, 5HT1A agonism)
- To briefly characterize what we know about the mechanism of action of these novel antidepressants
- To highlight the distinctive clinical profiles of the novel antidepressants
- To describe the mechanisms of action of medications for psychosis that do not block dopamine receptors.
- To highlight the distinctive clinical profile of non-dopamine blocking antipsychotic medications that are approved or being developed
Target Audience
Medical Students, Residents/Fellows, Psychiatrists
Estimated Time to Complete
Estimated Duration: 1.5 hours
Begin Date: January 1, 2026
End Date: January 1, 2029
How to Earn Credit
Participants who wish to earn 1.5 AMA PRA Category 1 Credit ™ or a certificate of participation may do so by completing all sections of the course including the evaluation. After evaluating the program, course participants will be provided with an opportunity to claim hours of participation and print an official CME certificate (physicians) or certificate of participation (non-physicians) showing the event date and hours earned.
Continuing Education Credit
In support of improving patient care, the American Psychiatric Association is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.
Physicians
The APA designates this enduring activity for a maximum of 1.5 AMA PRA Category 1 Credit ™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Faculty and Planner Disclosures
The American Psychiatric Association adheres to the ACCME’s Standards for Integrity and Independence in Accredited Continuing Medical Education. Any individuals in a position to control the content of a CME activity — including faculty, planners, reviewers or others — are required to disclose all relevant financial relationships with ineligible entities (commercial interests). All relevant conflicts of interest have been mitigated prior to the commencement of the activity.
Program Presenters
- Stephen Marder, MD (Chair, Presenter)
- John Krystal, MD (Presenter)
- Catherine Crone, MD (Moderator)
- Sehba Husain-Krautter, MD; PhD (Moderator)
Program Planners
- Vishal Madaan, MD. Chief of Education and Deputy Medical Director, APA.
Accessibility for Participants with Disabilities
The American Psychiatric Association is committed to ensuring accessibility of its website to people with disabilities. If you have trouble accessing any of APA’s online resources, please contact us at 202-559-3900 for assistance.
Technical Requirements
This internet-based CME activity is best experienced using any of the following:
- The latest and 2nd latest public versions of Google Chrome, Mozilla Firefox, or Safari
- Internet Explorer 11+
This Web site requires that JavaScript and session cookies be enabled. Certain activities may require additional software to view multimedia, presentation, or printable versions of the content. These activities will be marked as such and will provide links to the required software. That software may be: Adobe Acrobat Reader, Microsoft PowerPoint, and Windows Media Player.
Optimal System Configuration:
- Browser: Google Chrome (latest and 2nd latest version), Safari (latest and 2nd latest version), Internet Explorer 11.0+, Firefox (latest and 2nd latest version), or Microsoft Edge (latest and 2nd latest version)
- Operating System: Windows versions 8.1+, Mac OS X 10.5 (Leopard) +, Android (latest and 2nd latest version), or iOS/iPad OS (latest and 2nd latest version)
- Internet Connection: 1 Mbps or higher
Minimum Requirements:
- Windows PC: Windows 8.1 or higher; 1 GB (for 32-bit)/2 GB (for 64-bit) or higher RAM; Microsoft DirectX 9 graphics device with WDDM driver; audio playback with speakers for programs with video content
- Macintosh: Mac OS X 10.5 or higher with latest updates installed; Intel, PowerPC G5, or PowerPC G4 (867MHz or faster) processor; 512 MB or higher RAM; audio playback with speakers for programs with video content
For assistance: Contact educme@psych.org for questions about this activity | Contact learningcenter@psych.org for technical assistance