#Psychiatry #Psychopharmacology #PrecisionMedicine #ClinicalTrials #Neuropsychiatry

Key Updates

  1. Biomarker-Stratified Antidepressant Response
    A randomized trial in JAMA Psychiatry (Sept 2025) found that patients with treatment-resistant depression who carried the ANK3 biomarker had improved outcomes with liafensine, suggesting potential for genotype-guided prescribing (doi:10.1001/jamapsychiatry.2025.xxxxx).
  2. Global R&D Trends
    An analysis of 1,377 psychiatric drug clinical trials in China (2019–2024) reported a shift toward biomarker-based and exploratory designs, with depression (30.9%) and schizophrenia (22.2%) dominating pipelines. Fifty-two innovative agents are in active testing (Front Psychiatry, 2025; doi:10.3389/fpsyt.2025.1599038).
  3. Non-Hallucinogenic Psychoplastogens
    Novel compounds such as DLX-159 and bretisilocin show preclinical or early-phase efficacy in promoting plasticity without hallucinogenic effects, potentially expanding accessibility beyond tightly regulated psychedelic protocols (Delix/Gilgamesh trial updates, 2025).
  4. SIRT6 Modulation in Depression & Schizophrenia
    Forvisirvat (SP-624), a SIRT6 activator, is advancing in Phase II/III depression and Phase I/II schizophrenia trials, representing a mechanistically distinct class targeting epigenetic regulation (pipeline update, 2025).
  5. Predictive EEG Biomarkers
    Day-7 EEG motif analysis demonstrated the ability to classify antidepressant responders vs. non-responders with high accuracy, potentially shortening ineffective trials of therapy (arXiv preprint:2501.04441, 2025).

Clinical Takeaways

  • Biomarkers (genomic, EEG) may enable earlier, more precise treatment shifts.
  • Psychoplastogens could reduce barriers to psychedelic-based interventions.
  • Novel mechanistic targets (e.g., SIRT6) suggest a broadening antidepressant landscape.

References

  1. JAMA Psychiatry. 2025 Sep 10. doi:10.1001/jamapsychiatry.2025.xxxxx
  2. Zhang et al. Front Psychiatry. 2025;16:1599038. doi:10.3389/fpsyt.2025.1599038
  3. Delix Therapeutics pipeline. Accessed Sept 2025.
  4. Gilgamesh Pharmaceuticals trial registry. Accessed Sept 2025.
  5. 2025 Jan. arXiv:2501.04441