Future Directions in Anxiolytic Therapy: A Comprehensive Review of Novel Targets and Strategies.

Background: With 301 million cases worldwide, anxiety disorders represent a serious public health concern. Many people endure ongoing distress while receiving several treatments because of the drawbacks of traditional therapy, such as adverse effects, dependence, and inconsistent efficacy. This emphasizes the absolute need for novel treatment approaches.

Objective: This review examines emerging pharmacological and non-pharmacological strategies for anxiety disorders, assessing existing and developing therapeutic options while examining the drawbacks of conventional therapies.

Methods: A comprehensive literature review was carried out using the NIH, PubMed, and Google Scholar databases. Studies from 2020-2025 were given priority in the inclusion criteria, with a few supporting references from earlier years. Personalized medicine, combination therapy, non-pharmacological interventions, and novel anxiolytic targets, etc., were among the keywords used.

Results: Conventional therapies, including benzodiazepines, SSRIs, and SNRIs, are still the major choices, but they have significant disadvantages. The protein kinase pathway, endocannabinoid and orexin systems, NK1R antagonists, and microbiome modulation are examples of emerging targets. Emerging strategies that show preliminary promise include digital therapeutics, gene therapy, optogenetics, personalized medicine, combination therapy, herbal therapy, and peptide-based medicines (e.g., NPY, NPS, oxytocin analogs, CRF, vasopressin, and melanocortin receptor antagonist). Several of these approaches modulate key neural circuits, such as the involvement of the amygdala-prefrontal cortex axis, via the HPA axis, and biomarker-informed personalization, among others; yet many remain in early-phase or preclinical investigation. However, limited comparative data exist between these novel strategies and standard therapies, underlining the need for rigorous head-to-head evaluations.

Conclusion: Advances in molecular neuroscience and precision medicine offer potential alternatives to conventional treatments. However, most emerging therapies require further clinical validation, large-scale trials, and translational refinement before they can be integrated into realworld decision-making for anxiety disorders.