Herb-drug Interactions in Polypharmacy or Ashwagandha in Stress and Cognitive Disorders

Abstract Polypharmacy among older adults increases the risk of herb–drug interactions, particularly in regions such as the Caribbean where herbal medicine use is prevalent. Withania somnifera (Ashwagandha), an adaptogenic herb from Ayurvedic medicine, is increasingly used for managing stress, anxiety, depression, insomnia, and age-related cognitive decline. Its mechanisms involve modulation of the hypothalamic–pituitary–adrenal (HPA) axis, sympathetic–adrenal–medullary (SAM) activity, and GABAergic and serotonergic pathways. Despite reported therapeutic benefits, Ashwagandha’s diverse bioactive compounds and variability in preparations complicate the prediction of pharmacokinetic and pharmacodynamic interactions with conventional drugs. In multimorbid, polymedicated patients, such interactions may result in altered drug metabolism, additive pharmacological effects, or therapeutic failure. This review highlights the urgent need for drug reconciliation systems, pharmacovigilance, and well-designed clinical trials to evaluate Ashwagandha’s safety profile within polypharmacy settings. Greater awareness and evidence-based guidance are essential for healthcare professionals to optimize outcomes while minimizing risks in integrative medicine approaches.