Investigating efficacy and mechanisms of Nardostachys jatamansi DC. as an adjuvant to escitalopram in the treatment of major depressive disorder - A randomized double-blind placebo-controlled study with neurobiological measures

ABSTRACT: Background Major depressive disorder (MDD) affects approximately 332 million people globally, with high rates of partial response and treatment resistance. Depression is linked to autonomic dysfunction, altered cortical excitability, and can bring about observable changes in neurobiological markers. Nardostachys jatamansi DC., an Ayurvedic (Indian system of medicine) herb, has potential in alleviating depressive symptoms. This study evaluates the efficacy of N. jatamansi as an adjunct to conventional antidepressant therapy for depression, with the aim of improving treatment outcomes. Methods Sixty consenting MDD patients already on escitalopram (14.83±5.03 mg) for 7.8±5.6 months were recruited and randomized into two groups to receive either N. jatamansi or placebo, alongside escitalopram for two months. Assessments included depression rating scales, heart rate variability (HRV), cortical excitability measured via transcranial magnetic stimulation (TMS), serum brain derived neurotrophic factor (BDNF), and biochemical markers, including serum glutamate receptor antibodies at baseline and post-treatment. Results Adjunctive administration of N. jatamansi alongside escitalopram for two months resulted in statistically significant improvements in depressive symptoms and sleep quality. Concurrently, HRV analysis demonstrated improved autonomic balance, TMS revealed restoration of cortical excitability, and serum BDNF levels increased significantly in the Jatamansi group compared with placebo Conclusion The present findings suggest that adjunctive N. jatamansi may improve clinical outcomes in patients receiving escitalopram while modulating autonomic, neurophysiological, and biochemical markers associated with MDD. However, further research with a large sample size is necessary to strengthen and extend the validation of these findings. A deeper understanding of the underlying neurobiological mechanisms may offer valuable insights for identifying novel pharmacological targets.