A randomised placebo-controlled trial examining the efficacy and safety of an adjunct herbal medicine formulation in patients with major depressive disorder and poor response to anti-depressant therapy

INTERVENTION: Participants enrolled in the trial will receive either Active tablets or Placebo tablets as an adjunct prescription to their existing anti‐depressant medication for a period of eight weeks. Participants will be directed to take two tablets, orally, twice daily, two in the morning and two in the evening (total of 4 tablets per day). All participants will take Placebo study medication only for the first two weeks of the trial before being randomised to either Active or Placebo study medication for a further eight weeks. ‐ Active Tablets contain four concentrated herbal extracts (dry herb equivalent): Curcuma longa rhizome (6.4 g), Boswellia serrata resin (1.5 g), Bupleurum falcatum root (750 mg), and Centella asiatica leaf (1.5 g). Compliance will be assessed through count of return tablets. CONDITION: Depression;Anxiety; ; Depression ; Anxiety Mental Health ‐ Anxiety Mental Health ‐ Depression PRIMARY OUTCOME: Adequate response to treatment – Yes or No (binary outcome); Adequate response to treatment defined as an improvement of >50% or more on the Montgomery‐Asberg Depression Rating Scale (MADRS) [Randomisation and eight weeks after intervention commencement ] SECONDARY OUTCOME: Changes in sleep quality as assessed by PROMIS—Sleep Disturbance—Short Form[Randomisation, four weeks and eight weeks after intervention commencement] Mean Beck Depression Inventory II (BDI‐II) score[Randomisation, four weeks and eight weeks after intervention commencement] Mean Montgomery–Åsberg Depression Rating Scale (MADRS) score [Randomisation and eight weeks after intervention commencement] Mean Zung’s self‐rating anxiety scale (SAS) score[Randomisation, four weeks and eight weeks after intervention commencementent] Patient Global Impression of Change (PGI‐C) ‐ participant self‐report of change in mood/ emotional distress[Assessed at week four, week eight and at 12 weeks after intervention commencement] Serum level of brain derived neurotrophic factor (BDNF)[Randomisation and eight weeks after intervention commencement] Serum level of high sensitivity C‐reactive protein (Hs‐CRP)[Randomisation and eight weeks after intervention commencement] INCLUSION CRITERIA: ‐ Adults (18‐65 years) with previously diagnosed depression ‐ Presents with moderate to severe depression BDI‐II score >20 at time of study entry ‐ Currently taking one of the following anti‐depressant types: SSRI, SNRI, alpha‐2 agonists (mirtazapine), or bupropion.