The Kava Anxiety Depression Spectrum Study (KADSS): A randomized, placebo-controlled, cross-over trial using an aqueous extract of Piper methysticum

  • Jerome Sarris, The University of Queensland, Australia
  • Prof David Kavanagh, Queensland University of Technology, Australia
  • Assoc Professor Gerard Byrne, The University of Queensland, Australia
  • Assoc Professor Kerry Bone, University of New England, Australia
  • Assoc Professor Jon Adams, The University of Queensland, Australia
  • Dr Gary Deed, The University of Queensland, Australia

    • Background: Piper methysticum (Kava) has been withdrawn in European, British, and Canadian markets due to concerns over hepatotoxic reactions. The World Health Organization (WHO) recently recommended research into ‘aqueous’ extracts of the plant to establish safety and efficacy in treating anxiety disorders.
    Design and Participants: The Kava Anxiety Depression Spectrum Study (KADSS) was a 3-week placebo-controlled, double-blind, crossover trial involving 60 adult participants with elevated stable anxiety and varying levels of depressive symptoms.
    Intervention: 5 Kava tablets per day, 2 tablets morning, 2 tablets after lunch, 1 tablet in the evening (containing 250mg of kavalactones/day).
    Results: The aqueous extract of Kava reduced participants’ Hamilton Anxiety Scale score in the first controlled phase by -9.9 (CI: 7.1, 12.7) vs. -0.8 (CI: -2.7, 4.3) for placebo, and in the second controlled phase by -10.3 (CI: 5.8, 14.7) vs. +3.3 (CI: -6.8, 0.2). The pooled effect of Kava vs placebo across phases was highly significant (p<0.0001), with a very strong effect size (d=2.24, ηp2 = .428). Pooled analyses also revealed highly significant reductions in Beck Anxiety Scale anxiety and Montgomery-Asberg Depression Scale depression scores. The aqueous extract was found to be safe, with no serious adverse effects, and no clinical hepatotoxicity.
    Conclusions: The aqueous Kava preparation studied exerted significant anxiolytic and antidepressant activity, and appears to be safe. Kava may be recommended in cases of anxiety with comorbid depression. This should encourage further study, and consideration of globally re-introducing aqueous rootstock extracts of Kava for management of anxiety.