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Kava in the Treatment of Generalized Anxiety Disorder: A Double-Blind, Randomized, Placebo-Controlled Study

Sarris, Jerome MHSc, PhD*†; Stough, Con PhD; Bousman, Chad A. PhD, MPH*†; Wahid, Zahra T. BPsych (Hons); Murray, Greg MPsych, PhD; Teschke, Rolf MD§; Savage, Karen M. BSc(Hons); Dowell, Ashley BSc; Ng, Chee MD*; Schweitzer, Isaac MD*

Journal of Clinical Psychopharmacology: October 2013 - Volume 33 - Issue 5 - p 643–648
doi: 10.1097/JCP.0b013e318291be67
Original Contributions

Kava (Piper methysticum) is a plant-based medicine, which has been previously shown to reduce anxiety. To date, however, no placebo-controlled trial assessing kava in the treatment of generalized anxiety disorder (GAD) has been completed. A total of 75 participants with GAD and no comorbid mood disorder were enrolled in a 6-week double-blind trial of an aqueous extract of kava (120/240 mg of kavalactones per day depending on response) versus placebo. γ-Aminobutyric acid (GABA) and noradrenaline transporter polymorphisms were also analyzed as potential pharmacogenetic markers of response. Reduction in anxiety was measured using the Hamilton Anxiety Rating Scale (HAMA) as the primary outcome. Intention-to-treat analysis was performed on 58 participants who met inclusion criteria after an initial 1 week placebo run-in phase. Results revealed a significant reduction in anxiety for the kava group compared with the placebo group with a moderate effect size (P = 0.046, Cohen d = 0.62). Among participants with moderate to severe Diagnostic and Statistical Manual of Mental Disorders–diagnosed GAD, this effect was larger (P = 0.02; d = 0.82). At conclusion of the controlled phase, 26% of the kava group were classified as remitted (HAMA ≤ 7) compared with 6% of the placebo group (P = 0.04). Within the kava group, GABA transporter polymorphisms rs2601126 (P = 0.021) and rs2697153 (P = 0.046) were associated with HAMA reduction. Kava was well tolerated, and aside from more headaches reported in the kava group (P = 0.05), no other significant differences between groups occurred for any other adverse effects, nor for liver function tests. Standardized kava may be a moderately effective short-term option for the treatment of GAD. Furthermore, specific GABA transporter polymorphisms appear to potentially modify anxiolytic response to kava.

From the *Department of Psychiatry, University of Melbourne; †Centre forHuman Psychopharmacology, Swinburne University of Technology, Melbourne, Victoria, Australia; ‡Brain and Psychological Science Research Centre, Swinburne University of Technology; §Teaching Hospital Hanau, Department of Internal Medicine II, Goethe University of Frankfurt, Germany; and ∥Southern Cross Plant Science, Southern Cross University, Lismore, New South Wales, Australia.

Received June 19, 2012; accepted after revision December 31, 2012.

Reprints: Jerome Sarris, PhD, MHSc, The Melbourne Clinic, Department of Psychiatry, University of Melbourne, 2 Salisbury St, Richmond, Melbourne, Victoria, Australia (e-mail:

Dr Jerome Sarris is funded by an Australian National Health and Medical Research Council fellowship (NHMRC funding ID 628875), in a strategic partnership with The University of Melbourne and The Centre for Human Psychopharmacology at Swinburne University of Technology. Dr Chad Bousman is funded by a University of Melbourne John McKenzie Fellowship. The study was funded by Integria Healthcare and the NHMRC (ID 628875).

© 2013 by Lippincott Williams & Wilkins.