title: Kava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled study.
abstract: 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.
authors: Department of Psychiatry, University of Melbourne, Melbourne, Victoria, Australia. jsarris@unimelb.edu.au
authors: Jerome
authors: J
authors: Sarris
authors: Con
authors: C
authors: Stough
authors: Chad A
authors: CA
authors: Bousman
authors: Zahra T
authors: ZT
authors: Wahid
authors: Greg
authors: G
authors: Murray
authors: Rolf
authors: R
authors: Teschke
authors: Karen M
authors: KM
authors: Savage
authors: Ashley
authors: A
authors: Dowell
authors: Chee
authors: C
authors: Ng
authors: Isaac
authors: I
authors: Schweitzer
mesh_terms: D000328:Adult; D014151:Anti-Anxiety Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001008:Anxiety Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000523:psychology; D016009:Chi-Square Distribution; D004311:Double-Blind Method; D005260:Female; D050485:GABA Plasma Membrane Transport Proteins / Q000235:genetics; D006801:Humans; D020901:Kava; D008297:Male; D010597:Pharmacogenetics; D008517:Phytotherapy; D010936:Plant Extracts / Q000009:adverse effects / Q000627:therapeutic use*; D010946:Plants, Medicinal; D011110:Polymorphism, Genetic; D011569:Psychiatric Status Rating Scales; D013997:Time Factors; D016896:Treatment Outcome; D014739:Victoria; D055815:Young Adult
chemical_list: D014151:Anti-Anxiety Agents; D050485:GABA Plasma Membrane Transport Proteins; D010936:Plant Extracts