RESUMEN
OBJECTIVE: Previous randomised, double-blind, placebo-controlled studies have shown that Kava (a South Pacific medicinal plant) reduced anxiety during short-term administration. The objective of this randomised, double-blind, placebo-controlled study was to perform a larger, longer-term trial assessing the efficacy and safety of Kava in the treatment of generalised anxiety disorder and to determine whether gamma-aminobutyric acid transporter (SLC6A1) single-nucleotide polymorphisms were moderators of response. METHODS: The trial was a phase III, multi-site, two-arm, 16-week, randomised, double-blind, placebo-controlled study investigating an aqueous extract of dried Kava root administered twice per day in tablet form (standardised to 120 mg of kavalactones twice/day) in 171 currently non-medicated anxious participants with diagnosed generalised anxiety disorder. The trial took place in Australia. RESULTS: An analysis of 171 participants revealed a non-significant difference in anxiety reduction between the Kava and placebo groups (a relative reduction favouring placebo of 1.37 points; p = 0.25). At the conclusion of the controlled phase, 17.4% of the Kava group were classified as remitted (Hamilton Anxiety Rating Scale score < 7) compared to 23.8% of the placebo group (p = 0.46). No SLC6A1 polymorphisms were associated with treatment response, while carriers of the rs2601126 T allele preferentially respond to placebo (p = 0.006). Kava was well tolerated aside from poorer memory (Kava = 36 vs placebo = 23; p = 0.044) and tremor/shakiness (Kava = 36 vs placebo = 23; p = 0.024) occurring more frequently in the Kava group. Liver function test abnormalities were significantly more frequent in the Kava group, although no participant met criteria for herb-induced hepatic injury. CONCLUSION: While research has generally supported Kava in non-clinical populations (potentially for more 'situational' anxiety as a short-term anxiolytic), this particular extract was not effective for diagnosed generalised anxiety disorder.
Asunto(s)
Ansiolíticos/uso terapéutico , Trastornos de Ansiedad/tratamiento farmacológico , Kava/química , Extractos Vegetales/uso terapéutico , Adulto , Ansiolíticos/efectos adversos , Trastornos de Ansiedad/genética , Australia , Método Doble Ciego , Femenino , Proteínas Transportadoras de GABA en la Membrana Plasmática/genética , Humanos , Masculino , Persona de Mediana Edad , Fitoterapia , Extractos Vegetales/efectos adversos , Raíces de Plantas/química , Polimorfismo de Nucleótido Simple , Escalas de Valoración Psiquiátrica , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Partial or non-response to antidepressants in Generalized Anxiety Disorder (GAD) is common in clinical settings, and adjunctive biological interventions may be required. Adjunctive herbal and nutraceutical treatments are a novel and promising treatment option. L-theanine is a non-protein amino acid derived most-commonly from tea (Camellia sinensis) leaves, which may be beneficial in the treatment of anxiety and sleep disturbance as suggested by preliminary evidence. We conducted a 10-week study (consisting of an 8-week double-blind placebo-controlled period, and 1-week pre-study and 2-week post-study single-blinded observational periods) involving 46 participants with a DSM-5 diagnosis of GAD. Participants received adjunctive L-theanine (450-900â¯mg) or matching placebo with their current stable antidepressant treatment, and were assessed on anxiety, sleep quality, and cognition outcomes. Results revealed that adjunctive L-theanine did not outperform placebo for anxiety reduction on the HAMA (pâ¯=â¯0.73) nor insomnia severity on the Insomnia Severity Index (ISI; pâ¯=â¯0.35). However, LT treated participants reported greater self-reported sleep satisfaction than placebo (ISI item 4; pâ¯=â¯0.015). Further, a separation in favour of L-theanine was noted on the ISI in those with non-clinical levels of insomnia symptoms (ISIâ¯≤â¯14; pâ¯=â¯0.007). No significant cognitive effects (trail making time and the modified emotional Stroop) were revealed. While this preliminary study did not support the efficacy of L-theanine in the treatment of anxiety symptoms in GAD, further studies to explore the application of L-theanine in sleep disturbance are warranted.