[Effect of a special kava extract in patients with anxiety-, tension-, and excitation states of non-psychotic genesis. Double blind study with placebos over 4 weeks]. Kava-kava extract WS 1490 versus placebo in anxiety disorders--a randomized placebo-controlled 25-week outpatient trial. Kava treatment in patients with anxiety. A placebo-controlled study of Kava kava in generalized anxiety disorder. Clinical efficacy of kava extract WS 1490 in sleep disturbances associated with anxiety disorders. Results of a multicenter, randomized, placebo-controlled, double-blind clinical trial. Efficacy of kava-kava in the treatment of non-psychotic anxiety, following pretreatment with benzodiazepines. Treatment of anxiety, tension and restlessness states with Kava special extract WS 1490 in general practice: a randomized placebo-controlled double-blind multicenter trial. [Psychosomatic dysfunctions in the female climacteric. Clinical effectiveness and tolerance of Kava Extract WS 1490]. A randomized, placebo-controlled study of outpatient premedication for bone marrow biopsy in adults with lymphoma.
Clinical Efficacy of a Kava Extract in Patients with Anxiety Syndrome/Double-blind placebo controlled study over 4 weeks. In a randomized, placebo-controlled double-blind study two groups each containing 29 patients with anxiety syndrome not caused by psychotic disorders were treated for a period of 4 weeks with kava extract WS 1490 (Laitan) 3 x 100 mg/day or a placebo preparation. Therapeutic efficacy was assessed by the Hamilton-Anxiety-Scale (main target variable), the Adjectives-List and the Clinical-Global-Impression-Scale (secondary target variables) after 1, 2 and 4 weeks of treatment. The HAMA overall score of anxiety symptomatology revealed a significant reduction in the drug receiving group already after one week of treatment. This difference between the two groups of patients increased in the course of the study. The results of the secondary target variables were in agreement with the HAMA-score and demonstrate the efficacy of WS 1490 in patients with anxiety disorders. No adverse experiences caused by the medication were noted during the 4 week administration of WS 1490. 101 outpatients suffering from anxiety of non-psychotic origin (DSM-III-R criteria: agoraphobia, specific phobia, generalized anxiety disorder, and adjustment disorder with anxiety) were included in a 25-week multicenter randomized placebo-controlled double-blind trial with WS 1490, a special extract of kava-kava. In the main outcome criterion, the Hamilton Anxiety Scale (HAMA), there was a significant superiority of the test drug starting from week 8 on. WS 1490 was also found to be superior with respect to the secondary outcome variables. HAMA subscores somatic and psychic anxiety, Clinical Global Impression, Self-Report Symptom Inventory-90 Items revised, and Adjective Mood Scale. Adverse events were rare and distributed evenly in both groups. These results support WS 1490 as a treatment alternative to tricyclic antidepressants and benzodiazepines in anxiety disorders, with proven long-term efficacy and none of the tolerance problems associated with tricyclics and benzodiazepines. In several clinical trials, mainly conducted with a dose of 300 mg kava extract per day, kava has been employed successfully for the treatment of anxiety disorders. The goal of the placebo-controlled double-blind outpatient trial was to obtain more information on the dosage range and efficacy of a kava special extract WS 1490 in patients with non-psychotic anxiety. 50 patients were treated with a daily dose of 3 x 50 mg WS 1490 during a 4-week treatment period followed by a 2-week safety observation phase. In the active treatment group, the total score of the Hamilton anxiety scale (primary efficacy variable), showed a therapeutically relevant reduction in anxiety versus placebo (more than 4 points). In the secondary variables studied, HAMA 'somatic and psychic anxiety' subscales, the Erlangen anxiety, tension and aggression scale (EAAS), the brief personality structure scale (KEPS), the adjective checklist (EWL 60-S) and clinical global impressions scale (CGI), a trend in favour of the active treatment was detectable. WS 1490 was well tolerated and showed a safety profile with no drug-related adverse events or post-study withdrawal symptoms. It can be concluded that the applied 150 mg WS 1490 per day is an effective and safe treatment of non-psychotic anxiety syndromes in the described population.
                Copyright 2004 John Wiley & Sons, Ltd. We assessed the efficacy and safety of a botanical anxiolytic, Kava kava (Piper methysticum), in treating generalized anxiety disorder (GAD). Thirty-seven adults with DSM-IV GAD were randomly assigned to 4 weeks of double-blind treatment with kava or a matching placebo. Weekly efficacy assessments [Hamilton Anxiety Scale, Hospital Anxiety and Depression Scale (HADS), Self Assessment of Resilience and Anxiety (SARA)] and safety evaluations were conducted. Improvement was observed with both treatments but no differences were found in the principal analysis. Post-hoc analyses revealed significant differences based on baseline anxiety severity, whereby kava was superior on the SARA in low anxiety and placebo was superior on the HADS and SARA in high anxiety. Both treatments were well tolerated. Although kava was not superior to placebo, it would be premature to rule it out as efficacious in GAD. The aim of the present trial was to investigate the efficacy and safety of kava special extract WS 1490 in patients with sleep disturbances associated with anxiety, tension and restlessness states of non-psychotic origin.
                In a multicenter, randomized, double-blind clinical study, 61 patients received daily doses of 200 mg WS 1490 or placebo over a period of 4 weeks. Efficacy was measured by the sleep questionnaire SF-B, the Hamilton Anxiety Scale (HAMA), the Bf-S self-rating scale of well-being and the Clinical Global Impressions (CGI) scale.
                The confirmatory analysis of the two primary efficacy variables, the differences of sleep questionnaire SF-B sub-scores 'Quality of sleep' and 'Recuperative effect after sleep' after 4 weeks of double-blind treatment compared to baseline, demonstrated statistically significant group differences in favor of kava extract WS 1490 (P=0.007 and P=0.018, respectively). Superior effects of kava extract were also present in the HAMA psychic anxiety sub-score (P=0.002). More pronounced effects with respect to the self-rating of well-being and the global clinical evaluation also indicated superior therapeutic efficacy of kava extract. Safety and tolerability were good, with no drug-related adverse events or changes in clinical or laboratory parameters.
                We conclude that sleep disturbances associated with non-psychotic anxiety disorders can be effectively and safely treated with kava extract WS 1490. A 5-week randomized, placebo-controlled, double-blind study was carried out to investigate the efficacy of kava-kava special extract WS1490 in non-psychotic nervous anxiety, tension and restlessness states. During the first treatment week, the study dose drug was increased from 50 mg to 300 mg per day and pretreatment with benzodiazepines was tapered off over 2 weeks. These dosage adjustments were followed by 3 weeks of monotherapy with WS1490 or placebo. Outcome measures were the differences between baseline and end of treatment on the Hamilton Anxiety Scale (HAMA) and on a subjective well-being scale (Bf-S), as well as the benzodiazepine withdrawal symptoms. Changes in the Erlanger Anxiety, Tension and Aggression Scale (EAAS) and Clinical Global Impressions (CGI) were analyzed as secondary measures. Treatment safety was checked by interviews, adverse event reports and laboratory investigations. Forty patients (2x20) were included into the study. WS1490 was superior to placebo regarding the HAMA (P=0.01) and Bf-S (P=0.002) total scores and all secondary efficacy measures. The tolerance of WS1490 was not inferior to placebo. The study confirms the anxiolytic efficacy and good tolerance of WS1490 and shows that a further symptom reduction is possible after a change-over from benzodiazepine treatment. The efficacy and tolerability of 150 mg/d Kava special extract WS 1490 were investigated in a randomized, placebo-controlled, double-blind multicenter study in patients suffering from neurotic anxiety (DSM-III-R diagnoses 300.02, 300.22, 300.23, 300.29, or 309.24). 141 adult, male and female out-patients received 3 x 1 capsule of 50 mg/d WS 1490 or placebo for four weeks, followed by two weeks of observation without study-specific treatment. During randomized treatment the total score of the Anxiety Status Inventory (ASI) observer rating scale showed more pronounced decreases in the WS 1490 group than in the placebo group. Although a treatment group comparison of the post-treatment ASI scores was not significant (p > 0.05), an exploratory analysis of variance across the differences between treatment end and baseline, with center as a second factor, showed superiority of the herbal extract over placebo (p < 0.01, two-sided). 73% of the patients treated with WS 1490 exhibited ASI score decreases > 5 points versus baseline, compared to 56% for placebo. Significant advantages for WS 1490 were also evident in a structured well-being self-rating scale (Bf-S) and the Clinical Global Impressions (CGI), while the Erlangen Anxiety, Tension and Aggression Scale (EAAS) and the Brief Test of Personality Structure (KEPS) showed only minor treatment group differences. Although the results show consistent advantages for WS 1490 over placebo in several psychiatric scales and indicate significant improvements in the patients' general well-being, the differences versus placebo were not as large as in previous trials which employed 300 mg/d of the same extract. WS 1490 was well tolerated, with no influence on liver function tests and only one trivial adverse event (tiredness) attributable to the study drug. Within the framework of a randomized, placebo-controlled double-blind study, two groups each containing 20 patients with climacteric-related symptomatology were treated for a period of 8 weeks with kava WS 1490 extract 3 X 100 mg/day or a placebo preparation. The target variable - the HAMA overall score of anxiety symptomatology - revealed a significant difference in the drug-receiving group vis-à-vis the placebo group already after only 1 week of treatment. The course of such further parameters as depressive mood (DSI), subjective well-being (patient diary), severity of the disease (CGI), and the climacteric symptomatology (Kuppermann Index and Schneider scale) over the overall period of treatment demonstrate a high level of efficacy of kava extract WS 1490 in neurovegetative and psychosomatic dysfunctions in the climacteric, associated with very good tolerance of the preparation. The outpatient bone marrow biopsy and aspiration (BMBA) procedure performed with local anesthetic is often poorly tolerated in adults. This prospective, randomized, placebo-controlled, double-blind trial was designed to determine whether oral (p.o.) lorazepam and hydromorphone reduces pain and anxiety during BMBA. Eligible patients had lymphoma, had no prior BMBA, and were > or = 18 years old. Since patients had bilateral BMBA, each served as their own control. Patients were stratified by anxiety level using the Spielberger Trait Anxiety Scale and randomized to: A) placebo for the first BMBA and 2 mg lorazepam and 2 mg hydromorphone p.o. for the contralateral BMBA, or B) placebo for both BMBAS. Changes in pain and anxiety experienced between the first and second BMBA were measured by the Visual Analogue Scale (VAS) and the Spielberger State Anxiety Scale at the time of the BMBA and 24 hours later. Twenty-seven patients were enrolled and 25 were evaluable; there were 17 males and eight females. The median age was 57 years (range, 28-79 years). Overall, BMBA was reported as painful in both arms, with a median VAS pain score after the second BMBA of 3.9 (scale, 0-10) for arm A and 5.8 for arm B (P = 0.21). There was no difference in the change in pain, anxiety, or recalled anxiety between treatment arms (all P values > 0.05). The difference in the change in recalled pain was of borderline significance (P = 0.07) and consistent with benzodiazepine-induced anterograde amnesia.
Compared with placebo, kava extract is an effective symptomatic treatment for anxiety although, at present, the size of the effect seems small. The effect lacks robustness and is based on a relatively small sample. The data available from the reviewed studies suggest that kava is relatively safe for short-term treatment (1 to 24 weeks), although more information is required. Rigorous trials with large sample sizes are needed to clarify the existing uncertainties. Also, long-term safety studies of kava are required.