Research report
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

https://doi.org/10.1016/S0165-0327(02)00238-0Get rights and content

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: We conclude that sleep disturbances associated with non-psychotic anxiety disorders can be effectively and safely treated with kava extract WS® 1490.

Introduction

Anxiety disorders are among the most common types of mental illnesses (Pittler and Ernst, 2000), with a 12-month prevalence of approximately 17% and a lifetime prevalence of almost 25% among persons aged 15 to 54 years in the non-institutionalized population in the USA (Kessler et al., 1994). The core symptoms of these states are feelings of apprehension, uncertainty and fear which can be accompanied by a variety of other psychological and somatic manifestations. A very frequent symptom associated with anxiety disorders is disturbance of sleep with impairment of initiation, duration or quality of sleep (Ohayon et al., 2000). For the pharmacological treatment of anxiety disorders, drugs like tranquilizers, antidepressants and neuroleptics are widely used. Although these drugs have been proven to be effective in many cases, an increasing number of physicians and patients are reluctant to use synthetic psychopharmaceuticals because of disturbing side effects, dependence liability, development of tolerance and abuse potential (Lader, 1999, Pittler, 2000). Therefore, alternative treatment strategies with favorable side effect profiles, credible benefits and moderate costs are of particular interest, especially in primary care settings.

Because of their relaxant and hypnotic properties, extracts from the rhizome of the kava plant (Piper methysticum) have been used for centuries in the folk medicine of the South Seas Islands. The first botanical account of this plant was given in the 18th century by Johann Georg Forster (1754–1794). Numerous investigations with kava extracts have subsequently been carried out and several pharmacologically active kava lactones could be identified (Hänsel and Woelk, 1994, Hoelzl et al., 1994). Besides the proven anxiolytic effects of kava lactones (e.g., Holm et al., 1991), other investigations have revealed improvements in sleep quality without impairment of rapid eye movement (REM) sleep (Kretzschmar and Teschendorf, 1974, Emser and Bartylla, 1991). Other properties shown by kava lactones in pharmacological investigations include a positive influence on cerebral information processing (Münte et al., 1993), tranquilizing effects (Hänsel and Haas, 1984), local anesthesia (Kretzschmar and Teschendorf, 1974), anticonvulsive (Kretzschmar and Meyer, 1969) as well as spasmolytic (Kretzschmar, 1969) effects. In particular, pharmacological and clinical studies revealed no evidence of any potential for tolerance or dependency (Kretzschmar and Teschendorf, 1974).

The kava special extract WS® 1490 investigated in this clinical study is licensed in Germany1 for the treatment of anxiety, tension and restlessness states. WS® 1490, a monoextract from the dried root of the kava plant, is standardized to 70% kava and contains 30% of ancillary substances that promote its absorption. Several placebo and reference controlled clinical trials have confirmed the anxiolytic efficacy of WS® 1490: in the treatment of patients with anxiety, tension and restlessness states of non-psychotic origin, statistically significant superiority in comparison to placebo was demonstrated (e.g., Kinzler et al., 1991, Volz and Kieser, 1997, Warnecke, 1991). Woelk et al. (1993) did not find clinically relevant differences in efficacy between WS® 1490, oxazepam and bromazepam. In neurophysiological investigations, WS® 1490 increased the β/α ratio in the EEG, another indication of the extract’s anxiolytic properties (Johnson et al., 1991). In all clinical trials reported to date, WS® 1490 was very well tolerated. At therapeutic dosages, the increase in reaction time was negligible (Herberg, 1991, Herberg, 1993).

This study focused on the effect of WS® 1490 on sleep disturbances associated with anxiety, tension and restlessness states of non-psychotic origin.

Section snippets

Patients

The target population of the trial comprised adult, male and female out-patients suffering from sleep disturbances associated with syndromes of anxiety, tension or restlessness, which were not related to psychotic disorders. Patients with diagnoses of generalized anxiety disorder, agoraphobia, social phobia, common phobia or adaptation disorders [DSM-III-R 300.02, 300.22, 300.23, 300.29, 309.24; American Psychiatric Association (APA, 1987)] were considered primarily. Relevant sleep impairments

Patient population

A total number of 61 patients was included into the trial in three study centers (20, 21 and 20 patients, respectively). Due to overlapping of minor randomization imbalances in different strata, 34 study participants were assigned to WS® 1490 and 27 to placebo. At the end of the run-in period, four patients randomized a priori to the placebo group dropped out from the trial before starting double-blind treatment (lack of efficacy: 2 patients; withdrawal of informed consent: 1; relocation: 1).

Discussion

The study confirms the therapeutic effectiveness of the kava special extract WS® 1490 in patients with sleep disturbances associated with anxiety disorders of non-psychotic origin. Beyond the general anxiolytic effect of kava extract demonstrated in various controlled clinical trials (e.g., Pittler and Ernst, 2000), our results show that WS® 1490 is particularly effective in alleviating anxiety-related sleep disturbances.

The statistically significant improvements of the quality and recuperative

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