Beneficial effects of Silexan on sleep are mediated by its anxiolytic effect.

Disturbed sleep is among the most prevalent hyperarousal symptoms in anxiety disorders. Most drugs recommended for anxiety and insomnia have a sedating effect which is related to their beneficial effect on disturbed sleep. Silexan is a proprietary essential oil from Lavandula angustifolia. This drug has significant anxiolytic and sleep improving properties. Interestingly, these effects are not associated with sedation. Here we asked whether the positive effects on sleep are due to primary pharmacodynamic or secondary, disease related effects. We used the data from a double-blind, randomized study in which 212 patients were analyzed for efficacy after ten weeks' treatment with 80 mg/day Silexan or placebo. Anxiety and disturbed sleep were assessed using the Hamilton Anxiety Scale (HAMA) and the Pittsburgh Sleep Quality Index (PSQI), respectively. Regression-based mediation analysis was employed to estimate direct treatment effects and indirect effects mediated by anxiety control separately for each study group. Sobel's test was used to investigate the extent to which the mediator (HAMA change) contributes to the total effect of the independent variable (treatment) on the dependent variable (PSQI change). Compared to placebo, Silexan significantly reduced the total scores of the HAMA (p < 0.001) and of the PSQI (p = 0.002) after ten weeks, with clinically meaningful treatment group differences that were observed already after two and six weeks for HAMA and PSQI, respectively. Silexan had a statistically meaningful indirect effect on sleep (mediated by the effect on anxiety; p < 0.001) but no appreciable direct effect (p = 0.958). The ratio between the indirect and the total effect was determined to be 0.984, i. e., 98.4% of the total effect of Silexan on disturbed sleep were explained by the effect of Silexan on the symptoms of anxiety whereas 1.6% were attributable to a direct effect. The results indicate that Silexan exerts a secondary sleep improving effect almost exclusively through its anxiolytic action rather than by sedation. Findings are consistent with the drug's assumed mechanism of action.

RCT Entities:   Population Interventions Outcomes