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This is going to sound too good to be true. How would you like a medication that works as well as a benzodiazepine for anxiety but causes no dependence or withdrawal? It has no side effects except mild nausea in 3% of users and no known long-term risks. It has no interactions with any of the P450 cytochromes and no other known drug interactions. It’s been around for over a decade in Germany, where it’s widely used. And now, you can get it in the United States and perhaps in other countries without a prescription. In my local grocery store, it costs $17 for a month’s supply of the larger, more effective dose and half that for a dose that’s certainly an excellent placebo, if not better. And now comes a review that suggests that this medication works well for insomnia too. Do I have your attention?
Hi! Jim Phelps here for the Psychopharmacology Institute. It’s not really a medication after all. It’s extract of lavender. In Germany, the pill version is called Silexan. In the United States, the same compound in the same concentrations is available over the counter as CalmAid. My local supermarket carries it. But now I’m going to throw some cold water on all this enthusiasm. Here it goes: Nearly every randomized trial that I can find was conducted by researchers who received honoraria from its German manufacturer, and the most recent meta-analysis of its efficacy was funded by the company, which prepared the statistical analysis and drafted the manuscript. Basically, what we’re reading is advertisements. That doesn’t mean that it doesn’t work, but it raises some suspicions about whether it’s as good as the publications make it sound.
On the other hand, suppose it really is just an elegant placebo—cheap, apparently nearly harmless, and appealing. What doesn’t sound good about extract of lavender? As you know, placebos have very good results in the treatment of anxiety and insomnia. So, actually, I should be careful not to foster your disbelief. Indeed, I should promote it, just as do the authors of this new review, including regarding its effects on insomnia, because if you believe it’s a great approach, many of your patients will too and it will help them. Moreover, there are actually good biochemical reasons to think that extract of lavender actually is psychoactive. Like pregabalin, lavender extract also inhibits calcium channels with a net effect on glutamate and norepinephrine. According to this new review and a previous one in 2015, there are multiple reasons to believe that lavender extract really is doing something specific in the brain. But these reviews, like the randomized trials, have been authored by Dr. Siegfried Kasper along with authors in the direct employ of the manufacturer.
Well, back to the results. Lavender extract vs placebo for insomnia. In 1 study, as measured by the standard scale, the Pittsburgh Sleep Quality Index, lavender extract was associated with an 8-point drop vs a 6-point reduction with placebo. That difference was statistically significant. But clinically significant? How big is 2 points on the PSQI? Well, a small literature based on studies in sports medicine, acupuncture, and pulmonary disease suggests that a minimal clinically important difference on the PSQI is somewhere between 1.5 and 3 or 4. Suffice to say that a shift of 2 points is not huge but probably noticeable. Better, how about a head-to-head comparison with 0.5 mg of lorazepam? Reviewing the abstract of that study, it looks like it was fairly rigorous even though the second author is an employee of the Silexan manufacturer. The results in that context? Equal improvement in anxiety scores with Silexan and low-dose lorazepam 0.5 mg, including the insomnia subscore. But was the sample big enough to detect a difference? Unfortunately, the abstract doesn’t give us those numbers.
In summary, for now, we’re seeing the same results for insomnia that were seen for anxiety scores overall with extract of lavender vs placebo. If it weren’t for the direct connections to the manufacturer in these publications, we’d have good evidence for Silexan over the counter as an apparently safe alternative to benzodiazepines for anxiety and sleep. But we can definitely say that extract of lavender is at least as good as a placebo, knowing that placebos themselves can be highly effective for anxiety and sleep. It all depends on whether your patient believes the pills can help, which is determined by whether you believe they can help. And clearly, they can. Given the published data, you don’t have to worry about the ethical problems of recommending a placebo.
For more on this, a review of its efficacy for anxiety is presented by Moller et al. 2019. This review is linked here at the Psychopharmacology Institute.
Abstract
Effect of Anxiolytic Drug Silexan on Sleep – A Narrative Review
Erich Seifritz, Siegfried Kasper, Hans-Jürgen Möller, Hans-Peter Volz, Walter E Müller, Anne Eckert, Martin Hatzinger
Objectives: Silexan is an orally administered, proprietary essential oil from Lavandula angustifolia with significant anxiolytic and sleep improving properties. Here we present a narrative review that provides an overview of the available evidence of the effects of silexan on sleep.
Methods: We start with a summary of the pharmacological background and continue with presenting sleep-related results from controlled clinical trials with silexan. Then we report on a meta-analysis of item ‘insomnia’ from the Hamilton Anxiety Scale, which includes data from all randomised, placebo-controlled clinical trials with silexan in which the scale was administered. Finally, we summarise the results of a mediation analysis that was performed to elucidate the pathway of the effect of silexan on sleep.
Results: In randomised, placebo-controlled trials in patients suffering from anxiety disorders silexan had a significant anxiolytic effect and improved sleep along with recovery from anxiety. Mediation analysis demonstrates that more than 98% of the effect of silexan on sleep was mediated by its anxiolytic effect while the direct effect on sleep was marginal.
Conclusions: Silexan improves sleep as a result of its anxiolytic effect.
Keywords: Silexan; anxiety; lavender oil; narrative review; sleep.
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Reference
Seifritz, E., Kasper, S., Möller, H. J., Volz, H. P., Müller, W. E., Eckert, A., & Hatzinger, M. (2022). Effect of anxiolytic drug silexan on sleep – a narrative review. The World Journal of Biological Psychiatry: The Official Journal of the World Federation of Societies of Biological Psychiatry, 23(7), 493–500.
Related References
- Möller, H. J., Volz, H. P., Dienel, A., Schläfke, S., & Kasper, S. (2019). Efficacy of silexan in subthreshold anxiety: meta-analysis of randomised, placebo-controlled trials. European Archives of Psychiatry and Clinical Neuroscience, 269(2), 183-193.
- Kasper, S., Müller, W. E., Volz, H. P., Möller, H. J., Koch, E., & Dienel, A. (2018). Silexan in anxiety disorders: Clinical data and pharmacological background. The World Journal of Biological Psychiatry, 19(6), 412-420.
