Silexan shows clinically important adjusted mean value differences of over 0.2 points in MADRSLavender Oil Preparation Shows Potential for Treating Depression

BACKGROUND: Major depressive disorder (MDD) is characterized by depressed mood, anhedonia, and loss of energy, which can be accompanied by associated symptoms and co-morbidities. Psychiatric scales such as the Montgomery Åsberg Depression Rating Scale (MADRS) must account for the complex nature of depression. METHODS: The MADRS total score change between baseline and week 8 was the primary outcome measure in a randomized, double-blind clinical trial investigating the antidepressant efficacy of 8 weeks' treatment with silexan compared to sertraline and placebo in patients with mild or moderate MDD. We report on a pre-planned, exploratory analysis of the individual MADRS items. Treatment effects were assessed using analyses of covariance with baseline adjustment, based on an estimand strategy. RESULTS: 498 subjects (silexan 170, sertraline 171, placebo 157) were treated and analyzed. After 8 weeks, silexan was superior to placebo for 5 out of the 9 MADRS items analyzed ("apparent sadness", "reported sadness", "reduced appetite", "concentration difficulties", "lassitude"; P < .05) and showed clinically important adjusted mean value differences >0.2 points for 7 out of the 9 items. Item-level results for silexan and sertraline were mainly comparable. CONCLUSIONS: Silexan had a strong over-all antidepressant effect, with the most pronounced improvements affecting the cardinal symptoms of depression. TRIAL REGISTRATION: EudraCT2020-000688-22 first entered on 12/08/2020. Significance statement Patients with depressive disorders can show many different symptoms. To better characterize the clinical action of an antidepressant, it is therefore important to analyze not only the overall value of a depression scale but also the individual items that describe these symptoms. Silexan is a preparation from lavender oil whose antidepressant effect has been proven in a randomized, double-blind, placebo-controlled 8-week study in patients with mild or moderate major depressive disorder. Based on the individual items of the Montgomery Åsberg Depression Rating Scale that was used as the main outcome for efficacy, we found in an exploratory, hypothesis-generating analysis that silexan had a rather broad antidepressant effect in the participants of our study, with potentially clinically meaningful advantages over placebo for 7 out of the 9 individual items investigated. This applied in particular to the main symptoms of depression, namely sadness and lassitude. Our single-item analysis thus helps to understand the antidepressant effects of silexan in more detail. Significant outcomes In patients with mild to moderate major depressive disorder, lavender oil preparation silexan has a clinical profile similar to that of the selective serotonin re-uptake inhibitor sertraline based on an item-level analysis of the Montgomery-Åsberg Depression Rating Scale (MADRS). Silexan has a significant antidepressant effect that includes an alleviation of depressed mood, anhedonia, and loss of energy, the cardinal symptoms of depression. The broad improvement of symptoms of depression could not be explained by the proven anxiolytic efficacy silexan alone but indicates an independent, direct antidepressant effect. The present item-level analysis provides valuable and detailed additional insights into the therapeutic profiles of silexan and sertraline and may help clinicians to tailor antidepressant treatment to the specific symptoms of a patient. Limitations For item-level analyses of the MADRS, no validated thresholds for the assessment of the clinical importance of changes over time have been defined, taking into account that different items may have different thresholds. Even though our analyses were pre-defined, they were exploratory and did not include studywise type I error level control. Their generalizability beyond the study population is therefore limited.