Lavender oil preparation Silexan is effective in mild-to-moderate major depression: a randomized, placebo- and reference-controlled trial.

Anxiety and depressive disorders have overlapping symptoms and share common neurobiological pathways. Antidepressant drugs have been demonstrated to be efficacious in anxiety as well. Vice versa, it may also be promising to investigate the efficacy of anxiolytic drugs such as silexan in major depressive disorder (MDD). Patients with a mild or moderate, single or recurrent episode of MDD and a total score of 19-34 points on the Montgomery Åsberg Depression Rating Scale (MADRS) were randomized to receive 1 × 80 mg/d silexan, 1 × 50 mg/d sertraline, or placebo double-blind, double-dummy for 56 days. The primary outcome measure was the MADRS total score change between baseline and treatment end. Treatment groups were compared using a treatment policy estimand. 498 subjects (silexan 170, sertraline 171, placebo 157) were treated and analyzed. After 8 weeks, silexan and sertraline were superior to placebo for MADRS total score reduction, with absolute differences to placebo of 2.17 (95% confidence interval: 0.58; 3.76) points and 2.59 (1.02; 4.17) points, respectively (p < 0.01). Moreover, silexan was superior to placebo for alleviation of functional impairment according to the Sheehan Disability Scale with a difference of 2.40 (1.04; 3.76) points (p < 0.001). Both treatments were well tolerated; eructation was the most frequent adverse effect of silexan. The study confirms the antidepressant efficacy of silexan in mild or moderate MDD, including significant improvements in the subjects' functional capacity. The results for sertraline confirm the assay sensitivity of the trial. Both drugs were well tolerated.Trial registrationEudraCT2020-000688-22 first entered on 12/08/2020.

Baseline symptom severity and efficacy of Silexan in patients with anxiety disorders: A symptom-based, patient-level analysis of randomized, placebo-controlled trials.

The influence of baseline severity on the efficacy of Silexan, a proprietary essential oil from Lavandula angustifolia, in anxiety disorders has not been investigated in a pooled dataset. We report on an individual patient data analysis of all five double-blind, randomized, placebo-controlled trials with Silexan in anxiety disorders. Eligible participants received Silexan 80 mg/d or placebo for 10 weeks. Analyses were based on the Hamilton Anxiety Rating Scale (HAMA), its psychic and somatic anxiety subscores, and the Clinical Global Impressions (CGI) scale. To correlate baseline severity with outcome, patients were segregated into mild, moderate, and severe cases. Altogether 1,172 patients (Silexan, n = 587; placebo, n = 585) were analyzed. For the HAMA total score, we found a significant association between the score at baseline and the treatment effect of Silexan versus placebo at week 10 (p < 0.001). HAMA items from the somatic domain scored lower at baseline and showed less improvement than items from the psychic domain, particularly in patients with mild or moderate baseline symptoms. For CGI item 2 (global improvement), significant efficacy favoring Silexan were observed in mild, moderate, and severe baseline symptom severity. Although significant improvements were found for all subsets, the more severe the initial symptoms, the greater the treatment effects documented by the HAMA. Overall this analysis confirms that Silexan is an effective treatment option in early or mild stages of anxiety disorder. Given its favorable safety profile, Silexan can thus fill a therapeutic gap in the treatment of (subsyndromal) anxiety disorders.

Revisiting benzodiazepines (GABA Enhancers):A transdiagnostic and precision medicine approach.

Since the mid 1980's, there has been an increased focus on the side effects of benzodiazepines (GABA enhancers), and as a result there has been a decrease in their use. We have systematically reviewed recent studies of GABA enhancers in psychiatry, and highlight evidence of their utility which may impact their negative conceptualization in clinical practice. We propose a new perspective on the appropriate use of these medications and describeclinical reasoning underpinning the use of benzodiazepine (GABA enhancers) based on their effect on specific receptors. A translational approach, involving a more comprehensive characterization of GABA receptors and their neuroscience-based mechanisms allows for a more precise use of this medication class. By adopting a precision person-centered approach, instead of a categorical approach, supports the prescribing of GABA enhancers when a cross-cutting transdiagnostic assessment shows anxiety symptoms associated with clinical impairment.

The Interplay of Oxytocin and Attachment in Schizophrenic Patients: An fMRI Study.

BACKGROUND: Attachment theory offers an important framework for understanding interpersonal interaction experiences. In the present study, we examined the neural correlates of attachment patterns and oxytocin in schizophrenic patients (SZP) compared to healthy controls (HC) using fMRI. We assumed that male SZP shows a higher proportion of insecure attachment and an altered level of oxytocin compared to HC. On a neural level, we hypothesized that SZP shows increased neural activation in memory and self-related brain regions during the activation of the attachment system compared to HC. METHODS: We used an event-related design for the fMRI study based on stimuli that were derived from the Adult Attachment Projective Picture System to examine attachment representations and their neural and hormonal correlates in 20 male schizophrenic patients compared to 20 male healthy controls. RESULTS: A higher proportion of insecure attachment in schizophrenic patients compared to HC could be confirmed. In line with our hypothesis, Oxytocin (OXT) levels in SZP were significantly lower than in HC. We found increasing brain activations in SZP when confronted with personal relevant sentences before attachment relevant pictures in the precuneus, TPJ, insula, and frontal areas compared to HC. Moreover, we found positive correlations between OXT and bilateral dlPFC, precuneus, and left ACC in SZP only. CONCLUSION: Despite the small sample sizes, the patients' response might be considered as a mode of dysregulation when confronted with this kind of personalized attachment-related material. In the patient group, we found positive correlations between OXT and three brain areas (bilateral dlPFC, precuneus, left ACC) and may conclude that OXT might modulate within this neural network in SZP.

A factor analytic comparison of three commonly used depression scales (HAMD, MADRS, BDI) in a large sample of depressed inpatients.

BACKGROUND: Quantifying depression mainly relies on the use of depression scales, and understanding their factor structure is crucial for evaluating their validity. METHODS: This post-hoc analysis utilized prospectively collected data from a naturalistic study of 1014 inpatients with major depression. Confirmatory and exploratory factor analyses were performed to test the psychometric abilities of the Hamilton Depression Rating Scale, the Montgomery Asberg Depression Rating Scale, and the self-rated Beck Depression Inventory. A combined factor analysis was also conducted including all items of all scales. RESULTS: All three scales showed good to very good internal consistency. The HAMD-17 had four factors: an "anxiety" factor, a "depression" factor, an "insomnia" factor, and a "somatic" factor. The MADRS also had four factors: a "sadness" factor, a neurovegetative factor, a "detachment" factor and a "negative thoughts" factor, while the BDI had three factors: a "negative attitude towards self" factor, a "performance impairment" factor, and a "somatic" factor. The combined factor analysis suggested that self-ratings might reflect a distinct illness dimension within major depression. CONCLUSIONS: The factors obtained in this study are comparable to those found in previous research. Self and clinician ratings are complementary and not redundant, highlighting the importance of using multiple measures to quantify depression.

Recollecting Hanns Hippius: a stimulating pioneer of psychopharmacology and neuroscience.

Hanns Hippius (1925-2021) can be seen as a stimulating pioneer of Psychopharmacology and of Neuroscience. He was very influential in this area not only in Germany, but also on an international level. With reference to clinical psychopharmacology especially his activities for the development of Clozapine are of greatest importance. When he became Chairman of the Psychiatric Department of the Ludwig-Maximilians-University Munich (1971-1994), he established all necessary facilities for research in Psychopharmacology and Neuroscience, which was at that time a great progress in psychiatry. This was the base to establish a Munich school of clinical psychopharmacology and neuroscience. A majority of his co-workers did research in psychopharmacology and neuroscience and made their academic careers in this area and several achieved university chair positions in Germany, on which they could procreate the standards and knowledge of the Munich school of psychopharmacology and neuroscience. His engagement for psychopharmacology can be seen in addition in the fact that he was co-founder and one of the first presidents of CINP (1972-1974), the International College of Psychopharmacology. The recollections presented in this article describe the objective data as well as some personal experiences of the author.

Psychiatric manifestations of post-COVID-19 syndrome: the potential benefit of Silexan.

Objective: Psychiatric symptoms are common and bothersome in individuals with post-COVID-19 syndrome. Because they are often mixed and subthreshold, established treatment regimens cannot be applied. There is an urgent need to identify therapeutics for affected patients. Silexan, a proprietary essential oil from Lavandula angustifolia, has demonstrated efficacy against anxiety, comorbid symptoms, and subthreshold and mixed syndromes. The aim of the current narrative review is to examine the therapeutic potential of Silexan for psychiatric manifestations in patients with post-COVID-19 syndrome.Methods: We reviewed clinical evidence regarding the efficacy of Silexan and first clinical experience in patients with psychiatric symptoms attributable to the post-COVID-19 syndrome. Furthermore, we discussed potential modes of action based on nonclinical data.Results: Silexan has demonstrated therapeutic efficacy for the treatment of generalised anxiety disorder; subsyndromal anxiety disorders; comorbid depressive, somatic, and sleep disturbance symptoms; and mixed anxiety and depression. Emerging clinical experience also suggests the effectiveness and tolerability of Silexan for patients with post-COVID-19 syndrome. This can be explained by the fact that the therapeutic profile of Silexan overlaps with the spectrum of psychiatric symptoms in such patients.Conclusion: Preliminary findings indicate a promising potential of Silexan for the treatment of psychiatric manifestations in patients with post-COVID-19 syndrome.Key pointsAnxiety and mixed neuropsychiatric manifestations are commonly observed in patients with post-COVID-19 syndrome.Silexan has anxiolytic properties and can alleviate comorbid depressive, somatic, and sleep impairment symptoms.Silexan exhibits several biological mechanisms, such as neurotrophic and anti-inflammatory properties, which have the potential to positively impact post-COVID-19 disease.Silexan has a favourable safety profile and high acceptance among patients.Emerging data suggest that Silexan can alleviate neuropsychiatric symptoms in patients with post-COVID-19 syndrome.Silexan should be considered as a therapeutic in patients with psychiatric manifestations of post-COVID-19 syndrome.

Efficacy of Silexan in patients with anxiety disorders: a meta-analysis of randomized, placebo-controlled trials.

INTRODUCTION: We report on a meta-analysis of Silexan, a proprietary active substance produced from Lavandula angustifolia, in subthreshold anxiety, mixed anxiety and depressive disorder (MADD), and generalized anxiety disorder (GAD). METHODS: The present analyses are based on all currently completed 5 double-blind, randomized, placebo-controlled trials investigating Silexan in adult out-patients who received Silexan 1 × 80 mg/day or placebo for ten weeks according to random assignment (n = 1213). Efficacy was assessed based on the Hamilton Anxiety Rating Scale (HAMA), several anxiety self-rating scales, the Clinical Global Impression (CGI) scale, and the Short Form-36 (SF-36) health status questionnaire. RESULTS: After ten weeks' treatment, Silexan was significantly superior to placebo in reducing the HAMA total score (including the psychic and somatic anxiety sub-scores) and self-rated anxiety. Based on a ≥ 50% HAMA total score reduction, the responder rate ratio was 1.34 favoring Silexan, and the rate ratio of subjects much or very much improved according to the CGI was 1.51. Silexan was also significantly superior in improving the physical and mental health summary scores of the SF-36. There were no significant between-group differences concerning the occurrence of adverse events (AEs), serious AEs, and premature withdrawal due to AEs. CONCLUSIONS: This meta-analysis demonstrates that Silexan exerts significant anxiolytic effects in subthreshold anxiety, GAD and MADD that were consistently reflected in investigator ratings and patient-reported outcomes, including improvement of health-related life-quality, while showing favorable tolerability and safety.

Subthreshold depression - concept, operationalisation and epidemiological data. A scoping review.

PURPOSE: In diagnostic systems (e.g., DSM-5, ICD-10), depression is defined categorically. However, the concept of subthreshold depression (SD) has gained increasing interest in recent years. The purpose of the present paper was to review, based on a scoping review, the relevant papers in this field published between October 2011 and September 2020. MATERIALS AND METHODS: Of the 1,160 papers identified, 64 records could be included in further analysis. The scoping review was conducted using both electronic and manual methods. RESULTS: The main result of the analysis is that the operationalisation criteria used are highly heterogeneous, which also leads to very heterogenous epidemiological data. CONCLUSIONS: Clear conclusions are not possible scrutinising the reported results. Most definitions seem to be arbitrary, with considerable overlap (e.g., between SD and minor depression). The review also revealed that the impact of SD on quality of life and related parameters appear to be in the range of the respective impact of major depression (MD) and therapeutic approaches might be helpful for SD and also for the prevention of conversion from SD to MD. Keeping the presented difficulties in mind, a proposal for the definition of SD is made in the present paper in order to facilitate the discussion leading to more homogeneous criteria.

World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for treatment of anxiety, obsessive-compulsive and posttraumatic stress disorders - Version 3. Part I: Anxiety disorders.

AIM: This is the third version of the guideline of the World Federation of Societies of Biological Psychiatry (WFSBP) Task Force for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Posttraumatic Stress Disorders (published in 2002, revised in 2008). METHOD: A consensus panel of 33 international experts representing 22 countries developed recommendations based on efficacy and acceptability of available treatments. In total, 1007 RCTs for the treatment of these disorders in adults, adolescents, and children with medications, psychotherapy and other non-pharmacological interventions were evaluated, applying the same rigorous methods that are standard for the assessment of medications. RESULT: This paper, Part I, contains recommendations for the treatment of panic disorder/agoraphobia (PDA), generalised anxiety disorder (GAD), social anxiety disorder (SAD), specific phobias, mixed anxiety disorders in children and adolescents, separation anxiety and selective mutism. Selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are first-line medications. Cognitive behavioural therapy (CBT) is the first-line psychotherapy for anxiety disorders. The expert panel also made recommendations for patients not responding to standard treatments and recommendations against interventions with insufficient evidence. CONCLUSION: It is the goal of this initiative to provide treatment guidance for these disorders that has validity throughout the world.

World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for treatment of anxiety, obsessive-compulsive and posttraumatic stress disorders - Version 3. Part II: OCD and PTSD.

AIM: This is the third version of the guideline of the World Federation of Societies of Biological Psychiatry (WFSBP) Task Force for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Posttraumatic Stress Disorders which was published in 2002 and revised in 2008. METHOD: A consensus panel of 34 international experts representing 22 countries developed recommendations based on efficacy and acceptability of the treatments. In this version, not only medications but also psychotherapies and other non-pharmacological interventions were evaluated, applying the same rigorous methods that are standard for the assessment of medication treatments. RESULT: The present paper (Part II) contains recommendations based on published randomised controlled trials (RCTs) for the treatment of OCD (n = 291) and PTSD (n = 234) in children, adolescents, and adults. The accompanying paper (Part I) contains the recommendations for the treatment of anxiety disorders.For OCD, first-line treatments are selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioural therapy (CBT). Internet-CBT was also superior to active controls. Several second-line medications are available, including clomipramine. For treatment-resistant cases, several options are available, including augmentation of SSRI treatment with antipsychotics and other drugs.Other non-pharmacological treatments, including repetitive transcranial magnetic stimulation (rTMS), deep brain stimulation (DBS) and others were also evaluated.For PTSD, SSRIs and the SNRI venlafaxine are first-line treatments. CBT is the psychotherapy modality with the best body of evidence. For treatment-unresponsive patients, augmentation of SSRI treatment with antipsychotics may be an option. CONCLUSION: OCD and PTSD can be effectively treated with CBT and medications.

Beneficial effects of Silexan on co-occurring depressive symptoms in patients with subthreshold anxiety and anxiety disorders: randomized, placebo-controlled trials revisited.

Silexan is a proprietary active substance produced from Lavandula angustifolia, with proven anxiolytic efficacy in subthreshold and generalized anxiety disorder as well as in mixed anxiety and depressive disorder with beneficial impact on anxiety-related sleep disturbances. The pharmacological profile and clinical observations suggest that Silexan may also have an antidepressant effect. To investigate the effect of Silexan on co-occurring depressive symptoms, we present a meta-analysis of the five placebo-controlled clinical trials hitherto performed with Silexan in subthreshold anxiety (n = 3) and anxiety disorders (n = 2). Patients of all trials received Silexan 1 × 80 mg/day or placebo for 10 weeks according to random assignment. Assessment of the antidepressant effect was based on item 'depressed mood' from the Hamilton Anxiety Rating Scale (HAMA) administered in all trials and on the total scores of the Montgomery Åsberg Depression Rating Scale (MADRS) or the Hamilton Depression Rating Scale (HAMD) used in three trials. After 10-week treatment, patients receiving Silexan showed significantly more pronounced score reduction for HAMA item 'depressed mood' than those in the placebo group (p = 0.01). Significant superiority of Silexan over placebo could also be shown for mean MADRS or HAMD total score reduction (three studies; p < 0.01). Silexan-treated patients with more severe depressive symptoms at baseline showed more pronounced improvements than those with milder symptoms. Our meta-analysis clearly shows that Silexan has a beneficial effect on co-occurring depressive symptoms in patients with subthreshold anxiety and anxiety disorders and may, hence, lead to important therapeutic implications for depressive disorders.

Effect of anxiolytic drug silexan on sleep - a narrative review.

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.

Subsyndromal generalised anxiety disorder: operationalisation and epidemiology - a systematic literature survey.

The diagnosis of anxiety disorders, like other psychiatric disorders also, is operationalised since the introduction of diagnostic manuals. The diagnostic criteria of Generalised Anxiety Disorder (GAD) have been tightened in the last decades. This leads to the exclusion of patients with a high level of anxiety, but not fulfilling certain of the GAD-criteria, from effective treatment. Such so-called subsyndromal, subthreshold or subclinical GAD-states, however, often exhibit a comparable burden of disease like the full syndromal disorder and often tend to develop into the full syndromal disorder. The purpose of this review is - beside systematically reporting the papers found in respective data bases from 2013 onwards - to summarise the relevant data regarding definitions, epidemiology and consequences of subsyndromal anxiety states in order to give a comprehensive review.

Chronic vs non-chronic depression in psychiatric inpatient care - Data from a large naturalistic multicenter trial.

BACKGROUND: Around 20% - 30% of depressed individuals experience a chronic form of depression lasting two or more years. This naturalistic study investigates the characteristics and the course of chronic depressed patients (CD) during standard antidepressant treatment in comparison to not chronically depressed (NCD) patients. METHODS: Data of 954 patients were drawn from the prospective naturalistic, multicenter study of the German research network on depression, CD was met as classifier by 113 patients (11.8%), whereas 841 patients (88.2%) had non-chronic courses (NCD). RESULTS: CD was significantly associated with a low age at onset, use of benzodiazepines, psychotherapy at baseline, substance abuse, a depressive personality disorder and a low degree of extraversion. CD patients showed a longer hospital stay, lower remission rates, increased rates of suicidal ideation as well as higher depression scores at discharge. In addition, individuals with chronic depression continued to obtain higher neuroticism scores and lower extraversion scores at discharge. LIMITATION: Results were assessed by a post-hoc analysis, based on prospectively collected data. CONCLUSION: CD patients have an inferior outcome in clinical measures as well as personality dimensions (i.e. low extraversion) compared to non-CD patients. These findings support the notion that CD patients entering a setting of standard psychiatric inpatient care will show less benefit compared to non-CD patients, and that this difference as such may be used as a stratifying marker for providing specialized psychiatric treatment with optimized pharmacological and psychotherapeutic protocols.

The ongoing discussion on termination of life on request. A review from a German/European perspective.

BACKGROUND: Interest in the topic of termination of life has been growing for 2 decades. After legalisation of active euthanasia and assisted suicide (EAS) in the Netherlands in 2002, movements to implement similar laws started in other European countries. However, many people objected to legalisation on the basis of the experiences in the Netherlands and as a matter of principal. METHODS: This selected and focussed review presents the theoretical discussions about EAS and describes the respective parliamentary discussions in Germany and the data and experiences in the Netherlands. It also considers people with mental disorders in the context of termination-of-life services. RESULTS: So far, only a few European countries have introduced legislation on EAS. Legalisation of EAS in the Netherlands resulted in an unexpectedly large increase in cases. The number of people with mental disorders who terminate their lives on request remains low. CONCLUSIONS: Experience from the Netherlands shows that widening criteria for EAS has problematic consequences.KEY POINTSTermination of life on request, which a subgroup of people support, is a matter of ongoing debate.Because of several problematic aspects, including ethical considerations, only a few countries in the world allow active euthanasia or assisted suicide.Even if euthanasia is well regulated, legalising it can have problematic consequences that are difficult to control, such as an unwanted excessive increase in euthanasia cases.The well-documented experiences with the euthanasia law in the Netherlands serve as an example of what is to be expected when euthanasia is legalised.We need to pay close attention to the relationship between suicide and suicide prevention on the one hand and euthanasia acts and promotion of euthanasia on the other.Further ethical, psychological and legal research is needed. In particular, the role of palliative medicine in societies' approach to end-of-life care must be explored in much more detail.

No Abuse Potential of Silexan in Healthy Recreational Drug Users: A Randomized Controlled Trial.

BACKGROUND: Silexan is a lavender essential oil with established anxiolytic and calming efficacy. Here we asked whether there is a potential for abuse in human patients. METHODS: We carried out a phase I abuse liability single-center, double-blind, 5-way crossover study in healthy users of recreational central nervous system depressants. They received single oral doses of 80 mg (therapeutic dose) and 640 mg Silexan, 2 mg and 4 mg lorazepam (active control) and placebo in randomized order, with 4- to 14-day washout periods between treatments. Pharmacodynamic measures included validated visual analogue scales assessing positive, negative, and sedative drug effects and balance of effects; a short form of the Addiction Research Center Inventory; and a drug similarity assessment. The primary outcome measure was the individual maximum value on the drug liking visual analogue scale during 24 hours post-dose. RESULTS: Forty participants were randomized and 34 were evaluable for pharmacodynamic outcomes. In intraindividual head-to-head comparisons of the drug liking visual analogue scale maximum value, both doses of Silexan were rated similar to placebo whereas differences were observed between Silexan and lorazepam and between placebo and lorazepam (P < .001). These data were supported by all secondary measures of positive drug effects and of balance of effects. Differences between placebo and both doses of Silexan were always negligible in magnitude. Moreover, Silexan showed no sedative effects and was not perceived to be similar to commonly used drugs that participants had used in the past. CONCLUSIONS: Silexan did not exhibit any abuse potential in a standard abuse potential detection screen study and is unlikely to be recreationally abused.

Silexan does not affect driving performance after single and multiple dose applications: Results from a double-blind, placebo and reference-controlled study in healthy volunteers.

Anxiolytic drugs often have sedative effects that impair the ability to drive. Our double-blind, randomized crossover trial investigated the effect of Silexan, a non-sedating, anxiolytic herbal medicinal product, on driving performance in healthy volunteers. Part 1 aimed at demonstrating equivalence between 80 mg/d Silexan and placebo. Part 2 was performed to demonstrate superiority of 160 and 320 mg Silexan over 1 mg lorazepam and included a placebo arm for assay sensitivity. Driving performance was assessed in a validated, alcohol-calibrated simulator test. The primary outcome was the standard deviation of the lane position (SDLP). Secondary outcomes included driving errors and sleepiness. Fifty and 25 subjects were randomized in Parts 1 and 2, respectively. In Part 1, Silexan 80 mg was confirmed to be equivalent to placebo after single administration (equivalence range: δ = ±2 cm). The 95% confidence interval (CI) for the SDLP marginal mean value difference Silexan-placebo for single administration was -1.43; +1.38 and thus similar to the 95% CI of -1.45; +0.79 cm for 7 days' multiple dosing. In Part 2, 95% CIs for SDLP marginal mean value differences to lorazepam were -8.58; -5.42 cm for Silexan 160 mg and -8.65; -5.45 cm for 320 mg (p < 0.001). Confirmatory results were supported by secondary outcomes, where results for Silexan were comparable to placebo and more favorable than for lorazepam. The study demonstrates that single doses of up to 320 mg Silexan and multiple doses of 80 mg/d have no adverse effect on driving performance.