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.

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.

Factors associated with sick leave duration in patients suffering from major depressive disorder initiating antidepressant treatment: a real-world evidence study in Germany and Spain.

OBJECTIVE: To describe MDD patients starting antidepressant (AD) treatment by pharmacological approach and identify factors associated with a longer sick leave (SL) duration. METHODS: Retrospective study on IQVIA German Disease Analyser (specialists) and Spanish Longitudinal Patient Database (general practitioners and specialists). MDD patients initiating AD treatment between July 2016-June 2018 were grouped by therapeutic approach (AD monotherapy vs. combination/switch/add-on) and their characteristics were analysed descriptively. Multiple logistic regression models were run to evaluate factors affecting SL duration (i.e., >30 days). RESULTS: One thousand six hundred and eighty-five patients (monotherapy: 58%; combination/switch/add-on: 42%) met inclusion criteria for Germany, and 1817 for Spain (monotherapy: 83%; combination/switch/add-on: 17%). AD treatment influenced SL duration: combination/switch/add-on patients had a 2-fold and a 4-fold risk of having >30 days of SL than monotherapy patients, respectively in Germany and Spain. Patients with a gap of time between MDD diagnosis and AD treatment initiation had a higher likelihood of experiencing a longer SL both in Germany and Spain (38% higher likelihood and 6-fold risk of having >30 days of SL, respectively). CONCLUSIONS: A careful and timely selection of AD treatment approach at the time of MDD diagnosis may improve functional recovery and help to reduce SL, minimising the socio-economic burden of the disease.Key pointsThe major depressive disorder has a substantial impact on work absenteeism.The present study aimed to describe MDD patients starting antidepressant (AD) treatment depending on the pharmacological approach and to identify factors associated with longer sick leave (SL) duration.Patients receiving AD monotherapy had a lower likelihood of having more than 30 days of sick leave than those receiving AD combination/switch/add-on.Patients for whom a gap of time between MDD diagnosis and initiation of AD treatment was observed, showed a higher likelihood of having more than 30 days of sick leave.Because findings from this analysis relied on secondary data, the authors would like to claim the urgency of conducting prospective observational studies that further investigate the effect that different AD therapeutic approaches and timely initiation of treatment might exert on patients' recovery.

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.

Sick leave duration as a potential marker of functionality and disease severity in depression.

Objective: To discuss the impact of depression on work and how depression-related sick leave duration could be a potential indicator and outcome for measuring functionality in depression.Methods: Our review was based on a literature search and expert opinion that emerged during a virtual meeting of European psychiatrists that was convened to discuss this topic.Results: Current evidence demonstrates that depression-related sick leave duration is influenced by multiple disease-, patient- and work-related factors, together with societal attitudes towards depression and socioeconomic conditions. A wide variety of pharmacological and non-pharmacological treatments and work-based interventions are effective in reducing depression-related sick leave duration and/or facilitating return to work. Recent real-world evidence showed that patients treated with antidepressant monotherapy appear to recover their working life faster than those receiving combination therapy. Although depression-related sick leave duration was found to correlate with severity of depressive symptoms, it cannot be used alone as a viable marker for disease severity.Conclusions: Given its multifactorial nature, depression-related sick leave duration is not on its own a viable outcome measure of depression severity but could be used as a secondary outcome alongside more formal severity measures and may also represent a useful measure of functionality in depression. Key pointsDepression in the working population and depression-related sick leave have a profound economic impact on societyDepression-related sick leave duration is influenced by multiple disease-, patient- and work-related factors, together with societal attitudes towards depression and socioeconomic conditionsA wide variety of pharmacological and non-pharmacological treatments and work-based interventions have been shown to be effective in reducing depression-related sick leave duration and/or facilitating return to workIn terms of pharmacological intervention, recent real-world evidence has shown that patients treated with antidepressant monotherapy are able to recover their working life faster than those treated with combination therapyAlthough depression-related sick leave duration has been shown to correlate with severity of depressive symptoms, it is not a viable outcome measure of depression severity on its own, but could be used as secondary outcome alongside more formal clinician- and patient-rated severity measuresDepression-related sick leave duration may, however, represent a viable outcome for measuring functionality in depression.

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.

Predictors of sick leave days in patients affected by major depressive disorder receiving antidepressant treatment in general practice setting in Germany.

OBJECTIVE: To identify sick leave days (SLD) predictors after starting antidepressant (AD) treatment in patients affected by major depressive disorder (MDD), managed by general practitioners, with a focus on different AD therapeutic approaches. METHODS: Retrospective study on German IQVIA® Disease Analyser database. 19-64 year old MDD patients initiating AD treatment between July-2016 and June-2018 were grouped by therapeutic approach (AD monotherapy versus combination/switch/add-on). Data were analysed descriptively by AD therapeutic approach, while a zero-inflated Poisson (ZIP) multiple regression model was run to evaluate SLD predictors. RESULTS: 8,891 patients met inclusion criteria (monotherapy: 66%; combination/switch/add-on: 34%). All covariates had an influence on SLD after AD treatment initiation. Focussing on variables that physicians may more easily intervene to improve outcomes, it was found that the expected SLD number of combination/switch/add-on patients was 1.6 times that of monotherapy patients, and the expected SLD number of patients diagnosed with MDD before the decision to start AD treatment was 1.2 times that of patients not diagnosed with MDD. CONCLUSIONS: A patient tailored approach in the selection of AD treatment at the time of MDD diagnosis may improve functional recovery and help to reduce the socio-economic burden of the disease.KEY POINTSFew studies previously investigated the effect of antidepressant treatment approaches on sick leave days in major depressive disorder.To the authors' knowledge, this is the first study evaluating the effect of different antidepressant treatment approaches on sick leave days in major depressive disorder in German patients.Patients receiving antidepressant monotherapy treatment seemed to lose fewer working days than patients receiving antidepressants combination/switch/add-on therapy, both before and after starting treatment, even if differences were more pronounced after treatment has started.The use of antidepressant monotherapy or combination/switch/add-on therapy was the strongest predictor of sick leave days after starting antidepressant treatment: the expected number of sick leave days for the combination/switch/add-on group was 1.6 times that of the monotherapy group.Among factors associated with increased sick leave days, antidepressant therapeutic approach and the promptness of starting the antidepressant treatment when major depressive disorder is diagnosed, are those on which physicians may more easily intervene to improve outcomes.Findings from the present study suggest that a patient tailored approach may improve functional recovery and help reducing the socio-economic burden of the disease.

Rapid efficacy of aripiprazole in the treatment of catatonic depression/catatonia with consideration of the drug's unique receptor profile: a case report.

Catatonia is a widespread problem in psychiatric hospitals as approximately 10% of patients present with catatonic symptoms upon admission. Catatonia carries the risk of severe, even fatal complications. The first line treatment is usually electroconvulsive therapy (ECT) or benzodiazepines, but ECT may not be readily available and benzodiazepines may not always be effective. We describe the case of a patient presenting with severe symptoms of catatonic depression who completed a 3-day course of 25 mg aripiprazole that rapidly resolved his catatonic symptoms. Several cases have already been reported where administration of aripiprazole successfully resolved catatonic symptoms after other treatment options had failed. Aripiprazole's efficacy and advantages may lie in its unique receptor profile. It acts as a dopamine D2 receptor (D2 R) antagonist and partial D2 R agonist depending on the precise cellular milieu, which may explain its efficacy and favourable side effect profile compared to other antipsychotics used to treat catatonia. Aripiprazole also partially agonises D3 receptors and serotonin 2 C receptors (5-HT2 C), which may contribute to its antidepressant properties. Aripiprazole enhances gamma-aminobutyric acid (GABA) transmission in certain brain areas, and it is widely agreed that low GABA activity may contribute to catatonic symptoms. Pharmacokinetics studies show that peak plasma levels are reached rapidly, within 2-3 hours of intramuscular administration and 4-6 hours of oral administration. Administration of high-dose aripiprazole (>25 mg/day) should be considered as a viable alternative to ECT and benzodiazepines in patients presenting with catatonic symptoms. Aripiprazole also carries a much lower risk of complications compared to other antipsychotics.

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.

Efficacy of Silexan in subthreshold anxiety: meta-analysis of randomised, placebo-controlled trials.

Subthreshold psychiatric disorders do not fully meet the diagnostic criteria of syndromal disorders but may be associated with comparable disability. To investigate the anxiolytic effect of Silexan, an active substance from lavender oil for oral administration, in patients with subthreshold anxiety, a meta-analysis that included all published trials with Silexan in this indication was performed. Three randomised, placebo-controlled trials in subthreshold anxiety disorders (anxiety disorder not otherwise specified, restlessness and agitation, mixed anxiety and depressive disorder) were included. Eligible participants with a baseline Hamilton Anxiety Rating Scale (HAMA) total score ≥ 18 points received 1 × 80 mg/day Silexan or placebo for 10 weeks. Outcomes included the HAMA, the Pittsburgh Sleep Quality Index, the Zung Self-rating Anxiety Scale, the Clinical Global Impressions questionnaire and the SF-36 health status inventory. Data were analysed using meta-analysis based on pooled raw data of individual patients (random effects models). A total of 697 patients were assessed for efficacy. Silexan was superior to placebo in reducing the HAMA total score during 10 weeks' treatment [mean value difference, 95% confidence interval: 3.83 (1.28; 6.37) points]. Superiority was comparably pronounced for psychic and somatic anxiety as well as for observer- and self-rated anxiety. Silexan had a beneficial effect on sleep (secondary to the anxiolytic effect) without causing sedation and improved the patients' health-related quality of life. Adverse event incidence in both treatment groups was comparable [risk ratio: 1.06 (0.85; 1.33)]. Silexan has a significant and clinically meaningful anxiolytic effect in subthreshold anxiety. The results cannot be generalised to other lavender oil products.

Silexan in anxiety disorders: Clinical data and pharmacological background.

OBJECTIVES: Silexan is a lavender oil preparation available in 80-mg capsules. Here we review clinical trials investigating its anxiolytic efficacy, safety and tolerability in humans, as well as preclinical investigations supporting this therapeutic use. METHODS: Besides three selected publications reporting preclinical investigations, seven clinical trials are included, of which five had a treatment duration of 6 or 10 weeks. Primary outcome measure was the HAM-A total score reduction, while single items were assessed with regard to effects on concomitant depressive symptoms and on quality of sleep. RESULTS: In patients with subthreshold (subsyndromal) anxiety or generalised anxiety disorder (GAD), an anxiolytic effect of Silexan was evident after 2 weeks. HAM-A total score reductions between baseline and end of treatment were significantly superior to placebo in patients with subthreshold anxiety and comparable with those achieved under lorazepam or paroxetine in patients with GAD. In addition, Silexan had beneficial effects on typical concomitant symptoms of anxiety disorders, such as impaired sleep, somatic complaints, co-morbid depression or decreased quality of life. Except for mild gastrointestinal symptoms, Silexan did not induce any adverse effects and did not cause drug interactions, sedation or withdrawal symptoms at daily doses of 80 or 160 mg. CONCLUSIONS: Silexan is a safe and effective treatment in anxiety disorders.

Silexan in generalized anxiety disorder: investigation of the therapeutic dosage range in a pooled data set.

Silexan, a special active substance produced from Lavandula angustifolia, is efficacious in subsyndromal anxiety at a dose of 80 mg/day, but its effective dosage in generalized anxiety disorder (GAD) has yet to be defined. In two double-blind, placebo-controlled trials, daily doses of 10, 40, 80, and 160 mg silexan were administered for 10 weeks. A total of 925 adults with GAD according to Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria and a Hamilton Anxiety Scale (HAMA) total score of at least 18 points were analyzed for efficacy. We assessed the change versus baseline for the HAMA and the Covi Anxiety Scale, the Clinical Global Impressions scale, the Sheehan Disability Scale, and the SF-36 health status questionnaire using analysis of variance and covariance. Silexan 160 mg/day was superior to placebo for all efficacy outcomes investigated, with responder rates exceeding 60% on the basis of HAMA and Clinical Global Impressions criteria. For the 80 mg/day dosage, superiority over placebo could be shown in one trial as well as in the pooled analysis. The risk of adverse events under silexan was similar to placebo for all dosages investigated. In GAD silexan 160 mg/day is efficacious whereas 80 mg/day may represent the lower end of the therapeutic range. Daily doses up to 160 mg were well tolerated.

Pooled Analysis of Four Non-Interventional Studies: Effectiveness and Tolerability of the Antidepressant Agomelatine in Daily Practice.

INTRODUCTION: Meta-analyses are useful to increase knowledge and strengthen evidence about antidepressant treatment supplementary to individual studies. METHODS: A pooled analysis of four multicenter, open-label, prospective, non-interventional studies (2009-2013) was performed to provide further evidence about the antidepressant effectiveness and tolerability of agomelatine (25-50 mg/day) in a large number of non-selected German outpatients with major depressive disorder. The main analysis was performed after 12 weeks (n = 9601) and in subpopulations after 24 and 52 weeks by descriptive statistical methods. RESULTS: Overall, 60.1% of patients were pretreated with antidepressants. Concomitant psychiatric diseases (71.9%), co-medication with antidepressants (18.9%) and/or psychotropic medication (31.9%) were observed. Depressive symptoms improved according to the Clinical Global Impression (CGI) in 81% after 12 weeks, a response was observed in 78.7% (CGI-I ≤2), and remission in 34.5% of patients (CGI-S = 1 or 2). In subpopulations, response was documented in 79.3% (W24) and 75.9% (W52) and remission in 38.1% (W24) and 47.5% (W52), respectively. Over 12 weeks, adverse drug reactions (ADRs) were reported for 511 patients (5.32%), most frequently headache (0.92%) and nausea (0.75%), and serious adverse drug reactions (sADR) for 18 patients (0.19%). Between W12-W24 and W24-W52, ADRs were reported for 0.49%/0.99% and sADRs for 0.05%/0%, respectively. Overall, 49 patients (0.5%) showed clinically relevant transaminase elevations (AST/ALT >3 times upper normal value), with 19 patients (0.2%) showing preexisting elevations at the study start. One patient (0.03%) developed hepatitis with reversible symptoms after treatment discontinuation. ADR predominantly occurred within the first weeks of treatment. Mean weight and body mass index (BMI) remained unchanged over 24 weeks. CONCLUSION: In this pooled data analysis, 9601 depressed patients of clinical practice were evaluated over 12 weeks and subpopulations were also analyzed over 24 and 52 weeks. Agomelatine effectively reduced depressive symptoms (CGI-response and remission) with good general tolerability.

The relevance of 'mixed anxiety and depression' as a diagnostic category in clinical practice.

According to ICD-10 criteria, mixed anxiety and depressive disorder (MADD) is characterized by co-occurring, subsyndromal symptoms of anxiety and depression, severe enough to justify a psychiatric diagnosis, but neither of which are clearly predominant. MADD appears to be very common, particularly in primary care, although prevalence estimates vary, often depending on the diagnostic criteria applied. It has been associated with similarly pronounced distress, impairment of daily living skills, and reduced health-related quality of life as fully syndromal depression and anxiety. Although about half of the patients affected remit within a year, non-remitting patients are at a high risk of transition to a fully syndromal psychiatric disorder. The validity and clinical usefulness of MADD as a diagnostic category are under debate. It has not been included in the recently released DSM-5 since the proposed diagnostic criteria turned out to be not sufficiently reliable. Moreover, reviewers have disputed the justification of MADD based on divergent results regarding its prevalence and course, diagnostic stability over time, and nosological inconsistencies between subthreshold and threshold presentations of anxiety and depressive disorders. We review the evidence in favor and against MADD and argue that it should be included into classification systems as a diagnostic category because it may enable patients to gain access to appropriate treatment early. This may help to reduce patients' distress, prevent exacerbation to a more serious psychiatric disorder, and ultimately reduce the societal costs of this very common condition.