Silexan [1], an essential oil from Lavandula angustifolia flowers, is the active substance of a medicinal product for oral use in the treatment of anxiety disorders. It has been shown to be effective in the treatment of patients suffering from mixed anxiety and depression.

[1] Silexan® is a special essential oil from Lavandula angustifolia, Dr. Willmar Schwabe GmbH & Co. KG, Karlsruhe, Germany

The trial (ISRCTN36202964) was conducted to investigate the antidepressant efficacy of Silexan in patients with a major depressive episode compared to placebo and Sertraline.

Adult patients (≥18 years) suffering from a major depressive episode of mild to moderate severity according to ICD‑10 were included. Further inclusion criterion was a total score of 19 – 34 points in the Montgomery-Asberg-Depression Rating Scale (MADRS). Randomised patients took 80 mg Silexan, 50 mg Sertraline, or placebo once daily over 8 weeks. Primary efficacy endpoint was the change of the MADRS total score between baseline and week 8. Response (a reduction of the MADRS total score ≥50%), remission (MADRS total score <10 at the end of the treatment), the Patient Health Questionnaire PHQ-9, the Beck Depression Inventory, the Clinical Global Impressions, and the Sheehan Disability scale served as secondary endpoints.

The full analysis set consisted of 498 patients. Between the start and end of treatment, the MADRS total score decreased by 12.1 (13.3, 11.0) points (adjusted mean, 95% confidence interval) in patients treated with Silexan, by 12.6 (13.7, 11.5) points in patients treated with Sertraline, and by 9.95 (11.1, 8.77) points under placebo. The confirmatory analysis proved that Silexan was significantly superior to placebo (p<0.01, ANCOVA). Internal validity could be shown since the treatment effects of the active comparator Sertraline were also more pronounced compared to placebo (p<0.01). There were no relevant differences between Silexan and Sertraline. Response was achieved by 53.5% of the patients in the Silexan group, by 54.0% of the patients in the Sertraline group, and by 41.5% of the patients in the placebo group. 44.4% of the patients treated with Silexan were remitter, compared to 45.2% under Sertraline and 32.6% under placebo. In both active treatment groups responder and remission rates were higher than in the placebo group (p < 0.05). Results of the secondary endpoints were in line with the results of the primary endpoint.

In a large phase III clinical trial, Silexan was more effective than placebo and not different to Sertraline in patients with a major depressive episode. Treatment effects were clinically relevant.

S. Kasper Consultant of: In the past 3 years Dr Kasper served as a consultant or on advisory boards for Angelini, Biogen, Boehringer, Esai, Janssen, IQVIA, Mylan, Recordati, Rovi, Sage and Schwabe; and he has served on speakers bureaus for Angelini, Aspen Farmaceutica S.A., Biogen, Janssen, Recordati, Schwabe, Servier, Sothema, and Sun Pharma., Speakers bureau of: In the past 3 years Dr Kasper served as a consultant or on advisory boards for Angelini, Biogen, Boehringer, Esai, Janssen, IQVIA, Mylan, Recordati, Rovi, Sage and Schwabe; and he has served on speakers bureaus for Angelini, Aspen Farmaceutica S.A., Biogen, Janssen, Recordati, Schwabe, Servier, Sothema, and Sun Pharma., E. Seifritz Consultant of: Schwabe, Janssen, Speakers bureau of: Schwabe, Janssen, H.-P. Volz Consultant of: Schwabe, Janssen, Speakers bureau of: Schwabe, Janssen

Acute psychotic disorders are increasingly being diagnosed in people addicted to PASA part of these patients develops chronic psychotic disorders for reasons that still insufficently known.

The aim of the study was to determine preventive potential of antipsychotics in the development of chronic psychotic disorders as well as possible side effects of theur use.

The prospective retrospective qualitative study conducted in the period Septmeber 2017-September 2022.Data from medical records and electronic databases were used in the study.A structured questionnare for conductin research,a clinnical psychatic inteview,MMPI 202,tests to determine of ilegal PAS in body flluids.

According to the results of the study adequate treatment of the underlying desease,fewer or complete abscence of relapses,social and psychoteraapeutic support had the greater effects.In the group of opiate addicts an adequate dose of supstitution therapy it often played a crucial role.

In experimental conditions the hypotesis about the preventive effect of antipsychotics on the development of psychotic disorders in peoplle addicted to PAS.On the contrary a whole series of new questions has beenopened.

None Declared

Silexan manufactured from Lavandula angustifolia showed favorable safety and efficacy in subthreshold and generalized anxiety disorder (GAD), mixed anxiety and depressive disorder (MADD), and further, especially subsyndromal psychiatric manifestations including depression, sleep disturbances, restlessness, fatigue and pain.

Since the abovementioned clinical phenotypes were repeatedly observed in the course of the so-called post coronavirus-19 disease (COVID-19) syndrome, which were, importantly, of subsyndromal severity in the most cases, we were confident that Silexan will be efficacious also in this indication.

We report on three adult outpatients treated with Silexan due to psychiatric conditions that occurred in the context of a mild and short-lasting COVID-19 infection.

A 38-years old female experienced fatigue, brain fog, inner tension, restlessness and sad mood with weepiness after recovery of her respiratory COVID-19 infection. Since she did not remit under ongoing psychotherapy (PT), Silexan 80 mg p.o.q.d. was additionally employed and very well tolerated. She achieved full remission of her subthreshold symptoms within one month. A 27-years old male developed GAD including anxiety, inner tension, restlessness, irritability, muscle aches, difficulties in concentrating and in controlling feelings of worry after he recovered from respiratory COVID-19. Following his preference, PT and Silexan 80 mg p.o.q.d. were initiated and very well tolerated. Because of partial response, Silexan was increased to 80 mg twice daily after three weeks. After additional two weeks, he was able to enjoy everyday activities and to comply with working demands without relevant difficulties. A 38-years old female developed a post COVID-19 syndrome with fatigue, anxiety, depression, inner tension, tachycardia, hopelessness and rumination. Due to the current MADD Bupropion 150 mg and subsequently 300 mg p.o.q.d. and Hydroxyzine 25 mg on demand were administered. Although clinical improvement was achieved, the patient discontinued the treatment due to subjective exacerbation of tachycardia and refused any further treatment optimization. Once she agreed to phyto-psychopharmacotherapy, Silexan 80 mg p.o.q.d. was employed and, while well tolerated, increased to 80 mg twice daily after two weeks. The patient was increasingly able to participate at her working and social activities again and stayed stable for four months.

To our knowledge, this is the first report on administering Silexan in subsyndromal and full-blown anxiety and depression with cognitive and psychosomatic symptoms that occurred in the context of COVID-19. While substantial clinical improvements were achieved, no relevant adverse effects occurred.

None Declared

An interatrial communication is present in most neonates. The majority are considered the “normal” patency of the oval foramen, while a minority are abnormal atrial septal defects. Differentiation between the two with transthoracic echocardiography may be challenging, and no generally accepted method of classification is presently available. We aimed to develop and determine the reliability of a new classification of interatrial communications in newborns.

An algorithm was developed based on echocardiographic criteria from 495 newborns (median age 11[8;13] days, 51.5% females). The algorithm defines three main categories: patency of the oval foramen, atrial septal defect, and no interatrial communication as well as several subtypes. We found an interatrial communication in 414 (83.6%) newborns. Of these, 386 (93.2%) were categorised as patency of the oval foramen and 28 (6.8%) as atrial septal defects.

Echocardiograms from another 50 newborns (median age 11[8;13] days, 36.0% female), reviewed by eight experts in paediatric echocardiography, were used to assess the inter- and intraobserver variation of classification of interatrial communications into patency of the oval foramen and atrial septal defect, with and without the use of the algorithm. Review with the algorithm gave a substantial interobserver agreement (kappa = 0.66), and an almost perfect intraobserver agreement (kappa = 0.82). Without the use of the algorithm, the interobserver agreement between experienced paediatric cardiologists was low (kappa = 0.20).

A new algorithm for echocardiographic classification of interatrial communications in newborns produced almost perfect intraobserver and substantial interobserver agreement. The algorithm may prove useful in both research and clinical practice.

Although numerous effective antidepressant (AD) strategies are available for the treatment of major depressive disorder (MDD), many patients do not achieve satisfactory treatment response.

The aims of the present European, cross-sectional, multicenter, naturalistic study were (1) to determine the proportion of patients suffering from primary MDD who received additional psychotherapy to their ongoing psychopharmacotherapy and (2) to identify the associated socio-demographic and clinical patterns.

Patients receiving both treatments were compared to those lacking concomitant additional psychotherapy that was manual-driven psychotherapy (MDP) in all cases.

While 68.8% of a total of 1279 MDD patients received exclusively psychopharmacotherapy, 31.2% underwent a psychopharmacotherapy-MDP combination. The latter patient population was rather younger, higher educated, employed, exhibited an earlier mean age of MDD onset, lower severity of current depressive symptoms with lower odds of suicidality and higher rates of melancholic features, and comorbid asthma and migraine, and was generally treated with lower daily doses of their first-line ADs. Whereas agomelatine was more commonly dispensed in these patients, selective serotonin reuptake inhibitors were more often prescribed in MDD patients lacking additional MDP. No significant between-group differences were detected in terms of treatment outcome.

The fact that the employment of additional MDP was not related to better treatment outcome in MDD represents our major and clinically most relevant finding. Generally, MDP was employed in a minority of our patients who experienced rather beneficial socio-demographic and clinical characteristics. This might reflect an inferior accessibility of these psychotherapeutic techniques for patients who are more severely ill and less socio-economically privileged.

References Bartova L, Fugger G, Dold M, Swoboda MMM, Zohar J, Mendlewicz J, Souery D, Montgomery S, Fabbri C, Serretti A, Kasper S. Combining psychopharmacotherapy and psychotherapy is not associated with better treatment outcome in major depressive disor

The paper presents experiences in working with drug addicts in Ze-Do Canton after the outbreak of the COVID pandemic

The time frame in which the research was conducted was April 15, 2020 to April 15, 2021. Criteria for inclusion in the study were clinically and laboratory-proven dependence on psychoactive substances and participation in some of the types of treatment in our institution. Criteria for exclusion from the study due to population specificity were not defined

. The study was designed as a retrospective-prospective in which the following parameters were monitored: rate of retention in treatment, rate of relapse and overdose, deterioration of basic psychopathology, number of hospitalizations due to worsening addiction or comorbid psychopathology, suicide rate, incidence and prevalence of blood-borne hepatitis and HIV -a, incidence and prevalence of COVID in the addicted population and auto and hetero-destructive behavior of health care users.

The results of the study indicated an increased rate of abuse of substitution therapy, an increased rate of relapse, most often with stimulants, abuse of sedatives, antidepressants and anticholinergics, an increased rate of overdose but no deaths and an increased rate of hospitalization due to worsening basic psychopathology.

The study indicated a deterioration in the quality of health care of addicts to psychoactive substances caused by pandemic working conditions and a marked deterioration in basic psychopathology caused by social distancing and the impossibility of more frequent and direct contact with patients. continuous monitoring

No significant relationships.

The aim of the current study was to explore the effect of gender, age at onset, and duration on the long-term course of schizophrenia.

Twenty-nine centers from 25 countries representing all continents participated in the study that included 2358 patients aged 37.21 ± 11.87 years with a DSM-IV or DSM-5 diagnosis of schizophrenia; the Positive and Negative Syndrome Scale as well as relevant clinicodemographic data were gathered. Analysis of variance and analysis of covariance were used, and the methodology corrected for the presence of potentially confounding effects.

There was a 3-year later age at onset for females (P < .001) and lower rates of negative symptoms (P < .01) and higher depression/anxiety measures (P < .05) at some stages. The age at onset manifested a distribution with a single peak for both genders with a tendency of patients with younger onset having slower advancement through illness stages (P = .001). No significant effects were found concerning duration of illness.

Our results confirmed a later onset and a possibly more benign course and outcome in females. Age at onset manifested a single peak in both genders, and surprisingly, earlier onset was related to a slower progression of the illness. No effect of duration has been detected. These results are partially in accord with the literature, but they also differ as a consequence of the different starting point of our methodology (a novel staging model), which in our opinion precluded the impact of confounding effects. Future research should focus on the therapeutic policy and implications of these results in more representative samples.

Compare quetiapine+antidepressant (AD) with lithium+AD, and quetiapine monotherapy with lithium+AD in open, rater-blinded treatment.

Patients with treatment resistant depression (Thase et al 1997 stage 1 and 2) with severity of MADRS ≥25 received: quetiapine XR 300mg/day plus AD (SSRIs or venlafaxine) (n=229), lithium (monitored to between 0.6 to 1.0 meq/l) plus AD (n=221) or quetiapine XR alone (300mg/day) (n=225) for 6 weeks. Primary efficacy measure was change from baseline in MADRS total score. The pre-specified non-inferiority limit was 3 points on the MADRS.

Fewer patients discontinued on quetiapine+AD (15.2%) than lithium+AD (20.5%) and quetiapine monotherapy (21.5%). Quetiapine+AD and quetiapine monotherapy, were not inferior to lithium+AD in the primary (per protocol) analysis with a mean difference (97.5%CI) on the MADRS of -2.32 (-4.6 to -0.05) favouring add-on quetiapine and -0.97 (-3.24 to 1.31) favouring quetiapine monotherapy. This mandated superiority testing on the modified ITT population showing no significant difference at endpoint.

In a post hoc analysis discounting multiplicity, quetiapine+AD was significantly more effective than lithium+AD on the MADRS change from baseline, p=0.046. The advantage was observed at day 4 (p=0.007) and persisted throughout. Efficacy was supported by CGI-I (p=0.07). Quetiapine+AD showed a numerically greater advantage over lithium+AD in those with two failed treatments (Stage 2) rather than one (Stage 1).

Quetiapine+AD and quetiapine monotherapy, were non-inferior to lithium+AD in treatment resistant depression. There was an early significant and persistent efficacy advantage on MADRS for quetiapine augmentation compared with lithium augmentation of SSRI or venlafaxine treatment.

Serotonergic neurotransmission plays a key role in seasonal changes of mood and behaviour. Higher serotonin transporter availability in healthy human subjects in times of lesser light has been reported in recent studies. Furthermore, seasonal alterations of postsynaptic serotonin-1A receptors have been suggested by a recent animal study. Following that, this study aimed at identifying seasonal alterations of serotonin-1A receptor binding in the living human brain.

Thirty-six healthy, drug-naïve subjects were investigated using PET and the specific tracer [carbonyl-11C]WAY-100635. Regional serotonin-1A receptor binding (5-HT1A BPND) was related to the individual exposure to global radiation. Furthermore, the subjects were divided into two groups depending on individual exposure to global radiation, and the group differences in regional 5-HT1A BPND were determined.

Correlation analysis controlled for age and gender revealed highly significant positive correlations between regional postsynaptic 5-HT1A BPND and global radiation accumulated for 5 days (r=.32 to .48, p=.030 to .002). Highly significant differences in 5-HT1A BPND binding between subjects with low compared to high exposure to global radiation were revealed (T=-2.63 to -3.77, p .013 to .001). 20% to 30% lower 5-HT1A BPND was found in the subject group exposed to lower amount of global radiation.

Seasonal factors such as exposure to global radiation influence postsynaptic serotonin-1A receptor binding in various brain regions in healthy human subjects. In combination with seasonal alterations in serotonin turnover and 5-HTT availability revealed in recent studies, our results provide an essential contribution of molecular mechanisms in seasonal changes of human serotonergic neurotransmission.

Regional alterations of serotonergic neurotransmission and functional activation in the amygdalar region of patients with major depression are underpinning its important role in affective disorders. In this study we used fMRI and PET to describe functional and molecular alterations associtated with an astrocytoma in the left amygdalar region in a patient with organic depressive disorder compared to control subjects.

The serotonin-1A (5-HT1A) receptor binding (BPND) was quantified with PET (30 frames, 90 min, 4.4 mm FWHM) in 36 subjects using the radioligand [carbonyl-11C]WAY-100635, and a reference tissue model (MRTM2). In fMRI (3T, EPI inplane resolution 1.6*2.7 mm, 10 AC-PC orientated slices, ST = 3 mm, TE/TR = 31/1000 ms), 32 participants performed emotion discrimination and sensorimotor control tasks. Statistical analysis with SPM5 and unpaired t-tests were performed on molecular and functional data separately.

The astrocytoma was delineated in the serotonin-1A receptor distribution showing (p < 0.01, uncorrected) regional BPND decrease. The ipsilateral thalamus and bilateral habenula regions displayed (p < 0.001; uncorrected) BPND increase. The fMRI data showed significantly (p < 0.05; uncorrected) reduced activation in the affected amygdalar region, ipsilateral fusiform gyrus, bilateral orbitofrontal cortex and temporal regions and increased activation in the contralateral temporal pole.

Lower serotonin-1A receptor binding in the left amydala region reflects the glial provenance of the tumor. The increased receptor binding in the habenulae might be associated with altered monoaminergic neurotransmission and depressive symptoms according to the influence of the habenulae on monoaminergic nuclei. The functional data demonstrate neuroplastic changes beyond affected areas and might indicate compensatory mechanisms.

To compare the efficacy of aripiprazole and haloperidol for the treatment of acute relapse in chronic schizophrenia.

Across two 52-week double-blind studies, 1294 patients with acute relapse of chronic schizophrenia were randomized to aripiprazole 30 mg/day (n=861) or haloperidol 10 mg/day (n=433). The mean change in (Positive and Negative Syndrome Scale) PANSS Total score, PANSS Positive score were secondary endpoints in both studies. Post-hoc, a measure of excitement and hostility was derived from PANSS score items by factor analysis. The scales were administered at baseline and at each double-blind study visit (Weeks 1-8, 10, 12, 14, then every 4 weeks to Week 52).

Aripiprazole produced similar improvements to haloperidol in PANSS Total score (last observation carried forward, LOCF). Among those patients who completed the study, aripiprazole showed a significantly greater improvement in PANSS Total score compared with haloperidol at Weeks 26 and 52. A similar improvement in PANSS Positive score was seen with aripiprazole and haloperidol (LOCF and observed cases [OC]). Symptoms of excitement and hostility also improved similarly with both agents throughout the study (LOCF and OC).

Aripiprazole showed similar efficacy to haloperidol over the 52-week study, and significantly greater efficacy among those patients who stayed on treatment. Thus, aripiprazole is a useful agent for long-term maintenance therapy in schizophrenia.

Over the recent years, meta-analysis has become a very influential tool to synthesize information from multiple primary studies of similar design. Widespread use of increasingly complex statistical methods makes it ever more challenging to adequately assess the results reported and conclusions drawn in meta-analyses of psychopharmacological studies.

This study aimed to identify potential fallacies of meta-analytic reporting and interpretation by in-depth examination of recent publications on anti-depressant medication.

Published meta-analytic datasets were re-analysed and the results and possible interpretations obtained in this way were compared with the published results and interpretations.

Several widespread methodological problems were identified in the example studies. As most important among these appear the choice of effect size measures and modeling approaches, as well as the related risk of data dredging. Concerning the level of granularity, two pitfalls encountered were inappropriate aggregation of original data and lack of adequate subgroup analyses. Finally, a low level of transparency regarding data and methodology often hampers re-analysis and cross-checking of reported findings by peers.

The difficulty of replicating meta-analytic results on independent data leads to the often conclusive nature of meta-analytic findings, and therefore a realistic assessment of the limitations of the respective analysis is pertinent. To this end, practically relevant quality criteria for readers to bear in mind when dealing with meta-analytic publications are summarized in a ten point checklist for a rough assessment of the quality of meta-analyses by the reader.