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Stopping antidepressants can cause withdrawal (discontinuation) symptoms, the return of the original illness, and rebound. The latter means that the disease will return stronger, faster, or with greater likelihood than if it had not been treated with medication. The Psychiatry Working Group of the Drug Commission of the German Medical Association (AkdÄ) presents the scientific findings and provides practical recommendations for action. Withdrawal symptoms are multiform; unspecific physical symptoms are predominant. Distinguishing them from the recurrence of depressive symptoms can be difficult. Most of them are mild and self-limiting. There is insufficient evidence on the extent and frequency of rebound depression. The rebound risk implies that when establishing the medication, the short-term benefit must be weighed against the possible long-term risk of chronic depression or the possible need for long-term medication. Patients should be informed about the risk of withdrawal both as early as the joint decision-making process about treatment initiation and regularly during the course of treatment. Withdrawal should take place gradually, except in emergency situations, whereby small steps should be taken, especially in the low-dose range.Das Absetzen von Antidepressiva kann Absetzsymptome, die Wiederkehr der ursprünglichen Erkrankung und einen Rebound bewirken. Bei Letzterem kehrt die Erkrankung stärker, rascher oder mit größerer Wahrscheinlichkeit zurück, als wenn keine medikamentöse Behandlung erfolgt wäre. Absetzsymptome sind vielgestaltig; vorherrschend sind unspezifische körperliche Symptome. Ihre Abgrenzung von der Wiederkehr depressiver Symptome kann schwierig sein. Die Evidenz zu Ausmaß und Häufigkeit von Rebound-Depressionen ist unzureichend. Aufgrund des Rebound-Risikos muss bei der Indikationsstellung der kurzfristige Nutzen gegen die mögliche langfristige Gefahr einer Chronifizierung der Depression und gegen das eventuelle Erfordernis einer Dauermedikation abgewogen werden. Patienten sollten schon bei der gemeinsamen Entscheidung über eine Pharmakotherapie sowie regelmäßig im Behandlungsverlauf über die Absetzrisiken aufgeklärt werden. Ein Absetzen sollte außer in Notfallsituationen ausschleichend erfolgen, wobei insbesondere im Niedrigdosisbereich kleinschrittig reduziert werden sollte.

Background In a recent cross-sectional study, we highlighted psychosocial resilience factors associated with good mental health during the first COVID-19-lockdown. However, dynamic concepts of resilience suggest that people’s response to adversity can change over time. To better understand the emergence of resilience, we here examined individual dynamics of stressor resilience during the COVID-19 pandemic. Methods In a longitudinal experience sampling design, participants (N=200) completed six weekly questionnaires assessing current stressor exposure, mental health burden, and resilience factors. We used linear mixed models to investigate within- and between-subject associations between stressor resilience and protective factors. Results Weekly stressor resilience scores were positively associated with subject-level variation in the resilience factors positive appraisal use, positive appraisal of the COVID-19 pandemic, and general self-efficacy (ps

Previous studies suggest a common brain network including the right inferior frontal gyrus and pre-supplementary motor area integral to various types of emotional interference inhibition, i.e. suppression of task-irrelevant stimuli to pursue goal-directed behavior in the context of emotional distraction. This network reacts differently to emotional interference in individual subjects and exhibits a specific spectral signature in the beta-band. Here we analyze 64 channel surface EEG data during emotional interference inhibition operationalized by a Flanker task with preceding emotionally salient stimuli to determine “true phase” estimates and perform real-time (predictive) phase estimation of task-related beta-band oscillations. EEG data was spectrally analyzed, signal-to-noise ratios (SNRs) of periodic components of the power spectra calculated, and non-causal phase estimations (i.e. using data extending both directions around the time point of interest) performed to yield “true phase” estimates of task-related beta oscillations after Flanker signal presentation. Causal phase estimation of task-related EEG beta oscillations was achieved using an autoregressive forward prediction algorithm on data preceding the time point of interest only. Results show that real-time (i.e. causal) phase estimation of beta oscillations in the emotional Flanker task is feasible with satisfactory circular deviations of “true phase” estimates, but needs individual optimization of phase estimation parameters (i.e. window size [samples], FIR filter order, number of samples removed at data window edge, order of the autoregressive model). Findings have implications for the design of real-time EEG-triggered brain oscillation-synchronized TMS experiments to causally study the role of task-related beta-band activity for emotional interference inhibition. This study was supported by the Boehringer Ingelheim Foundation.“

AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca2+-impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability (ID) and neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE). In functional expression studies, mutations lead to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification. Our results show that de-novo variants in GRIA2 can cause neurodevelopmental disorders, complementing evidence that other genetic causes of ID, ASD and DEE also disrupt glutamatergic synaptic transmission. © 2019, The Author(s).

Resilience is associated with a positive and resource-oriented perspective. Therefore, it seems especially attractive for health promotion and prevention. In recent years, interventions to foster resilience have been increasingly developed, which train resilience factors and are mainly conducted in a face to face group format.The question is raised what potential internet-based interventions (i-interventions) that train resilience factors have for health promotion and prevention.Based on a narrative overview, the possibilities for i‑interventions that train resilience factors for health promotion and prevention are investigated and the state of research is described.The effects of the i‑interventions presented here, which aim at fostering resilience, on measures of mental health and well-being are heterogeneous and vary between low to high effects. Stronger evidence for the efficacy of these measures exists for more general i‑interventions that also train resilience factors but are conceptualized for the prevention of specific disorders, such as depression or for stress reduction.Given the heterogeneous nature of intervention contents, theoretical foundations and therapeutic methods used, the heterogeneity of the evidence is discussed. In addition, perspectives for the further development of resource-oriented resilience interventions are outlined.

Stress-related mental disorders are the most prevalent and cost-intensive disorders of our time. On the other hand, the maintenance of mental health despite stressors, i. e. resilience, is a frequent phenomenon. Research on psychological resilience and its underlying mechanisms offers innovative possibilities for health promotion. It requires a consistent understanding of resilience and adequate methods of operationalization.Modern concepts of the definition, operationalization and assessment of resilience as well as its implications for study designs in resilience research.Analysis and discussion of current works and expert recommendations for the design of resilience research.Resilience research is undergoing a period of transition. Based on a new understanding of resilience as a dynamic and modifiable process, new approaches for operationalization and assessment were proposed. These include, for example, a transdiagnostic approach and the identification of resilience mechanisms, the consideration of stressor exposure in measuring the construct, and longitudinal cohort studies.In the upcoming decades, further profitable findings from current prospective longitudinal studies can be expected. One challenge for future resilience research consists in the continuous dissemination and implementation of the approaches described.

Borderline personality disorders (BPD) are severe mental diseases which place high pressure on the psychiatric healthcare system. Nowadays, well-tested, disorder-specific treatment concepts are available also for inpatient treatment in Germany. These show very good and long-term improvements in the psychopathology as well as posttreatment social participation; however, prerequisites for the implementation of these evidence-based inpatient psychotherapy programs are well-trained treatment teams and appropriate financing of resource expenditure.The aim was to formulate a definition of normative needs for treatment duration and intensity for a guideline-conform, empirically proven and effective inpatient treatment of borderline personality disorder as well as the derived personnel requirements in comparison to the currently available resources within the framework of the Psychiatry Personnel Act (Psych-PV).The resource requirements were established based on evaluated hospital ward models, the recommendations of the S2 guidelines and the criteria of specialist societies and compared with the personnel stipulations according to the Psych-PV.The results for a normatively established treatment program showed a pronounced deficit in the financing of the evaluated resource requirements, even when the stipulations laid down in the Psych-PV were implemented to 100 %.Disorder-specific inpatient treatment programs for borderline personality disorder have been scientifically proven to be highly effective; however, resource analyses show that the personnel requirements necessary for effective implementation of these programs are much higher than those allocated by the funding according to the Pysch-PV. The current underfunding leads to inadequate treatment outcomes with high readmission rates and as a result high direct and indirect costs of illness.

Bei geringer Wirksamkeit hat die Gabe von Antipsychotika zur Behandlung neuropsychiatrischer Storungen bei Demenz eine hohe Rate unerwunschter Wirkungen. Die Risiken sind zum Teil schwerwiegend und schliesen eine erhohte Rate zerebrovaskularer Ereignisse sowie eine erhohte Mortalitat ein. Wenngleich neuropsychiatrische Symptome bei Demenzen sehr haufig sind, besteht der Eindruck, dass Antipsychotika moglicherweise zu haufig ohne klare Indikation und vor allen Dingen zu lange verordnet werden. Antipsychotika sollen erst nach Ausschopfung aller nichtpharmakologischen Interventionsmoglichkeiten eingesetzt werden. Unverzichtbar sind eine prazise Definition des Behandlungsziels und eine konsequente Therapiekontrolle.

Remission, i.e. the complete absence of symptoms, is the major goal in the treatment of major depressive disorders because residual symptoms cause less functioning and a worse outcome. Despite several treatment steps, numerous patients do not reach complete remission of symptoms. In these patients, it is necessary to rule out several possible causes, including inadequate pharmacotherapy, to confirm the diagnosis of treatment-resistant depression (TRD). In the treatment of TRD, pharmacotherapy plays a central role. Nonpharmacological treatment strategies such as psychotherapy, electroconvulsive therapy, and other brain stimulation methods are also used for TRD treatment and are discussed elsewhere in this issue. Regarding complex pharmacotherapy of TRD, only a limited number of randomized-controlled trials have been done. In consequence, treatment decisions are often based on clinical experience, case series, and uncontrolled studies. Nevertheless, there are some interesting new developments, which are summarized and assessed on the basis of existing evidence in this article. Afore, we present an overview of the most important definitions, epidemiologic data, diagnostic needs and methods for treatment optimization. We end with a critical view on the present and future development of antidepressant drugs.

Consult letters are the main way of relaying information between attending physicians involved in patient treatment at different levels of care and should therefore reach continuing care physicians with minimal delay. The quality assurance project described here was intended to reduce dispatch times for inpatient consult letters at our department of psychiatry and psychotherapy. To accomplish this, different measures were put to work at two levels of intervention. These included standardizing work flow, centralizing and optimizing work distribution in the secretaries' office, enabling faster access to typewritten consult letters by way of central data storage on the clinic's server, sending email notifications to all persons involved, using a central office for signing letters, and prompt monitoring and reporting of consult letter delays. These interventions helped reduce the average delay of dispatching consult letters from 29 days to 11. All in all, the project led to a high degree of workplace satisfaction for all persons involved and should be adaptable to other departments and units without difficulty. In our own department, ward-specific consult letter efficiency has become an important quality indicator.

ZusammenfassungIn den vergangenen Jahrzehnten wurden mehr als 30 randomisiert kontrollierte Therapiestudien zur pharmakotherapeutischen Behandlung der Borderline-Persönlichkeitsstörung publiziert. Dies ist mehr als bei jeder anderen Persönlichkeitsstörung, aber wenig im Vergleich zu anderen Erkrankungen wie etwa Depressionen und Schizophrenien. Daher geben die hier dargestellten Empfehlungen zur Pharmakotherapie nur einen groben Orientierungsrahmen. Kein Medikament ist zur Therapie zugelassen, und Psychotherapie sollte grundsätzlich bevorzugt werden. Dennoch kann eine Therapie mit Stimmungsstabilisierern und ggf. Antipsychotika der 2. Generation einzelne psychopathologische Symptome, z. B. Impulsivität oder Schwierigkeiten in der Kontrolle von Wut und Ärger positiv beeinflussen. Medikamente sollten kurzfristig und mit klaren Zielen verordnet werden. Polypharmazie ist wenn immer möglich zu vermeiden.

Methylation of the promoter of brain-derived neurotrophic factor exon IV and antidepressant response in major depression

There is evidence from both human and animal research that 5‐hydroxytryptamine (5‐HT)3 receptor antagonists, particularly tropisetron, exert analgesic and antiinflammatory effects. However, the underlying mechanisms of these effects have not yet been investigated in detail. Therefore, the antiinflammatory effects of tropisetron and ondansetron were investigated in human monocytes. In human monocytes, both lipopolysaccharide (LPS)‐stimulated tumour necrosis factor (TNF)‐α and interleukin (IL)‐1β secretion were dose‐dependently inhibited by tropisetron starting at a concentration of 5 μg/mL and reaching maximal levels at 25 μg/mL (IC50: 32 μg/mL and 12 μg/mL, respectively). LPS‐induced IL‐6 and PGE2 release was only slightly inhibited at high doses, whereas LPS‐induced release of IL‐8 and matrix metalloprotease (MMP)‐9 was not affected. In conclusion, our data show that the binding of tropisetron to 5‐HT3 receptors results in antiinflammatory effects through inhibition of TNF‐α/IL‐1β, which might explain th...

Eine Metaanalyse legt nahe, dass die Gabe einer Z-Substanz die Wirkung von Antidepressiva boostern konnte. Allerdings lohnt es sich, die Effektstarke einmal genauer anzusehen.

The neuropeptide substance P is a major mediator of neurogenic inflammation and immunomodulatory activities within the central and peripheral nervous system. In several cell types, substance P induces the expression of proinflammatory cytokines that have been implicated in the pathogenesis of different neuropathologies. Substance P preferentially binds to NK-1, a receptor of the neurokinin family, but how the receptor-elicited signal is translated into inflammatory gene expression is not yet understood. In this work, we describe that in U373 MG astrocytoma cells, nanomolar concentrations of substance P potently triggered activation of NF-kappa B, a transcription factor involved in the control of cytokine expression and apoptosis. Substance P-induced NF-kappa B activation was associated with the increased mRNA expression and secretion of IL-8, an NF-kappa B-controlled target gene. The stimulatory effect of substance P was specific, since an NK-1-selective receptor antagonist completely prevented NF-kappa B activation in response to substance P, but not IL-1 beta. In addition, we show that the activity of substance P required mobilization of intracellular calcium and formation of reactive oxygen intermediates as second messengers. Our results suggest that NF-kappa B may be an important component controlling neurogenic inflammation within the peripheral and central nervous system.

Antipsychotics, when used to treat neuropsychological symptoms associated with dementia, are associated with low effectiveness but a high risk of side effects. Some of these unwanted effects are severe and include an increased rate of cerebrovascular events and increased mortality. Although neuropsychiatric symptoms are frequently associated with dementia, it appears that antipsychotics are often used without clear indications and for too long time periods. Antipsychotics should be used only when all non-pharmacological strategies have failed. A clear definition of the treatment target in advance and a continuous monitoring of the therapy are mandatory.

Empirical evidence supports the existence of significant executive deficits in patients with major depressive disorder (MDD) as compared to non-depressed controls. Nevertheless, the effect size of executive dysfunctions in unipolar, non-psychotic MDD as well as their relationship to antidepressant treatment is ambiguous.Meta-analytic methods were used to assess the severity of executive dysfunctions in unipolar, non-psychotic MDD as compared to healthy controls and to investigate their course during antidepressant treatment.Fifteen studies comparing the executive functions of 375 patients with DSM-IV MDD and 481 healthy controls were analysed. Furthermore, in three studies, including 122 patients with MDD, the Stroop test performance was examined before and after antidepressant treatment. Patients with MDD performed 0.439 up to 1.18 (P0.0001) standard mean differences worse than healthy controls. The Stroop performance improved during the course of treatment (P = 0.0001).We revealed significant executive dysfunctions in patients with unipolar, non-psychotic MDD compared with healthy controls and an improvement of the Stroop performance during the course of treatment. Future studies with different test procedures are needed to further investigate the influence of antidepressant treatment on executive functions.

We tested the hypothesis that extracts from St. John's wort interfere with protein synthesis induced by substance P (SP), a neuropeptide which has been implicated in the etiopathology of depression and anxiety. Using human astrocytoma cells, which express functional neurokinin (NK)-1-receptors, we investigated whether extracts from St. John's wort are able to inhibit SP-induced synthesis of the cytokine interleukin-6 (IL-6). We found a potent and dose-dependent inhibition of SP-induced IL-6 synthesis by various extracts from St. John's wort. These results do not only give further evidence of the anti-inflammatory effects of St. John's wort, but also lend support to the hypothesis that the antidepressant effect of St. John's wort is, at least in part, a result of its inhibitory effects on SP-induced protein synthesis.

The study examined the ability of trained General Practitioners (GPs) to carry out guideline based diagnostics and therapy of dementia. The article reports the GP-related findings.100 GPs took part in the prospective multi-centre study. 34 GPs started self-guided medical dementia care after attending a special training. The control group of 66 GPs referred patients suspected of dementia to specialist centres. Time of recruiting was 13 months. In case of dementia diagnosis patients and caregivers received professional psychosocial counselling.Trained GPs reported improvements of sensitization and qualification through the project. The cross-linkage of GPs' medical dementia care and psychosocial counselling found a broad acceptance of the participants (GPs, patients, caregivers). 92 of the 156 included patients were diagnosed as dementia. Guideline conformity was violated in 65.4 % of all cases concerning structural imaging and in 30.1 % regarding laboratory tests. "Unspecified Dementia" was the most frequent ICD-10-diagnosis by GPs.Despite the broad acceptance of the project a limited guideline-conformity as well as the diagnostic uncertainty suggests that the implemented training is only a first step towards GP guided dementia care. To extend GPs guided dementia care and to improve the quality of GPs dementia diagnostics and therapy sensitization of more GPs for active dementia care as well as supervised practical training will be necessary.

Pharmacological neuroenhancement refers to the use of psychoactive substances by healthy subjects with the purpose of cognitive enhancement, e.g., vigilance, concentration, memory, or mood. "Brain doping", however, refers to the illicit use of a subcategory of these substances such as prescription drugs. This subcategory includes psychostimulants (e.g., amphetamines, methylphenidate), modafinil, antidementia drugs (acetylcholine-esterase inhibitors, memantine), and antidepressants (selective serotonin reuptake inhibitors) which are being prescribed for the treatment of ADHD (attention deficit/hyperactivity disorder), Alzheimer's disease, and depression. Only psychostimulants and modafinil show significant effects on concentration, attentiveness, and vigilance in healthy subjects. However, a general use by healthy persons can not be justified because of relevant side effects and safety risks. Caffeine for pharmacological neuroenhancement can be seen as an equally effective alternative. "Brain doping" raises numerous ethical and social concerns that require a continued discussion. Demands of liberalization should be critically questioned.

We analyzed i) the effects of serious life events (SLE) on impulsive aggression, and ii) modulating effects of the COMT Val(158)Met polymorphism on the association between SLEs and impulsive aggression in borderline personality disorder (BPD).One hundred and twelve female BPD patients from Germany were included in this study. Impulsive aggression was assessed by the Buss-Durkee-Hostility Inventory (BDHI).Childhood sexual abuse was associated with lower BDHI sum score (P = 0.003). In COMT Val(158)Val carriers, but not in Val/Met and Met/Met carriers, childhood sexual abuse and the cumulative number of SLEs were associated with lower BDHI sum scores (P0.05).This study analyzing a specific gene x environment interaction in female BPD patients suggests an association between SLEs and impulsive aggression, as well as a modulating effect of the COMT Val(158)Val genotype on the relation between SLEs and impulsive aggression.

Until today the pharmacological therapy of Alzheimer's disease (AD) is still limited to symptomatic temporary improvement or stabilization of cognitive performance and activities of daily living, and the reduction of neuropsychiatric symptoms of the disease. Available symptomatic treatment options are the acetylcholinesterase inhibitors (ACh-I) donepezil, galantamine, rivastigmine, and the partial N-Methyl-D-Aspartat-(NMDA)-antagonist memantine. Further substances with symptomatic targets, especially selective acetylcholine and histamine receptors, are currently under development. Numerous of disease-modifying substances mainly targeting components of the amyloidogenic pathway of AD are presently studied in different phases of preclinical and clinical trials. Against earlier expectations which derived from promising preclinical immunization studies the breakthrough of disease-modification in AD is not in sight yet. Aim of this review is to summarize established pharmacological treatment options and the stage of development of upcoming symptomatic and disease-modifying substances of AD.

Remission, i.e. the complete absence of symptoms, is the major goal in the treatment of major depressive disorders because residual symptoms cause less functioning and a worse outcome. Despite several treatment steps, numerous patients do not reach complete remission of symptoms. In these patients, it is necessary to rule out several possible causes, including inadequate pharmacotherapy, to confirm the diagnosis of treatment-resistant depression (TRD). In the treatment of TRD, pharmacotherapy plays a central role. Nonpharmacological treatment strategies such as psychotherapy, electroconvulsive therapy, and other brain stimulation methods are also used for TRD treatment and are discussed elsewhere in this issue. Regarding complex pharmacotherapy of TRD, only a limited number of randomized-controlled trials have been done. In consequence, treatment decisions are often based on clinical experience, case series, and uncontrolled studies. Nevertheless, there are some interesting new developments, which are summarized and assessed on the basis of existing evidence in this article. Afore, we present an overview of the most important definitions, epidemiologic data, diagnostic needs and methods for treatment optimization. We end with a critical view on the present and future development of antidepressant drugs.