Effects of dosage in new users of lamotrigine inducing epidermal necrolysis: Results of the German Registry of Severe Skin Reactions.

OBJECTIVE: This study was undertaken to determine the impact of dosage in new users of lamotrigine (LTG) and the concomitant intake of valproic acid (VPA) on epidermal necrolysis (EN). METHODS: A total of 102 EN cases with exposure to LTG were identified (1992-2018) in the German Registry of Severe Skin Reactions. All cases are validated by an independent expert committee. Six cases were excluded due to lack of exposure in the relevant time frame. Causality assessment was performed with ALDEN (Algorithm for Assessment of Drug Causality in EN) on definite/probable cases (≥12 years; n = 84). Evaluation of dosing regimen was restricted to cases with complete LTG dosing history (n = 74). RESULTS: Demography showed a mean age of 42.4 years, female predominance (69%), and low mortality (7.3%). Epilepsy was the indication for use in 87.5%. LTG was the very probable cause in 71.4% and probable cause in 28.6%. On average, one additional antiseizure medication was taken, most frequently VPA (43/84). Combined LTG/VPA treatment showed no statistically significant difference in morbidity or mortality. Mean time latency from initiation of LTG to reaction onset was 24.2 days, varying between 21 days with high initial dose and 29.2 days with low initial dose. Low initial LTG dose (n = 9) revealed higher mortality (22.2%) and higher severity (5/9) than high initial dose (n = 35, mortality = 14.3%, 14/35 higher severity). No patient died when the starting dose was as recommended. The highest mortality (25%) was found in patients with no dose increase (n = 8), which correlated with higher age. Despite the recommended or low initial dose, 52.7% of patients developed EN, in contrast to 39.2% with a slow, recommended, or no dose escalation. SIGNIFICANCE: Neither the initial dose, dose escalation, nor the combination with VPA seems to influence the general occurrence of EN. However, EN patients with the recommended starting dose and the recommended dose escalation had the best outcome in terms of clinical severity and mortality.

[Recommendations for the prevention, diagnosis, and therapy of addiction in the elderly]. / Recommandations pour la prévention, le diagnostic et la thérapie des addictions à l'âge avancé.

In old age, the chronic use of substances such as alcohol and sedatives, and more recently opioids, is a major public health and personal problem. Despite this, relatively little attention has been paid to the disorders associated with the use of these substances. These recommendations have been formulated by the Swiss Society for Elderly Psychiatry and Psychotherapy (SPPA) in collaboration with the Swiss Nurses' Association (SNA) and the Swiss Society for Addiction Medicine (SSAM). They provide a summary of the knowledge about addiction disorders in old age for the benefit of those working with patients, with the aim of strengthening prevention, early detection and appropriate interventions.

À l'âge avancé, la consommation chronique de substances comme l'alcool et les sédatifs, et plus récemment les opioïdes, représente un important problème pour les personnes concernées et de santé publique. Malgré cela, relativement peu d'attention a été accordée aux troubles associés à la consommation de ces substances. Les présentes recommandations ont été formulées par la Société suisse de psychiatrie et psychothérapie de la personne âgée (SPPA) en collaboration avec l'Association suisse des infirmières et infirmiers (ASI) et la Société suisse de médecine de l'addiction (SSMA). Elles mettent à la disposition des intervenants auprès des patients un résumé des connaissances au sujet des troubles addictifs à l'âge avancé, avec comme objectif de renforcer la prévention et le dépistage précoce, et des interventions adaptées.

Improved Alertness Is Associated with Early Increase in Serum Brain-Derived Neurotrophic Factor and Antidepressant Treatment Outcome in Major Depression.

BACKGROUND/AIMS: In major depression cognitive impairment is common and may persist despite improvement in psychopathology. So far it is unclear how closely related improvement in cognitive functioning is to the clinical course of depression. Further, it is unclear whether recovery from cognitive impairment is linked to changes in serum brain-derived neurotrophic factor (sBDNF). The objectives of this study were (1) to explore the predictive value of cognitive impairment for therapeutic outcome, and (2) to assess the association between cognitive performance and sBDNF levels over a 6-week course of antidepressant treatment. METHODS: Twenty-five adult patients suffering from major depression underwent standardized treatment with duloxetine. Both severity of depression as assessed by the Hamilton Depression Rating Scale and sBDNF levels were measured at baseline, and after 1, 2 and 6 weeks of treatment. Cognitive performance, i.e. alertness, working memory, and divided attention, was assessed at baseline, after 1 week, and at the end of treatment after 6 weeks. RESULTS: Higher performance in alertness and divided attention at baseline correlated with less severe depression at week 6. During the first week of treatment, a greater increase in sBDNF was associated with a greater improvement in alertness at week 6. CONCLUSION: Greater alertness at baseline was a predictor of favorable antidepressive treatment outcome. Moreover, the early increase in sBDNF correlated with improvement in attention functioning. Thus, recovery from cognitive impairment and an early increase in sBDNF seem to be associated.

[Recommendations for the diagnostic and therapy of behavioural and psychological symptoms of dementia (BPSD)].

INTRODUCTION: The «Recommendations for the Diagnosis and Treatment of Behavioral and Psychological Symptoms of Dementia (BPSD)¼ were developed in parallel with the Swiss National Dementia Strategy 2014-2019 under the auspices of the Swiss Society for Geriatric Psychiatry and Psychotherapy (SGAP) and mark the beginning of a series of recommendations for geriatric psychiatric disorders. They depict the evidence-based state of knowledge about diagnostics and therapy, based on the clinical experience of the experts, and are designed for interprofessional and interdisciplinary use. The non-pharmacological intervention options and pharmacotherapy are discussed in detail. This paper is the revised version of the 2014 publication and compiles the development in this area for everyday clinical practice.

[Physical Activity and Mental Health in the Elderly]. / Körperliche Aktivität und psychische Gesundheit: Fokus Alter.

Physical Activity and Mental Health in the Elderly Abstract. The aging process is closely linked to physiological changes. These physiological changes may lead to an increased vulnerability for developing somatic and mental disorders. Reduced physical activity/sedentary behaviour can enhance this process. In contrast, physical training and sports counteract this process, in particular in the elderly, who may thus gain or maintain a younger biological age. Physical fitness is associated with better mental health in the elderly. Sports and physical activity over the course of life have shown to be of preventive value concerning the development of depression and dementia in old age. Also late-life depression and cognitive impairment (MCI, mild cognitive impairment) can be improved by regular, continuous physical exercise. Some data furthermore suggest that even patients with dementia benefit from physical exercise, especially on behalf of the behavioural and psychic symptoms of dementia (BPSD).

Sports Psychiatry in Competitive Sports.

Mental complaints and illnesses are common health problems in competitive sports, and mental health, like physical health and performance, is an integral dimension in competitive sports. The promotion of mental health and safe management of mental complaints and illnesses in competitive sports requires a qualified medical discipline for mental health: sports psychiatry as well as an interdisciplinary and interprofessional understanding of care and cooperation. In the following article, sports psychiatry in competitive sports will be addressed and (i) mental health promotion and prevention, (ii) the tandem concept of interprofessional care and collaboration, (iii) diagnosis, treatment, and aftercare of mental disorders and illnesses, and (iv) education and training in sports psychiatry will be presented and discussed.

[Sports Psychiatry in Competitive Sports - Interdisciplinary and Interprofessional Care and Collaboration]. / Sportpsychiatrie und -psychotherapie im Leistungssport.

Sports Psychiatry in Competitive Sports - Interdisciplinary and Interprofessional Care and Collaboration Abstract. Mental complaints and illnesses are common health problems in competitive sports, and mental health, like physical health and performance, is an integral dimension in competitive sports. The promotion of mental health and safe management of mental complaints and illnesses in competitive sports requires a qualified medical discipline for mental health: sports psychiatry as well as an interdisciplinary and interprofessional understanding of care and cooperation. In the following article, sports psychiatry in competitive sports will be addressed and (i) mental health promotion and prevention, (ii) the tandem concept of interprofessional care and collaboration, (iii) diagnosis, treatment, and aftercare of mental disorders and illnesses, and (iv) education and training in sports psychiatry will be presented and discussed.

Violence and Abuse in Competitive Sports.

Violence and abuse in competitive sports, such as physical and emotional abuse, physical and emotional neglect and sexual abuse, affect children, adolescents and adults alike and lead to severe physical, psychological and social consequences. In current medical and educational care concepts of athletes, there is a lack of consistent integration of sports/psychiatric, clinical psychological and psychotherapeutic, developmental pediatric and developmental psychological expertise. Problem areas arise from fine lines between harassment, non-physical and physical violence. The present position paper includes recommendations for the development of a concept for the protection of mental health in competitive sports and for coping with mental stress and psychological disorders by qualified medical experts in mental health, i.e., child, adolescent and adult psychiatrists with specific expertise in competitive sports: sports psychiatrists. According to the recommendations, experts should also have and further develop competence in other fields, especially in ethics, child protection, protection against violence and abuse in competitive sports, awareness of and dealing with transgression of boundaries, knowledge about child development, and transparency in training structures and relationships.

[Violence and Abuse in Competitive Sports]. / Gewalt und Missbrauch im Leistungssport.

Violence and Abuse in Competitive Sports Abstract. Violence and abuse in competitive sports, such as physical and emotional abuse, physical and emotional neglect and sexual abuse, affect children, adolescents and adults alike and lead to severe physical, psychological and social consequences. In current medical and educational care concepts of athletes, there is a lack of consistent integration of sports/psychiatric, clinical psychological and psychotherapeutic, developmental pediatric and developmental psychological expertise. Problem areas arise from fine lines between harassment, non-physical and physical violence. The present position paper includes recommendations for the development of a concept for the protection of mental health in competitive sports and for coping with mental stress and psychological disorders by qualified medical experts in mental health, i.e., child, adolescent and adult psychiatrists with specific expertise in competitive sports: sports psychiatrists. According to the recommendations, experts should also have and further develop competence in other fields, especially in ethics, child protection, protection against violence and abuse in competitive sports, awareness of and dealing with transgression of boundaries, knowledge about child development, and transparency in training structures and relationships.

[Recommendations for the Prevention, Diagnostics and Therapy of Addiction Disorders in the Elderly]. / Empfehlungen für die Prävention, Diagnostik und Therapie der Abhängigkeitserkrankungen im Alter.

Recommendations for the Prevention, Diagnostics and Therapy of Addiction Disorders in the Elderly Abstract. Although the chronic consumption of alcohol and sedatives, and increasingly opioids, represents a major problem in old age with consequential damage for those affected, little attention has been paid to the substance abuse disorders in old age. The aim of the present recommendations, a collaboration work of the Swiss Society for Geriatric Psychiatry and Psychotherapy (SGAP), Swiss Nurses Association (SBK) and Swiss Society of Addiction Medicine (SSAM), is to summarize the current state of knowledge in prevention, diagnostics and therapy of substance abuse disorders in old age for an interprofessional clinical team. They are intended to help strengthen prevention and early diagnosis, and consciously emphasize psychotherapy and nursing intervention options.

[Recommendations for the Diagnosis and Therapy of Psychotic Disorders in the Elderly]. / Empfehlungen für die Diagnostik und Therapie psychotischer Erkrankungen im Alter.

Recommendations for the Diagnosis and Therapy of Psychotic Disorders in the Elderly Abstract. Psychotic disorders in the elderly cover a wide range of causes and manifestations. They often occur as part of a depression, dementia, substance abuse or delirium. While psychosis can occur with a first manifestation in advanced age, many patients with chronic psychotic disorders reach a high age. Many elderly individuals are also affected by cognitive impairment and somatic conditions, making a third-party history most relevant. The associated changes in life and the complexity of the individual situation needs to be integrated into the diagnosis and treatment. The presented recommendations have been developed under the lead of the Swiss Society of Old Age Psychiatry (SGAP) in collaboration with the Swiss Association of Nurses (SBK) and the subcommittees for gerontological and psychiatric nursing of the association of nursing science (VFP) as well as further professional societies. We aim to make current knowledge concerning diagnosis and treatment available to the interprofessional teams working in in- and outpatients' settings.

Impact of psychostimulants and atomoxetine on the expression of 8-hydroxyguanine glycosylase 1 in human cells.

Oxidative DNA damage as one sign of reactive oxygen species induced oxidative stress is an important factor in the pathogenesis of various psychiatric disorders. Altered levels of DNA base damage products as well as the expression of the main repair enzyme 8-hydroxyguanine glycosylase 1 have been described. The aim of the present study was to examine the effects of drugs (amphetamine, methylphenidate and atomoxetine) used in the treatment of attention deficit-hyperactivity disorder on the expression of this enzyme via reverse transcriptase-polymerase chain reaction in human neuroblastoma SH-SY5Y and human monocytic U-937 cells at concentrations of 50, 500 and 5,000 ng/ml. We observed decreased expression of this enzyme for all applied substances. In U-937 cells, the significance level was reached after treatment with 5,000 ng/ml amphetamine as well as after treatment with 50, 500 and 5,000 ng/ml atomoxetine. Incubation of SH-SY5Y cells with 50 and 5,000 ng/ml amphetamine and 5,000 ng/ml methylphenidate led to significant decreases of 8-hydroxyguanine glycosylase 1. As a positive correlation between the expression of 8-hydroxyguanine glycosylase 1 and the level of oxidative DNA damage products has been described, we accordingly consider these substances (amphetamine, methylphenidate and atomoxetine) to possibly play a protective role in this process.

Impact of plant extracts tested in attention-deficit/hyperactivity disorder treatment on cell survival and energy metabolism in human neuroblastoma SH-SY5Y cells.

Plant extracts such as Hypericum perforatum and Pycnogenol have been tested as alternatives to the classical ADHD drugs. It has been possible to describe neuroprotective effects of such plant extracts. A reduction of ADHD symptoms could be shown in clinical studies after the application of Pycnogenol, which is a pine bark extract. The impacts of the standardized herbal extracts Hypericum perforatum, Pycnogenol and Enzogenol up to a concentration of 5000 ng/mL on cell survival and energy metabolism in human SH-SY5Y neuroblastoma cells has been investigated in the present examination. Hypericum perforatum significantly decreased the survival of cells after treatment with a concentration of 5000 ng/mL, whereas lower concentrations exerted no significant effects. Pycnogenol( induced a significant increase of cell survival after incubation with a concentration of 32.25 ng/mL and a concentration of 250 ng/mL. Other applied concentrations of Pycnogenol failed to exert significant effects. Treatment with Enzogenol did not lead to significant changes in cell survival.Concerning energy metabolism, the treatment of cells with a concentration of 5000 ng/mL Hypericum perforatum led to a significant increase of ATP levels, whereas treatment with a concentration of 500 ng/mL had no significant effect. Incubation of cells with Pycnogenol and Enzogenol exerted no significant effects.None of the tested substances caused any cytotoxic effect when used in therapeutically relevant concentrations.

Continuous sleep EEG monitoring in PD patients with and without sleep attacks.

The pathogenesis of sleep attacks in Parkinson's disease (PD) is still unresolved. We investigated seven matched pairs of PD patients with and without a history of sleep attacks using continuous sleep EEG recording. According to the event marker altogether 12 sleep attacks were identified in three patients with a history of sleep attacks. All sleep attacks were characterized by NREM stage 1 and 2 sleep, whereas no sleep onset REM episodes were recorded. Five sleep attacks fulfilled our criteria for microsleep episodes lasting less than 120 s. The cumulative duration of microsleep episodes during the day was 27.7+/-20 min in patients with a history of sleep attacks vs. 6.4+/-4.1 min in patients without a history of sleep attacks (p=0.03), i.e., the majority of microsleep episodes were not perceived by the patients. In summary, our study suggests that sleep attacks are intrusions of NREM stage 1 and 2 sleep into wakefulness and can be identical to microsleep episodes. Future studies should systematically address the awareness of short sleep episodes in patients with PD and other disorders with increased daytime sleepiness.

[Treatment of insomnia]. / Therapie der Insomnie.

The prevalence of insomnia is high in the population of western industrial countries (up to 35 %). Sleep disturbance may consequently lead to an impairment of cognitive functions, mood disturbance and metabolic alterations. Therefore, the confirmation of insomnia and its diagnostic characterization is of great importance. Treatment of insomnia is based on its aetiology and intensity. For secondary insomnia treatment of the basic disorder is mandatory. Before the initiation of a symptomatic pharmacological treatment the application of non-pharmacological interventions should be considered. Efficacious pharmacological interventions are non-benzodiazepine hypnotics for a limited time span. If a longer treatment of insomnia is necessary, hypnotic antidepressants and hypnotic neuroleptics (without anti-cholinergic action) can be applied taking the specific side effects into account. Classical benzodiazepines and substances with anti-cholinergic properties should be avoided in particular in long-term treatment and in elderly subjects due to its side effect profile.

Effects of antidepressants on mRNA levels of antioxidant enzymes in human monocytic U-937 cells.

Alterations of antioxidant enzyme activities have been described in a number of psychiatric disorders including major depression. Subsequently, the present study examined the effects of different types of antidepressants (desipramine, imipramine, maprotiline and mirtazapine) in different concentrations (10(-5), 10(-6) and 10(-7) M) on the mRNA levels of various enzymes of the antioxidant system, including both intracellular superoxide dismutase isoforms, glutathione peroxidase and catalase as well as several enzymes of the glutathione metabolism in monocytic U-937 cells after short- and long-term treatment (2.5 and 24 h) via RT-PCR. Results indicated mainly short-term decreases in the mRNA levels of antioxidant enzymes after treatment with these substances in all the concentrations used. In addition, after long-term treatment, significant increases in the mRNA levels were seen in the cases of Cu, Zn superoxide dismutase, gamma-glutamyl-cysteine synthetase, glutathione-S-transferase and glutathione reductase, including the impacts of all the antidepressants used in concentrations of 10(-6) M and 10(-7) M. Based on the large number of significant effects of all types of antidepressants tested on various antioxidant enzymes, we suggest that antioxidant enzymes may represent important targets in the course of antidepressive treatment.

Effect of flumazenil-augmentation on microsleep and mood in depressed patients during partial sleep deprivation.

The antidepressive effect of sleep deprivation (SD) in depressed patients disappears after sleep of the recovery night and after early morning naps. Both can provoke a rapid relapse into depression in SD-responders. In addition, the occurrence of short episodes of sleep (termed microsleep, MS) during partial SD (PSD) is associated with SD-nonresponse, suggesting that MS during the time awake may be related to relapse or PSD-nonresponse. The GABA-benzodiazepine receptor antagonist flumazenil augments vigilance and reduces NonREM-sleep pressure in early morning recovery sleep in volunteers after SD. Therefore, in this study 27 patients with major depression were subjected to a PSD. In a double blind randomized design either flumazenil or placebo was orally applied during PSD in order to examine whether the application of flumazenil reduces sleep propensity and thus, increases antidepressant efficacy of PSD. EEG was registered continuously for 60h by a portable device for the assessment of microsleep episodes at baseline and during PSD. Flumazenil application significantly suppressed frequency and total amount of MS. While the antidepressant efficacy of PSD was not different between flumazenil and placebo during PSD, the subjective mood improved after the recovery night in patients treated with flumazenil. It is concluded that GABAergic mechanisms are involved in the regulation of MS during PSD, which may be related to a mood stabilizing effect after the recovery night. However, the mechanisms underlying the association between the occurrence of MS during PSD and mood variation have to be further clarified.

Use it or lose it! Cognitive activity as a protec-tive factor for cognitive decline associated with Alzheimer's disease.

Because of the worldwide aging of populations, Alzheimer's disease and other dementias constitute a devastating experience for patients and families as well as a major social and economic burden for both healthcare systems and society. Multiple potentially modifiable cardiovascular and lifestyle risk factors have been associated with this disease. Thus, modifying these risk factors and identifying protective factors represent important strategies to prevent and delay disease onset and to decrease the social burden. Based on the cognitive reserve hypothesis, evidence from epidemiological studies shows that low education and cognitive inactivity constitute major risk factors for dementia. This indicates that a cognitively active lifestyle may protect against cognitive decline or delay the onset of dementia. We describe a newly developed preventive programme, based on this evidence, to stimulate and increase cognitive activity in older adults at risk for cognitive decline. This programme, called "BrainCoach", includes the technique of "motivational interviewing" to foster behaviour change. If the planned feasibility study is successful, we propose to add BrainCoach as a module to the already existing "Health Coaching" programme, a Swiss preventive programme to address multiple risk factors in primary care.

Electroencephalographic sleep profiles in treatment course and long-term outcome of major depression: association with DEX/CRH-test response.

Altered electroencephalographic (EEG) sleep patterns are among the most prominent neurobiological findings in depression. Several of these alterations have been suggested to be associated with an unfavorable long-term outcome. However, the impact of pathological sleep parameters on a more recurrent course of illness or vice versa still warrants clarification. Underlying mechanisms may involve systems known to be related to both sleep regulation and long-term course of depression such as the hypothalamic-pituitary-adrenocortical (HPA) axis. Thus, EEG sleep profiles of patients with depression were examined to determine whether (1) the retrospective clinical course of depression, and (2) the prospective long-term outcome in follow-up are associated with EEG sleep parameters. To elucidate related mechanisms HPA system functioning was evaluated by using the combined DEX/CRH test. Fifteen patients with affective disorders who participated in an earlier controlled antidepressant treatment study over 6 weeks were consecutively enrolled in an exploratory follow-up study. The retrospective analysis revealed that during the acute state of depression predominantly sleep continuity measures were associated with the number of previously experienced episodes. While this relation disappeared during treatment and did not correlate with the prospective course, decreased slow wave sleep variables especially in the first sleep period and increased rapid eye movement density were predictive for the occurrence of recurrences in follow-up and, hence, probably reflect more trait-like markers. Additionally, EEG sleep variables unfavorable for long-term outcome were related to excessive stress hormone response in the DEX/CRH-test. These disturbances may reflect important mechanisms responsible of causing and maintaining the disease process of depression.

The combined DEX-CRH test in treatment course and long-term outcome of major depression.

Neuroendocrine studies strongly suggest that the hypothalamic-pituitary-adrenocortical (HPA) system plays a crucial role in the development and course of depression. The interaction between the disease process and HPA system function in long-term course, however, is unclear. Since improvement of HPA system deterioration has been demonstrated to be associated with treatment response, the question has arisen whether the course of therapy response as reflected by, for example, early improvement or response (after 1 or 2 weeks of therapy) is also based on HPA system dysfunction and whether the course of HPA regulation during treatment is only a state marker or has additional predictive implications for long-term outcome. In order to elucidate these questions a long-term study was carried out to investigate whether HPA system disturbance is associated (1) with the course of treatment response, predominantly early treatment response, during acute depression and (2) with the long-term course of depression, i.e. number of episodes. Twenty patients with affective disorders who participated in earlier controlled antidepressant treatment studies over 6 weeks were enrolled in an exploratory follow-up study. Using the combined DEX/CRH test it was demonstrated that (1) early improvement, early treatment response and beneficial treatment outcome after 6 weeks were associated with a lower HPA system activity and that (2) in long-term course of depression the HPA system deterioration increases in parallel with the number of previous episodes. These findings suggest that HPA system alterations are closely related to treatment response and long-term outcome of depression.