[Dramatic changes in the age structure for medical specialists in the field of mental health]. / Dramatische Veränderungen der Altersstruktur bei Fachärzten im Bereich psychischer Gesundheit.

BACKGROUND: Over the past 20 years the importance of treatment of people with mental and neurological disorders has greatly increased. Parallel to this development it has become more difficult to attract young physicians to this field. The aim of this study was to examine the development of the number of physicians specialized in the care of patients suffering from neurological, mental and psychosomatic disorders with special consideration of the age structure. MATERIAL AND METHODS: The analyses were based on the number of professionally active physicians and specialized physicians published by the German Medical Association for the years 2000-2020. Separate age groups were looked at for psychiatry and psychotherapy (PPT), psychosomatic medicine and psychotherapy (PMPT), Nervenheilkunde (formerly psychiatry and neurology together, NHK) and neurology. RESULTS: In comparison to the year 2000 the number of specialized physicians working in PPT (4736 vs. 12,053), neurology (2226 vs. 8355) and PMPT (3543 vs. 4130) increased in 2020, while the number of specialists actively working in NHK decreased (5184 vs. 2301). Parallel to this the proportion of women increased. Dramatic changes occurred concerning the age structure. Currently, 77.7% of specialists working in NHK and 59.7% working in PMPT are over 60 years old. In 2020 there were 2988 specialists aged over 60 years in the discipline of PPT compared to only 1070 under 40 years, which is dramatically different from 20 years earlier when only 181 were over 60 years but 1491 were under 40 years old. CONCLUSION: The overaging of professional specialists and the shortage of junior physicians jeopardize modern and adequate provision of care for mentally ill patients. Possible solutions include a marked increase in medical school capacities as well as strategies to convince young physicians to work in the disciplines of PPT and PMPT.

Telemedical care and quality of life in patients with schizophrenia and bipolar disorder: results of a randomized controlled trial.

BACKGROUND: Schizophrenia and bipolar disorder are serious psychiatric disorders with a high disease burden, a high number of years of life lived with disability and a high risk for relapses and re-hospitalizations. Besides, both diseases are often accompanied with a reduced quality of life (QoL). A low level of quality of life is one predictor for relapses. This study examines whether a telemedical care program can improve QoL. METHODS: Post stationary telemedical care of patients with severe psychiatric disorders" (Tecla) is a prospective controlled randomized intervention trial to implement and evaluate a telemedical care concept for patients with schizophrenia and bipolar disorder. Participants were randomized to an intervention or a control group. The intervention group received telemedical care including regular, individualized telephone calls and SMS-messages. QoL was measured with the German version of the WHOQOL-BREF. Effects of telemedicine on QoL after 6 months and treatment*time interactions were calculated using linear regressions (GLM and linear mixed models). RESULTS: One hundred eighteen participants were recruited, thereof 57.6% men (n = 68). Participants were on average 43 years old (SD 13). The treatment*time interaction was not significant. Hence, treatment had no significant effect either. Instead, gender is an influencing factor. Further analysis showed that social support, the GAF-level and QoL-values at baselines were significant determinants for the improvement of QoL. CONCLUSION: The telemedicine care concept Tecla was not significant for QoL in patients with severe psychiatric disorders. More important for the QoL is the general social support and the level of global functioning of the patients. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00008548, registered 21 May 2015 - retrospectively registered, https://www.drks.de/drks_web/setLocale_EN.do.

Predictors of medication adherence among patients with severe psychiatric disorders: findings from the baseline assessment of a randomized controlled trial (Tecla).

BACKGROUND: Schizophrenia and bipolar disorder are characterized by a high disease burden. Antipsychotic medication is an essential part of the treatment. However, non-adherence is a major problem. Our aim was to examine potential determinants of non-adherence for patients with severe mental disorders. METHODS: Baseline data of the study "Post stationary telemedical care of patients with severe psychiatric disorders" (Tecla) were used. Medication adherence was assessed with the Medication Adherence Report Scale German version (MARS-D). A logistic regression was calculated with age, sex, education, employment status, level of global functioning, social support and intake of typical and atypical antipsychotics as predictors. RESULTS: N = 127 participants were included in the analysis (n = 73 men, mean age 42 years). The mean MARS-D Score was 23.4 (SD 2.5). The most common reason for non-adherence was forgetting to take the medicine. Significant positive determinants for adherence were older age (OR 1.02, 95% CI 1.011-1.024, p < 0.0001), being employed (OR 2.46, 95% CI 1.893-3.206, p < 0.0001), higher level of global functioning (overall measure of how patients are doing) (OR 1.02, 95% CI 1.012-1.028, p < 0.0001), having social support (OR 1.02, 95% CI 1.013-1.026, p < 0.0001), and intake of typical antipsychotics (OR 2.389, 95% CI 1.796-3.178, p < 0.0001). A negative determinant was (female) sex (OR 0.73, 95% CI 0.625-0.859, p = 0.0001). CONCLUSIONS: Especially employment, functioning and social support could be promising targets to facilitate adherence in patients with schizophrenia or bipolar disorder. TRIAL REGISTRATION: This study is retrospectively registered at the German Clinical Trials Register with the trial registration number DRKS00008548 at 21/05/2015.

The transition from primary to secondary school as stressful life event provoking risky drinking behaviors.

This study is based on a drug prevention project for children in the German-Polish border region known as "Pomerania." The aim of this project was to minimize risk behaviors while developing social skills as protective factors through project-specific training interventions. The present study especially investigates the development of social skills and risk behaviors at German and Polish primary schools in the critical transitional period from primary to secondary school. Data on German 4th graders and Polish 6th graders were collected by means of a longitudinal and control group design through 3rd-party assessment from teachers. The data on social skills was collected through the use of standardized assessment instruments. The study established that social skills could indeed be increased through training and that risk behaviors decreased in both of the treatment groups. The control group showed altogether an increase in risk behavior and a decrease in coping skills. In the Polish treatment group, even risk behaviors which had been detected previously decreased. The German control group showed an increase in risk behaviors and a decrease in coping skills. In the case of the younger German pupils, the effectiveness of the interventions was exhibited indirectly. Despite variations in age and cultural differences, the effects of training were noticeable in children from both countries. The intervention program offered the children adequate assistance in order to successfully cope with this stressful life event. It promoted the development of social skills while minimizing risk behaviors.

Validation of life-charts documented with the personal life-chart app - a self-monitoring tool for bipolar disorder.

BACKGROUND: Long-term monitoring in bipolar affective disorders constitutes an important therapeutic and preventive method. The present study examines the validity of the Personal Life-Chart App (PLC App), in both German and in English. This App is based on the National Institute of Mental Health's Life-Chart Method, the de facto standard for long-term monitoring in the treatment of bipolar disorders. METHODS: Methods have largely been replicated from 2 previous Life-Chart studies. The participants documented Life-Charts with the PLC App on a daily basis. Clinicians assessed manic and depressive symptoms in clinical interviews using the Inventory of Depressive Symptomatology, clinician-rated (IDS-C) and the Young Mania Rating Scale (YMRS) on a monthly basis on average. Spearman correlations of the total scores of IDS-C and YMRS were calculated with both the Life-Chart functional impairment rating and mood rating documented with the PLC App. 44 subjects used the PLC App in German and 10 subjects used the PLC App in English. 118 clinical interviews from the German sub-sample and 97 from the English sub-sample were analysed separately. RESULTS: The results in both sub-samples are similar to previous Life-Chart validation studies. Again statistically significant high correlations were found between the Life-Chart function rating assigned through the PLC App and well-established observer-rated methods. Again correlations were weaker for the Life-Chart mood rating than for the Life-Chart function impairment. No relevant correlation was found between the Life-chart mood rating and YMRS in the German sub-sample. CONCLUSION: This study gives further evidence for the validity of the Life-Chart method as a valid tool for the recognition of both manic and depressive episodes. Documenting Life-Charts with the PLC App (English and German) does not seem to impair the validity of patient ratings.

An observational study of inflammation in the central nervous system in patients with bipolar disorder.

OBJECTIVES: The potential influence of infections and immunological changes on the aetiology and pathogenesis of bipolar disorder (BD) has been discussed. Our aim was to detect intrathecal specific antibody synthesis against the neurotropic infectious agents that have previously been linked to BD. METHODS: Paired cerebrospinal fluid (CSF) and serum samples from 40 patients with BD were analysed using the enzyme-linked immunosorbent assay to detect the concentration of antibodies against the following neurotropic infectious pathogens: Toxoplasma gondii (T. gondii), herpes simplex virus (HSV) types 1 and 2, cytomegalovirus (CMV), and Epstein-Barr virus (EBV). The specific antibody index (AI) was calculated, and an AI > 1.4 was considered to be evidence of intrathecal specific antibody synthesis. Twenty-six patients with pseudotumour cerebri served as controls. RESULTS: Eight out of 40 patients with BD displayed specific intrathecal antibody synthesis against at least one of the tested neurotropic agents compared to only one patient in the control group (p = 0.061, not significant). Of these eight patients with BD, no significant prevalence of any particular neurotropic pathogen was evident. Five out of 40 patients with BD showed oligoclonal bands in the CSF, suggestive of a chronic immune reaction in the central nervous system (CNS). CONCLUSIONS: We found evidence for increased production of antibody in the CSF of individuals with BD. However, the trend for polyspecific intrathecal antibody synthesis, as well as the presence of oligoclonal bands, might indicate activation of the intrathecal humoral immune system in a subgroup of patients with BD, as it is known to be associated with autoimmune disorders of the CNS.

Impact of alcohol-related video sequences on functional MRI in abstinent alcoholics.

The object of this study was the identification of brain areas that were significantly more connected than other regions with a previously identified reference region, the posterior cingulate cortex, during the presentation of visual cues in alcoholics. Alcohol-related and neutral video sequences were presented to 30 alcoholics who had been abstinent for at least 4 days. Participants underwent a psychometric assessment before and after the presentation of the video sequences. Functional MRI data were acquired. Psychophysiological interaction analyses were carried out. Participants reported a significant increase in craving and arousal after the presentation of alcohol-related video sequences. The simple contrast alcohol versus neutral was found not to be significantly different in the present study. The brain regions that were found to correlate significantly more with the posterior cingulate cortex under the alcohol-related condition were the inferior parietal lobe, the medial temporal lobe, the inferior frontal gyrus, the postcentral gyrus, and the precuneus. The involvement of these regions in processes of memory, self-control, and self-reflection with a particular focus on alcohol dependence and craving will be discussed.

Clinical management and burden of bipolar disorder: results from a multinational longitudinal study (WAVE-bd).

Bipolar disorder is a mood disorder which requires complex treatment. Current treatment guidelines are based on the results of published randomized clinical trials and meta-analyses which may not accurately reflect everyday clinical practice. This multi-national, multi-centre, observational cohort study describes clinical management and clinical outcomes related to bipolar disorder in real-life settings, assesses between-country variability and identifies factors associated with clinical outcomes. Adults from 10 countries in Europe and South America who experienced at least one mood episode in the preceding 12 months were included. Overall, 2896 patients were included in the analyses and followed for at least 9 months across a retrospective and prospective study phase. Main outcome measures were the number and incidence rate of mood episodes (relapses and recurrences) and healthcare resource use including pharmacological treatments. Relapses and recurrences were reported in 18.2 and 40.5% of patients, respectively; however, the reported incidence rate of relapses was higher than that of recurrences [1.562 per person-year (95% CI 1.465-1.664) vs. 0.691 per person-year (95% CI 0.657-0.726)]. Medication use was high during all episode types and euthymia; the percentage of patients receiving no medication ranged from 11.0% in mania to 6.1% in euthymia. Antipsychotics were the most commonly prescribed drug class in all disease phases except for patients with depression, where antidepressants were more frequently prescribed. Visits to the psychiatrist were the most frequently used healthcare resource. These results provide a description of treatment patterns for bipolar disorder across different countries and indicate factors related to relapse and recurrence.

Predictability of alcohol relapse by hippocampal volumetry and psychometric variables.

We examined the relationship between relapse risk/duration of abstinence and hippocampal volume as well as the moderating role of various psychological factors in 34 patients who fulfilled the diagnostic criteria for alcohol dependence according to ICD-10 and DSM-IV and 16 healthy controls (9 females and 7 males). This study is part of a single-blind, placebo-controlled, parallel-group treatment trial with the anticraving substance acamprosate administered for 3 months. Patients underwent a psychometric evaluation and a measurement of the hippocampus with magnetic resonance imaging before beginning medication (T0). At 2, 4, 8, and 12 weeks after treatment, abstinence was evaluated by phone. Afterwards all patients switched to a long-term open label study with acamprosate. Hippocampal volume did not constitute a predictive factor for relapse probability in abstinent alcoholics. Furthermore, stress level, depressivity, gender, and treatment with the anticraving substance acamprosate did not show a significant correlation with relapse probability. The current investigation could not identify significant risk factors for relapses after successful alcohol withdrawal. Further studies are required to identify crucial factors which are responsible for successful or unsuccessful relapse prevention.

The impact of acamprosate on cue reactivity in alcohol dependent individuals: a functional magnetic resonance imaging study.

Alcohol cue-induced brain activation has been studied extensively in alcoholics. However, little is known about the impact of standard treatment protocols on this phenomenon. The current study aimed at investigating the impact of the anticraving substance acamprosate on alcohol cue-related brain activity. Patients underwent a functional magnetic resonance imaging investigation before the beginning of medication with acamprosate or placebo (T0) and 2 weeks later (T1). All patients also received psychiatric inpatient treatment including psychotherapeutic interventions. Twenty-nine patients were included in the T0 analysis and 22 patients in the T1 analysis. At T0, a cluster in the left and right posterior cingulate cortex, covering parts of the retrosplenial cortex, was significantly associated with alcohol versus neutral cue exposure. At T1, no significant cluster was found for the alcohol-versus-neutral contrast. The analysis of the impact of acamprosate on cue-related activity in the posterior cingulate cortex cluster revealed no significant difference to placebo. These results provide further evidence for the involvement of the posterior cingulate cortex in alcohol cue exposure. However, in comparison with psychiatric inpatient treatment alone, there was no additional effect of acamprosate on cue-related brain activity.

Impaired functioning in euthymic patients with bipolar disorder--HSV-1 as a predictor.

There is a possible association between infectious agents and psychiatric disorders. Previous studies in the US provided evidence for cognitive impairment correlated with Herpes simplex virus type 1 (HSV-1) infection. For a replication study in Europe we chosed individuals diagnosed with bipolar disorder to analyse the correlation with HSV-1 infection. Antibody prevalence was analyzed by using solid phase immunoassay techniques. Cognitive functioning was tested with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Form A, the Trail Making Test A&B, and two subtests from the WAIS III: the Letter Number Sequencing Task and the subtest on information. History and psychopathology was assessed using structured interviews and validated rating scales (SCID, HRSD-21, YMRS, PANSS). Additionally, we investigated social functioning and quality of life using self-assessment-scales (SAS, LQLP). Prevalence rates of antibodies against diverse infectious agents did not differ significantly between patients and controls. We found a significant correlation between cognitive impairment in patients with bipolar disorder and the prevalence of antibodies directed against HSV-1. Cognitive functions were significantly impaired including language, attention, and immediate memory. The results of this study confirm previous findings suggesting that HSV-1 affects cognitive functions in patients with bipolar disorder. This may also result in more impaired functioning, less quality of life and difficulties in social adjustment.

Clinical management and burden of bipolar disorder: a multinational longitudinal study (WAVE-bd study).

BACKGROUND: Studies in bipolar disorder (BD) to date are limited in their ability to provide a whole-disease perspective--their scope has generally been confined to a single disease phase and/or a specific treatment. Moreover, most clinical trials have focused on the manic phase of disease, and not on depression, which is associated with the greatest disease burden. There are few longitudinal studies covering both types of patients with BD (I and II) and the whole course of the disease, regardless of patients' symptomatology. Therefore, the Wide AmbispectiVE study of the clinical management and burden of Bipolar Disorder (WAVE-bd) (NCT01062607) aims to provide reliable information on the management of patients with BD in daily clinical practice. It also seeks to determine factors influencing clinical outcomes and resource use in relation to the management of BD. METHODS: WAVE-bd is a multinational, multicentre, non-interventional, longitudinal study. Approximately 3000 patients diagnosed with BD type I or II with at least one mood event in the preceding 12 months were recruited at centres in Austria, Belgium, Brazil, France, Germany, Portugal, Romania, Turkey, Ukraine and Venezuela. Site selection methodology aimed to provide a balanced cross-section of patients cared for by different types of providers of medical aid (e.g. academic hospitals, private practices) in each country. Target recruitment percentages were derived either from scientific publications or from expert panels in each participating country. The minimum follow-up period will be 12 months, with a maximum of 27 months, taking into account the retrospective and the prospective parts of the study. Data on demographics, diagnosis, medical history, clinical management, clinical and functional outcomes (CGI-BP and FAST scales), adherence to treatment (DAI-10 scale and Medication Possession Ratio), quality of life (EQ-5D scale), healthcare resources, and caregiver burden (BAS scale) will be collected. Descriptive analysis with common statistics will be performed. DISCUSSION: This study will provide detailed descriptions of the management of BD in different countries, particularly in terms of clinical outcomes and resources used. Thus, it should provide psychiatrists with reliable and up-to-date information about those factors associated with different management patterns of BD. TRIAL REGISTRATION NO: ClinicalTrials.gov: NCT01062607.

The Hypomania Checklist-32 and the Mood Disorder Questionnaire as screening tools--going beyond samples of purely mood-disordered patients.

BACKGROUND: Bipolar disorders are often not recognized. Several screening tools have been developed, e.g., the Hypomania Checklist-32 (HCL-32) and the Mood Disorder Questionnaire (MDQ) to improve this situation. Whereas the German HCL-32 has been used in non-clinical samples, neither the HCL-32 nor the MDQ has been validated in German samples of mood-disordered patients. Additionally, hardly any prior study has included patients with non-mood disorders or has considered potential effects of comorbid conditions. Therefore the goal of this study was to test the validity of both scales in a diverse patient sample while also taking into account psychiatric comorbidity. METHOD: A multi-site study was conducted involving seven centers. Patients (n=488) completed the HCL-32 and MDQ and were independently interviewed with the Structured Clinical Interview for DSM (SCID). RESULTS: Sensitivity for bipolar I was similar for HCL-32 and MDQ (.88 and .84) but slightly different for bipolar II (.90 and .83), specificity, however, was higher for MDQ. In general, a comorbid condition led to increased scores in both tools regardless of whether the primary diagnosis was bipolar or not. LIMITATIONS AND DISCUSSION: Although we included not just mood-disordered patients, detailed subgroup analyses for all diagnostic categories were not possible due to sample sizes. In summary, HCL-32 and MDQ seem fairly comparable in detecting bipolar disorders although their effectiveness depends on the goal of the screening, psychiatric comorbidity, and potentially the setting.

Efficacy of quetiapine monotherapy in rapid-cycling bipolar disorder in comparison with sodium valproate.

BACKGROUND: Rapid-cycling bipolar disorder is often characterized by a lack of response to psychopharmacological treatment, and a standard therapy has not been developed yet. The aim of this study was to examine the long-term efficacy and safety of a monotherapy with quetiapine or sodium valproate (VPA) in patients with rapid-cycling bipolar disorder. METHODS: This open-label, randomized, parallel group monotherapy pilot study was conducted at 3 German centers. A sample of 38 remitted or partly remitted patients with bipolar disorder and rapid cycling (quetiapine n = 22; VPA n = 16) were treated with quetiapine or VPA (flexible dose design) for 12 months. RESULTS: Forty-one percent of the patients with quetiapine and 50% with VPA completed the trial. On the basis of ITT-LOCF, Life Chart Method data showed that patients being treated with quetiapine had significantly less moderate to severe depressive days than patients on VPA (mean +/- SD, 11.7 +/- 16.9 days vs 27.7 +/- 24.9 days; P = 0.04) while they did not differ in the number of days with manic or hypomanic symptoms. Furthermore, according to the Clinical Global Impression Scale, bipolar version, the responder rates tended to be higher for quetiapine than for VPA. There were no differences found evaluating the Hamilton Depression Rating Scale, the Montgomery-Asberg Depression Scale, and the Young Mania Rating Scale. The incidence of adverse events, especially of orthostatic dysregulation, sedation, and weight gain, was significantly higher in the quetiapine group. CONCLUSIONS: In this study, quetiapine was more effective than VPA on the number of depressive days and similar to VPA in the treatment of manic symptoms. Quetiapine was associated with a greater incidence of side effects, particularly orthostatic dysregulation, sedation, and weight gain.

Attitudes of patients and family members towards implantable psychiatric medication.

INTRODUCTION: Medication is a necessary part of treatment for severe psychiatric illnesses such as schizophrenia and nonadherence to prescribed medication is one of the most important public health issues in psychiatry today. The devastating consequences of nonadherence have motivated the development of novel therapeutic strategies, including a new long-term implantable medication delivery system. METHODS: The current study assesses attitudes towards implantable medication in psychiatric patients and their family members. Patients included in the study had diagnoses of Schizophrenia, Schizoaffective Disorder, Mood or Anxiety related disorders. RESULTS: 49.62% of patients and 74.47% of family members endorse support for implantable medication. CONCLUSIONS: This study demonstrates that implants may be an acceptable alternative to oral and injectable medication for a subset of psychiatric patients and their families.

Effects of substance P and its antagonist L-733060 on long term potentiation in guinea pig hippocampal slices.

The neuropeptide substance P (SP) has been suggested to be involved in several physiological and pathological conditions including learning and memory and the processing of pain. This study investigated for the first time acute effects of SP and the neurokinin-1 (NK-1) receptor antagonist L-733060 on long term potentiation (LTP) in the hippocampus. Electrically evoked fEPSP was tested under the influence of SP in the CA1 region of the guinea pig hippocampus. Concentrations of 1 and 10 microM SP increased fEPSP slopes to 114.3+/-4.5% and 115.8+/-2.7%, respectively. A threshold concentration was found at 0.1 microM SP. The SP-specific NK-1 receptor antagonist L-733060 did not influence fEPSP in a concentration of 1 microM. In experiments with LTP, a significant increase of potentiations after 60 min was seen with 1 microM SP. Even if the initial baseline increase due to SP (1 microM) was subtracted, potentiations were bigger compared to controls. L-733060 (1 microM) suppressed the excitatory effects of 1 microM SP nearly complete and subsequent induced LTP was not increased. In conclusion, SP has excitatory effects in the hippocampus and is able to facilitate LTP via activation of the NK-1 receptor.

Assessing cerebral dysfunction with probe-evoked potentials in a CNV task -- a study in alcoholics.

OBJECTIVES: Contrary to event-related potential (ERP) components N1, N2 and P3, slow ERPs have rarely been used in assessing cerebral dysfunction in mental disorders. Focussing on slow waves (SWs) and on patients with mild cerebral dysfunction, we recorded ERPs in alcoholics using a dual task design. METHODS: ERPs to auditory probes presented either 1s before the warning or 1s before the imperative stimulus of a visual contingent negative variation (CNV) paradigm were recorded from 33 scalp electrodes in 27 alcoholics following detoxification and 12 healthy controls. Independent component analysis (ICA) was used to separate potentially overlapping spatial components. RESULTS: In alcoholics compared to controls, probe ERPs showed increased N2, decreased P3 and increased negative SWs of two types appearing pre- and post-P3, respectively. Both negative SWs significantly correlated with neuropsychological indices reflecting verbal intelligence and memory functions. The increase in probe-evoked N1 and P3 potentials during CNV, putatively associated with enhanced cortical excitability, significantly correlated with clinical features of protracted alcohol withdrawal syndrome in alcoholics. CONCLUSIONS: Our experimental approach revealed two types of negative SWs which strongly correlated with neuropsychological deficits of mildly impaired patients. It is suggested that our methods might enhance diagnostic efficiency of ERPs. An electrophysiological measure of protracted alcohol withdrawal might be useful for managing central nervous system dysfunction in alcoholics.

St John's wort (Hypericum perforatum) modulates evoked potentials in guinea pig hippocampal slices via AMPA and GABA receptors.

The effects of an ethanolic extract of the plant Hypericum perforatum L. (St John's wort) (HYP) and its hydrosoluble fraction (HYPWS) on electrically evoked population spikes and fEPSP were investigated in this study. Concentration dependent (10(-6) to 10(-4) g/l) excitatory effects were found. Above concentrations of 10(-3) g/l, HYP reduced the evoked responses, whereas HYPWS further increased them. Paired pulse facilitation was unaffected with HYPWS (10(-4) to 10(-2) g/l). The excitatory effects of HYPWS were amplified by the GABA(A) and GABA(B) receptor antagonists bicuculline and phaclofen, respectively. These excitations were antagonised by the AMPA receptor antagonist CNQX. Excitations caused by hypericum were not antagonised by the NMDA receptor antagonists D-APV and MK801, the metabotropic glutamate receptor (type I and II) antagonist MCPG, or the L-type calcium channel blocker verapamil. Hypericin and hyperforin, two components of H. perforatum, were found not to be responsible for the excitatory effects of the extract.

Effects of the atypical antidepressant trimipramine on neuronal excitability and long-term potentiation in guinea pig hippocampal slices.

Acute effects of the atypical tricyclic antidepressant (TCA) trimipramine on long-term potentiation (LTP) were investigated in this study. Electrically evoked population spikes (PS) were tested under the influence of trimipramine in the CA1 region of the hippocampus. A concentration of 10 microM trimipramine reduced PS amplitudes to 85.1 +/- 8.8%. They were reduced to 12.2 +/- 8.5% with 50 microM trimipramine. In experiments with LTP, trimipramine 10 microM was applied. Only 8 of 10 tested slices showed LTP. These potentiations were smaller than in the control experiments. LTP could not be induced with 50 microM trimipramine. In conclusion, the influence of trimipramine on LTP is similar to other TCA. It is contended that this contributes to the antidepressant effect of the drug.