Dreaming during a pandemic: Low incorporation of COVID-19-specific themes and lucidity in dreams of psychiatric patients and healthy controls

The present study examined the impact of the COVID-19 pandemic on the emotional quality of dreams, the incorporation of pandemic-related themes, and the occurrence of lucid dreaming. Dream reports and lucidity ratings of psychiatric outpatients (n = 30) and healthy controls (n = 81) during two lockdowns in Germany were compared to those of healthy controls (n = 33) before the pandemic. Results confirmed previous reports that pandemic-specific themes were incorporated into dreams. Overall, however, incorporation into dreams was rare. Contrary to expectations, psychiatric outpatients did not differ from controls in the frequency of dream incorporation of pandemic-related content. Moreover, incorporation was independent of psychiatric symptoms and loneliness. Loneliness was, however, associated with threat-related content, suggesting that it represents a risk for bad dreams but not for crisis-specific dream incorporation. Regarding lucid dreaming, both groups had similar scores for its underlying core dimensions, i.e., insight, control, and dissociation, during the two lockdowns. Scores for control and dissociation but not insight were lower compared to the pre-pandemic sample. Our working hypothesis is that REM sleep during lockdowns intensified as a means of increased emotional consolidation, rendering the associated mental state less hybrid and thereby less lucid. (AU)

Dreaming during a pandemic: Low incorporation of COVID-19-specific themes and lucidity in dreams of psychiatric patients and healthy controls.

The present study examined the impact of the COVID-19 pandemic on the emotional quality of dreams, the incorporation of pandemic-related themes, and the occurrence of lucid dreaming. Dream reports and lucidity ratings of psychiatric outpatients (n = 30) and healthy controls (n = 81) during two lockdowns in Germany were compared to those of healthy controls (n = 33) before the pandemic. Results confirmed previous reports that pandemic-specific themes were incorporated into dreams. Overall, however, incorporation into dreams was rare. Contrary to expectations, psychiatric outpatients did not differ from controls in the frequency of dream incorporation of pandemic-related content. Moreover, incorporation was independent of psychiatric symptoms and loneliness. Loneliness was, however, associated with threat-related content, suggesting that it represents a risk for bad dreams but not for crisis-specific dream incorporation. Regarding lucid dreaming, both groups had similar scores for its underlying core dimensions, i.e., insight, control, and dissociation, during the two lockdowns. Scores for control and dissociation but not insight were lower compared to the pre-pandemic sample. Our working hypothesis is that REM sleep during lockdowns intensified as a means of increased emotional consolidation, rendering the associated mental state less hybrid and thereby less lucid.

Off-label use of antidepressants, antipsychotics, and mood-stabilizers in psychiatry.

Off-label drug prescribing in psychiatry is increasing. Many psychotropic drugs are approved for psychopathologic syndromes rather than based on international standard diagnostic classification systems which might facilitate the clinical decision for off-label prescriptions. The objective of this study was to analyze the prevalence and category of off-label use of psychotropic drugs. The study was conducted in 10 psychiatric hospitals in Germany over a period of 2 years. Prescription data of all patients were retrospectively analyzed after identification of antidepressants, antipsychotics, and mood-stabilizers, which were classified as off-label according to the German prescribing information and diagnostic classification according to ICD-10. In total, 53,909 patient cases (46% female) with a mean age of 46.8 (SD: 18) years were included in the study. 30.2% of the cases received at least one off-label prescription of a psychotropic drug during hospital stay. Off-label prevalence rates differed markedly between different diagnostic groups (ICD-10 F0/G3: 47%, F1: 33%, F2: 25%, F3: 21%, F4: 27%, F6: 46%, F7: 84%). The most often off-label prescribed drugs were quetiapine and mirtazapine for organic mental disorders (F0/G3), valproate and quetiapine in patients with disorders due to psychoactive substance use (F1), valproate in patients with psychotic disorders (F2), and risperidone and olanzapine in patients with affective disorders (F3). The prevalence rate of psychotropic off-label prescriptions is high if restricted to product description and ICD-10 diagnosis. Therefore, current psychiatric guidelines should drug-specifically issue this problem by defining psychiatric off-label indications based on a clear benefit-risk assessment.

Adapting to a major crisis: Sleep and mental health during two lockdowns.

The present study aimed at investigating the impact of the pandemic on sleep and mental health in healthy individuals (n = 78) as well as in psychiatric outpatients (n = 30) during the first and the second lockdown in Germany, in March and November 2020, respectively. Sleep quality and anxiety were worse in patients compared with controls during both lockdowns. Further, patients but not controls exhibited higher levels of depression and overall psychiatric symptomatology during the second lockdown. No differences were found in the perceived threat evoked by the pandemic. The data suggest that healthy individuals adapt flexibly to the difficult situation over the time course of the pandemic, whereas psychiatric patients seem to get worse, indicating difficulties in adapting to stressful circumstances.

Pharmacotherapy, drug-drug interactions and potentially inappropriate medication in depressive disorders.

INTRODUCTION: The aim of this study was to describe the number and type of drugs used to treat depressive disorders in inpatient psychiatry and to analyse the determinants of potential drug-drug interactions (pDDI) and potentially inappropriate medication (PIM). METHODS: Our study was part of a larger pharmacovigilance project funded by the German Innovation Funds. It included all inpatients with a main diagnosis in the group of depressive episodes (F32, ICD-10) or recurrent depressive disorders (F33) discharged from eight psychiatric hospitals in Germany between 1 October 2017 and 30 September 2018 or between 1 January and 31 December 2019. RESULTS: The study included 14,418 inpatient cases. The mean number of drugs per day was 3.7 (psychotropic drugs = 1.7; others = 2.0). Thirty-one percent of cases received at least five drugs simultaneously (polypharmacy). Almost one half of all cases received a combination of multiple antidepressant drugs (24.8%, 95% CI 24.1%-25.5%) or a treatment with antidepressant drugs augmented by antipsychotic drugs (21.9%, 95% CI 21.3%-22.6%). The most frequently used antidepressants were selective serotonin reuptake inhibitors, followed by serotonin and norepinephrine reuptake inhibitors and tetracyclic antidepressants. In multivariate analyses, cases with recurrent depressive disorders and cases with severe depression were more likely to receive a combination of multiple antidepressant drugs (Odds ratio recurrent depressive disorder: 1.56, 95% CI 1.41-1.70, severe depression 1.33, 95% CI 1.18-1.48). The risk of any pDDI and PIM in elderly patients increased substantially with each additional drug (Odds Ratio: pDDI 1.32, 95% CI: 1.27-1.38, PIM 1.18, 95% CI: 1.14-1.22) and severity of disease (Odds Ratio per point on CGI-Scale: pDDI 1.29, 95% CI: 1.11-1.46, PIM 1.27, 95% CI: 1.11-1.44), respectively. CONCLUSION: This study identified potential sources and determinants of safety risks in pharmacotherapy of depressive disorders and provided additional data which were previously unavailable. Most inpatients with depressive disorders receive multiple psychotropic and non-psychotropic drugs and pDDI and PIM are relatively frequent. Patients with a high number of different drugs must be intensively monitored in the management of their individual drug-related risk-benefit profiles.

Investigating Nuisance Effects Induced in EEG During tACS Application.

Transcranial alternating-current stimulation (tACS) in the frequency range of 1-100 Hz has come to be used routinely in electroencephalogram (EEG) studies of brain function through entrainment of neuronal oscillations. It turned out, however, to be highly non-trivial to remove the strong stimulation signal, including its harmonic and non-harmonic distortions, as well as various induced higher-order artifacts from the EEG data recorded during the stimulation. In this paper, we discuss some of the problems encountered and present methodological approaches aimed at overcoming them. To illustrate the mechanisms of artifact induction and the proposed removal strategies, we use data obtained with the help of a schematic demonstrator setup as well as human-subject data.

Polypharmacy and the risk of drug-drug interactions and potentially inappropriate medications in hospital psychiatry.

PURPOSE: The aim of this study was to analyze the epidemiology of polypharmacy in hospital psychiatry. Another aim was to investigate predictors of the number of drugs taken and the associated risks of drug-drug interactions and potentially inappropriate medications in the elderly. METHODS: Daily prescription data were obtained from a pharmacovigilance project sponsored by the Innovations Funds of the German Federal Joint Committee. RESULTS: The study included 47 071 inpatient hospital cases from eight different study centers. The mean number of different drugs during the entire stay was 6.1 (psychotropic drugs = 2.7; others = 3.4). The mean number of drugs per day was 3.8 (psychotropic drugs = 1.6; others = 2.2). One third of cases received at least five different drugs per day on average during their hospital stay (polypharmacy). Fifty-one percent of patients received more than one psychotropic drug simultaneously. Hospital cases with polypharmacy were 18 years older (p < 0.001), more likely to be female (52% vs. 40%, p < 0.001) and had more comorbidities (5 vs. 2, p < 0.001) than hospital cases without polypharmacy. The risks of drug-drug interactions (OR = 3.7; 95% CI = 3.5-3.9) and potentially inappropriate medication use in the elderly (OR = 2.2; CI = 1.9-2.5) substantially increased in patients that received polypharmacy. CONCLUSION: Polypharmacy is frequent in clinical care. The number of used drugs is a proven risk factor of adverse drug reactions due to drug-drug interactions and potentially inappropriate medication use in the elderly. The potential interactions and the specific pharmacokinetics and -dynamics of older patients should always be considered when multiple drugs are used.

Predicting the risk of drug-drug interactions in psychiatric hospitals: a retrospective longitudinal pharmacovigilance study.

OBJECTIVES: The aim was to use routine data available at a patient's admission to the hospital to predict polypharmacy and drug-drug interactions (DDI) and to evaluate the prediction performance with regard to its usefulness to support the efficient management of benefits and risks of drug prescriptions. DESIGN: Retrospective, longitudinal study. SETTING: We used data from a large multicentred pharmacovigilance project carried out in eight psychiatric hospitals in Hesse, Germany. PARTICIPANTS: Inpatient episodes consecutively discharged between 1 October 2017 and 30 September 2018 (year 1) or 1 January 2019 and 31 December 2019 (year 2). OUTCOME MEASURES: The proportion of rightly classified hospital episodes. METHODS: We used gradient boosting to predict respective outcomes. We tested the performance of our final models in unseen patients from another calendar year and separated the study sites used for training from the study sites used for performance testing. RESULTS: A total of 53 909 episodes were included in the study. The models' performance, as measured by the area under the receiver operating characteristic, was 'excellent' (0.83) and 'acceptable' (0.72) compared with common benchmarks for the prediction of polypharmacy and DDI, respectively. Both models were substantially better than a naive prediction based solely on basic diagnostic grouping. CONCLUSION: This study has shown that polypharmacy and DDI can be predicted from routine data at patient admission. These predictions could support an efficient management of benefits and risks of hospital prescriptions, for instance by including pharmaceutical supervision early after admission for patients at risk before pharmacological treatment is established.

Current use of anticholinergic medications in a large naturalistic sample of psychiatric patients.

Due to the high number of psychotropic drugs with anticholinergic potential, patients taking psychotropic drugs are at high risk for anticholinergic adverse drug reactions (ADRs). The aim of this study was to analyze the prevalence and type of pharmacodynamic anticholinergic drug-drug interactions in psychiatric patients. The retrospective longitudinal analysis used data from a large pharmacovigilance study conducted in ten German psychiatric hospitals. Anticholinergic burden of drugs was defined as "strong" or "moderate" based on current literature. Number and type of anticholinergic drugs were assessed. In total, 27,396 patient cases (45.6% female) with a mean age of 47.3 ± 18.3 years were included. 17.4% (n = 4760) of patients were ≥ 64 years. 35.4% of the patients received between one and four anticholinergic drugs simultaneously. A combination of drugs with anticholinergic potential was detected in 1738 cases (6.3%). Most prescribed drugs were promethazine (n = 2996), olanzapine (n = 2561), biperiden (n = 1074), and doxepin (n = 963). Patients receiving anticholinergic combinations were younger (45.7 vs. 47.4 years, p < 0.01) and had a longer inpatient stay (median 18 vs. 26.5 days, p < 0.001). The prevalence of anticholinergic drug use in psychiatry is high. Further efforts need to focus on reducing the rate of anticholinergics and inappropriate medication especially in the elderly. Anticholinergic ADRs can be prevented by avoiding high-risk drug combinations. Replacing tricyclic antidepressants and first-generation antihistamines with drugs with lower anticholinergic potential and avoiding biperiden could reduce 59.3% of anticholinergic drug application.

Pharmacodynamic Drug-Drug interactions of QT-prolonging drugs in hospitalized psychiatric patients.

At least 170 approved drugs are linked to QT prolongation, which can lead to serious adverse drug reactions (ADRs), such as Torsade de Pointes (TdP). The aim of this study was to analyze the prevalence and type of pharmacodynamic drug-drug interactions (DDIs) between QT-prolonging drugs in psychiatry. The present retrospective analysis used data from a large pharmacovigilance study, conducted in 10 psychiatric hospitals in Germany. Patients medication lists were screened for QT-prolonging drugs, classified according to the Arizona Center for Education and Research on Therapeutics (AZCERT). In total, 27,396 patient cases (46% female) with a mean (± standard deviation) age of 47 ± 18 years were included in the study. Altogether, 83% of the cases received at least one and up to eight QT-prolonging drugs at the same time. Combination of drugs with a known or possible risk for TdP (according to the AZCERT) was detected in 13,670 cases (50%). Most frequently prescribed psychotropic high-risk drugs (n = 48,995) were the antipsychotics pipamperone (n = 6202), quetiapine (n = 5718), prothipendyl (n = 4298), and risperidone (n = 4265). The replacement of high-risk drugs such as tricyclic antidepressants, levomepromazine, melperone, and promethazine with more tolerable drugs could avoid 11% of QT-prolonging drugs and increase the tolerability of psychopharmacological treatment. More than 80% of psychiatric patients receive at least one QT-prolonging drug during their hospital stay, and almost 50% of these drugs are combined in clinical practice. For the prevention of cardiac ADRs, the physician should evaluate the risk for QT prolongation for each drug and patient-specific risk factors before prescribing these drugs or drug combinations.

[Quality of treatment outcomes in alcohol- and substance-related disorders: an evaluation of inpatients from ten psychiatric hospitals]. / Ergebnisqualität bei alkohol- und substanzbezogenen Störungen: eine Auswertung stationär behandelter Patienten aus 10 psychiatrischen Kliniken.

AIM OF THE STUDY: Alcohol and substance-related disorders (ICD 10 F1x.x) are among the most frequent diagnoses made in hospitalized patients requiring somatic and psychiatric care. In order to assess the success of treatment, it is important to establish and implement outcome indicators in practice. METHOD: In 2016, global treatment indicators for admission and at discharge were collected at 10 Vitos clinics in Hesse (CGI and GAF). More than 10,000 patients with ICD10 F1x diagnoses were included in the evaluation. RESULTS: The evaluations show significant improvements of the clinical status as well as differences in treatment duration, remissions and gender differences. CONCLUSION: The study suggests that global indicators of outcome quality are useful in the assessment of treatment success of alcohol and substance-related disorders. Limitations of the study design, instruments and sample are critically reviewed.

Potentially inappropriate medication in older psychiatric patients.

PURPOSE: Many psychotropic drugs are listed as potentially inappropriate medication (PIM) in the older population. Potentially inappropriate means that prescription of those drugs in older adults may cause significant harm. The objective of this study was to analyze the prevalence and sort of PIM prescribing in a naturalistic, real-world psychiatric setting. METHODS: The retrospective analysis gathered data from a large pharmacovigilance study, conducted at 10 psychiatric hospitals. Data from inpatients aged ≥ 65 years were included for the analysis. The number and sort of PIM, as defined by the German PRISCUS list, were controlled by analyzing the patients' medication profile. RESULTS: In total, 4760 patient cases (59.2% female) with a mean (mean ± standard deviation (SD)) age of 77.33 ± 7.77 years were included into the study. Altogether, 1615 cases (33.9%) received at least 1 PRISCUS-PIM per day (regular and as-needed medication included). The most frequently prescribed PRISCUS-PIM (n = 2144) were zopiclone > 3.75 mg/day (n = 310), lorazepam > 2 mg/day (n = 269), haloperidol > 2 mg/day (n = 252), and diazepam (n = 182). Cases with PRISCUS-PIM were younger (75.7 vs. 78.2 years, p < 0.001) and had a longer (26 vs. 22 days, p < 0.001) hospital length of stay. Replacing benzodiazepines and z-substances, haloperidol > 2 mg, tricyclic antidepressants, first generation antihistaminergic drugs, and clonidine by non-PIM could reduce 69.9% of PRISCUS-PIM-prescribing. CONCLUSIONS: The prevalence of PRISCUS-PIM is high in the hospitalized psychiatric setting. Rational deprescribing of inappropriate anticholinergics, benzodiazepines, and antipsychotics in the older population is a key component to reduce the risk of adverse drug reactions. More tolerable medications should be prescribed.

Prevalence and sort of pharmacokinetic drug-drug interactions in hospitalized psychiatric patients.

Psychiatric patients are high-risk patients for the development of pharmacokinetic drug-drug interactions (DDIs), leading to highly variable (victim) drug serum concentrations. Avoiding and targeting high-risk drug combinations could reduce preventable adverse drug reactions (ADRs). Pharmacokinetic cytochrome P450 (CYP)-mediated DDIs are often predictable and, therefore, preventable. The retrospective, longitudinal analysis used informations from a large pharmacovigilance study (Optimization of pharmacological treatment in hospitalized psychiatric patients study, study number 01VSF16009, 01/2017), conducted in 10 psychiatric hospitals in Germany. Medication data were examined for the co-prescription of clinically relevant CYP inhibitors or inducers and substrates of these enzymes (victim drugs). In total, data from 27,396 patient cases (45.6% female) with a mean (mean ± standard deviation (SD)) age of 47.3 ± 18.3 years were available for analysis. CYP inhibitors or inducers were at least once prescribed in 14.4% (n = 3946) of the cases. The most frequently prescribed CYP inhibitors were melperone (n = 2504, 28.1%) and duloxetine (n = 1324, 14.9%). Overall, 51.0% of the cases taking melperone were combined with a victim drug (n = 1288). Carbamazepine was the most frequently prescribed CYP inducer (n = 733, 88.8%). Combinations with victim drugs were detected for 58% (n = 427) of cases on medication with carbamazepine. Finally, a DDI was detected in 43.6% of the cases in which a CYP inhibitor or inducer was prescribed. The frequency of CYP-mediated DDI is considerably high in the psychiatric setting. Physicians should be aware of the CYP inhibitory and inducing potential of psychotropic and internistic drugs (especially, melperone).

Hormone replacement therapy with L-thyroxine promotes working memory and concentration in thyroidectomized female patients after differentiated thyroid carcinoma.

Objective: It is well established that long-term hypothyroidism is associated with cognitive deficits. Based on recent literature, we hypothesized that pharmacologically induced euthyroidism would lead to improved cognitive performance compared to a hypothyroid state. Methods: We analyzed data from 14 nondepressed thyroidectomized female patients after differentiated thyroid carcinoma during hypothyroidism (due to a four-week withdrawal of thyroid hormone, T1) and euthyroidism brought about by substitution with L-thyroxine (T2). At both measurement points, patients completed a cognitive test battery as our dependent measure and Beck's Depression Inventory to control depressive states. Results: A Wilcoxon signed-rank tests revealed a significant improvement in the Rey­Osterrieth complex figure test (cognitive reproduction), Z = −3.183, p = 0.001, and the D2 concentration score, Z = −1.992, p = 0.046 in euthyroidism compared to hypothyroidism. Conclusions: Our results confirm that hormone replacement therapy with L-thyroxine promotes cognitive reproduction and concentration in thyroidectomized female patients after differentiated thyroid carcinoma.

QTc Time Correlates with Amitriptyline and Venlafaxine Serum Levels in Elderly Psychiatric Inpatients.

INTRODUCTION: Many antidepressants cause QT prolongation but the classification of cardiac risk of these drugs varies markedly in different published lists. This retrospective study analyzed the correlation of QTc time with amitriptyline and venlafaxine serum level in elderly psychiatric inpatients. METHODS: Elderly inpatients aged≥65 years for whom venlafaxine or amitriptyline serum level had been measured were selected retrospectively from a therapeutic drug monitoring database and screened for an electrocardiogram measurement at the time of blood withdrawal. The correlation of amitriptyline or venlafaxine serum levels with QTc time was examined by using Pearson's correlation analysis. RESULTS: Amitriptyline serum levels (n=11) correlated significantly with QTc time (r=0.918, p<0.001, CI 95%). Venlafaxine serum levels (n=27) also correlated significantly with QTc time (r=0.382, p<0.05, CI 95%). DISCUSSION: Amitriptyline and venlafaxine induce QT prolongation depending on drug concentrations in blood. Its extent, however, is very low when drug serum levels are within the therapeutic range. Future pharmacokinetic studies that correlate drug serum level and QT time should classify the cardiac risk of drugs based on the grade of the regression line in relation to the therapeutic range.

Insight and Dissociation in Lucid Dreaming and Psychosis.

Dreams and psychosis share several important features regarding symptoms and underlying neurobiology, which is helpful in constructing a testable model of, for example, schizophrenia and delirium. The purpose of the present communication is to discuss two major concepts in dreaming and psychosis that have received much attention in the recent literature: insight and dissociation. Both phenomena are considered functions of higher order consciousness because they involve metacognition in the form of reflective thought and attempted control of negative emotional impact. Insight in dreams is a core criterion for lucid dreams. Lucid dreams are usually accompanied by attempts to control the dream plot and dissociative elements akin to depersonalization and derealization. These concepts are also relevant in psychotic illness. Whereas insightfulness can be considered innocuous in lucid dreaming and even advantageous in psychosis, the concept of dissociation is still unresolved. The present review compares correlates and functions of insight and dissociation in lucid dreaming and psychosis. This is helpful in understanding the two concepts with regard to psychological function as well as neurophysiology.

A template model of embodiment while dreaming: Proposal of a mini-me.

Dreams are usually centered around a dream self capable of tasks generally impossible in waking, e.g. flying or walking through walls. Moreover, the bodily dream self appears relatively stable and insensitive to changes of the embodied wake self, raising the question of whether and to what extent the dream self is embodied. To further explore its determinants, we tested whether the dream self would be affected by either pre-sleep focused attention to a body part or by its experimental alteration during the day. Choosing a repeated-measures design, we analyzed how often key words reflecting the experimental manipulations appeared in the dream reports. Results suggest that the dream self is not affected by these manipulations, strengthening the hypothesis that, in the majority of dreams, the dream self is only weakly embodied, utilizing a standard template of embodiment akin to a prototype of self operating independently from the physical waking self.

Predictors for symptom re-exacerbation after targeted stepwise drug discontinuation in first-episode schizophrenia: Results of the first-episode study within the German research network on schizophrenia.

BACKGROUND: After a first episode in schizophrenia guidelines recommend antipsychotic maintenance treatment (MT) for at least 1year. Recent RCTs on subsequent targeted intermittent treatment (IT) after stepwise drug discontinuation yielded noticeably higher relapse rates than during MT also in first-episode patients. Nevertheless, about 50% of patients remain stable under IT. Given the potential adverse effects of antipsychotics and the preference of many patients to discontinue drugs, valid predictors for the feasibility of IT are urgently needed to support decision making. METHODS: Based on a one-year RCT phase comparing MT with IT in first-episode patients after 1year of MT, conducted within the German Research Network on Schizophrenia (GRNS), predictors for deterioration under IT in 19 feasible patients were identified by logistic regression analysis. RESULTS: Deterioration occurred in 10 patients (52.6%). Univariate analyses indicated a lower PANSS positive score after acute treatment as well as after one year of MT as significant predictors; in multivariate logistic regression, in addition to the lower PANSS positive score after acute treatment, reaching enduring remission and having had a deterioration both during MT evolved as significant predictors and indicate a higher risk for deterioration. CONCLUSIONS: Although limited by the small sample size, our findings suggest that patients who show a favorable response and full and enduring symptom remission during antipsychotic treatment, as well as those with marked deterioration despite MT should rather be recommended to remain on treatment because they are at higher risk for symptom re-exacerbation after (stepwise) drug discontinuation.

Induction of self awareness in dreams through frontal low current stimulation of gamma activity.

Recent findings link fronto-temporal gamma electroencephalographic (EEG) activity to conscious awareness in dreams, but a causal relationship has not yet been established. We found that current stimulation in the lower gamma band during REM sleep influences ongoing brain activity and induces self-reflective awareness in dreams. Other stimulation frequencies were not effective, suggesting that higher order consciousness is indeed related to synchronous oscillations around 25 and 40 Hz.