[Cannabinoid Drugs in the Treatment of Psychiatric Disorders - Data from the German Federal Institute for Drugs and Medical Devices]. / Cannabisarzneimittel in der Behandlung psychischer Störungen ­ Befunde aus der Cannabis-Begleiterhebung des Bundesinstituts für Arzneimittel und Medizinprodukte.

BACKGROUND: Since 2017 physicians in Germany can prescribe cannabis based medicines or medical cannabis with subsequent funding by the statutory health insurance system. METHODS: Physicians prescribing cannabinoid drugs were legally required to take part in a survey conducted by the Federal Institute for Drugs and Medical Devices. This study analyses data from 16.809 case reports that were collected from 30.3.2017 to 31.12.2021. RESULTS: There were 5582 cases documenting the use of cannabinoid drugs in psychiatric disorders. More than half of the prescriptions were Dronabinol. 80% of the treatments concerned somatoform disorders. Most of the treatments for other psychiatric disorders also targeted pain. Doctors reported a positive effect on symptoms in at least 75% of the cases. DISCUSSION: Most patients with psychiatric disorders received cannabinoid drugs for pain. The evidence from randomized controlled clinical trials for the use of cannabinoid drugs in psychiatric indications is weak.

Assessing complex PTSD and PTSD: validation of the German version of the International Trauma Interview (ITI).

Background: With the introduction of the ICD-11 into clinical practice, the reliable distinction between Posttraumatic Stress Disorder (PTSD) and Complex Posttraumatic Stress Disorder (CPTSD) becomes paramount. The semi-structured clinician-administered International Trauma Interview (ITI) aims to close this gap in clinical and research settings.Objective: This study investigated the psychometric properties of the German version of the ITI among trauma-exposed clinical samples from Switzerland and Germany.Method: Participants were 143 civilian and 100 military participants, aged M = 40.3 years, of whom 53.5% were male. Indicators of reliability and validity (latent structure, internal reliability, inter-rater agreement, convergent and discriminant validity) were evaluated. Confirmatory factor analysis (CFA) and partial correlation analysis were conducted separately for civilian and military participants.Results: Prevalence of PTSD was 30% (civilian) and 33% (military) and prevalence of CPTSD was 53% (civilians) and 21% (military). Satisfactory internal consistency and inter-rater agreement were found. In the military sample, a parsimonious first-order six-factor model was preferred over a second-order two-factor CFA model of ITI PTSD and Disturbances in Self-Organization (DSO). Model fit was excellent among military participants but no solution was supported among civilian participants. Overall, convergent validity was supported by positive correlations of ITI PTSD and DSO with DSM-5 PTSD. Discriminant validity for PTSD symptoms was confirmed among civilians but low in the military sample.Conclusions: The German ITI has shown potential as a clinician-administered diagnostic tool for assessing ICD-11 PTSD and CPTSD in primary care. However, further exploration of its latent structure and discriminant validity are indicated.

This study validated the German International Trauma Interview (ITI), a semi-structured clinician-administered diagnostic interview for ICD-11 Posttraumatic Stress Disorder and Complex Posttraumatic Stress Disorder.Internal reliability, inter-rater agreement, latent structure, and convergent validity were explored in trauma-exposed clinical and military samples from five different in- and outpatient centres in Germany and German-speaking Switzerland.The findings supported the German ITI's reliability, inter-rater agreement, convergent validity and usefulness from a patient perspective. Future research should explore its factor structure and discriminant validity, for which differences between the samples were found.

What to think or how to think - is symptom reduction in posttraumatic symptomatology associated with change in posttraumatic cognitions or perseverative thinking? A latent change score model approach.

OBJECTIVE: Patients with posttraumatic stress disorder (PTSD) report changes in what they think of the world and themselves, referred to as posttraumatic cognitions, and changes in how they think, reflected in increased perseverative thinking. We investigated whether pre-post therapy changes in the two aspects of thinking were associated with pre-post therapy changes in posttraumatic symptom severity. METHOD: 219 d clinic patients with posttraumatic stress symptoms received trauma-focused psychotherapy with cognitive behavioral and metacognitive elements. The posttraumatic cognitions inventory (PTCI), the perseverative thinking questionnaire (PTQ), and the Davidson trauma scale (DTS) were applied at two occasions, pre- and post-therapy. Using latent change score models, we investigated whether change in PTCI and change in PTQ were associated with change in DTS and its subscales. We then compared the predictive value of PTQ and PTCI in joint models. RESULTS: When jointly modeled, change in overall DTS score was associated with change in both PTCI and PTQ. Concerning DTS subscales, reexperiencing and avoidance were significantly associated with change in PTCI, but not in PTQ. CONCLUSION: Results indicate that both aspects of cognition may be valuable targets of psychotherapy. A focus on posttraumatic cognitions might be called for in patients with severe reexperiencing and avoidance.

Step away from depression-results from a multicenter randomized clinical trial with a pedometer intervention during and after inpatient treatment of depression.

Evidence for the effectiveness of physical activity (PA) in the treatment of depression prevails for outpatients with mild and moderate symptom levels. For inpatient treatment of severe depression, evidence-based effectiveness exists only for structured and supervised group PA interventions. The Step Away from Depression (SAD) study investigated the effectiveness of an individual pedometer intervention (PI) combined with an activity diary added to inpatient treatment as usual (TAU). In this multicenter randomized controlled trial, 192 patients were randomized to TAU or TAU plus PI. The two primary outcomes at discharge were depression-blindly rated with the Montgomery-Åsberg Depression Rating Scale (MADRS)-and average number of daily steps measured by accelerometers. Secondary outcomes were self-rated depression and PA, anxiety, remission and response rates. Multivariate analysis of variance (MANOVA) revealed no significant difference between both groups for depression and daily steps. Mean MADRS scores at baseline were 29.5 (SD = 8.3) for PI + TAU and 28.8 (SD = 8.1) for TAU and 16.4 (SD = 10.3) and 17.2 (SD = 9.9) at discharge, respectively. Daily steps rose from 6285 (SD = 2321) for PI + TAU and 6182 (SD = 2290) for TAU to 7248 (SD = 2939) and 7325 (SD = 3357). No differences emerged between groups in secondary outcomes. For severely depressed inpatients, a PI without supervision or further psychological interventions is not effective. Monitoring, social reinforcement and motivational strategies should be incorporated in PA interventions for this population to reach effectiveness.

The mediating role of attachment and anger: exploring the impact of maternal early-life maltreatment on child abuse potential.

Background: Maternal early-life maltreatment (ELM) increases the risk of subsequent child maltreatment, but the underlying mechanisms of these intergenerational effects remain largely unknown. Identifying these mechanisms is crucial for developing preventive interventions that can break the cycle of abuse. Notably, previous research has shown that ELM often results in attachment insecurity and altered anger characteristics. Therefore, this study determines whether these characteristics mediate the relationship between maternal history of ELM and child abuse potential. Methods: The study sample included 254 mothers, of whom 149 had experienced ELM to at least a moderate degree. Maternal ELM was assessed using the Childhood Experience of Care and Abuse (CECA) interview. Attachment insecurity, trait anger and anger expression, and maternal abuse potential were assessed using the Vulnerable Attachment Questionnaire (VASQ), State-Trait Anger Expression Inventory (STAXI), and Child Abuse Potential Inventory (CAPI), respectively. Results: The severity of maternal ELM predicted higher child abuse potential, with attachment insecurity and anger suppression mediating this effect. Specifically, higher levels of maternal ELM were associated with greater attachment insecurity and increased anger suppression, resulting in a higher child abuse potential. Although higher levels of trait anger were directly associated with higher child abuse potential, this parameter did not mediate the relationship with ELM. In addition, no significant associations were observed between outwardly expressed anger and ELM or child abuse potential. All analyses were adjusted for maternal mental disorders, years of education, and relationship status. Discussion: Attachment insecurity and anger suppression may serve as pathways linking the maternal history of ELM to the risk of child abuse, even when considering maternal psychopathology. Overall, our findings indicate that interventions aimed at strengthening attachment and improving anger suppression may be beneficial for all mothers with ELM history and high child abuse potential, not just those who suffer from mental illness.

Treating nightmares in posttraumatic stress disorder with dronabinol: study protocol of a multicenter randomized controlled study (THC PTSD-trial).

BACKGROUND: Distressing nightmares are a core symptom of posttraumatic stress disorder (PTSD) and contribute to psychiatric comorbidity, impaired physical health and decreased social functioning. No specific pharmacological treatment for PTSD-related nightmares is yet approved. Preliminary clinical data indicate that cannabinoid agonists can improve nightmares and overall PTSD symptoms in patients with PTSD. The primary objective of the study is to examine the efficacy of oral dronabinol (BX-1) versus placebo in reducing nightmares in patients with PTSD. The secondary objectives of the study are to examine the efficacy of oral BX-1 in reducing other PTSD symptoms. METHODS: The study is designed as a multi-centric, double-blind, randomized (1:1), placebo-controlled, parallel group interventional trial. Eligible patients will be randomized to BX-1 or placebo, receiving a once-daily oral dose before bedtime for 10 weeks. Primary efficacy endpoint is the Clinician-Administered PTSD Scale (CAPS-IV) B2 score for the last week, measuring frequency and intensity of nightmares. Secondary efficacy endpoints are other disorder-specific symptoms in patients with PTSD. Further, tolerability and safety of dronabinol will be assessed. DISCUSSION: This randomized controlled trial will provide evidence whether treating patients with PTSD and nightmares with dronabinol is safe and efficacious. TRIAL REGISTRATION: NCT04448808, EudraCT 2019-002211-25.

The Affect Intolerance Scale (AIS), German version: A validation study in a student and clinical sample of patients with trauma-related disorders.

BACKGROUND AND OBJECTIVES: The Affect Intolerance Scale (AIS) assesses two core concepts of emotion regulation: appraisals of negative emotions as threatening and proneness to emotional avoidance. Maladaptive emotion regulation is associated with various psychopathologies. We translated and validated the AIS in a German student and clinical sample of patients with trauma-related disorders. METHODS: 340 patients, 161 with post-traumatic stress disorder and 179 with adjustment disorder, and 322 students were enrolled. We employed exploratory and confirmatory factor analyses in a cross-validation design to investigate construct validity, convergent and discriminant validity, and reliability. RESULTS: We replicated the originally described two-factor structure in both samples. Cronbach's α was 0.947 in the student and 0.950 in the clinical sample. AIS subscales showed moderate to high correlations with convergent and low correlations with discriminant measures. AIS total scores were significantly larger in the clinical sample, controlled for gender and age. LIMITATIONS: This study provides a unified cross-validation model in a clinical and a student sample at the cost of reduced sample sizes. CONCLUSIONS: The AIS is a valid measure of affect intolerance with the discriminative ability to distinguish between patients with trauma-related disorders and students. Test redundancy within both sub-constructs of the AIS might lead to biased estimates but allows for increased test precision, rendering the AIS a tool suitable for individual treatment monitoring.

Sparse models for predicting psychosocial impairments in patients with PTSD: An empirical Bayes approach.

OBJECTIVE: Posttraumatic stress disorder (PTSD) is associated with psychosocial impairments, which represent a relevant focus for therapy. Previous results on the clinical predictors of these psychosocial impairments were inconsistent. The data analyzed in these contexts often suffer from a high number of correlated predictors and small sample sizes, entailing the risk of model overfitting. In Bayesian regression, the problem of overfitting can be mitigated by usage of specific zero-centered (regularizing) prior distributions. In this study, we used the 2 most common Bayesian regression models, the Bayesian Ridge and the Bayesian Lasso, to predict psychosocial impairments in 192 patients of a day clinic for the treatment of PTSD. METHOD: Predictions were based on specific dimensions of PTSD symptoms previously revealed by factor analyses, as well as posttraumatic cognitions, depressive symptoms, comorbid disorders, and demographics. The variance of the prior distribution was estimated through empirical Bayes (maximum marginal likelihood) and an approximation to the posterior distribution was obtained with stochastic variational inference and with a local approximation (Laplace approximation). RESULTS: Severe psychosocial impairments were mainly related to depressive symptoms and symptoms from the amnesia and numbing dimension of PTSD, while gender, posttraumatic cognitions, and reexperience and avoidance symptoms had no impact. As expected, the model coefficients were shrunken to zero when regularizing prior distributions were used, particularly for the Bayesian Lasso. CONCLUSION: Depressive and numbing symptoms are the main clinical correlates of psychosocial impairments in patients with PTSD. Usage of Bayesian and regularized regression can contribute to the generalizability and interpretability of research results. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Predicting outcome of daycare cognitive behavioural therapy in a naturalistic sample of patients with PTSD: a machine learning approach.

Background: Identifying predictors for treatment outcome in patients with posttraumatic stress disorder (PTSD) is important in order to provide an effective treatment, but robust and replicated treatment outcome predictors are not available up to now. Objectives: We investigated predictors of treatment outcome in a naturalistic sample of patients with PTSD admitted to an 8-week daycare cognitive behavioural therapy programme following a wide range of traumatic events. Method: We used machine learning (linear and non-linear regressors and cross-validation) to predict outcome at discharge for 116 patients and sustained treatment effects 6 months after discharge for 52 patients who had a follow-up assessment. Predictions were based on a wide selection of demographic and clinical assessments including age, gender, comorbid psychiatric disorders, trauma history, posttraumatic symptoms, posttraumatic cognitions, depressive symptoms, general psychopathology and psychosocial functioning. Results: We found that demographic and clinical variables significantly, but only modestly predicted PTSD treatment outcome at discharge (r = 0.21, p = .021 for the best model) and follow-up (r = 0.31, p = .026). Among the included variables, more severe posttraumatic cognitions were negatively associated with treatment outcome. Early response in PTSD symptomatology (percentage change of symptom scores after 4 weeks of treatment) allowed more accurate predictions of outcome at discharge (r = 0.56, p < .001) and follow-up (r = 0.43, p = .001). Conclusion: Our results underscore the importance of early treatment response for short- and long-term treatment success. Nevertheless, it remains an unresolved challenge to identify variables that can robustly predict outcome before the initiation of treatment.

Antecedentes: La identificación de los predictores para el resultado de tratamiento en pacientes con trastorno de estrés postraumático (TEPT) es importante para proporcionar un tratamiento eficaz, pero hasta ahora no se dispone de predictores de respuesta de tratamiento robustos y replicables.Objetivos: Investigamos los predictores de resultado de tratamiento en una muestra naturalista de pacientes con TEPT ingresados a un programa de tratamiento cognitivo conductual tipo hospital de día de ocho semanas, después de una amplia gama de eventos traumáticos.Método: Utilizamos el aprendizaje automático (regresores lineales y no lineales y validación cruzada) para predecir el resultado al alta para 116 pacientes y los efectos sostenidos del tratamiento a los seis meses del alta para 52 pacientes que tuvieron una evaluación de seguimiento. Las predicciones se basaron en una amplia selección de evaluaciones demográficas y clínicas que incluyen edad, género, trastornos psiquiátricos comórbidos, antecedentes de trauma, síntomas postraumáticos, cogniciones postraumáticas, síntomas depresivos, psicopatología general y funcionamiento psicosocial.Resultados: Encontramos que las variables clínicas y demográficas predijeron de manera significativa, pero solo modestamente, el resultado del tratamiento del TEPT al momento del alta (r = 0.21, p= .21 para el mejor modelo) y el seguimiento (r = 0.31, p = .026). Entre las variables incluidas, las cogniciones postraumáticas más severas se asociaron negativamente con el resultado del tratamiento. La respuesta temprana en la sintomatología de TEPT (cambio porcentual del puntaje en los síntomas después de cuatro semanas de tratamiento) permitió predicciones más precisas de los resultados al alta (r = 0.56, p < .001) y el seguimiento (r = 0.43, p = .001).Conclusiones: Nuestros resultados subrayan la importancia de una respuesta temprana al tratamiento para el éxito del tratamiento a corto y largo plazo. No obstante, sigue siendo un desafío sin resolver identificar variables que puedan predecir de manera sólida el resultado antes del inicio del tratamiento.

Reduced Resting-State Connectivity in the Precuneus is correlated with Apathy in Patients with Schizophrenia.

A diagnosis of schizophrenia is associated with a heterogeneous psychopathology including positive and negative symptoms. The disconnection hypothesis, an early pathophysiological framework conceptualizes the diversity of symptoms as a result of disconnections in neural networks. In line with this hypothesis, previous neuroimaging studies of patients with schizophrenia reported alterations within the default mode network (DMN), the most prominent network at rest. The aim of the present study was to investigate the functional connectivity during rest in patients with schizophrenia and with healthy individuals and explore whether observed functional alterations are related to the psychopathology of patients. Therefore, functional magnetic resonance images at rest were recorded of 35 patients with schizophrenia and 41 healthy individuals. Independent component analysis (ICA) was used to extract resting state networks. Comparing ICA results between groups indicated alterations only within the network of the DMN. More explicitly, reduced connectivity in the precuneus was observed in patients with schizophrenia compared to healthy controls. Connectivity in this area was negatively correlated with the severity of negative symptoms, more specifically with the domain of apathy. Taken together, the current results provide further evidence for a role DMN alterations might play in schizophrenia and especially in negative symptoms such as apathy.

New Graph-Theoretical-Multimodal Approach Using Temporal and Structural Correlations Reveals Disruption in the Thalamo-Cortical Network in Patients with Schizophrenia.

Schizophrenia has been understood as a network disease with altered functional and structural connectivity in multiple brain networks compatible to the extremely broad spectrum of psychopathological, cognitive, and behavioral symptoms in this disorder. When building brain networks, functional and structural networks are typically modeled independently: Functional network models are based on temporal correlations among brain regions, whereas structural network models are based on anatomical characteristics. Combining both features may give rise to more realistic and reliable models of brain networks. In this study, we applied a new flexible graph-theoretical-multimodal model called FD (F, the functional connectivity matrix, and D, the structural matrix) to construct brain networks combining functional, structural, and topological information of magnetic resonance imaging (MRI) measurements (structural and resting-state imaging) to patients with schizophrenia (n = 35) and matched healthy individuals (n = 41). As a reference condition, the traditional pure functional connectivity (pFC) analysis was carried out. By using the FD model, we found disrupted connectivity in the thalamo-cortical network in schizophrenic patients, whereas the pFC model failed to extract group differences after multiple comparison correction. We interpret this observation as evidence that the FD model is superior to conventional connectivity analysis, by stressing relevant features of the whole-brain connectivity, including functional, structural, and topological signatures. The FD model can be used in future research to model subtle alterations of functional and structural connectivity, resulting in pronounced clinical syndromes and major psychiatric disorders. Lastly, FD is not limited to the analysis of resting-state functional MRI, and it can be applied to electro-encephalography, magneto-encephalography, etc.

Opioid tolerance in methadone maintenance treatment: comparison of methadone and levomethadone in long-term treatment.

BACKGROUND: This study aimed to investigate the development of opioid tolerance in patients receiving long-term methadone maintenance treatment (MMT). METHODS: A region-wide cross-sectional study was performed focusing on dosage and duration of treatment. Differences between racemic methadone and levomethadone were examined. All 20 psychiatric hospitals and all 110 outpatient clinics in Berlin licensed to offer MMT were approached in order to reach patients under MMT fulfilling the DSM IV criteria of opiate dependence. In the study, 720 patients treated with racemic methadone or levomethadone gave information on the dosage of treatment. Out of these, 679 patients indicated the duration of MMT. RESULTS: Treatment with racemic methadone was reported for 370 patients (54.5%), with levomethadone for 309 patients (45.5%). Mean duration of MMT was 7.5 years. We found a significant correlation between dosage and duration of treatment, both in a conjoint analysis for the two substances racemic methadone and levomethadone and for each substance separately. These effects remained significant when only patients receiving MMT for 1 year or longer were considered, indicating proceeding tolerance development in long-term treatment. When correlations were compared between racemic methadone and levomethadone, no significant difference was found. CONCLUSIONS: Our data show a tolerance development under long-term treatment with both racemic methadone and levomethadone. Tolerance development did not differ significantly between the two substances.

[Methadone and levomethadone - dosage and side effects]. / Methadon und Levomethadon - Dosierung und Nebenwirkungen.

OBJECTIVE: The aim of our survey was to assess the dosage and the frequency of side effects in patients with opioid dependency receiving opioid maintenance therapy (OMT). METHODS: A region-wide anonymous survey was carried out in the city of Berlin. The dosage, the frequency of side effects, data on the dependence disorder and type of OMT was assessed. RESULTS: Out of all 5032 patients receiving OMT in Berlin 986 participated in the study. Of all included patients 460 were treated with methadone, 371 with levomethadone. The average dose of levomethadone was significantly higher than the dose of methadone even when adequately adjusting for differential effect sizes. In the total sample, 484 participants reported side effects. The most frequent named ones were sweating and sedation. The incidence of the side effects irritability and gastrointestinal troubles was significantly higher under OMT with levomethadone, although when an adjustment for dosage was performed. CONCLUSIONS: Levomethadone is dosed significantly higher than methadone. After an adjustment for dosage was performed, some of the specific side effects occurred more often under OMT with levomethadone. The results of our survey support the use of methadone as first line treatment for OMT.

Binge eating disorder and menstrual cycle in unmedicated women with bipolar disorder.

OBJECTIVE: Weight increase is a problem in women with bipolar disorder (BD). Furthermore, there is evidence that both binge eating disorder (BED) and menstrual cycle abnormalities occur more frequently in women with affective disorders than in the general population. We investigated whether there is a clinical link between the two disorders and menstrual cycle. METHOD: Epidemiological and clinical variables associated with both BD and BED were assessed as well as menstrual cycle influence. RESULTS: The prevalence of BED in the sample was 28.8%. Menstrual cycle significantly influenced BED in all participants in that BED became worse prior to menses. 80% of the participants noticed regular weight gain prior to menses. DISCUSSION: BED is a common comorbidity in unmedicated subjects with BD, as is overweight. In women with BD menstrual cycle should be taken into consideration, as it can worsen the BD itself and associated comorbidities such as BED and overweight. Alteration in menstrual cycle-associated eating behavior should be routinely assessed in women with BD.

Gender differences in psychotic bipolar mania.

OBJECTIVE: This study examined gender differences in the prevalence and types of psychotic symptoms in bipolar mania. METHODS: Participants were drawn from consecutive admissions to the psychiatric clinic in Chemnitz, Germany, in 2005. The diagnosis of bipolar disorder, manic episode was made within 24 hours of admission, and the severity of mania was assessed using the Young Mania Rating Scale (YMRS) and the German version of the Altman Self-Rating Mania Scale. Data collected for each patient included age at the onset of bipolar illness, number of previous episodes, social functioning between episodes, and duration of hospitalization for the index episode. Based on the Task Force for Methods and Documentation in Psychiatry system, psychotic symptoms were classified as hallucinations (visual, auditory, olfactory, tactile, acousma, somatic); delusions (paranoid, reference, guilt, grandeur, religious, erotomania, hypochondriac, poverty, jealousy); and ego disorder (thought control, thought broadcasting). RESULTS: One hundred thirty-seven women and 109 men met the criteria for an acute manic episode, of whom 93 women and 62 men had psychotic symptoms. Compared with psychotic men, psychotic women had more delusions and hallucinations, both overall and per patient, and more delusions of reference and paranoid delusions. Psychotic women had more mixed states compared with psychotic men. Psychotic women differed from both psychotic men and nonpsychotic women on a number of clinical and social variables: they had higher YMRS scores and more previous episodes of depression despite an earlier onset of illness. CONCLUSION: Women with bipolar mania exhibited a specific pattern of psychotic symptoms that appeared to be associated with greater severity of the acute episode, more mixed states, and a more severe course of illness.