Differential efficacy of lithium and carbamazepine in the prophylaxis of bipolar disorder: Results of the MAP study

In a randomized clinical trial with an observation period of 2.5 years, the differential efficacy of lithium versus carbamazepine was compared in 171 bipolar patients (DSM-IV). In order to investigate the efficacy of the two drugs in clearly defined subsamples, a series of subgroup analyses was carried out. First, patients with a bipolar I disorder (n = 114) were analyzed separately. In these patients, lithium was superior to carbamazepine. In contrast, carbamazepine was at least equally as efficacious as lithium in the subsample of patients with bipolar II disorder or bipolar disorder not otherwise specified (n = 57). In a second analysis on differential efficacy, the whole sample was subdivided into a classical subgroup (bipolar I patients without mood-incongruent delusions and without comorbidity; n = 67) and a nonclassical subgroup including all other patients (n = 104). Classical bipolar patients had a significantly lower hospitalization rate under lithium than under carbamazepine prophylaxis (26 vs. 62%, p = 0.012). For the nonclassical group, a tendency in favor of carbamazepine was found. In a third step, we analyzed the impact of episode sequence on differential efficacy. In a global view, the episode sequence prior to the index episode was not correlated to differential efficacy. Our results might, however, indicate that patients with an episode sequence of mania-depression-free interval responded better to lithium. Besides differential efficacy, suicidal behavior and patients' satisfaction with treatment were investigated. Regarding suicidal behavior, a trend in favor of lithium was found. The data on patients' satisfaction were significantly in favor of carbamazepine. In conclusion, lithium appears to be superior to carbamazepine in classical bipolar cases and might have additional impact on proneness to suicide. The distinctly larger group of patients with nonclassical features might profit more from carbamazepine which seems to be well accepted by the patients. Hence, treatment alternatives to lithium a re desirable for the majority of bipolar patients. Copyright (C) 2000 S. Karger AG, Basel

Zur Prädiktion des Erfolgs einer Lithiumprophylaxe bei bipolar affektiven Störungen

Die vorliegende Arbeit beinhaltet drei wesentliche Teile. Zunächst wird eine systematische quantitative Literaturübersicht zur Prognose der Lithiumresponse durchgeführt. Hierbei wurden in einer Serie von Metaanalysen insgesamt 21 Variablen als Prädiktoren für die Lithiumresponse identifiziert. Im zweiten Teil werden auf Grundlage dieser systematischen Literaturübersicht verschiedene Prognoseinstrumente entwickelt. Diese Prognoseinstrumente umfassen eine für die klinische Anwendung optimierte Lithium-Response-Skala, sowie eine Reihe multivariater Verfahren. Im letzen Hauptabschnitt der vorliegenden Arbeit wird die praktische Eignung und prognostische Kraft dieser Prognoseinstrumente anhand eines umfangreichen Datensatzes evaluiert. Im Ergebnis hat sich die Verwendung der Lithium-Response-Skala hinsichtlich prognostischer Kraft und praktischer Verwendbarkeit am besten bewährt

Validation of the German version of the subarachnoid haemorrhage outcome tool (SAHOT)

Objective:The subarachnoid haemorrhage (SAH) outcome tool (SAHOT) is the first SAH-specific patient reported outcome measure, and was developed in the UK. We aimed to validate the SAHOT outside the UK, and therefore endeavored to adapt the SAHOT into German and to test its psychometric properties. Methods:We adapted and pilot tested the German version. We applied the SAHOT, Quality of Life after Brain Injury, Hospital Anxiety and Depression Scale, and EuroQol questionnaires in a cohort of 89 patients with spontaneous SAH after discharge. We assessed internal consistency by Cronbach’s α, test-retest reliability by intraclass correlation, and validity by Pearson correlations with established measures. Sensitivity to change was evaluated following neurorehabilitation by effect sizes. Results:The translation of SAHOT resulted in a German version that is semantically and conceptually equivalent to the English version. Internal consistency was good regarding the physical domain (α = 0.83) and excellent for the other domains (α = 0.92–0.93). Test–retest reliability indicated a high level of stability with an intraclass correlation of 0.85 (95% CI: 0.83–0.86). All domains correlated moderately or strongly with established measures (r = 0.41–0.74; p < 0.01). SAHOT total scores showed moderate sensitivity to change (Cohen’s d = −0.68), while mRS and GOSE showed no significant sensitivity to change. Conclusion:The SAHOT can be adapted to other health care systems and societies than the UK. The German version of the SAHOT is a reliable and valid instrument, and can be used in future clinical studies and individual assessment after spontaneous SAH

Physical Exercise Training versus Relaxation in Allogeneic stem cell transplantation (PETRA Study) – Rationale and design of a randomized trial to evaluate a yearlong exercise intervention on overall survival and side-effects after allogeneic stem cell transplantation

Background: Allogeneic stem cell transplantation (allo-HCT) is associated with high treatment-related mortality and innumerable physical and psychosocial complications and side-effects, such as high fatigue levels, loss of physical performance, infections, graft-versus-host disease (GvHD) and distress. This leads to a reduced quality of life, not only during and after transplantation, but also in the long term. Exercise interventions have been shown to be beneficial in allo-HCT patients. However, to date, no study has focused on long-term effects and survival. Previous exercise studies used ‘usual care’ control groups, leaving it unclear to what extent the observed effects are based on the physical effects of exercise itself, or rather on psychosocial factors such as personal attention. Furthermore, effects of exercise on and severity of GvHD have not been examined so far. We therefore aim to investigate the effects and biological mechanisms of exercise on side-effects, complications and survival in allo-HCT patients during and after transplantation. Methods/design: The PETRA study is a randomized, controlled intervention trial investigating the effects of a yearlong partly supervised mixed exercise intervention (endurance and resistance exercises, 3–5 times per week) in 256 patients during and after allogeneic stem cell transplantation. Patients in the control group perform progressive muscle relaxation training (Jacobsen method) with the same frequency. Main inclusion criterion is planned allo-HCT. Main exclusion criteria are increased fracture risk, no walking capability or severe cardiorespiratory problems. Primary endpoint is overall survival after two years; secondary endpoints are non-relapse mortality, median survival, patient reported outcomes including cancer related fatigue and quality of life, physical performance, body composition, haematological/immunological reconstitution, inflammatory parameters, severity of complications and side-effects (e.g. GvHD and infections), and cognitive capacity. Discussion: The PETRA study will contribute to a better understanding of the physiological and psychological effects of exercise training and their biological mechanisms in cancer patients after allo-HCT. The ultimate goal is the implementation of optimized intervention programs to reduce side-effects and improve quality of life and potentially prognosis after allogeneic stem cell transplantation. Trial registration: ClinicalTrials.gov Identifier: NCT0137439

Reduced vagal activity in borderline personality disorder is unaffected by intranasal oxytocin administration, but predicted by the interaction between childhood trauma and attachment insecurity

Individuals with borderline personality disorder (BPD) show self-regulatory deficits, associated with reduced heart-rate variability (HRV). However, results on reduced HRV in BPD remain heterogeneous, thus encouraging the search for developmental constructs explaining this heterogeneity. The present study first examined predictors of reduced resting-state HRV in BPD, namely the interaction between self-reported adult attachment insecurity and childhood trauma. Second, we investigated if alterations in resting-state HRV are modified by intranasal oxytocin administration, as oxytocin may enhance HRV and is implicated in the interaction between childhood trauma and disturbed attachment for the pathogenesis of BPD. In a randomized, placebo-controlled trial, 53 unmedicated women with BPD and 60 healthy controls (HC) self-administered either 24 I.U. of oxytocin or placebo and underwent a 4-min electrocardiogram. Our results replicate significantly reduced HRV in women with BPD, explained up to 16% by variations in childhood trauma and attachment insecurity. At high levels of acute attachment insecurity, higher levels of childhood trauma significantly predicted reduced HRV in BPD. However, our results do not support a significant effect of oxytocin on mean HRV, and no interaction effect emerged including childhood trauma and attachment insecurity. Our findings highlight a complex interaction between reduced vagal activity and developmental factors in BPD

Impact of a Mechanism-Based Anti-Aggression Psychotherapy on Behavioral Mechanisms of Aggression in Patients With Borderline Personality Disorder

Introduction: Aggressive behavior is highly prevalent in patients with borderline personality disorder (BPD) and represents a major burden for patients and their environment. Previous studies have hypothesized threat hypersensitivity, among other mechanisms, as a biobehavioral mechanism underlying aggressive behavior in patients with BPD. The effects of a 6-week mechanism-based anti-aggression psychotherapy (MAAP) for the group setting were tested in comparison to the effects of a non-specific supportive psychotherapy (NSSP) on this hypothesized mechanism and their relation to the effects on aggressive behavior. Methods: To assess mechanisms of reactive aggression, 38 patients with BPD (20 in MAAP and 18 in NSSP) and 24 healthy controls participated in an emotion classification task before and after therapy or at a similar interval of 7 weeks for controls, respectively. In addition, current reactive aggressive behavior was assessed by the externally directed overt aggression score of the Overt Aggression Scale Modified (OAS-M) at both time points. Mixed linear models were used to test for group differences and differential treatment effects. Results: Consistent with previous findings, patients showed longer response latencies and misclassified faces as angry more often than healthy controls. Comparing pre- and post-treatment measurements, the MAAP group showed an increase in response latency in classifying angry faces, whereas the NSSP group showed a decrease in latency. Furthermore, the difference between pre- and post-treatment response latencies in classifying emotional faces correlated with the reductions in reactive aggression in the MAAP group, but not in the NSSP group or healthy controls. Conclusion: The results suggest an impact of MAAP on threat sensitivity as well as cognitive control, which has also been previously hypothesized as a biobehavioral mechanism underlying reactive aggression in patients with BPD. In addition, our findings shed light on the importance of these two biobehavioral mechanisms underlying reactive aggression as mechanisms of change addressed by MAAP. Further studies are needed to determine whether the behavioral change is stable over time and to what extent this change is related to a stable reduction in reactive aggression in a larger group of patients with BPD

Self-esteem instability and affective instability in everyday life after remission from borderline personality disorder

Background: Borderline personality disorder (BPD) is defined by a pervasive pattern of instability. According to prior findings and clinical theories, self-esteem instability and affective instability are key features of BPD. Previous e-diary studies showed that instability in self-esteem is heightened and that it is highly intertwined with affective instability in BPD in comparison to healthy controls (HC). The present study sought to extend these findings by adding symptomatologically remitted BPD patients (BPD-REM), i.e. former patients with BPD who met four or fewer BPD criteria within the past year, as a comparison group. Methods: To examine differences regarding self-esteem instability and affective instability, we used e-diaries for repeatedly collecting data on self-esteem, valence, and tense arousal 12 times a day for four consecutive days while participants underwent their daily life activities. Determining three different state-of-the-art instability indices and applying multilevel analyses, we compared 35 BPD-REM participants with previously reported 60 acute BPD patients (BPD-ACU) and 60 HC. Results: Our results revealed that self-esteem instability was significantly lower in the BPD-REM compared to the BPD-ACU group, irrespective of the instability index. In contrast, there were no significant differences regarding affective instability between the BPD-REM participants and those in the BPD-ACU group. The comparison between the BPD-REM with the HC indicated both a significantly higher instability in self-esteem as well as significantly heightened affective instability in the BPD-REM participants. Moreover, even though the associations were not significant, we found tentative support for the assumption that affective changes that are accompanied by changes in self-esteem are experienced as more burdensome and negatively impact the quality of life of remitted BPD participants. Conclusions: This study builds on growing evidence for the importance of self-esteem instability in BPD. Whereas affective instability has been reported in various psychiatric disorders and might indeed constitute a transdiagnostic marker of affective dysregulation, our results indicate that self-esteem instability might be a specific symptom that construes the unique pathology in BPD

Digital phenotyping: Towards replicable findings with comprehensive assessments and integrative models in bipolar disorders

Background: Digital phenotyping promises to unobtrusively obtaining a continuous and objective input of symptomatology from patients\u27 daily lives. The prime example are bipolar disorders, as smartphone parameters directly reflect bipolar symptomatology. Empirical studies, however, have yielded inconsistent findings. We believe that three main shortcomings have to be addressed to fully leverage the potential of digital phenotyping: short assessment periods, rare outcome assessments, and an extreme fragmentation of parameters without an integrative analytical strategy. Methods: To demonstrate how to overcome these shortcomings, we conducted frequent (biweekly) dimensional and categorical expert ratings and daily self-ratings over an extensive assessment period (12 months) in 29 patients with bipolar disorder. Digital phenotypes were monitored continuously. As an integrative analytical strategy, we used structural equation modelling to build latent psychopathological outcomes (mania, depression) and latent digital phenotype predictors (sleep, activity, communicativeness). Outcomes: Combining gold-standard categorical expert ratings with dimensional self and expert ratings resulted in two latent outcomes (mania and depression) with statistically meaningful factor loadings that dynamically varied over 299 days. Latent digital phenotypes of sleep and activity were associated with same-day latent manic psychopathology, suggesting that psychopathological alterations in bipolar disorders relate to domains (latent variables of sleep and activity) and not only to specific behaviors (such as the number of declined incoming calls). The identification of latent psychopathological outcomes that dimensionally vary on a daily basis will enable to empirically determine which combination of digital phenotypes at which days prior to an upcoming episode are viable as digital prodromal predictors. (DIPF/Orig.