Martin Hautzinger

Psychoanalytic and cognitive-behavior therapy of chronic depression: study protocol for a randomized controlled trial.

BackgroundDespite limited effectiveness of short-term psychotherapy for chronic depression, there is a lack of trials of long-term psychotherapy. Our study is the first to determine the effectiveness of controlled long-term psychodynamic and cognitive-behavioral (CBT) treatments and to assess the effects of preferential vs. randomized assessment.Methods/designPatients are assigned to treatment according to their preference or randomized (if they have no clear preference). Up to 80 sessions of psychodynamic or psychoanalytically oriented treatments (PAT) or up to 60 sessions of CBT are offered during the first year in the study. After the first year, PAT can be continued according to the ‘naturalistic’ usual method of treating such patients within the system of German health care (normally from 240 up to 300 sessions over two to three years). CBT therapists may extend their treatment up to 80 sessions, but focus mainly maintenance and relapse prevention. We plan to recruit a total of 240 patients (60 per arm). A total of 11 assessments are conducted throughout treatment and up to three years after initiation of treatment. The primary outcome measures are the Quick Inventory of Depressive Symptoms (QIDS, independent clinician rating) and the Beck Depression Inventory (BDI) after the first year.DiscussionWe combine a naturalistic approach with randomized controlled trials(RCTs)to investigate how effectively chronic depression can be treated on an outpatient basis by the two forms of treatment reimbursed in the German healthcare system and we will determine the effects of treatment preference vs. randomization.Trial registrationhttp://www.controlled-trials.com/ISRCTN91956346

Aims and structure of the German Research Consortium BipoLife for the study of bipolar disorder

BackgroundBipolar disorder is a severe and heterogeneous mental disorder. Despite great advances in neuroscience over the past decades, the precise causative mechanisms at the transmitter, cellular or network level have so far not been unraveled. As a result, individual treatment decisions cannot be tailor-made and the uncertain prognosis is based on clinical characteristics alone. Although a subpopulation of patients have an excellent response to pharmacological monotherapy, other subpopulations have been less well served by the medical system and therefore require more focused attention. In particular individuals at high risk of bipolar disorder, young patients in the early stages of bipolar disorder, patients with an unstable highly relapsing course and patients with acute suicidal ideation have been identified as those in need.StructureA research consortium of ten universities across Germany has therefore implemented a 4xa0year research agenda including three randomized controlled trials, one epidemiological trial and one cross-sectional trial to address these areas of unmet needs. The topics under investigation will be the improvement of early recognition, specific psychotherapy, and smartphones as an aid for early episode detection and biomarkers of lithium response. A subset of patients will be investigated utilizing neuroimaging (fMRI), neurophysiology (EEG), and biomaterials (genomics, transcriptomics).ConclusionsThis article aims to outline the rationale, design, and methods of these individual studies.

Does Childhood Maltreatment Moderate the Effect of the Cognitive Behavioral Analysis System of Psychotherapy versus Supportive Psychotherapy in Persistent Depressive Disorder

that compared CBASP with supportive psychotherapy (SP) [5] . CBASP targets specific maladaptive interpersonal behaviors that are associated with PDD and CM [6] . We have therefore hypothesized that CBASP is more effective than SP in patients retrospectively reporting CM. For the full description of the study, refer to the published protocol [7] and the main results [5] . Hereafter, only the aspects pertaining to the subgroup analysis will be reiterated. The acute treatment phase consisted of 24 sessions of CBASP or SP over 20 weeks. The primary outcome was depression severity as assessed by the 24-item version of the clinician-rated Hamilton Rating Scale for Depression (HRSD-24) at the end of the acute treatment phase. CM was assessed using the short form of the Childhood Trauma Questionnaire (CTQ-SF). The CTQ-SF consists of 28 self-report items that assess CM before the age of 18. It consists of 5 subscales: emotional abuse, physical abuse, sexual abuse, emotional neglect, and physical neglect. For this analysis, the presence of CM was defined as at least moderate to severe self-reported CM in at least one of these subscales. References for the outcome measures can be found at http://bit.ly/PPS484412. The statistical analysis was prespecified in the study protocol. It was performed on the modified intention-to-treat population that included all randomized patients for whom CTQ-SF data were available (256 out of 268, 95.5%). Missing outcome data at week 20 were imputed using the last observation carried forward method. The primary analysis was an analysis of covariance including fixed effects of group allocation, baseline HRSD-24 score, trial site, and presence of CM as main effects and the “treatment × presence of CM” interaction. The hypothesis that CM has a moderating influence on the efficacy of treatment was tested with the interaction term. We also conducted secondary exploratory analyses to discover which subtypes of CM have a moderating effect. Three quarters of the patients ( n = 190, 74.2%) reported at least moderate to severe CM. The most common forms of CM were emotional neglect ( n = 167, 65.5%) and emotional abuse ( n = 151, 59.0%) (see supplemental Table 1 at http://bit.ly/PPS484412). As reported previously [5] , CBASP was superior to SP in the reduction of depressive symptoms with a between-group effect of d = 0.31 at 20 weeks. Our main analysis revealed that the presence of CM had a moderating influence on the efficacy of treatment ( F 1, 244 = 4.253, p = 0.040; Fig. 1 ). The between-group effect was d = 0.49 in favor of CBASP in the subgroup of patients who reported CM ( d = –0.10 with no CM). The main effect of CM was not statistically significant ( F 1, 244 = 1.888, p = 0.171) indicating that CM did not predict outcome independent of treatment allocation. With regard to subtypes of CM, secondary analyses found that only emotional abuse had a significant moderating effect on the efficacy of treatment ( F 1, 244 = 6.866, p = 0.009). Here, the betweengroup effect was d = 0.60 in favor of CBASP in the subgroup of patients who reported CM ( d = –0.06 with no CM). This result can also be considered statistically significant if the threshold for sigIn the treatment of major depression, childhood maltreatment (CM) has been associated with an unfavorable outcome [1] . One possible exception might be psychotherapy with the cognitive behavioral analysis system of psychotherapy (CBASP). One study in patients with persistent depressive disorder (PDD) demonstrated that CBASP was more effective in those reporting CM than those not reporting CM [2] . CBASP is a treatment model that has been developed specifically for patients with PDD. In 2 trials comparing CBASP to other forms of psychotherapy, CBASP appeared to be superior to interpersonal psychotherapy (IPT) [3] and to other evidence-based psychotherapies including IPT and cognitive behavioral therapy (CBT) [4] . It is unclear however, whether the superiority of CBASP compared to other methods of psychotherapy is influenced by CM. The goal of the present study was to examine the impact of CM on the efficacy of CBASP in a prospective, multicenter, evaluator-blinded randomized clinical trial of unmedicated adult outpatients (18–65 years old) with early-onset PDD Received: June 28, 2017 Accepted after revision: October 19, 2017 Published online: January 6, 2018

The association between adherence and outcome in an Internet intervention for depression

BACKGROUNDnAdherence to Internet interventions is often reported to be rather low and this might adversely impact the effectiveness of these interventions. We investigated if patient characteristics are associated with adherence, and if adherence is associated with treatment outcome in a large RCT of an Internet intervention for depression, the EVIDENT trial.nnnMETHODSnPatients were randomized to either care as usual (CAU) or CAU plus the Internet intervention Deprexis. A total of 509 participants with mild to moderate depressive symptoms were included in the intervention group and of interest for the present study. We assessed depression symptoms pre and post intervention (12 weeks). Patient characteristics, a self-rating screening for mental disorders, attitudes towards online interventions, and quality of life were assessed before randomization.nnnRESULTSnAdherence in this study was good with on average seven hours of usage time and eight number of sessions spent with the intervention. Some of the patient characteristics (age, sex, depressive symptoms, and confidence in the effectiveness of the program) predicted higher number of sessions in different models (explaining in total between 15 and 25% of variance). Older age (β = .16) and higher depressive symptoms (β = .15) were associated with higher usage duration. Higher adherence to the program predicted a greater symptom reduction in depressive symptoms over 12 weeks (number of sessions: β = .13, usage duration: β = .14), however, this prediction could mostly be explained by receiving guidance (β = .27 and .26).nnnLIMITATIONSnReceiving guidance and symptom severity at baseline were confounded since only participants with a moderate symptom severity at baseline received e-mail support. Therefore no firm conclusions can be drawn from the association we observed between baseline symptom severity and usage intensity.nnnCONCLUSIONSnWe conclude that older age was associated with adherence and adherence was positively associated with outcome. The effects we have found were small however suggesting that adherence might also be influenced by further variables.

Psychotherapie depressiver Störungen

BACKGROUNDnDepressive disorders are associated with axa0high burden of suffering and significantly reduce the well-being and the self-esteem of affected patients. Psychotherapy is one of the main treatment options for depressive disorders.nnnOBJECTIVEnThe aim of this article is to present the current evidence for antidepressive psychotherapeutic treatments.nnnMATERIAL AND METHODSnDuring the revision of the German S3- and National Disease Management Guideline (NDMG) on unipolar depression in 2015, axa0comprehensive and systematic evidence search was conducted. The results of this search along with axa0systematic update are summarized.nnnRESULTSnThe most intensively investigated psychotherapeutic method is cognitive behavioral therapy (CBT), which proved to be effective in many trials. Evidence also exists for psychodynamic psychotherapy and interpersonal therapy (IPT), followed by systemic therapy and client-centered psychotherapy; however, the evidence is less robust.nnnCONCLUSIONnPsychotherapy alone or in combination with pharmacotherapy was shown to be an effective treatment option. Psychotherapy represents axa0key element in the treatment of depressive disorders.ZusammenfassungHintergrundDepressive Störungen beeinträchtigen wie kaum eine andere Erkrankung in zentraler Weise das Wohlbefinden und das Selbstwertgefühl von Patienten. Neben der Pharmakotherapie gehört die Psychotherapie zu den primären Behandlungsstrategien bei depressiven Störungen.Ziel der ArbeitZiel ist die Darstellung des aktuellen Wissens zu psychotherapeutischen Behandlungen bei depressiven Störungen.Material und MethodenIm Rahmen der 2015 durchgeführten Revision der aktuell gültigen S3- bzw. Nationalen VersorgungsLeitlinie (NVL) Unipolare Depression erfolgte eine systematische Evidenzrecherche. Die Ergebnisse zu verschiedenen psychotherapeutischen Verfahren in Verbindung mit einem systematischen Rechercheupdate werden in komprimierter Form dargestellt.ErgebnisseDie kognitive Verhaltenstherapie (KVT) ist das am häufigsten untersuchte Psychotherapieverfahren, ihre Wirksamkeit ist durch zahlreiche Studien belegt. Wirksamkeitsnachweise zur Behandlung depressiver Störungen liegen auch für die tiefenpsychologisch fundierte Psychotherapie und die interpersonelle Therapie (IPT) vor, gefolgt von der systemischen Therapie und der Gesprächspsychotherapie (GPT); die Evidenz ist aber weniger robust.DiskussionDie Wirksamkeit psychotherapeutischer Behandlungen alleine oder in Kombination mit pharmakologischen Behandlungen kann als sehr gut gesichert betrachtet werden. Psychotherapie stellt einen zentralen Bestandteil der Behandlung depressiver Störungen dar.AbstractBackgroundDepressive disorders are associated with axa0high burden of suffering and significantly reduce the well-being and the self-esteem of affected patients. Psychotherapy is one of the main treatment options for depressive disorders.ObjectiveThe aim of this article is to present the current evidence for antidepressive psychotherapeutic treatments.Material and methodsDuring the revision of the German S3- and National Disease Management Guideline (NDMG) on unipolar depression in 2015, axa0comprehensive and systematic evidence search was conducted. The results of this search along with axa0systematic update are summarized.ResultsThe most intensively investigated psychotherapeutic method is cognitive behavioral therapy (CBT), which proved to be effective in many trials. Evidence also exists for psychodynamic psychotherapy and interpersonal therapy (IPT), followed by systemic therapy and client-centered psychotherapy; however, the evidence is less robust.ConclusionPsychotherapy alone or in combination with pharmacotherapy was shown to be an effective treatment option. Psychotherapy represents axa0key element in the treatment of depressive disorders.

Association of comorbid personality disorders with clinical characteristics and outcome in a randomized controlled trial comparing two psychotherapies for early-onset persistent depressive disorder

BACKGROUNDnPersistent depressive disorder (PDD) is associated with high rates of comorbid personality disorders (PD). The association of comorbid PD and clinical characteristics has not been systematically studied in PDD. Results regarding effects on treatment outcome are heterogeneous.nnnMETHODSnWe analyzed the association of comorbid personality disorders with clinical characteristics and outcome in a randomized controlled trial comparing the disorder-specific Cognitive Behavioral Analysis System of Psychotherapy (CBASP) with nonspecific supportive psychotherapy (SP) in patients with early-onset PDD. The main outcome measure was the Hamilton Rating Scale for Depression (HRSD-24). Further baseline measures were comorbid axis-I diagnoses (SCID-I), quality of life (QLDS), global functioning (GAF), interpersonal problems (IIP-64) and childhood maltreatment (CTQ).nnnRESULTSnOut of the 268 patients, 103 (38.4%) met criteria for at least one PD. PD was associated with higher rates of axis I comorbidities (mainly anxiety disorders) and interpersonal problems (patients with PD were more vindictive, more self-sacrificing, less assertive and more inhibited socially than patients without PD). There was no significant main effect of PD on treatment outcome and no significant interaction between PD and treatment group.nnnLIMITATIONSnThe main limitation was the exclusion of patients with certain personality disorders (antisocial, schizotypal, and borderline personality disorders). Furthermore, the study was underpowered to find interaction effects of small size.nnnCONCLUSIONnPersistently depressed patients with and without comorbid PD primarily seemed to differ in the rate of axis I comorbidity and the severity of interpersonal problems. Treatment outcomes appear to be not significantly affected by the presence of PD.

Gene set enrichment analysis and expression pattern exploration implicate an involvement of neurodevelopmental processes in bipolar disorder.

BACKGROUNDnBipolar disorder (BD) is a common and highly heritable disorder of mood. Genome-wide association studies (GWAS) have identified several independent susceptibility loci. In order to extract more biological information from GWAS data, multi-locus approaches represent powerful tools since they utilize knowledge about biological processes to integrate functional sets of genes at strongly to moderately associated loci.nnnMETHODSnWe conducted gene set enrichment analyses (GSEA) using 2.3 million single-nucleotide polymorphisms, 397 Reactome pathways and 24,025 patients with BD and controls. RNA expression of implicated individual genes and gene sets were examined in post-mortem brains across lifespan.nnnRESULTSnTwo pathways showed a significant enrichment after correction for multiple comparisons in the GSEA: GRB2 events in ERBB2 signaling, for which 6 of 21 genes were BD associated (PFDR = 0.0377), and NCAM signaling for neurite out-growth, for which 11 out of 62 genes were BD associated (PFDR = 0.0451). Most pathway genes showed peaks of RNA co-expression during fetal development and infancy and mapped to neocortical areas and parts of the limbic system.nnnLIMITATIONSnPathway associations were technically reproduced by two methods, although they were not formally replicated in independent samples. Gene expression was explored in controls but not in patients.nnnCONCLUSIONSnPathway analysis in large GWAS data of BD and follow-up of gene expression patterns in healthy brains provide support for an involvement of neurodevelopmental processes in the etiology of this neuropsychiatric disease. Future studies are required to further evaluate the relevance of the implicated genes on pathway functioning and clinical aspects of BD.

Erste Erfahrungen zur Implementierbarkeit einer internet-basierten Selbsthilfe zur Überbrückung der Wartezeit auf eine ambulante Psychotherapie

INTRODUCTIONnNumerous studies prove the efficacy of internet-based self-help programs, but integration into the health-care system was rarely investigated. The present study addresses the implementation of an internet-based self-help program into routine care of patients with depressive symptoms waiting for psychotherapy at the university outpatient center.nnnMATERIAL AND METHODSnPatients waiting for outpatient psychotherapy were randomly assigned to either a control group or an intervention group that received access to the internet-based program Deprexis during the waiting period. Depressive symptoms were assessed before and after waiting. Additionally, expectations and program use of participants were exploratively examined.nnnRESULTSnOnly half of the patients who were informed about the study were interested in participation. Participants used about half of the modules in the program Deprexis. Depressive symptoms were reduced in both groups during the waiting time. However, the symptom improvements were not significant.nnnDISCUSSIONnIntegration of internet-based self-help programs into the German health-care system should include support by a psychotherapist. Preferences of participants should also be considered to enhance adherence and efficacy of the program.nnnCONCLUSIONnInternet-based self-help programs for use in the waiting time for outpatient psychotherapy of patients with depression should involve guidance.

Meditation and the brain –neuronal correlates of mindfulness as assessed with near infrared spectroscopy

Mindfulness meditation as a therapeutic intervention has been shown to have positive effects on psychological problems such as depression, pain or anxiety disorders. In this study, we used functional near-infrared spectroscopy (fNIRS) to detect differences in hemodynamic responses of meditation experts (14 participants) and a control group (16 participants) in a resting and a mindfulness condition. In both conditions, the sound of a meditation bowl was used to find group differences in the auditory system and adjacent cortical areas. Different lateralization patterns of the brain were found in expert meditators while being in a resting state (amplified left hemisphere) or being in mindfulness state (amplified right hemisphere). Compared to the control group, meditation experts had a more widespread pattern of activation in the auditory cortex, while resting. In the mindfulness condition, the control group showed a decrease of activation in higher auditory areas (BA 1, 6 and 40), whereas the meditation experts had a significant increase in those areas. In addition, meditation expert had highly activated brain areas (BA 39, 40, 44 and 45) beyond the meditative task itself, indicating possible long-term changes in the brain and their positive effects on empathy, meta cognitive skills and health.

Psychotherapie depressiver Störungen: Evidenz bei chronischer Depression und bei Komorbidität

ZusammenfassungHintergrundObwohl eine große Zahl von Studien die generelle Wirksamkeit psychotherapeutischer Behandlungen depressiver Störungen zeigt, variiert die Wirksamkeit in Abhängigkeit von therapeuten- und patientenseitigen Einflussfaktoren sowie der Art des depressiven Störungsbildes.Ziel der ArbeitZiel ist die zusammenfassende Darstellung des aktuellen Wissens zu psychotherapeutischen Behandlungen bei Patienten mit chronischen bzw. therapieresistenten depressiven Störungen und bei Patienten mit psychischen oder somatischen Komorbiditäten.Material und MethodenIm Rahmen der 2015 durchgeführten Revision der aktuell gültigen S3- bzw. Nationalen VersorgungsLeitlinie (NVL) Unipolare Depression erfolgte eine systematische Evidenzrecherche zu Psychotherapie bei spezifischen Patientengruppen. Diese Ergebnisse in Verbindung mit einem systematischen Rechercheupdate werden dargestellt.ErgebnisseFür die spezifischen Patientengruppen der chronisch depressiven bzw. therapieresistenten Patienten sowie mit komorbiden psychischen oder somatischen Erkrankungen liegen Hinweise für die Wirksamkeit von Psychotherapie im Hinblick auf die Reduktion depressiver Symptome vor. Insbesondere für depressive Patienten mit psychischen Komorbiditäten ist die Evidenzlage allerdings noch nicht ausreichend.DiskussionBasierend auf der aktuellen Evidenz und/oder auf klinischem Expertenkonsens empfiehlt die NVL eine alleinige Psychotherapie oder eine Kombination mit Antidepressiva bei den meisten der genannten Patientengruppen. Es bestehen Kenntnislücken, die deutlich machen, dass weitere wissenschaftliche Bemühungen notwendig sind, um die Behandlung spezifischer depressiver Patientengruppen weiter zu verbessern.AbstractBackgroundPsychotherapy has been shown to be an effective treatment option for depressive disorders; however, its effectiveness varies depending on patient and therapist characteristics and the individual form of the depressive disorder.ObjectivesThe aim of this article is to present the current evidence for psychotherapeutic antidepressive treatments for patients with chronic and treatment-resistant depression as well as for patients with mental and somatic comorbidities.Material and methodsDuring the revision of the currently valid German S3- and National Disease Management Guideline (NDMG) on unipolar depression published in 2015, axa0comprehensive and systematic evidence search including psychotherapy for specific patient groups was conducted. The results of this search along with axa0systematic update are summarized.ResultsPsychotherapy has been shown to be effective in reducing depressive symptoms in patients suffering from chronic and treatment-resistant depression and in patients with mental and somatic comorbidities. The evidence is insufficient particularly for patients with mental comorbidities.ConclusionBased on the current evidence and clinical expertise the NDMG recommends psychotherapy alone or in combination with pharmacotherapy to treat most of these depressive patient groups. Evidence gaps were identified, which highlight the need for further research.BACKGROUNDnPsychotherapy has been shown to be an effective treatment option for depressive disorders; however, its effectiveness varies depending on patient and therapist characteristics and the individual form of the depressive disorder.nnnOBJECTIVESnThe aim of this article is to present the current evidence for psychotherapeutic antidepressive treatments for patients with chronic and treatment-resistant depression as well as for patients with mental and somatic comorbidities.nnnMATERIAL AND METHODSnDuring the revision of the currently valid German S3- and National Disease Management Guideline (NDMG) on unipolar depression published in 2015, axa0comprehensive and systematic evidence search including psychotherapy for specific patient groups was conducted. The results of this search along with axa0systematic update are summarized.nnnRESULTSnPsychotherapy has been shown to be effective in reducing depressive symptoms in patients suffering from chronic and treatment-resistant depression and in patients with mental and somatic comorbidities. The evidence is insufficient particularly for patients with mental comorbidities.nnnCONCLUSIONnBased on the current evidence and clinical expertise the NDMG recommends psychotherapy alone or in combination with pharmacotherapy to treat most of these depressive patient groups. Evidence gaps were identified, which highlight the need for further research.