Age-adjusted high-dose chemotherapy followed by autologous stem cell transplantation or conventional chemotherapy with R-MP as first-line treatment in elderly primary CNS lymphoma patients - the randomized phase III PRIMA-CNS trial.

BACKGROUND: Older primary central nervous system lymphoma (PCNSL) patients have an inferior prognosis compared to younger patients because available evidence on best treatment is scarce and treatment delivery is challenging due to comorbidities and reduced performance status. High-dose chemotherapy and autologous stem cell transplantation (HCT-ASCT) after high-dose methotrexate (MTX)-based immuno-chemotherapy has become an increasingly used treatment approach in eligible elderly PCNSL patients with promising feasibility and efficacy, but has not been compared with conventional chemotherapy approaches. In addition, eligibility for HCT-ASCT in elderly PCNSL is not well defined. Geriatric assessment (GA) may be helpful in selecting patients for the best individual treatment choice, but no standardized GA exists to date. A randomized controlled trial, incorporating a GA and comparing age-adapted HCT-ASCT treatment with conventional chemotherapy is needed. METHODS: This open-label, multicenter, randomized phase III trial with two parallel arms will recruit 310 patients with newly diagnosed PCNSL > 65 years of age in 40 centers in Germany and Austria. The primary objective is to demonstrate that intensified chemotherapy followed by consolidating HCT-ASCT is superior to conventional chemotherapy with rituximab, MTX, procarbazine (R-MP) followed by maintenance with procarbazine in terms of progression free survival (PFS). Secondary endpoints include overall survival (OS), event free survival (EFS), (neuro-)toxicity and quality of life (QoL). GA will be conducted at specific time points during the course of the study. All patients will be treated with a pre-phase rituximab-MTX (R-MTX) cycle followed by re-assessment of transplant eligibility. Patients judged transplant eligible will be randomized (1:1). Patients in arm A will be treated with 3 cycles of R-MP followed by maintenance therapy with procarbazine for 6 months. Patients in arm B will be treated with 2 cycles of MARTA (R-MTX/AraC) followed by busulfan- and thiotepa-based HCT-ASCT. DISCUSSION: The best treatment strategy for elderly PCNSL patients remains unknown. Treatments range from palliative to curative but more toxic therapies, and there is no standardized measure to select patients for the right treatment. This randomized controlled trial will create evidence for the best treatment strategy with the focus on developing a standardized GA to help define eligibility for an intensive treatment approach. TRIAL REGISTRATION: German clinical trials registry DRKS00024085 registered March 29, 2023.

Two-Year Follow-Up after Treatment with the Cognitive Behavioral Analysis System of Psychotherapy versus Supportive Psychotherapy for Early-Onset Chronic Depression.

BACKGROUND: Evidence on the long-term efficacy of psychotherapeutic approaches for chronic depression is scarce. OBJECTIVE: To evaluate the effects of the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) compared to Supportive Psychotherapy (SP) 1 year and 2 years after treatment termination. METHODS: In this study, we present 1- and 2-year follow-up assessments of a prospective, multicenter, evaluator-blinded, randomized clinical trial of outpatients with early-onset chronic major depression (n = 268). The initial treatment included 32 sessions of CBASP or SP over 48 weeks. The primary outcome was the rate of "well weeks" (Longitudinal Interval Follow-Up Evaluation; no/minimal symptoms) after 1 year and 2 years. The secondary outcomes were, among others, clinician- and self-rated depressive symptoms, response/remission rates, and quality of life. RESULTS: Of the 268 randomized patients, 207 (77%) participated in the follow-up. In the intention-to-treat analysis, there was no statistically significant difference between CBASP and SP patients in experiencing well weeks (CBASP: mean [SD] of 48.6 [36.9] weeks; SP: 39.0 [34.8]; rate ratio 1.26, 95% CI 0.99-1.59, p = 0.057, d = 0.18) and in remission rates (CBASP: 1 year 40%, 2 years 40.2%; SP: 1 year 28.9%, 2 years 33%) in the 2 years after treatment. Statistically significant effects were found in favor of CBASP 1 year after treatment termination regarding the rate of well weeks, self-rated depressive symptoms, and depression-related quality of life. CONCLUSIONS: CBASP lost its superiority over SP at some point between the first and the second year. This suggests the necessity of maintenance treatment for early-onset chronically depressed patients remitted with CBASP during the acute therapy phase, as well as the sequential integration of other treatment strategies, including medication for those who did not reach remission.

An Internet-Based Self-Help Intervention for Skin Picking (SaveMySkin): Pilot Randomized Controlled Trial.

BACKGROUND: In spite of the psychosocial burden and medical risks associated with skin picking disorder, the health care system does not provide sufficient treatment for affected individuals to date. Therefore, an internet-based self-help program for skin picking was developed to offer easily accessible support for this population. OBJECTIVE: This pilot study evaluated the internet-based self-help program SaveMySkin. The 12-week program is based on cognitive-behavioral therapy and contains comprehensive information and exercises, a daily supportive monitoring system, and dermatological and psychological counseling via internet chat. Primary objectives were the investigation of attitudes and expectations toward the program, intervention effects on skin picking severity, user satisfaction, adherence, and willingness to participate. Secondary outcomes included the feasibility of study procedures, adequacy of assessment instruments, effects on skin picking-related impairment, dimensions of skin picking, and general psychological impairment. METHODS: A two-arm randomized controlled trial was conducted in a sample of 133 participants (female: 124/133, 93.2%; mean age 26.67 [SD 6.42]) recruited via the internet. Inclusion required a minimum age of 17 years and at least mild skin picking severity. Participants were randomly allocated to the intervention (64/133, 48.1%) or waitlist control group (69/133, 51.9%). All assessments were conducted online and based on self-report. RESULTS: The willingness to participate was very high in the study, so the initially planned sample size of 100 was exceeded after only 18 days. Participant expectations indicate that they believed the program to be beneficial for them (131/133, 98.5%) and provide a feeling of support (119/133, 89.5%). Reasons for study participation were insufficient outpatient health care (83/133, 62.4%) and flexibility regarding time (106/133, 79.7%) and location (109/133, 82.0%). The post-assessment was completed by 65.4% (87/133) of the sample. The majority of the intervention group who completed the entire post-assessment were satisfied with SaveMySkin (28/38, 74%) and agreed that the program is an appropriate support service (35/38, 92%). On average, participants viewed 29.31 (SD 42.02) pages in the program, and 47% (30/64) of the intervention group used the monitoring at least once a week. In comparison with the control group, the intervention group displayed substantial improvements in the skin picking severity total score (Cohen d=0.67) and especially on the subscale Symptom Severity (Cohen d=0.79). No effects on secondary outcomes were found. CONCLUSIONS: This study confirms the need for easily accessible interventions for skin picking disorder and the high interest in internet-based self-help within the target population. It provides important insights into the attitudes toward online support and actual user experiences. Participant feedback will be used to further enhance the intervention. Our results point to the preliminary efficacy of SaveMySkin and may lay the foundation for future research into the efficacy and cost-effectiveness of the program in a multicenter clinical trial. TRIAL REGISTRATION: German Clinical Trial Register DRKS00015236; https://www.drks.de/drks_web/navigate.do? navigationId=trial.HTML&TRIAL_ID=DRKS00015236. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1016/j.conctc.2018.100315.

The assessment of skin picking in adolescence: psychometric properties of the Skin Picking Scale-Revised (German version).

BACKGROUND: Skin picking disorder has received growing attention since the release of DSM-5, yet there are no evidence-based assessment instruments for adolescent samples. AIM: The present study examines the psychometric properties of the Skin Picking Scale-Revised (SPS-R, German version) in adolescents. METHODS: A total of 76 adolescents (96% female) completed the SPS-R, the Clinical Psychological Diagnostic System (KPD-38), and a questionnaire assessing demographics and clinical characteristics online. RESULTS: The SPS-R had high internal consistency (α = 0.89) and significant small-to-medium correlations with reduced competence skills, psychological impairment, general life satisfaction, social support, and social problems on the KPD-38. Similar to prior findings for adults, an exploratory factor analysis suggested a two-factor model for the SPS-R in adolescents. Group comparisons failed to show significant differences on SPS-R scores between participants with and without dermatological conditions. CONCLUSIONS: The current results suggest that the SPS-R can be useful in adolescent samples as a reliable and valid instrument for the assessment of skin picking severity. Future research investigating scale validity and factor structure in a clinical sample of adolescent skin pickers is warranted.

Internet-Delivered Disease Management for Recurrent Depression: A Multicenter Randomized Controlled Trial.

BACKGROUND: Strategies to improve the life of patients suffering from recurrent major depression have a high relevance. This study examined the efficacy of 2 Internet-delivered augmentation strategies that aim to prolong symptom-free intervals. METHODS: Efficacy was tested in a 3-arm, multicenter, open-label, evaluator-blind, randomized controlled trial. Upon discharge from inpatient mental health care, 232 adults with 3 or more major depressive episodes were randomized to 1 of 2 intervention groups (SUMMIT or SUMMIT-PERSON) or to treatment as usual (TAU) alone. Over 12 months, participants in both intervention arms received, in addition to TAU, intense monitoring via e-mail or a smartphone, including signaling of upcoming crises, assistance with personal crisis management, and facilitation of early intervention. SUMMIT-PERSON additionally offered regular expert chats. The primary outcome was 'well weeks', i.e. weeks with at most mild symptoms assessed by the Longitudinal Interval Follow-Up Evaluation, during 24 months after the index treatment. RESULTS: SUMMIT compared to TAU reduced the time with an unwell status (OR 0.48; 95% CI 0.23-0.98) through faster transitions from unwell to well (OR 1.44; 95% CI 0.83-2.50) and slower transitions from well to unwell (OR 0.69; 95% CI 0.44-1.09). Contrary to the hypothesis, SUMMIT-PERSON was not superior to either SUMMIT (OR 0.77; 95% CI 0.38-1.56) or TAU (OR 0.62; 95% CI 0.31-1.24). The efficacy of SUMMIT was strongest 8 months after the intervention. CONCLUSIONS: The fully automated Internet-delivered augmentation strategy SUMMIT has the potential to improve TAU by reducing the lifelong burden of patients with recurrent depression. The fact that the effects wear off suggests a time-unlimited extension.

[A Self-Report Instrument for the Assessment of Dermatillomania: Reliability and Validity of the German Skin Picking Scale-Revised]. / Ein Selbstbeurteilungsinstrument zur Erfassung von Dermatillomanie: Reliabilität und Validität der deutschsprachigen Version der Skin Picking Scale-Revised.

At least since the introduction of the official diagnosis Excoriation (Skin-Picking) Disorder in the DSM-5 [1], dermatillomania is an important and growing field of research. Despite the high importance currently a huge lack of German assessment instruments exists. Aim of the present study was the examination of the psychometric properties of the German translation of the Skin Picking Scale-Revised [2]. For this purpose an open online study has been conducted. The analysis of N=2 065 data sets indicated a high internal consistency with Cronbachs Alpha being 0.93. Furthermore positive associations with the 3 problem areas psychological impairment, general physical condition, social problems as well as with reduced competence skills, general life satisfaction and social support indicate a good constructvalidity. Another sign for validity is a significant effect in terms of gender: As expected women showed higher skin picking scores than men. Overall the results of the present study suggest that the German version of the SPS-R can be seen as a reliable and valid instrument for the assessment of dermatillomania.

The temporal dynamics of cognitive reactivity and their association with the depression risk: an exploratory study.

BACKGROUND: Cognitive reactivity is the change in depressive thinking in response to negative mood. Previous research indicates that cognitive reactivity is an important variable in the etiology and course of depression. The present study tested which time interval after a negative mood induction is critical for the prediction of the depression risk. METHODS: Participants suffering from a major depressive disorder were recruited when entering inpatient treatment. At the end of inpatient treatment they completed an experimental procedure to assess their depressive thinking once before and twice after a negative mood induction. Subsequently, patients were followed up for 26 weeks. RESULTS: The immediate change in depressive thinking in response to the negative mood induction was negatively associated with future depression. The delayed change did not predict the depression risk. CONCLUSION: The negative association between the immediate change in depressive thinking and the depression risk is not in line with results from previous studies on cognitive reactivity. Previous research on emotion context insensitivity and the avoidance of negative thoughts offers hypotheses which could account for this result. Further research is needed to shed light on the processes underlying cognitive reactivity.

Coping with delusions in schizophrenia and affective disorder with psychotic symptoms: the relationship between coping strategies and dimensions of delusion.

BACKGROUND: Self-generated coping strategies and the enhancement of coping strategies are effective in the treatment of psychotic symptoms. Evaluating these strategies can be of clinical interest to develop better coping enhancement therapies. Cognitive models consider delusions as multidimensional phenomena. Using a psychometric approach, the relationship between coping and the dimensions of delusion were examined. METHODS: Thirty schizophrenia spectrum patients with delusions and 29 patients with affective disorder with psychotic symptoms were interviewed using the Heidelberg Coping Scales for Delusions and the Heidelberg Profile of Delusional Experience. Analyses of variance were conducted to investigate differences between the groups, and Spearman's rank-based correlations were used to examine the correlations between coping factors and the dimensions of delusion. RESULTS: Schizophrenia spectrum patients used more medical care and symptomatic coping, whereas patients with affective disorder engaged in more depressive coping. In the schizophrenia spectrum sample, the action-oriented, the cognitive, and the emotional dimensions of delusion were related to coping factors. In patients with affective disorder, only the action-oriented dimension was related to coping factors. CONCLUSION: Patients with schizophrenia and affective disorder cope differently with delusions. The dimensions of delusion are related to coping and should be regarded when using cognitive therapy approaches to enhance coping strategies.

Preliminary Evidence for a Nexus between Rumination, Behavioural Avoidance, Motive Satisfaction and Depression.

UNLABELLED: The present study tested a theoretically derived link between rumination and depressive symptoms through behavioural avoidance and reduced motive satisfaction as a key aspect of positive reinforcement. Rumination, behavioural avoidance, motive satisfaction and levels of depression were assessed via self-report measures in a clinical sample of 160 patients with major depressive disorder. Path analysis-based mediation analysis was used to estimate the direct and indirect effects as proposed by the theoretical model. Operating in serial, behavioural avoidance and motive satisfaction partially mediated the association between rumination and depressive symptoms, irrespective of gender, medication and co-morbid anxiety disorders. This is the first study investigating the associations between behavioural avoidance, rumination and depression in a clinical sample of depressed patients. The findings are in line with an understanding of rumination in depression as also serving an avoidance function. KEY PRACTITIONER MESSAGE: Rumination, avoidance, motive satisfaction and levels of depressive symptoms were examined in a clinical sample of 160 outpatients with major depressive disorder. Path analysis-based mediation analysis revealed that, operating in serial, avoidance and motive satisfaction partially mediated the link between rumination and levels of depressive symptoms. Findings support an understanding of rumination in depression as serving an avoidance function.

Prediction of symptoms of emotional distress by mood regulation expectancies and affective traits.

Three studies examined negative mood regulation expectancies (NMRE) and affective traits as independent predictors of self-reported symptoms of emotional distress. NMRE represent individuals' beliefs that they can alleviate unpleasant emotional states. Stronger NMRE are associated with more adaptive coping, more positive cognition during negative moods, more effective responses under stress and less emotional distress. Affective traits represent long-term tendencies toward particular affective experiences; they confer risk for specific symptoms of emotional distress. In Study 1, NMRE, trait negative affect (TNA) and trait positive affect (TPA) were all independently associated with depression among students and staff of a German university. In Study 2, in prospective analyses among U.S. college students traits exhibited hypothesised relationships with anxiety and depressive symptoms, and NMRE uniquely predicted anhedonic depression. Study 3 revealed independent prediction of change in symptoms over time by NMRE among U.S. college students, whereas traits were not associated with change in distress, anxiety and depression symptoms. Results suggest independent roles for NMRE and traits in the development of depression and anxiety symptoms and highlight the importance of NMRE as a potential target of therapeutic intervention in the process of symptom change.

High-dose chemotherapy and autologous haematopoietic stem-cell transplantation in older, fit patients with primary diffuse large B-cell CNS lymphoma (MARTA): a single-arm, phase 2 trial.

BACKGROUND: Available treatments for older patients with primary diffuse large B-cell CNS lymphoma (PCNSL) offer progression-free survival of up to 16 months. We aimed to investigate an intensified treatment of high-dose chemotherapy and autologous haematopoietic stem-cell transplantation (HSCT) in older patients with PCNSL. METHODS: MARTA was a prospective, single-arm, phase 2 study done at 15 research hospitals in Germany. Patients aged 65 years or older with newly diagnosed, untreated PCNSL were enrolled if they had an Eastern Cooperative Oncology Group performance status of 0-2 and were fit for high-dose chemotherapy and autologous HSCT. Induction treatment consisted of two 21-day cycles of high-dose intravenous methotrexate 3·5 g/m2 (day 1), intravenous cytarabine 2 g/m2 twice daily (days 2 and 3), and intravenous rituximab 375 mg/m2 (days 0 and 4) followed by high-dose chemotherapy with intravenous rituximab 375 mg/m2 (day -8), intravenous busulfan 3·2 mg/kg (days -7 and -6), and intravenous thiotepa 5 mg/kg (days -5 and -4) plus autologous HSCT. The primary endpoint was progression-free survival at 12 months in all patients who met eligibility criteria and started treatment. The study was registered with the German clinical trial registry, DRKS00011932, and recruitment is complete. FINDINGS: Between Nov 28, 2017, and Sept 16, 2020, 54 patients started induction treatment and 51 were included in the full analysis set. Median age was 71 years (IQR 68-75); 27 (53%) patients were female and 24 (47%) were male. At a median follow-up of 23·0 months (IQR 16·8-37·4), 23 (45%) of 51 patients progressed, relapsed, or died. 12-month progression-free survival was 58·8% (80% CI 48·9-68·2; 95% CI 44·1-70·9). During induction treatment, the most common grade 3-5 toxicities were thrombocytopenia and leukopenia (each in 52 [96%] of 54 patients). During high-dose chemotherapy and autologous HSCT, the most common grade 3-5 toxicity was leukopenia (37 [100%] of 37 patients). Treatment-related deaths were reported in three (6%) of 54 patients, all due to infectious complications. INTERPRETATION: Although the primary efficacy threshold was not met, short induction followed by high-dose chemotherapy and autologous HSCT is active in selected older patients with PCNSL and could serve as a benchmark for comparative trials. FUNDING: Else Kröner-Fresenius Foundation, Riemser Pharma, and Medical Center-University of Freiburg.

Preliminary reliability and validity of the Spanish Generalized Expectancies for Negative Mood Regulation Scale.

OBJECTIVE: This article introduces a Spanish version of the Generalized Expectancies for Negative Mood Regulation Scale (NMR-S) and tests the reliability and the validity of the new questionnaire. METHODS: A sample of 360 students from Chile completed the NMR-S along with instruments measuring depressive symptoms, social desirability, coping, and emotion regulation. RESULTS: A factor analysis indicated that the NMR-S has a one-dimensional structure. The reliability of the new instrument was α = 0.89. The concurrent validity of the NMR-S was supported by correlations with measures of coping, emotion regulation, and depressive symptoms. Furthermore, the NMR-S predicted depressive symptoms when controlling for emotion regulation and coping. CONCLUSIONS: The findings are the first evidence to support the reliability and validity of the NMR-S.

[Eating disorders on the internet: an experimental study on the effects of pro-eating disorders websites and self-help websites]. / Essstörungen im Internet: Eine experimentelle Studie zu den Auswirkungen von Pro-Essstörungs- und Selbsthilfewebsites.

Pro-eating disorders (ED) websites are assumed to have a negative impact on internet users because these sites promote ED as a lifestyle, and present an extreme thin ideal as well as extreme weight loss measures. We tested the impact of reading pro-ED contents in a sample of 421 women. The participants were randomly assigned to one of 3 conditions in which they were exposed to either a pro-ED blog, a self-help blog, or a neutral control blog. Post-exposure negative affect was higher in participants of the pro-ED and the self-help conditions compared to the neutral blog condition. Participants with an elevated risk for developing an ED had a lower appearance self esteem after exposure to the pro-ED, or the self-help blog. According to the study, a subgroup of high risk individuals might be affected by ED-related internet content. The implications of this study are discussed in the context of the ongoing controversy around pro-ED websites.

Planning and problem-solving training for patients with schizophrenia: a randomized controlled trial.

BACKGROUND: The purpose of this study was to assess whether planning and problem-solving training is more effective in improving functional capacity in patients with schizophrenia than a training program addressing basic cognitive functions. METHODS: Eighty-nine patients with schizophrenia were randomly assigned either to a computer assisted training of planning and problem-solving or a training of basic cognition. Outcome variables included planning and problem-solving ability as well as functional capacity, which represents a proxy measure for functional outcome. RESULTS: Planning and problem-solving training improved one measure of planning and problem-solving more strongly than basic cognition training, while two other measures of planning did not show a differential effect. Participants in both groups improved over time in functional capacity. There was no differential effect of the interventions on functional capacity. CONCLUSION: A differential effect of targeting specific cognitive functions on functional capacity could not be established. Small differences on cognitive outcome variables indicate a potential for differential effects. This will have to be addressed in further research including longer treatment programs and other settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT00507988.

Generalized expectancies for negative mood regulation and major depressive disorder: the role of previous depressive episodes and comorbid mental disorders.

BACKGROUND: Generalized expectancies for negative mood regulation (NMR) have important consequences for the ability to regulate negative mood. This study tests two resulting hypotheses. NMR expectancies should correlate with the number of previous depressive episodes. Furthermore, there should be a correlation between NMR expectancies and the number of DSM-IV axis I disorders comorbid to depression. In order to test these hypotheses with an efficient instrument, this article presents the NMR-SF as a short form of the NMR Scale. METHODS: During inpatient treatment, a sample of 40 depressed patients was interviewed by a clinical psychologist with the Structural Clinical Interview for DSM-IV to assess the number of previous depressive episodes as well as the number of axis I comorbidities. Patients completed the NMR-SF to measure NMR expectancies. Additionally, a nonclinical sample of 560 participants completed the NMR-SF to test its reliability and validity. RESULTS: The findings indicate that the NMR-SF is reliable and valid. In the clinical sample, NMR expectancies did not correlate significantly with the number of previous depressive episodes. There was a significant correlation between NMR expectancies and the number of comorbid mental disorders. CONCLUSION: Previous depressive episodes do not seem to result in lower NMR expectancies. The findings are in line with the hypothesis that NMR expectancies are involved in the etiology of mental disorders comorbid to depression.

Development of an Emotion-Sensitive mHealth Approach for Mood-State Recognition in Bipolar Disorder.

Internet- and mobile-based approaches have become increasingly significant to psychological research in the field of bipolar disorders. While research suggests that emotional aspects of bipolar disorders are substantially related to the social and global functioning or the suicidality of patients, these aspects have so far not sufficiently been considered within the context of mobile-based disease management approaches. As a multiprofessional research team, we have developed a new and emotion-sensitive assistance system, which we have adapted to the needs of patients with bipolar disorder. Next to the analysis of self-assessments, third-party assessments, and sensor data, the new assistance system analyzes audio and video data of these patients regarding their emotional content or the presence of emotional cues. In this viewpoint, we describe the theoretical and technological basis of our emotion-sensitive approach and do not present empirical data or a proof of concept. To our knowledge, the new assistance system incorporates the first mobile-based approach to analyze emotional expressions of patients with bipolar disorder. As a next step, the validity and feasibility of our emotion-sensitive approach must be evaluated. In the future, it might benefit diagnostic, prognostic, or even therapeutic purposes and complement existing systems with the help of new and intuitive interaction models.

Impact of Baseline Characteristics on the Effectiveness of Disorder-Specific Cognitive Behavioral Analysis System of Psychotherapy (CBASP) and Supportive Psychotherapy in Outpatient Treatment for Persistent Depressive Disorder.

Importance: In the treatment of persistent depressive disorder (PDD), disorder-specific Cognitive Behavioral Analysis System of Psychotherapy (CBASP) has been shown to be superior to Supportive Psychotherapy (SP) in outpatients. It remains to clear which subgroups of patients benefit equally and differentially from both psychotherapies. Objective: To identify those patient-level baseline characteristics that predict a comparable treatment effectiveness of CBASP and SP and those that moderate the differential effectiveness of CBASP compared to SP. Design, setting and participants: In this analysis of a 48-week multicenter randomized clinical trial comparing CBASP to SP in adult antidepressant-free outpatients with early-onset PDD, we evaluated baseline variables from the following domains as potential predictors and moderators of treatment effectiveness: socio-demography, clinical status, psychosocial and global functioning, life quality, interpersonal problems, childhood trauma, treatment history, preference for psychotherapy, and treatment expectancy. Interventions: A 48-week treatment program with 32 sessions of either CBASP or SP. Main outcomes and measures: Depression severity measured by the 24-item Hamilton Rating Scale for Depression (HRSD-24) at week 48. Results: From N = 268 randomized outpatients, N = 209 completed the 48-week treatment program. CBASP completers had significantly lower post-treatment HRSD-24 scores than SP completers (meanCBASP=13.96, sdCBASP= 9.56; meanSP= 16.69, sdSP= 9.87; p = 0.04). A poor response to both therapies was predicted by higher baseline levels of clinician-rated depression, elevated suicidality, comorbid anxiety, lower social functioning, higher social inhibition, moderate-to-severe early emotional or sexual abuse, no preference for psychotherapy, and the history of at least one previous inpatient treatment. Moderator analyses revealed that patients with higher baseline levels of self-rated depression, comorbidity of at least one Axis-I disorder, self-reported moderate-to-severe early emotional or physical neglect, or at least one previous antidepressant treatment, had a significantly lower post-treatment depression severity with CBASP compared to SP (all p < 0.05). Conclusions and relevance: A complex multifactorial interaction between severe symptoms of depression, suicidality, and traumatic childhood experiences characterized by abuse, social inhibition, and anxiety may represent the basis of non-response to psychotherapy in patients with early onset PDD. Specific psychotherapy with CBASP might, however, be more effective and recommendable for a variety of particularly burdened patients compared to SP.

Combining baseline characteristics to disentangle response differences to disorder-specific versus supportive psychotherapy in patients with persistent depressive disorder.

Does the pre-treatment profile of individuals with persistent depressive disorder (PDD) moderate their benefit from disorder-specific Cognitive Behavioral System of Psychotherapy (CBASP) versus supportive psychotherapy (SP)? We investigated this question by analyzing data from a multi-center randomized clinical trial comparing the effectiveness of 48 weeks of CBASP to SP in n  =  237 patients with early-onset PDD who were not taking antidepressant medication. We statistically developed an optimal composite moderator as a weighted combination of 13 preselected baseline variables and used it for identifying and characterizing subgroups for which CABSP may be preferable to SP or vice versa. We identified two distinct subgroups: 58.65% of the patients had a better treatment outcome with CBASP, while the remaining 41.35% had a better outcome with SP. At baseline, patients responding more favorably to CBASP were more severely depressed and more likely affected by moderate-to-severe childhood trauma including early emotional, physical, or sexual abuse, as well as emotional or physical neglect. In contrast, patients responding more favorably to SP had a higher pre-treatment global and social functioning level, a higher life quality and more often a recurrent illness pattern without complete remission between the episodes. These findings emphasize the relevance of considering pre-treatment characteristics when selecting between disorder-specific CBASP and SP for treating PDD. The practical implementation of this approach would advance personalized medicine for PDD by supporting mental health practitioners in their selection of the most effective psychotherapy for an individual patient.