Clinical trials

This prospective, non-randomised, pre-post feasibility study evaluates CHANGE, a novel 8-session modularized cognitive behavioral group psychotherapy for young adults (18-25 years) with psychiatric disorders receiving inpatient or day-care treatment. All eligible participants (planned n=30) receive the intervention in addition to treatment-as-usual; there is no control arm. The primary aim is to assess feasibility, acceptability and appropriateness of the intervention (SMI (a German scale for feasibility), SAI (a German scale for acceptability), AIS (a German scale for appropriateness) scales; recruitment, retention, adherence and dropout rates). Secondary outcomes include perceived competence, self-efficacy (SWE), motivation (FEVER), satisfaction, quality of life (WHOQOL-BREF) and level of functioning (GAF), assessed before (T0) and after (T1) the intervention.

With disease-modifying therapies emerging for dementia and related conditions, identifying cognitive decline as early as possible is increasingly important. This prospective, single-center, repeated-measures study evaluates whether VR-based eye-tracking pupillometry can provide a practical, non-invasive biomarker of cognitive impairment and its progression over time. Pupil responses are linked to brain arousal systems relevant to cognitive dysfunction, including the locus coeruleus, which is affected early in Alzheimer's disease. Adults aged 18-80 years will be assigned to one of four cohorts (n=35 per cohort): i) Alzheimer's disease (supported by CSF biomarkers), ii) mild cognitive impairment (MCI) without Alzheimer's Disease, iii) depressive disorder with cognitive impairment, iv) healthy controls. Participants will undergo initial assessments at baseline and follow-up visits after 3 and 6 months. At each visit, pupil responses and behavioral metrics are recorded during a pupillary light reflex paradigm, a resting-state fixation block, a working-memory task (N-back), and a reward task. Pupillometric and behavioral metrics will be compared across cohorts and related to routine neuropsychological measures (MoCA, CERAD) and available clinical biomarkers (CSF markers; blood biomarkers). The primary objective is to determine whether task-evoked pupil response profiles sensitively quantify cognitive impairment, differ between cohorts, and track change over time. The long-term goal is to validate an easy-to-use, outpatient-compatible assessment to support objective characterization and monitoring of cognitive disorders.

This is a monocentric, randomized pilot study conducted at the Max Planck Institute of Psychiatry, Munich. The study investigates the effects of two different intermittent theta-burst stimulation (iTBS) schedules on biological and clinical outcomes in patients with depression and comorbid Post-COVID-19 condition (PCC). Participants will be randomized into two arms, both receiving a total of 30 active iTBS sessions applied to the left dorsolateral prefrontal cortex (DLPFC) at 90% resting motor threshold using a PowerMAG 100 ppTMS stimulator: * Standard Arm: One iTBS session per day, five days per week, over six weeks. * Intensified Arm: Six iTBS sessions per day, approximately one-hour apart, over five consecutive days. The primary outcomes are changes in immunological blood markers (C-reactive protein \[CRP\], tumor necrosis factor \[TNF\], interleukin-1β \[IL-1β\], interleukin-6 \[IL-6\]) and depressive symptomatology measured by Beck Depression Inventory-II (BDI-II) and Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes include fatigue (Fatigue Severity Scale \[FSS\], Fatigue Scale for Motor and Cognitive Functions \[FSMC\], Post-Exertional Malaise questionnaire \[PEM\]), sleep quality (Pittsburgh Sleep Quality Index \[PSQI\]), daytime sleepiness (Epworth Sleepiness Scale \[ESS\]), functioning (Sheehan Disability Scale \[SDS\]), anxiety (Beck Anxiety Inventory \[BAI\]) and an exploratory adverse effect screening. Follow-up assessments will be performed three days after treatment completion and again at three months post-intervention to evaluate both short- and medium-term effects. Biospecimen collection will include approximately 141 ml of peripheral blood per participant across three time points (baseline, post-treatment, +3 days). Samples will be analyzed for inflammatory markers and securely stored in the institutional biobank of the Max Planck Institute of Psychiatry in accordance with data protection and ethical guidelines. Safety and tolerability will be continuously monitored, including documentation of adverse events. The results of this pilot study are expected to provide preliminary evidence on whether accelerated iTBS protocols may exert differential effects on neuroinflammatory processes and depressive symptomatology in patients with Post-COVID-19 condition, thereby informing larger controlled clinical trials.

Invasive vagus nerve stimulation (VNS) is an approved treatment of treatment-resistant depression (TRD) in Europe and in USA. Because of the associated possible surgical complications as well as side effects, invasive VNS is applied limitedly in the treatment of depression. Transcutaneous auricular VNS (tVNS), on the other hand, is a non-invasive alternative to traditional invasive VNS. tVNS is still considered an experimental treatment for depression. This is due to the limited high-quality evidence from randomized clinical studies, the not yet fully understood biological mechanisms of action, along with overall limited knowledge about the optimal stimulation parameters. To address these issues, the AddVNS study was initiated. The AddVNS study intends to recruit n=86 patients of the Max Planck Institute of Psychiatry with depression. The patients participating in the AddVNS study are going to receive either tVNS or sham tVNS for a period of 6 weeks. The primary objective of the study is to identify biological, psychological, socio-economic, and clinical biomarkers associated with treatment progression and response to treatment in patients with depression undergoing tVNS. To achieve this, an exploratory design with an assessment of many different parameters including psychophysiology, imaging, blood-based multi-omics, microbiome, psychometrics and neuropsychology will be used.

DECIDE- Deep phenotyping for clinical inferring response in treatment resistant depression -Study Building upon the "Biobanking" initiative at the Max Planck Institute of Psychiatry, the present project aims to identify clinically relevant subtypes of treatment-resistant depression (TRD) through Clinical Deep Phenotyping (CDP). According to clinical trials, 30-40% of the patients suffering from TRD benefit from lithium treatment. By collecting multimodal biological and clinical-diagnostic markers, such as structural and functional brain imaging via magnetic resonance imaging (MRI), brain signals from electroencephalography, comprehensive blood tests, assessment of perception and cognition through neuropsychological testing, as well as the evaluation of specific depression symptoms and psychological and other comorbidities using standardized questionnaires, a bio-clinical signature will be identified using multivariate machine learning algorithms as an integration method. This signature aims to predict the response to lithium therapy in TRD. Prospectively, such an algorithm could later personalize the treatment decision of 'lithium administration in TRD'. This concept is in line with the Research Domain Criteria (RDoC) of the National Institute of Mental Health (NIH) and aims to offer lithium therapy as a personalized treatment strategy for TRD. Specifically, this means that the likelihood of treatment response can be estimated before administration based on the results of the present study, thus enabling lithium to be offered specifically to those patients who are likely to benefit from it. The study design is non-interventional, meaning the decision for lithium treatment is made for patients according to clinical routine in accordance with the recommendation of the German National Treatment Guideline (NVL) independent of study enrollment. Study participation does not influence treatment decisions for the patients.