This is a monocentric, randomized pilot study conducted at the Max Planck Institute ofPsychiatry, Munich. The study investigates the effects of two different intermittenttheta-burst stimulation (iTBS) schedules on biological and clinical outcomes in patientswith depression and comorbid Post-COVID-19 condition (PCC). Participants will berandomized into two arms, both receiving a total of 30 active iTBS sessions applied tothe left dorsolateral prefrontal cortex (DLPFC) at 90% resting motor threshold using aPowerMAG 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]) anddepressive symptomatology measured by Beck Depression Inventory-II (BDI-II) andMontgomery-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 QualityIndex [PSQI]), daytime sleepiness (Epworth Sleepiness Scale [ESS]), functioning (SheehanDisability Scale [SDS]), anxiety (Beck Anxiety Inventory [BAI]) and an exploratoryadverse effect screening. Follow-up assessments will be performed three days aftertreatment completion and again at three months post-intervention to evaluate both short-and medium-term effects. Biospecimen collection will include approximately 141 ml ofperipheral blood per participant across three time points (baseline, post-treatment, +3days). Samples will be analyzed for inflammatory markers and securely stored in theinstitutional biobank of the Max Planck Institute of Psychiatry in accordance with dataprotection and ethical guidelines. Safety and tolerability will be continuouslymonitored, including documentation of adverse events. The results of this pilot study areexpected to provide preliminary evidence on whether accelerated iTBS protocols may exertdifferential effects on neuroinflammatory processes and depressive symptomatology inpatients with Post-COVID-19 condition, thereby informing larger controlled clinicaltrials.
Not Provided
Device: Intermittent theta-burst stimulation (iTBS) using PowerMAG 100 ppTMS
iTBS at 90% resting motor threshold; bursts of 3 pulses at 50 Hz repeated at 5 Hz; ~3
minutes per session; applied to left dorsolateral prefrontal cortex; 30 total sessions;
schedule per arm as specified.
Inclusion Criteria:
- Age 18-65 years
- Capacity to consent (legally competent, written informed consent including data
protection)
- Diagnosis of depression (at least moderate severity, BDI-II ≥ 20), including major
depressive episode in bipolar disorder
- Comorbid diagnosis of Post-COVID-19 condition (WHO definition)
- Insufficient improvement of depressive symptoms under psychopharmacological
treatment
- Stable psychopharmacological medication for at least 4 weeks prior to start of iTBS
Exclusion Criteria:
- Age <18 years or >65 years
- Pregnancy, planned pregnancy, or breastfeeding
- Legal guardianship or cognitive impairment preventing valid informed consent
- Severe developmental disorder or intellectual disability
- Acute or chronic substance abuse (alcohol, prescription drugs, or illicit drugs)
- Current treatment with benzodiazepines or Z-substances
- Acute suicidality
- Psychotic symptoms
- Severe neurological disorder (e.g., major brain injury, neurodegenerative disease)
- Ongoing treatment with another neurostimulation method (ECT, TMS, VNS)
- Contraindications to TMS, including: Intracranial metal, implants, shunts, Cochlear
implant, pacemaker, implantable defibrillator, History of seizures or epileptiform
EEG
- Severe general medical illness (e.g., anemia requiring transfusion, severe
arrhythmias, cardiomyopathy)
Max-Planck-Institute of Psychiatry
Munich 2867714, Bavaria 2951839, Germany
Investigator: Reception Outpatient Clinic
Contact: 0049-089-30622-1402
Ambulanz@psych.mpg.de
Alexandros Balaskas, MD
0049-089-30622-1402
Ambulanz@psych.mpg.de
Angelika Erhardt-Lehmann, MD, Prof.
Angelika Erhardt-Lehmann, MD, Prof., Principal Investigator
Max-Planck-Institute of Psychiatry