Stepped Care aiTBS 2 Depression Study (Ghent)
Condition: Depressive Disorder, Major; Treatment Resistant Depression; Melancholia
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant; Depressive Disorder, Major
Study type: Interventional

Summary: 
      Antidepressant-free unipolar melancholic depressed patients (at least stage 2
      treatment-resistant) will be selected by a certified psychiatrist, who will administer
      (semi-)structured clinical interviews. Because concomitant antidepressant treatment can
      confound outcome results, all patients will go through a medication washout before entering
      the study and they will be free from any antidepressant, neuroleptic and mood stabilizer for
      at least two weeks before entering the treatment protocol. Only habitual benzodiazepine
      agents will be allowed.

      STEP 1: Patients will be treated with in total 20 accelerated intermittent Theta Burst
      Stimulation (aiTBS) sessions (3000 pulses/session) over the left dorsolateral prefrontal
      cortex, which will be spread over 4 days. On each stimulation day, a given patient will
      receive 5 sessions with a between-session delay of 15 minutes. Patients will be randomized to
      receive either the real aiTBS or sham treatment (first week). However, the sham group will
      receive real aiTBS treatment with 10 days' time interval. The investigators expect that real
      aiTBS treatment and not sham will result in a significant and clinical meaningful response.

      STEP 2: To optimize treatment and reduce relapse following the iTBS treatment, in a stepped
      care approach, all patients then continue with cognitive control training (CCT) ten days
      later. This CCT consists of 20 sessions, spread over 4 weeks. Patients will be randomized to
      receive either real CCT or a control training. During this follow-up treatment, all patients
      will be prescribed antidepressant medication (SSRI) again. As iTBS treatment effects are
      known to decline over time, the investigators expect that combining aiTBS with a follow-up
      CCT therapy will stabilize the clinical effects over time compared to receiving the iTBS
      treatment alone.

      For baseline comparisons, patients will be closely matched for gender and age with
      never-depressed, medication-free healthy volunteers. No volunteer will undergo treatment.
    


Intervention name(s): aiTBS; CCT; SSRI
Intervention type(s): Device; Behavioral; Drug
Intervention description(s): In the active aiTBS arm, the patients will receive 100 cycli of thetaburst trains of 2s, separated by an inter-train-interval of 6 seconds, delivered on the left dorsolateral prefrontal cortex (DLPFC; i.e. 3000 pulses per session). On each stimulation day, a given patient will receive 5 sessions with a between-session interval of 15 minutes. The treatment protocol of in total 20 aiTBS sessions will be spread over 4 days (i.e. 60.000 pulses in total). The sham coil has been specifically developed to mimic the real one.; By training working memory processing, the CCT aims at modulating similar prefrontal cortex regions as being stimulated previously by aiTBS, namely the DLPFC. thereby possibly stabilizing clinical effects of aiTBS over time. In total 20 sessions of CCT vs. control training (of approximately 25 minutes per session), will be spread over a period of 4 weeks.; All patients will be prescribed antidepressant medication (SSRI) again when starting the CCT (vs. control training).
Other intervention name(s): accelerated intermittent thetaburst stimulation; cognitive control training; selective serotonin reuptake inhibitor
Intervention MeSH terms: Serotonin; Selective Serotonin Reuptake Inhibitors
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Major depressive disorder; Treatment resistant depression; Accelerated intermittent thetaburst stimulation; Cognitive control training; Neuroimaging