Stepped Care AiTBS 2 Depression Study (Ghent)

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.

Conditions

• Depressive Disorder, Major
• Treatment Resistant Depression
• Melancholia

Interventions

DEVICE

aiTBS

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.

BEHAVIORAL

CCT

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.

DRUG

SSRI

All patients will be prescribed antidepressant medication (SSRI) again when starting the CCT (vs. control training).

Sponsors & Collaborators

• University Hospital, Ghent

  lead OTHER

Principal Investigators

• Chris Baeken, Prof. · Ghent University, University Hospital Ghent

• Ernst Koster, Prof. · University Ghent

• Rudi De Raedt, Prof. · University Ghent

• Gilles Pourtois, Prof. · University Ghent

• Marie-Anne Vanderhasselt, Prof. · Ghent University, University Hospital Ghent

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

FACTORIAL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2017-10-05

Primary Completion

2023-12-31

Completion

2023-12-31

Countries

• Belgium

Study Locations