Intermittent Theta-burst Stimulation for Major Depression: an Intensity-response Study
Recruiting · NCT06392867 · Interventional (participants receive a specific treatment) · Lead sponsor: The Hong Kong Polytechnic University
View the official record on ClinicalTrials.gov →Interventions studied
What this trial is about
The United States Food and Drug Administration (FDA) approved intermittent theta-burst stimulation (iTBS) in 2018 as a form of repetitive transcranial magnetic stimulation (rTMS). Hospitals worldwide use it to treat major depressive disorder (MDD). It is safe, effective, even for depressed patients unable to respond to standard pharmacological treatment and is more efficient than standard rTMS. In accordance with the approved treatment protocol, patients experience considerable sensory discomfort at a stimulation intensity of 120% of their resting motor threshold (rMT). Antidepressant effects of iTBS are believed to be mediated by modulating prefrontal excitability. There is still a lack of evidence to support the choice of 120% rMT as the optimal stimulation intensity, and the presumed superiority of higher stimulation intensities over lower intensities has yet to be proven. This knowledge gap has clinical implications since more tolerated treatments may lead to greater adherence, resulting in improved outcomes. The current study proposes a randomized, triple-arm, controlled trial to compare the efficacy of iTBS at 75% (iTBS75) and 120% (iTBS120) rMT with sham iTBS (SiTBS). Based on the following considerations, SiTBS was selected to be compared with iTBS75 and iTBS120: SiTBS will reveal placebo antidepressant effects and serve as a control. iTBS75 is selected because iTBS at 80% aMT exhibits significant excitatory effects on the motor cortex and corresponds to approximately 70% rMT. There is however, a distance of about 12.7mm between the coil and the motor cortex, whereas 14.4mm separates the coil from the dorsolateral prefrontal cortex (DLPFC). Accordingly, a resting motor threshold of 70% at the motor cortex corresponds to a distance-adjusted rMT of 75% at the DLPFC. Lastly, iTBS120 is chosen as the standard stimulation intensity in current iTBS depression trials. It is our intention to investigate the potential antidepressant effects of iTBS treatment at a much lower stimulation intensity than the one currently employed by most centers in the United States and approved in these centers. Thus, our study can contribute to establishing a treatment regimen with increased adherence and lower withdrawal rates.
Who can take part
Inclusion criteria
- are aged between 18 and 70;
- have a MDD diagnosis, single or recurrent episode, diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, fifth edition criteria and confirmed by means of the Mini-International Neuropsychiatric Interview (MINI);
- have a score of at least 18 on the 17-item Hamilton Rating Scale for Depression (HDRS17) in their current episode;
- have failed to have a clinically significant response to two or more standard antidepressant treatments during their current episode;
- have received stable psychopharmacological treatment within 4 weeks prior to screening; and
- have normal thyroid function, Complete Blood Count, electrolytes, and liver enzyme levels based on pre-study blood work.
Exclusion criteria
- have a history of substance abuse or dependence in the past 3 months;
- have a concomitant major unstable medical illness, cardiac pacemaker or implanted medication pump;
- show active suicidal intent (MADRS item 10 score \>4);
- are pregnant;
- have a lifetime MINI diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms;
- have a metal implant or any other common MRI and TMS exclusion criteria;
- take antiepileptic drugs or benzodiazepines corresponding to a dose of \>1 mg lorazepam per day;
- have had initiation or dose change of any psychotropic medication in the 4 weeks prior to screening or
- have undergone TMS in the past.
Where it is running
1 location listed.
- The Hong Kong Polytechnic University - Hong Kong, Hong Kong