Efficacy of prefrontal theta-burst stimulation in refractory depression: a randomized sham-controlled study

Abstract

Theta-burst transcranial magnetic stimulation could modulate cortical excitability and has the potential to treat refractory depression. However, there has been a lack of large randomized studies of the antidepressant efficacy of different forms of theta-burst stimulation, such as intermittent and continuous theta-burst stimulation. A randomized sham-controlled study was conducted to investigate antidepressant efficacy of theta-burst stimulation and to compare efficacy among left-prefrontal intermittent theta-burst stimulation, right-prefrontal continuous theta-burst stimulation and a combination of them in patients showing different levels of antidepressant refractoriness. A group of 60 treatment-refractory patients with recurrent major depressive disorder were recruited and randomized to four groups (Group A: continuous theta-burst stimulation; Group B: intermittent theta-burst stimulation; Group C: a combination of continuous and intermittent theta-burst stimulation; and Group D: sham theta-burst stimulation; 15 patients were included in each group). After 2 weeks of theta-burst stimulation treatment, depression improved in all groups. Groups B and C had better antidepressant responses (as reflected by % decreases in depression score) than Groups A and D (P = 0.001, post hoc analysis: B > A, B > D, C > A, and C > D), even after controlling for age and refractoriness scores. The mean antidepressant effect was highest in Group C and followed by that in Group B. Additionally, a significant placebo effect was found in patients with low refractoriness; this disappeared in patients with moderate-to-high refractoriness. A significant correlation existed between refractoriness scores and treatment responses. Treatment refractoriness was a significant factor negatively predicting efficacy of theta-burst stimulation (P = 0.039). This randomized sham-controlled study demonstrated that active theta-burst stimulation is a well-tolerated form of repetitive transcranial magnetic stimulation and has good antidepressant efficacy, particularly in depressed subjects within a certain range of treatment refractoriness.

Interindividual variability in response to continuous theta-burst stimulation in healthy adults

“…Application of cTBS to M1 and other brain areas has been used to measure abnormalities in cortical plasticity and to assess therapeutic responses to interventions aimed at restoring normal cortical plasticity in several neurological and psychiatric disorders, including Alzheimer’s disease (Freitas et al, 2011a), autism spectrum disorders and fragile X syndrome (Oberman et al, 2010, 2012, 2014, 2016), dementia (Cantone et al, 2014), epilepsy (Carrette et al, 2016), essential tremor (Chuang et al, 2014), hemispatial neglect (Cazzoli et al, 2012; Koch et al, 2012), major depression (Li et al, 2014), multiple sclerosis (Mori et al, 2013), obsessive-compulsive disorders (Wu et al, 2010; Suppa et al, 2014), Parkinson’s disease (Koch et al, 2009), schizophrenia (Poulet et al, 2009; Eberle et al, 2010; McClintock et al, 2011), stroke (Ackerley et al, 2010; Hsu et al, 2012; Di Lazzaro et al, 2013, 2016), tinnitus (Forogh et al, 2014), and Tourette syndrome (Suppa et al, 2014). …”

Theta-burst transcranial magnetic stimulation in depression: when less may be more

“…In this issue of Brain, Li et al (2014) provide the first direct evidence that intermittent TBS applied to the left dorsolateral prefrontal cortex or a combination of intermittent plus continuous TBS applied to the left and right dorsolateral prefrontal cortex, respectively, are significantly more effective than continuous TBS or sham TBS in treatment-resistant depression. Response rates after 10 treatment sessions were 40% for intermittent TBS and 66.7% for the combination of intermittent plus continuous TBSconsiderably higher than those reported in the high frequency repetitive TMS studies.…”

“…Treatmentresistant depression is associated with significantly greater medical costs and productivity loss than treatment-responsive forms, highlighting the need for more effective non-pharmacological strategies. In this issue of Brain, Li et al (2014). report data from a randomized sham-controlled study to show that a modified form of repetitive transcranial magnetic stimulation (TMS) produces therapeutic benefits in patients with treatment-resistant depression.…”

Emerging antidepressants to treat major depressive disorder

“…A 2014 study compared continuous TBS, intermittent TBS, a combination of continuous and intermittent TBS and sham TBS. Intermittent TBS combined with continuous TBS was most effective for treating depression (Li et al, 2014). Another study provided intermittent enhancing TBS to the left dorsolateral prefrontal cortex (dlPFC) and inhibiting constant TBS (cTBS) to the right dlPFC, or bilateral sham stimulation.…”