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

This scientific commentary refers to 'Efficacy of prefrontal theta-burst stimulation in refractory depression: a randomized sham-controlled study', by Li et al., (doi:10.1093/brain/awu109). Major depressive disorder is associated with increased mortality, significant morbidity, and substantial impairments in functioning. It is estimated that by the year 2020, depression will be second only to heart disease in terms of disease burden as measured by disability-adjusted life years (Murray and Lopez, 1996). Treatment-resistant depression is conventionally defined as a failure to respond to at least two adequate medication trials or as a relapse during treatment; it represents a common dimension of this illness that translates into significant public healthcare costs. Only one-third of patients with major depressive disorder achieve full remission of their symptoms after a single trial of antidepres-sant medication and even with multiple medication trials, 30–40% of patients fail to respond fully (Keller et al., 1992). Treatment-resistant 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. High frequency (e.g. 10 Hz) repetitive TMS applied to the left dorsolateral prefrontal cortex is an FDA approved treatment for adults with resistant depression. A number of large multicentre studies and recent meta-analyses have indicated that high frequency repetitive TMS has reasonable therapeutic efficacy compared to sham stimulation. For example, O'Reardon et al. (2007) reported response rates of 24.5% with high frequency repetitive TMS compared to 13.7% with sham repetitive TMS following 6 weeks of treatment. In a recent meta-analysis, Berlim et al. (2014) reported response rates of 29.3% with high frequency repetitive TMS compared to 10.4% with sham repetitive TMS. Collectively, these results indicate that high frequency repetitive TMS can be effective in treatment-resistant depression, but there is clearly scope for improvement. Modification of repetitive TMS parameters such as stimulus frequency and duration may be one means of enhancing repetitive TMS efficacy. Conventional high frequency repetitive TMS paradigms , such as those used in the abovementioned trial (O'Reardon et al., 2007), deliver 3000 pulses of 10 Hz stimulation over the course of 37.5 min. An alternative approach is theta-burst stimulation (TBS), in which a three-pulse 50-Hz burst is applied at 5 Hz. In intermittent TBS, a …