Research reveals "Brain stimulation (e.g., rTMS)"  

as one of the treatment options in the future...

By Cheng-Ta Li, M.D., Ph.D.

Major depressive disorder (MDD) is very common (~10%), associated with stress levels, and can affect anyone of any age, income or social class. Despite the importance of MDD, many patients did not improve following current medication treatments and remained depressed for long. MDD, also called unipolar depressive disorder, is the third leading cause of disease burden now. Strikingly but not unexpectedly, by the year of 2030, MDD would become the leading cause of disease burden globally, based on the prediction data released by World Health Organization. One of the main reasons for such huge burden associated with MDD is the high prevalence of medication-resistant depression (MRD) The MRD has been studied widely and large epidemiological research showed that more than 30% of MDD patients failed to respond to repeated and sequential antidepressant trials in adequate dosage and duration. The longer length of untreated depression is associated with more brain deficits and lower possibility of responses to treatments. It has been estimated that individuals classified as MRD-likely used approximately twice as many medical services then individuals classified as depressed but MRD-unlikely.

We have been studying the issue of MRD for years. In 2010, we published a pioneer MRI paper which compared gray matter volumes between remitting and non-remitting MDD (1). The non-remitting patients had more gray matter deficits which also explained their cognitive problems. We also found the limbic-cortical dysregulation is involved in MRD (2) and impaired prefronto-thalamic connectivity plays a key role in the pathophysiology of it (3). Bilateral prefrontal hypoactivity as a characteristic feature of MRD has also been demonstrated in our previous study (4)

Since more prominent brain abnormalities associated with MRD, direct stimulation to brain regions critically involved in MRD could treat depression more effectively. There are some different ways that could stimulate our brain, including repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and deep brain stimulation (DBS)…etc. Among these tools, rTMS has most of the research and has been approved as a treatment option for drug-irresponsive depression in some countries like Canada and the United States. However, it is still a research tool and not indicated for depression treatment in Taiwan. The repetitive magnetic stimulation by rTMS induced a short electric current under the stimulation coil (as the attached figure below). Following the safety guideline, rTMS is relatively safe and could significantly improve a certain portion of refractory depression.

References:  

1.  Li CT, Lin CP, Chou KH, Chen IY, Hsieh JC, Wu CL, et al. Structural and cognitive deficits in remitting and non-remitting recurrent depression: a voxel-based morphometric study. NeuroImage 2010;50:347-56.

2.  Li CT, Wang SJ, Hirvonen J, Hsieh JC, Bai YM, Hong CJ, et al. Antidepressant mechanism of add-on repetitive transcranial magnetic stimulation in medication-resistant depression using cerebral glucose metabolism. Journal of affective disorders 2010;127:219-29.

3.  Li CT, Chen LF, Tu PC, Wang SJ, Chen MH, Su TP, et al. Impaired prefronto-thalamic functional connectivity as a key feature of treatment-resistant depression: a combined MEG, PET and rTMS study. PloS one 2013;8:e70089.

4. Li CT, Su TP, Wang SJ, Tu PC, Hsieh JC. Prefrontal glucose metabolism in medication-resistant major depression. Br J Psychiatry. 2015 Apr;206(4):316-23.

Figure: A demonstration of rTMS principle and application to a subject (TMS Machine is truncated)