Treatment-Resistant Depression

Depression is the second most common cause of disability-adjusted life years (DALYs) in the age category 15-44 years for both sexes combined. The Global Burden of Disease Study predicts that by 2020, depression will be a significant cause of DALYs in all age groups regardless of sex. By 2030, it will be the single biggest health burden, amounting to 15% out of all health conditions worldwide, outranking heart attacks and cancer.

What is even more alarming is that around 2-15% of all patients with major depression are resistant to treatment, which some experts may define as a lack of response to two adequate trials of anti-depressants. For these patients with treatment-resistant depression (TRD), other treatment options would include brain stimulation techniques like transcranial magnetic stimulation (TMS).

It has been hypothesized that depressed patients have decreased activity in an area of the brain called the left prefrontal cortex. Thus, most trials studying the efficacy of TMS in the treatment of depression would use protocols that would deliver high-frequency TMS to the left side of the brain to provide stimulation. In the past, researchers would use the standard localization method to locate the prefrontal cortex. This method first involves the location of the motor site of the brain. The coil is slowly moved over the scalp and TMS is applied until a twitching of a hand muscle is achieved. Once the motor site is located, the coil is then moved 5cm in a forward direction along the scalp surface. This is the assumed location of the prefrontal cortex.

With advanced technology, studies have also gotten more sophisticated with the use of magnetic resonance imaging (MRI) to ensure proper placement of the TMS coil over the prefrontal cortex. One such study was published in the Journal of Neuropsychopharmacology in 2009. Fitzgerald et al randomized 51 patients with TRD receiving TMS to two groups: standard localization and MRI-localized method. The study showed a significant decrease in depression scores among patients in the MRI group, showing that MRI localization has the capacity to enhance the benefits of rTMS

In another randomized trial involving 199 participants with moderate TRD, George et al had all participants undergo an MRI to locate the prefrontal cortex. They reported that participants were four times more likely to achieve remission of their symptoms when they received high-frequency rTMS for three weeks as compared to those who received sham stimulation.

While the results of trials are encouraging, it should be noted that rTMS may not be effective for all patients with depression. Predictors of a poor response include patients with psychotic symptoms like hallucinations, longer duration of depressive episodes and elderly patients

TMS has been found to be relatively safe with headache and scalp discomfort as the most common side effects. Thus, repetitive TMS (rTMS) was recently approved by the Food and Drug Administration for the treatment of patients with unipolar depression that is not improved after one round of anti-depressants. This represents an important step leading to a more widespread use of TMS in the management of TRD.
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References:

1. Dell’Osso et al. Meta-Review of Metanalytic Studies with Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Major Depression. Clinical Practice and Epidemiology in Mental Health, 2011; 7:167-177.
2. George et al. Daily Left Prefrontal Transcranial Magnetic Stimulation Therapy for Major Depressive Disorder. Archives of General Psychiatry, May 2010; 67(5): 507-516,
3. Fitzgeral et al. A Randomized Trial of rTMS Targeted with MRI Based Neuro-navigation in Treatment-Resistant Depression. Neuropsychopharmacology, 2009; 34:1255=1262.