TMS Relieves Symptoms in Teens With Resistant Depression

Daniel M. Keller, PhD

March 10, 2014

MUNICH — Repetitive transcranial magnetic stimulation (rTMS) may help relieve symptoms in teens with treatment-resistant depression, new research suggests. Researchers also found that among responders, rTMS also raised levels of the neurotransmitter glutamate in the dorsolateral left prefrontal cortex (DLPFC).

rTMS is a noninvasive intervention that uses a pulsating magnetic field applied to the scalp to induce electric currents in brain cortical neurons and thus modulate cortical excitability. Few studies have been performed on the effects of rTMS in children.

While at the University of Calgary in Alberta, Canada, Sarah Pradhan, a medical student at the Royal College of Surgeons in Dublin, Ireland, conducted a study on the effects of rTMS in the treatment of major depressive disorder in children.

Speaking here at the 22nd European Congress of Psychiatry (EPA), she said her study involved 11 patients aged 15 to 21 years (4 females, 7 males) who were resistant to previous therapies, such as selective serotonin reuptake inhibitors (SSRIs).

Study patients received rTMS at the same time each weekday for 3 weeks. They were assessed clinically at baseline and weekly during treatment, using Hamilton Depression Rating Scale (HAM-D) scores to assess depressive symptoms. Magnetic resonance spectroscopy was used to measure neurochemicals, and magnetic resonance imaging was performed.

Seven patients responded to the rTMS treatments.

There was a 62% decrease in HAM-D scores, from 25.43 to 9.57, and another 30% decrease in Children's Depression Rating Scale scores, from 74.43 to 52.14 [P = .002]," Pradhan reported. The investigators also found a 78% decrease in Hamilton Anxiety Rating Scale scores, from 23.86 ± 9.65 to 5.29 ± 3.55 (P = .001).

Table. Effect of rTMS on Depression Scores and Left DLPFC Glutamate Levels

  Responders (n = 7) Nonresponders (n = 4)
  Pretreatment Posttreatment % Change (P-value) Pretreatment Posttreatment % Change (P-value)
HAM-D* 25.43 ± 7.85 9.57 ± 1.51 62% ↓ (.001) 26 16 38% ↓ (-)
HAM-A* 23.86 ± 9.65 5.29 ± 3.55 78% ↓ (.001) 22 15 32% ↓ (-)
DLPFC glutamate level 8.73 ± 1.21 9.77 ± 1.18 12% ↑ (.038) 11.87 ± 0.47 10.75 ± 0.13 9% ↓ (.013)

*HAM-D: Hamilton Depression Rating Scale score; HAM-A: Hamilton Anxiety Rating Scale score; estimated from graph in presentation; mmol/kg wet weight.

Few Adverse Events

Treatment responders "had a greater than 50% decrease in Hamilton depression scores, and they had a lower pretreatment glutamate concentration," which rose in the left DLPFC with treatment, Pradhan said. "They also had clinical alleviation of depressive symptoms and anxiety symptoms."

Nonresponders had a higher baseline glutamate concentration, which decreased after treatment.

"They had comorbid social phobia," which has been linked to higher baseline glutamate levels [and] "which we think may be predictive of poor treatment response," said Pradhan.

Adverse effects were minimal. Some patients complained of scalp discomfort during the treatments. Some also had mild posttreatment headaches.

Pradhan concluded that rTMS shows promise as a safe and effective therapy for adolescent major depressive disorder. But the study was small and the technology still very experimental, so further work is needed to validate it for this indication.

But with 350 million people worldwide suffering from major depression and many resistant to current therapies, "it is important to have some other type of intervention for these people so they don't give up and so there are always alternate therapies available," she said.

Logical Connection

Session chair Anastasiya Nestsiarovich, MD, of the Republican Research and Practice Center of Mental Health in Minsk, Belarus, who was not involved in the study, called the work "high quality" with "big biological theoretical significance."

"Of course, it's doing something biologic related to glutamate metabolic [pathways]," Dr. Nestsiarovich said. "We all know that this system of glutamate is extremely important in the developing of depression, so this is logical that it is connected."

The benefits and risks for any treatment have to be weighed. In the case of rTMS in this study, the adverse effects were fairly benign.

"Any instrument, I think, has its own adverse effects, but still, it's very good that we have a choice.... We can use medications, which also have a lot of adverse effects.... Perhaps the use [of rTMS] is much more than the damage," she said.

Sarah Pradhan and Dr. Nestsiarovich report no relevant financial relationships. There was no commercial funding for the study.

22nd European Congress of Psychiatry (EPA). Session FC02. Presented March 2, 2014.

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