As of late, the World Health Organization has thrown the spotlight onto depression, which it has recently cited as the leading cause of ill health and disability worldwide. While many who experience depression are able to find relief through antidepressants, often in conjunction with therapy, the struggle for remission continues for those who suffer from treatment-resistant depression. Of the estimated 20% of adolescents that experience depression before reaching adulthood, about 30-40% do not show a response to first-line treatments (1). These patients, classified as “treatment-resistant,” are often faced with significant mortality rates due to suicide and considerable mental anguish that extends into adulthood. While there are several treatment options for treatment-resistant depression, their side effects and invasive nature often make them poor candidates for use on children. The development of new techniques such as rTMS, therefore, have become a priority for advancing the treatment of depression in adolescent patients.

“Treatment-resistant depression” (TRD) is a term used to describe cases of major depressive disorder (MDD) that cannot be resolved by at least two antidepressants. Currently, there are only a few treatments available to teens suffering from treatment-resistant depression (2). The first course of action is often a simple gradual increase of the dosage of antidepressant until the patient’s depressive symptoms disappear— once the dosage limit is reached, however, it is unsafe to increase it further, and practitioners must look to other options if the patient’s symptoms remain unresolved. Another possibility involves switching to a different class of antidepressants. Patients who do not respond to selective serotonin reuptake inhibitors (SSRIs) can be switched to monoamine oxidase inhibitors (MAOIs) or bupropion— however, as MAOIs have a tendency to interact lethally with other drugs and bupropion places patients at a high risk for epileptic seizures, this option may not be ideal for all patients. A third and highly aggressive treatment option for treatment-resistant depression is electroconvulsive therapy, which is often reserved for only the most severe cases of TRD. While about 60-77% of adolescents with TRD respond to electroconvulsive therapy, about half of participants experience a relapse of depression within a year. Furthermore, the treatment has major side effects, including cognitive impairment, seizures, and memory loss.

The statistics for treatment-resistant depression are certainly sobering, but a new and promising treatment on the rise may be able to turn the tables. Repetitive transcranial magnetic stimulation (rTMS), a noninvasive procedure involving the placement of an electromagnetic coil on the skull above the left dorsolateral prefrontal cortex (DLPFC), has already been approved by the Food and Drug Administration for the treatment of depression in adults who do not show a response to traditional antidepressant medications (3). During the procedure, the electromagnetic coil placed on the patient’s skill repeatedly generates magnetic currents that pass through the skull and create corresponding electrical currents in the neurons below. Depending on the rate at which the pulses are generated, rTMS has the ability to either increase or decrease the firing rates of neurons, thereby creating long-lasting changes in the pathways of brain areas that modulate depression and other mood disorders.  

Several recent studies on adolescent subjects have revealed the effectiveness of rTMS in treating treatment-resistant depression in adolescents. In a recently-published review by colleagues at Johns Hopkins Hospital (Magavi et al. 2017), it was shown that 63% of adolescents in nine out of ten examined studies responded to rTMS and experienced a decrease in the severity of their depression within 2-8 weeks of beginning treatment. In eight of the studies, patients were administered 20-30 rTMS treatments over the course of 1-8 weeks using a figure-eight-shaped electromagnetic coil. Several of the studies used the Children’s Depression Rating Scale- Revised (CDRS-R) as a measure of the severity of the patients’ depression. These studies found that pre-treatment scores indicating moderate to severe depression fell to scores in the mild depression range after treatment with rTMS. In three of the studies, improvements in depressive symptoms were accompanied by improvements in anxiety-related symptoms, while another study also showed additional improvements in mood disorder- and autism-related symptoms. In six of the studies, the benefits of the treatment lasted for a minimum of six months. In one study that performed a long-term follow-up of adolescent subjects after rTMS treatment (Mayer et al. 2012), treatment benefits were found to last for up to 3 years, indicating the potential longstanding benefits of rTMS treatment.

Like most treatments, rTMS is not without its risks. The most common adverse effect of rTMS treatment was reported by the vast majority of studies to be scalp pain or discomfort, which most patients were able to tolerate. This likely occurs due to accidental magnetic stimulation of facial nerves or pain receptors in the scalp by the rTMS coil. Three studies examined by Magavi et al. reported an onset of seizures after the first rTMS session— however, as these patients were also receiving antidepressants that increase one’s risk of seizures, it was not entirely clear if the seizures reported were caused solely by the rTMS treatment itself.

Despite a lack of large-scale studies, research suggests that rTMS may be an encouraging long-term solution to treatment-resistant depression in adolescents. Already approved as a treatment for adults, its noninvasive nature and minimal side effects makes it a good candidate for use in children, while its mitigation of mood disorder and anxiety-related symptoms, as recorded in several studies, may hint at its potential efficacy in the treatment of various other mental illnesses. Researchers have already begun to pursue future research directions, such as developing new electromagnetic coils that can target deeper brain regions and performing more studies aimed at testing rTMS efficacy in adolescents. While the projects are still in their early stages, rTMS remains a promising new approach for tackling adolescent treatment-resistant depression.

 

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Posted by Shravi Lam

Shravi is a freshman pursuing a major in Neuroscience and a minor in Bioethics. As a member of the clinical medicine team, Shravi aims to keep her readers updated with the latest advancements in translational research and clinical techniques. Outside of HMR, Shravi is actively involved in research exploring the molecular mechanisms of mood disorders, and serves as a volunteer and Clinical Experience Coordinator in the JHH Pediatric Emergency Department. She is especially interested in bridging the gap between scientists and clinicians, and hopes to bring together laboratory research and clinical medicine through her work with HMR.