Major depression is often difficult to diagnose accurately. Even when the diagnosis is properly made, standard treatment approaches (e.g., psychotherapy, medications, or their combination) are often inadequate to control acute symptoms or maintain initial benefit. Additional obstacles involve safety and tolerability problems, which frequently preclude an adequate course of treatment. This leaves an important gap in our ability to properly manage major depression in a substantial proportion of patients, leaving them vulnerable to ensuing complications (eg, employment-related disability, increased risk of suicide, comorbid medical disorders, and substance abuse). Thus, there is a need for more effective and better tolerated approaches. Transcranial magnetic stimulation is a neuromodulation technique increasingly used to partly fill this therapeutic void. In the context of treating depression, we critically review the development of transcranial magnetic stimulation, focusing on the results of controlled and pragmatic trials for depression, which consider its efficacy, safety, and tolerability.
Keywords: electroconvulsive therapy, treatment-resistant depression, major depression, transcranial magnetic stimulation
It’s been called “brain zapping” and “jumper cables for the mind.” Scientists prefer the more professional-sounding neologism electroceuticals. Whatever you call it, the interest in using electricity to treat certain types of mental disorders, including depression, is growing rapidly. That’s because numerous studies over the past several years show that it works.
The National Institute of Mental Health says conservatively that brain stimulation therapies “can play a role in treating certain mental disorders.” Brain stimulation therapies, the NIMH explains, involve activating or inhibiting the brain directly with electricity. The electricity can be given directly by electrodes implanted in the brain or non-invasively through electrodes placed on the scalp. The electricity can also be induced by using magnetic fields applied to the head. “While these types of therapies are less frequently used than medication and psychotherapies, they hold promise for treating certain mental disorders that do not respond to other treatments,” the NIMH concludes.
Repetitive transcranial magnetic stimulation (rTMS) is a form of brain stimulation therapy used to treat depression and anxiety. It has been in use since 1985. The therapy involves using a magnet to target and stimulate certain areas of the brain.
The U.S. Food and Drug Administration approved rTMS as a treatment for major depression when other treatments haven’t been effective. Sometimes doctors use rTMS in addition to traditional treatments.
In 2001, a research assistant at the Harvard Medical School-affiliated McLean Hospital noticed an intriguing pattern. One of her tasks was to escort study participants to and from a magnetic resonance imaging (MRI) machine where they received brain scans. All of the participants had bipolar disorder and were depressed; the scans involved an experimental form of MRI that measured the effect of medication changes on their brain chemistry.
The lifetime prevalence of major depressive disorder (MDD) is nearly 20%, and up to half of individuals diagnosed with the disorder do not respond to first-line treatment.1 A case of MDD is considered treatment-resistant once the patient has been taking an antidepressant for at least 6 weeks with no improvement in symptoms. Treatment-resistant depression (TRD) is associated with increased depressive symptoms and more severe educational, occupational, and social functioning, and patients with TRD “are at greater risk of hospitalization for their psychiatric illness, are more likely to abuse drugs and alcohol, and at increased risk of attempting suicide,” according to the National Alliance on Mental Illness (NAMI).
For a long time, it was thought that people with autism spectrum disorder lacked emotion, that even the higher-functioning among them navigated the world like logical robots oblivious to “real” feelings. More recently, research has shown their social issues are more likely to stem from difficulty expressing emotion or reading the emotions of others.
Though he wasn’t diagnosed with autism until he was 40, John Elder Robison felt isolated and disconnected throughout his entire youth and early adulthood. But in 2008, at 50, he took part in what became a three-year research project looking at brain function in individuals with autism spectrum disorders and exploring the use of transcranial magnetic stimulation (TMS) to help them.
Major depressive disorder (MDD) is a common debilitating condition where only one third of patients achieve remission after the first antidepressant treatment. Inadequate efficacy and adverse effects of current treatment strategies call for more effective and tolerable treatment options. Transcranial magnetic stimulation (TMS) is a noninvasive approach to manipulate brain activity and alter cortical excitability. There has been more than 15 years of research on the use of repetitive form of TMS (rTMS) for the treatment of patients with depression, which has shown it to be an effective antidepressant treatment. Even though rTMS treatment has shown efficacy in treating depression, there is a high degree of interindividual variability in response. A newer form of rTMS protocol, known as theta-burst stimulation (TBS), has been shown to produce similar if not greater effects on brain activity than standard rTMS. TBS protocols have a major advantage over standard rTMS approaches in their reduced administration duration. Conventional rTMS procedures last between 20 and 45 min, as compared to TBS paradigms that require 1 to 3 min of stimulation. Recently, a small number of studies have suggested that TBS has similar or better efficacy in treating depression compared to rTMS. Optimization, identification of response predictors, and clarification of neurobiological mechanisms of TBS is required if it is to be further developed as a less time intensive, safe, and effective treatment for MDD.
Although accelerated repetitive Transcranial Magnetic Stimulation (rTMS) paradigms and intermittent Theta-burst Stimulation (iTBS) may have the potency to result in superior clinical outcomes in Treatment Resistant Depression (TRD), accelerated iTBS treatment has not yet been studied. In this registered randomized double-blind sham-controlled crossover study, spread over four successive days, 50 TRD patients received 20 iTBS sessions applied to the left dorsolateral prefrontal cortex (DLPFC). The accelerated iTBS treatment procedure was found to be safe and resulted in immediate statistically significant decreases in depressive symptoms regardless of order/type of stimulation (real/sham). While only 28% of the patients showed a 50% reduction of their initial Hamilton Depression Rating Scale score at the end of the two-week procedure, this response rate increased to 38% when assessed two weeks after the end of the sham-controlled iTBS protocol, indicating delayed clinical effects. Importantly, 30% of the responders were considered in clinical remission. We found no demographic predictors for response. Our findings indicate that only four days of accelerated iTBS treatment applied to the left DLPFC in TRD may lead to meaningful clinical responses within two weeks post stimulation.
