Low Field Magnetic Stimulation is a new treatment for depression that uses low strength, high frequency electromagnetic fields to produce rapid improvements in mood in depressed subjects.
LFMS can produce a rapid improvement in mood in depressed subjects. Our recent report  described a mean reduction of 3 points on the Hamilton Depression Rating Scale (17 item, HDRS) in actively treated subjects (n=63) compared to sham-treated subjects. The subjects in this study were a combined group of depressed subjects with either Bipolar Disorder (BPD, n=41) or Major Depressive Disorder (MDD, n=22); the treatment in this study was delivered by the table-top sized LFMS device that was developed at McLean Hospital. This study was performed to replicate the original observation of antidepressant effects made in 2004 , as well as follow pre-clinical results with the Forced Swim Test that produced behavioral results comparable to those of fluoxetine . It was also performed to validate the newly designed LFMS Device. In both clinical studies the antidepressant effect occurred immediately upon treatment, and was characterized by a decrease in symptoms of depression and anxiety. The rapidly improved mood occurred in subjects with BPD as well as those with MDD; there were no reports of induced mania.
Because this clinical study was a replication of the original study it did not include a robust follow-up of extended effects, nor was it a study of multiple visits or duration of effect. It served to establish the clinical effect of the newly designed device and to determine the effect size of the antidepressant treatment for use in estimating power for later studies. It benefited from being a single-site, single-rater study, which may have resulted in less observational variance and a stronger result than might be possible in a larger study. A strength of the study is that the sham treatment in the LFMS device is particularly robust because there is no physical sensation associated with the treatment. Sham treatment is indistinguishable from active treatment to both the staff and the subject. Results, corrected for multiple comparisons, are shown above.
The LFMS Device and Treatment
The LFMS Device is a 14-inch diameter cylinder that produces a series of electric field pulses. It is powered by a small audio amplifier and controlled by a PC. It covers the top of the head (down to the eyebrows) and operates without producing any physical sensation.
The series of 1kHz electric field pulses are distributed throughout the cortex. The 14-inch cylinder contains a shaped magnetic coil driven with a time-varying waveform. The magnetic field waveform is a 500Hz alternating trapezoid; this magnetic field waveform induces a series of electric field pulses in the head of the subject. The electric field pulses alternate in sign, have duration of 0.25 milliseconds, and are delivered every millisecond for 20 minutes.
The electric fields induced by the LFMS Device are evenly distributed throughout the cortex. Unlike other electromagnetic treatments, there is no focal point or target in the head. While different brain regions may be more susceptible to LFMS, the exposure is uniform. While the field is uniform throughout the cortex, it has limited penetration and does not reach subcortical structures. A Finite Element Method calculation of the field has been performed that demonstrates this, and is shown in the figure to the left.
The electric field in LFMS does not directly activate neurons. At < 1 V/m it is 1/200 the strength of TMS, but is sufficient to modulate dendritic membrane voltages in cortical regions. Volkow et al  recently observed this modulation of local neuronal activity using FDG-PET and an MRI based stimulator, which together modified regional cerebral blood flow during stimulation.
Characteristics of LFMS
LFMS is distinguished from most other depression treatments by the rapid onset of its effects on mood. Rapid antidepressant effects have also been observed with DBS [15, 16] and ketamine , but these experimental treatments are not comparable, relying on implanted devices with high strength electric fields (> 100 V/m) or on pharmaceuticals with significant side effects. LFMS is also characterized by the global distribution of its electromagnetic fields; by the magnitude of those fields that modulate rather than override neuronal function; and by the frequency of its electric field pulses. These differences suggest that an unknown mechanism of action is responsible for the effects of LFMS. With the current need for rapid and effective antidepressant treatments, it is important to both understand this new mechanism and to increase its effect.
The LFMS Device was developed at McLean Hospital to deliver one component of an experimental Magnetic Resonance protocol that improved mood in depressed subjects with BPD . Prompted by these preliminary clinical findings in depressed BPD patients, a prototype system containing a small MRI-style coil was subsequently used to reproduce these electromagnetic pulses for preclinical studies. Antidepressant-like behavioral effects of LFMS were demonstrated in the forced swim test (FST) , an animal model sensitive to antidepressant treatments . We hypothesized that an LFMS device that produced this waveform would rapidly improve depressed mood in patients with either BPD or MDD. We designed and constructed this LFMS device, and calculated the estimated distribution and penetration of the LFMS-induced electromagnetic fields in the brain using the finite element method (FEM). We then conducted a randomized, double blind, sham controlled study of LFMS using this new device in a large group of stably medicated, but still symptomatically depressed, BPD and MDD patients and observed rapid (within 20 minutes) elevation of mood (Cohen’s effect size d=0.55 BPD, 0.69 MDD, 0.73 combined) .
Effects on Anxiety
LFMS has its effects along the dimensions of depression and anxiety, and this suggests that applications in anxiety-based disorders could be explored. A detailed examination of the responses to the HDRS in the recent study shows that the largest effects are in the “psychic anxiety” and “somatic anxiety” items, along with “depressed mood” and “work and interest”. A similar examination of the PANAS Scale results shows that the improvement is in many of the anxiety related items on the negative scale such as “ distressed”, “upset”, “scared”, “irritable” and “jittery” along with changes in many items on the positive scale such as “enthusiasm”, “pride”, and “inspiration”. Based on this pattern of results, we propose that LFMS may offer relief from symptoms of PTSD, including symptoms of depressed mood, anxiety, and irritability. It is possible that increases in positive items pertaining to self-direction and focus may indicate the potential to alleviate certain symptoms of hyper-arousal and other symptoms of salience associated with PTSD.
Because of this, the LFMS group is discussing pilot studies of the effects of LFMS in three of the leading anxiety based disorders: Post Traumatic Stress Disorder (PTSD), Obsessive Compulsive Disorder (OCD), and geriatric agitation. The symptoms of anxiety in these three disorders are often accompanied by symptoms of depression[19, 20] ; while LFMS might not address the fear-related arousal of PTSD, the compulsions of OCD, or the dementia associated with geriatric agitation it may provide relief from other comorbid symptoms.
The Need for New Treatments for Depression
Depression is the third largest cause of disability in the developed world . It has lifetime prevalence in the USA of 20% in the form of Major Depressive Disorder (MDD) [2, 3] and as a characteristic of Bipolar Disorder (BPD) it has a prevalence of 4-5%. BPD presents a particular challenge because those with BPD spend a greater part of their time in a state of depression . However, they are limited in their use of antidepressant medications because of a risk of kindling a manic episode . Typical antidepressant treatments require 4-6 weeks to produce an antidepressant response . Electroconvulsive Therapy (ECT), which is still considered one of the most effective treatments for depression, takes up to 4 weeks to be effective . While ECT has a high remission rate of over 65% it does have side effects that increase its personal cost . Overall, many patients fail to respond to their first antidepressant treatment; up to 40% fail to remit in clinical trials .
LFMS produces a rapid improvement in mood, within one hour. It could help to address the need for rapid and effective treatments for depression as a standalone treatment, or as a bridge during the initial period of a treatment course with pharmaceuticals.
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