Expanding the electrotherapeutic toolkit: a perspective on transcranial pulsating electromagnetic fields (T-PEMF).

The multifocal application of transcranial lowvoltage pulsed electromagnetic fields (T-PEMF) has been shown to have an antidepressant effect in patients suffering from treatment-resistant depression (1). This proof-of-principle study had a sham-controlled, double blind study design in which sham (n = 25) or active (n = 25) T-PEMF treatment was self-administered by the patients on all weekdays for 5 weeks while pre-existing pharmacotherapy was continued. In this issue, Strassø et al. (2014) (2) report the results of a randomised, double blind, dose-remission study in which patients with treatment-resistant depression self-administered a 30-min session of T-PEMF twice a day for 8 weeks. T-PEMF was administered in augmentation to their pre-existing antidepressant pharmacotherapy. In all, 34 patients received an active T-PEMF session in the morning and a sham T-PEMF in the afternoon, whereas 31 patients received two active T-PEMF sessions in the morning and afternoon. A Hamilton Depression Scale (HAM-D17) score of 7 or less defined remission. In both groups, T-PEMF treatment induced a marked remission rate in more than 65% of the patients after 8 weeks of T-PEMF treatment. Contrary to the author’s expectations, there was no dose effect as remission rates were comparable for one versus two daily T-PEMF sessions. In contrast, the duration of T-PEMF treatment was found to have a strong impact on remission rates with a marked increase in remission rate by an extension of the treatment period from 5 weeks (remission rate <33%) to 8 weeks (remission rate >65%). The results imply that the remission rates following T-PEMF augmented depression therapy markedly improved as a function of treatment duration. Together, the published data suggest that T-PEMF may be a therapeutic option for therapy-resistant depression and call for larger replication studies across multiple centers. The possible neuropsychiatric application of T-PEMF has widened the therapeutic use of T-PEMF stimulation which is mainly used in orthopedics as an FDA approved technique to stimulate bone growth since 1979 (3,4,5,6). The study by Strassø et al. (2014) also points to complex dose–response relationships between the T-PEMF protocol and its anti-depressive action. This calls for future studies that unravel the neurobiological mechanisms mediating the anti-depressive effect of T-PEMF. Such studies will provide a framework according to which T-PEMF can be optimised and may identify early markers that indicate whether a patient will benefit from a prolonged T-PEMF treatment. Electromagnetic fields and electric currents have been used as a potential cure for a wide range conditions since the time of Paracelsus (7) and the past years have evidenced a growing number of noninvasive brain stimulation (NIBS)-based neuropsychiatric therapies (8,9). T-PEMF adds to the range of currently available interventional NIBS techniques such as repetitive transcranial magnetic stimulation (rTMS) (10), transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS) (11), transcranial random noise stimulation (tRNS) (12), or static magnetic field stimulation (13). Future research should make an effort to compare the clinical and neurobiological effects of T-PEMF to other interventional approaches that apply constant or time-varying electric currents or electromagnetic fields through the intact skull to treat depression or other brain disorders. All these NIBS techniques are able to alter neural excitability and efficacy, but they greatly vary in three factors ultimately determining the specific effect of stimulation: the spatial distribution, the strength and the temporal variation of the electric field produced in the brain (14). To better understand the physiological mechanisms targeted by T-PEMF compared with other NIBS techniques it is important to realise how these factors differ in T-PEMF: In contrast to all other NIBS approaches which aim at modulating a specific cortical target area, T-PEMF causes diffuse, multifocal brain stimulation of several brain regions. The T-PEMF