Transcranial alternating current stimulation (tACS) as a treatment for fibromyalgia syndrome?

Abstract

We have read with great interest the recent report on a pilot clinical trial of transcranial alternating current stimulation (tACS) for the treatment of fibromyalgia syndrome (FMS) [1]. In this pilot study, 11 patients with FMS received 10 days of tACS combined and 10 days of transcranial random noise stimulation (tRNS), both combined with physical therapy, in a randomized, double-blind cross-over study. Fifteen patients completed one arm of the study. The authors individualized stimulation by comparing the topology of spectral amplitude in 5 canonical bands (delta, theta, alpha1, alpha2, and beta) from resting-state EEG with healthy controls; 11 of 15 participants received stimulation at 30 Hz, whereas the remaining 4 participants received stimulation at 4 Hz for the tACS condition. While the idea for this trial is certainly exciting, we are concerned about several pronounced shortcomings of the presented results that we feel have not received sufficient attention in the published manuscript. First, the reported clinical improvement is puzzling and does not seem to support a clinical efficacy of the employed protocol. We had to consult the supplementary materials to find the numbers reported for the preregistered symptom outcomes of the study, Visual Analog Scale for pain (VAS) and Short-Form 36-Item Health Survey (SF-36). It seems that there was no second baseline assessment after crossing over participants, which is highly concerning. Also, it seems that for the reported median values, the effect of tACS and tRNS on VAS were exactly the same (first row of table T6) and the impact on SF-36 was nearly identical (final row of table T2). Not reporting these null findings for the primary outcomes in the main paper is a highly questionable practice. Rather, the report seems to be based on the fact that nine responded to tACS and seven responded to tRNS, hardly an impressive difference that does not seem to have been tested with an appropriate statistical method. Detailed and precise reporting of findings is key for reproducible science and for advancing the field. Second, we are concerned about the lack of details and the choice of methods for non-invasive brain stimulation. It seems that the stimulation paradigm employed may not actually be tACS since it appears that the amplitude was modulated between 1 and 2 mA, which seems to suggest that there was a DC offset included in the stimulation, which is not justified and may severely impact the interpretation of the results. Overall, the methods as reported are unclear as to the stimulation waveform for tACS. We are also surprised by the choice of tRNS as a control condition since tRNS may have a similar effect to tACS by means of stochastic resonance [2] and an active-placebo control condition or a control frequency would have provided more convincing evidence for successful target engagement by tACS. Furthermore, at least one previous study has found that the application of tRNS was effective at reducing self-reported pain for patients with multiple sclerosis [3]. Third, no evidence is presented if the study blind was successfully maintained. The authors made an unusual choice of a spectrum from 0 to 100 Hz for tRNS when tRNS has been shown to be more effective when applied at higher-frequencies > 100 Hz [4]. Similar to tACS, the stimulation may * Flavio Frohlich [email protected]