Which is the best transcranial direct current stimulation protocol for migraine prevention? A systematic review and critical appraisal of randomized controlled trials

Abstract

Background: Transcranial direct current stimulation (tDCS) could counteract the pathophysiological triggers of migraine attacks by modulating cortical excitability. Several pilot randomized controlled trials (RCTs) assessed the efficacy of tDCS for migraine prevention. We reviewed and summarized the state of the art of tDCS protocols for migraine prevention, discussing study results according to the stimulations parameters and patients' populations.

Main body: We combined the keywords 'migraine', 'headache', 'transcranial direct current stimulation', and 'tDCS' and searched Pubmed, Scopus, and Web of Science, from the beginning of indexing to June 22, 2021. We only included RCTs comparing the efficacy of active tDCS with sham tDCS to decrease migraine frequency, intensity, and/or acute drug utilization. The risk of bias of each RCT was assessed by using the RoB-2 tool (Cochrane Collaboration). Thirteen RCTs (from 2011 to 2021) were included in the review. The included patients ranged from 13 to 135. RCTs included patients with any migraine (n=3), chronic migraine (n=6), episodic migraine (n=3) or menstrual migraine (n=1). Six RCTs used cathodal and five anodal tDCS, while two RCTs compared the efficacy of both cathodal and anodal tDCS with that of sham. In most of the cathodal stimulation trials, the target areas were the occipital regions, with reference on central or supraorbital areas. In anodal RCTs, the anode was usually placed above the motor cortical areas and the cathode on supraorbital areas. All RCTs adopted repeated sessions (from 5 to 28) at variable intervals, while the follow-up length spanned from 1 day up to 12 months. Efficacy results were variable but overall positive. According to the RoB-2 tool, only four of the 13 RCTs had a low risk of bias, while the others presented some concerns.

Conclusions: Both anodal and cathodal tDCS are promising for migraine prevention. However, there is a need for larger and rigorous RCTs and standardized procedures. Additionally, the potential benefits and targeted neurostimulation protocols should be assessed for specific subgroups of patients.

Keywords: Transcranial direct current stimulation; migraine; migraine prevention; non-pharmacological treatment.

Fig. 1

PRISMA 2020 flowchart of study selection

Fig. 2

Overview of transcranial direct current stimulation schedules in the included randomized controlled trials. Each dot represents a single session. *cross-over trial; each group of dots represents a different intervention

Fig. 3

Overview of transcranial direct current stimulation montages in the included randomized controlled trials. Blue squares/rectangles indicate cathodes, while red squares/rectangles indicate anodes. Electrodes’ shape and dimension reflect the differences in RCTs stimulation setups. Solid lines connect the electrodes pairs that have been tested in different stimulation conditions in each RCT. The positions of anodes and cathodes are identified according to the international 10/20 electroencephalographic system. *This study assessed both cathodal and anodal stimulation. **10/10 electroencephalographic system

Fig. 4

Adherence of available randomized controlled trials on transcranial direct current stimulation to the guideline recommendations for clinical trials of neuromodulation devices for the treatment of migraine in adults [14]. A green circle indicates that the criterion was met; a red circle, that it was not met; an amber circle, that it was not specified

Fig. 5

Results of the available randomized controlled trials comparing transcranial direct current stimulation to sham procedure. The list is taken from the guidelines of clinical trials of neuromodulation devices for the treatment of migraine in adults [14]. More detailed quantitative reports are provided in Supplemental file 1. Green circles indicate that tDCS was entirely superior to sham, amber circles that tDCS was partially superior to sham, red circles that tDCS was note superior to sham; cells were left empty if outcomes were not reported

Fig. 6

Proportion of patients with tingling, itching, headache, and pain during tDCS in the included randomized controlled trials. No difference between active and sham groups was significant

Fig. 7

Unmet needs in transcranial direct current stimulation trials for migraine prevention