Authors
Participants
Study
Treatment
Results
Antal et al. [17]
MO = 12
MA = 14
Randomized sham-controlled trial
Cathode over V1
No reduction was observed in attacks frequency in both groups (tDCS and sham) despite patients under real stimulation experienced a tendency to a reduction in the number of migraine-related days, attacks duration, and pain intensity
Dasilva et al. [18]
CM = 13
Randomized sham-controlled trial
Anode over M1
More significant reduction in pain intensity after 4 months with tDCS than sham
Auvichayapat et al. [19]
M = 37
Randomized sham-controlled trial
Anode over M1
Significant more reduction in attacks frequency, number of abortive medications, and pain intensity with tDCS than sham
Viganò et al. [5]
MO = 10
Open-label study
Anode over V1
Reduction in attacks frequency, migraine days, attack duration, and acute treatment intake after 2 months of tDCS
Rocha et al. [20]
M = 15
Randomized, double-blinded, parallel group-controlled, pilot trial
Cathode over V1
No reduction was observed in attacks frequency, pain intensity, and duration in patients under real tDCS as compared with patients under sham stimulation. A significant reduction of number of acute drugs intake was observed with tDCS, but with sham
Przeklasa-Muszyńska et al. [21]
MO = 12
MA = 18
Open-label study
Anode over M1
The consumption of analgesics and triptans, pain intensity, attacks duration, and the number of headache days decreased after tDCS
Andrade et al. [22]
M = 13
Pilot, double-blind, placebo-controlled, randomized trial
Anode over M1 or DLPFC
Group under DLPFC stimulation exhibited a better clinical performance compared with groups under M1 and sham stimulations. On intragroup comparison, groups DLPFC and M1 exhibited a greater reduction in headache impact and pain intensity and a higher quality of life after real treatment. No significant change was found in the group under sham stimulation
In fact, in two sham-controlled studies for migraine prevention, where repeated cathodal tDCS, aimed to reduce cortical excitability, was applied over the visual cortex, no differences were found in the clinical outcome between verum and sham. In the first one [17], a randomized sham-controlled trial, 26 migraine patients (12 without aura, 14 with aura) were enrolled. The verum was a cathodal constant current of 1 mA intensity applied for 15 min over Oz; the sham stimulation was obtained by the same protocol, but the stimulator was switched off after 30 s. Sessions were daily for 3 days/week. During the first 3 weeks, all the patients underwent sham stimulation, while during the following 3 weeks, 13 patients had verum and 13 still sham. Comparing the outcomes, no differences were found between groups about frequency, duration, and migraine-related days, but in the verum group, a slight reduction of pain intensity was observed. A similar protocol (1 daily session, 3 days/week) was used in the second randomized, double-blinded, parallel group-controlled, pilot trial [20]. In this study, ten migraineurs were treated for 4 weeks with 20-min sessions of cathodal tDCS over the visual cortex and compared with five patients assigned to sham stimulation; no difference was found between groups in frequency, duration, or intensity of attacks besides a slight reduction in painkiller use in the verum group. Only one investigation proposed anodal tDCS instead of cathodal, with the objective to increase the visual cortex preactivation level. In this open uncontrolled “proof-of-concept” study [5], ten migraineurs without aura underwent daily sessions (twice a week) for consecutive 8 weeks. Anodal tDCS was a 15-min stimulation (intensity: 1 mA) over the visual cortex. During the second month of treatment, there was a significant reduction in attack frequency (−38%), migraine days (−48%), attack duration (−60%), and acute drug intake (−28%) in comparison with the baseline. Unfortunately, in this study—uncontrolled and open—authors also included some migraineurs taking preventative medications; thus, these results need to be confirmed in a large randomized sham-controlled trial.
8.3.2 Other Cortical Areas
Starting from the observation that chronic migraine is associated to structural and functional abnormalities in the pain-related networks [23], in a randomized sham-controlled, double-blinded study, tDCS was applied with anode electrode placed over the motor cortex (contralateral to the most painful side) and the cathode placed over the contralateral supraorbital area. tDCS was delivered in ten 20-min sessions over 4 weeks; the verum group (ten patients) received current of 2 mA, whereas in the sham group (five patients), the same intensity was delivered only in the first 30 s. Although only a trend for reduction of headache intensity was found in the active group at the end of the study, a 4-month follow-up revealed a significant improvement in subjective pain perception and a trend for reduced attack duration [18]. An identical protocol was performed on 50 women suffering from episodic migraine (30 without aura and 20 with aura). In the verum group (30 patients), a significant reduction in headache duration, attack frequency, and pain intensity was observed at the end of the study [21].
In another sham-controlled study where tDCS was applied by anodal stimulation over the motor cortex, 37 episodic migraine patients were treated with anodal (N = 20) or sham (N = 17) stimulation (intensity: 1 mA) for 20 min over 20 consecutive days. In the verum group, attack frequency and abortive medications were significantly reduced at week 4 and 8 after treatment, and the pain intensity was significantly reduced at weeks 4, 8, and 12 [19]. In a very recent sham-controlled randomized investigation, a small group of 13 chronic medical refractory migraine patients received tDCS over the motor cortex (M1) or the left dorsolateral prefrontal cortex (DLPFC). They underwent 12 20-min sessions of anodal tDCS (intensity of 2 mA) for 1 month. After the treatment, both the M1 group (six patients) and the DLPFC group (four patients) had a significant reduction of pain intensity and headache impact with respect to the sham group (three patients), with a better outcome in the DLPFC-treated patients [22].
8.4 Conclusions
Transcranial direct current stimulation (tDCS) seems to disclose promising horizons in headache treatment. Although multiple repetitive sessions of stimulation are needed to obtain positive outcomes, the devices are not expensive and are portable so that patients, when appropriately trained, may be able to treat themselves also in a domestic setting. Controlled studies based on the rationale that in migraine the cerebral cortex is hyperexcitable, and thus using cathodal tDCS inhibition, found no significant therapeutic effect. By contrast, when activation of the visual cortical areas was obtained by anodal tDCS, a significant improvement was obtained in migraine attack frequency and duration [5]. Unfortunately, this protocol was not yet proposed in a sham-controlled randomized trial, which could confirm this beneficial effect.
Similarly, anodal tDCS applied over other cortical areas, mainly the primary motor cortex but also DLPFC, seems to be promising in episodic and chronic migraine prevention; some small placebo-controlled trials are available to sustain these findings, which should be replicated in larger groups of patients.
In summary, although at the present tDCS cannot yet be proposed as an established treatment for migraine prophylaxis, it offers many future opportunities to improve migraineurs’ quality of life, and most of them only need to be explored.

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