Efficacy of prefrontal-occipital transcranial direct current stimulation for refractory chronic migraine

Abstract

Introduction

Patients with chronic migraine (CM) frequently demonstrate resistance to conventional medical therapies, likely attributable to the multifactorial pathophysiology underlying their pain. Transcranial direct current stimulation (tDCS) has recently emerged as a promising non-invasive neuromodulation technique for migraine prophylaxis. In this study, we evaluate the efficacy of a tDCS protocol in treating CM patients, both with and without medication-overuse headache (MOH).

Method

Thirty patients diagnosed with chronic migraine (CM) underwent treatment with tDCS (2 mA, 20 min/session) targeting the anodal right dorsolateral prefrontal cortex (DLPFC) and cathodal occipital region for three days each week over two weeks, followed by once-weekly sessions for an additional six weeks.

Results

The tDCS demonstrated significant efficacy in pain reduction for CM patients, regardless of MOH comorbidity. After eight weeks, tDCS had significantly reduced severe migraine days (VAS score > 7), awakening migraine episodes, and mean headache intensity and duration. The maximum effects were observed for headache duration and the number of severe headache days. A reduction of more than 50% in the mean headache duration was achieved in 80% of participants. Similarly, 70% of patients demonstrated >50% decrease in severe headache days (VAS >7). Treatment was well-tolerated, with no serious adverse effects reported during the study period.

Conclusion

TDCS appears to be an effective, well-tolerated, non-invasive treatment for CM patients, including cases with MOH. The significant reductions in headache duration, intensity, and frequency suggest that tDCS may be a valuable option for those resistant to standard medical therapies.

Trial registration

Iranian Registry of Clinical Trials IRCT20140624018213N2. Registered 17 June 2026. Retrospectively registered.

Introduction

Chronic migraine (CM) is defined as the occurrence of headaches on 15 or more days per month for more than three months, with at least 8 days a month showing typical migraine features [1, 2]. Patients with CM make up the largest proportion of those referred to specialized headache clinics [3]. CM affects 1% to 2% of the global population and is associated with a higher burden of the disease than episodic migraine (EM), which is characterized by headache recurring less than 15 days/month. The transformation from EM to CM occurs in 2.5% of the patients per year. Most CM cases experience nearly constant migraine symptoms with disabling headaches that are highly disruptive to daily life and work and are associated with medication overuse and high medical costs [4, 5].

Patients with chronic migraine (CM) often exhibit resistance to pharmacological treatments, suboptimal medication adherence, and heightened sensitivity to adverse effects, which together complicate management [1]. These challenges likely reflect the interplay of multiple contributing factors, including electrophysiological changes, psychiatric comorbidities, and the frequent occurrence of medication overuse headache (MOH) [6]. Accumulating evidence suggests that non‑pharmacological therapies for chronic migraine may address key mechanisms involved in pain processing while reducing the burden of treatment‑related adverse effects [7].

Invasive and non-invasive neurostimulation procedures have been introduced for both preventive and acute migraine treatment. However, the heterogeneity of their efficacy is high, and further research is needed to properly assess their clinical benefits [8]. The FDA has approved four noninvasive neuromodulation devices for acute migraine treatment: external trigeminal nerve stimulation, single-pulse transcranial magnetic stimulation, noninvasive vagus nerve stimulation, and remote electrical neuromodulation [9, 10]. Transcranial direct current stimulation (tDCS) has recently emerged as a promising non-invasive neuromodulation approach for migraine prevention. The tDCS device is technically simple, can be manufactured locally, and can cost significantly less than other advanced neuromodulation or biological treatments for migraine. This safe technique delivers constant, low direct electrical current via scalp electrodes, modulating cortical excitability without reported severe side effects. The applied current alters neuronal activity at targeted sites through anode/cathode polarization, potentially correcting migraine-related electrophysiological abnormalities [6, 11, 12].

Anodal tDCS enhances cortical excitability in underlying regions, while cathodal tDCS suppresses it [13, 14]. Both modalities have been investigated clinically, with cathodal stimulation specifically modulating occipital cortex activity by reducing hyper-responsivity of the visual cortex (VC) [15, 16]. Anodal tDCS primarily targets the motor (M1) or dorsolateral prefrontal (DLPFC) regions, exerting inhibitory effects on thalamocortical pain pathways. The DLPFC and medial prefrontal cortex (mPFC) are critically involved in pain perception, mediating cognitive functions including pain anticipation, appraisal, and modulation [13]. However, current evidence demonstrates variability in optimal stimulation targets, with no consensus yet established in the literature [17, 18].

Psychological comorbidities, particularly depression and anxiety, significantly impact CM by increasing MOH risk and reducing treatment response [19, 20]. As tDCS effectively modulates mood-related brain regions, its stimulation of these areas may concurrently alleviate both migraine symptoms and associated psychological disorders through common neural pathways.

Despite the promising findings regarding the use of tDCS in migraine management, there remains a significant gap in the literature concerning its long-term effects and optimal stimulation parameters. Accordingly, the present single‑arm open‑label observational study was designed to evaluate short‑ to mid‑term clinical outcomes of a fixed dual‑site tDCS protocol in patients with chronic migraine, with a specific focus on differences between patients with and without MOH.

Method

This cross-sectional study was conducted at the Headache Research Center of Sina Hospital, a tertiary referral center affiliated with Tehran University of Medical Sciences, between January and June 2023. We enrolled adult participants (aged 18–65 years) meeting the International Classification of Headache Disorders, 3rd edition (ICHD-3) diagnostic criteria for CM, including both patients with and without MOH [2]. Patients were eligible if they had documented failure of ≥ 3 preventive migraine treatments at therapeutic dosages for ≥ 3 months each within the preceding 6-month period, despite adequate adherence. An expert neurologist verified the eligibility criteria during the recruitment.

Per the International Headache Society guidelines for neuromodulation trials for migraine, patients who had a nerve block (past 3 months) or were treated with botulinum toxin A(past 6 months) were excluded [21]. Patients with substance use disorders or other primary/secondary headache diagnoses were also excluded. No enrolled participants presented with any tDCS contraindications, including: chronic dermatological conditions affecting electrode placement sites, cranial metallic implants or neurostimulation devices, epilepsy diagnosis, or significant head trauma within the preceding 12 months. None of the patients had previously experienced tDCS. Before study initiation, all participants provided written informed consent and committed to maintaining comprehensive headache diaries throughout the treatment period. Additionally, each patient had prospectively documented at least one month of pre-treatment headache data through daily diary recordings, establishing reliable baseline measurements.

Ethical approval was obtained from Tehran University of Medical Sciences in Tehran, Iran, with certificate No. IR.TUMS.NI.REC.1402.008. According to national regulations at the time of initiation, this study did not require registration in a clinical trials registry. The aims, methods of intervention, and the period of the study were described to the patients, and written informed consent was obtained from all participants.

Participants received stimulation while seated in a rested, relaxed position. We administered tDCS using a pair of carbon-rubber electrodes (4 × 4 cm) housed in saline-soaked (3% NaCl) sponges. Using the 10–20 EEG system, we positioned the anode at F4 (right DLPFC) and the cathode at Oz (occipital cortex). This fixed montage was applied uniformly across participants without adjustment for pain laterality, maintaining consistent stimulation parameters throughout the study cohort.

TDCS was administered three days a week for two weeks and once a week for an additional six weeks. During each session, a current of 2 mA was delivered for 20 min, with a fade-in and fade-out period of 30 s.

We evaluated the effectiveness of the stimulation protocol by analyzing various factors, including the average number of migraine days (with a visual analogue scale (VAS) score greater than 2), the number of severe migraine days (VAS score greater than 7), the frequency of awakening migraine days per week, the average headache intensity, and the average duration of headaches (measured in hours per attack) each week [22]. Awakening migraine days were included as an outcome measure because such attacks are commonly associated with greater migraine severity, disability and sleep disturbance [23]. Outcomes were assessed by comparing baseline measures with 8-week post-intervention data, evaluating treatment effects relative to pretreatment status.

The patients were asked to complete the Depression-Anxiety-Stress Scale (DASS-21) questionnaire at the baseline pre-intervention visit. DASS21 is a 21-item questionnaire used to measure and screen psychiatric comorbidities and abnormal emotional states. This is not a clinical diagnostic measure and is primarily used in research and non-clinical samples to determine those who may be susceptible to the development of psychopathologies (DASS-21).

The DASS consists of three domains, each containing seven questions. Each question is scored on a Likert scale ranging from 0 to 3, and the final score for each domain is calculated by summing the scores of the related questions. The validity and reliability of the Farsi version of this questionnaire have been confirmed by Sahebi et al. [14, 24], where the Cronbach’s alpha scores for depression, anxiety, and stress were 77%, 79%, and 78%, respectively [25].

The continuous data are expressed as mean ± standard deviation (SD), and the categorical data as numbers and percentages. For comparison of means (continuous variables), the two-sample t-test or Wilcoxon rank sum test was used where appropriate. Repeated-measures analysis of variance (ANOVA) was used to investigate the effect of tDCS at the group level and between subgroups, with estimated marginal means applied to evaluate changes over time and between groups. The time points (t0, t1, t2, t3, t4, t5, t6, t7, and t8) represent the within-group effect (time) and the subgroup effect between groups (e.g., patients with MOH vs. patients without MOH). The data were analyzed using SPSS 24.0 software. The statistician was blinded to the treatment groups. A two-sided P value < 0.05 was considered statistically significant.

Results

A total of 30 patients diagnosed with chronic migraine without aura were enrolled. Table 1 summarizes demographics and clinical features of the study population. Table 2 demonstrates 8-week tDCS outcomes across headache parameters.

Table 1.

Demographic and clinical information of study population

Sociodemographic and clinical variables		Results
Gender	female	25 (83.3%)
	male	5 (16.7%)
Age		37.5 ± 12.5
Side of pain	bilateral	19 (63.3%)
	right-sided	4 (13.3%)
	left-sided	5 (16.7%)
Co-diagnosis of MOH		17 (56.7%)
Presence of aura		0
Total Dass21 score		27

Table 2.

Effect of 8-week tDCS therapy on headache parameters

Parameter	Pre-interventional period	After 8-week tDCS therapy
No. of headache days (per week)	6.33	> 50% decrease	16 (53.3%)
		30–50% decrease	4 (13.3%)
		< 30% decrease	10 (33.3%)
No. of severe headache days (per week)	5.70	> 50% decrease	21 (70%)
		30–50% decrease	-----
		< 30% decrease	8 (26.7%)
No. of awakening headaches (per week)	1.57	> 50% decrease	12 (40.0%)
		30–50% decrease	2 (6.7%)
		< 30% decrease	3 (10.0%)
Mean duration of headaches (Hours per attack)	54.50	> 50% decrease	24 (80%)
		30–50% decrease	-----
		< 30% decrease	6 (20%)
Mean intensity of headache (per week)	8.90	> 50% decrease	12 (40%)
		30–50% decrease	6 (20%)
		< 30% decrease	12 (40%)

Figure 1 displays the estimated marginal means for improvement across four key migraine parameters: headache frequency, severe headache day, headache intensity, and headache duration. The therapeutic effects reached maximal clinical benefit at 4 weeks (8 sessions) in all participants. Notably, treatment efficacy was independent of headache laterality.

Fig. 1.

Estimated marginal means for improvement percentage of headache day frequency (Hday), severe headache day(SHday), headache duration (Hduration) and headache intensity (Hintensity)over time in weeks

Figure 2 presents comparative therapeutic outcomes between chronic migraine patients with and without MOH. Analysis revealed that the concomitant diagnosis of MOH did not significantly affect the improvement in headache frequency, severe headache day, headache intensity, or headache duration over time, indicating comparable tDCS efficacy regardless of MOH status.

Fig. 2.

Improvement in headache day frequency (Hday), severe headache day(SHday), headache duration (Hduration) and headache intensity (Hintensity) over time in weeks for patients with and without MOH

We conducted repeated-measures analysis of four key migraine parameters: monthly headache days, severe headache days (VAS ≥ 7), mean headache intensity (VAS), and awakening headache frequency. As detailed in Table 3, all parameters demonstrated significant monotonic decreases across the nine assessment timepoints, indicating progressive clinical improvement throughout the intervention period. Repeated-measures ANOVA revealed significant temporal reductions in all primary outcomes for both MOH and non-MOH subgroups. Table 4 demonstrates parallel decreasing trajectories across all nine assessment points, confirming comparable therapeutic progression regardless of MOH comorbidity status. Participants demonstrated significant clinical improvements, with the MOH subgroup achieving a mean of 3.57 ± 0.42 monthly headache days compared to 3.86 ± 0.48 days in non-MOH patients (p-value = 0.650). These values for severe headache were 1.83 ± 0.49 and 3.06 ± 0.56 (p-value = 0.110), for headache intensity were 5.89 ± 0.47 and 5.21 ± 0.54(p-value = 0.350), for headache duration were 17.24 ± 5.09 and 31 ± 5.64(p-value = 0.080), and for awakening headache were 0.41 ± 0.24 and 0.65 ± 0.27(p-value = 0.510), respectively.

Table 3.

Result of repeated measure ANOVA for variables in the study over time

Variables	Before TDCS treatment	After TDCS treatment								p-value
		1st Week	2nd Week	3rd Week	4th Week	5th Week	6th Week	7th Week	8th Week
Headache days	6.33 ± 1.06	5 ± 2.08	3.97 ± 2.3	3.27 ± 2.1	3 ± 2.1	2.87 ± 2.2	2.9 ± 2.2	2.9 ± 2.2	3.07 ± 2.1	< 0.001
Severe Headache	5.70 ± 1.9	3.23 ± 2.7	2.10 ± 2.5	1.73 ± 2.4	1.70 ± 2.3	1.67 ± 2.3	1.77 ± 2.4	1.73 ± 2.4	1.70 ± 2.3	< 0.001
Headache intensity	8.90 ± 1.3	6.60 ± 2.2	5.57 ± 2.3	5.23 ± 2.3	4.87 ± 2.6	4.93 ± 2.4	4.77 ± 2.6	4.90 ± 2.4	4.63 ± 2.34	< 0.001
Headache duration	53.72 ± 29.4	39.97 ± 32.9	22.34 ± 26.6	18.31 ± 24.8	15.45 ± 22.2	15.31 ± 22.2	15.52 ± 22.1	15.48 ± 22.5	14.59 ± 22.3	< 0.001
Awaking Headache	1.56 ± 0.35	0.86 ± 0.30	0.40 ± 0.20	0.33 ± 0.18	0.36 ± 0.19	0.36 ± 0.19	0.26 ± 0.17	0.26 ± 0.17	0.26 ± 0.17	0.001

Table 4.

Result of repeated measure ANOVA for variables in the study between subject

Group		Before TDCS treatment	After TDCS treatment								within subject effect	Between subject
			1st Week	2nd Week	3rd Week	4th Week	5th Week	6th Week	7th Week	8th Week
Headache days	with MOH	6.0 ± 1.2	4.41 ± 1.9	3.94 ± 2.1	3.35 ± 1.7	2.94 ± 1.56	2.82 ± 1.6	2.76 ± 1.82	2.88 ± 1.7	3.06 ± 1.5	F = 28.21 df = 2.41 P < 0.001*	F = 0.19 df = 1 P = 0.650
	without MOH	6.7 ± 0.6	5.77 ± 2.0	4.0 ± 2.6	3.15 ± 2.7	3.0 ± 2.78	2.92 ± 2.8	3.0 ± 2.7	2.92 ± 2.8	3.08 ± 2.7
Severe Headache	with MOH	5.35 ± 2.2	2.82 ± 2.3	1.47 ± 2.1	1.18 ± 1.9	1.12 ± 1.9	1.06 ± 1.6	1.24 ± 1.9	1.18 ± 1.9	1.12 ± 1.9	F = 33.33 df = 2.04 P < 0.001*	F = 2.65 df = 1 P = 0.110
	without MOH	6.15 ± 1.3	3.77 ± 3.2	2.92 ± 2.8	2.46 ± 2.8	2.46 ± 2.8	2.46 ± 2.8	2.46 ± 2.8	2.46 ± 2.8	2.46 ± 2.8
Headache intensity	with MOH	8.88 ± 1.4	6.88 ± 1.9	5.59 ± 2.3	5.41 ± 1.8	5.29 ± 2.28	5.24 ± 1.78	5.29 ± 2.31	5.35 ± 1.8	5.12 ± 1.7	F = 31.25 df = 2.66 P < 0.001*	F = 0.88 df = 1 P = 0.350
	without MOH	8.92 ± 1.2	6.23 ± 2.6	5.54 ± 2.47	5 ± 2.9	4.31 ± 3.11	4.54 ± 3.1	4.08 ± 2.9	4.31 ± 2.9	4 ± 2.9
Headache duration	with MOH	50.5 ± 29.3	36.3 ± 30.1	15.94 ± 18.4	9.38 ± 6.9	8.63 ± 7.09	8.5 ± 6.3	8.88 ± 6.6	9.38 ± 8.4	7.69 ± 6.1	F = 24.61 df = 2.04 P < 0.001*	F = 3.27 df = 1 P = 0.080
	without MOH	57.6 ± 30.3	44.4 ± 36.8	30.23 ± 33.2	29.31 ± 33.7	23.85 ± 30.9	23.6 ± 31.06	23.69 ± 30.9	23 ± 31.3	23.08 ± 31.2
Awaking Headache	with MOH	1.47 ± 1.6	0.76 ± 1	0.35 ± 0.86	0.24 ± 0.56	0.29 ± 0.77	0.29 ± 0.77	0.12 ± 0.33	0.12 ± 0.33	0.12 ± 0.33	F = 8.37 df = 1.56 P = 0.002*	F = 0.43 df = 1 P = 0.510
	without MOH	1.69 ± 2.3	1 ± 2.2	0.46 ± 1.3	0.46 ± 1.39	0.46 ± 1.3	0.46 ± 1.3	0.46 ± 1.3	0.46 ± 1.3	0.46 ± 1.3

* Significant at p < 0.05 level

According to the DASS21 scoring system, 18 cases (72%) experienced extremely severe depression, 17 cases (63.0%) experienced extremely severe anxiety, and 18 cases (66.7%) experienced extremely severe feelings of stress. The majority of patients with comorbid psychological symptoms also fell into the “extremely severe” category: 87.5% for combined depression and anxiety, 84.3% for depression and stress, 83.4% for stress and anxiety, and 86.7% for all three domains combined (Table 5). No significant association was found between an improvement in the intensity, duration, or frequency of headaches and the total DASS21 score or the DASS subscale.

Table 5.

Frequency of depression, anxiety, and stress severity levels among chronic migraine patients based on DASS-21 scores

DASS21	N (%)
	Normal	Mild	Moderate	Severe	Extremely severe
Depression	3 (12%)	3 (12%)	1 (4%)	0 (0%)	18 (72%)
Anxiety	6 (22.2%)	1 (3.7%)	3 (11.1%)	0 (0%)	17 (63.0%)
Stress	6 (22.2%)	2 (7.4%)	1 (3.7%)	0 (0%)	18 (66.7%)
Depression and anxiety	1 (6.25%)	1 (6.25%)	0 (0%)	0 (0%)	14 (87.5%)
Depression and stress	2 (10.52%)	0 (0%)	1 (5.2%)	0 (0%)	16 (84.28%)
Stress and anxiety	3 (16.6%)	0 (0%)	0 (0%)	0 (0%)	15 (83.4%)
Depression and Stress and anxiety	2 (13.3%)	0 (0%)	0 (0%)	0 (0%)	13 (86.7%)

Three patients (10%) showed no clinical improvement in any of the headache parameters. Only one patient reported a worsening of headache intensity and duration. None of the patients reported serious side effects. A mild burning sensation and pain were reported by three patients.

Discussion

The present study demonstrated the significant efficacy of tDCS for reducing pain in patients with CM with or without MOH. After eight weeks of treatment, the number of patients with no clinical improvement was very small. The mean duration of headache and the number of severe headache days were the parameters most affected by tDCS. A decrease in the mean duration of headache of over 50% was seen in more than 80% of cases. The number of severe headache days decreased by more than 50% in 70% of patients.

Existing tDCS trials have enrolled both chronic and episodic migraine populations [21, 22], while some others specifically targeted CM patients with comorbid MOH [17]. These studies have systematically evaluated the therapeutic potential of selective cathodal or anodal stimulation across core migraine outcomes [15, 16, 26]. Andrade et al. evaluated tDCS treatment for CM patients. After twelve sessions of 2-mA, 20- minute anodal stimulation of the left primary motor (M1) or DLPFC, they found it a safe and effective technique for reducing the pain intensity and improving the quality of life. However, they proposed that the site of cortical stimulation might affect a patient’s response to treatment [27]. Our right DLPFC anodal targeting was guided by Mastria et al., who identified this region’s dual role in MOH pathophysiology and psychological comorbidities (depression/anxiety) in chronic migraine. They also applied tDCS to patients with CM using anodal right-prefrontal and cathodal occipital stimulation [1]. This approach seems to specifically address the neurobehavioral aspects of medication overuse. We applied the same protocol for all patients regardless of the dominant side of pain. It was found that the therapeutic response by the patients was not affected by the dominant side of pain. Additionally, positioning the cathode on the occipital cortex could affect both the psychological comorbidities of migraine and the hyper-responsivity of the visual cortex. Our dual-stimulation approach - combining anodal right DLPFC and cathodal occipital tDCS - builds upon the work of Mansour et al. [17]. Their findings demonstrated that combined prefrontal anodal and occipital cathodal stimulation significantly reduced both weekly migraine days and severe migraine episodes in MOH patients, though only occipital stimulation showed sustained long-term effects at 3-month follow-up. A systematic review found that tDCS targeting M1 and VC reduced headache frequency, while stimulation of DLPFC and M1 decreased pain intensity. VC inhibition also lowered both headache frequency and pain severity, whereas M1 inhibition only reduced pain severity without affecting frequency [12]. While recent meta-analytic evidence confirms tDCS efficacy in reducing migraine pain intensity, attack frequency, and analgesic consumption, it highlights persistent challenges in protocol standardization and study design quality [14].

Standard tDCS protocols typically employ two electrodes (25–35 cm2 surface area) delivering 2 mA current for 20-minute sessions. Treatment regimens have varied substantially across studies, comprising 5 to 28 sessions administered at different intervals, with follow-up assessments conducted between 1 day and 12 months post-intervention [12, 15–18, 27–30]. It has been demonstrated that repeated tDCS administration over a period of four or more weeks yields sustained reductions in both pain intensity and duration, with therapeutic effects persisting beyond the cessation of treatment [26]. In a comparative study examining treatment frequency, 30 female patients with CM received either one or two daily tDCS sessions targeting DLPFC over 10 days. While both regimens significantly reduced migraine-related disability, the twice-daily protocol did not confer additional clinical benefits compared to once-daily stimulation [25]. We administered tDCS at 2 mA intensity for 20 min per session. The treatment protocol consisted of three daily sessions per week for the initial two weeks, followed by once-weekly sessions for an additional six weeks. Clinical improvement in our patient cohort plateaued following eight tDCS sessions, though subjective reports of partial or complete symptom relief were noted by multiple participants as early as the first session. Our findings demonstrate that this tDCS protocol constitutes an effective preventive intervention for treatment-refractory CM. The intervention demonstrated excellent tolerability, with no serious adverse effects documented, supporting its safety profile as a non-pharmacological therapeutic approach. While prior studies similarly report no serious adverse events, transient mild side effects—including tingling, itching, headache, and localized discomfort—have been documented [12, 16].

The co-occurrence of MOH and migraine represents a highly disabling condition that significantly impairs quality of life. Current pharmacological options for MOH management remain limited, primarily consisting of topiramate, CGRP receptor antagonists, monoclonal antibodies, and botulinum toxin [31]. Our analysis demonstrated no significant differences in headache parameter improvement between patient groups with and without MOH. Based on these findings, we propose tDCS as a viable adjunctive therapeutic approach for migraine patients with comorbid MOH who exhibit suboptimal response to conventional treatments.

A notable finding was the high baseline psychiatric burden in our patients, with the majority scoring in the “extremely severe” range for depression, anxiety, and stress on the DASS-21. This highlights that our sample represents a particularly complex and refractory subgroup of chronic migraine patients, which is crucial for interpreting the results. The lack of association between headache improvement and DASS-21 scores suggests that in this severely affected population, the intervention’s effect on pain may operate through pathways not immediately mediated by acute mood changes. Consequently, while the results are promising for this severe phenotype, their generalizability to chronic migraine populations with lower psychiatric comorbidity may be limited.

This study has several other important limitations. First, the small sample size restricts the statistical power for definitive conclusions and precludes meaningful subgroup analyses, such as comparing efficacy between patients with and without MOH; a lack of observed difference in such subgroups may reflect this inadequate power rather than a true equivalence. Second, the 8-week post-treatment follow-up period is insufficient to determine the long-term sustainability of the clinical effects observed or to monitor for any potential delayed adverse events. These constraints are compounded by the lack of a control group and the challenges associated with effective blinding in tDCS trials. Therefore, large-scale, double-blind, randomized controlled trials with longer follow-up durations and comparative protocols are needed to validate these preliminary findings, optimize stimulation parameters, and robustly assess the intervention’s durability and safety profile for chronic migraine prevention.

Conclusion

Transcranial direct current stimulation is a safe, low-cost neuromodulation therapy for CM patients, including those with MOH. It serves as a complementary or alternative option for pharmacological treatments, especially in drug-resistant cases. The current study demonstrated marked improvement in all headache parameters using a protocol targeting the anode over the right DLPFC and the cathode over the occipital cortex. Further studies are recommended to establish standardized tDCS protocols for migraine prevention and expand its therapeutic applications.

Authors’ contributions

N.R contributed to the study design, acquisition of data and writing of the manuscript. M.T. contributed to patient diagnosis, study design, and manuscript revision. E.J contributed to the study design and revision of the manuscript. A.B contributed in data analysis and statistics.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Declarations

Ethics approval and consent to participate

This study was conducted in compliance with the Declaration of Helsinki. It was approved by Ethics Committee of Tehran University of Medical Sciences, with approval code [IR.TUMS.NI.REC.1402.008]. The study involved anonymous survey data collection with minimal risk. Informed consent was obtained from all individual participants included in the study.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.