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Abstract

Background:

Although migraine is the second most prevalent form of headache, its preventive treatment has some contraindications and complications. It has been postulated that lacosamide reacts with collapsin response mediator protein 2 and prevents its phosphorylation, inhibiting calcitonin gene-related peptide release in the trigeminal system, which might have a role in migraine management.

Objective:

Our study aimed mainly to evaluate the efficacy and safety of lacosamide as an alternative medication to topiramate for the prevention of migraine, especially in patients who had contraindications to topiramate and other approved antiseizure medications used for migraine prevention.

Design:

Our study included two parallel groups: the lacosamide and the topiramate groups.

Methods:

We recruited episodic migraine patients between the ages of 18 and 65; the lacosamide group received lacosamide 50 mg once daily for 1 week, then twice daily from the 8th day till the 90th day); while the topiramate group received topiramate 50 mg once daily for 1 week, then 50 mg twice daily from the 8th day till the 90th day.

Results:

There was not a statistically significant difference between the lacosamide and topiramate in the absolute change in monthly migraine days (MMD) at 90 days with p-value 0.34, there was no significant difference between lacosamide and topiramate groups regarding the percentage of patients with ⩾50% reduction in the baseline migraine days frequency in the last 4 weeks of the treatment period with a p-value 0.11. In total, 14.0 (4.7%) patients in the lacosamide group and 24.0 (8.0%) in the topiramate group stopped treatment prematurely due to intolerance to drug-related adverse effects, hazard ratio 2.83, 95% confidence interval (1.34–4.72), p-value 0.03.

Conclusion:

In episodic migraine patients, the regular use of lacosamide 50 mg Bid for 3 months yielded reductions in the MMD, migraine days that required acute medications, and Headache Impact Test-6 score comparable to those achieved using topiramate 50 mg Bid. Lacosamide was more tolerable than topiramate in episodic migraine patients.

Trial registration:

Prospectively registered on clinicaltrials.gov, NCT06243692—January 29, 2024; https://clinicaltrials.gov/study/NCT06243692.

Plain language summary

Lacosamide versus topiramate in migraine

It has been postulated that lacosamide reacts with CRMP-2 and prevents its phosphorylation, inhibiting CGRP release in the trigeminal system, which might have a role in migraine management; our study aimed mainly to evaluate the efficacy and safety of lacosamide as an alternative medication to topiramate for prevention of migraine, especially in patients who had contraindications to topiramate and other approved antiseizure medications used for migraine prevention. We recruited migraine patients between the ages of 18 and 65; the study was double-blinded randomized trial and had two groups: lacosamide group who received lacosamide 50mg once daily for one week, then twice daily from 8th day till 90th day); topiramate group who received topiramate 50 mg once daily for one week then 50 mg twice daily from 8th day till 90th day. We concluded that, in episodic migraine patients, the regular use of lacosamide 50mg Bid for three months yielded reductions in the monthly migraine days, migraine days that required acute medications, and HIT6 score comparable to those achieved using topiramate 50 mg Bid. Lacosamide was more tolerable than topiramate in episodic migraine patients.

Keywords

Egypt episodic migraine lacosamide topiramate

Introduction

Migraine is a common disorder associated with recurrent attacks of headache that persist from 4 to 72 h, leading to clinical and socioeconomic dysfunctions.^1,2

Although many studies demonstrated the important role of using appropriate preventive treatment in migraine patients to achieve both clinical and socioeconomic improvement,³ many epidemiological studies showed that only around 5% of migraine patients received their preventive treatment regularly.^4,5

Many randomized controlled trials (RCTs) showed that using calcitonin gene-related peptide monoclonal antibodies (CGRP-mAbs), including eptinezumab, erenumab, galcanezumab, and fremanezumab, led to a significant reduction in episodic migraine attack frequency compared to placebo without significant adverse effects.^6–10

The European Headache Federation recommends using anti-CGRP therapies for migraine prevention due to their long-term efficacy and safety.¹¹

Due to economic and logistical difficulties, anti-CGRP medications are still not widely available in developing countries, so there is a need to evaluate other oral medications to be used as migraine preventive therapy.¹²

Topiramate is widely used as migraine preventive therapy in middle- and low-income countries. Topiramate blocks glutamate’s excitatory effect. It has a sodium channel blocking effect and a carbonic anhydrase inhibiting effect.¹³

Although topiramate is an approved antiseizure medication for migraine prevention, it has many contraindications and could produce many side effects.¹²

Lacosamide, a third-generation antiseizure amino acid molecule with the chemical formula R-2-acetamido-N-benzyl-3-methoxypropionamide, was synthesized as an anticonvulsive drug candidate and has demonstrated antinociceptive effects in animal models, including a rat model for painful diabetic neuropathy.¹⁴

It shows rapid absorption and almost complete oral bioavailability, and about 95% of the oral lacosamide is renally excreted. Lacosamide binds minimally (15%) to plasma proteins, limiting the drug-drug interactions in poly-medicated patients.¹⁵

It has a novel molecular mode of action, which involves the delay or blockage of voltage-gated sodium channels (VGSCs). In contrast, the second mechanism involves interacting with collapsin response mediator protein 2 (CRMP2), preventing phosphorylation, and inhibiting CGRP release in the trigeminal system.¹⁶ CGRP is a peptide that produces vasodilation and inflammation in leptomeningeal and extracranial vessels, causing the pulsating pain associated with migraines.¹⁷

Our study aimed to evaluate the safety and efficacy of lacosamide as an antiseizure medication that may be a new alternative to topiramate in episodic migraine prevention.

Methods

Study design

We executed our double-blinded randomized controlled study and screened all episodic migraine patients diagnosed following The International Classification of Headache Disorders 3 (ICHD-3)¹⁸ and sought medical advice in Kafr-Elsheikh University Hospital, Kafr-Elsheikh General Hospital, and Al Obour Hospital in the time from February 1, 2024 to July 1, 2025, we enrolled the last patient in our trial on March 10, 2025. We followed up with patients for 3 months.

We randomly assign our patients to receive either lacosamide or topiramate in a one-to-one ratio.

Participants

Our study included two parallel groups: the (A) group, which included 300 patients who received lacosamide, and the (B) group, which included 300 patients who received topiramate.

Eligibility criteria

The study recruited participants between the ages of 18 and 65 who were diagnosed with episodic migraine following ICHD-3.¹⁸

The detailed inclusion and exclusion criteria are available in the Supplemental Material.

Interventions

All of our patients underwent randomization and routine laboratory tests, and magnetic resonance imaging of the brain.

The study had two parallel groups: the (A) group, which consisted of 300 patients who received (lacosamide 50 mg once daily for 1 week, then twice daily from the 8th day till 90th day)¹⁹; the (B) group which consisted of 300 patients who received (topiramate 50 mg once daily for 1 week then 50 mg twice daily from 8th day till 90th day).¹²

The detailed study interventions are available in the Supplemental Material.

Outcome assessment

Primary outcome

The absolute change in migraine days in each group’s last 4 weeks of the treatment period (migraine day was defined as a calendar day when the patient reported four continuous hours of headache meeting ICHD-3 criteria for migraine).

Secondary outcomes

Our trial involved three efficacy endpoints including; the percentage of patients who achieved ⩾50% reduction in the baseline headache days frequency in the last 4 weeks of the treatment period,²⁰ the absolute change in the number of migraine days that required receiving acute headache medications in the last 4 weeks of the treatment period compared to baseline, the absolute change in the Headache Impact Test-6 (HIT-6) score in the last 4 weeks of the treatment period compared to baseline.

Our trial included secondary safety and tolerability outcomes: the safety outcome was evaluated by assessing the rate of treatment-emergent adverse events in each group via regular follow-up, while the tolerability was assessed by monitoring the number of patients who prematurely discontinued treatment due to treatment-emergent adverse effects in each group.

Sample size

After using Power Analysis & Sample Size System (PASS, V12; NCSS, Kaysville, Utah, USA), we determined that a total of 560 migraine patients would provide 80% power to detect a mean difference of 1.5 migraine days per 4 weeks (primary outcome) in the lacosamide group as compared with the topiramate group, with a final two-sided significance level of 95%, alpha error of 5%, assuming the reduction in migraine days per 4 weeks 4.5 ± 0.77 migraine days in the topiramate group²¹ and an overall dropout rate of 5%. The final size of our trial was 600 patients, 300 patients in each group.

Randomization and blinding

Our study was double-blinded to the investigators and the patients; an independent statistician generated a blocked randomization sequence using computer-generated random numbers with a block size of 4, and all the investigators included in the study did not know the block size. In a one-to-one ratio, participants were randomly assigned to receive either topiramate or lacosamide by a specially trained and qualified nurse. All the investigators included in the study did not know the patients’ assignments. We prepared sequentially numbered opaque Pill boxes and 600 labels for each drug, drug A or B. According to the randomization chart, we attached the number to the box. Patients were recruited sequentially and were given enrollment numbers starting from 1, which were mentioned in their files. Files carrying the same number as the patient enrollment number were then opened, and the patients were assigned to receive drugs A or B based on their randomization. Drug A included lacosamide 50 mg tablets, and Drug B included topiramate 50 mg tablets.

Statistical analysis of the data

We used the IBM SPSS software package, version 29.0 (IBM Corp., Armonk, NY, USA), to analyze our data and base all efficacy and safety analyses on the intention-to-treat principle. Both the primary and secondary outcomes underwent separate statistical analyses. Depending on their distribution, as determined by the Shapiro–Wilk test, we described numerical data as means, standard deviation, or median and interquartile range (IQR). We also reported categorical data using numbers and percentages. The Mann–Whitney U test was used to compare the irregularly distributed numerical data, while Pearson’s Chi-square was utilized to correlate categorical data. All statistical analyses were two-sided, and differences with a p-value of <0.05 were considered statistically significant. To avoid type 1 statistical error in the analysis of secondary efficacy outcomes, we used correction for multiple comparisons, and secondary efficacy outcomes differences with an adjusted p-value of <0.02 were considered statistically significant.

Survival analysis was performed using the Kaplan–Meier test and log-rank method to assess the hazard of premature treatment discontinuation due to intolerable drug-related side effects in each group. The Cox regression method obtained the hazard ratio (HR) at a 95% confidence interval (CI). Statistical significance is established when the CI does not cross the null value.

Results

Six hundred (153 males and 447 females) patients underwent randomization and were divided into two parallel groups. The lacosamide group consisted of 300 patients, and the topiramate group consisted of 300 patients; 555 patients (131 males and 424 females) completed the study during the 3-month follow-up period, as shown in Figure 1.

Figure 1.

Study flow diagram.

There were no statistically significant differences between the two study groups regarding the baseline characteristics, as shown in Table 1.

Table 1.

Baseline criteria of participants.

Demographic data	Lacosamide arm(n = 300)	Topiramate arm(n = 300)
Age in years, median (IQR)^a	27.4 (15.6–40.5)	28.2 (16.1–40.2)
Sex^b
Female, no. (%)	228 (76.0%)	219 (73.0%)
Migraine characters^a
Baseline MMD, median (IQR)^a	6.8 (6.5–9.0)	6.5 (6.0–9.0)
Disease duration in years, median (IQR)^a	2.5 (2.0–4.2)	2.8 (2.0–4.0)
Attack duration in hours, median (IQR)^a	6.5 (5.5–8.0)	6.3 (5.0–8.0)
HIT-6 score at baseline, median (IQR)^a	46.5 (42.3–57.0)	45.4 (42.8–56.6)
Migraine days that required acute medications at baseline, median (IQR)^a	4.5 (4.0–7.0)	4.3 (4.0–7.0)
Migraine site of maximal intensity^a
Frontal	140 (46.7%)	134 (44.7%)
Temporal	39 (13.0%)	51 (17.0%)
Parietal	26 (8.7%)	30 (10.0%)
Occipital	94 (31.3)	85 (28.3)
Migraine pain location^a
Holocranial	154 (51.3%)	175 (58.3%)
Hemicranial	49 (16.3%)	42 (14.0%)
Side locked	12 (4.0%)	9 (3.0%)
Side predominant	85 (28.3%)	74 (24.7%)
Migraine subtypes^b
Migraine with aura, no. (%)	82 (27.3%)	74 (24.7%)
Migraine without aura, no. (%)	218 (72.7%)	226 (75.3%)
Migraine-associated symptoms^b
Photophobia, no. (%)	249 (83.0%)	241 (80.3%)
Phonophobia, no. (%)	239 (79.7%)	231 (77.0%)
Nausea, no. (%)	231 (77.0%)	228 (76%)
Dizziness, no. (%)	204 (68.0%)	207 (69.0%)
Vomiting, no. (%)	120 (40.0%)	105 (35.0%)

Median (IQR).

Percentage.

HIT, Headache Impact Test-6; IQR, interquartile range; MMD, monthly migraine days.

In our study, we found that at the 90-day mark, the lacosamide group showed a 2.56 ± 1.52-day reduction in monthly migraine days (MMD) relative to baseline with a p-value of 0.001, while the topiramate group showed a 2.65 ± 1.28-day reduction in MMD relative to baseline with a p-value of 0.001. There was no statistically significant difference between the lacosamide and topiramate in the absolute change in MMD at 90 days, with a p-value of 0.34, as shown in Table 2.

Table 2.

Analysis of efficacy outcomes in all patients.

Clinical outcomes	Lacosamide arm(n = 300)	Topiramate arm(n = 300)	p-Value
Primary efficacy outcome
Absolute change in MMD at 90 days of the treatment compared to baseline, median (IQR)^a	3.0 (1.0–4.0)	3.0 (1.0–4.0)	0.34
Secondary efficacy outcome
Patients with ⩾50% reduction in the baseline migraine days frequency in the last 4 weeks of the treatment period, no. (%)^b	53.0 (17.7%)	69.0 (23.0%)	0.11
Absolute change in HIT-6 score at 90 days of the treatment compared to baseline, median (IQR)^a	2.0 (2.0–3.8)	2.0 (1.0–4.0)	0.51
Absolute change in migraine days requiring acute medications at 90 days compared to baseline, median (IQR)^a	1.0 (1.0–2.0)	2.0 (1.0–2.0)	0.18

Median (interquartile range: IQR).

Percentage.

IT-6, Headache Impact Test-6; IQR, interquartile range; MMD, monthly migraine days.

We also found that, at the 90-day mark, there was no significant difference between lacosamide and topiramate groups regarding the percentage of patients with ⩾50% reduction in the baseline migraine day frequency in the last 4 weeks of the treatment period, with a p-value of 0.11, as shown in Table 2.

Moreover, we found that at the 90-day mark, the lacosamide group showed a 2.58 ± 1.51-point reduction in HIT-6 scores relative to baseline, with a p-value of 0.001, while the topiramate group showed a 2.78 ± 1.84 point reduction in HIT-6 scores relative to baseline, with a p-value of 0.001. There was no statistically significant difference between the lacosamide and topiramate in the absolute reduction in HIT-6 score at 90 days, with a p-value of 0.34, as shown in Table 2.

Our study found that at the 90-day mark, the lacosamide group showed a 1.76 ± 1.1 days reduction in the MMD that required acute medications relative to baseline, with a p-value of 0.002, while topiramate showed a 1.75 ± 0.91 days reduction in MMD that required acute medications relative to baseline, with a p-value of 0.001. There was no statistically significant difference between the lacosamide and topiramate in the absolute change in the MMD requiring acute medications at 90 days, with a p-value of 0.17, as shown in Table 2.

Our study showed that the topiramate group had statistically significantly higher percentages of decreased appetite and numbness compared to lacosamide, with p-values of 0.007 and 0.03, respectively, while the lacosamide group had statistically significantly higher percentages of dizziness, with a p-value of 0.03, as shown in Table 3.

Table 3.

Analysis of the safety of each treatment.

Adverse effects, no. (%)^a	Lacosamide arm(n = 300)	Topiramate arm(n = 300)	p-Value
Fatigue	2.0 (0.7%)	4.0 (1.3%)	0.41
Gastritis	4.0 (1.3%)	3.0 (1.0%)	0.70
Vomiting	7.0 (2.3%)	5.0 (1.7%)	0.56
Diarrhea	4.0 (1.3%)	3.0 (1.0%)	0.70
Decrease appetite	2.0 (0.7%)	12.0 (4.0%)	0.007*
Renal stones	1.0 (0.3%)	3.0 (0.9%)	0.32
Numbness	3.0 (1.0%)	11.0 (3.7%)	0.03*
Dizziness	9.0 (3.0%)	2.0 (0.7%)	0.03*
Memory impairment	2.0 (0.7%)	8.0 (2.7%)	0.06
Sleep disturbance	2.0 (0.7%)	4.0 (1.3%)	0.41

Percentage.

Statistically significant at p-value < 0.05.

Our trial showed that 39.0 (13.0%) in the lacosamide group and 65.0 (21.7%) in the topiramate group had drug-related side effects, HR 1.89, 95% CI (1.27–2.83), p-value 0.008, also 14.0 (4.7%) patients in the lacosamide group and 24.0 (8.0%) in the topiramate group stopped treatment prematurely due to intolerance to drug-related adverse effects, HR 2.83, 95% CI (1.34–4.72), p-value 0.03, as shown in Table 4 and Figure 2.

Table 4.

Analysis of the tolerability of each treatment.

Adverse effects, no. (%)^a	Lacosamide arm(n = 300)	Topiramate arm(n = 300)	Hazard ratio (95% CI)	p-Value
Patients with any adverse effects, no. (%)^a	39.0 (13.0%)	65.0 (21.7%)	1.89 (1.27–2.83)	0.01*
Patients who prematurely discontinued treatment due to intolerable adverse effects, no. (%)^a	14.0 (4.7%)	24.0 (8.0%)	2.83 (1.34–4.72)	0.03*

Percentage.

Statistically significant at p-value < 0.05.

CI, confidence interval.

Figure 2.

Cumulative probability of treatment discontinuation due to drug-related side effects.

Discussion

Anti-CGRP MAbs showed significant effectiveness and tolerability,²² compared to placebo and conventional oral preventive drugs,²³ and therefore they represent a valuable option for migraine prevention.²⁴ However, the use of anti-CGRP MAbs in daily clinical practice is limited due to economic, logistic difficulties, and the national reimbursement policies, which are driven by the thought that these treatment options are expensive.²⁵ The limitation of anti-CGRP MAbs is present not only in low-income African and Asian countries but also in European countries such as Spain, where anti-CGRP MAbs can be prescribed only after failure of three or more preventive treatments, one of them being onabotulinumtoxin A in case of chronic migraine.²⁵

The limited availability of anti-CGRP MAbs increases the need to assess the safety and efficacy of other new cheap oral medications that can be used as migraine preventive therapy, other than the traditional class I migraine preventives like propranolol and topiramate, which have many side effects and contraindications.¹²

Lacosamide, a third-generation antiseizure amino acid molecule, is an anticonvulsive drug that has a novel molecular mode of action, which involves the delay of blockage of VGSCs, and interaction with CRMP2, preventing its phosphorylation and inhibiting CGRP release in the trigeminal system.¹⁶

Our study aimed to evaluate the efficacy and safety of lacosamide as an alternative medication to topiramate for the prevention of migraine, especially in patients who cannot tolerate topiramate or other approved antiseizure medications for migraine prevention.

We followed up our patients for 3 months following the guidelines of the international headache society (IHS) for trials for migraine prevention which recommended the follow-up period to be at least 3 months,²⁶ moreover, many migraine prevention clinical trials followed up patients for 3 months such as PROMISE-1 trial where the primary efficacy analysis was based on data captured through week 12⁷ and ARISE trial where the key assessments of the safety and efficacy outcomes were at week 12.⁹

All of our patients had migraine for at least 1 year before enrollment in our trial following the guidelines of the IHS,²⁶ while the median duration of migraine in our study was form 2 to 3 years, around 25% of our patients had migraine for more than 4 years, moreover, our study involved only episodic migraine patients and it is known that older age and subsequently longer migraine duration were associated with increased risk of transformation of episodic migraine to chronic one.^27,28

The patients in both groups reported a median of approximately 6–7 monthly (range 6–9) migraine days following the guidelines of the IHS which recommended including patients who had at least four migraine attacks per 4 weeks,²⁶ our study focused on episodic migraine patients, and many studies showed that the more frequent monthly migraine attacks, the higher the risk of chronification of episodic migraine.^29,30

We used the HIT-6 score only, as the migraine disability assessment test (MIDAS) and HIT-6 scores are positively correlated. At the same time, the HIT-6 evaluated the patients’ subjective impressions concerning the effects of headaches on their daily life activities, the MIDAS, on the other hand, looked for more concrete responses of the number of days of work or school were missed in the last 3 months. The MIDAS score showed difficulty in evaluating the impact of headaches on household tasks and social affairs after work. Furthermore, a MIDAS score is influenced by the patient’s employment status. Those who are employed may get a score of 2 rather than 1 for each of questions 1 and 2, and 3 and 4, as they may have been disabled at work and home. Those who are unemployed and not attending school would only get a score of 1 for each of those questions since they cannot be disabled at work, only at home. The MIDAS may be somewhat confusing for patients. Specifically, as items #2 and #4 instruct patients not to include days that they counted in items #1 and #3, which can sometimes be overlooked by patients, yielding an exaggerated total score.³¹

We found that the regular use of lacosamide for 3 months yielded significant reductions in the MMD at 90 days compared to baseline, HIT score at 90 days compared to baseline, the migraine days that required acute medications at 90 days compared to baseline, and a significant increase in patients who achieved more than 50% reduction in the MMD. Moreover, lacosamide’s efficacy results were comparable to those achieved in the topiramate group.

Lacosamide efficacy results were comparable to topiramate’s, as it shared with topiramate in blocking VGSCs and inhibiting cortical hyper-responsiveness to stimuli. Moreover, lacosamide interacted with CRMP2, inhibiting CGRP release in the trigeminal system and reducing the CGRP-mediated vasodilation and inflammation in leptomeningeal and extracranial vessels.¹⁶

In addition, the ability of lacosamide to reduce the HIT score agreed with many trials,^14,32–34 which showed that using lacosamide in patients with neuropathic pain or trigeminal neuralgia was associated with improvements in the quality of sleep, patient global impression of change, quality of life, and pain interference owing to its sodium channel blocking properties and sodium channels are known to play a major role in pain signaling pathways.³⁵

Our trial showed that lacosamide was more tolerable than topiramate, as significantly fewer patients prematurely discontinued treatment due to its side effects. Moreover, patients on topiramate experienced significantly higher rates of paresthesia and decreased appetite.

Our findings aligned with Yang et al.,¹⁶ Hou et al.,³⁶ Shin et al.,³⁷ and Luk et al.³⁸ who stated that lacosamide was well tolerated, especially in epileptic patients. Moreover, Brodie et al.³⁹ found that topiramate use significantly increases the incidence of paresthesia and weight loss compared to lacosamide use.

The patients in the lacosamide group did not experience significant cardiac adverse effects, as most of our patients aged from 18 to 30 years, received relatively low doses of oral lacosamide (50 mg Bid), and had no history of cardiac diseases; the cardiac adverse effects of lacosamide were dose dependent. The risk of cardiac adverse events is higher in elderly patients, those with a history of previous cardiac diseases, and patients who received rapid infusions of intravenous lacosamide.^40,41 Moreover, many studies showed that the effects of lacosamide on cardiac rhythm and blood pressure were clinically insignificant.^41,42

Study limitations and conclusions

Study limitations

Our trial had some advantages, as it was the first double-blinded RCT worldwide to compare lacosamide versus topiramate in migraine patients. However, it had some limitations: the relatively small sample; second, all the patients were Egyptian; third, the relatively short follow-up period; fourth, the study population was representative of the lower range of episodic migraine population, so we need to pursue a larger-scale, long-term, randomized trial powered for both safety and efficacy to establish the durability, validity, and generalizability of the results.

Conclusion

In episodic migraine patients, the regular use of lacosamide 50 mg Bid for 3 months yielded reductions in the MMD, migraine days that required acute medications, and HIT6 score comparable to those achieved using topiramate 50 mg Bid. Lacosamide was more tolerable than topiramate in episodic migraine patients.

Supplemental Material

sj-doc-2-tan-10.1177_17562864251396529 – Supplemental material for Lacosamide versus topiramate in episodic migraine: a randomized controlled double-blinded trial

Supplemental material, sj-doc-2-tan-10.1177_17562864251396529 for Lacosamide versus topiramate in episodic migraine: a randomized controlled double-blinded trial by Mohamed G. Zeinhom, Mohamed Fouad Elsayed Khalil, Mohamed Almoataz, Tarek Youssif Omar Youssif, Ahmed Mohamed Ali Daabis, Hossam Mohamed Refat, Ahmed Ahmed Mohamed Kamal Ebied, Shady S. Georgy, Ahmed Zaki Omar Akl, Mohamed Ismaiel, Salah Ibrahim Ahmed, Hesham Farouk Eissa, Asmaa Ibrahem Desouky Mostafa Ibrahem, Asmaa Mohammed Hassan, Mohamed Elshafei, Amir Ahmed Elsaeed Egila and Sherihan Rezk Ahmed in Therapeutic Advances in Neurological Disorders

Supplemental Material

sj-docx-1-tan-10.1177_17562864251396529 – Supplemental material for Lacosamide versus topiramate in episodic migraine: a randomized controlled double-blinded trial

Supplemental material, sj-docx-1-tan-10.1177_17562864251396529 for Lacosamide versus topiramate in episodic migraine: a randomized controlled double-blinded trial by Mohamed G. Zeinhom, Mohamed Fouad Elsayed Khalil, Mohamed Almoataz, Tarek Youssif Omar Youssif, Ahmed Mohamed Ali Daabis, Hossam Mohamed Refat, Ahmed Ahmed Mohamed Kamal Ebied, Shady S. Georgy, Ahmed Zaki Omar Akl, Mohamed Ismaiel, Salah Ibrahim Ahmed, Hesham Farouk Eissa, Asmaa Ibrahem Desouky Mostafa Ibrahem, Asmaa Mohammed Hassan, Mohamed Elshafei, Amir Ahmed Elsaeed Egila and Sherihan Rezk Ahmed in Therapeutic Advances in Neurological Disorders

Footnotes

Appendix

Acknowledgements

None.

Declarations

ORCID iDs

Mohamed G. Zeinhom

Mohamed Ismaiel

Supplemental material

Supplemental material for this article is available online.

References

Ahmed

Mohamed

AAM

Salem

, et al. Association of white matter hyperintensities with migraine phenotypes and response to treatment. Acta Neurol Belg 2023; 123(5): 1725–1733.

Farid

Zeinhom

Ahmed

, et al. Factors influencing the occurrence and characteristics of white matter hyperintensities on the brain imaging of migraine patients. Neurol Sci 2025; 46(10): 5253–5262.

Feigin

Nichols

Alam

, et al. Global, regional, and national burden of neurological disorders, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2019; 18(5): 459–480.

Zhou

Tan

, et al. Diagnosis and treatment status of migraine: a clinic-based study in China. J Neurol Sci 2012; 315(1): 89–92.

Lipton

Munjal

Alam

, et al. Migraine in America Symptoms and Treatment (MAST) study: baseline study methods, treatment patterns, and gender differences. Headache 2018; 58(9): 1408–1426.

Goadsby

Reuter

Hallström

, et al. A controlled trial of erenumab for episodic migraine. N Engl J Med 2017; 377(22): 2123–2132.

Ashina

Saper

Cady

, et al. Eptinezumab in episodic migraine: a randomized, double-blind, placebo-controlled study (PROMISE-1). Cephalalgia 2020; 40(3): 241–254.

Reuter

Goadsby

Lanteri-Minet

, et al. Efficacy and tolerability of erenumab in patients with episodic migraine in whom two-to-four previous preventive treatments were unsuccessful: a randomised, double-blind, placebo-controlled, phase 3b study. Lancet 2018; 392(10161): 2280–2287.

Dodick

Silberstein

Bigal

, et al. Effect of fremanezumab compared with placebo for prevention of episodic migraine: a randomized clinical trial. JAMA 2018; 319(19): 1999–2008.

10.

Stauffer

Dodick

Zhang

, et al. Evaluation of galcanezumab for the prevention of episodic migraine: the EVOLVE-1 randomized clinical trial. JAMA Neurol 2018; 75(9): 1080–1088.

11.

Sacco

Amin

Ashina

, et al. European Headache Federation guideline on the use of monoclonal antibodies targeting the calcitonin gene related peptide pathway for migraine prevention—2022 update. J Headache Pain 2022; 23(1): 67.

12.

Zeinhom

Elsayed Khalil

Omar Youssif

, et al. Efficacy and tolerability of valproate versus topiramate in migraine prevention, a randomized controlled multi-center trial. J Clin Neurosci 2025; 135: 111156.

13.

Afshari

Rafizadeh

Rezaei

A comparative study of the effects of low-dose topiramate versus sodium valproate in migraine prophylaxis. Int J Neurosci 2012; 122(2): 60–68.

14.

Shaibani

Fares

Selam

, et al. Lacosamide in painful diabetic neuropathy: an 18-week double-blind placebo-controlled trial. J Pain 2009; 10(8): 818–828.

15.

Bialer

Johannessen

Kupferberg

, et al. Progress report on new antiepileptic drugs: a summary of the Eigth Eilat Conference (EILAT VIII). Epilepsy Res 2007; 73(1): 1–52.

16.

Yang

Peng

Zhang

, et al. Safety and tolerability of lacosamide in patients with epilepsy: a systematic review and meta-analysis. Front Pharmacol 2021; 12(September): 694381.

17.

Cernuda-Morollón

Larrosa

Ramón

, et al. Interictal increase of CGRP levels in peripheral blood as a biomarker for chronic migraine. Neurology 2013; 81(14): 1191–1196.

18.

Olesen

Bes

Kunkel

, et al. The international classification of headache disorders, 3rd edition (beta version). Cephalalgia 2013; 33(9): 629–808.

19.

Elgamal

Ahmed

Nahas

, et al. The effect of lacosamide on calcitonin gene-related peptide serum level in episodic migraine patients: a randomized, controlled trial. Acta Neurol Belg 2024; 124(3): 965–972.

20.

Meissner

Fässler

Rücker

, et al. Differential effectiveness of placebo treatments: a systematic review of migraine prophylaxis. JAMA Intern Med 2013; 173(21): 1941–1951.

21.

Chowdhury

Bansal

Duggal

, et al. TOP-PRO study: a randomized double-blind controlled trial of topiramate versus propranolol for prevention of chronic migraine. Cephalalgia 2022; 42(4–5): 396–408.

22.

Nguyen

Ho Quang Tri

Nguyen Ngoc Dan

, et al. Safety, efficacy, and compliance of moderate-to-high dose eptinezumab and erenumab in chronic migraine patients with medication-overuse headache: an updated systematic review and meta-analysis. J Headache Pain 2025; 26(1): 99.

23.

Reuter

Ehrlich

Gendolla

, et al. Erenumab versus topiramate for the prevention of migraine—a randomised, double-blind, active-controlled phase 4 trial. Cephalalgia 2021; 42(2): 108–118.

24.

Drellia

Kokoti

Deligianni

, et al. Anti-CGRP monoclonal antibodies for migraine prevention: A systematic review and likelihood to help or harm analysis. Cephalalgia 2021; 41(7): 851–864.

25.

Lazaro-Hernandez

Caronna

Rosell-Mirmi

, et al. Early and annual projected savings from anti-CGRP monoclonal antibodies in migraine prevention: a cost-benefit analysis in the working-age population. J Headache Pain. 2024; 25(1): 21.

26.

Tfelt-Hansen

Pascual

Ramadan

, et al. Guidelines for controlled trials of drugs in migraine: third edition. A guide for investigators. Cephalalgia 2012; 32(1): 6–38.

27.

Kong

Buse

DC.

Predictors of episodic migraine transformation to chronic migraine: a systematic review and meta-analysis of observational cohort studies. Cephalalgia 2019; 40(5): 503–516.

28.

Buse

Greisman

Baigi

, et al. Migraine progression: a systematic review. Headache 2019; 59(3): 306–338.

29.

Torres-Ferrús

Ursitti

Alpuente

, et al. From transformation to chronification of migraine: pathophysiological and clinical aspects. J Headache Pain 2020; 21(1): 42.

30.

Lipton

Buse

Nahas

, et al. Risk factors for migraine disease progression: a narrative review for a patient-centered approach. J Neurol 2023; 270(12): 5692–5710.

31.

Sauro

Rose

Becker

, et al. HIT-6 and MIDAS as measures of headache disability in a headache referral population. Headache 2010; 50(3): 383–395.

32.

Finnerup

Attal

Haroutounian

, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol 2015; 14(2): 162–173.

33.

Rauck

Shaibani

Biton

, et al. Lacosamide in painful diabetic peripheral neuropathy: a phase 2 double-blind placebo-controlled study. Clin J Pain 2007; 23(2): 150–158.

34.

Carmland

Kreutzfeldt

Holbech

, et al. Effect of lacosamide in peripheral neuropathic pain: study protocol for a randomized, placebo-controlled, phenotype-stratified trial. Trials 2019; 20(1): 588.

35.

Carmland

Kreutzfeldt

Holbech

, et al. The effect of lacosamide in peripheral neuropathic pain: a randomized, double-blind, placebo-controlled, phenotype-stratified trial. Eur J Pain 2024; 28(1): 105–119.

36.

Hou

Peng

Zhang

, et al. Clinical efficacy and safety of lacosamide as an adjunctive treatment in adults with refractory epilepsy. Front Neurol 2021; 12: 712717.

37.

Shin

Y-W

Moon

Cho

, et al. Tolerability of lacosamide rapid dose titration: a randomized, multicenter, prospective, open-label study. Epilepsy Behav 2021; 115: 107663.

38.

Luk

Tatum

Patel

, et al. The safety of lacosamide for treatment of seizures and seizure prophylaxis in adult hospitalized patients. Neurohospitalist 2012; 2(3): 77–81.

39.

Brodie

Kelly

Stephen

LJ.

Prospective audits with newer antiepileptic drugs in focal epilepsy: insights into population responses?

Epilepsy Behav 2014; 31: 73–76.

40.

Hoy

SM.

Lacosamide: a review of its use as adjunctive therapy in the management of partial-onset seizures. CNS Drugs 2013; 27(12): 1125–1142.

41.

Kim

Lee

Bae

E-K

, et al. Cardiac effects of rapid intravenous loading of lacosamide in patients with epilepsy. Epilepsy Res 2021; 176: 106710.

42.

Y-T

Lin

C-H

C-J

, et al. Evaluation of cardiovascular concerns of intravenous lacosamide therapy in epilepsy patients. Front Neurol 2022; 13: 891368.

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