Comparison of the effects of Mirtazapine and Topiramate on headache severity in patients with migraine

Comparison of the effects of Mirtazapine and Topiramate in treatment of migraine

This study will be a randomized controlled clinical trial with two parallel groups, including an intervention group receiving mirtazapine and a control group receiving topiramate. The study will be a phase II trial conducted on 60 patients with migraine. Eligible patients will be randomly allocated to one of the two study groups in a 1:1 ratio. A computer-generated block randomization method with variable block sizes will be used to generate the randomization sequence using R statistical software.

Setting: The Neurology Department of Atieh 2 Hospital in Tehran; Study population: 60 patients with migraine who meet the eligibility criteria; Blinding type: Double-blind; Blinding procedure: Both the patients and the outcome assessors will be blinded to the patients’ treatment allocation to either the mirtazapine or topiramate group.

Inclusion criteria: Diagnosis of migraine with at least 4 migraine days per month; history of migraine for more than one year; history of at least two previous preventive migraine treatments with treatment failure. Exclusion criteria: Presence of a serious comorbid disease other than migraine that may affect the study outcomes; concomitant use of medications that may affect the course of migraine or the efficacy of the study medications

Intervention group: Patients with migraine who will receive mirtazapine at a starting dose of 15 mg once daily, with the dose increased to a target dose of 30 mg once daily as tolerated. Control group: Patients with migraine who will receive topiramate at a starting dose of 25 mg once daily, with the dose gradually increased to a target dose of 50 mg once daily as tolerated.

Headache severity score based on MIDAS questionnaire

Eligible patients, following the verification of inclusion and exclusion criteria and the procurement of informed consent, will be randomized in a 1:1 ratio into one of the two treatment groups: the mirtazapine group or the topiramate group. The unit of randomization will be the individual (patient), with each patient being assigned to only one of the two study groups. To generate the randomization sequence, a computer-based block randomization method with variable block sizes will be employed to minimize the predictability of subsequent allocations. This sequence will be generated using R statistical software by an independent researcher who is not involved in the patient recruitment or assessment process. In this process, the total required sample size will first be determined, followed by the generation of the allocation sequence in a 1:1 ratio, ensuring that within each block, the number of allocations to both groups is equal to maintain a balanced total number of patients in both groups as much as possible. No stratification will be applied in this study, and all eligible patients will be placed within a single randomization sequence. Following the generation of the randomization sequence by the independent researcher, a unique code will be assigned to each patient. Patients will be numbered according to their order of enrollment after eligibility is confirmed, and each patient will be assigned to one of the two treatment groups based on the randomization code corresponding to their number. To ensure allocation concealment and prevent bias by withholding treatment allocation information from the investigator responsible for recruitment, the randomization sequence will be generated and maintained by an independent individual outside of the recruitment and assessment process. Consequently, the investigator responsible for enrolling patients will remain unaware of whether a patient is assigned to the mirtazapine or topiramate group until all inclusion criteria have been fully met, informed consent has been obtained, and the patient is formally registered in the study. Once formal enrollment is complete, allocation will be performed based on the pre-determined sequence, thereby minimizing the possibility of intentional selection or group changes based on prior knowledge.

This study is a randomized, single-blind clinical trial. The assessors will be blinded to the type of intervention (i.e., which medication is being administered). Drug coding and labeling will be performed by an independent individual or organization that is not involved in the implementation of the intervention or the assessment of outcomes.