Background:: Migraine is a debilitating neuroinflammatory disorder. Patients with migraine often experience elevated levels of depression, anxiety, and stress, which are associated with the frequency and severity of migraine attacks. Curcumin has been shown to have regulatory effects on depression, anxiety, and stress, as well as analgesic properties through various mechanisms. The objective of this study was to assess the impact of nanocurcumin supplementation on depression, anxiety, stress, and clinical manifestations in patients with migraine. Methodology:: This study was conducted as a randomized, double-blind clinical trial. A total of forty-four patients with episodic migraines were recruited for the trial. Stratified randomization was employed to ensure a balanced distribution of participants based on BMI and sex. The patients were equally assigned to two groups using permuted block randomization: 1) the intervention group, which received 80 mg of nano-curcumin, and 2) the placebo (control) group, which received a paraffin-based placebo. The intervention and control periods lasted for 2 months. Anthropometric and demographic data, clinical signs and symptoms (including headache frequency, duration, and severity as reported by the patients), as well as stress, anxiety, and depression scores (using the Dass-21 questionnaire), were recorded before and after the study. The collected data were analyzed using SPSS 22. For normally distributed data, paired t-tests and independent t-tests were utilized. Non-normal data were analyzed using the Wilcoxon test and Mann-Whitney U test. The chi-squared test was employed for categorical variables. To account for confounding factors, the ANCOVA test was conducted. A p-value of ≤ 0.05 was considered statistically significant. The intention-to-treat method was applied to address outliers and missing data. Results:: Based on the findings, the current study demonstrates that supplementation with nano-curcumin can effectively mitigate symptoms of depression and anxiety (p < 0.05). Regarding stress, a noticeable reduction within the nano-curcumin group was observed, although it did not reach statistical significance when compared between groups (p > 0.05). Moreover, nano-curcumin exhibited a significant decrease in the frequency, duration, and severity of headaches (p < 0.05). Conclusion:: Our research findings have shown that supplementation with nano-curcumin can effectively decrease the frequency, severity, and duration of headaches while also alleviating symptoms of depression and anxiety in comparison to the placebo group. Hence, curcumin exhibits significant potential as an adjuvant therapy to enhance the treatment of migraines.
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