The Effect of Flunarizine Prophylactic Treatment on Headache Frequency and Plasma Glutamate Levels in Chronic Tension-type Headache Patients

Background: Previous research has shown that flunarizine may be used for the prophylactic treatment of migraine and that plasma glutamate level monitoring in patients with migraine can serve as a biomarker of response to treatment. Our aim was to assess the efficacy of flunarizine and the correlation of glutamate levels in Chronic Tension-type Headache (CTTH) with response to medication. Methods: We studied 19 patients with diagnosis of CTTH according to International Classification of Headache Disorder, 2nd edition criteria. The level of plasma glutamate was measured before and after 8-weeks prophylactic treatments. Subjects were randomized into three interventional groups (flunarizine 5 mg, flunarizine 10 mg and placebo). Glutamate levels were measured by means of Glutamate ELISA Kit KA1909 Abnova.        Results: Flunarizine 5 mg group had lower mean plasma glutamate levels significantly compared to placebo (p < 0.00; 95% CI: 0.40-1.07). Flunarizine 10 mg group had lower mean of plasma glutamate levels significantly compared to placebo (p< 0.00; 95% CI: 0.53-1.27). However, there were no significant differences of mean plasma glutamate levels between flunarizine 5 mg group and flunarizine 10 mg group (p < 0.37; 95% CI: -(0.54) - 0.21). There were no significant differences in headache frequency reduction among the three interventional groups. Conclusions: The usage of flunarizine as prophylactic treatment can reduce plasma glutamate levels significantly in CTTH patients. Either flunarizine or placebo showed no significant difference in reducing headache frequency in CTTH patients.