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

Abstract

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.

The effectiveness of botulinum toxin for chronic tension-type headache prophylaxis: A systematic review and meta-analysis

“…This effect remained robust in leaveone-out sensitivity analyses (online Supplementary Table S6) and when sensitivity analyses were performed after grouping the studies based on the risk of bias (online Supplementary Figure S3B). The funnel plot was asymmetric (online Supplementary Figure S4B)-possibly due to the limited number of studies; 12 [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] 12 12 a…”

“…Symptomatic medications (e.g., acetaminophen, NSAIDS) remain the mainstay of management of TTH (15), yet, patients with CTTH often require prophylactic medications (16) (e.g., tricyclic antidepressants, SNRIs) along with complementary interventions (17) (e.g., acupuncture, biofeedback) aimed at decreasing headache frequency or intensity. However, due to limitations in understanding the pathophysiology of CTTH, increased co-occurrence of CTTH with medication overuse headache (18), and limited efficacy plus undue adverse effects of medications, pharmacological management of CTTH remains a challenge (19).…”