Glutamate Levels in Cerebrospinal Fluid and Triptans Overuse in Chronic Migraine


  • Domingos Sávio deSouza Vieira MD,

  • Maria da Graça Naffah-Mazzacoratti MD, PhD,

  • Eliova Zukerman MD,

  • Carlos Augusto Senne Soares MD,

  • Esper Abräo Cavalheiro MD, PhD,

  • Mario Fernando Prieto Peres MD, PhD, FACP

  • From the Hospital Israelita Albert Einstein—Instituto Israelita de Ensino e Pesquisa—Instituto do Cérebro, São Paulo, Brazil (Drs. Vieira, Zukerman, Soares, Cavalheiro, and Peres); and Universidade Federal de São Paulo—Departamento de Neurologia e Neurocirurgia, São Paulo, Brazil (Drs. Vieira, Naffah-Mazzacoratti, Cavalheiro, and Peres).

Address all correspondence to Mario Fernando Prieto Peres, Al. Joaquim Eugenio de Lima, 881 cj 708, 01403-001 São Paulo, Brazil.


Objective.—Chronic migraine (CM) is a common disorder, affecting 2% to 3% of the general population. Glutamate is implicated in cortical spreading depression, trigeminovascular activation, central sensitization, and may be linked to migraine chronification. Triptans brought a novel option for the acute migraine treatment. As the development of central sensitization impacts upon the effectiveness of triptan therapy, we hypothesized that glutamate might be related to triptan response mechanisms.

Methods.—We studied 19 patients diagnosed with CM according to the International Headache Society (2004) criteria. Patients were divided in those overusing analgesics (NSAIDs); those without overuse, and those overusing triptans.

Results.—Cerebrospinal fluid (CSF) glutamate levels were similar in patients overusing acute medications (0.335 ± 0.225 μmol) compared to those without overuse (0.354 ± 0.141 μmol), P= NS). In contrast, patients overusing triptans had CSF glutamate levels significantly lower than that observed in nonoverusers (0.175 ± 0.057 vs 0.354 ± 0.141 μmol, P= 0.015), and significantly higher than controls (0.175 ± 0.057 vs 0.109 ± 0.066 μmol, P= 0.039). In triptan overusers, CSF glutamate levels, although lower, were not significantly different from patients overusing other types of analgesics.

Conclusions.—Our study showed lower glutamate levels in CSF of CM patients overusing triptans. Glutamate may be implicated in triptan response mechanisms, triptans may work in part by reducing extracellular glutamate levels in the brain.