Glutamatergic modulatory therapy for Tourette syndrome

Tourette syndrome (TS) is a neuropsychiatric disorder characterized by the presence of chronic, fluctuating motor and vocal (phonic) tics. The disorder is commonly associated with a variety of comorbidities including obsessive–compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), school problems, anxiety, and depression. Therapeutically, if tics are causing psychosocial or physical problems, symptomatic medications are often prescribed, typically alpha-adrenergic agonists or dopamine antagonists. Recognizing that therapy is often ineffective and frequently associated with unacceptable side-effects, there is an ongoing effort to identify new tic-suppressing therapies. Several lines of evidence are presented that support the use of glutamate modulators in TS including glutamate’s major role in cortico-striatal-thalamo-cortical circuits (CSTC), the recognized extensive interaction between glutamate and dopamine systems, results of familial genetic studies, and data from neurochemical analyses of postmortem brain samples. Since insufficient data is available to determine whether TS is definitively associated with a hyper- or hypo-glutamatergic state, potential treatment options using either glutamate antagonists or agonists are reviewed. Data from studies using these agents in the treatment of OCD are presented. If validated, modulation of the glutamate system could provide a valuable new pharmacological approach in the treatment of tics associated with Tourette syndrome.