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The neural basis of generalized anxiety disorder (GAD) is poorly characterized. The effect of chronic administration (12 weeks) of paroxetine, a selective serotonin reuptake inhibitor, on N-acetylaspartate (NAA), a marker of neuronal viability, was evaluated in adults with GAD using proton magnetic resonance spectroscopic imaging ((1)H MRSI) at 1.5 T. We hypothesized that, pretreatment abnormalities in hippocampal NAA/creatine (NAA/Cr) would normalize with symptomatic improvement. Nine GAD patients (mean age = 41.7 year; 4 females) received 12 weeks of open-label paroxetine treatment, flexibly dosed up to 60 mg/day. Clinical outcome was assessed with the Hamilton Anxiety Rating Scale (HAM-A). Multislice ( 1)H MRSI scans were performed at unmedicated baseline and following 6 and 12 weeks of treatment. Ten untreated healthy volunteers (HVs) (mean age = 37.1 year; 4 females) received scans at the same intervals. All patients achieved remission (HAM-A

Anxiety disorders are among the most prevalent psychiatric disorders, but they represent a particular challenge for treatment. The standard first-line treatments, including antidepressants, benzodiazepines, and buspirone, result in significant response rates for a majority of patients; however, unfavorable side effect profiles or risk for dependency for particular agents might limit their use by anxious patients, who often have low thresholds for medication discontinuation. Novel pharmacologic agents that modulate particular receptors, ion channels, or transporters relevant to glutamatergic neurotransmission may represent a new approach to the treatment of anxiety disorders, with generally more favorable side effect profiles. Although the role of glutamate in the pathophysiology of anxiety disorders is still being elucidated, the use of these agents in treatment of anxiety disorders and commonly comorbid conditions such as substance abuse and mood disorders will continue to increase.

Objective: There is a need to identify novel pharmacotherapies for anxiety disorders. The authors examined the safety and efficacy of riluzole, an antiglutamatergic agent, in adult outpatients with generalized anxiety disorder., Method: In an 8-week, open-label, fixed-dose study, 18 medically healthy patients with DSM-IV generalized anxiety disorder received treatment with riluzole (100 mg/day) following a 2-week drug-free period. The primary efficacy measure was the Hamilton Anxiety Rating Scale (HAM-A) score at endpoint., Results: Twelve of the 15 patients who completed the trial responded positively to riluzole. At 8 weeks, eight of the 15 patients had HAM-A score indicating remission of their anxiety. The median time to response was 2.5 weeks., Conclusions: Riluzole appears to be an effective, well-tolerated, and rapidly acting anxiolytic medication for some patients with generalized anxiety disorder. Larger, placebo-controlled studies are indicated.