Brain-derived neurotrophic factor in generalized anxiety disorder: Results from a duloxetine clinical trial

Abstract

Brain-derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of depression and anxiety, but has not been examined systematically in generalized anxiety disorder (GAD). The objective of this study was to examine the relationship between baseline BDNF level and treatment response in patients with GAD. Patients (N=168) were from China, met criteria for DSM-IV GAD, had a Hospital Anxiety and Depression Rating Anxiety (HADS-A) subscale score ≥10, and a Sheehan Disability Scale (SDS) global functioning total score ≥12 at baseline. Study design was double-blind therapy for 15 weeks with duloxetine 60-120 mg or placebo. Efficacy measures included the HADS-A and Hamilton Anxiety Rating Scale (HAMA) total score. Change from baseline to endpoint for BDNF by treatment group was analyzed using ANCOVA models with baseline BDNF level as a covariate. No significant association was found between baseline plasma BDNF levels and anxiety illness severity. Patients who received duloxetine (n=88) had a significantly greater mean increase in plasma BDNF level (957.80 picograms/ml) compared with patients who received placebo (n=80; 469.93 pg/mL) (P=.007). Patients who met response and remission criteria (with either treatment) had greater mean increases in BDNF at endpoint from baseline (P≤.05) but when compared with nonresponders and nonremitters, respectively, the differences in mean increase were not statistically significant between groups. BDNF levels significantly increased with duloxetine treatment for GAD, but response and remission outcomes were not clearly related to an increase in plasma BDNF level.