Anxiolytic-like effect of phytoestrogen genistein in rats with long-term absence of ovarian hormones in the black and white model

Postmenopause is mainly characterized by a reduction of ovarian hormones, which is accompanied by a major incidence of physical disorders and mood swings. Clinical and experimental evidence suggest that phytoestrogens could be used to ameliorate these alterations associated with menopause. However, the phytoestrogen effects on anxiety in rats with long-term absence of ovarian hormones, is unknown. Consequently, in the present study the authors compared the anxiolytic-like effect of phytoestrogen genistein (0.25, 0.5 y 1.0 mg/kg, i.p.) in Wistar rats with 12-weeks postovariectomy in the black and white model and in the open field test, and it was compared with diazepam (1.0 mg/kg, i.p.). In the black and white model, genistein (0.5 y 1.0 mg/kg) and diazepam reduced the latency to enter and increased the time spent into the white compartment; also, significantly increased frequency and time spent in exploration toward white compartment was seen, as compared with the control group (p < 0.05). In the open field test, genistein and diazepam increased grooming and rearing, without significant changes in locomotor activity, as compared with the control group. In conclusion, phytoestrogen genistein produces an anxiolytic-like effect in Wistar rats with long-term absence of ovarian hormones in the black and white model, supporting the hypotheses that phytoestrogens could be used to ameliorate anxiety associated with menopause.     

Efficacy and safety of duloxetine in the treatment of generalized anxiety disorder: a flexible-dose, progressive-titration, placebo-controlled trial

Generalized anxiety disorder (GAD), a prevalent and chronic illness, is associated with dysregulation in both serotonergic and noradrenergic neurotransmission. Our study examined the efficacy, safety, and tolerability of duloxetine hydrochloride, a dual reuptake inhibitor of serotonin and norepinephrine, for short-term treatment of adults with GAD. In a 10-week, double-blind, progressive-titration, flexible-dose trial, 327 adult outpatients with a DSM-IV-defined GAD diagnosis were randomized to duloxetine 60-120 mg (DLX, N=168) or placebo (PLA, N=159) treatment. The primary efficacy measure was mean change from baseline to endpoint in Hamilton Anxiety Scale (HAMA) total score. Secondary outcome measures included response rate (HAMA total score reduction > or =50% from baseline), Clinician Global Impression-Improvement (CGI-I) scores, and Sheehan Disability Scale (SDS) scores. Patients who received duloxetine treatment demonstrated significantly greater improvement in HAMA total scores (P=.02); a higher response rate (P=.03), and greater improvement (P=.04) than patients who received placebo. Duloxetine-treated patients were also significantly more improved than placebo-treated patients on SDS global functional (P<.01) and work, social, and family/home impairment scores (P<.05). The rate of discontinuation due to adverse events (AEs) was higher for the duloxetine group compared with the placebo group (P=.002). The AEs most frequently associated with duloxetine were nausea, dizziness, and somnolence. Duloxetine was an efficacious, safe, and well-tolerated treatment that resulted in clinically significant improvements in symptom severity and functioning for patients with GAD.