Two-Week Treatment With the Selective Serotonin Reuptake Inhibitor Citalopram Reduces Contextual Anxiety but Not Cued Fear in Healthy Volunteers: A Fear-Potentiated Startle Study

Chronic treatment with selective serotonin reuptake inhibitors (SSRIs) alleviates both anxiety symptoms and associated physiologic disturbances in anxious patients. However, limited research considers the degree to which chronic SSRI treatment influences anxiety in healthy individuals. This study examined the effect of 2-week citalopram treatment on two threat responses: short-and long-duration-potentiated startle. Prior work suggests that these two responses provide neurally and functionally distinct models of fear and anxiety, respectively, in rodents. Healthy volunteers (n=53) received either placebo or citalopram (20 mg per day) for 2 weeks under double-blind conditions. They were each tested twice, before and after treatment. Participants were exposed to three conditions, including one in which predictable aversive shocks were signaled by a cue, a second in which unpredictable shocks were anticipated, and a third in which no shocks were administered. Aversive states were indexed by acoustic startle. Phasic fear-potentiated startle to the threat cue, as well as sustained startle potentiation to the experimental context in the predictable and unpredictable conditions, were investigated. Citalopram affected neither baseline startle nor short-duration fear-potentiated startle to discrete threat cues. However, citalopram reduced long-duration startle potentiation in the predictable conditions. These results are consistent with the hypothesis that short-and long-duration aversive states are mediated by distinct neural systems. They suggest that citalopram alleviates symptoms of anticipatory anxiety, not fear, by acting on mechanisms underlying long-duration aversive states.