Effects of changes in brain 5-HT activity on indicators of cortical arousal

Clinical studies on fluoxetine have reported occasional symptoms of increased fatigue in depressed patients. On the other hand, experimental studies in healthy subjects have demonstrated evidence for fluoxetine-induced increases in cortical arousal. The present placebo-controlled study with 24 healthy subjects was designed to answer the following questions: Does fluoxetine increase measures of cortical arousal and decrease feelings of alertness, and does the 5HT2 receptor blocker ritanserin produce inverse effects to fluoxetine? Analyses of covariance revealed the following results: Fluoxetine produced a slight increase, ritanserin a marked decrease in critical flicker fusion frequency. Time perception was slightly improved by both drugs. Self-ratings on alertness and energy were significantly reduced by both fluoxetine and ritanserin as compared to placebo. Effects for fatigue were increased accordingly. Possible underlying neurophysiological mechanisms and specificity of the effects for cortical as opposed to limbic arousal will be discussed.