FLUOXETINE - ACTIVATING AND SEDATING EFFECTS

Serotonin uptake inhibitors are generally considered activating antide pressants. To assess the rates and temporal patterns of activation and sedation as well as dose-effect relationships, adverse event data wer e evaluated from a fixed-dose study comparing placebo and fluoxetine, 5,20 and 40 mg/day, in the treatment of major depressive disorder (n = 363) and the pooled data from two fixed-dose studies comparing placeb o and fluoxetine, 20, 40 and 60 mg/day, in the treatment of major depr essive disorder (n = 746). The adverse events 'nervousness', 'anxiety' , 'agitation' and 'insomnia' were considered indicative of activation; 'somnolence' and 'asthenia' were considered indicative of sedation. A ctivation and sedation were both statistically significant treatment-e mergent phenomena (p less-than-or-equal-to 0.05), but dose-effect rela tionships differed. Activation rates were relatively stable between 5 mg/day and 40 mg/day, but they increased at 60 mg/day. Sedation rates increased linearly up to 40 mg/day, and then were comparable at 40 mg/ day and 60 mg/day. Discontinuations due to either phenomenon were unco mmon. The temporal patterns of first occurrences and persistence of ac tivation and sedation differed. First occurrences of activation peaked early and declined over time at all doses. First occurrences of sedat ion also peaked early at all doses, but there may have been greater va riability in first occurrences of sedation over time in patients recei ving lower doses. The persistent occurrences of sedation may decline l ess over time than the persistent occurrences of activation.