Objective: The first objective of this paper was to describe the pattern of remission, response and recovery in patients with major depression who were randomised for treatment with fluoxetine or nortriptyline. The second objective was to report on the demographic and diagnostic predictors of the response and recovery in these depressed patients. Method: One hundred and ninety-five patients with major depression were recruited for this outpatient study. After a detailed clinical and neurobiological evaluation patients were randomized to receive either fluoxetine or nortiptyline as an initial antidepressant treatment. Results: Of the 195 depressed patients randomised to treatment, 154 completed an adequate 6-week trial of either fluoxetine or nortriptyline as their initial antidepressant. Of the 41 patients who did not complete an adequate trial the dropout rate was higher on those randomized to nortriptyline (p = 0.02). There was also an important interaction of drug and gender in determining dropouts in that women did not complete an adequate trial with nortriptyline and men did not complete an adequate trial with fluoxetine (p = 0.002). Of the 154 patients who completed an adequate 6-week antidepressant trial there were no significant differences in 6-week measures of depression severity or of percentage improvement. However, if we use an intention to treat analysis and dichotomise outcomes into response, remission or recovery; then recovery rates were significantly higher with fluoxetine than nortriptyline (p = 0.005). Using an intention to treat analysis fluoxetine was superior to nortriptyline in women, in those less than 25-years old, and in those with atypical depression. Independent of drug, those with chronic depressions had a poorer outcome. Conclusion: In this sample of depressed patients randomized to nortriptyline or fluoxetine the change in depressive symptoms over 6 weeks were comparable between fluoxetine and nortriptyline. However, when we look at the more clinically important variable of recovery then fluoxetine was superior to nortriptyline. Predictors of a poorer response to nortriptyline were gender, young age and atypical depression. The results challenge traditional beliefs that selec-tive serotonin re-uptake inhibitors (SSRIs) and tricyclic antidepressant have comparable efficacy.
