Patterns and predictors of remission, response and recovery in major depression treated with fluoxetine or nortriptyline

Abstract

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 selective serotonin re-uptake inhibitors (SSRIs) and tricyclic antidepressant have comparable efficacy.

DSM-IV Depression with Atypical Features: Is It Valid?

“…All studies compared depressed patients having atypical features with other depressed patients, five including an undifferentiated group having neither melancholic nor atypical features. In all four studies that included patients with melancholic illness, those with atypical features differed (McGinn et al, 1996;Fountoulakis et al, 2004;Bruder et al, 2002;Joyce et al, 2002). In all five studies including an undifferentiated group, those with atypical features differed (McGinn et al, 1996;Anisman et al, 1999;Fountoulakis et al, 2004;Bruder et al, 2002;Joyce et al, 2002).…”

“…Unless atypical depression is differentiated from depressed patients with neither melancholic nor atypical features, applying atypical criteria could be a cumbersome way of saying melancholia is not present. McGinn et al (1996), Anisman et al (1999), Fountoulakis et al (2004), Bruder et al (2002, Stewart et al (1998), andJoyce et al (2002), partially answered the challenge of Parker et al (2002) (see Table 6). All studies compared depressed patients having atypical features with other depressed patients, five including an undifferentiated group having neither melancholic nor atypical features.…”

“…In all four studies that included patients with melancholic illness, those with atypical features differed (McGinn et al, 1996;Fountoulakis et al, 2004;Bruder et al, 2002;Joyce et al, 2002). In all five studies including an undifferentiated group, those with atypical features differed (McGinn et al, 1996;Anisman et al, 1999;Fountoulakis et al, 2004;Bruder et al, 2002;Joyce et al, 2002). One study did not differentiate which patients without atypical depression had melancholia, but did show good imipramine response in those without atypical depression relative to those with atypical depression (Stewart et al, 1998) (see Table 5 for proportions responding).…”

“…This was accounted for by those with atypical depression having no better improvement on drug than placebo, whereas patients without atypical depression had a robust imipramine effect. Joyce et al (2002) randomly assigned 195 patients with major depression to treatment with nortriptyline or fluoxetine. Among patients without atypical depression, the two drugs were equally effective, and did not differ between those with melancholia (fluoxetine response: 56%; nortriptyline response: 39%) and with undifferentiated depression (fluoxetine response: 57%; nortriptyline response: 43%).…”

A polymorphism of the GTP-cyclohydrolase I feedback regulator gene alters transcriptional activity and may affect response to SSRI antidepressants

“…Full details of the patient characteristics, treatment protocol and 6-week outcome have been fully elucidated in an earlier study. 21 Of these 195 patients, 57% were women and the mean age was 31.6 year. Of the 100 patients randomized to fluoxetine, 86 completed an adequate 6-week antidepressant trial, whereas of the 95 randomized to nortriptyline, 68 completed an adequate 6-week antidepressant trial.…”