| pA2
online © Copyright 2003 The British Pharmacological Society |
023P
University of Surrey Summer Meeting June 2003 |
Comparison
of fluoxetine and nortriptyline in the treatment of moderate to severe
major depression: a double blind and randomised trial
|
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Depression is an international
public health issue with impairments in social and occupational functioning,
increased comorbidity of psychiatric and medical conditions, and an increased
risk of mortality among depressed individuals as a few of its consequences.
There is an impression among psychiatrists that selective serotonin reuptake
inhibitors may not work as well as tricyclic antidepressants in severe
depression and/or melancholia (Siegfried, 1997). On the other hand, there
is a general belief that selective serotonin reuptake inhibitors have
superiority over the tricyclic antidepressants regarding side effects
and in particular cardiovascular effects. The objective of this double
blind study was to compare the efficacy and safety of fluoxetine and nortriptyline
in patients with moderate to severe major depression.
48 adult outpatients who met the Diagnostic and Statistical Manual of
Mental Disorders, 4th edition for major
depression based on the structured clinical interview for DSM IV participated
in the trial. Patients have a baseline Hamilton Rating Scale for Depression
score of at least 20. In this double-blind, single-centre trial, patients
were randomly assigned to receive nortriptyline 150 mg/day (Group 1) or
fluoxetine 60 mg/day (Group 2) for a 6-week study. The outcome of the
two groups was assessed using Hamilton Depression Rating Scale, a side
effect checklist and a regular ECG assessment. 11 patients dropped out
over the trial leaving 37 subjects who met the DSM IV criteria for major
depression and completed the trial. Patients were assessed by a third
year resident of psychiatry at baseline and after 1, 2, 4 and 6 weeks
after the medication started. The principal measure of the outcome was
the 17-item HAM-D. The rater used standardized instructions in the use
of HAM-D. A two-way repeated measures analysis of variance (time- treatment
interaction) was used. The two groups as a between-subjects factor (group)
and the five measurements during treatment as the within-subjects factor
(time) were considered. In addition, a one-way repeated measures analysis
of variance with a two-tailed post-hoc Tukey mean comparison test were
performed in the change from baseline in each group. To compare the two
groups at baseline and the outcome of two groups at the end of the trial,
an unpaired Student's t-test with a two?sided P value was used. To compare
the demographic data, Fisher's exact test was performed.
The present study suggests that the efficacy of nortriptyline is superior
to fluoxetine in this group of major depressed patients (F=6.10, d.f.
= 1, P=0.01). The changes at the endpoint compared to baseline were: -20.3±8.12
(mean±SD) and -16.82±11.08 for nortriptyline and fluoxetine
respectively. A significant difference was observed on the change of scores
of the Hamilton Depression rating scale at week 6 compared to baseline
in the two groups (t=2.01, d.f.=46, P=0.04). No significant differences
were observed between dropout rates in the two groups but autonomic side
effects were significantly more frequent for nortriptyline than for fluoxetine
whereas there was no significant difference in cardiovascular effects
in particular QTc prolongation. Indeed, QTc prolongation was more frequent
in the fluoxetine group.
The results of the current study provide evidence in favour of an efficacy
advantage of nortriptyline over fluoxetine in the treatment of moderate
to severe depression. A larger study is warranted.
Siegfried, K. (1997). J. Clin. Psychopharmacol. 17 (Suppl),
19S-28S.