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Antidepressant Class Differentially Effective in the Treatment of Melancholic Depression

Melancholic depressed patients who are 40 years or older, especially men, appear to show a superior response to the tricyclic antidepressant drug (TCA) nortriptyline, whereas younger patients, especially women, show a superior response to the serotonin reuptake inhibitor (SSRI) fluoxetine.

SSRIs and TCAs appear to be equally effective in adults with major depression, however, some studies suggest that TCAs may be superior to SSRIs in depressed patients with melancholic features.

Peter R. Joyce, PhD, with the Department of Psychological Medicine, Christchurch School of Medicine and Health Sciences, Christchurch, New Zealand, evaluated data they had previously published and assessed the impact of age and gender on the antidepressant response to nortriptyline and fluoxetine.

Their study included 113 patients with melancholic depression. The researchers used two contrasting definitions of melancholia [DSM-IV criteria and the Mental State Examination for Psychomotor Retardation and Agitation (CORE)].

All patients were randomised to receive either fluoxetine or nortriptyline. A response was defined as an improvement of 60% or more on the Montgomery Asberg Depression Rating Scale over 6 weeks of antidepressant treatment on an intention to treat basis. Response rates were examined by age, and by age and gender.

The researchers report that melancholic depressed patients aged 40 years or older, especially men, had a superior response to nortriptyline compared with fluoxetine based on CORE criteria. For nortriptyline, the response rate increased from 32% in patients less than 25 years to 67% in those 40 years or over, while with fluoxetine, the response rate decreased from 67% to 38%.

Likewise, with DSM-IV criteria, the response rates of melancholic patients aged 40 years or older were 60% with nortriptyline and 53% with fluoxetine, while in the melancholic patients 18-24 years the response rates were 69% with fluoxetine and 44% with nortriptyline.

"These findings raise interesting questions about their impact on the neurobiological basis of depressive disorders," the authors suggest. They note that one recent study found that the availability of serotonin 1A receptors might decrease with age, especially in men. In addition, men appear to tolerate TCAs better than SSRIs overall.

"We would suggest that clinicians carefully reappraise their clinical practice in managing older melancholic patients as the SSRIs may be less useful than suggested in some efficacy studies," Dr. Joyce and colleagues conclude.
Acta Psychiatr Scand 2003;108:1:20-23. "A differential response to nortriptyline and fluoxetine in melancholic depression: the importance of age and gender"

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