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Fluoxetine Efficacy vs Comparative Drugs: An Overview

Published online by Cambridge University Press:  06 August 2018

Malcolm Lader
Malcolm Lader*
Affiliation:
Institute of Psychiatry, London
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Extract

The tricyclic antidepressants (TCAs) were discovered accidentally by pharmaceutical chemists seeking first, better antihistamines and then antipsychotic agents. Careful clinical assessment revealed the antidepressant properties and suggested that the closer the patient resembled the classical textbook description of ‘endogenous’ depression, the more likely was an adequate clinical response to occur (Kuhn, 1958). However, it was quickly realised that the TCAs possess a plethora of side-effects, particularly sedation and symptoms related to their anticholinergic effects.

Despite much research over the past 25 years, it is unclear how TCAs effect clinical improvement. The two main neurotransmitters involved in some way are noradrenaline (Schildkraut, 1965) and 5-hydroxytryptamine (5-HT; serotonin; Van Praag, 1977). It was proposed that TCAs acted by blocking the reuptake of one or other or both of these neurotransmitters, thereby increasing their concentration in the synaptic cleft. However, as well as these acute effects, chronic effects, such as a decrease in the number of central beta-adrenoceptors (‘down-regulation’) occur, and these are probably more relevant to the clinical action.

Type
Research Article
Information
The British Journal of Psychiatry , Volume 153 , Issue S3: Progress in Antidepressant Therapy , September 1988 , pp. 51 - 58
Copyright
Copyright © 1988 The Royal College of Psychiatrists 

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