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Clinical investigations into antidepressive mechanisms

I. Antihistaminic and cholinolytic effects: Amitriptyline versus promethazine

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Abstract

It is assumed that established antidepressants exert their clinical efficacy by potentiation or decrease of central noradrenergic and serotonergic neurotransmission. However, recent experimental work suggests that antihistaminic and/or cholinolytic effects may also be involved.

This double-blind controlled study compared amitriptyline (catecholamine potentiating, antihistaminic, cholinolytic) with promethazine (antihistaminic, cholinolytic) in 50 severely depressed inpatients over a 30-day treatment period.

Analysis of the Hamilton depression rating scale revealed significant clinical superiority of amitriptyline over promethazine in such major depressive symptoms as depressed mood, suicidal ideation, psychic anxiety, and sleep disturbances. No significant difference was evident as far as autonomous side effects were concerned. Similar results were found by analysis of the AMP rating system.

It is concluded that antihistaminic or cholinolytic effects per se do not explain the antidepressants' efficacy. However, potentiation of noradrenergic neurotransmission by cholinolytic activity might be the major antidepressive mechanism.

Zusammenfassung

Gegenwärtig wird angenommen, daß die gebräuchlichen Antidepressiva klinisch durch eine Potenzierung oder eine Verringerung zentraler noradrenerger und serotoninerger Neurotransmission wirken. Allerdings lassen neuere experimentelle Arbeiten erwarten, daß auch antihistaminerge und/oder cholinolytische Effekte beteiligt sein könnten.

Diese kontrollierte Studie verglich Amitriptylin (katecholamin-potenzierend, anthihistaminerg, cholinolytisch) mit Promethazin (antihistaminerg, cholinolytisch) bei 50 stark depressiven Patienten über eine 30tägige Behandlungsperiode.

Die Analyse der Hamilton Depressionsskala ergab eine signifikante klinische Überlegenheit des Amitriptylin über Promethazin bei depressiven Kernsymptomen wie: gedrückte Stimmung, Suizidneigung, Angst und Schlafstörungen. Bezüglich der vegetativen Nebenwirkungen ergaben sich keine signifikanten Unterschiede. Ähnliche Befunde wurden mit Hilfe des AMP-Systems erhoben.

Es wird geschlossen, daß antihistaminerge oder cholinolytische Wirkungen per se nicht die klinischen Effekte der Antidepressiva erklären. Vielmehr scheint die Potenzierung noradrenerger Neurotransmission durch cholinolytische Aktivität der wesentliche antidepressive Mechanismus zu sein.

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  1. Psychiatrisches Krankenhaus der Universität München, D-8000, München, Germany

    Helmut Beckmann & Max Schmauß

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  1. Helmut Beckmann
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  2. Max Schmauß
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Supported by the Deutsche Forschungsgemeinschaft

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Beckmann, H., Schmauß, M. Clinical investigations into antidepressive mechanisms. Arch. F. Psychiatr. U. Z. Neur. 233, 59–70 (1983). https://doi.org/10.1007/BF00540037

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  • DOI: https://doi.org/10.1007/BF00540037

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