Geriatric psychiatry: serotonin specificity as a new approach

Vernon M Neppe MD, PhD

Educational Objectives

To educate in the area of serotonin and particularly the serotonin 1A receptor subtype.
To discuss the clinical implications of the serotonin 1A receptor with regard to management options and problems.
To examine the evolution of the new antidepressants in psychogeriatrics.
To delineate specific geriatric related problems.

Abstract

The serotonin receptors modulate a variety of basic functions at a large number of levels. These functions reflect serotonin 1A neuromodulators as well. Because of the low toxicity, remarkable toleration, significant experience in geropsychiatry and the medically ill, and the ostensible lack of abuse, serotonin 1A related compounds have significant potential application in geriatric psychiatry and medical illness.

Serotonin 1A receptor action can be measured relatively specifically by the azapirones. These act as partial agonists postsynaptically and full agonists at the autoreceptor. Non-specifically, beta2 -adrenergic receptor blockers (like propranolol) produce overall serotonin 1A receptor antagonist effects. Beta-blockers have limited application in the elderly, despite their role of serotonin 1A. The perspectives in akathisia and aggression may be relevant. The benzodioxines, an experimental group, which includes eltoprazine, act as partial agonists postsynaptically on both 5HT 1A and 1B receptors, and have potential application in aggression. Particularly interesting is a possible link of the neural growth factor S100ß with serotonin 1A and Alzheimerâs disease.

Specific serotonin modulators are evaluated using the azapirones as the pharmacologic probe. Buspirone as the only marketed azapirone is approved for use only in anxiety and mixed anxiety depressive states, however, clinical experience in several other areas is interesting. Low doses of buspirone probably act presynaptically as anti-aggressive agents and speculatively help akathisia; medium doses act post-synaptically possibly as antagonists modulating anxiety; higher doses are weak agonists and may correspond with weak antidepressant effects, some modulation of obsessionality, and even possible effects on the irritability of the manic. Such doses also may induce mild akathisia: this may imply a serotonin 1A modulating role, but this is complex as serotonin re-uptake blockers like fluoxetine which act broadly also induce akathisia; moreover this can be blocked by buspirone. Finally extremely high doses of buspirone appear very promising antitardive dyskinesia agents: as these effects may be blocked by cyproheptadine, this too may be via serotonin 1A neuromodulation of the known partial dopamine agonist effects of buspirone in conventionally supra-therapeutic doses.