How Antidepressants Work: Cautionary Conclusions Based on Clinical and Laboratory Studies of the Longer-Term Consequences of Antidepressant Drug Treatment

  1. Ruth Porter Organizer,
  2. Gregory Bock Organizer and
  3. Sarah Clark
  1. Dennis L. Murphy Chairmna,
  2. Charanjit S. Aulakh and
  3. Nancy A. Garrick

Published Online: 28 SEP 2007

DOI: 10.1002/9780470513361.ch7

Ciba Foundation Symposium 123 - Antidepressants and Receptor Function

Ciba Foundation Symposium 123 - Antidepressants and Receptor Function

How to Cite

Murphy, D. L., Aulakh, C. S. and Garrick, N. A. (2007) How Antidepressants Work: Cautionary Conclusions Based on Clinical and Laboratory Studies of the Longer-Term Consequences of Antidepressant Drug Treatment, in Ciba Foundation Symposium 123 - Antidepressants and Receptor Function (eds R. Porter, G. Bock and S. Clark), John Wiley & Sons, Ltd., Chichester, UK. doi: 10.1002/9780470513361.ch7

Author Information

  1. Laboratory of Clinical Science, National Institute of Mental Health, NIH Clinical Center, 10/3D41, 9000 Rockville Pike, Bethesda, Maryland 20892, USA

Publication History

  1. Published Online: 28 SEP 2007

ISBN Information

Print ISBN: 9780471910893

Online ISBN: 9780470513361

SEARCH

Keywords:

  • monoamine oxidase-inhibiting antidepressants;
  • antidepressant drug action;
  • β-adrenoceptors;
  • brain neurotransmitter systems;
  • random-assignment trials

Summary

Time-dependent alterations in the functional activity of adrenergic and serotonergic neurotransmitter systems and, in particular, a frequently observed down-regulation of brain β-adrenoceptors have been implicated in antidepressant drug effects. Current studies of catecholamine and serotonin neurotransmitter systems suggest that the net physiological output changes in neuroendocrine responses, blood pressure, sleep and motor activity which follow various anti-depressant treatments in psychiatric patients, normal controls and different experimental animals are not indicative of a common response pattern to all therapeutically effective agents. Rather, antidepressant treatment effects differ according to many variables, including the pre-existing state of the organism (e.g. depressed, stressed or normal), the species, the duration of treatment and the particular brain or peripheral circuits investigated. Examples are cited from our studies of the effects of monoamine oxidase inhibitors and other antidepressants on noradrenergic–serotonergic interactions that affect melatonin release and other neuroendocrine responses, on some additional functional end-points, and on depressive mood and other symptoms in patients with depression or other tricyclic-responsive disorders. These examples illustrate the complexity found in attempts to identify a unitary mechanism of antidepressant drug action.