© 2001 The Royal College of Psychiatrists
REVIEW ARTICLE |
How antidepressants work
New perspectives on the pathophysiology of depressive disorder
Department of Psychiatry, University of Dundee, Dundee
Correspondence: Professor Ian C. Reid, Department of Psychiatry, University of Dundee, Ninewells Hospital, Dundee DDI 9SY
Declaration of interest Our laboratory has received research funding from Organon Laboratories and Wyeth UK.
Background New research in animals is beginning to change radically our understanding of the biology of stress and the effects of antidepressant agents.
Aims To relate recent findings from the basic neurosciences to the pathophysiology of depressive disorder.
Method Drawing together findings from molecular and physiological studies in rats, social studies in primates and neuropsychological studies in humans, we review the neurotrophic and neuroplastic effects of antidepressants and stress.
Results Stress and antidepressants have reciprocal actions on neuronal growth and vulnerability (mediated by the expression of neurotrophins) and synaptic plasticity (mediated by excitatory amino acid neurotransmission) in the hippocampus and other brain structures. Stressors have the capacity to progressively disrupt both the activities of individual cells and the operating characteristics of networks of neurons throughout the life cycle, while antidepressant treatments act to reverse such injurious effects.
Conclusions We propose a central role for the regulation of synaptic connectivity in the pathophysiology of depressive disorder.
This article has been cited by other articles:
 |
|
 |
|
  A. Tylee and P. Walters Onset of action of antidepressants BMJ, May 5, 2007; 334(7600): 911 - 912. [Full Text] [PDF]
|
|
|
|
 |
|
 C. Weze, H. L. Leathard, J. Grange, P. Tiplady, and G. Stevens Healing by Gentle Touch Ameliorates Stress and Other Symptoms in People Suffering with Mental Health Disorders or Psychological Stress Evid. Based Complement. Altern. Med., March 1, 2007; 4(1): 115 - 123. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Smith and D. H. R. Blackwood Depression in young adults Adv. Psychiatr. Treat., January 1, 2004; 10(1): 4 - 12. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Harmer, S. A. Hill, M. J. Taylor, P. J. Cowen, and G. M. Goodwin Toward a Neuropsychological Theory of Antidepressant Drug Action: Increase in Positive Emotional Bias After Potentiation of Norepinephrine Activity Am J Psychiatry, May 1, 2003; 160(5): 990 - 992. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Zuess An Integrative Approach to Depression: Part 2--Assessment and Treatment Complementary Health Practice Review, April 1, 2003; 8(2): 99 - 115. [Abstract] [PDF]
|
|
|
|
|
|
J. Zuess An Integrative Approach to Depression: Part 1--Etiology Complementary Health Practice Review, January 1, 2003; 8(1): 9 - 24. [Abstract] [PDF]
|
|
|
|
 |
|
 T. Saarelainen, P. Hendolin, G. Lucas, E. Koponen, M. Sairanen, E. MacDonald, K. Agerman, A. Haapasalo, H. Nawa, R. Aloyz, et al. Activation of the TrkB Neurotrophin Receptor Is Induced by Antidepressant Drugs and Is Required for Antidepressant-Induced Behavioral Effects J. Neurosci., January 1, 2003; 23(1): 349 - 357. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Shakesby, R. Anwyl, and M. J. Rowan Overcoming the Effects of Stress on Synaptic Plasticity in the Intact Hippocampus: Rapid Actions of Serotonergic and Antidepressant Agents J. Neurosci., May 1, 2002; 22(9): 3638 - 3644. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. H. Zaman, R. Zaman, I. Reid, and C. Stewart Long-term potentiation and changes seen in depression Authors' reply The British Journal of Psychiatry, December 1, 2001; 179 (6): 559 - 560. [Full Text]
|
|