Emerging targets for the treatment of depressive disorder
by
Macritchie KA, Young AH.
Department of Psychiatry, Leazes Wing,
Royal Victoria Infirmary,
Newcastle upon Tyne, NE1 4LP, UK.
a.h.young@ncl.ac.uk
Expert Opin Ther Targets 2001 Oct;5(5):601-612


ABSTRACT

New agents offering novel mechanisms of action are required in the treatment of depressive disorder. Established agents targeting monoamine systems are unsatisfactory because of full and partial treatment resistance, delay in the onset of their effect and the occurrence of side effects. The monoamine hypothesis of depression is now recognised to provide an incomplete explanation of the pathophysiology of depression. New theories have recently developed and new targets for treatment have emerged. We briefly review some important candidate systems and therapeutic targets in depression: the hypothalamic-pituitary-adrenal axis (HPA) and the glucocorticoid and corticotrophin-releasing factor receptors, synaptic plasticity and neurotrophins and the N-methyl-D-aspartate (NMDA) receptor. The putative role of the neuropeptides substance P and neuropeptide Y, the nicotinic system and the potential therapeutic benefits of cannabinoids are also reviewed. Vagal nerve stimulation (VNS) and transcranial magnetic stimulation, serendipitous advances in treatment, are discussed briefly.
SSRIs
NARIs
5-HT2
Recovery
Serotonin
Anhedonia
Noradrenaline
Antidepressants
Biogenic amines
Tyrosine hydroxylase
Tryptophan hydroxylase
Noradrenaline depletion
Catecholamine depletion
An individualised approach
How do antidepressants work?
Males, females, serotonin and depression
The monoamine hypothesis of depression
The neurotrophic effects of antidepressants
The catecholamine hypothesis of depression
An historical analysis of the creation of the concept of an antidepressant
Selective publication of clinical trials leads to unrealistic estimates of antidepressant efficacy


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