The pharmacology of putative early-onset
antidepressant strategies
by
Blier P. Department of Psychiatry,
McKnight Brain Institute,
University of Florida, Room L4-100,
PO Box 100256, Gainesville,
FL 32610-0383, USA. blier@psych.med.ufl.edu
Eur Neuropsychopharmacol. 2003 Mar;13(2):57-66

ABSTRACT

Depression is a serious and burdensome illness. Although selective serotonin reuptake inhibitors (SSRIs) have improved safety and tolerability of antidepressant treatment efficacy, the delay in the onset of action have not been improved. There is evidence to suggest that the delay in onset of therapeutic activity is a function of the drugs, rather than the disease. This suggests that research into the biological characteristics of depression and its treatments may yield faster-acting antidepressants. Emerging evidence from clinical studies with mirtazapine, venlafaxine and SSRI augmentation with pindolol suggests that these treatments may relieve antidepressant symptoms more rapidly than SSRIs. The putative mechanism of action of faster-acting antidepressant strategies presented here purports that conventional antidepressants acutely increase the availability of serotonin (5-hydroxytryptamine, 5-HT) or noradrenaline (NA), preferentially at their cell body level, which triggers negative feedback mechanisms. After continued stimulation, these feedback mechanisms become desensitised and the enhanced 5-HT availability is able to enhance 5-HT and/or NA neurotransmission. Putative fast-onset antidepressants, on the other hand, may uncouple such feedback control mechanisms and enhance 5-HT and/or NA neurotransmission more rapidly. Further studies are required to characterise in detail the interactions between NA and 5-HT systems and to definitively establish the early onset of candidate antidepressants such as mirtazapine, venlafaxine and pindolol augmentation.

TCAs
SSRIs
RIMAs
Options
Bupropion
Amineptine
Reboxetine
Nefazodone
Mirtazapine
Venlafaxine
21st century
Antidepressants
Tranylcypromine
Atypical depression
Retarded depression
New antidepressants
The monoamine hypothesis
Pleasure, pain and motivation
Treatment-resistant depression

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