History and evolution of the
monoamine hypothesis of depression

by
Hirschfeld RM
Department of Psychiatry and Behavioral Sciences,
University of Texas Medical Branch,
Galveston 77555-0188, USA.
rohirsch@utmb.edu
J Clin Psychiatry 2000; 61 Suppl 6:4-6


ABSTRACT

The symptoms of depression can be improved by agents that act by various mechanisms to increase synaptic concentrations of monoamines. This finding led to the adoption of the monoamine hypothesis of depression, first put forward over 30 years ago, which proposes that the underlying biological or neuroanatomical basis for depression is a deficiency of central noradrenergic and/or serotonergic systems and that targeting this neuronal lesion with an antidepressant would tend to restore normal function in depressed patients. The hypothesis has enjoyed considerable support, since it attempts to provide a pathophysiologic explanation of the actions of antidepressants. However, in its original form it is clearly inadequate, as it does not provide a complete explanation for the actions of antidepressants, and the pathophysiology of depression itself remains unknown. The hypothesis has evolved over the years to include, for example, adaptive changes in receptors to explain why there should be only a gradual clinical response to antidepressant treatment when the increase in availability of monoamines is rapid. Still, the monoamine hypothesis does not address key issues such as why antidepressants are also effective in other disorders such as panic disorder, obsessive-compulsive disorder, and bulimia, or why all drugs that enhance serotonergic or noradrenergic transmission are not necessarily effective in depression. Despite these limitations, however, it is clear that the development of the monoamine hypothesis has been of great importance in understanding depression and in the development of safe and effective pharmacologic agents for its treatment.
1990s
SSRIs
NARIs
Options
Serotonin
Anhedonia
Mechanisms
SSRIs/SNRIs
Comparisons
Noradrenaline
Neuropeptide Y
New anxiolytics
Biogenic amines
Chronic depression
New antidepressants
Antidepressant medication
The monoamine hypothesis
SNaRIs, NaSSAs, and NaRIs
New ways to treat depression
The Neurobiology of Depression (pdf)
Monoamines and 'novel' antidepressants
Mood enhancement via stem cell therapy
The future of depression psychopharmacology


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