Hostname: page-component-cd9895bd7-7cvxr Total loading time: 0 Render date: 2024-12-23T06:24:13.879Z Has data issue: false hasContentIssue false

The Future of Depression Psychopharmacology

Published online by Cambridge University Press:  07 November 2014

Abstract

Along with the development of selective sertonin reuptake inhibitors there has been a tremendous widening of the definition of depression and an impressive decrease in the placebodrug difference in controlled studies. In the early 1960s, about one third of depressed patients improved with placebo and two thirds with active compounds. Current controlled studies suggest that the situation has certainly not improved. The Sequenced Treatment Alternatives to Relieve Depression Study found that response rates to new compounds after the failure of the first antidepressant are low. The monoamine hypothesis of depression was formulated in the mid 1960s based on the antidepressant efficacy of the monoamine reuptake inhibitors, monoamine oxidase inhibitors, and the depressogenic effects of reserpine as a monoamine depleter. However, no monoamine-related finding has been found that is diagnostic for depression. A second major hypothesis regarding depression has been the stress cortisol hypothesis. However, blood cortisol levels are not diagnostic of depression. Psychiatric clinicians are convinced that there are patients for whom antidepressants have made the difference between life and death. However, physicians may generalize unjustifiably based on single dramatic cases to a much larger diagnostic group. Perhaps there are many causes of different types of human sadness, and perhaps only some of these involve mechanisms related to monoamines. Thus, perhaps only some kinds of depression are responsive to monoamine affecting antidepressants.

Type
Review Articles
Copyright
Copyright © Cambridge University Press 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1.Ban, TA. The role of serendipity in drug discovery. Dialogues Clin Neurosci. 2006;8:335344.Google Scholar
2.Klein, DF. The loss of serendipity in psychopharmacology. JAMA. 2008;299:10631065.Google Scholar
3.Turner, EH, Matthews, AM, Linardatos, E, Tell, RA, Rosenthal, R. Selective publication of antidepressant trials and its influence on apparent efficacy. N Engl J Med. 2008;358:252260.Google Scholar
4.Nelson, JC. The STAR*D study: a four-course meal that leaves us wanting more. Am J Psychiatry. 2006;163:18641866.Google Scholar
5.Belmaker, RH, Agam, G. Major depressive disorder. N Engl J Med. 2008;358:5568.Google Scholar
6.Meyer, JH, Ginovart, N, Boovariwala, A, et al.Elevated monoamine oxidase a levels in the brain: an explanation for the monoamine imbalance of major depression. Arch Gen Psychiatry. 2006;63:12091216.Google Scholar
7.Wakefield, JC, Schmitz, MF, First, MB, Horwitz, AV. Extending the bereavement exclusion for major depression to other losses: evidence from the National Comorbidity Survey. Arch Gen Psychiatry. 2007;64:433440.Google Scholar
8.Horwitz, AV, Wakefield, JC. The Loss of Sadness: How Psychiatry Transformed Normal Sorrow into Depressive Disorder. New York, NY: Oxford Press; 2007.CrossRefGoogle Scholar
9.Lacasse, JR. Leo, J. Serotonin and depression: a disconnect between the advertisements and the scientific literature. PLoS Med. 2005;2:e392.Google Scholar
10.Groopman, J. How Doctors Think. New York, NY: Mariner Books; 2008.Google Scholar
11.Carroll, BJ, Cassidy, F, Naftolowitz, D, et al.Pathophysiology of hypercortisolism in depression. Acta Psychiatr Scand Suppl. 2007;(433):90103.Google Scholar
12.Yehuda, R, Teicher, MH, Trestman, RL, Levengood, RA, Siever, LJ. Cortisol regulation in posttraumatic stress disorder and major depression: a chronobiological analysis. Biol Psychiatry. 1996;40:7988.Google Scholar