The future of depression psychopharmacology
Belmaker RH. Beer-Sheva Mental Health Center,
Ben Gurion University of the Negev, Israel.
CNS Spectr. 2008 Aug;13(8):682-7.


Along with the development of selective serotonin reuptake inhibitors there has been a tremendous widening of the definition of depression and an impressive decrease in the placebo-drug 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.
Biogenic amines
Noradrenaline depletion
Catecholamine depletion
An individualised approach
New ways to treat depression
How do antidepressants work?
Monoamines and 'novel' antidepressants
Males, females, serotonin and depression
The monoamine hypothesis of depression
Mood enhancement via stem cell therapy
The catecholamine hypothesis of depression
Treatment-resistant depression; new therapies
Are SSRI antidepressants little better than placebos?
Antidepressant comparisons: remission and response
Depression and antidepressants: remission, dropouts, and ADRs
The placebo vs nocebo effect: opioid and dopaminergic substrates
Does early improvement triggered by antidepressants predict response/remission?
Selective publication of clinical trials leads to unrealistic estimates of antidepressant efficacy

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