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Background
Main goal
Description
End results
Background
Axis I psychiatric disorders such as depression and anxiety are the serious disabling illnesses which cause the greatest burden for societies from developed countries. Dominating pharmacotherapy include first-generation antidepressants (tricyclic antidepressants and monoamine oxidase inhibitors), and more recently developed, second-generation antidepressants. Although the efficacy of both groups of medications is similar, currently due to their relatively favorable side effect profile, the second-generation antidepressants play a prominent role in the medical management of depressive patients. Nevertheless: nausea, headache, diarrhea, fatigue, dizziness, sweating, tremor, dry mouth and weight gain are commonly reported adverse events for those drugs, and there is also a risk for rare but severe adverse actions such as suicidality, hyponatremia, seizures, or serotonin syndrome. Moreover, regardless the mechanism of action, all marketed drugs require 3–5 weeks administration to achieve therapeutic efficacy and several systematic reviews have concluded that no one antidepressant performs better than any other. Despite significant progress in our basic knowledge, we are still far from the optimal treatment of Axis I psychiatric disorders and all efforts for new drug development are justified. The recent developments in neuroscience offer new knowledge concerning depression and anxiety, with such innovative therapeutic targets as glutamatergic system, especially metabotropic glutamate (mGlu) receptors. New approaches concern also the serotonergic (5-HT) system, where novel strategies involve combined mechanisms such as the inhibition of the 5-HT reuptake + blockade of 5-HT1A receptors as well as direct action through recently identified receptors subtypes (i.e. 5-HT6 and 5-HT7). Moreover, there are data suggesting that interactions between both systems might be crucial for antidepressant or anxiolytic activity at the preclinical level.
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