Ketaminaren eragin antidepresiboak. Ekintza mekanismo berriak farmako antidepresiboen bilaketarako

Abstract

Unlike in other areas of Medicine, in Psychiatry, etiological hypotheses are based on pharmacological evidences. In this way, the development of antidepressant drugs began in the 1950s, once the effects of several drugs against tuberculosis were observed. Since the first antidepressants potentiated monoaminergic neurotransmission, the monoaminergic hypothesis was generated, and the research on depression was based on the deficits of serotonin, noradrenaline and dopamine. Since then, the monoaminergic hypothesis and its variations have conditioned the development of antidepressant drugs. However, research performed in the last years has demonstrated that stress and depression produce neuronal atrophy and a loss of neurons, which is accompanied by a reduction in cortical and hippocampal volumes. According to these new findings, depression would not be a disorder of a specific area, but an alteration of the neural circuits that control mood, cognition and memory. The latest preclinical and clinical studies on depression show that ketamine (a dissociative anesthetic) produces amazing, fast and long-lasting antidepressant effects. Basic research shows that ketamine produces a rapid increase in synaptic connections, reversing the neuronal atrophy induced by depression. These evidences have stimulated the search for new antidepressant drugs, proposing new mechanism of action to achieve this objective.