B Acad Nat Med Paris
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Since the 1950s, the therapeutic arsenal against depression has grown considerably. From the discovery of monoamine oxidase inhibitors (MAOI) to the antidepressant effect of ketamine, these pharmacological breakthroughs made the history of psychiatry. They also guided the research about the pathophysiology of depression, one of the most devasting diseases, which affects between 10 and 20 % of general population. ⋯ Ketamine's effects are spectacular both in terms of their very short onset time, and because they are observed even in treatment-resistant depression. Just as MAOIs and tricyclic antidepressants allowed the "monoaminergic hypothesis of depression" to emerge, to unravel the mechanisms of ketamine's antidepressant effects should allow the understanding of the role of glutamatergic system, or that of neuro-inflammation, in the neurobiology of depression. Ketamine might also help to refine our understanding of the cognitive pathophysiology of depression, or even to deeply transform the clinical representations about what depression is.
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Antipsychotic drugs are one of the oldest drugs that can change the brain activity. These drugs are mainly used in schizophrenia and the first drug that was judged as efficacious in the treatment of psychosis has been chlorpromazine. ⋯ Three main issues could explain this failure: the exact causes of schizophrenia is still unknown, we still used the idea that one drug could improve all the symptoms of schizophrenia and it is clear that the group of schizophrenics disease could be different disease with different causes. We propose to review the different drugs that have been tested and we will discuss why the most recent genetic studies could help us to propose new pharmacological targets to treat schizophrenia.