Depression is a chronic and recurrent illness that can affect at least 20% of the population at some period in their lifetime, according to a number of studies carried out. Moreover, according to the WHO, by 2020 emotional state disorders could be the foremost or second cause for sick leave from work in the developed countries. Current ant-depressive therapies, nevertheless, are far from optimum.
This was the theme of the PhD presented by the pharmacologist and biochemist from the Basque province of Gipuzkoa, Jorge Emilio Ortega Calvo, undertaken at the Faculty of Medicine and Odontology of the University of the Basque Country (UPV/EHU). Basically it was a study in which an analysis was undertaken of the action mechanisms of current antidepressant pharmacological drugs and new antidepressant treatment strategies put forward and that could be useful in the near future in order to address the failings in the current ones.
The PhD entitled, Nuevas estrategias de potenciación antidepresiva basadas en la interacción entre los sistemas noradrenérgico y serotonérgico centrales. Estudio mediante microdiálisis cerebral in vivo (New strategies of antidepressive boosting based on the interaction between the central noradrenergic and serotonergic systems. A study using in vivo cerebral microdialysis) was directed by Professor of Pharmacology, José Javier Meana Martínez and lecturer in Pharmacology, Luis Felipe Callado Hernando, and which obtained excellent cum laude. While carrying out the PhD, Mr Ortega had the opportunity to spend time at a pharmaceutical multinational in the United States, concretely at the Eli Lilly Laboratories.
Jorge Emilio Ortega Calvo graduated in Pharmacy and Biochemistry from the UPV/EHU and is currently carrying out research in the pharmacological laboratory at the University.
Greater braking effect than normal
What this study proposes is, on the one hand, to make advances in our knowledge about a highly prevalent illness – depression - which is still largely of unknown etiology and, on the other, to develop treatment strategies that are more efficacious than the current ones.
Depression is mainly related to disorders with or deficiencies of the neurotransmitters, noradrenaline and serotonine. In the process of depression, the levels of noradrenaline and serotonine in a number of cerebral areas are altered. The task of anti-depressive drugs is to balance, as it were, these levels. However, the biggest drawback in the current treatment of this illness is that only 60-70% of patients respond to treatment. Moreover, when a person starts to be treated, they normally require at least between two and four weeks before symptoms begin to improve and, on not observing any type of short-term improvement, many stop taking the medication.
Due to this, the aim of this PhD was to study the action mechanisms of these drugs in order to, on the one hand, identify treatments that act from the start and, on the other, try to improve the situation for patients who in principle do not respond to this treatment.
To this end, the usual treatments are combined with new targets – the antagonist pharmaceutical drugs of the adrenoceptors a2 that help to boost or increase neurotransmission existing in the brain. Given that it has been observed that in post-mortem brains of patients previously diagnosed with depression and who had committed suicide, these adrenoceptors were found to be altered, their function increased and there was a greater braking effect than normal. This braking impeded the neurotransmission systems from functioning correctly. “If we stop this greater braking effect in those persons suffering depression, it could be that the anti-depressive pharmacological drug might start to act”, he added.
The approach to this study involved animals using the technique of in vivo cerebral microdialysis; “that is, using surgery we introduce probes in certain cerebral zones, and we collected and measured the amount of neurotransmitters in these areas, in order to subsequently see how they are modified on administering different pharmaceutical drugs”.
The results of the thesis point to the fact that the new strategies proposed are able, on the one hand, of improving the percentage response as regards the number of persons responding to treatment and, on the other, of shortening the time period between the initiation of treatment and therapeutic response. “Which may indicate that if all this is taken to the level of a clinical study and trials with patients suffering from depression are begun, perhaps there will be a faster response and amongst a greater number of patients” he stated.
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