The Implications of Adverse Pharmacologic Reactions and Complex Pathogenic Mechanisms in Schizophrenia

Puiu Olivian Stovicek, Dragoş Marinescu, Liana Păuna-Cristian, Ileana Marinescu


Schizophrenia is a major health problem in which diversification and increase in the quality of antipsychotic molecules did not yield the anticipated results. that the etiopathogenesis of schizophrenia accounts for a combination of genetic factors forming the genetic spectrum of vulnerability for schizophrenia. The neurodevelopmental anomalies correlated with the gestational period and obstetric traumatisms raises major pharmacological management issues. The two levels of vulnerability (genetic and neurodevelopmental) are the basis of the pathogeny of side effects induced by antipsychotic medication. The most severe side effects are related to extrapyramidal symptoms, hyperhomocysteinemia, hypofrontality, impairment of the neurovascular unit and neuronal metabolic processes. Understanding these particular mechanisms will allow the clinician to identify the pathogenic model of schizophrenia, customized for each specific case. The adverse drug reaction decreases the compliance and adherence to the treatment, determining repeated discontinuations with psychotic relapses, and may trigger psychopathogenic bursts deteriorating the structural and cerebral functional balance. The type of psychotropic medication must be taken into account, as well as the concomitant medication administered for comorbidities associated with schizophrenia. The cerebral vascular modifications are correlated with the metabolic syndrome induced by antipsychotic medication. This complex syndrome, associated also with modifications in the homocysteine metabolism, determines weight gain, obesity, high blood pressure, ischemic cardiopathy, hyperglycemia and dyslipidemia. Identification of possible biological or neuroimaging markers helps and their early correction may prevent the onset of neurodegenerative evolution and irreversible cerebral atrophies, as well as decrease the risk of side effect that may endanger the life of the schizophrenic patient. The complexity of the pathogenic mechanisms requires a prophylactic behavior, not based on therapeutic switch, but on the proactive, customized pharmacologic intervention, addressing the pathogenic chains.


dopamine, extrapyramidal symptoms, homocysteine, prolactin, hypofrontality

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