THERAPEUTIC EFFECTS OF THE ATYPICAL AND TYPICAL ANTIPSYCHOTICS IN THE TREATMENT OF SCHIZOPHRENIA

The epidemiologic studies concerning schizophrenia are in close relation to the used diagnosis criteria (ICD 10 International Classification of Diseases World Health Organization and DSM IV TR - Diagnostic and Statistical Manual of Mental Disorders American Psychiatric Association) as well as to the studied population(1). The annual incidence in the case of schizophrenia is estimated between 0,1 and 0,5 in 1000 inhabitants. The incidence varies with age and sex young men and women between 35 and 39 years of age presenting high rates of the disease. (3). The risk for the entire period of life of having schizophrenia is situated between 7 and 9 in 1000 inhabitants, and the prevalence in the European countries is situated between 2,5 and 5,3 in 1000 inhabitants, estimating that the prevalence of the disease is similar in different countries if evaluated in comparable modalities (4). For the purpose of clarifying the aetiology of the disease, epidemiology studies have been conducted on selected groups of population, like twins of families of the people who had the disease. The results of these studies made stronger the idea of the genetic determinism of schizophrenia (5). Swanson and collaborators reached the conclusion that the violent manifestations in schizophrenia are five times more frequent with these people than with persons having manifested other psychic diseases. (6). The model stress vulnerability of the aetiopathogeny of schizophrenia which analyzes and groups a series of factors and hypothesis which render the multifactor image of schizophrenia developed and imposed itself starting with Ciompi (7) Zubin and Steinhauer (8) (9) giving credit to the idea of a specific biologic vulnerability which is triggered by stress and leads to schizophrenic symptoms. Stress can have genetic, biological and psychosocial or environmental background. The analysis of the genetic factors involved in the aetiopathogeny of schizophrenia concluded the polygenic theory seems more compatible with the presentation of schizophrenia (10) (11) (12), and the children with non-affected parents present a higher degree of vulnerability if they are raised by schizophrenic parents (13). The psycho-pharmacological research outlined the aetiopathogenical hypothesis based on the dopaminergic in the etiopathology of schizophrenia, using the observations of Van Rossum

regarding the hallucinogen effect of dopamine mimetic drugs. Starting from the finding that drugs determine an increase of the level of dopamine in the structures of the brain, increase outlined by the plasmatic level and in the cerebrospinal fluid of the homovanilic acid (HVA) - a metabolite of dopamine it was proven that the neuroleptics influence the improvement of the psychotic symptomatology in schizophrenia by diminishing the levels of dopamine. All of these observations would prove that the increased activity of dopamine might be the major cause of schizophrenia (14) (15) (16) (17) (18). The research in the field of the neurotransmitters outlined other hypothesis as well: The noradrenalin hypothesis correlates the variations +/- of the noradrenalin with the psychomotric turmoil from schizophrenia and the negative elements; The hypothesis of the Y-amynobutiric (GABA) acid- proves the inversely proportional relationship between the GABA activity and the dopamine activity (19); The serotonin hypothesis - more complex involves the serotonin activity in the genesis of suicidal and impulsive behaviours. The reported mechanisms show an increase of the 5hidroxytriptamine (5-HT2 , a metabolite of serotonin) to some chronic schizophrenics, but the main emphasis is on the antagonism at the level of the serotonin receptors 5-HT2 for diminishing psychotic disorders and preventing the appearance of movement disorders, linked to the dopamine antagonism at level D2 (20) (21) (22). hallucinogen some endogenous amines can be at the basis of the endogenous hallucinogen synthesis, in an abnormal methylation process. the glutamate hypothesis - refers to the appearance of the positive and negative

symptoms in schizophrenia as a consequence of the hypo-function of the receptors of the type glutamate N- methyl -d-aspartate (NMDA) (19). The neuro-development and neuro-degenerative theory is based on the fact that during the second trimester of the foetal development abnormal neuronal migrations are produced, having theories stating also that the appearance of the symptoms of schizophrenia are due to the abnormal neuronal functioning during the adolescence (23), (24). The familial factors are incriminated in the families of schizophrenic patients with high level of expressed emotions (EE), which determine more frequent relapses than in the families with lower level of the EE. The expressed emotions have been defined as an excessively involved, intrusive behaviour, regardless if it is hostile and critical or controlling and infantilizing (25) (26)

(27). The modern treatment of schizophrenia benefits from the present therapeutic strategies, with precise objectives (28): the early recognition of the debut of the disease; therapy under maximum efficiency conditions of the acute episode and of the prevention of the acutisations; the early anticipation of therapeutic resistance and of relapses; The limitations of the adverse effects and the increase of the compliance to the long term treatment.