CYP2D6 genotyping in patients on psychoactive drug therapy.

The polymorphic isoenzyme CYP2D6 has a major role in the oxidative metabolism of many deal of psychoactive drugs. Its six mutant alleles (null alleles *3, *4, *5, *6, *7 and *8) encode for inactive enzyme molecules. A carrier of two mutant alleles is considered a poor metabolizer phenotype, while a carrier of only one damaged allele is considered an intermediate metabolizer phenotype. The aim of the study was to assess the prevalence of null alleles in a group of psychiatric patients suffering from depression (n=49) and schizophrenia (n=86) in comparison with healthy individuals (n=145) by the method of multiplex allele specific PCR. Only CYP2D6*3,*4 and *6 mutant alleles were found in the study subjects. No significant difference between the depression and control groups was found for allele prevalence, genotype or phenotype distribution (p>0.05). However, a significant difference was observed between schizophrenic patients and controls for allele frequency (p=0.002), genotype distribution (p=0.016), and phenotype prevalence (p=0.018). The odds ratio of 2.542 for 2D6*4 suggested a significant association between this allele and schizophrenia, significantly contributing to poor metabolizer phenotype (odds ratio=5.020). The relationship between CYP2D6 gene polymorphism and side effects in schizophrenic patients undergoing long-term psychoactive drug therapy was investigated. A significant difference was obtained for allele prevalence (p=0.002), genotype (p=0.029), and phenotype (p=0.002) distribution between patients without and with side effects. A relative risk of 2.626 and 5.333 for 2D6*4 and 2D6*6, respectively, and of 7.08 for poor metabolizer phenotype suggested a significant association between the hereditary susceptibility for a particular type of drug metabolism (defect alleles) and side effects. These preliminary results suggest that the CYP2D6 genotyping appears to be useful for predicting risks for side effects of psychoactive drugs in schizophrenic patients, but their usefulness should be further explored.

[Sertraline in the treatment of premenstrual dysphoric disorder]. / Sertralin u lijecenju predmenstrualnog disforicnog poremecaja.

About 75% of women in reproductive age have some premenstrual changes. It is estimated that 2% to 10% of women experience symptoms severe enough to interfere with their professional or social activities and they meet the DSM-IV criteria for PMDD, premenstrual dysphoric disorder. Benzodiazepines and antidepressants have been shown to be effective treatments for PMDD; GnRH agonists are the second choice. New findings support the opinion that intermittent dosing of some antidepressants, e.g. selective serotonin reuptake inhibitors, is equivalent in efficacy to continuous drug treatment. The aim of the present study was to analyze the characteristics of premenstrual symptoms. In addition, the authors wanted to estimate the efficacy of intermittent sertraline dosing in the treatment of women with premenstrual dysphoric disorder. The study involved women employed in Vrapce Psychiatric Hospital. One hundred and thirty seven of them were examined for the presence of premenstrual symptoms. Seven women with PMDD were included in the treatment with sertraline. Symptoms were monitored with daily reports using the Calendar of Premenstrual Experiences (COPE). Six women completed the study. In three of them, sertraline given during the luteal phase produced significant improvements of premenstrual symptoms.

Effects of (DesGly9-Arg8) vasopressin on cognitive processes in alcoholic patients.

The effect of intranasally administered (DesGly9-Arg8) vasopressin (DGAVP) on certain aspects of cognitive functions of alcoholic patients was studied. The investigation was carried out in 103 chronic alcoholic patients. None of the patients suffered from Korsakoff's syndrome, portal encephalopathy or brain damage of other etiology. The trial was double-blind, placebo controlled. Psychological testing, which included certain aspects of attention, short-term and long-term memory and spatial orientation, was carried out on the day before (baseline measurements), on the last day (II), and seven days after the last administration of DGAVP (III). No treatment effect of DGAVP was observed. The results show that investigations with humans are infinitely more complex than those with animals, since a number of physiological and socio-psychological factors must be controlled. In this study of alcoholics two such factors: 1) duration of abstinence and 2) adaptation to test situation were identified.

[Cognitive function in alcoholics in a double-blind study of piracetam]. / Kognitivne sposobnosti alkoholicara u dvostruko slijepom pokusu s piracetamom.

The effects of piracetam on cognitive functions have been studied in alcoholic patients. The investigation was carried out on 27 alcoholics who were admitted to hospital with acute withdrawal syndrome. The trial was performed under double-blind condition. Thirteen patients were treated with piracetam and 14 with placebo. The performance of patients treated with piracetam (experimental group) was significantly better at the Block-Design retest, as compared with the control subjects. This was associated with comparatively good perceptual organization, visual motor coordination and abstract reasoning in these patients. Similar kind of performance of these patients has been achieved in the tests used to measure psychomotor speed and attention capacity. Our findings agree well with some observations of the clinicians and may stimulate further research in this field.

[Neuropsychological defects in alcoholics with the withdrawal syndrome]. / Neuropsiholoski deficiti alkoholicara u apstinencijskom sindromu.

The aim of the present study was to analyse the correlation between the neuropsychological functioning and the intensity of the recent withdrawal syndrome. The authors compares two groups of alcoholics hospitalized for the acute withdrawal syndrome: of the predelirious character (N = 23) and alcoholic delirium (N = 21). Both groups of patients were treated identically in order to suppress the acute withdrawal syndrome. On the tenth day of the treatment the scores on the Gross Evaluation Scale and the Scale of Medical Risks were identical (p less than 0.01) in both groups of patients. On the fifteenth day of hospitalization, after five days without any psychopharmacological therapy, the patients underwent psychological testing: the Wechsler-Bellevue test, separately for the complete, verbal, and nonverbal scales and the Bender-Gestalt test. Statistically significant differences between the two groups of patients were found in the complete scale (p less than 0.05) and the verbal scale (p less than 0.05) of the Wechsler-Bellevue test, as well as in the subtests of the verbal scale: achievement (p less than 0.05), cognition (p less than 0.05), and concepts (p less than 0.01). These differences may be understood as a result of the intensity of the recent withdrawal syndrome, i.e., the patient just cured of delirium showed more serious disturbances in the complete scale and some subtests of the verbal scale of the Wechsler-Bellevue test.