MDR1 in paroxetine-induced sexual dysfunction.

Paroxetine-induced sexual dysfunction represents a frequent treatment complication of otherwise efficient antidepressants. The genetic polymorphism of pharmacokinetic genes may contribute to the occurrence of such dysfunctions. This study presents the effect of MDR1 gene polymorphisms on sexual function in 18 women with bulimia nervosa, 18 women with anxiety disorders, and 19 healthy control subjects. It also deals with the relation between MDR1 gene polymorphisms and paroxetine-induced sexual dysfunction. The results demonstrated that MDR1 G2677T/A gene polymorphism allele carriers treated with paroxetine presented with difficulties with orgasm (p = .008) and lubrication (p < .001).

Relevance of CYP2D6 variability in first-episode schizophrenia patients treated with risperidone.

OBJECTIVE: The objective of this prospective, naturalistic study, conducted in first-episode psychosis patients from a Central-European population, was to assess the utility of Cytochrome P-450 2D6 (CYP2D6) genotype testing under normal clinical setting. METHODS: A total of 35 patients diagnosed for the first time with schizophrenia or acute schizophrenia-like psychotic disorder and treated with risperidone were enrolled in the study. These patients underwent sequentiation of the CYP2D6 gene and evaluations of symptoms and severity of adverse effects using the PANSS and UKU scales, respectively. Doses of antipsychotics and other co-medication were monitored as well. In statistical analysis, Fisher's exact test was used to compare ratios and the Wilcoxon rank-sum test was used in the comparison of continual variables. RESULTS: PM patients showed a significantly lower reduction in psychotic symptoms and a greater severity of psychotic symptoms following risperidone treatment and higher doses of antipsychotics not metabolized by CYP2D6, which were used as co-medication. CONCLUSIONS: Based on these results, patients with the PM genotype experiencing first-episode schizophrenia don't appear to be optimal recipients of risperidone treatment. However, as the main limitation of this study was the relatively small sample-size, replication with a larger scale study is needed to confirm these findings.

Links among paroxetine-induced sexual dysfunctions, gender, and CYP2D6 activity.

The aim of the study was to compare the distribution of therapeutic efficacy and sexual dysfunction during maintenance paroxetine treatment in 17 males and 38 females genotyped and phenotyped to determine their CYP2D6 metabolic status. Clinical results were monitored on scales Clinical Global Impression-Severity of Illness Scale (CGIS) and Arizona Sexual Experience Scale (ASEX). The phenotype procedure showed 7 males and 12 females with extensive metabolic status (EM) and 10 males and 26 females with poor metabolic status (PM). No variation in therapeutic efficacy between male and female subjects classified as PM and those marked as EM was found. A significantly higher rate of sexual dysfunction (p = 0.01) was recorded among females with a PM phenotype.

Dexamethasone suppression test in first-episode schizophrenia.

OBJECTIVES: Higher rates of dexamethasone test (DST) nonsuppression in schizophrenia have been attributed to depressive symptoms, suicidality and negative symptoms. No study concerning first-episode schizophrenia has yet been published. DESIGN: In patients hospitalised for the first time with first-episode schizophrenia the DST has been performed before, at the end of the acute treatment and after one year. At the same time the clinical evaluation with PANSS was performed. A cortisol value >5 microgram/dl in either of the postdexamethasone samples indicated nonsuppression of cortisol. RESULTS: A total of 56 males were included. 18% of pts were DST nonsuppressors at medication-free baseline, 5% and 16% after acute treatment and after one year respectively. After 1 year 42/56 of patients fulfilled the criteria of remission. The rate of nonsuppression was 21.4%, 5% and 16.4% in remitters and 7%, 7% and 14.3% in nonremitters. Significant differences in the whole group were found between postdexamethasone cortisolemia at discharge on the one hand and on admission and at the one-year follow-up on the other. Significant correlations were observed between postdexamethasone cortisolemia and negative symptoms at the end of acute treatment. MAIN FINDINGS: In first-episode schizophrenia the short-term treatment led to a decrease in cortisolemia and rates of nonsuppression and an increase at a one-year follow-up. CONCLUSIONS: Rates of DST nonsuppression in schizophrenia including first-episode schizophrenia are influenced by the stage of illness and medication status. The impairment of feedback regulation of cortisol secretion may be related to different biopathogenetic mechanisms depending on the phase of the illness.

Gender differences in efficacy and sexual function in long-term trazodone treatment (preliminary results).

Objects. To evaluate the effect of trazodone on depressive or anxiety symptoms and sexual function depending on patient gender. Method. A total of 111 patients (59 men, 52 women) subjected to long-term treatment with trazodone were studied. The effect of the therapy was recorded according to the Clinical Global Impression - Severity of Illness (CGI-S) scale. The incidence of sexual dysfunction was assessed on the Utvalg for Kliniske Undersogelser (UKU) scale. Results. The effect of the therapy was similar in both genders. The incidence of diminished sexual desire was low and comparable in both genders; orgasmic dysfunctions were present only in women at the level of statistical significance. A positive correlation between the severity of the illness and the occurrence of diminished sexual desire and orgasmic dysfunction was found in women but not in men. Conclusion. The occurrence of sexual dysfunctions in trazodone therapy was lower than in population. It seems that trazodone is an effective therapy of depressive and anxiety symptoms in both genders and it is convenient for sexually active patients, because the occurrence of sexual dysfunctions was present the general to a low degree.

Relationship between CYP 2D6 metabolic status and sexual dysfunction in paroxetine treatment.

This article describes the incidence of sexual dysfunction in 30 patients subjected to long-term treatment by paroxetine in dependence on the P 450 CYP 2D6 isoenzyme metabolic status. Measured on the Arizona Sexual Experience Scale (ASEX; McGahuey, Delgado, & Gelenberg, 1999), the incidence of sexual dysfunction in patients converted to CYP 2D6 poor metabolizers was markedly higher compared with patients who had no history of such conversion, a difference that reached the level of statistical significance. Our article discusses the incidence of sexual dysfunction in connection with reduced CYP 2D6 capacity.