ISSN:0271-0749    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The objective was to examine effects of risperidone on hostility and compare these effects with those of haloperidol.On the basis of risperidone's pharmacologic profile, we hypothesized that risperidone has a selective effect on hostility and that this effect is greater than that of haloperidol. The data were obtained in a multicenter clinical trial of risperidone under placebo-controlled, double-blind conditions (duration, 9 weeks). The patients were 139 patients with the diagnosis of DSM-III-R schizophrenia. Hostility was measured by the "hostility" item of the Positive and Negative Syndrome Scale. Change in hostility served as a dependent variable in the analyses. Change in "psychosis" was applied as a covariate; it helped us examine changes in hostility that were unrelated to change in psychosis (selective effect). Risperidone had a greater selective effect on hostility than did haloperidol or placebo. This finding should encourage tests of risperidone as a treatment for patients who show frequent overt physical aggression. (J Clin Psychopharmacol 1995;15:243-249).

ISSN:0271-0749    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The pharmacokinetics of amitriptyline (AMI) have been extensively studied, and a large interindividual variability between oral dose and concentration of the drug in plasma has been documented.The aim of this study was twofold: first, to compare AMI kinetics in depressed patients with those of healthy controls and, second, to describe the relationship between AMI levels in plasma and hypothalamic-pituitary-adrenal (HPA) system changes during depression. Thirty-eight patients with a DSM-III-R diagnosis of major depression and 13 healthy control persons received 75 mg of AMI daily for 6 weeks. Levels of AMI and nortriptyline in plasma were determined, and neuroendocrine testing with the combined dexamethasone-suppression/CRH-stimulation test (DST) was done before AMI administration and after weeks 1, 3, and 6 of medication. AMI levels in plasma were significantly higher in the patient group compared with controls during the entire treatment period, whereas nortriptyline levels did not differ between the two groups. Drug levels correlated significantly with age, but gender had no effect on the concentration of the drug in plasma. Twenty-two patients remitted after treatment. There was no difference in drug levels between responders and nonresponders. Fifteen patients were DST nonsuppressors before treatment: 23 patients and all controls suppressed cortisol after dexamethasone. DST suppressors had significantly higher AMI levels in plasma at weeks 3, 5, and 6 compared with DST nonsuppressors. In comparison to patients with high AMI levels in plasma, those with low drug concentration had higher postdexamethasone cortisol and adrenocorticotropic hormone levels and an increased hormone release after additional CRH. The pharmacokinetics of AMI are different in depressed patients compared with normal controls, and HPA status may determine different metabolic pathways of AMI in patients. (J Clin Psychopharmacol 1995;15:250-258).

ISSN:0271-0749    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

This study was designed to evaluate the relative and absolute bioavailability of triazolam, 0.25 mg, after the administration of the marketed oral tablet and a sublingual prototype wafer; an intravenous dose was used as a reference. Twelve men were evaluated in a three-way crossover study; study days were separated by 1 week. A single dose was administered to each subject at approximately 8 a.m.; serial blood samples were obtained for the determination of triazolam concentration. The fraction absorbed relative to intravenous was 20% higher in the sublingual than in the oral treatment (p = 0.0128); the difference between treatments was greatest in the first 2 hours as indicated by the area under the curve from 0 to 2 hours (p < 0.05). The extraction ratio ranged from 0.05 to 0.25, and the predicted availability after oral administration was 86% with a range of 75 to 95%. In contrast, the observed mean absolute availability was 44% (oral) and 53% (sublingual). A potential explanation for this discrepancy between predicted and observed bioavailability is that after oral administration, a fraction of triazolam may be metabolized by cytochrome P450IIIA4 in the gut wall, with a separate fraction subject to first-pass metabolism in the liver. Although this study was not designed to identify sites of triazolam metabolism, the proposed explanation is consistent with the occurrence of P450IIIA4 in the stomach, small intestine, and liver. Doses administered sublingually avoid first-pass metabolism, producing earlier and higher peak concentrations than do doses administered orally. (J Clin Psychopharmacol 1995:15:259-262).

ISSN:0271-0749    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Dextromethorphan is primarily metabolized to dextrorphan by cytochrome P450 2D6 (CYP2D6), a genetically polymorphic enzyme in humans.Dextrorphan is an active metabolite that produces phencyclidine-like behavioral effects in animals and exhibits anticonvulsant and neuroprotective properties in a variety of experimental models. In these studies, we examined the effects of CYP2D6 phenotype and quinidine inhibition on the pharmacokinetics of dextromethorphan and its metabolites in humans. After a single oral dose of dextromethorphan HBr (30 mg), the major metabolites in the plasma of extensive metabolizers (N = 5) were conjugated dextrorphan and conjugated 3-hydroxymorphinan. Free dextrorphan concentrations were about 100-fold less than the conjugated dextrorphan, and dextromethorphan was not detectable. Pretreatment of these subjects with 100 mg of quinidine, a selective inhibitor of CYP2D6, significantly suppressed the formation of dextrorphan and elevated the concentrations of dextromethorphan (t1/2, 16.4 hours). In poor metabolizers (N = 4) given the same dose, dextromethorphan was the major component in the plasma with a t1/2of 29.5 hours. Present at concentrations 5- to 10-fold less were conjugated dextrorphan and the other two metabolites. Urinary recovery studies indicated that the inhibition by quinidine was reversible and that the elimination of dextromethorphan primarily depends on CYP2D6 activity rather than renal elimination. These data demonstrated that the CYP2D6 phenotype and the concurrent administration of quinidine significantly affect the disposition of dextromethorphan and the formation of the active metabolite dextrorphan and are important factors to be considered in studies of the pharmacologic and behavioral effects of dextromethorphan. (J Clin Psychopharmacol 1995;15:263-269).

ISSN:0271-0749    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Adult attention deficit/hyperactivity disorder (ADHD) is an increasingly recognized disorder with associated psychiatric comorbidity and impairment.Although pharmacotherapy serves an important role in treating ADHD and other concurrent psychiatric disorders in children and adolescents, the use of pharmacotherapeutics for adults with ADHD remains less established. In this report, the effectiveness and dosing parameters of the various agents investigated for adult ADHD are reviewed. A systematic review of the available literature identified 7 studies (N = 193 subjects) of psychostimulants and 10 studies of nonstimulant medications (N = 167 subjects) including antidepressants, antihypertensives, and amino acids for the treatment of ADHD in adults. The majority of double-blind investigations were with the psychostimulants, with the nonstimulant agents, generally antidepressants, studied under open conditions. There was considerable variability in diagnostic criteria, dosing parameters, and response rates between the various studies. Under controlled conditions, the aggregate literature shows that the stimulants had a clinically and statistically significant effect on reducing ADHD symptoms. Open studies on the nonserotonergic antidepressants (tricyclics, bupropion, and monoamine oxidase inhibitors) also show a moderate anti-ADHD effect. The literature appears to support the use of robust doses of both stimulants and antidepressants for ADHD in adults. Further controlled studies applying stringent diagnostic criteria and outcome methodology are necessary to define the range of pharmacotherapeutic options for adults with ADHD. (J Clin Psychopharmacol 1995;15:270-279).

ISSN:0271-0749    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Little is known about factors that may predict the response of dysthymia or other forms of chronic depression to treatment with antidepressant medication.We investigated several sociodemographic and clinical variables for their relationship to the acute treatment response to desipramine in subjects with DSM-III-R dysthymia. Subjects with DSM-III-R dysthymia were treated with desipramine in an open fashion for 10 weeks. Various clinical and sociodemographic variables were assessed at baseline. Ratings of depressive symptoms and severity and determination of categorical outcome were done during treatment. Baseline extended family adjustment as measured by the Social Adjustment Scale Self-Report was significantly better in the responders compared with the nonresponders (2.1 +/- 0.5 vs. 2.6 +/- 0.8; t = 2.84, df = 52.11, p = 0.006). There was a trend (p = 0.06) for overall baseline social impairment (SAS-SR) to be higher in nonresponders versus responders. Older age was a significant predictor of higher depressive severity (Cornell Dysthymia Rating Scale) and global impairment in the last week of the study. No other variable significantly distinguished responders from nonresponders. Although few of the variables that were examined were found to affect acute treatment response, better extended family adjustment as reported on the SAS-SR was a significant predictor of good acute treatment response to desipramine in patients with dysthymia. (J Clin Psychopharmacol 1995;15:280-283).

ISSN:0271-0749    

出版商:OVID    

年代:1995

数据来源: OVID

ISSN:0271-0749    

出版商:OVID    

年代:1995

数据来源: OVID

ISSN:0271-0749    

出版商:OVID    

年代:1995

数据来源: OVID

ISSN:0271-0749    

出版商:OVID    

年代:1995

数据来源: OVID