ISSN:0271-0749    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

In this study, the authors investigated the relationship between the metabolism of clomipramine (C) and the genotypes of cytochrome P450 (CYP)CYP2C19andCYP2D6. Fifty-one Japanese patients (18 men and 33 women) were administered 10 to 250 mg/day of C by mouth and maintained on the same daily dose of C for at least 2 weeks to obtain steady-state concentrations. Plasma levels of C and its metabolitesN-desmethylclomipramine (DC), 8-hydroxyclomipramine, and 8-hydroxy-N-desmethylclomipramine (HDC) were determined by high-performance liquid chromatography. The allele frequencies ofCYP2C19*2, CYP2C19*3, CYP2D6*5,andCYP2D6*10were 27.5%, 12.8%, 2.9%, and 43.1%, respectively. Subjects who were homozygous for mutated alleles ofCYP2C19showed approximately 75% higher concentrations of C corrected by dose and body weight compared with those who were homozygous for wild-type alleles. Also, subjects who were homozygous for mutated alleles ofCYP2C19showed an approximately 68% higher value of C/DC compared with those who were homozygous for wild-type alleles. No significant difference in the ratio of DC/HDC was observed between subjects who were homozygous for mutated alleles ofCYP2D6and those who were homozygous for wild-type alleles. These results suggest that genotypingCYP2C19is useful for grossly predicting the risk of getting high plasma concentrations of C and the low individual capacity to demethylate C because there is marked interindividual variability within each genotype. However, the genotyping ofCYP2D6is not useful for predicting the individual capacity to hydroxylate DC.

ISSN:0271-0749    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Selective serotonin reuptake inhibitors (SSRIs) are known to induce delayed orgasm and ejaculation. However, different SSRIs may differentially delay ejaculation. A double-blind, fixed-dose study in healthy men with lifelong rapid ejaculation was performed to evaluate potential differences between clinically relevant doses of two selective serotonin reuptake inhibitors, paroxetine and citalopram, in their effects on ejaculation. Thirty men with an intravaginal ejaculation latency time (IELT) less than 1 minute were randomly assigned to receive paroxetine (20 mg/day) and citalopram (20 mg/day) for 5 weeks, after taking half the dosage in the first week. During the 1-month baseline and 6-week treatment period, IELTs were measured at home by using a stopwatch procedure. The trial was completed by 23 men. Analysis of variance revealed a between-group difference in the evolution of IELT delay over time (p= 0.0004); the IELT after paroxetine and citalopram gradually increased from 18 and 21 seconds to approximately 170 and 44 seconds, respectively. Paroxetine 20 mg/day exerted a strong delay (8.9-fold increase), whereas citalopram 20 mg/day mildly delayed ejaculation (1.8-fold increase). These results indicate that paroxetine leads to a significant delay in orgasm and ejaculation, whereas citalopram seems to have less of an effect on it.

ISSN:0271-0749    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The 1-week single-blind placebo lead-in has long been a standard in double-blind psychopharmacology clinical trials. Although a lead-in period is often necessary (e.g., to receive laboratory results before randomization), some authors have demonstrated that the standard single-blind placebo lead-in’s performance was similar to having a lead-in in which placebo was not administered. The single-blind placebo lead-in did not decrease postrandomization placebo response, nor did it increase drug–placebo differences. To eliminate a higher percentage of placebo responders before randomization and to reduce potential biases in baseline ratings, the authors designed and implemented two depression studies with a double-blind variable placebo lead-in period. In these designs, both the patients and personnel at the investigative sites were blinded to the length of the placebo lead-in period and the start of the active treatment period. Approximately 28% of the patients in the double-blind placebo lead-in studies met criteria to be placebo lead-in responders, as compared with fewer than 10% from two single-blind placebo lead-in studies conducted in a similar time frame. Although all patients continued in the study (including placebo lead-in responders), the primary efficacy analysis prospectively excluded double-blind placebo lead-in responders. Analysis of postrandomization changes revealed that double-blind placebo lead-in responders, even when continuing to receive placebo treatment, maintained their response. At the study endpoint, these placebo lead-in responders had significantly lower severity scores than their counterparts who were not lead-in responders. The prospective removal of lead-in responders thus resulted in an increase in mean endpoint placebo group severity scores. This resulted in an increased drug–placebo treatment difference in one of the two studies but had no effect on the treatment difference in the other study.

ISSN:0271-0749    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Published reports document 20–40% lower mean serum clozapine concentrations in smokers compared with nonsmokers due to enzyme induction. Despite the increase in nonsmoking psychiatric facilities in the United States, previous studies have not tracked individual changes in serum clozapine levels after smoking cessation. Clozapine level changes were analyzed in 11 patients at Oregon State Hospital who were on stable clozapine doses, before and after implementation of a hospital-wide nonsmoking policy. A mean increase in clozapine levels of 71.9% (442.4 ng/ml ± 598.8 ng/ml) occurred upon smoking cessation (p< .034) from a baseline level of 550.2 ng/ml (± 160.18 ng/ml). One serious adverse event, aspiration pneumonia, was associated with a nonsmoking serum clozapine level of 3066 ng/ml. Elimination of statistically extreme results generated a mean increase of 57.4 % or 284.1 ng/ml (± 105.2 ng/ml) for the remaining cases (p<.001) and permitted construction of a linear model which explains 80.9% of changes in clozapine levels upon smoking cessation (F= 34.9;p= .001): clozapine level as nonsmoker = 45.3 + 1.474 (clozapine level as smoker). These findings suggest that significant increases in clozapine levels upon smoking cessation may be predicted by use of a model. Those with high baseline levels should be monitored for serious adverse events.

ISSN:0271-0749    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

In addition to dopamine, serotonin (5-hydroxytryptamine, 5-HT) has been reported to play an important role in schizophrenia. Besides blocking dopamine, atypical antipsychotics also block 5-HT receptors. The clinical efficacy of the atypical antipsychotic clozapine is associated with the 5-HT antagonistic action of the drug and a high serotonergic tone before treatment. The atypical antipsychotic olanzapine has a receptor-binding profile similar to that of clozapine. The present study investigated whether treatment with olanzapine blocks hormone release induced by the 5-HT2c agonist m-chlorophenylpiperazine (m-CPP) and, if so, whether this 5-HT antagonistic effect is related to treatment response. Eighteen male schizophrenic patients participated in this study. All patients were challenged with m-CPP (0.5 mg/kg orally) in a double-blind, randomized, placebo-controlled design after a drug-free period of at least 2 weeks. Adrenocorticotropic hormone (ACTH), cortisol, and prolactin plasma levels were measured every 30 minutes up to 210 minutes after challenge. Patients were treated for 6 weeks with 10 mg olanzapine daily in an open design, after which the challenge tests were repeated. Olanzapine significantly blocked m-CPP-induced ACTH, cortisol, and prolactin release, suggesting that it is a potent 5-HT2c antagonistin vivo.This 5-HT antagonistic effect of olanzapine was not significantly correlated with treatment response. Also, no significant correlation was found between m-CPP-induced hormone release before treatment and clinical response after treatment with olanzapine. These findings suggest that olanzapine is a potent 5-HT2c antagonistin vivobut that this is unrelated to its clinical efficacy in this nonrefractory sample of schizophrenic patients.

ISSN:0271-0749    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Risperidone is an atypical antipsychotic drug which has been suggested to be beneficial for the treatment of elderly patients with psychotic symptoms. In this study, we assessed the short-term efficacy and the safety of risperidone in geropsychiatric inpatients with psychotic symptoms. The sample population included 110 elderly inpatients with psychotic disorders. Assessment for drug efficacy using the Brief Psychiatric Rating Scale, Sandoz Clinical Assessment-Geriatric scale, and Clinical Global Impression scale was conducted at baseline and also at 4 weeks subsequent to risperidone treatment commencement. Subsequent to commencing risperidone treatment, 80 patients completed a 4-week therapeutic evaluation. Seventy (87.5%) of the 80 patients experienced mild to substantial improvement using the Clinical Global Impression scale. Adverse effects were monitored in all 110 patients. The most commonly detected adverse effects were weakness of legs or walking problems (43/110; 39.1%) and dizziness (32/110; 29.1%). Peripheral edema was noted in 18 (16.4%) patients. Risperidone, in low doses, appeared to have been effective in this sample of patients older than 65 years with psychotic symptoms. The mean dose (2.1 ± SD 1.4 mg/day) applied was lower then that suggested for young patients and was related to the each specific patient diagnosis. Peripheral edema and walking problems were commonly observed adverse effects for these elderly patients, such problems having not been seen to the same extent in previous studies of young patients.

ISSN:0271-0749    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Nonlinear mixed effects modeling was used to estimate the effects of clonazepam-carbamazepine interaction on clearance values using 359 serum levels gathered from 183 pediatric and adult epileptic patients (age range, 0.3–26.8 years) during their clinical routine care. Patients received the administration of clonazepam and/or carbamazepine. The final model describing clonazepam clearance was CL = 179.0 · TBW−0.231· 1.22CBZ, where CL is total body clearance (mL/kg/h) and TBW is total body weight (kg); CBZ = 1 for concomitant administration of carbamazepine and CBZ = zero otherwise. The final model describing carbamazepine clearance was CL = 92.7 · TBW−0.394· DOSE0.397· 0.795CZP, where DOSE is the daily dose of carbamazepine (mg/kg/day); CZP = 1 for concomitant administration of clonazepam and CZP = zero otherwise. Concomitant administration of clonazepam and carbamazepine resulted in a 22% increase in clonazepam clearance and a 20.5% decrease in carbamazepine clearance.

ISSN:0271-0749    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The objective of this paper was to study prospectively the course of clinically relevant thyroid dysfunction in a cohort of patients on long-term lithium treatment. Patients (N = 150) who had undergone a cross-sectional evaluation of their thyroid function in 1989, when they were at different stages of lithium treatment, were followed up for the presence of thyroid autoimmunity, hypothyroidism, and goiter during a further period of lithium exposure of up to ten years. The following annual rates of newly developed thyroid dysfunction were observed: autoimmunity (1.4%), subclinical hypothyroidism (1.7%), and goiter (2.1%). Subjects with thyroid autoimmunity had a higher chance of requiring substitution treatment with levothyroxine for subclinical hypothyroidism compared with subjects with no evidence of thyroid autoimmunity (13/32 = 41% versus 7/118 = 6%). Subjects (N = 15) who were prescribed carbamazepine in addition to lithium showed a significant decrease of TSH concentrations. In patients already being treated with lithium for several years, the overall incidence of hypothyroidism, goiter, and thyroid autoimmunity were comparable with those reported for the general population. However, lithium exposure may represent an additional risk factor for hypothyroidism in women and/or in the presence of thyroid autoimmunity.

ISSN:0271-0749    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Although previous studies have shown that the human attention system is partially affected by chlorpheniramine, the effects of chlorpheniramine on human auditory selective attention have not yet been explored. This study examines the effects of a single dose of 4 mg ofdextro-chlorpheniramine on human auditory selective attention by means of the evaluation of the event-related brain potential (ERP) processing negativity (PN). The study sample consisted of 20 healthy male humans, who received either a single 4-mg dose ofdextro-chlorpheniramine or a placebo in a double-blind design. The subjects were given a dichotic listening task, in which they were instructed to press a response button upon detecting deviant tones (target) while their ERPs were recorded. In parallel, subjective tests evaluated the daytime sleepiness, overall vigor, and affect of the subjects. Results showed that the auditory selective attention is impaired under the effects of chlorpheniramine, as reflected by an attenuation of PN amplitude and by a decrease of performance in the group of subjects who took a single 4-mg dose ofdextro-chlorpheniramine. No subjective change in the daytime sleepiness, overall vigor, or affect of the subjects was observed. This lack of conscious awareness of the side effects may lead to situations of risk in tasks for which auditory information is important, because no subjective indicators of attention impairment are available to the subjects.

ISSN:0271-0749    

出版商:OVID    

年代:2001

数据来源: OVID