ISSN:0271-0749    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0271-0749    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

A 3-year open-label study was conducted to determine the long-term safety and efficacy of quetiapine monotherapy in schizophrenia and schizoaffective disorder.Twenty-three male outpatients previously stable but with inter-episode residual symptoms on classical antipsychotics and/or risperidone and who had complained of side effects were selected. To initiate quetiapine, patients were hospitalized for 13 days and then treated as outpatients. Quetiapine dosage was adjusted according to therapeutic effects.Only five patients (21.7%) completed 77 to 96 weeks of the study. Initial dose was 261 ± 65.6 mg/day (mean ± S.D.) administered in divided doses, with an ending dose of 487 ± 209.6 mg/day, corresponding with an 86.6% dose increase over the course of the study. For those completing 12 weeks or less (n = 11), mean ending dose was 362 ± 184.8 mg/day a 38.7% dose increase over baseline. For those completing 25 weeks or more (n = 12), mean ending dose was 592 ± 178.2 mg/day, a 126.8% dose increase over baseline. Six of the seven patients who relapsed after being stabilized on quetiapine for at least three months met criteria for supersensitivity psychosis (SSP).Therapeutic tolerance and rebound psychosis were found to develop with quetiapine in male patients with a history of chronic treatment with classical antipsychotics. Seeman and Tallerico3have proposed pharmacologic explanations for quetiapine and clozapine drug-induced rebound phenomena. (J Clin Psychopharmacol 2002;22:347–352)

ISSN:0271-0749    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Response predictors of risperidone or other newer atypical antipsychotics for schizophrenia treatment remain unclear. This study aimed to investigate the influence of patient demographics on risperidone efficacy for schizophrenia. One hundred twenty-one newly hospitalized patients who had schizophrenia with acute exacerbation entered this prospective, 6-week risperidone trial. The target dose was 6 mg/day, or lower in case of side effects. Consequently, the mean ± SD dose remained quite stable after week 2 and reached 4.4 ± 1.3 mg/day at week 6. Efficacy and side effect assessments were conducted biweekly. The mean total score of the Positive and Negative Syndrome Scale (PANSS) declined during the trial, particularly within the first 4 weeks. Further, of the various efficacy scores (and their natural logarithm values) collected, only the logarithm of the PANSS total score was selected to serve as the response value, because it was normally distributed and thus suitable for regression analyses. After adjusting the effects of treatment duration (weeks 0–6) and other patient-related variables with the generalized estimating equation method, each 1-week increase in duration of prior hospitalizations raised the PANSS total by 0.04% (p= 0.002) and each 1-year increment in the education duration decreased the PANSS by 0.94% (p= 0.04). Gender, age, age at illness onset, duration of illness, diagnosis subtype, or number of prior hospitalizations, however, did not significantly impact the response value. These preliminary results suggest that longer hospitalization duration and shorter education predict higher symptomatology. Further studies with longer observation and larger samples in not only acutely ill patients but also other populations (e.g., first-episode patients) are warranted.

ISSN:0271-0749    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Patients with schizophrenia show a loss of sensory (motor) gating, which is reflected in a reduced prepulse inhibition (PPI) of the startle reflex. Furthermore, patients with schizophrenia habituate less than healthy subjects. From previous studies, it is clear that typical antipsychotics have little or no effect on either sensorimotor gating or habituation, while only limited data is available on the effects of atypical antipsychotics on these processes.Forty-four schizophrenic patients (27 stable on typical and 17 stable on atypical antipsychotics) and 35 healthy control subjects were tested in a PPI paradigm. The prepulse and startle stimuli were pure tones of 1500 Hz (duration 40ms, intensity 80 dB and 110 dB respectively), with a fixed interstimulus interval of 120 milliseconds. Block effects in PPI and startle amplitude to the pulse alone trials (habituation) were analyzed over the three groups, using comedication (i.e., benzodiazepines) as a covariate.Main effect for block was found for startle amplitude (habituation), while main effects for group and block were found for percentage PPI. Further analysis displayed significant differences in PPI between the patients treated with typical antipsychotics and the healthy control group, while patients treated with atypical antipsychotics did not differ from either the healthy control group, or the patients treated with typical antipsychotics. Furthermore, post-hoc division of the patients treated with atypical antipsychotics in patients treated with clozapine and risperidone revealed that this superiority from atypical antipsychotics over typical antipsychotics appeared to be mainly based on the effects of clozapine.Patients with schizophrenia who are treated with atypical antipsychotics appear to have levels of sensorimotor gating that are more consistent with healthy controls than patients who are treated with typical antipsychotics. Furthermore, within the class of atypical antipsychotics, clozapine appears most potent in restoring this process.

ISSN:0271-0749    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

HIV infection and psychotic illnesses frequently coexist. The atypical antipsychotic olanzapine is metabolized primarily by CYP1A2 and glucuronosyl transferases, both of which are induced by the HIV protease inhibitor ritonavir. The purpose of this study was to determine the effect of ritonavir on the pharmacokinetics of a single dose of olanzapine. Fourteen healthy volunteers (13 men; age range, 20–28 years) participated in this open-label study. Subjects received olanzapine 10 mg and blood samples were collected over a 120-hour post-dose period. Two weeks later, subjects took ritonavir 300 mg twice daily for 3 days, 400 mg twice daily for 4 days, and 500 mg twice daily for 4 days. The next morning, after 11 days of ritonavir, olanzapine 10 mg was administered and blood sampling was repeated. Plasma samples were analyzed for olanzapine with HPLC. We compared olanzapine noncompartmental pharmacokinetic parameter values before and after ritonavir with a paired Studentttest. Ritonavir reduced the area under the plasma concentration-time curve of olanzapine from 501 ng · hr/mL (443–582) to 235 ng · hr/mL (197–294) (p< 0.001), the half-life from 32 hours (28–36) to 16 hours (14–18) (p= 0.00001), and the peak concentration from 15 ng/mL (13–19) to 9 ng/mL (8–12) (p= 0.002). Olanzapine oral clearance increased from 20 L/hr (18–23) to 43 L/hr (38–51) (p< 0.001) after ritonavir. Ritonavir significantly reduced the systemic exposure of olanzapine in volunteers. Patients receiving this combination may ultimately require higher olanzapine doses to achieve desired therapeutic effects.

ISSN:0271-0749    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

We investigated the effect of theCYP2C19andCYP2D6genotypes on the metabolism of amitriptyline (AT) in Japanese psychiatric patients. Steady-state concentrations of AT and its metabolites (nortriptyline [NT], trans-10-hydroxy-nortriptyline [EHNT], cis-10-hydroxy-nortriptyline [ZHNT], trans-10-hydroxy-amitriptyline [EHAT], and cis-10-hydroxy-amitriptyline [ZHAT]) in 50 patients were determined by high-performance liquid chromatography. Significantly higher plasma concentrations of AT corrected for dose and body weight in the subjects with two mutated alleles ofCYP2C19than in those with no mutated alleles ofCYP2C19were observed (no mutated alleles vs. two mutated alleles: 36.0 ± 18.2 vs. 64.0 ± 25.2 ng/mL/mg/kg,p= 0.025). A significantly higher AT/NT ratio was seen in the subjects with two mutated alleles ofCYP2C19than in those with no mutated alleles ofCYP2C19(no mutated alleles vs. two mutated alleles: 1.27 ± 0.59 vs. 3.40 ± 1.02,p= 0.001). A trend for higher NT/EHNT ratio in the subjects with two mutated alleles ofCYP2D6than in those with no mutated alleles ofCYP2D6was observed (no mutated alleles vs. two mutated alleles: 0.73 ± 0.39 vs. 1.31 ± 0.81,p= 0.068). A trend for higher plasma concentrations of total hydroxylated metabolites of AT (EHAT + ZHAT) corrected for dose and body weight in the subjects with two mutated alleles ofCYP2C19than in those with no mutated alleles ofCYP2C19was found (no mutated alleles vs. two mutated alleles: 9.5 ± 5.8 vs. 17.8 ± 8.9,p= 0.051). Therefore, the genotype ofCYP2C19is one of the important determinants of the plasma concentrations of AT and the capacity to desmethylate AT. Mother compound AT is shunted via hydroxylation pathways from AT to EHAT and ZHAT in the subjects with homozygotes of mutated alleles ofCYP2C19in order to compensate for the decreased capacity to desmethylate AT.

ISSN:0271-0749    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

In a previous study, of 41 depressed patients who had not responded to fluoxetine 20 mg/day, 53% were treated with high-dose fluoxetine (40–60 mg/ day) and responded (i.e., their 17-item Hamilton Rating Scale for Depression [HAM-D-17] score was <7) versus 29% and 25% of patients treated with fluoxetine plus lithium (300–600 mg/day) or fluoxetine plus desipramine (25–50 mg/day), respectively. We wanted to assess whether these findings could be replicated in a larger sample of depressed outpatients. We identified 101 outpatients with major depressive disorder (52 men and 49 women; mean age, 41.6 + 10.6 years) who were either partial responders (n = 49) or nonresponders (n = 52) to 8 weeks of treatment with fluoxetine 20 mg/ day. These patients were randomized to 4 weeks of double-blind treatment with high-dose fluoxetine (40–60 mg/day), fluoxetine plus lithium (300–600 mg/day), or fluoxetine plus desipramine (25–50 mg/day). In the overall group of patients (N = 101), there was no significant difference in response rates across the three treatment groups (high-dose fluoxetine, 42.4%; fluoxetine plus desipramine, 29.4%; fluoxetine plus lithium, 23.5%). Dropout rates were also comparable, ranging from 9.1% (high-dose fluoxetine) to 14.7% (fluoxetine plus desipramine and fluoxetine plus lithium). There were also no significant differences in response rates across the three treatment groups among partial responders (high-dose fluoxetine, 50.0%; fluoxetine plus desipramine, 33.3%; fluoxetine plus lithium, 33.3%) and nonresponders (high-dose fluoxetine, 35.3%; fluoxetine plus desipramine, 26.3%; fluoxetine plus lithium, 12.5%). At the end of the study, the mean lithium level was 0.37 + 0.15 mEq/L (n = 27; range, 0.1–0.8 mEq/L) among lithium-treated patients, and the mean desipramine level was 104.7 + 58.8 ng/mL (n = 22; range, 25–257 ng/mL). There were no significant relationships between lithium or desipramine blood levels and degree of improvement (as measured by the change in HAM-D-17 score). We found no significant differences in efficacy among these three treatment strategies among patients who had failed to respond adequately to 8 weeks of treatment with fluoxetine 20 mg/day, although the high-fluoxetine group was associated with nonsignificantly higher response rates in both partial responders and nonresponders.

ISSN:0271-0749    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Several recent clinical trials have established that reboxetine, a new selective norepinephrine reuptake inhibitor (selective NRI), is effective and safe for the treatment of major depression. However, the effects of reboxetine on specific symptoms of anxiety, agitation, and insomnia have not been reported. Data were obtained from nine short-term, double-blind, randomized clinical trials in patients with major depression. After initial titration, patients received reboxetine 8 to 10 mg per day. The effects on specific HAM-D symptoms of agitation, anxiety, and insomnia were compared between reboxetine-and placebo-treated patients. In addition, the incidence of treatment-emergent agitation, anxiety, and insomnia side effects with reboxetine were examined. Compared with placebo, the proportion of patients with improvement on the HAM-D agitation item and the HAM-D anxiety and insomnia factors from baseline was significantly greater with reboxetine at most assessment intervals. In general, the incidence of agitation-or anxiety-related side effects was comparable with reboxetine and placebo. Although reboxetine was associated with a significant (p< 0.05) increase in treatment-emergent insomnia reported as an adverse effect during the first week of treatment, very few reports of insomnia were made at subsequent evaluations. The incidence of treatment-emergent agitation or anxiety was comparable between treatment groups.

ISSN:0271-0749    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The clinical profile of reboxetine, a selective noradrenaline reuptake inhibitor, was compared with that of the selective serotonin reuptake inhibitor fluoxetine and placebo in a double-blind, multicenter, parallel-group clinical trial of patients with major depression. Among the 381 patients treated with reboxetine 8 to 10 mg/day, fluoxetine 20 to 40 mg/day, or placebo for up to 8 weeks, a statistically significant greater reduction in the mean Hamilton Rating Scale for Depression (21-item HAM-D) total score (the primary efficacy variable) was seen for both active treatment groups compared with placebo (p< 0.024). A significantly greater proportion of patients treated with either reboxetine or fluoxetine also achieved a response (≥50% reduction in HAM-D) or remission (HAM-D ≤10 points) than those who received placebo (p< 0.01 for both analyses). Similar findings were recorded in a subpopulation of severely ill patients, with statistically significantly greater decreases in the mean HAM-D total score between both active treatment groups compared with placebo (p< 0.024). Additional efficacy assessments (Montgomery-Åsberg Depression Rating Scale, Clinical Global Impression) reflected the primary efficacy analysis, with both active treatments offering comparable efficacy that was superior to that of placebo.Reboxetine and fluoxetine are more effective than placebo in the treatment of major depression. Futhermore, both antidepressants are well tolerated but possess different adverse event profiles.

ISSN:0271-0749    

出版商:OVID    

年代:2002

数据来源: OVID