ISSN:0271-0749    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Selective action at limbic cortical dopamine D2-like receptors is a putative mechanism of atypical antipsychotic efficacy with few extrapyramidal side effects. Although risperidone is an atypical antipsychotic with high affinity for D2receptors, low-dose risperidone treatment is effective without inducing extrapyramidal symptoms. The objective was to test the hypothesis that treatment with low-dose risperidone results in ‘limbic selective’ D2/D3receptor blockadein vivo.Dynamic single photon emission tomography (SPET) sequences were obtained over 5 hours after injection of [123I]-epidepride (∼150 MBq), using a high-resolution triple-headed brain scanner (Marconi Prism 3000XP). Kinetic modelling was performed using the simplified reference region model to obtain binding potential values. Estimates of receptor occupancy were made relative to a normal volunteer control group (n = 5). Six patients treated with low-dose risperidone (mean = 2.6 mg) showed moderate levels of D2/D3occupancy in striatum (49.9%), but higher levels of D2/D3occupancy in thalamus (70.8%) and temporal cortex (75.2%). Occupancy values in striatum were significantly different from thalamus (F (1,4) = 26.3, p < 0.01) and from temporal cortex (F (1,4) = 53.4, p < 0.01). This is the first study to evaluate striatal and extrastriatal occupancy of risperidone. Low dose treatment with risperidone achieves a similar selectivity of limbic cortical over striatal D2/D3receptor blockade to that of atypical antipsychotics with lower D2/D3affinity such as clozapine, olanzapine and quetiapine. This finding is consistent with the relevance of ‘limbic selective’ D2/D3receptor occupancy to the therapeutic efficacy of atypical antipsychotic drugs.

ISSN:0271-0749    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

In this 6-week, open-label trial, combat veterans meeting DSM-IV criteria for posttraumatic stress disorder (PTSD) were treated with the atypical antipsychotic quetiapine. The starting dose was 25 mg at bedtime with subsequent titration based on tolerability and clinical response. Primary outcome was measured using the Clinician Administered PTSD Scale (CAPS). Secondary assessments of efficacy included the Positive and Negative Symptom Scale (PANSS), the Hamilton Rating Scale for Depression, and the Clinical Global Impression Scale. Safety and tolerability evaluations included neurologic ratings, vital signs, and assessment of treatment-emergent side effects. Eighteen of 20 patients enrolled in the study completed 6 weeks of open-label treatment. The dose range of quetiapine was 25 to 300 mg daily, with an average of 100±70 mg/d. There was significant improvement in CAPS scores, from 89.8±15.7 to 67.5±21.0 (t=4.863, df=18,P<0.005), and composite PANSS ratings from baseline to endpoint. General psychopathology (PANSS) and depressive symptoms (HRSD) were also reduced at the 6-week end point. There were no serious adverse events and no clinically significant changes in vital signs or neurologic ratings. This preliminary open trial suggests that quetiapine is well tolerated and may have efficacy in reducing PTSD symptoms in patients who have not had an adequate response other medications. Studies utilizing a randomized, controlled trial design and larger sample sizes are needed to better define the potential role of quetiapine and other atypical antipsychotics in the treatment of PTSD.

ISSN:0271-0749    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

The objective of this single-blind study was to compare the efficacy and safety of venlafaxine extended-release and nortriptyline in elderly patients with moderate to severe major depression. In- and out-patients (N=68) with unipolar major depression were randomized to receive 6-month treatment with either nortriptyline or venlafaxine. Outcomes of the two groups were compared using measures including the Hamilton Depression Rating Scale (HDRS) and the Newcastle Scale. Side effects were assessed with the UKU side-effect rating scale. Of the 34 venlafaxine-treated patients, 22 were remitters, 7 were nonremitters, and 5 dropped out. The intent-to-treat remission rate was 71% (22 of 31). Of the 34 who received nortriptyline, 21 were remitters, 7 were nonremitters, and 6 dropped out. The intent-to-treat remission rate was 70% (21 of 30). These results suggest that the remission rate with a therapeutic plasma level of nortriptyline is similar to the remission rate with a standard dose of venlafaxine in this group of elderly major depressed patients. No significant differences were observed between dropout rates in the two groups, but autonomic side-effects were significantly more frequent for nortriptyline than for venlafaxine. These results confirm the efficacy and safety of venlafaxine extended-release for treating elderly major depression.

ISSN:0271-0749    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Many patients fail to achieve an adequate response to a given antidepressant trial. The best-studied augmentation agents, lithium and thyroid supplementation are less commonly used. Augmenting antidepressants with bupropion has become an increasingly common strategy in the treatment of resistant depression. Several case reports and 2 open label studies suggest efficacy of this strategy. The purpose of this study is to further examine the utility of bupropion sustained release (SR) augmentation in patients with inadequate response to selective serotonin reuptake inhibitors. Patients who met DSM-IV criteria for major depression and had failed to achieve adequate response to an SSRI were considered for this study. Eligible patients were required to have a score of 16 on the 24-item Hamilton Depression Rating Scale (HDRS). Patients were treated openly for 6 weeks with bupropion SR added to their existing antidepressant. The dose range of bupropion was 150 to 300 mg per day. At each visit, patients were assessed using the Beck Depression Inventory (BDI), the Hamilton Depression Ratings Scale (HDRS), and the Clinical Global Impression (CGI). Twenty-eight patients (12 men, 16 women) entered the study. Twenty-five patients completed the six-week trial. With respect to the clinical benefit of bupropion SR augmentation, 15 out of 28, or 54% of patients, were classified as responders, showing a decrease in their HDRS or BDI scores of 50% or more between baseline and Week 6. This prospective, open-label trial supports the use of bupropion SR in the augmentation of SSRIs and venlafaxine. Placebo controlled trials should be completed to further evaluate the efficacy of this strategy.

ISSN:0271-0749    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Antidepressant drug trials have been criticised because they study atypical populations of depressive patients. The present cross-sectional database analysis was designed to define what constitutes a typical population of patients receiving antidepressants. From a database covering a population of 1,057,053 residents in Piedmont, Italy, and including all community (i.e. outside hospitals) prescriptions reimbursed by the National Health System, all prescriptions of antidepressant drugs dispensed during the first six months of 2000 were extracted. Using the general practice patient code all records were attributed to a sample of patients receiving antidepressants. During the study period 22,135 patients were dispensed one or more prescriptions, yielding a prevalence of use of 27.6 (CI 27.1, 28.0) per 1,000 females and 13.7 (CI 13.4, 14.0) per 1,000 males (female/male ratio 2.01). The prevalence of use progressively increased with age, with the highest rates in subjects over 75 years. The distribution of patients by number of antidepressant prescriptions showed that nearly 50% received only one or two prescriptions over the six months surveyed. Moreover, 18,676 subjects (84%) were prescribed antidepressants together with other medications. These data suggest shifting the focus of antidepressant drug trials from selected to non-selected populations of patients, including the elderly and patients with medical comorbidity, enrolled using entry criteria as close as possible to those adopted in everyday clinical practice. The high proportion of occasional antidepressant users suggests that clinical trials should follow all patients, without excluding those who fail to continue the study medication.

ISSN:0271-0749    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Subchronic intranasal treatment with argininevasopressin (AVP) has been shown to exert a strong ameliorating effect on sleep and slow wave sleep (SWS) deficits in elderly. However, AVP is also a potent stimulus of the pituitary-adrenal stress system, which is usually inhibited during early, SWS-rich sleep. A disinhibition of pituitary-adrenal activity during sleep is correlated with aging and is considered a pathologic factor contributing to various age-related diseases. Here, we examined whether the beneficial effect of prolonged intranasal AVP administration on sleep in aged would be associated with a concomitant decrease in pituitary-adrenal inhibition and effects on other neuroendocrine features of sleep. Twenty-six healthy elderly (mean 72.9 yr) with mild sleep complaints were investigated in a placebo controlled double-blind study. One group was treated daily each morning and evening with intranasal AVP (2×20 IU) for 10 weeks, the other received placebo. During polysomnographical recordings taken at the beginning and end of the treatment period, blood was sampled every 15 min. Intranasal AVP increased SWS on average by +21.5 min (p<0.02). The effect persisted on the night after acute withdrawal of the peptide treatment with no rebound occurring. Notably, rather than increasing pituitary-adrenal activity, AVP decreased the early sleep cortisol nadir on average by 0.5 μg/dl (p<0.05). AVP did not induce any measurable changes in fluid balance or cardiovascular activity. Overall, results indicate a promoting effect of AVP on SWS in aged accompanied by a beneficial rather than impairing influence on the neuroendocrine pattern of sleep.

ISSN:0271-0749    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

We examined the effectiveness of reboxetine, a norepinephrine reuptake inhibitor (NRI), compared with placebo for the treatment of patients with severe major depression (defined as a score on the 17-item Hamilton Rating Scale for Depression [HAM-D] ≥25). Data were obtained from four prospective, double-blind, randomized, placebo-controlled clinical trials of the efficacy of reboxetine (8 to 10 mg/d) over 4 to 8 weeks in patients with major depression. In three of the trials, reboxetine produced a significantly greater reduction than placebo in mean HAM-D scores from baseline to the last clinical assessment (p < 0.001). There were significantly more responders to treatment (defined as a reduction in HAM-D score >50% between baseline and the last follow-up observation) treated with reboxetine than placebo in three trials. The overall mean responder rate with reboxetine was 63% (range: 56–74%) compared with 36% (range: 20–52%) with placebo. These results demonstrate that reboxetine is significantly more effective than placebo in a subgroup of patients with severe depression.

ISSN:0271-0749    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Alprazolam, a benzodiazepine anxiolytic, was evaluated in anxious patients prior to oral surgery. This population represents a possible acute screening model for novel anxiolytic agents. Healthy subjects, preselected for a moderate to high degree of dental anxiety based upon Corah’s Dental Anxiety Scale, were enrolled in a three-arm parallel design study and randomly assigned to receive double-blind placebo (N=15), alprazolam 0.25 mg (N=16) or alprazolam 1 mg (N=16). Subjective selfreported anxiety was rated using the State Anxiety Inventory and visual analog scales. Objective measures included galvanic skin conductance, heart rate variability, blood pressure, pulse rate, and respiration. At 90 minutes after dosing, there were statistically significant (p<0.05) reductions compared with placebo in subjective anxiety and skin conductance mean level for the alprazolam-treated subjects. Changes from pre-dose (mean ± SEM) at 90 minutes in the placebo, alprazolam 0.25 mg, and alprazolam 1 mg groups were −4.73 ± 2.79, −13.75 ± 2.49, and −12.81 ± 2.32 for the State Anxiety Inventory and 5.44 ± 6.71, −31.88 ± 5.88, and −32.34 ± 5.32 mm for analog anxiety scores. Corresponding skin conductance mean level at 100 minutes in the three groups (respectively) changed 0.64 ± 0.24, −0.53 ± 0.21, −0.71 ± 0.22 microSiemens. The 0.25 mg and 1 mg dosages of alprazolam were not differentiated. Changes in heart rate variability, blood pressure, pulse rate, and respiration did not reflect subjective anxiety. Overall, the oral surgery anticipation anxiety model was found to be a sensitive test for benzodiazepine anxiolytic activity and may represent a potential screening model for evaluation of investigational agents.

ISSN:0271-0749    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

A variety of drugs targeted towards the central nervous system are associated with cardiac side effects, some of which are linked with reports of arrhythmia and sudden death. Some psychotropic drugs, particularly tricyclic antidepressants (TCAs) and antipsychotic agents, are correlated with iatrogenic prolongation of the QT interval of the electrocardiogram (ECG). In turn, this is associated with the arrhythmiatorsades de pointes(TdP). This review discusses the association between psychotropic agents, arrhythmia and sudden death and, focusing on TCAs and antipsychotics, considers their range of cellular actions on the heart; potentially pro-arrhythmic interactions between psychotropic and other medications are also considered. At the cellular level TCAs, such as imipramine and amitriptyline, and antipsychotics, such as thioridazine, are associated with inhibition of potassium channels encoded byHERG.In many cases this cellular action correlates with ECG changes and a risk of TdP. However, not all psychotropic agents that inhibit HERG at the cellular level are associated equally with QT prolongation in patients, and the potential for QT prolongation is not always equally correlated with TdP. Differences in risk between classes of psychotropic drugs, and between individual drugs within a class, may result from additional cellular effects of particular agents, which may influence the consequent effects of inhibition of repolarizing potassium current.

ISSN:0271-0749    

出版商:OVID    

年代:2003

数据来源: OVID