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

摘要:

The authors investigated the relationship of desipramine concentrations in plasma to response, side effects, and dose in depressed patients over 75 years of age to determine if these "very old" patients were unusually sensitive to treatment.Thirty-four elderly patients consecutively hospitalized for nonpsychotic, unipolar major depression were treated with a fixed dose desipramine regimen for 4 weeks. Twelve nonresponding patients received a second trial at an increased dose. Comparisons were made with data from younger patients previously published by the authors. At comparable doses, steady-state desipramine concentrations in plasma in the elderly patients did not differ from those observed in younger patients. Response at levels in blood < 115 ng/ml was low, only 6 (21%) of 28 patient trials resulted in response. At levels greater or equal to 115 ng/ml, 6 (46%) of 13 patient trials were effective. These rates were not significantly different. Inspection of the data revealed that a concentration in plasma of 105 ng/ml significantly separated responders and nonresponders (chi squared = 3.93, df = 1, p <0.05), but even at levels greater or equal to 105 ng/ml, the response rate was still low relative to rates in prior studies of younger patients treated for a similar duration. The serious adverse reaction rate, 7 of 34, was similar to that previously observed in younger patients. This sample of "very old" elderly was not unusually "sensitive" to antidepressant drug treatment. In fact, the low rate of response observed at usually adequate levels in blood suggested "resistance" to treatment. The findings underscore the need for more effective drug treatments in the depressed elderly. (J Clin Psychopharmacol 1995;15:99-105).

ISSN:0271-0749    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

It is presently contraindicated to use the antimigraine drug sumatriptan with selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, or lithium.Consequently, many patients undergoing these pharmacotherapies for psychiatric disorders may not benefit from the therapeutic effect of sumatriptan in acute migraine attacks. Because sumatriptan does not appear to cross the blood-brain barrier and has a short half-life, it was deemed relatively safe to prescribe sumatriptan with antidepressant treatments. Fourteen patients receiving fluoxetine, fluvoxamine, sertraline, moclobemide, lithium, or buspirone did not experience significant side effects when they took oral sumatriptan for the relief of migraine on a total of 103 episodes. It is concluded that the combined use of sumatriptan with the above-mentioned antidepressant treatments may be safe. (J Clin Psychopharmacol 1995;15:106-109).

ISSN:0271-0749    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

This open clinical trial investigated the potential short-term efficacy and safety of divalproex sodium in the treatment of adolescents and young adults with bipolar affective disorder in an acute manic phase. Fifteen subjects were treated for 7 weeks with divalproex sodium (mean drug level in blood +/- the standard deviation at trial completion, 642.85 +/- 183.08 micro mol/liter) and were assessed weekly with the Modified Mania Rating Scale (MMRS), the Brief Psychiatric Rating Scale (BPRS), the Global Assessment Scale (GAS), and the Clinical Global Impressions Scale (CGI). Of the 15 subjects who entered the study, 8 showed marked improvement on the MMRS (pre-post decrease of greater or equal to 75%), 4 showed moderate improvement (pre-post decrease of 50 to 74%), 1 showed some improvement (pre-post decrease of 25 to 49%), 1 showed no improvement and was withdrawn before the seventh study week because of lack of response, and 1 withdrew because of side effects. The mean MMRS score was significantly changed by 7 weeks of treatment in the 13 subjects who completed the 7-week trial (69.54 +/- 24.21 to 18.08 +/- 8.70; t = 7.72; p < 0.0001), as were the BPRS (36.31 +/- 12.22 to 12.00 +/- 4.22; t = 7.53; p < 0.0001), the GAS (30.23 +/- 9.05 to 54.69 +/- 9.40; t = 7.50; p < 0.0001), and the CGI (5.38 +/- 0.96 to 2.38 +/- 0.87; t = 10.01; p <0.0001). Divalproex sodium was generally well tolerated with minimal reports of side effects in study completers. Total scores on the Valproic Acid Side Effects Scale were lower at the end of treatment than at baseline (11.77 +/- 8.99 to 5.46 +/- 3.33; t = 3.04; p < 0.01). We speculate that this was the result of the more accurate reporting of side effects by the adolescents when their manic symptoms were controlled. Three patients developed major side effects during the study that included benign transient elevation of the liver enzymes (N = 1) and sedation and dizziness (N = 1); one showed a decrease to below normal values in peripheral measures of thyroxine and cortisol, which were controlled by lowering the dose of divalproex sodium. (J Clin Psuchopharmacol 1995;15:110-116).

ISSN:0271-0749    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Sertraline is an effective antidepressant acting as a selective serotonin reuptake inhibitor.The subjective and behavioral effects of sertraline were studied and compared with the effects of alprazolam and dextroamphetamine in a within-subject, randomized, double-blind study in 20 volunteers aged 18 to 46 years. These subjects were experienced but nondependent users of central nervous system depressants who had the ability to reliably distinguish secobarbital, 150 mg, from placebo and to report positive subjective effects of secobarbital in an experimental setting. The following drug conditions were tested: sertraline, 100 and 200 mg; alprazolam, 1 mg; dextroamphetamine, 10 mg; and placebo. Drug effects were assessed with an objective test of psychomotor performance, subject-rated questionnaires, and observer-rated scales. Both alprazolam and dextroamphetamine were distinguishable from placebo on most measures, but sertraline produced effects discernable from placebo on only a few measures. At 1 hour postdrug administration, dextroamphetamine and alprazolam produced positive effects on several measures of elation, euphoria, and drug liking greater than placebo and both doses of sertraline. In contrast, sertraline produced higher scores on measures of dysphoria and physical unpleasantness than did the other drug conditions. Observer ratings of satisfaction with the drug and other pharmacologic effects were consistent with these findings. Results from this study indicate that sertraline, at the doses tested, does not possess the behavioral effects profile considered to be indicative of abuse potential when compared with alprazolam and dextroamphetamine. (J Clin Psychopharmacol 1995;15:117-124).

ISSN:0271-0749    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

In vitro preparations of human liver microsomes were used to study the inhibiting effects of two selective serotonin reuptake inhibitor (SSRI) antidepressants, paroxetine and fluvoxamine, on metabolism via hydroxylation of alprazolam and of desipramine.These reactions are mediated by Cytochromes P450-3A4 and P450-2D6, respectively. Paroxetine was a highly potent inhibitor of desipramine hydroxylation; the inhibition constant (Ki) value of 2.0 micro Meter indicated greater inhibiting potency than fluoxetine or norfluoxetine. The in vitro data predicted in vivo impairment of desipramine clearance by coadministration of paroxetine which was in the same range as observed in a clinical study. Fluvoxamine, by contrast, was a much weaker inhibitor of desipramine hydroxylation, having a Kivalue (16.6 micro Meter) similar to those of sertraline and desmethylsertraline. For hydroxylation of alprazolam, paroxetine was a relatively weak inhibitor, approximately comparable to fluoxetine, whereas fluvoxamine showed inhibiting capacity similar to that of norfluoxetine. The in vitro data predicted the degree of impairment of alprazolam clearance observed in vivo during fluvoxamine coadministration. The in vitro model can therefore provide clinically relevant data on prediction of potential drug interactions with SSRIs. (J Clin Psychopharmacol 1995:15:125-131).

ISSN:0271-0749    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The effects on sleep of two well known hypnotics, lormetazepam and zolpidem, during experimentally induced environmental noise were compared with placebo.In a double-blind, crossover study, 12 normal volunteers were subjected to prerecorded traffic noise with a mean noise level of 52 dB(A) and peaks to 77 dB(A) continuously for 8 hours in bed. Both hypnotics increased total sleep time, predominantly stage 2 sleep. A significant decrease in the number of sleep stage transitions, arousals, and awakenings longer than 3 minutes was found only with lormetazepam. No significant effects on rapid eye movement (REM) and slow wave sleep were observed. Latencies to persistent sleep and REM sleep onset were not different for either active treatment compared with placebo. Only after lormetazepam was performance on the morning reaction time test significantly affected. However, no differences were found in the subjective sleep quality and alertness ratings. Changes in the distribution of sleep stages throughout the night were related to the elimination half-life characteristics of the hypnotics, but few trends were detected. Both the protective properties against environmental noise of the hypnotics studied and the validity of the model of induced sleep disturbance in evaluating hypnotic agents are discussed. (J Clin Psychopharmacol 1995:15:132-137).

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